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The political crackdown during the 20th Century finds in the International Events a special place for the hosting Countries to spread their ideologies to the visitors and to all the other Countries attending the event. National Pavilions become the subject of propaganda, and their architectural language became an important part of the collective identity’s reclaimed logic, even if it wasn’t always real. Paris International Exposition of 1937 is a paradigmatic case: it’s a mirror of that time and of the prewar period’s international tensions. Born under the auspices of peace, it finally results the most relevant expression of the relation between Power and Architecture.

Background: Prehabilitation (Prehab) programs aim to optimize patients psycho-physical condition before surgery, to improve post-operative outcomes. Although functional benefits of Prehab are known, the clinical impact does not yet have concrete evidence. The objective of this study is to evaluate the efficacy of Prehab, associated with Enhanced Recovery After Surgery (ERAS) and surgical rehabilitation (Rehab), in frail colorectal oncological patients in terms of morbidity and hospitalization., Patients and Methods: The cohort of patients undergoing Prehab between January 2020 and December 2022 (Prehab group) is compared with the historical cohort of patients operated on in the period 01/2018-12/2019, not undergoing Prehab (no-Prehab group). Prehab scheme: multimodal (physiotherapy, clinical nutrition and psychological support). All patients followed an ERAS path. Only Prehab patients followed a surgical Rehab by a dedicated nurse case-manager. Propensity score matching (PSM) and weighting (PSW) analyses were used for statistical analysis., Primary Objectives: complications at 30 days and hospital stay., Secondary Objectives: functional outcomes., Results: In 3 years of preliminary enrollment, 36 patients completed the program: 22 in person, 16 in tele-prehab. The Prehab group experienced fewer complications than the no-Prehab group (PSM: 31 % vs 53 % p = 0.02; PSW: 31 % vs 51 % p = 0.02), less severe complications (CCI>20 PSM: 17 % vs 33 % p = 0.074; PSW: 17 % vs 53 % 0.026) and shorter hospital stay (4.5 vs 6 days; p = 0.02). Finally, prehabilitated patients improved their preoperative functional capacity and reduced anxiety levels., Conclusion: The strategy of combining Prehab with ERAS and Rehab has positively influenced post-operative clinical outcomes as well as functional parameters in our series., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Early-life stress (ELS) exposure increases the risk for mental disorders, including cognitive impairments later in life. We have previously demonstrated that an early diet with low ω6/ω3 polyunsaturated fatty acid (PUFA) ratio protects against ELS-induced cognitive impairments. Several studies have implicated the neuroimmune system in the ELS and diet mediated effects, but currently the molecular pathways via which ELS and early diet exert their long-term impact are not yet fully understood. Here we study the effects of ELS and dietary PUFA ratio on hippocampal mRNA and miRNA expression in adulthood, both under basal as well as inflammatory conditions. Male mice were exposed to chronic ELS by the limiting bedding and nesting material paradigm from postnatal day(P)2 to P9, and provided with a diet containing a standard (high (15:1.1)) or protective (low (1.1:1)) ω6 linoleic acid to ω3 alpha-linolenic acid ratio from P2 to P42. At P120, memory was assessed using the object location task. Subsequently, a single lipopolysaccharide (LPS) injection was given and 24 h later hippocampal genome-wide mRNA and microRNA (miRNA) expression was measured using microarray. Spatial learning deficits induced by ELS in mice fed the standard (high ω6/ω3) diet were reversed by the early-life protective (low ω6/ω3) diet. An integrated miRNA - mRNA analysis revealed that ELS and early diet induced miRNA driven mRNA expression changes into adulthood. Under basal conditions both ELS and the diet affected molecular pathways related to hippocampal plasticity, with the protective (low ω6/ω3 ratio) diet leading to activation of molecular pathways associated with improved hippocampal plasticity and learning and memory in mice previously exposed to ELS (e.g., CREB signaling and endocannabinoid neuronal synapse pathway). LPS induced miRNA and mRNA expression was strongly dependent on both ELS and early diet. In mice fed the standard (high ω6/ω3) diet, LPS increased miRNA expression leading to activation of inflammatory pathways. In contrast, in mice fed the protective diet, LPS reduced miRNA expression and altered target mRNA expression inhibiting inflammatory signaling pathways and pathways associated with hippocampal plasticity, which was especially apparent in mice previously exposed to ELS. This data provides molecular insights into how the protective (low ω6/ω3) diet during development could exert its long-lasting beneficial effects on hippocampal plasticity and learning and memory especially in a vulnerable population exposed to stress early in life, providing the basis for the development of intervention strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. AK was funded by NWO Food Cognition and Behavior., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years., Methods: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement., Results: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability., Conclusions: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously., Competing Interests: Competing interests: The authors report the following relationships: speaker honoraria, advisory board or steering committee fees, research support and/or conference travel support from Acthelion (EKH, RA), Almirall (MT, FG, RB, CRT, JLS-M), Bayer (MT, AL, PS, RA, MT, CB, JL-S, EP, VVP, RB, DS, RA, JO, JLSM, SH, CR, AGK, TC, NS, BT, MS, CAS), BioCSL (TK, AGK, BT), Biogen (TK, TS, DH, EKH, MT, GI, AL, MG, PD, PG, VJ, AVW, FG, PS, DF, RA, RH, CB, JLS, EP, VVP, FG, RB, RA, CRT, JP, JO, MB, JLSM, SH, CR, CSh, OGerlach, AGK, TC, BS, NS, BT, MS, HB), Biologix (RA), BMS/Celgene (EKH, AL), Genpharm (RA), Genzyme-Sanofi (TK, EKH, MT, GI, AL, MG, PD, PG, AVW, FG, PS, DF, RA, RH, MT, CB, JLS, EP, EP, VVP, FG, RB, RB, DS, CRT, JP, JO, MB, JLSM, SH, O Gerlach, AGK, HB), GSK (RA), Innate Immunotherapeutics (AGK), Lundbeck (EP), Merck / EMD (TK, DH, EKH, MT, GI, AL(Merck Serono), MG, PD, PG, VJ, AVW, PS, DF, RA, RH, MT, CB, JLS, EP, VVP, FG, RB, DS, RA, JO, MB, JLSM, CR, FM, O Gerlach, AGK, TC, BS, MS, HB), Mitsubishi (FG),Novartis (TK, TS, DH, EKH, MT, GI, AL, MG, PD, PG, VJ, AVW, FG, PS, DF, RA, RH, MT, CB, JLS, EP, VVP, FG, RB, DS, RA, CRT, JP, JO, MB, JLSM, SH, CR, FM, CSh, OG, AGK, TC, NS, BT, MS, HB), ONO Pharmaceuticals (FG), Roche (TK, EKH, AL, MT, CB, VVP, BT), Teva (TK, DH, EKH, MT, GI, AL, MG, PD, PG, VJ, FG, PS, DF, RH, MT, CB, JLS, VVP, RB, DS, RA, JP, JO, JLSM, CR, AGK, TC, MS, CAS), WebMD (TK), UCB (EP)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Limited longitudinal studies have been conducted on gait impairment progression overtime in non-disabled people with multiple sclerosis (PwMS). Therefore, a deeper understanding of gait changes with the progression of the disease is essential. The objective of the present study was to describe changes in gait quality in PwMS with a disease duration ≤ 5 years, and to verify whether a change in gait quality is associated with a change in disability and perception of gait deterioration. We conducted a multicenter prospective cohort study. Fifty-six subjects were assessed at baseline (age: 38.2 ± 10.7 years, Expanded Disability Status Scale (EDSS): 1.5 ± 0.7 points) and after 2 years, participants performed the six-minute walk test (6MWT) wearing inertial sensors. Quality of gait (regularity, symmetry, and instability), disability (EDSS), and walking perception (multiple sclerosis walking scale-12, MSWS-12) were collected. We found no differences on EDSS, 6MWT, and MSWS-12 between baseline and follow-up. A statistically significant correlation between increased EDSS scores and increased gait instability was found in the antero-posterior (AP) direction (r = 0.34, p = 0.01). Seventeen subjects (30%) deteriorated (increase of at least 0.5 point at EDSS) over 2 years. A multivariate analysis on deteriorated PwMS showed that changes in gait instability medio-lateral (ML) and stride regularity, and changes in ML gait symmetry were significantly associated with changes in EDSS (F = 7.80 (3,13), p = 0.003, R 2 = 0.56). Moreover, gait changes were associated with a decrease in PwMS perception on stability ( p < 0.05). Instrumented assessment can detect subtle changes in gait stability, regularity, and symmetry not revealed during EDSS neurological assessment. Moreover, instrumented changes in gait quality impact on subjects' perception of gait during activities of daily living.

