Focal lesions induce large-scale percolation of sleep-like intracerebral activity in awake humans.

Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.

The rise of organ donation after circulatory death: a narrative review.

Solid organ transplantation saves and transforms lives. The original type of organ donation from deceased patients was controlled donation after circulatory death, previously referred to as non-heart beating organ donation. The rise of donation after circulatory death in the UK came about through advances in critical care and transplant medicine and support from several key organisations in developing a robust ethical, legal and professional framework. The transplant waiting list reached a historic peak in 2009-2010 of 8000 patients, but fell by 25% to 6000 in 2017-2018. There has also been a steady rise in the number of deceased donors and the number of donations after circulatory death. The contribution of donation after circulatory death to the total number of donations rose steadily between 2000 and 2012 and has remained about 40% since. Although the situation has improved for patients waiting for a transplant, deaths and long waits remain common. Changes to legislative, technical and peri-mortem procedures may greatly change future practices in donation after circulatory death in the UK.

Suppression of interictal spikes during phasic rapid eye movement sleep: a quantitative stereo-electroencephalography study.

Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.

Adaptation and psychometric properties of the Italian version of the Non-Motor Symptoms Questionnaire for Parkinson's disease.

Although non-motor symptoms (NMS) of Parkinson's disease (PD) are very common also in early stages of the disease, they are still under-recognized. Screening tools for non-motor symptoms, such as non-motor symptoms questionnaire (NMSQuest), help clinicians to recognize NMS and to evaluate if patients could require further assessment or specific treatments. To validate an adapted Italian version of NMSQuest and study its psychometric properties, Italian PD patients self-completed Italian NMSQuest, and then underwent a standard clinical evaluation including motor assessment (by Hoehn and Yahr staging, unified Parkinson's disease rating scale part III) and non-motor assessment (by Montreal cognitive assessment, Beck depression inventory, neuropsychiatric inventory, Epworth sleepiness scale, scale for outcomes in Parkinson's disease-Autonomic and movement disorder society-sponsored revision of the unified Parkinson's disease rating scale part I). Somatic comorbidities were quantified using the modified cumulative illness rating scale (CIRS). Seventy-one subjects were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean duration of disease 6.3 ± 4.6 years; H&Y median 2). Italian NMSQuest showed adequate satisfactory clinimetrics in terms of data quality, precision, acceptability, internal consistency and reliability. A significant correlation was found between NMSQuest and most of non-motor assessment scales, while no significant correlation appeared with motor severity as well as with age of patients, disease duration, levodopa equivalent daily dose, L-DOPA/dopamine agonists assumption and CIRS total score. The Italian version of the NMSQuest resulted as a reliable instrument for screening NMS in Italian PD patients.

Designing a new scoring system (QualyP Score) correlating the management of cardiopulmonary bypass to postoperative outcomes.

AIM: The aim of this study was to ascertain if a score, directly derived from CPB records, could correlate to major postoperative outcomes. METHODS: An additive score (QualyP Score) was created from 10 parameters: peak lactate value during CPB, peak VCO(2)i, lowest DO(2)i/VCO(2)i, peak respiratory quotient, CPB time, cross-clamp time, lowest CPB temperature, circulatory arrest, ultrafiltration during CPB, number of packed red cells transfused intraoperatively. The PerfSCORE was calculated, as well. Multivariable logistic regression models were built to detect the independent predictors of: peak lactate >3 mmol/L during the first three postoperative days; the incidence of acute kidney injury network (AKIN) 1-2-3; respiratory insufficiency; mortality. RESULTS: The mean score was 4.8±2.6 (0-10). A QualyP Score ≥1 was predictive of postoperative acidosis (OR=1.595). A score ≥2 was predictive of AKIN 2 (OR=1.268) and respiratory insufficiency (OR=1.526). A score ≥5 was predictive of AKIN 3 (OR=1.848) and mortality (OR=1.497). CONCLUSIONS: QualyP Score may help to provide a quality marker of perfusion, emphasizing the need for goal-directed perfusion strategies.

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.

Simultaneous stereo-EEG and high-density scalp EEG recordings to study the effects of intracerebral stimulation parameters.

