How Task Interactivity Shapes Action Observation.

Action observation triggers imitation, a powerful mechanism permitting interpersonal coordination. Coordination, however, also occurs when the partners' actions are nonimitative and physically incongruent. One influential theory postulates that this is achieved via top-down modulation of imitation exerted by prefrontal regions. Here, we rather argue that coordination depends on sharing a goal with the interacting partner: this shapes action observation, overriding involuntary imitation, through the predictive activity of the left ventral premotor cortex (lvPMc). During functional magnetic resonance imaging (fMRI), participants played music in turn with a virtual partner in interactive and noninteractive conditions requiring 50% of imitative/nonimitative responses. In a full-factorial design, both perceptual features and low-level motor requirements were kept constant throughout the experiment. Behaviorally, the interactive context minimized visuomotor interference due to the involuntary imitation of physically incongruent movements. This was paralleled by modulation of neural activity in the lvPMc, which was specifically recruited during the interactive task independently of the imitative/nonimitative nature of the social exchange. This lvPMc activity reflected the predictive decoding of the partner's actions, as revealed by multivariate pattern analysis. This demonstrates that, during interactions, we process our partners' behavior to prospectively infer their contribution to the shared goal achievement, generating motor predictions for cooperation beyond low-level imitation.

Are clinical practice guidelines for low back pain interventions of high quality and updated? A systematic review using the AGREE II instrument.

BACKGROUND: Clinical practice guidelines (CPGs) provide recommendations for practice, but the proliferation of CPGs issued by multiple organisations in recent years has raised concern about their quality. The aim of this study was to systematically appraise CPGs quality for low back pain (LBP) interventions and to explore inter-rater reliability (IRR) between quality appraisers. The time between systematic review search and publication of CPGs was recorded. METHODS: Electronic databases (PubMed, Embase, PEDro, TRIP), guideline organisation databases, websites, and grey literature were searched from January 2016 to January 2020 to identify GPCs on rehabilitative, pharmacological or surgical intervention for LBP management. Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool to evaluate CPGs quality and record the year the CPGs were published and the year the search strategies were conducted. RESULTS: A total of 21 CPGs met the inclusion criteria and were appraised. Seven (33%) were broad in scope and involved surgery, rehabilitation or pharmacological intervention. The score for each AGREE II item was: Editorial Independence (median 67%, interquartile range [IQR] 31-84%), Scope and Purpose (median 64%, IQR 22-83%), Rigour of Development (median 50%, IQR 21-72%), Clarity and Presentation (median 50%, IQR 28-79%), Stakeholder Involvement (median 36%, IQR 10-74%), and Applicability (median 11%, IQR 0-46%). The IRR between the assessors was nearly perfect (interclass correlation 0.90; 95% confidence interval 0.88-0.91). The median time span was 2 years (range, 1-4), however, 38% of the CPGs did not report the coverage dates for systematic searches. CONCLUSIONS: We found methodological limitations that affect CPGs quality. In our opinion, a universal database is needed in which guidelines can be registered and recommendations dynamically developed through a living systematic reviews approach to ensure that guidelines are based on updated evidence. LEVEL OF EVIDENCE: 1 TRIAL REGISTRATION: REGISTRATION PROSPERO DETAILS: CRD42019127619 .

Evidence-Based Medicine (EBM) is properly perceived but its application is still limited in the orthopedic clinical practice: an online survey among the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) members.