Throughout the current COVID-19 pandemic, preventing nosocomial COVID-19 outbreaks has been a significant challenge for hospitals. It is essential to understand the ways in which SARS-CoV-2 spreads in healthcare settings to apply proper infection prevention and control (IPC) measures. The objectives of this study are to report on the hospital's response to a COVID-19 cluster and the transmission dynamics in a hospital ward of Geriatrics, Rehabilitation and Long term care. The study will focus specifically on how insufficient air replacement and directional airflow in indoor settings may have contributed to the transmission of the virus.

A growing number of scientific contributions suggest that COVID-19 infection can lead to impairment of cognition, mainly in executive functions and memory domains, even in the absence of frank neurological pathologies.The primary objective of this retrospective study is to evaluate the frequency and type of inefficiencies in a selection of cognitive tests administered to a sample of subjects who, following infection, required invasive assisted ventilation and were admitted to rehabilitation wards for the treatment of functional impairment.Fifty-seven subjects were enrolled. The recruited patients undergone an assessment of verbal and visuospatial memory and executive functions, upon entry into the rehabilitation department, after discharge from intensive care. The following tests were administered: Rey Auditory Verbal Learning Test (AVLT) (immediate and delayed recall), Rey-Osterrieth Complex Figure Test (ROCFT) (copy and delayed recall), Stroop Color-Word Test, and Trail Making Test (TMT, A and B).Deficient scores, in beyond 25% of subjects, were found in the copy of the ROCFT (32.1% of subjects), and in the delayed recall of ROCFT (27.2%). Between 10 and 20% of patients presented an abnormal result in delayed recall of AVLT (16.07%), and Stroop Test (time, 15.6%, error, 11.5%). Less than 10% of the sample had abnormal performances on TMT (A, 3.5%, and B, 9.4%), and in AVLT immediate recall (8.9%). Correlations of the performances with age, sex, and education were also found.This paper highlights the high incidence of abnormal cognitive performances in this specific subpopulation of patients with COVID-19 infection.

The balance of people with multiple sclerosis (PwMS) is commonly assessed during neurological examinations through clinical Romberg and tandem gait tests that are often not sensitive enough to unravel subtle deficits in early-stage PwMS. Inertial sensors (IMUs) could overcome this drawback. Nevertheless, IMUs are not yet fully integrated into clinical practice due to issues including the difficulty to understand/interpret the big number of parameters provided and the lack of cut-off values to identify possible abnormalities. In an attempt to overcome these limitations, an instrumented modified Romberg test (ImRomberg: standing on foam with eyes closed while wearing an IMU on the trunk) was administered to 81 early-stage PwMS and 38 healthy subjects (HS). To facilitate clinical interpretation, 21 IMU-based parameters were computed and reduced through principal component analysis into two components, sway complexity and sway intensity, descriptive of independent aspects of balance, presenting a clear clinical meaning and significant correlations with at least one clinical scale. Compared to HS, early-stage PwMS showed a 228% reduction in sway complexity and a 63% increase in sway intensity, indicating, respectively, a less automatic (more conscious) balance control and larger and faster trunk movements during upright posture. Cut-off values were derived to identify the presence of balance abnormalities and if these abnormalities are clinically meaningful. By applying these thresholds and integrating the ImRomberg test with the clinical tandem gait test, balance impairments were identified in 58% of PwMS versus the 17% detected by traditional Romberg and tandem gait tests. The higher sensitivity of the proposed approach would allow for the direct identification of early-stage PwMS who could benefit from preventive rehabilitation interventions aimed at slowing MS-related functional decline during neurological examinations and with minimal modifications to the tests commonly performed.

Although there are increasing reports on the prevalence of Listeria monocytogenes in wild species, this is the first case of listeriosis in sea turtle. An adult female Caretta caretta was rescued after being stranded alive along the coast of the Abruzzo region (Italy) in summer 2021. The turtle died in 6 days due to respiratory failure. The necropsy showed widespread organ lesions, such as yellow foci of necrosis in many organs, gastrointestinal erosions, pericarditis, and granulomatous pneumonia. Microbiological and histological analyses were performed on several organs. Listeria monocytogenes was isolated from multiple organs, indicating a case of septicaemic listeriosis, and the genome was sequenced and characterized. All the colonies analysed belonged to the same strain serogroup IVb, ST388, and CC388.

Objective: To investigate the correlations between clinical, functional, and radiological outcomes in inpatients with coronavirus disease 2019 (COVID-19)., Methods: In this observational study, we recruited inpatients affected by moderate COVID-19 disease. The clinical evaluation comprised the Cumulative Illness Rating Scale (CIRS), numerical rating scale (NRS), modified Rankin scale (mRS), and the modified Borg dyspnea scale (mBDS). Respiratory involvement was assessed with computed tomography (CT) and graded with a CT-severity score (CT-SS). We retrospectively assessed functioning using the International Classification of Functioning, Disability and Health (ICF) codes of the Clinical Functioning Information Tool (ClinFIT) COVID-19 in the acute phase. Correlation analysis was performed 1) between clinical, instrumental, and functional parameters and 2) between ICF categories., Results: The data showed statistically significant moderate correlations between CT-SS and the following categories: b152 "emotional functions" and b440 "respiratory functions"., Conclusion: This is the first study to use the ICF framework in people with a moderate form of COVID-19 in the acute phase. Considering the correlations between some ICF categories and radiological findings, our results support the use of the ClinFIT COVID-19 for a comprehensive assessment of COVID-19 patients.

