Early aphasia rehabilitation is associated with functional reactivation of the left inferior frontal gyrus a pilot study

Background and Purpose—Early poststroke aphasia rehabilitation effects and their functional MRI (fMRI) correlates were investigated in a pilot, controlled longitudinal study. Methods—Twelve patients with mild/moderate aphasia (8 Broca, 3 anomic, and 1 Wernicke) were randomly assigned to daily language rehabilitation for 2 weeks (starting 2.2 [mean] days poststroke) or no rehabilitation. The Aachen Aphasia Test and fMRI recorded during an auditory comprehension task were performed at 3 time intervals: mean 2.2 (T1), 16.2 (T2), and 190 (T3) days poststroke. Results—Groups did not differ in terms of age, education, aphasia severity, lesions volume, baseline fMRI activations, and in task performance during fMRI across examinations. Rehabilitated patients significantly improved in naming and written language tasks (P<0.05) compared with no rehabilitation group both at T2 and T3. Functional activity at T1 was reduced in language-related cortical areas (right and left inferior frontal gyrus and middle temporal gyrus, right inferior parietal lobule and superior temporal gyrus) in patients compared with controls. T2 and T3 follow-ups revealed a cortical activation increase, with significantly greater activation in the left hemisphere areas in rehabilitated patients at T2 and T3, and a time×treatment effect at T2 in the left inferior Broca area after rehabilitation. Left inferior frontal gyrus activation at T2 significantly correlated with naming improvement. Conclusions—Early poststroke aphasia treatment is useful, has durable effects, and may lead to early enhanced recruitment of brain areas, particularly the left inferior frontal gyrus, which persists in the chronic phase

Cocción óhmica de masas batidas libre de gluten

El objetivo de este trabajo fue evaluar experimentalmente la cocción de masa batida libre de gluten mediante un sistema de calentamiento óhmico, y realizar un modelo matemático simple del sistema, como así también realizar comparaciones con el horneado tradicional.Facultad de Ingenierí

Efficacy of fingolimod and interferon beta-1b on cognitive, MRI, and clinical outcomes in relapsing-remitting multiple sclerosis: an 18-month, open-label, rater-blinded, randomised, multicentre study (the GOLDEN study)

: Cognitive impairment (CI) affects 40-65% of multiple sclerosis (MS) patients. This study attempted evaluating the effects of fingolimod and interferon beta-1b (IFN β-1b) on CI progression, magnetic resonance imaging (MRI) and clinical outcomes in relapsing-remitting MS (RRMS) patients over 18&nbsp;months. The GOLDEN study was a pilot study including RRMS patients with CI randomised (2:1) to fingolimod (0.5&nbsp;mg daily)/IFN β-1b (250&nbsp;µg every other day). CI was assessed via Rao's Brief Repeatable Battery and Delis-Kaplan Executive Function System test. MRI parameters, Expanded Disability Status Scale scores and relapses were measured. Overall, 157 patients were randomised, of whom 30 discontinued the study (fingolimod, 8.49%; IFN β-1b, 41.18%; p&nbsp;≤&nbsp;0.0001). Patients randomised to fingolimod had more severe clinical and MRI disease characteristics at baseline compared with IFN β-1b. At Month (M) 18, both treatment groups showed improvements in all cognitive parameters. At M18, relapse rate, total number and volume of T2/T1 gadolinium-enhancing lesions were higher with IFN β-1b, as well as the percentage brain volume change during the study. Safety and tolerability of both treatments were similar to previous studies. Both treatments showed improvements in cognitive parameters. Fingolimod demonstrated significantly better effects on MRI parameters and relapse rate. Imbalance in baseline characteristics and the drop-out pattern may have favoured IFN β-1b. A longer duration trial may be needed to observe the complete expression of differential effects on CI scales reflecting the between-groups differences on MRI. Although limited in size, the GOLDEN study confirms the favourable benefit-risk profile of fingolimod reported in previous studies

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

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

Grand Rounds: Could Occupational Exposure to n-Hexane and Other Solvents Precipitate Visual Failure in Leber Hereditary Optic Neuropathy?

CONTEXT: Leber hereditary optic neuropathy (LHON) is a maternally inherited loss of central vision related to pathogenic mutations in the mitochondrial genome, which are a necessary but not sufficient condition to develop the disease. Investigation of precipitating environmental/occupational (and additional genetic) factors could be relevant for prevention. CASE PRESENTATION: After a 6-month period of occupational exposure to n-hexane and other organic solvents, a 27-year-old man (a moderate smoker) developed an optic neuropathy. The patient had a full ophthalmologic and neurologic investigation, including standardized cycloergometer test for serum lactic acid levels and a skeletal muscle biopsy. His exposure history was also detailed, and he underwent genetic testing for LHON mitochondrial DNA mutations. The patient suffered a sequential optic neuropathy with the hallmarks of LHON and tested positive for the homoplasmic 11778G → A/ND4 mutation. Routine laboratory monitoring revealed increased concentrations of urinary 2.5 hexandione (n-hexane metabolite) and hippuric acid (toluene metabolite) in the period immediately preceding the visual loss. DISCUSSION: In a subject carrying an LHON mutation, the strict temporal sequence of prolonged appreciable occupational exposure followed by sudden onset of visual loss must raise a suspicion of causality (with a possible further interaction with tobacco smoke). RELEVANCE: In this article, we add to the candidate occupational/environmental triggers of LHON and highlight the need for appropriate case–control (and laboratory) studies to validate the causal effect of mixed toxic exposures