PURPOSE: To evaluate the knowledge and awareness of Evidence-Based Medicine (EBM) among members of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA). METHODS: A questionnaire was developed that explored the following areas: (i) respondents' attitudes to EBM; (ii) their motivation to implement EBM in daily practice; (iii) their educational background, knowledge and skills related to accessing and interpreting information; (iv) their level of attention to, and use of, scientific literature; (v) access to and availability of evidence; (vi) perceived barriers in using EBM in clinical practice. The resulting data were analyzed using descriptive statistics, and the correlation between age, educational background and country was further investigated. RESULTS: Two-hundred and eighty-eight ESSKA members (11% of the total population) compiled the questionnaire. The participants covered all the five continents and an expected prevalence of European professionals (77%) was observed. The vast majority of participants were medical doctors (91%), mainly specialized in knee surgery with minimal involvement in research. 97% of the participants declared having some knowledge of EBM, acquired mainly during their professional education, with some geographical differences. The youngest clinicians and those from Eastern Europe reported the greatest difficulty in using EBM in daily practice. The application of EBM in clinical practice is positively affected by the time dedicated to research and negatively correlates with the time dedicated to patient care. CONCLUSIONS: The results of this survey highlight the need for further investigation into the main reasons behind the limited diffusion of the EBM approach, despite the medical community's knowledge and interest in the concept. A wider application of EMB would upgrade clinical practice, linking medical knowledge and scientific evidence to patients' needs which would result of benefit to patients, but also more in general to the health system.

Modular implant design affects metal ion release following metal-on-metal hip arthroplasty: a retrospective study on 75 cases.

Metal-on-Metal (MoM) total hip arthroplasty (THA) has been associated to wear and metal-ions release, controversially related to a variety of clinical complications. Little is known about the relevant design-dependent parameters involved in this process. The present study investigated the correlation between metal ion release in blood and revision rate as a function of: (i) specific MoM implant modular design parameters, (i.e. acetabular cup and femoral head diameters, taper adapter material and size, femoral neck material and modularity and stem size); (ii) MoM bilaterality. Co and Cr ions concentration levels in blood of 75 patients were retrospectively-evaluated with a mean follow-up of 4.8 years (range: 1.8-6.3). Patients were divided in a unilateral and a bilateral group. Statistical analysis was performed to find any significant difference related to acetabular cup diameter, femoral head diameter, taper adapter material/size, neck material/size and stem size. The bilateral MoM group had 4-times higher metal ion levels in blood than the unilateral one (p=0.017 only Cr), related to a higher revision rate (30% vs 20%): differences were 10-times higher particularly with a 48 mm femoral head diameter (p=0.012) and a Ti-alloy neck (p=0.041). Within the monolateral group using a shorter taper adapter and a shorter neutrally-oriented neck demonstrated higher ion levels (p=0.038 only Cr and p=0.008 only Co, respectively). The aforementioned design-features and MoM bilaterality are important risk-factors for metal-ion release in modular MoM THA.

An overview of different health indicators used in the European Health Systems.

INTRODUCTION: In the European Union three different health systems could be defined according to service delivery, financing, and economic policies: Beveridge, Bismarck and Mixed system. Although health systems are hardly to compare, various organizations are developing methods assessing performance. In the present work the performance of the three systems were evaluated using European Community Health Indicators according to Organization for Economic Cooperation and Development. METHODS: The study has been conducted among the 28 states of the European Union using the following indicators: Standardized death rate for diseases of the circulatory system, standardized death rate of malignant neoplasms, road traffic accidents with injury, life expectancy at birth, incidence of Human Immunodeficiency Virus (HIV), infant deaths, pure alcohol consumption, infants vaccinated against Diphtheria Tetanus Pertussis (DTP), public and total expenditure on health over the period 2001-2010. RESULTS: The variation of health indicators over the observational time shows similar trend of circulatory system diseases and malignant neoplasms death rates, road accidents with injury, infant deaths, life expectancy at birth, public and total health expenditure. Some differences in the trend of HIV incidence, alcohol intake and DTP vaccination rates arise among systems. Grouping countries by health system paradigm and geographical area, resulted in a relevant heterogeneity (I2 ≥ 90%, Pvalue < 0.0001). No clear superiority of a given health delivery system was found with respect to other paradigms. CONCLUSIONS: In accordance with the evidence of our study, it can be stated that best performances are more likely to be linked to country specific economic factors. In conclusion, it was not possible to identify the best health system model.