Background: The advancement of physiopathological knowledge of tendon structures has shown that, in conditions of overload, there is the onset of both degenerative phenomena, such as the production of metalloproteases, apoptosis of tendon cells and neoangiogenesis, and regenerative and protective phenomena, such as the production of IGF-1 and nitric oxide. Tendinopathy results from the imbalance between these two groups of factors, leading to degeneration, weakening, and fissuring of the tendons, with the presence of local pain. The aim of the study was to evaluate the efficacy and tolerability of cetylated fatty acids (CFA) patch formulation in the control of acute localized shoulder pain and recovery of function in patients with tendinopathies., Methods: A prospective, single-center, no-profit observational study conducted in accordance with Good Clinical Practice. Thirty patients with recent onset shoulder pain symptoms (1-3 months) related to bursitis and tenosynovitis, with a diagnosis of shoulder tendon pathology confirmed by ultrasound examination, was evaluated for shoulder pain and function using the Constant Murley Score. Patients used 1 patch containing CFA for 8 h per day for 10 days. At 10 (V1) and 35 (V2) days after the first visit (V0), the Constant Score, treatment compliance and product tolerability were evaluated., Results: Thirty patients completed the treatment. At V0 the mean Constant Score (CS) was 32.37 ± 11.86, during V1 the mean CS was 50.68 ± 14.30, and at V3 the mean CS was 51.07 ± 15.29. The CS increased significantly between V0 and V1 (p < 0.0001) but did not vary significantly between V1 and V2 (p = 1). The tolerability of the product was excellent., Conclusions: Application of the CFA-based patch for 10 consecutive days in patients with shoulder tendinopathies was effective in reducing local pain and resulted in a good recovery of function. The results achieved at day 10 were maintained for 25 days, until the follow-up visit at day 35. CFA-based patch, thanks to their efficacy and tolerability, seems to be a promising solution to improve pain and functionality in subject with shoulder tendinopathy., Trial Registration: The study was approved by the Ethics Committee of Azienda USL Toscana Nord Ovest (protocol code 2018RIAB105) and conducted in accordance with Good Clinical Practice and the ethical principles outlined in the Declaration of Helsinki., (© 2022. The Author(s).)

Background: Turning the head while walking (an action often required during daily living) is particularly challenging to maintain balance. It can therefore potentially reveal subtle impairments in early-stage people with multiple sclerosis who still show normal locomotion (NW-PwMS). This would help in identifying those subjects who can benefit from early preventive exercise aimed at slowing the MS-related functional decline., Objectives: To analyze if the assessment of walking with horizontal head turns (WHHT) through inertial sensors can discriminate between healthy subjects (HS) and NW-PwMS and between NW-PwMS subgroups. To assess if the discriminant ability of the instrumented WHHT is higher compared to clinical scores. To assess the concurrent validity of the sensor-based metrics., Methods: In this multicenter study, 40 HS and 59 NW-PwMS [Expanded Disability Status Scale (EDSS) ≤ 2.5, disease duration ≤ 5 years] were tested. Participants executed Item-6 of the Fullerton Advanced Balance scale-short (FAB-s) wearing three inertial sensors on the trunk and ankles. The item required to horizontally turn the head at a beat of the metronome (100 bpm) while walking. Signals of the sensors were processed to compute spatiotemporal, regularity, symmetry, dynamic stability, and trunk sway metrics descriptive of WHHT., Results: Mediolateral regularity, anteroposterior symmetry, and mediolateral stability were reduced in NW-PwMS vs. HS ( p ≤ 0.001), and showed moderate discriminant ability (area under the receiver operator characteristic curve [AUC]: 0.71-0.73). AP symmetry and ML stability were reduced ( p ≤ 0.026) in EDSS: 2-2.5 vs. EDSS: 0-1.5 subgroup (AUC: 0.69-0.70). The number of NW-PwMS showing at least one abnormal instrumented metric (68%) was larger ( p ≤ 0.002) than the number of participants showing abnormal FAB-s-Item6 (32%) and FAB-s clinical scores (39%). EDSS: 2-2.5 subgroup included more individuals showing abnormal instrumented metrics (86%) compared to EDSS: 0-1.5 subgroup (57%). The instrumented metrics significantly correlated with FAB-s-Item6 and FAB-s scores (|Spearman's r | ≥ 0.37, s | ≥ 0.37, p < 0.001), thus demonstrating their concurrent validity., Conclusion: The instrumented assessment of WHHT provided valid objective metrics that discriminated, with higher sensitivity than clinical scores, between HS and NW-PwMS and between EDSS subgroups. The method is a promising tool to complement clinical evaluation, and reveal subclinical impairments in persons who can benefit from early preventive rehabilitative interventions., 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 © 2022 Carpinella, Gervasoni, Anastasi, Di Giovanni, Tacchino, Brichetto, Confalonieri, Solaro, Rovaris, Ferrarin and Cattaneo.)

Major depressive disorder (MDD) is a complex mental disorder where the neurochemical, neuroendocrine, immune, and metabolic systems are impaired. The microbiota-gut-brain axis is a bidirectional network where the central and enteric nervous systems are linked through the same endocrine, immune, neural, and metabolic routes dysregulated in MDD. Thus, gut-brain axis abnormalities in MDD patients may, at least in part, account for the symptomatic features associated with MDD. Recent investigations have suggested that the oral microbiome also plays a key role in this complex molecular picture of relationships. As on one hand there is a lot of what we know and on the other hand little of what we still need to know, we structured this review focusing, in the first place, on putting all pieces of this complex puzzle together, underlying the endocrine, immune, oxidative stress, neural, microbial neurotransmitters, and metabolites molecular interactions and systems lying at the base of gut microbiota (GM)-brain-depression interphase. Then, we focused on promising but still under-explored areas of research strictly linked to the GM and potentially involved in MDD development: (i) the interconnection of GM with oral microbiome that can influence the neuroinflammation-related processes and (ii) gut phageome (bacteria-infecting viruses). As conclusions and future directions, we discussed potentiality but also pitfalls, roadblocks, and the gaps to be bridged in this exciting field of research. By the development of a broader knowledge of the biology associated with MDD, with the inclusion of the gut/oral microbiome, we can accelerate the growth toward a better global health based on precision medicine., 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 © 2021 Scassellati, Marizzoni, Cattane, Lopizzo, Mombelli, Riva and Cattaneo.)

Cerebral palsy (CP) is still the most common cause of disability developing in infancy. How such a complex disorder affects adult life raises important questions on the critical issues to consider and the most appropriate care pathway right from early childhood. We conducted a multicenter study on a sample of 109 individuals with CP followed up from infancy and recalled for an assessment at ages ranging between 18 and 50 years (mean age 26 years). Semi-structured interviews and specific questionnaires (SF36, LIFE-H and Hollingshead Index) were conducted to assess general psychological state, quality of life, and socio-economic conditions. Our findings showed a globally positive perception of quality of life, albeit with lower scores for physical than for mental health. Our cases generally showed good scores on participation scales, though those with more severe forms scored lower on parameters such as mobility, autonomy, and self-care. These findings were investigated in more depth in interviews, in which our participants painted a picture showing that gradual improvements have been made in several aspects over the years, in the academic attainment and employment, for instance. On the downside, our sample reported persistent limitations on autonomy in daily life. As for the more profound psychological domain, there was evidence of suffering due to isolation and relational difficulties in most cases that had not emerged from the questionnaires. Our data have possible implications for the management of CP during childhood, suggesting the need to avoid an exclusive focus on motor function goals, and to promote strategies to facilitate communication, participation, autonomy, and social relations., (© 2021. Fondazione Società Italiana di Neurologia.)