BACKGROUND: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. OBJECTIVE: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. METHODS: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. RESULTS: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. CONCLUSIONS: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.

Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

Atrial fibrillation ablation induces reverse remodelling and impacts cardiac function.

AIM: Atrio-ventricular anatomo-functional response to successful surgical atrial fibrillation (AF) ablation has been poorly investigated. Determinants of AF recurrence following surgical ablation are still debated. METHODS: Sixty-nine patients underwent AF ablation during major cardiac surgery. Main outcomes were clinical and echocardiographic results after monopolar and/or bipolar ablation were recorded. Secondary outcomes were freedom from AF, rehospitalization and congestive heart failure (CHF) at follow-up. Predictors of AF-recurrence were evaluated. RESULTS: Fifty-three patients (76.8%) were in sinus rhythm (SR) at 31.4±10.6 months of mean follow-up. Overall freedom from AF-recurrence was 61.4±6.6%, from hospital readmission 89.9±3.6%, from CHF 91.9±5.05%. Compared to AF-patients, SR-patients demonstrated better freedom from re-hospitalization (98.1±1.9% vs. 62.5±12.1%; P=0.0001) and CHF (94.7±5.1% vs. 77.8±13.9%; P=0.006). At follow-up SR-patients demonstrated atrial (preoperative 5.9±1.2 cm vs. follow-up 5.2±1.0; P=0.01) and ventricular reverse remodelling (preoperative LVDd 5.8±1.6cm vs. follow-up 5.0±1.3 cm; P=0.002 - preoperative LVDs 4.2±1.8 cm vs. follow-up 3.8±1.2 cm; P=0.045). E/A ratio was normal in 90.6% of SR-patients (69.6% of the total population of the study). TDI at the level of the left lateral annulus showed an improved left ventricular systole (Sm), and diastole (Em, E/Em) for SR-patients compared to AF-patients (Sm 9.30±1.66 vs. 7.81±1.41, P=0.001; Em: 10.55±1.87 vs. 7.44±0.40, P=0.001; E/Em: 0.06±0.02 vs. 0.11±0.05, P=0.0001). Preoperative atrial diameter (OR=23.9; P=0.002) and tricuspid insufficiency at follow-up (OR=3.5; P=0.008) were independent predictors of AF-recurrence. Neither etiology, nor duration of AF, nor even ablation technique influenced SR recovery (P=NS for all measurement). CONCLUSION: Radiofrequency AF ablation achieves 76.8% of SR recovery at follow-up. Maintenance of SR improves clinical, haemodynamic and echocardiographic results.

How to cope in heterogeneous coastal environments: Spatio-temporally endogenous circadian rhythm of valve gaping by mussels.

Transitional coastal zones are subject to high degrees of temporal fluctuation in environmental conditions, with these patterns varying in space. Gaining an in depth understanding of how sessile organisms cope with and respond to such environmental changes at multiple scales is needed to i) advance fundamental knowledge, ii) predict how organisms may react to stressors and iii) support the management of halieutic resources in transitional coastal areas. We addressed this question using mussels (Mytilus galloprovincialis) as model system. Valve-gaping sensor were deployed at multiple sites within the southern Venice Lagoon over a period of 6 months, to investigate the existence of periodicity in valve-gaping and its relationship with environmental variables, such as temperature and chlorophyll-a. Gaping behaviour was found to have periodic rhythms, of ~12 h and ~ 24 h, which were most pronounced in the inner part of lagoon part and were strongest during summer months. In autumn, the dual periodicity became weaker and mostly the 12 h remained. Gaping was closely linked with tide, but the relationship in terms of phasing varied upon location. Surprisingly, no clear direct relationships were found with chlorophyll-a, but food delivery may be mediated by tide itself. The results highlight the heterogeneity of behaviour and the endogenic nature of circadian rhythms in space and time. These findings have important implications for management of transitional areas where tidal alteration may have impacts on key behaviours, and emphasize the importance of characterizing their rhythms before using these as stress indicator. Moreover, the described tidal relationships should be included in growth models of bivalves in these systems.

Sinusal localization of nodal micrometastases is a prognostic factor in breast cancer.