European cardiovascular mortality over the last three decades: evaluation of time trends, forecasts for 2016.

BACKGROUND: The circulatory diseases, in particular ischemic heart diseases and stroke, represent the main causes of death worldwide both in high income and in middle and low income countries. Our aim is to provide a comprehensive report to depict the circulatory disease mortality in Europe over the last 30 years and to address the sources of heterogeneity among different countries. METHODS: Our study was performed using the WHO statistical information system - mortality database - and was restricted to the 28 countries belonging to the European Union (EU-28). We evaluated gender and age time series of all circulatory disease mortality, ischemic heart diseases, cerebrovascular diseases, pulmonary and other circulatory diseases and than we performed forecast for 2016. Mortality heterogeneity was evaluated by countries using the Cochrane Q statistic and the I-squared index. RESULTS: Between 1985 and 2011 SDR for deaths attributable to all circulatory system diseases decreased from 440.9 to 212.0 x 100,000 in EU-28 and a clear uniform reduction was observed. Heterogeneity among countries was found to be consistent, therefore different analysis were carried out considering geographical area. CONCLUSIONS: We forecast a reduction in European cardiovascular mortality. Heterogeneity among countries could only in part be explained by both geographical and health expenditure factors.

Effects of bioactive fatty acid amide derivatives in zebrafish scale model of bone metabolism and disease.

The endocannabinoid system (which includes fatty acid derivatives, receptors, and metabolizing enzymes) is involved in a variety of physiological processes, including bone metabolism in which it regulates the function of osteoblasts and osteoclasts, as well as differentiation of their precursors. The zebrafish (Danio rerio) provides a useful animal model for bone research since zebrafish bones develop rapidly and are anatomically similar to mammalian bones. Putative orthologues and paralogs of endocannabinoid genes have recently been identified in zebrafish, demonstrating the presence of cannabinoid type 1 (CB1) and type 2 (CB2) receptors with affinity to endocannabinoid ligands. To identify therapeutic molecules potentially useful in bone-related diseases, we evaluated the in vivo effects of exposure to long-chain fatty acid amides in adult zebrafish. Using a well-established zebrafish scale model, we found that anandamide and N-linoleoylethanolamine are able to stimulate bone formation by increasing alkaline phosphatase activity in physiological conditions. In addition, they prevent the alteration of bone markers in a prednisolone-induced osteoporosis model in adult zebrafish scales, whereas their esterified forms do not. These data suggest that long-chain fatty acid amides are involved in regulating bone metabolism in zebrafish scales and that the CB2 receptor is a key mediator in this process.

The adult zebrafish as polyhedric model for skeletal studies.

In the last decade, several examples have been produced by scientific literature about zebrafish as a model to study human bone diseases. In fish, bone turnover, reparation and remodeling of the adult bone tissue cannot be studied in embryonic or juvenile stages. In addition, fins and scales represent unique anatomical features useful to study adult bone metabolism and diseases. For these reasons, the adult zebrafish represents an innovative and readily available resource for studying the bone metabolism at cellular and molecular level. Although the adult fish is less used than the embryo, several applications have been found in the last years with the production of innovative pathological models in adult zebrafish, helpful to understand the mechanisms of bone physiopathology. The use of mutants, regenerating organs, transgenic fish and scales have increased the power of this model in the last years.

Wnt signaling pathway inhibitors as promising diagnostic serum markers of osteolytic bone metastasis.