Purpose: Italian expenditure for vitamin D greatly increased in the last few years, reaching €314 million ($376.8 million) in 2019. In Italy, the main cause of the increase in public spending for vitamin D is the marketing of high-cost medicines. At national and regional levels, some interventions have been performed to reduce expenditure, but spending has continued to increase. The aim of this work is to propose a new saving strategy determined by an analysis of a significant sample of the market., Methods: Data on the use of vitamin D formulations, including data for the different active substances that represent its pharmaceutical analogue and composition of groups of equivalence, were extrapolated from the Italian Medicines Agency transparency lists and from the Farmadati database. Data on pharmaceutical expenditure were obtained from the Data Warehouse of Liguria Region; the composition of this expenditure was analyzed in detail, focusing on the characteristics of the pharmaceutical preparations and their cost (price per defined daily dose)., Findings: Vitamin D expenditure paralleled that of cholecalciferol, the most used active ingredient, which in Liguria increased from €643,352 ($772,022.4) in 2010 to €8,006,574 ($9,607,888.8) in 2019 (increase of 1144%). Spending focused on high-cost formulations, exceeding 90% of total cholecalciferol cost in 2019. We simulated a possible optimization of the expense for cholecalciferol by applying a revised price to all the cholecalciferol consumptions in high-cost products because these formulations do not have an added therapeutic value, finding that the saving would be at least 60%. National data on the detailed expenditure composition for vitamin D are not available, but we found a strong resemblance between total cholecalciferol expenditure time series in Italy and the Liguria Region., Implications: The expense of cholecalciferol and consequently the expense of vitamin D could be optimized by modifying the reimbursement of high-cost formulations. At a national level, savings should be proportional to that estimated for the Liguria Region. On the basis of the 2019 data, Italian savings with respect to total cholecalciferol expenditure should be €170.65 million ($204.78 million); per capita cholecalciferol expenditure would shift from €4.66 ($5.59) to €1.84 ($2.21)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Among multiple sclerosis (MS) susceptibility genes, the strongest non-human leukocyte antigen (HLA) signal in the Italian population maps to the TNFSF14 gene encoding LIGHT, a glycoprotein involved in dendritic cell (DC) maturation. Through fine-mapping in a large Italian dataset (4,198 patients with MS and 3,903 controls), we show that the TNFSF14 intronic SNP rs1077667 is the primarily MS-associated variant in the region. Expression quantitative trait locus (eQTL) analysis indicates that the MS risk allele is significantly associated with reduced TNFSF14 messenger RNA levels in blood cells, which is consistent with the allelic imbalance in RNA-Seq reads (P < 0.0001). The MS risk allele is associated with reduced levels of TNFSF14 gene expression (P < 0.01) in blood cells from 84 Italian patients with MS and 80 healthy controls (HCs). Interestingly, patients with MS are lower expressors of TNFSF14 compared to HC (P < 0.007). Individuals homozygous for the MS risk allele display an increased percentage of LIGHT-positive peripheral blood myeloid DCs (CD11c + , P = 0.035) in 37 HCs, as well as in in vitro monocyte-derived DCs from 22 HCs (P = 0.04). Our findings suggest that the intronic variant rs1077667 alters the expression of TNFSF14 in immune cells, which may play a role in MS pathogenesis., Competing Interests: Conflict of interest For the following authors this is the conflict of interest statement. No conflict of interest for all the other authors. Prof. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Associate Editor of  Radiology, and Associate Editor of Neurological Sciences; received compensation for consulting services and/or speaking activities from Alexion, Almirall, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Dr. Gajofatto received fees from Biogen and Merck to participate in advisory boards. Dr. Vittorio Martinelli received compensation for speaking and/or for consultancy and support for travel expenses and participation in Congresses from Biogen, Merck-Serono, Novartis, Roche, Genzyme and Teva Pharmaceutical Industries. Prof. Filippo Martinelli Boneschi has received compensation for consulting services and/or speaking activities from Teva Pharmaceutical Industries, Sanofi Genzyme, Merck-Serono, Biogen Idec, Roche, Medday, Excemed, and received research support from Merck, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and Fondazione Cariplo., (Copyright © 2021 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Freezing of Gait (FoG) is a common symptom in Parkinson's Disease (PD) occurring with significant variability and severity and is associated with increased risk of falls. FoG detection in everyday life is not trivial, particularly in patients manifesting the symptom only in specific conditions. Various wearable devices have been proposed to detect PD symptoms, primarily based on inertial sensors. We here report the results of the validation of a novel system based on a pair of pressure insoles equipped with a 3D accelerometer to detect FoG episodes. Twenty PD patients attended a motor assessment protocol organized into eight multiple video recorded sessions, both in clinical and ecological settings and both in the ON and OFF state. We compared the FoG episodes detected using the processed data gathered from the insoles with those tagged by a clinician on video recordings. The algorithm correctly detected 90% of the episodes. The false positive rate was 6% and the false negative rate 4%. The algorithm reliably detects freezing of gait in clinical settings while performing ecological tasks. This result is promising for freezing of gait detection in everyday life via wearable instrumented insoles that can be integrated into a more complex system for comprehensive motor symptom monitoring in PD.

Background: Neuro-muscular fatigue (ANM) in the upper limbs can cause impaired coordination and dexterity. The main purpose of the study was to investigate whether ANM induced by a working day produced a reduction in digital dexterity in a population of dental health workers (OSD). Secondary objective was to investigate whether there were relationships between any reductions in dexterity and independent socio-demographic variables (gender, age and profession)., Methods: A cohort of OSD was assessed before and at the end of a working day of at least 7 hours using the Functional Dexterity Test (FDT). The effects of ANM (time), of the tested limb (dominance), and of their interaction on dexterity were investigated using two-way ANOVA. A multiple linear regression model was applied to explore the relationship between dexterity performance and independent variables., Results: A total of 50 OSDs were included. The net time of the FDT at the end of the day was always higher than in the morning. The ANOVA showed a significant difference for time (p <0.001) and side (p <0.001), but an effect from the interaction between the two factors was not identified (p = 0.428). The worsening of manual dexterity appears to be weakly correlated with age on both sides, and with the profession in the dominant limb., Conclusion: The ANM appears to have negatively affected the dexterity of both hands in the sample examined. The results of this study may be useful for planning the OSD's work agenda more carefully.