BACKGROUND: Breast cancer micrometastases are frequently found during pathological examination of sentinel lymph nodes and complete axillary lymph node dissection. Despite this, their clinical relevance is still debated. The aim of this study is to investigate features that affect disease-free survival (DFS) and overall survival (OS) in patients with nodal micrometastases from breast cancer. MATERIAL AND METHODS: We retrospectively investigated the outcome of 122 patients with nodal micrometastases from breast cancer followed up for 60 months. RESULTS: At univariate analysis, worse DFS was related to features of primary tumor (multifocality P = 0.002; size >2 cm, P = 0.022; grade P = 0.022; absence of estrogen P < 0.001 and progesterone P < 0.001 receptors; HER-2 overexpression P = 0.006; vascular invasion P = 0.039; proliferative fraction > or =20% P = 0.034) and micrometastases (sinusal localization P = 0.010). Among the above-mentioned features, two were strongly associated with worse DFS in the multivariate model, i.e. negative receptorial status [hazard ratio (HR) = 11.24, 95% confidence interval (CI) 4.06-31.09; P < 0.001] and sinusal localization of micrometastasis (HR = 3.66, 1.18-11.36; P = 0.025). The OS was influenced by multifocality (P < 0.001) and receptor status (P = 0.005). CONCLUSION: Our results indicate that in patients affected by breast cancer, in addition to the well-known pathological features of primary tumor, sinusal localization of micrometastasis strongly impacts on the prognosis.

The future of primary paediatric care in Europe: reflections and Report of the EPA/UNEPSA Committee.

BACKGROUND: Changes in the scope of the field of paediatrics and the variability in primary paediatric care (PPC) and practice throughout Europe motivated the European Paediatric Association and Union of National European Paediatric Societies and Associations (EPA/UNEPSA) to establish a working group to discuss definitions of paediatric coverage in terms of age limits, find common denominators in the provision of PPC and examine the challenges and goals of 21st century paediatrics relevant to the continent. These issues were presented at the 2008 Europaediatrics in Istanbul, where a consensus declaration was drawn up and accepted by the EPA/UNEPSA Executive Committee. AIM: To present an outline of the essential elements of the 2008 EPA/UNEPSA Executive Committee consensus declaration. CONCLUSION: The definition of basic characteristics and the establishment of requirements for optimal PPC and practice are important steps in overcoming the differences among European countries and pave the way for an acceptable formulation of standardized high-quality paediatric medical care in Europe.

Long-range phase synchronization of high-frequency oscillations in human cortex.

Inter-areal synchronization of neuronal oscillations at frequencies below ~100 Hz is a pervasive feature of neuronal activity and is thought to regulate communication in neuronal circuits. In contrast, faster activities and oscillations have been considered to be largely local-circuit-level phenomena without large-scale synchronization between brain regions. We show, using human intracerebral recordings, that 100-400 Hz high-frequency oscillations (HFOs) may be synchronized between widely distributed brain regions. HFO synchronization expresses individual frequency peaks and exhibits reliable connectivity patterns that show stable community structuring. HFO synchronization is also characterized by a laminar profile opposite to that of lower frequencies. Importantly, HFO synchronization is both transiently enhanced and suppressed in separate frequency bands during a response-inhibition task. These findings show that HFO synchronization constitutes a functionally significant form of neuronal spike-timing relationships in brain activity and thus a mesoscopic indication of neuronal communication per se.

Inflammatory response after cardiopulmonary bypass: a randomized comparison between conventional hemofiltration and steroids.