Despite the clinical importance of bone metastases, we still know little about their onset and progression and current diagnostic tools lack the sensitivity and specificity required for clear early diagnosis. We therefore need to continue studying the pathogenesis of bone metastatic invasion in order to improve diagnosis. The Wnt pathway has been described as having an important role in bone carcinogenesis and metastatic progression. This study investigated the diagnostic potential of the two main Wnt inhibitors, sclerostin and DKK-1, to improve the detection of osteolytic bone metastases. We measured sclerostin and DKK-1, MMP-2 and MMP-9, the bone resorption marker TRAP5b and the metastatic marker survivin in a control group of healthy patients, in patients with primary tumors and in a group with metastasis. Sclerostin and DKK-1 were clearly high in primary tumor patients and even higher in metastatic patients, compared to controls. The close correlations with metastatic markers and bone resorption markers make sclerostin and DKK-1 promising as new biomarkers in the diagnosis of bone osteolytic metastases.

Plasma endocannabinoid behaviour in total knee and hip arthroplasty.

Endocannabinoids are a class of lipid mediators involved in a wide range of physiological pathways including pain perception, and immunological defences. In particular, the involvement of endocannabinoids in bone metabolism and bone resorption has recently been studied. Moreover, one study on total knee arthroplasty describes the probable role of endocannabinoids in pain perception after surgery. The aim of the present study was to evaluate variations of endocannabinoid concentrations in patients undergoing total hip or total knee arthroplasty before and after surgery. Sera from 23 patients were collected at three different times: before surgery and at two different times during rehabilitation, and endocannabinoids were quantified by HPLC-MS/MS analysis. Mean values of endocannabinoids in presurgical serum samples were: 6.11±0.5 ng/ml for N-palmitoylethanolamide, 1.39±0.08ng/ml for N-stearoylethanolamide, 4.84±0.04 ng/ml for N-oleoylethanolamide, 0.44±0.03ng/ml for N-arachidonoylethanolamide, 0.84±0.05ng/ml for N-linoleoylethanolamide, 0.17±0.01ng/ml for N-α-linolenoylethanolamide. Statistical analysis showed a significant decrease of all the endocannabinoids after surgery, while there were no remarkable differences between total hip and total knee arthroplasties or between genders. Moreover, the results show no significant correlation between endocannabinoid concentrations and C-reactive protein and Erythrocyte sedimentation rate. The present study shows for the first time a specific and univocal behaviour of six endocannabinoids and N-acylethanolamides in orthopaedic surgery, suggesting the endocannabinoid system as a possible pharmacological target for presurgical therapeutics.

Predictors of renal survival in ANCA-associated vasculitis. Validation of a histopatological classification schema and review of the literature.

OBJECTIVES: In 2010 a histopathological classification of ANCA-associated glomerulonephritis was proposed to predict the outcomes at diagnosis. Our aim was to validate the proposed classification in our cohort of patients and to compare the studies already published. METHODS: The data of 93 patients who underwent kidney biopsy in a single Italian centre within 15 years were retrospectively collected. RESULTS: The 10-year renal and patients' survival were 60% and 81%, respectively. Biopsies were classified as 21% focal, 30% crescentic, 39% mixed and 10% sclerotic. Survival without ESRD at 5 years was 82% in focal, 37% in crescentic, 81% in mixed and 51% in sclerotic group. The Kaplan-Meier analysis highlights that renal survival was not different between sclerotic and crescentic groups (p=0.9) but both had a significantly worse prognosis than focal (p=0.04 and 0.015 respectively) and mixed groups (p=0.05 and 0.03 respectively). Focal and mixed groups had the same renal survival (p=0.7). At multivariate analysis the independent predictors of end-stage renal disease were less than 20% of normal glomeruli at kidney biopsy (p=0.022), high serum creatinine (p=0.009) and arterial hypertension at presentation (p= 0.006). CONCLUSIONS: In our cohort, the proposed histological classification was not predictive of renal prognosis. The focal and the mixed classes had the same prognosis and a significantly better renal outcome than both the crescentic and the sclerotic classes. At multivariate analysis among the histological features only less than 20% of normal glomeruli defines the renal prognosis together with renal function and arterial hypertension at baseline.