Background: Parasites of the family Spirorchiidae cause disease and mortality in marine and freshwater turtles; two species, Hapalotrema mistroides and Neospirorchis sp., are reported in the resident population of loggerhead turtles of the Mediterranean Sea, with the first being the most widespread. In vivo diagnosis of spirorchidiasis can represent a challenge in guaranteeing prompt control and treatment of the disease and is currently limited to copromicroscopy. The aim of this study was the development of a real time PCR assay with TaqMan probe for the detection of H. mistroides infection in the blood of live loggerhead turtles, Caretta caretta, hospitalized in rehabilitation centres. Its potential use for in vivo diagnosis is explored., Results: The developed real time PCR successfully detected H. mistroides DNA from both positive controls and experimental blood samples of live loggerhead sea turtles, showing good specificity, sensitivity and good reaction efficiency. Two out of three turtles which had demonstrated positivity at copromicroscopy also tested positive to this blood assay; DNA of H. mistroides was detected within the blood of one sea turtle, which tested negative for copromicroscopy., Conclusions: This study describes a specific and rapid molecular assay to detect H. mistroides infection from live sea turtles and highlights for the first time the presence of DNA of this species in turtle blood samples. Since this assay is able to detect low amounts of the parasitic free DNA in blood samples, its application could be helpful for in vivo diagnosis of H. mistroides infection as well as for epidemiological purposes.

Background: Idiopathic cervical dystonia (ICD) is a focal dystonia affecting neck muscles. Botulinum neurotoxin (BoNT) is the first-line treatment of ICD and different physical therapies (including exercise) are often proposed as adjunct treatments. However, the actual effectiveness of exercise in ICD is unclear. The aim of the current work is to assess the potential effectiveness of the Sensorimotor Perceptive Rehabilitation Integrated (SPRInt) exercise program as adjunct therapy for ICD., Methods: Fifteen ICD patients received BoNT injections in the neck muscles and, 12 weeks later, received BoNT a second time and SPRInt started. SPRInt consists in 18 exercise sessions in which augmented feedback of movement (including visual and acoustic feedback) is extensively used. Dystonia burden was measured by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patients were evaluated immediately before, 6 and 12 weeks after each BoNT injection., Results: Six weeks after the first BoNT injection (i.e., at BoNT peak effect), TWSTRS total score was better than baseline and remained improved at 12 weeks. TWSTRS disability domain slightly improved 6 weeks after the first BoNT injection, but after 6 more weeks returned to its baseline level. Disability improved more at SPRInt end (i.e., 6 weeks after the second BoNT injection), being even lower than after toxin alone. With a single-subject analysis, 4/10 patients who did not improve disability after BoNT improved after SPRInt plus BoNT., Conclusions: SPRInt plus BoNT can be more effective than BoNT alone in improving cervical dystonia patients' difficulties in the activities of daily living., Trial Registration: www.ClinicalTrials.gov, identifier NCT03247868 (https://register.clinicaltrials.gov).

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern., Objective: We explored the clinical management of inpatients with COVID-19 in Italy., Methods: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed., Results: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%., Conclusions: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available., (© 2020 S. Karger AG, Basel.)

Regular practice of sport activities yields psychophysical benefits for both the general population and persons affected by physical or intellectual impairments. Practicing competitive sport may add further value to these benefits. The objective of this observational cross-sectional study was to investigate the role of competitive sport practice in enhancing self-perceived psychophysical well-being of some select participants, using the Psychological General Well-Being Index and the Short Form-12 indices. We recruited at national events 100 young Italian competitive swimmers affected by physical or intellectual impairment. These respondents' results were compared with those of a control group of 100 Italian participants who did not practice competitive sport but who were also affected by physical or intellectual impairment, randomly selected from rehabilitation clinics and communities of young people with disabilities. Scores of psychological and emotional well-being were higher by 40% or more for the practitioners of competitive sport ( p  < .0001; Cohen's effect size d  ≥ 1.3). While our study's results suggest possible positive psychophysical benefits to competitive sport practice for young people affected by physical or intellectual impairment, longitudinal research is needed to be certain that our results are not due to self-selection into sports participation of those persons with disabilities who have a uniquely higher sense of well-being.

In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3 days to 11.5 months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.

Background: A variety of interventions has been proposed for symptomatology relief in primary headaches. Among these, manual trigger points (TrPs) treatment gains popularity, but its effects have not been investigated yet., Objective: The aim was to establish the effectiveness of manual TrP compared to minimal active or no active interventions in terms of frequency, intensity, and duration of attacks in adult people with primary headaches., Methods: We searched MEDLINE, COCHRANE, Web Of Science, and PEDro databases up to November 2017 for randomized controlled trials (RCTs). Two independent reviewers appraised the risk-of-bias (RoB) and the grading of recommendations, assessment, development, and evaluation (GRADE) to evaluate the overall quality of evidence., Results: Seven RCTs that compared manual treatment vs minimal active intervention were included: 5 focused on tension-type headache (TTH) and 2 on Migraine (MH); 3 out of 7 RCTs had high RoB. Combined TTH and MH results show statistically significant reduction for all outcomes after treatment compared to controls, but the level of evidence was very low. Subgroup analysis showed a statistically significant reduction in attack frequency (no. of attacks per month) after treatment in TTH (MD -3.50; 95% CI from -4.91 to -2.09; 4 RCTs) and in MH (MD -1.92; 95% CI from -3.03 to -0.80; 2 RCTs). Pain intensity (0-100 scale) was reduced in TTH (MD -12.83; 95% CI from -19.49 to -6.17; 4 RCTs) and in MH (MD -13.60; 95% CI from -19.54 to -7.66; 2RCTs). Duration of attacks (hours) was reduced in TTH (MD -0.51; 95% CI from -0.97 to -0.04; 2 RCTs) and in MH (MD -10.68; 95% CI from -14.41 to -6.95; 1 RCT)., Conclusion: Manual TrPs treatment of head and neck muscles may reduce frequency, intensity, and duration of attacks in TTH and MH, but the quality of evidence according to GRADE approach was very low for the presence of few studies, high RoB, and imprecision of results.

Objective: To study the immunomodulatory effect of teriflunomide on innate and adaptive immune cell populations through a pilot, open-label, observational study in a cohort of patients with relapsing-remitting MS., Methods: Blood lymphocytes were isolated from 10 patients with MS before and after 3 or 12 months of treatment. Adaptive and innate immune cell subsets were analyzed by flow cytometry as follows: B cells (memory, regulatory, and mature subsets), T cells (effector and regulatory subsets), and natural killer (NK) cells (CD56 dim and CD56 bright subsets)., Results: Our results show that teriflunomide significantly reduces absolute counts of total CD19 + B cells and mature and regulatory B-cell subsets. T cells were affected to a lesser extent, with a trend in reduction of absolute counts for both T effector CD4 + cells (Th1, Th17 and Th1/17) and T regulatory CD8 + and CD4 + cells. Teriflunomide had no detectable effect on NK-cell numbers., Conclusions: In our small cohort, teriflunomide treatment affects mainly and significantly on B-cell numbers, while having a milder effect on T-cell numbers. Larger cohorts are necessary to confirm these findings and understand the effect of teriflunomide on the functionality of these cells.