AIM: Recent reports have shown anti-inflammatory effects with conventional hemofiltration (CUF) in patients undergoing cardiopulmonary bypass (CPB). The aim of this study was to evaluate the immunological and the hemodynamic response to CUF or metilprednisolone in patients undergoing coronary artery bypass grafting. METHODS: Twenty-four consecutive patients were prospectively randomized to receive CUF (12 patients, Group A) or metilprednisolone (12 patients, Group B). Hemodynamic response was evaluated by Swan-Ganz catheter, immunological response was analyzed by IL-2, IL-4, IL-6, TNF-alpha, IFN-gamma, IL-10 before anesthetic induction (T0), at aortic-declamping (T1), at the end of surgery (T2), ITU admission (T3) and 24 hours (T4). Troponin I was measured at the same time-points. Hematological and coagulative controls were performed. RESULTS: Morbidity and mortality were comparable between the two groups. Group A demonstrated lower cardiac index at T1 (2.1 +/- 0.69 L/min m2 vs. 3.917 +/- 1.28, P = 0.034) without significantly higher indexed-systemic-vascular-resistances at the end of surgery (1 101 +/- 434.3 dyne s cm(-5) m(-2) vs. 797.7 +/- 316.67, P = 0.233). When proinflammatory and anti-inflammatory cytokines were considered, all improved during the postoperative time course, without differences between the 2 Groups (P = NS). Hematological and coagulative data were similar in the two groups, in terms of white blood cells, platelets, prothrombin time, and activated partial thromboplastin time (P = NS). CONCLUSIONS: Anti-inflammatory action of CUF was comparable to steroids, thus determining a similar proinflammatory response to CPB. However, hemodynamics was slightly impaired by CUF. Therefore, there is no reason to prefer CUF to steroids in patients undergoing elective CABG.

Body perfusion during adult cardiopulmonary bypass is improved by pulsatile flow with intra-aortic balloon pump.

PURPOSE: To evaluate if the use of an intra-aortic balloon pump (IABP) during cardioplegic arrest improves body perfusion. METHODS: 158 coronary artery bypass graft (CABG) patients were randomized to linear cardiopulmonary bypass (CPB) (n=71, Group A) or automatic 80 bpm intra-aortic balloon pump (IABP) induced pulsatile CPB (n=87, Group B). We evaluated hemodynamic response by Swan-Ganz catheter, inflammation by cytokines, coagulation and fibrinolysis, transaminase, bilirubin, amylase, lactate and renal function (estimated glomerular filtration rate (eGFR), creatinine, and incidence of renal insufficiency and failure). RESULTS: IABP induced Surplus Hemodynamic Energy was 15.8-/+4.9 mmHg, with higher mean arterial pressure during cross-clamping (p=0.001), and lower indexed systemic vascular resistances during cross-clamping (p=0.001) and CPB discontinuation (p=0.034). IL-2 and IL-6 were lower, while IL-10 proved higher in Group B (p<0.05). Group B showed lower chest drainage (p<0.05), transfusions (p<0.05), INR (p<0.05), and AT-III (p=0.001), together with higher platelets, aPTT (p<0.05), fibrinogen (p<0.05) and D-dimer (p<0.05). Transaminases, bilirubin, amylase, lactate were lower in Group B (p<0.05); eGFR was better in Group B from ITU-arrival to 48 hours, both in preoperative kidney disease Stages 1-2 (p<0.03) and Stage 3 (p<0.05), resulting in lower creatinine from ITU-arrival to 48 hours (p<0.03). Incidence of renal insufficiency (p=0.004) and need for renal replacement therapy (p=0.044) was lower in Group B Stage 3. Group B PaO2/FiO2 and lung compliance improved from aortic declamping to the first day (p<0.003) with shorter intubation time (p=0.01). CONCLUSION: Pulsatile flow by IABP improves whole-body perfusion during CPB.

Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism. OBJECTIVE: To describe the effects of PAS on ALS patients before and after Riluzole intake compared with healthy subjects. METHODS: PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical significance was calculated using RM-ANOVA. RESULTS: In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 (p < 0.05). In ALS patients, a significant increase in MEP amplitude was also observed after 60 min (p < 0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity. After two weeks of riluzole intake, no MEP amplitude increase was evident after PAS at any time point. In three monomelic-onset ALS patients, a long lasting sensorimotor facilitation was evident only in the hemisphere corresponding to the affected side and appeared in the opposite hemisphere when the patients manifested contralateral symptoms. CONCLUSIONS: PAS may be considered a useful tool when investigating NMDA-mediated neocortical networks in ALS patients and the modulation of such networks after anti-glutamatergic drug intake.

Intercepting Parkinson disease non-motor subtypes: A proof-of-principle study in a clinical setting.