Perisurgical and intra-rehabilitative salivary steroid hormone profiles in bicompartmental arthroplasty.

Sex hormones play a role in pain perception, a key variable in evaluating the progression and treatment of osteoarthritis. The aim of this study was to determine the relationship between salivary concentrations of four steroid hormones and functional/clinical outcomes after hip and knee arthroplasty. Saliva samples were collected from 24 otherwise healthy patients with osteoarthritis before surgery, on admission to rehabilitation, and at hospital discharge. Salivary concentrations of testosterone, 17ß-estradiol, dehydroepiandrosterone (DHEA), and cortisol were immunoassayed. Changes in hormone levels were compared with clinical outcomes, as assessed by functional independence measure (FIM®), Barthel Index (BI), and visual analog scale for pain (VAS) scores. Changes in testosterone levels were significantly inversely correlated with VAS (r= -0.53, p=0.043) and FIM® and BI scores in all patients (r= -0.30, p= 0.043, and r= -0.35, p=0.031, respectively). The testosterone to cortisol ratio was inversely correlated with BI scores in all patients (r= -0.30, p=0.040), and in the men (r= -0.55, p=0.005) and the women (r= -0.28, p=0.042) when analyzed separately. Changes in salivary testosterone concentrations closely correlated with clinical outcome measurements for total hip and knee arthroplasty. Clinical outcome after arthroplasty was generally better among the men.

Bone-muscle unit activity, salivary steroid hormones profile, and physical effort over a 3-week stage race.

Muscle traction and bone metabolism are functionally linked and co-regulated by a series of factors. Although a role for steroid hormones was hypothesized, a clear definition of the bone-muscle interconnection still lacks. To investigate this relationship, we studied bone metabolism, muscle activity, and salivary steroid hormones profile in relation with the physical effort across a cycling stage race, a model of effort in absence of load. Nine pro-cyclists were recruited; body weight and power output/energy expenditure were recorded. Diet was kept constant. Saliva was collected at days -1, 4, 8, 12, 14, 19, and 23; blood and urine were collected at days -1, 12, and 23. Salivary steroid hormones [cortisol, dehydroepiandrosterone (DHEA), testosterone, and estradiol], serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and creatine kinase (CK) activities, plasma sclerostin, and urinary calcium and phosphorous were measured. Cortisol remained constant, testosterone decreased at day 4, and estradiol and DHEA firstly increased and then returned to basal levels. Hormone concentrations were not correlated with plasma volume shifts. LDH, CK, AST, sclerostin, and urinary calcium and phosphorous increased. DHEA and estradiol correlated with the physical effort and the bone-muscular markers. A relationship between muscle activity, in absence of load, and bone resorption emerged under a putative regulation by DHEA and estradiol.

Salivary steroid hormone response to whole-body cryotherapy in elite rugby players.

Saliva represents a low stress, not-invasively collected matrix that allows steroid hormone monitoring in athletes by reflecting type, intensity and duration of exercise. Whole body cryotherapy (WBC) consists of short whole-body exposures to extremely cold air (-110° to -140°C) which, despite being initially used to treat inflammatory diseases, is currently acquiring increasing popularity in sports medicine. Cryostimulation practice is now widely accepted as an effective treatment to accelerate muscle recovery in rugby players. The aim of this work was to study the changes of steroid hormones in saliva of rugby players after both 2 and 14 consecutive WBC sessions, in order to investigate the effects of the treatment on their salivary steroid hormonal profile. Twenty-five professional rugby players, belonging to the Italian National Team, underwent a 7-day cryotherapy protocol consisting of 2 daily sessions. Saliva samples were taken in the morning prior to the start of the WBC, in the evening after the end of the second WBC, and in the morning of the day after the last WBC session. The samples were analyzed for cortisol, DHEA, testosterone and estradiol using competitive enzyme-linked immunosorbent assays. Cortisol and DHEA showed a reduction already after the 2 WBC sessions of the first day; after 14 consecutive WBC sessions cortisol, DHEA, and estradiol levels decreased, while testosterone increased as did the testosterone to cortisol ratio. These results were confirmed by the fact that the majority of subjects showed variations exceeding the critical difference (CD). In conclusion, we found that WBC acutely affects the salivary steroid hormone profile, and the results are evident already after only one twice-daily session. Most significantly, after one-week of consecutive twice-daily WBC sessions, all the hormones were modified. This is the first experimental report that links changes in the hormonal asset to WBC.