Importance: Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS)., Objective: To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD., Design, Setting, and Participants: A prospective cohort study of consecutive patients aged 18 to 45 years with first-ever acute ischemic stroke enrolled in the multicenter Italian Project on Stroke in Young Adults was conducted between January 1, 2000, and June 30, 2015. In a case-control design, the study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differs between patients whose IS was due to CEAD (CEAD IS) and those whose IS was due to a cause other than CEAD (non-CEAD IS) and compared the characteristics of patients with CEAD IS with and without migraine., Main Outcomes and Measures: Frequency of migraine and its subtypes in patients with CEAD IS vs non-CEAD IS., Results: Of the 2485 patients (mean [SD] age, 36.8 [7.1] years; women, 1163 [46.8%]) included in the registry, 334 (13.4%) had CEAD IS and 2151 (86.6%) had non-CEAD IS. Migraine was more common in the CEAD IS group (103 [30.8%] vs 525 [24.4%], P = .01), and the difference was mainly due to migraine without aura (80 [24.0%] vs 335 [15.6%], P < .001). Compared with migraine with aura, migraine without aura was independently associated with CEAD IS (OR, 1.74; 95% CI, 1.30-2.33). The strength of this association was higher in men (OR, 1.99; 95% CI, 1.31-3.04) and in patients 39.0 years or younger (OR, 1.82; 95% CI, 1.22-2.71). The risk factor profile was similar in migrainous and non-migrainous patients with CEAD IS (eg, hypertension, 20 [19.4%] vs 57 [24.7%], P = .29; diabetes, 1 [1.0%] vs 3 [1.3%], P > .99)., Conclusions and Relevance: In patients with IS aged 18 to 45 years, migraine, especially migraine without aura, is consistently associated with CEAD. This finding suggests common features and warrants further analyses to elucidate the underlying biologic mechanisms.

We studied 8 patients with spinal cord stimulation (SCS) devices which had been previously implanted to treat neuropathic chronic pain secondary to Failed Back Surgery Syndrome. The aim of our study was to investigate the effects of SCS on posture and gait by means of clinical scales (Short Form Health Survey-36, Visual Analogue Scale for pain, and Hamilton Depression Rating Scale) and instrumented evaluation with 3D Gait Analysis using a stereophotogrammetric system. The latter was performed with the SCS device turned both OFF and ON. We recorded gait and posture using the Davis protocol and also trunk movement during flexion-extension on the sagittal plane, lateral bending on the frontal plane, and rotation on the transversal plane. During and 30 minutes after the stimulation, not only the clinical scales but also spatial-temporal gait parameters and trunk movements improved significantly. Improvement was not shown under stimulation-OFF conditions. Our preliminary data suggest that SCS has the potential to improve posture and gait and to provide a window of pain-free opportunity to optimize rehabilitation interventions.

Objective: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated., Methods: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH., Results: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones., Conclusions: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background and Purpose: Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level., Methods: Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression., Results: During a time course of 9.5 years, 1931 subjects (1434 LS and 497 dICH; mean age, 71.3±13.3 years; males, 55.5%) qualified for the analysis. Current smoking was associated with LS (odds ratio [OR], 2.17; P<0.001). Conversely, dICH cases were more likely to be hypertensive (OR, 1.87; P<0.001), excessive alcohol consumers (OR, 1.70; P=0.001), and more frequently under treatment with warfarin (OR, 2.05; P=0.010) and statins (OR, 3.10; P<0.001). Hypercholesterolemia, diabetes mellitus, and antiplatelet treatment were not associated with a specific small vessel disease manifestation., Conclusions: The risk factor profile of dICH differs from that associated with LS. This might be used for disease risk stratification at individual level., (© 2016 American Heart Association, Inc.)

The involvement of the musculoskeletal system with other mild pleiotropic manifestations represents a clinical criterion, called "systemic features," to d iagnose Marfan's syndrome. We aimed to investigate the features of the hands and feet redressable contractures present in a group of Marfan patients. In 13 patients with previously diagnosed Marfan's syndrome, an accurate clinical examination was performed. In particular the characterization of the musculoskeletal system by visual analogic scale to measure muscle pain (VAS) and muscle strength (MRC system) was carried out; the Beighton scale score was used to evaluate the articular hypermobility. Ultrasound examination (US) was performed to detect deep-superficial flexor tendons and extensor tendons of both hands, and the short and long flexor and extensor tendons of the fingers and toes in static and dynamic positions. The ImageJ program was adopted to measure a profile of tendon echo-intensity. A reduction of the thickness of all tendons was detected by US in our patients; the VAS and Beighton scale scores were in normal ranges. The profile of tendon echo-intensity showed different textural details in all Marfan patients. This study provides evidence for other contractures' localization, and for altered findings of the tendons in patients with Marfan syndrome and finger/toe contractures. These changes may be associated with structural modifications in connective tissue.

The red palm weevil (RPW; Rhynchophorus ferrugineus) is spreading worldwide and severely harming many palm species. However, most studies on RPW focused on insect biology, and little information is available about the plant response to the attack. In the present experiment, we used metabolomics to study the alteration of the leaf metabolome of Phoenix canariensis at initial (1st stage) or advanced (2nd stage) attack by RPW compared with healthy (unattacked) plants. The leaf metabolome significantly varied among treatments. At the 1st stage of attack, plants showed a reprogramming of carbohydrate and organic acid metabolism; in contrast, peptides and lipid metabolic pathways underwent more changes during the 2nd than 1st stage of attack. Enrichment metabolomics analysis indicated that RPW attack mostly affected a particular group of compounds rather than rearranging plant metabolic pathways. Some compounds selectively affected during the 1st rather than 2nd stage (e.g. phenylalanine; tryptophan; cellobiose; xylose; quinate; xylonite; idonate; and iso-threonate; cellobiotol and arbutine) are upstream events in the phenylpropanoid, terpenoid and alkaloid biosynthesis. These compounds could be designated as potential markers of initial RPW attack. However, further investigation is needed to determine efficient early screening methods of RPW attack based on the concentrations of these molecules., (© 2015 Institute of Botany, Chinese Academy of Sciences.)

Unlabelled: Red Palm Weevil (RPW, Rhynchophorus ferrugineus Olivier) threatens most palm species worldwide. Until now, no studies have analyzed the gene regulatory networks of Phoenix canariensis (Chabaud) in response to RPW attacks. The aim of this study was to fill this knowledge gap. Providing this basic knowledge is very important to improve its management., Results: A deep transcriptome analysis was performed on fully expanded leaves of healthy non-infested trees and attacked trees at two symptom stages (middle and late infestation). A total of 54 genes were significantly regulated during middle stage. Pathway enrichment analysis showed that phenylpropanoid-related pathways were induced at this stage. More than 3300 genes were affected during late stage of attacks. Higher transcript abundances were observed for lipid fatty acid metabolism (fatty acid and glycerolipids), tryptophan metabolism, phenylpropanoid metabolism. Key RPW-modulated genes involved in innate response mediated by hormone crosstalk were observed belonging to auxin, jasmonate and salicylic acid (SA) pathways. Among transcription factors, some WRKYs were clearly induced. qRT-PCR validation confirmed the upregulation of key genes chosen as validation of transcriptomic analysis., Conclusion: A subset of these genes may be further analyzed in future studies to confirm their specificity to be induced by RPW infestations.