The construct of non-motor symptoms (NMS) subtyping in Parkinson Disease (PD) is emerging as a line of research in the light of its potential role in etiopathological interpretation of PD heterogeneity. Different approaches of NMS subtyping have been proposed: an anatomical model suggests that NMS aggregate according to the underpinning pathology; other researchers find aggregation of NMS according to the motor phenotype; the contribution of genetic background to NMS has also been assessed, primarily focusing on cognitive impairment. We have analyzed NMS burden assessed through an extensive clinical and neuropsychological battery in 137 consecutive non-demented PD patients genotyped for MAPT haplotypes (H1/H1 vs H2 carriers) in order to explore the applicability of the "anatomo-clinical", "motor" or "genetic" models for subtyping PD in a clinical setting; a subsequent independent analysis was conducted to verify a possible cluster distribution of NMS. No clear-cut NMS profiles according to the previously described models emerged: in our population, the autonomic dysfunctions and depressive symptoms represent the leading determinant of NMS clusters, which seems to better fit with the hypothesis of a "neurotransmitter-based" model. Selective preferential neurotransmitter network dysfunctions may account for heterogeneity of PD and could address translational research.

Functional Clustering approach for the analysis of Stereo-EEG activity patterns in correspondence of epileptic seizures.

In this study, a functional clustering approach is proposed and tested for the identification of brain functional networks emerging during sleep-related seizures. Stereo-EEG signals recorded in patients with Type II Focal Cortical Dysplasia (FCD type II), were analyzed. This novel approach is able to identify the network configuration changes in pre-ictal and early ictal periods, by grouping Stereo-EEG signals on the basis of the Cluster Index, after wavelet multiscale decomposition. Results showed that the proposed method is able to detect clusters of interacting leads, mainly overlapped on the Epileptogenic Zone (EZ) identified by a clinical expert, with distinctive configurations related to analyzed frequency ranges. This suggested the presence of coupling activities between the elements of the epileptic system at different frequency scales.

Validation of the Italian version of the Non Motor Symptoms Scale for Parkinson's disease.

OBJECTIVE: To validate the adapted Italian version of the Non-Motor Symptoms Scale (NMSS), a tool to assess non-motor symptoms (NMS) in Parkinson's disease (PD). METHODS: A cross cultural adaptation of the NMSS into Italian and a psychometric analysis of the translated version of the NMSS was carried out in patients with PD from two university centres-affiliated hospitals. The quality of data and the acceptability, reliability and construct validity of NMSS were analyzed. The following standard scales were also applied: Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale (UPDRS) part III, Montreal Cognitive Assessment, Beck Depression Inventory, Neuropsychiatric Inventory, Epworth Sleepiness Scale, Autonomic Scale for Outcomes in Parkinson's disease-Motor, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part I and Modified Cumulative Illness Rating Scale (CIRS). Levodopa equivalent daily dose (LEDD) was calculated. RESULTS: Seventy-one patients with PD were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean length of disease 6.3 ± 4.6 years; H&Y median: 2). Mean NMSS was 39.76 (SD 31.9; skewness 0.95). The total score of NMSS was free of floor or ceiling effects and showed a satisfactory reliability (Cronbach's alpha coefficient on total score was 0.72 [range for domains: 0.64-0.73], SEM value was 3.88 [½ SD = 31.90]). Significant positive correlations were found among total NMSS and other NMS standard tests, but no significant correlation appeared with UPDRS part III, CIRS and LEDD. CONCLUSIONS: The Italian NMSS is a comprehensive and helpful measure for NMS in native Italian patients with PD.

Ischaemic preconditioning of the vasculature: an overlooked phenomenon for protecting the heart?

Exposing the heart to brief episodes of ischaemia protects the myocardium and vascular endothelial cells against functional damage and cell death caused by subsequent prolonged ischaemia. Elucidation of the mechanisms that are involved in this phenomenon known as 'ischaemic preconditioning' and identification of drugs that mimic the protective response have the potential to improve the prognosis of myocardial infarction and other cardiac syndromes dramatically. This article focuses on recent findings on the effects of ischaemic preconditioning of the coronary vasculature, which highlight the endothelium as an important target for a successful therapeutic approach to myocardial ischaemia-reperfusion injury.