Differential expression of interleukin-2 by anti-CD3-stimulated peripheral blood mononuclear cells in patients with psoriatic arthritis and patients with cutaneous psoriasis.

The differences in systemic T-cell responses between patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis (Ps) are still largely unknown. To determine differential features that could be used to distinguish PsA from Ps, we compared the cytokine secretion profile of circulating T cells in patients with PsA, patients with cutaneous Ps and control subjects. We determined Th1, Th2 and Th17 cytokine secretion of anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) using a cytokine bead array. Normality of data distribution was assessed by the Shapiro-Wilk test, and statistical significance was calculated by the Mann-Whitney test. Phenotypic characterization of circulating T cells was performed by fluorescence-activated cell sorting analysis. We found that the major systemic differences distinguishing PsA from cutaneous Ps were the increased secretion of interleukin (IL)-2 by α-CD3-stimulated PBMCs and a higher percentage of circulating CD3+ T cells expressing the proliferation marker CD71 in PsA. These results indicate IL-2 as a possible biomarker of PsA, and suggest a role of circulating T cells with high proliferative capacity in the pathogenesis of PsA.

Reciprocal regulation of calcium-/phosphate-regulating hormones in cyclists during the Giro d'Italia 3-week stage race.

Calcium and phosphate are essential for cell functions, and their serum concentrations result from the balance between intestinal absorption, bony storage, and urinary excretion. Fibroblast growth factor 23 (FGF23), expressed by osteocytes and osteoblasts, acts in the kidney, leading to hypophosphatemia and low 1,25-dihydroxycholecalciferol synthesis, but suppresses parathyroid function. The aim of this study was to explore the effects of a high-energy demanding cycling race on this bone-kidney-parathyroid axis. We studied nine cyclists during the 2011 Giro d'Italia stage race. Pre-analytical and analytical phases followed academic and anti-doping recommendations. Serum parathyroid hormone (PTH), 25(OH)D, total calcium, inorganic phosphorus, and plasma FGF23 were measured on days -1, 12, and 22 and corrected for changes in plasma volume. Dietary calcium and phosphorus, anthropometric parameters (height, weight, and body mass index) and indexes of metabolic effort (net energy expenditure, power output) were recorded. Dietary calcium and phosphorus intakes were kept at the same levels throughout the race. Twenty-five (OH)D, PTH, and calcium concentrations remained stable. FGF23 increased 50% with a positive correlation with the indexes of metabolic effort and, consequently, phosphorous decreased, although only in the first half. The strong metabolic effort acts on the bone-kidney-parathyroid system, and the rise in FGF23 plasma concentration might be aimed at maintaining calcium and phosphorus homeostasis.

Modifications of biochemical parameters related to protein metabolism and renal function in male soccer players after a match.

AIM: The impact of a soccer match on parameters related to protein catabolism and renal function was evaluated in male players. METHODS: Blood was collected before and immediately after a 90 minutes soccer match from 19 athletes of two first division teams in Brazil. Red blood cells (RBC), hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC), ammonia, uric acid, urea and creatinine were analyzed. The modification of plasma volume was calculated, and biochemical values were corrected for this change. Urea/creatinine ratio and equations to estimate the glomerular filtration rate (eGFR) were used to assess kidney function. RESULTS: Plasma volume decreased from pre- to post-match. Post-match values higher than the pre-match ones were observed for RBC, Hb and Ht, as a consequence of plasma volume decrease. An increase in ammonia and creatinine concentrations post-match in comparison with pre-match values was registered, without changes in uric acid and urea levels. A reduction in urea/creatinine ratio and in eGFR was observed post-match, suggesting a decrease of renal function. CONCLUSION: A soccer match induced alterations in parameters linked to renal function and protein metabolism in male athletes. Particular attention should be paid in the monitoring of the ammonia concentration as an indicator of metabolic activity and energy requirement during prolonged exercise.

Progressive improvement of patient and renal survival and reduction of morbidity over time in patients with lupus nephritis (LN) followed for 20 years.

Whether the long-term patient and renal survival of those diagnosed with lupus nephritis (LN) has improved over the decades is still debated. Eighty-nine patients diagnosed between 1968 and 1990 entered this study and their outcome was evaluated after 20 years. At presentation 54% of patients had class IV LN, 39.3% had renal insufficiency and 59.5% had nephrotic syndrome. Patients were divided into two groups: Group 1 consisted of 30 patients diagnosed between 1968 and 1980; Group 2 consisted of 59 patients diagnosed between 1981 and 1990. In Group 1 patient survival at 20 years was 84% versus 95% in Group 2 (p=0.05). Survivals without end-stage renal failure were respectively 75% and 84% at 20 years (p=0.05). Survivals without severe infection at 20 years were 44% in Group 1 and 66.5% in Group 2 (p=0.02). Survivals without cardiovascular events at 20 years were: 53% in Group 1 and 90% in Group 2 (p=0.005). At presentation, patients in Group 1 had higher serum creatinine (1.96 vs 1.15 mg/dl, p=0.01), higher activity index (8 vs 5.5, p=0.01), lower hematocrit (31% v s6%, p=0.008) and lower serum C4 levels (p=0.04) than Group 2 patients. Patients in Group 1 also received less frequent methylprednisolone pulses (43% vs 81%, p=0.0006). In Italian patients with LN, long-term life expectancy and renal survival progressively improved over the decades, while morbidity progressively declined. An earlier referral and refinement of therapy achieved this goal.

Mental images across the adult lifespan: a behavioural and fMRI investigation of motor execution and motor imagery.

Motor imagery (M.I.) is a mental state in which real movements are evoked without overt actions. There is some behavioural evidence that M.I. declines with ageing. The neurofunctional correlates of these changes have been investigated only in two studies, but none of the these studies has measured explicit correlations between behavioural variables and the brain response, nor the correlation of M.I. and motor execution (M.E.) of the same acts in ageing. In this paper, we report a behavioural and functional magnetic resonance imaging (fMRI) experiment that aimed to address this issue. Twenty-four young subjects (27 ± 5.6 years) and twenty-four elderly subjects (60 ± 4.6 years) performed two block-design fMRI tasks requiring actual movement (M.E.) or the mental rehearsal (M.I.) of finger movements. Participants also underwent a behavioural mental chronometry test in which the temporal correlations between M.I. and M.E. were measured. We found significant neurofunctional and behavioural differences between the elderly subjects and the young subjects during the M.E. and the M.I. tasks: for the M.E. task, the elderly subjects showed increased activation in frontal and prefrontal (pre-SMA) cortices as if M.E. had become more cognitively demanding; during the M.I. task, the elderly over-recruited occipito-temporo-parietal areas, suggesting that they may also use a visual imagery strategy. We also found between-group behavioural differences in the mental chronometry task: M.I. and M.E. were highly correlated in the young participants but not in the elderly participants. The temporal discrepancy between M.I. and M.E. in the elderly subjects correlated with the brain regions that showed increased activation in the occipital lobe in the fMRI. The same index was correlated with the premotor regions in the younger subjects. These observations show that healthy elderly individuals have decreased or qualitatively different M.I. compared to younger subjects.