In sedentary patients suffering of metabolic syndrome, we evaluated the effects of mild exercise program (EP) on the efficiency of the oxygen delivery system. The prescription of exercise (40 min/session, 3 times/week) was tailored at workload corresponding to ∼90% individual anaerobic threshold (AT). EP improved significantly by ∼10% peak values of oxygen consumption (VO2) and heart rate (HR). Furthermore, in response to steady state workload at 90% AT, EP shortened the time constant of VO2, HR and the ratio VO2/HR (reflecting arterio-venous O2 concentration difference) by ∼6s. EP also decreased the elastic respiratory work due to a change in breathing pattern implying a larger contribution of respiratory rate, at the expense of tidal volume during exercise hyperventilation. In all subjects the perceived fatigue (Borg) decreased after training. This study supports a positive effect of a mild EP for the adaptive response of the oxygen chain to face metabolic needs compatible with daily life in patients affected by metabolic syndrome., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The etiopathogenesis of Carpal Tunnel Syndrome (CTS) is multifactorial and most cases are classified as idiopathic (Thurston 2013). A randomized controlled trial was performed to compare the effectiveness of Fascial Manipulation(®) (FM) and Low-Level Laser Therapy (LLLT) for CTS. This prospective trial included 42 patients (70 hands with symptoms) with clinical and electroneuromyographic diagnosis of CTS. The patients were randomly assigned to receive multiple sessions of FM or multiple session of LLLT. The Visual Analogic Scale (VAS) and Boston Carpal Tunnel Questionnaire (BCTQ) were performed at baseline, end of treatment and after three months. The group that received FM showed a significant reduction in subjective pain perception and an increased function assessed by BCTQ at the end of the treatment and follow-up. The group that received LLLT showed an improvement in the BCTQ at the end of the treatment but the improvement level was not sustained at the three month follow-up. FM is a valid alternative treatment for CTS., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To investigate the prevalence of connective tissue abnormalities in patients with spontaneous cervical artery dissections (sCeAD)., Methods: We systematically assessed clinically detectable signs of connective tissue aberration in a series of consecutive patients with sCeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) by a standard examination protocol including 68 items, and performed extensive molecular investigation for hereditary connective tissue disorders in all patients with sCeAD., Results: The study group included 84 patients with sCeAD (mean age, 44.5 ± 7.8 years; 66.7% men) and 84 patients with non-CeAD IS. None of the patients with sCeAD met clinical or molecular diagnostic criteria for established hereditary connective tissue disorder. Connective tissue abnormalities were detected more frequently in the group of patients with sCeAD than in the group of those with non-CeAD IS (mean number of pathologic findings, 4.5 ± 3.5 vs 1.9 ± 2.3; p < 0.001). Eighty-one patients (96.4%) in the sCeAD group had at least one detectable sign compared with 55 patients (66.7%) in the group with non-CeAD IS (p < 0.001). Skeletal, ocular, and skin abnormalities, as well as craniofacial dysmorphisms, were the clinical signs more strongly associated with sCeAD. Signs suggesting connective tissue abnormality were also more frequently represented in patients with sCeAD than in patients with traumatic CeAD (28.6%, p < 0.001; mean number of pathologic findings, 1.7 ± 3.7, p = 0.045)., Conclusions: Connective tissue abnormalities are frequent in patients with sCeAD. This reinforces the hypothesis that systemic aberrations of the connective tissue might be implicated in the pathogenesis of the disease., (© 2014 American Academy of Neurology.)

Objective: American, Japanese, and Canadian centers have demonstrated that noninvasive intermittent positive pressure ventilatory support (NVS) can be used continuously and in the long-term by people with Duchenne muscular dystrophy as a definitive alternative to tracheostomy mechanical ventilation. The aim of this study was to report this for the first time in Europe., Design: In this study, more than 300 patients with Duchenne muscular dystrophy were followed. End-tidal carbon dioxide, oxyhemoglobin saturation, and vital capacity were measured at each visit. Of the 300 patients, 79 used NVS for 8 hrs or more per day and 20 of these became continuously dependent on NVS., Results: A total of 20 patients have continuously depended on NVS for survival, for a total of 336 patient-years, up to 16 yrs in one case. Nocturnal NVS was begun for symptomatic hypoventilation when the vital capacity had decreased to a mean of 831 ± 173 ml, and continuous dependence on NVS was necessary when the vital capacity had decreased below 297 ± 113 ml., Conclusions: Noninvasive respiratory management can prolong survival without resorting to tracheotomy and without hospitalization.

Context: In adults with Prader-Willi syndrome (PWS), abnormal body composition with decreased lean body mass and skeletal muscle (SM) volume has been related to altered GH secretion and may possibly contribute to greatly reduced motor capacity., Objective: The scope of the study was to test the hypothesis that GH treatment has favorable effects on SM characteristics and motor performance in adults with PWS., Design, Setting, and Participants: Fifteen obese PWS subjects (nine males and six females; age range, 19-35 y; body mass index, 37.7-59.9 kg/m(2)) were investigated before and after 12 (GH12) and 24 (GH24) months of GH treatment., Main Outcome Measures: SM cross-sectional area and SM attenuation were determined with computed tomography at the lumbar and midthigh levels. Maximal isometric handgrip strength and isokinetic knee extension peak torque were measured. Motor performance was evaluated with different indoor walking tests, whereas exercise endurance was assessed with a treadmill incremental test to exhaustion., Results: A condition of severe GH deficiency was found in six patients (40%). GH treatment significantly increased lean body mass (GH12, P < .05; GH24, P < .05), reduced percentage of body fat (GH12, P < .05; GH24, P < .05), and augmented SM cross-sectional area and SM attenuation of both lumbar (GH12, P < .01; GH24, P < .001) and thigh muscles (GH24, P < .05). Handgrip strength increased by 7% at GH12 (P < .05) and by 13% at GH24 (P < .001). Peak torque of knee extension extrapolated at zero angular velocity was significantly higher at GH24 (P < .01), and exercise endurance rose by 13% (P < .05) and 17% (P < .05) before exhaustion at GH12 and GH24, respectively, whereas no change was detected with walking tests. No significant difference in the response to GH treatment was detected between patients with and without GH deficiency., Conclusion: Long-term GH treatment in adult PWS patients improves body composition and muscle size and quality and increases muscle strength and exercise tolerance independently from the GH secretory status.

Objective: To test the hypothesis that the effect of antithrombotic medications on the risk of intracerebral hemorrhage (ICH) varies according to the location of the hematoma., Methods: Consecutive patients with ICH were enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy). Multivariable logistic regression models served to examine whether risk factors for ICH and location of the hematoma (deep vs lobar) predict treatment-specific ICH subgroups (antiplatelets-related ICH and oral anticoagulants [OACs]-related ICH)., Results: A total of 870 (313 lobar ICH, 557 deep ICH) subjects were included. Of these, 223 (25.6%) were taking antiplatelets and 77 (8.8%) OACs at the time of stroke. The odds of antiplatelet-related ICH increased with aging (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.03-1.07) and hypertension (OR 1.86; 95% CI 1.22-2.85) but had no relation with the anatomical location of ICH. Conversely, lobar location of the hematoma was associated with the subgroup of OAC-related ICH (OR 1.70; 95% CI 1.03-2.81) when compared to the subgroup of patients taking no antithrombotic medications. Within the subgroup of patients taking OACs, international normalized ratio (INR) values were higher in those with lobar ICH as compared to those with deep ICH (2.8 ± 1.1 vs 2.2 ± 0.8; p = 0.011). The proportion of patients with lobar hematoma increased with increasing intensity of anticoagulation, with a ~2-fold increased odds of lobar compared to deep ICH (odds 2.17; p = 0.03) in those exposed to overanticoagulation (INR values >3.0)., Conclusions: OACs, as opposed to antiplatelets, predispose to lobar location of brain hematomas according to a dose-response relationship.

Unlabelled: Up to date studies have assessed costs and outcomes of rehabilitation in outpatients. Aim of the current prospective study was to evaluate the rehabilitative and economical effectiveness of an outpatient rehabilitative practice., Methods: The study was performed in 349 patients admitted for rehabilitation due to sequelae of orthopaedic surgery (repair of rotator cuff tear, anterior cruciate ligament reconstruction), limbs fracture (should, wrist, foot), whiplash neck pain, and chronic spinal pain (low back pain and neck pain). All patients were submitted to rehabilitation. Before and after rehabilitation, range of motion of joint or pain were assessed. Economical effectiveness and rehabilitative effectiveness in range of motion and pain were considered as outcome measures., Results: Rehabilitative effectiveness was 71.9%+/-30%. Length of rehabilitation (beta=0.29) and initial joint status (beta=0.36) had the strongest relationship with rehabilitative effectiveness. Rehabilitative effectiveness was higher in patients with sequelae of anterior cruciate ligament reconstruction. Economical effectiveness was 48.0%+01 and was related to length of rehabilitation (beta=0.11) only. Economical effectiveness was higher in low back pain carried out in group (136%+/-0.0)., Conclusions: The study gives evidence that in outpatient rehabilitation the rehabilitative effectiveness is higher than economical one. In addition, the study shows that rehabilitative treatments carried out in group only have higher economical effectiveness. These data must be considered useful in planning the ambulatory rehabilitation.

Early Parkinson's disease (PD), in which the motor disorder is mostly unilateral, allows to investigate the presence of side-related pathophysiological changes in the responses to balance perturbations prior to any confounding effect of therapy. These patients offer the possibility of answering the question whether the initial abnormalities affect spinal circuits or supra-spinal sensori-motor loops. Toe-down rotation of a supporting platform evokes in standing subjects a double-burst medium-latency response (MLR) in the stretched tibialis anterior (TA) muscle. The former burst (MLR1) is fed by group II spindle fibres through a spinal circuit, the latter (MLR2) travels through supraspinal pathways. This perturbation was used to separately test both reflex pathways in both the unaffected and affected side. Ten patients with unilateral PD (7 of which de-novo) and 10 normal subjects (NS) were recruited. 1. Body sway and centre of feet pressure (CFP) were recorded during quiet standing; 2. Rotations of the supporting platform were administered with both legs on the platform during free stance (Control) and 3. While holding onto a stable rail (Holding); 4. Separate perturbations to either leg (Leg-on or Leg-off) were also delivered to avoid the effect of concurrent ipsi- and contralateral inputs on MLR. The EMG of TA and Sol muscles were recorded bilaterally. 1. Position and sway of CFP were similar in NS and PD. 2. Under Control condition, there were no differences in area of TA MLR1 and MLR2 of both limbs between NS and PD. 3. During Holding, both bursts were reduced in amplitude in both NS and PD, but less so for the MLR1 on the PD affected side. 4. During single-leg perturbation, both bursts were reduced in amplitude in both NS and PD, both ipsi- and contralateral to the perturbation; however, in PD, MLR2 was much less reduced in the unperturbed affected side Leg-off. The differences in the responses to stretch between NS and early PD are not accounted for by changes in postural attitude, or by different amplitudes of the Control responses. The asymmetrical reduction of the MLR1 by Holding in PD indicates mostly unilateral impairment of the descending pathways modulatory to spinal group II circuits. Single-leg perturbation unveils a larger excitability of the supraspinal loop mediating the MLR2 on the affected side. These changes are early markers of basal ganglia malfunctions, and are related to both their descending effect on the spinal cord and their ascending influence onto the cortex., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: A high falls-related mortality rate in the elderly is not exclusively related to injuries. Moreover, the risk of falls increases with urinary disorders such as nocturia. The aim of this study was to investigate the role of nocturia in falls-related long-term mortality in elderly subjects., Design: Longitudinal study., Setting and Participants: The "Osservatorio Geriatrico Regione Campania" was a cross-sectional study performed in 1992 in Campania, a region of Southern Italy., Main Measurements: Long-term mortality (12 years' follow-up) in 178 elderly subjects (mean age 74.0 ± 6.3 years) with falls and 1110 elderly subjects (mean age 75.2 ± 6.4 years) without falls at baseline was measured. Subjects were then stratified for the presence/absence of nocturia., Key Results: In our sample, the prevalence of falls was 13.8% and the prevalence of nocturia was 45.7%. Long-term mortality was 51.3% in nonfallers and 62.9% in fallers (P < .05). In the absence of nocturia, long-term mortality was similar in nonfallers and fallers (49.0% vs 46.7%; P = .514, NS). In contrast, in the presence of nocturia, long-term mortality was higher in fallers than in nonfallers (74.5% vs 53.6%; P < .05). Cox regression analysis confirmed the predictive role of falls on long-term mortality in the presence of nocturia (hazard ratio 60; 95% confidence interval 1.01-2.57; P < .05) but not in the absence of nocturia (hazard ratio = 1.27; 95% confidence interval 0.81-1.99; P = .28)., Conclusions: Our data suggest that falls are related to an increased risk of long-term mortality in the elderly much more in the presence of nocturia. This phenomenon is probably related to the high comorbidity that usually affects elderly subjects with nocturia., (Copyright © 2012 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.)

Besides ocular diseases, also cerebral damage may cause colour vision deficits; cerebral lesions may be associated with a variety of clinical conditions that impair colour processing. This study presents procedures and normative data for a rapid, comprehensive seven-test battery aimed at assessing colour perception, colour naming and object colour knowledge. The norms, obtained from 96 healthy Italian participants, allow normality/pathology judgements on the basis of one-sided tolerance limits, after adjusting the score of each test for the demographic variables of the proband subjects. We also report, as an example, use of the battery in a stroke patient; this patient was chosen because her lesion affected the left temporal-occipital cortex, an area sometimes associated with a deficit of colour processing. The patient resulted normal on colour perception and colour name retrieval, but defective on object colour knowledge probed using the stimulus name. For the sound definition of the functional locus of cognitive impairment at the single case level, a multi-faceted set of tasks is necessary.