The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

SIRT1 and thrombosis

Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating thrombosis, modulating key pathways including endothelial activation, platelet aggregation, and coagulation. Furthermore, SIRT1 displays anti-inflammatory activity both in vitro, in vivo and in clinical studies, particularly via the reduction of oxidative stress. On these bases, several studies have investigated the therapeutic potential of targeting SIRT1 for the prevention of thrombosis. This review provides a comprehensive and critical overview of the main preclinical and clinical studies and of the current understanding of the role of SIRT1 in thrombosis

Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018

Objectives Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers. DesignCase-control study. SettingCases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies. MethodsWe selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for &gt;5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses. ResultsThe whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower. ConclusionsWe found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry

Memory rehabilitation for people with multiple sclerosis

Background: This is an update of the Cochrane review ‘Memory rehabilitation for people with multiple sclerosis’ (first published in the Cochrane Library 14 March 2012, Issue 3). Impairments in cognitive function, particularly memory, are common in people with multiple sclerosis (MS) and can potentially affect their ability to complete functional activities. There is evidence from single-case or small group studies that memory rehabilitation can be beneficial for people with MS, but findings from randomised controlled trials (RCTs) and systematic reviews have been inconclusive. Objectives: To determine whether people with MS who received memory rehabilitation showed: 1. better outcomes in their memory functions compared to those given no treatment or receiving a placebo control; and 2. better functional abilities, in terms of activities of daily living, mood, and quality of life, than those who received no treatment or a placebo. Search methods: We searched the Trials Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (2 June 2015) and the following electronic databases: The NIHR Clinical Research Network Portfolio database (NIHR CRN) (from 2010 to June 2015), The Allied and Complementary Medicine Database (AMED) (2010 to June 2015), British Nursing Index (BNI) (2010 to June 2015), PsycINFO (2011 to June 2015), and CAB Abstracts (2010 to June 2015). Start dates for the electronic databases coincided with the last search for the previous review. We handsearched relevant journals and reference lists. Selection criteria: We selected RCTs or quasi-randomised trials ofmemory rehabilitation or cognitive rehabilitation for people with MS in which a memory rehabilitation treatment group was compared to a control group. Selection was conducted independently first and then confirmed through group discussion. We excluded studies that included participants whose memory deficits were the result of conditions other than MS unless we could identify a subgroup of participants with MS with separate results. Data collection and analysis: Three review authors were involved in this update in terms of study selection, quality assessment, and data extraction. We contacted investigators of primary studies for further information where required. We conducted data analysis and synthesis in accordance with the Cochrane Handbook for Systematic Reviews ofInterventions (Higgins 2011). We performed a ’best evidence’ synthesis based on the methodological quality of the primary studies included. Main results: We added seven studies during this update, bringing the total to 15 studies, involving 989 participants. The interventions involved various memory retraining techniques, such as computerised programmes and training on internal and external memory aids. Control groups varied in format from assessment-only groups, discussion and games, non-specific cognitive retraining, and attention or visuospatial training. The risk of bias of the included studies was generally low, but we found eight studies to have high risk of bias related to certain aspects of their methodology. We found significant effect of intervention on objective assessments of memory in both the immediate and long-term follow-ups: standardised mean difference (SMD) 0.23 (95% confidence interval (CI) 0.05 to 0.41) and SMD 0.26 (95% CI 0.03 to 0.49), respectively. We also found significant effect of intervention for quality of life in the immediate follow-up (SMD 0.23 (95% CI 0.05 to 0.41)). These findings showed that the intervention group performed significantly better than the control group. We also found a significant difference for activities of daily living (ADL) in the long-term follow-up (SMD -0.33 (95% CI -0.63 to -0.03)), showing that the control groups had significantly less difficulty completing ADLs than the intervention groups. We found no significant effects, either immediate or long-term, on subjective reports of memory problems (SMD 0.04 (95% CI -0.19 to 0.27) and SMD 0.04 (95% CI -0.19 to 0.27)); on mood (SMD 0.02 (95% CI -0.16 to 0.20) and SMD -0.01 (95% CI -0.21 to 0.20)); and on immediate follow-up for ADL (SMD -0.13 (95% CI -0.60 to 0.33)) and in the long term for quality of life (SMD 0.16 (95% CI -0.03 to 0.36)). We could not complete a sensitivity analysis of intention-to-treat in comparison with per-protocol analysis, due to insufficient information from the included papers. However, a sensitivity analysis of high- versus low-risk studies suggested that while quality of the trials did not affect most outcomes, differences were seen in the objective memory outcomes (both at immediate and long term) and quality of life (immediate) outcome, with studies with higher risk of bias inflating the overall effect size estimates for these outcomes, and the test of overall effect changing from being statistically significant to not significant when studies at high risk of bias were excluded. This suggests that lower-quality studies may have positively influenced the outcomes. Authors’ conclusions: There is some evidence to support the effectiveness of memory rehabilitation on memory function, as well as on quality of life. However, the evidence is limited and does not extend to subjective reports of memory functioning or mood. Furthermore, the objective measures used are not ecologically valid measures, and thus potentially limit generalisability of these findings into daily life. Further robust RCTs of high methodological quality and better quality of reporting, using ecologically valid outcome assessments, are still needed

Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study

Background. Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. Methods. Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. Results. At multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. Conclusion. This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS