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L’art. 2, commi 7-10, l. 27 settembre 2021, n. 134 ha introdotto disposizioni immediatamente precettive miranti a incentivare la compiuta identificazione dell’indagato e dell’imputato apolide, di cui non si conosce la cittadinanza, nonché del cittadino non appartenente all’Unione europea. Le norme incidono sulla disciplina del casellario giudiziale interno ed europeo e con esso del sistema c.d. ECRIS-TCN, come imposto dal Regolamento UE 2019/816 del 17 aprile 2019, fondato sulla raccolta all’interno dei singoli Paesi dell’Unione europea del Codice unico identificativo.

Analisi diacronica delle problematiche probatorie più rilevanti nei procedimenti per "fatti di mafia" con proiezioni sul convincimento del giudice e sul contraddittorio probatorio. Il preteso ruolo normante della giurisprudenza viene posto a raffronto con frizioni dogmatiche e ricadute operative dimostrando la fragilità degli accertamenti in tema di indicatori della partecipazione alla associazione, della base indiziaria e della "messa a disposizione".

Instantaneous arterial pressure-flow (or velocity) relationships indicate the existence of a cerebral critical closing pressure (CrCP), with the slope of the relationship expressed by the resistance-area product (RAP). In 194 healthy subjects (20–82 years, 90 female), cerebral blood flow velocity (CBFV, transcranial Doppler), arterial blood pressure (BP, Finapres) and end-tidal CO2 (EtCO2, capnography) were measured continuously for five minutes during spontaneous fluctuations of BP at rest. The dynamic cerebral autoregulation (CA) index (ARI) was extracted with transfer function analysis from the CBFV step response to the BP input and step responses were also obtained for the BP-CrCP and BP-RAP relationships. ARI was shown to decrease with age at a rate of −0.025 units/year in men (p = 0.022), but not in women (p = 0.40). The temporal patterns of the BP-CBFV, BP-CrCP and BP-RAP step responses were strongly influenced by the ARI (p

KEY POINTS Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia. ABSTRACT Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70 years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO2 (capnography) and heart rate (ECG) were performed for 5 min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis. The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP made a highly significant contribution during normocapnia (P

Background: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. Methods: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6–34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30–49%; 2: in the range 50–69%; 3: in the range 70–99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. Results: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). Conclusion: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

To identify the clinical profile and aura characteristics of patients with Migraine with Aura (MwA) having acute cerebral ischemia, we compared stroke phenotype and risk factors in stroke patients with (S+MwA+) or without (S+MwA−) MwA and aura features in MwA patients with (S+MwA+) or without (S−MwA+) stroke. In this retrospective multicenter case–control study, we reviewed stroke phenotypes and vascular risk factors in S+MwA+ and S+MwA− patients younger than 60 years and risk factors and aura type, duration, onset age, and the frequency in the previous year in S+MwA+ patients and S−MwA+ subjects matched for age and disease history, investigated for patent foramen ovale (PFO). 539 stroke (7.7% S+MwA+) and 94 S−MwA + patients were enrolled. S+MwA+ patients were younger (p =.0.004) and more frequently presented PFO [OR 4.89 (95% CI 2.12–11.27)], septal interatrial aneurism [OR 2.69 (95% CI 1.15–6.27)] and cryptogenic ischemic stroke (CIS) [OR 6.80 (95% CI 3.26–14.18)] than S+MwA− subjects. Significant atherosclerosis was not detected in S+MwA+ patients. Compared to S−MwA+, S+MwA+ patients were characterized by visual [OR 3.82 (95% CI 1.36–10.66)] and shorter-lasting (20.0 min IQr 13.1 vs 30.0 min IQr 25.0; p

L'articolo analizza le costanti e le variabili della risposta legislativa e giurisprudenziale al contrasto dei fenomeni mafiosi. La lotta al terrorismo negli anni ’70 è infatti stata condotta sfruttando il rudimentale armamentario offerto della prima prevenzione antimafia e – a sua volta – ha fornito le basi di risposta all’offensiva contro la mafia negli anni ’80 sul versante relativo alle istituzioni investigative, penitenziarie, politico amministrative. Lungo questo continuum nella dimensione contemporanea i “buoni” risultati ottenuti sul fronte mafioso hanno aperto la strada al contrasto delle nuove forme di terrorismi interni e internazionali di matrice religiosa con una progressiva implementazione del “doppio binario”.Oltre alla triplice dimensione della strumentazione giuridica, degli apparati di polizia e della metodologia giudiziaria di intervento, la mobilitazione contro terrorismo e mafia ha negli anni determinato una vera e propria mutazione del ruolo del giudice che si è riflessa specularmente sulla morfologia delle imputazioni processuali. La tesi trova conferma analizzando il ruolo di alcuni uomini chiave nel contrasto alle due manifestazioni criminali, nel ruolo del pentimento nella disarticolazione delle associazioni e, infine, nell'evoluzione della disciplina della chiamata di correo.

Objective: The reliability of dynamic cerebral autoregulation (dCA) parameters, obtained with transfer function analysis (TFA) of spontaneous fluctuations in arterial blood pressure (BP), require statistically significant values of the coherence function. A new algorithm (COHmax) is proposed to increase values of coherence by means of the automated, selective removal of sub-segments of data. Approach: Healthy subjects were studied at baseline (normocapnia) and during 5% breathing of CO2 (hypercapnia). BP (Finapres), cerebral blood flow velocity (CBFV, transcranial Doppler), end-tidal CO2 (EtCO2, capnography) and heart rate (ECG) were recorded continuously during 5 min in each condition. TFA was performed with sub-segments of data of duration (SEGD) 100 s, 50 s or 25 s and the autoregulation index (ARI) was obtained from the CBFV response to a step change in BP. The area-under-the curve (AUC) was obtained from the receiver-operating characteristic (ROC) curve for the detection of changes in dCA resulting from hypercapnia. Main results: In 120 healthy subjects (69 male, age range 20–77 years), CO2 breathing was effective in changing mean EtCO2 and CBFV (p < 0.001). For SEGD = 100 s, ARI changed from 5.8 ± 1.4 (normocapnia) to 4.0 ± 1.7 (hypercapnia, p < 0.0001), with similar differences for SEGD = 50 s or 25 s. Depending on the value of SEGD, in normocapnia, 15.8% to 18.3% of ARI estimates were rejected due to poor coherence, with corresponding rates of 8.3% to 13.3% in hypercapnia. With increasing coherence, 36.4% to 63.2% of these could be recovered in normocapnia (p < 0.001) and 50.0% to 83.0% in hypercapnia (p < 0.005). For SEGD = 100 s, ROC AUC was not influenced by the algorithm, but it was superior to corresponding values for SEGD = 50 s or 25 s. Significance: COHmax has the potential to improve the yield of TFA estimates of dCA parameters, without introducing a bias or deterioration of their ability to detect impairment of autoregulation. Further studies are needed to assess the behaviour of the algorithm in patients with different cerebrovascular conditions.

Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia.Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70 years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO

Purpose This study aims to critically analyse the Law 9 January 2019, n. 3, on “Measures to fight crimes against the public administration and on the transparency of political parties and movements” (so-called bribe-destroyer law). Design/methodology/approach This paper draws on reports, legal scholarship and other open-source data to examine a legislative innovation for the corruption in Italy in relation to the general guarantees of the trial process and with the controversial paradigm of the national perception index of bribery. Findings The Italian legislative initiative that will be examined is innovative in nature and goes beyond the constitutional and conventional principles on procedural guarantees. The new initiative needs to be integrated into the international and European action against bribery that targets criminal proceeds, and at the same time, be anchored in respect for human rights during the process. Research limitations/implications The new initiative needs to be integrated into the international and European action against bribery that targets criminal proceeds, and at the same time, be anchored in respect for human rights during the process. Practical implications Despite the aggressiveness and lofty proclamations by those who aspire to fight corruption from the highest levels, the goal of rehabilitating Italy from one of the seven “deadly sins” that delay economic growth still seems far off. Social implications In the absence of public ethics, the increase in criminalisation does not seem sufficient on its own to guarantee the containment of the phenomenon. Originality/value This study examines the strengths and weaknesses of the important new law, its compatibility with human rights standards and its relationship to international standards of anti-bribery policies. The aggressive legislation critically relies on the pervasive and persistent lack of perception of corruption as a crime. In the confiscation (and now also reparation) of equivalent that normally addresses assets accumulated in a lawful manner, the periculum is even presumed in re ipsa and the classical aims of caution undergo a total torsion revealing an authoritarian face that takes on the meaning of anticipating further sanctioning contents. Finally, the presence of many levels of sanctioning in relation to the same fact poses serious problems of violation of the ne bis in idem rule.

Background: White matter hyperintensities (WMH) are a common finding in aged individuals affected by carotid artery disease and are a risk factor for first-ever and recurrent stroke. We investigated if white matter damage increases the risk of brain microembolism during carotid artery stenting (CAS), as evaluated by the appearance of new areas of restricted diffusion on diffusion-weighted images (DWI). Methods: We evaluated 47 patients with severe internal carotid artery (ICA) stenosis undergoing CAS, comparing preprocedural clinical, ultrasound and radiological characteristics. WMH volume was computed on FLAIR images before CAS. After CAS, the DWI scan was looked over for areas of restricted diffusion (DWI lesions). A first univariate analysis was adopted to compare groups according to the occurrence of DWI lesions. Then, the variable DWI lesion was modelled by means of a logistic regression model. Results: Seventeen patients developed at least 1 DWI lesion after CAS. Compared with non-DWI, DWI patients were more commonly treated in the left ICA (p = 0.007) and had a more severe WMH damage (p = 0.027). Indeed, the risk of a DWI lesion was higher in left versus right stenosis (OR = 9.0, 95% CI 1.9-42.7, p = 0.005) and increased for each log-unit of WMH lesion load (OR = 7.05, 95% CI 1.07-46.49, p = 0.042). A WMH lesion load of at least 5.25 cm3 had a 50% probability of occurrence of a new DWI lesion. Conclusions: Treated side and preexisting white matter damage are risk conditions for brain microembolism during CAS. This should be taken into account to optimize severe carotid artery disease management.

Objective: Transfer function analysis (TFA) of dynamic cerebral autoregulation (dCA) requires smoothing of spectral estimates using segmentation of the data (SD). Systematic studies are required to elucidate the potential influence of SD on dCA parameters. Approach: Healthy subjects (HS, n = 237) and acute ischaemic stroke patients (AIS, n = 98) were included. Cerebral blood flow velocity (CBFV, transcranial Doppler ultrasound) was recorded supine at rest with continuous arterial blood pressure (BP, Finometer) for a minimum of 5 min. TFA was performed with durations SD = 100, 50 or 25 s and 50% superposition to derive estimates of coherence, gain and phase for the BP–CBFV relationship. The autoregulation index (ARI) was estimated from the CBFV step response. Intrasubject reproducibility was expressed by the intraclass correlation coefficient (ICC). Main results: In HS, the ARI, coherence, gain, and phase (low frequency) were influenced by SD, but in AIS, phase (very low frequency) and ARI were not affected. ICC was excellent (>0.75) for all parameters, for both HS and AIS. For SD = 100 s, ARI was different between HS and AIS (mean ± sdev: 5.70 ± 1.61 vs 5.1 ± 2.0; p < 0.01) and the significance of this difference was maintained for SD = 50 s and 25 s. Using SD = 100 s as reference, the rate of misclassification, based on a threshold of ARI ⩽ 4, was 6.3% for SD = 50 s and 8.1% for SD = 25 s in HS, with corresponding values of 11.7% and 8.2% in AIS patients, respectively. Significance: Further studies are warranted with SD values lower than the recommended standard of SD = 100 s, to explore possibilities of improving the reproducibility, sensitivity and prognostic value of TFA parameters used as metrics of dCA.

Aims An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance. Methods A hundred metabolic syndrome patients without diabetes underwent GST gene polymorphism analysis and a sub-sample 36 patients were randomly selected to investigate the correlation between GST gene polymorphisms and GV, and sympatho-vagal (SV) balance and arterial stiffness. Results GSTM1 showed a significant association with several GV, arterial stiffness, and SV balance indexes. In particular, the GSTM1 deletion positively correlates with lower values of these indexes when compared to the presence of the gene. Conclusions Therefore, we suggested a global influence of GSTM1 deletion on the GV, arterial stiffness, and SV balance pathways in MetS patients, probably also interacting with AMP-activated protein kinase (AMPK) regulation. Our novel findings indicate GSTM1 could be a risk locus in MetS development and shed light novel scenarios on the role of glucose fluctuations in neurological impairments.

Background: Neuromodulation techniques, i.e. repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), can modify cerebral hemodynamics. High frequency rTMS appeared to decrease cerebral vasomotor reactivity (VMR), while there is still poor evidence about the effect of low frequency (LF) rTMS on cerebral blood flow (CBF) and VMR. Hypothesis: The present study aimed to test if LF rTMS decreases CBF and increases cerebral VMR. Monolateral or bilateral hemispheric involvement and duration of the effect were considered. A possible role of autonomic nervous system in CBF and VMR modulation was also investigated. Methods: Twenty-four right-handed healthy subjects underwent randomly real (12) or sham (12) 20-min 1-Hz rTMS on left primary motor cortex. Mean flow velocity and VMR of middle cerebral arteries were evaluated by means of transcranial Doppler before (T0), after 10 min (T1) and after 2 (T2), 5 (T3) and 24 h (T4) from rTMS. Heart rate variability (HRV) was studied within the same timing interval, assessing low frequency/high frequency (LF/HF) ratio as index of autonomic balance. Results: After real rTMS compared with sham stimulation, MFV decreased bilaterally at T1 (F = 3.240, P = .030) while VMR increased bilaterally (F = 5.116, P = .002) for at least 5 h (T3). LF/HF ratio decreased early after real rTMS (F = 2.881, P = .040). Conclusion: 1-Hz rTMS may induce a bilateral long-lasting increase of VMR, while its effect on MFV is short-lasting. Moreover, HRV changes induced by rTMS suggest a possible autonomic nervous system modulation.

Neurovascular coupling (NVC) and dynamic cerebral autoregulation (dCA) are both impaired in the acute phase of ischemic stroke, but their reciprocal interactions are difficult to predict. To clarify these aspects, the present study explored NVC in a healthy volunteer population during a surrogate state of impaired dCA induced by hypercapnia. This study aimed to test whether hypercapnia leads to a depression of NVC through an impairment of dCA. Continuous recordings of middle cerebral arteries cerebral blood flow velocity (CBFv), blood pressure (BP), heart rate, and end-tidal CO2 were performed in 19 right-handed subjects (aged >45 yr) before, during, and after 60 s of a passive paradigm during normocapnia and hypercapnia. The CBFv response was broken down into subcomponents describing the relative contributions of BP (VBP), critical closing pressure (VCrCP), and resistance area product (VRAP). VRAP reflects myogenic activity in response to BP changes, whereas VCrCP is more indicative of metabolic control. The results revealed that hypercapnia significantly affected NVC, with significant reductions in the relative contribution of VCrCP to the paradigm-induced increase in CBFv. The present study suggests that hypercapnia impairs both dCA and NVC, probably acting through an impairment of the metabolic component of CBF control.

The effect of carotid artery stenting (CAS) on cognitive function is still debated. Cerebral microembolism, detectable by post-procedural diffusion-weighted imaging (DWI) lesions, has been suggested to predispose to cognitive decline. Our study aimed at evaluating the effect of CAS on cognitive profile focusing on the potential role of cerebral microembolic lesions, taking into consideration the impact of factors potentially influencing cognitive status (demographic features, vascular risk profile, neuropsychological evaluation at baseline and magnetic resonance (MR) markers of brain structural damage). Thirty-seven patients with severe carotid artery stenosis were enrolled. Neurological assessment, neuropsychological evaluation and brain MR were performed the day before CAS (E0). Brain MR with DWI was repeated the day after CAS (E1), while neuropsychological evaluation was done after a 14-month median period (E2). Volumes of both white matter hyperintensities and whole brain were estimated at E0 on axial MR FLAIR and T1w-SE sequences, respectively. Unadjusted ANOVA analysis showed a significant CAS*DWI interaction for MMSE (F=7.154(32), p=.012). After adjusting for factors potentially influencing cognitive status CAS*DWI interaction was confirmed for MMSE (F=7.092(13), p=.020). Patients with DWI lesions showed a mean E2-E0 MMSE reduction of -3.1, while group without DWI lesions showed a mean E2-E0 MMSE of +1.1. Our study showed that peri-procedural brain microembolic load impacts negatively on cognitive functions, independently from the influence of patients-related variables.

Rare metabolic diseases may sometimes arise acutely and endanger human life if not immediately recognized and treated. Marchiafava Bignami disease is an uncommon neurologic disorder described in alcohol abusers and characterized by an acute severe damage of brain white matter. Even more rarely, it has been reported in non-alcohol addicted patients, but never in vegetarian people. This is a case report of a young vegetarian woman, accustomed to drink high amounts of tea, who, three weeks after her first natural childbirth, developed serious motor and cognitive disturbances. A timely brain magnetic resonance (MR) allowed us to identify Marchiafava Bignami disease and she healed few hours after the administration of parenteral steroids and vitamins. We advise to suspect Marchiafava Bignami Disease in all patients presenting with non-obvious acute generalized motor and cognitive disturbances, also if non alcoholics, and to collect the nutritional habits in all patients with suspected symptoms. In these cases a timely brain MRI is warranted, since brain imaging is typical and patients may recover after a prompt treatment.

Background and Purpose An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer’s disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. Methods Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). Results Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. Conclusions Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains.

Stroke can present, among other signs, with headache. Here, we describe the case of a man suffering from severe orbitary pain and autonomic dysfunction secondary to dorsolateral medullary ischemia. The anatomical relationship between lesion and symptomatology could be an indirect sign of hypothalamospinal tract involvement in the genesis of autonomic dysfunction and headache resembling a trigeminal autonomic cephalalgia.

OBJECTIVE The effect of glycemic variability (GV) on cardiovascular risk has not been fully clarified in type 2 diabetes. We evaluated the effect of GV, blood pressure (BP), and oxidative stress on intima-media thickness (IMT), left ventricular mass index (LVMI), flow-mediated dilation (FMD), and sympathovagal balance (low frequency [LF]/high frequency [HF] ratio) in 26 type 2 diabetic patients (diabetes duration 4.41 ± 4.81 years; HbA1c 6.70 ± 1.25%) receiving diet and/or metformin treatment, with no hypotensive treatment or complications. RESEARCH DESIGN AND METHODS Continuous glucose monitoring (CGM) data were used to calculate mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA)-2, mean blood glucose (MBG), mean postprandial glucose excursion (MPPGE), and incremental area under the curve (IAUC). Blood pressure (BP), circadian rhythm, and urinary 15-F2t-isoprostane (8-iso-prostaglandin F2α [PGF2α]) were also evaluated. Subjects were divided into dipper (D) and nondipper (ND) groups according to ΔBP. RESULTS IMT and LVMI were increased in ND versus D (0.77 ± 0.08 vs. 0.68 ± 0.13 [P = 0.04] and 67 ± 14 vs. 55 ± 11 [P = 0.03], respectively). MBG, MAGE, and IAUC were significantly associated with LF/HF ratio at night (r = 0.50, P = 0.01; r = 0.40, P = 0.04; r = 0.41, P = 0.04, respectively), MPPGE was negatively associated with FMD (r = −0.45, P = 0.02), and CONGA-2 was positively associated with LVMI (r = 0.55, P = 0.006). The Δsystolic BP was negatively associated with IMT (r = −0.43, P = 0.03) and with LVMI (r = −0.52, P = 0.01). Urinary 8-iso-PGF2α was positively associated with LVMI (r = 0.68 P < 0.001). CONCLUSIONS An impaired GV and BP variability is associated with endothelial and cardiovascular damage in short-term diabetic patients with optimal metabolic control. Oxidative stress is the only independent predictor of increased LV mass and correlates with glucose and BP variability.

Background: Over time, exposure to cerebrovascular risk factors and carotid artery disease may cause multiple asymptomatic brain cortical and subcortical microinfarcts, which are commonly found at brain autopsy. So far, lack of convenient neuroimaging tools limited the investigation of grey matter ischemic damage in vivo. We applied the Double Inversion Recovery (DIR) sequence to explore the impact of carotid artery disease on intracortical ischemic lesion load in vivo, taking into account the impact of demographic characteristics and vascular risk factors. Methods: DIR was acquired in 62 patients with common cerebrovascular risk factors stratified in three groups according to carotid artery disease severity. Intracortical lesions scored on DIR (DIRlns) were classified by vascular territory, lobe and hemisphere. White matter hyperintensities (WMHs) volume was also quantified on Fluid Attenuated Inversion Recovery sequence (FLAIR). Results: Among demographic characteristics and cerebrovascular risk variables explored, General Linear Model indicated that age and carotid artery disease were significantly associated to DIRlns. After correcting for age, DIRlns load was found to be significantly dependent on carotid artery stenosis severity (F(2, 58) = 5.56, p = 0.006). A linear positive correlation between DIRlns and WMHs was found after correcting for age (p = 0.003). Conclusions: Carotid disease severity is associated with DIRlns accrual. Microembolism and impaired cerebral hemodynamics may act as physiopathological mechanisms underlying cortical ischemic damage. The role of other factors, such as small vessel disease and the possible interaction with carotid disease, remains to be further explored.

Essential tremor (ET) is the most common movement disorder, with a prevalence of 4% in patients aged >65 years. Alchol sensitivity is a secondary criteria for ET diagnosis. A discordance between patient’s perceived disability and real disability could be observed in real world, so requiring a most objective diagnostic tool to measure reproducible parameters. Neurophysiological tremor study (NTS) may be useful to this aim. NTS has been conducted by an accelerometer, placed in the distal extremity of the more involved upper limb, which measures the amplitude and the frequency of the tremor, at rest, during posture maintenance and voluntary movement. We performed NTS before and after alchol test. The amount of alchol to be dispensed to each patient is calculated by Widmark formula, in order to obtain an alcholemia within a range of 0.6–0.7 mg/dl. Five patients affected by ET have been registered. A significant (>50%) decrease of tremor’s amplitude has been observed, while a less evident effect on tremor’s frequency has been found. Alchol responsivness of neurophysiological registration parameters may be an adjunctive method to objectively quantify clinical improvement, and, according to our experience, to predict therapy responsiveness.

PaCO2 affects cerebral blood flow (CBF) and its regulatory mechanisms, but the interaction between neurovascular coupling (NVC), cerebral autoregulation (CA), and cerebrovascular reactivity to CO2 (CVR), in response to hypercapnia, is not known. Recordings of cerebral blood flow velocity (CBFv), blood pressure (BP), heart rate, and end‐tidal CO2 (EtCO2) were performed in 18 subjects during normocapnia and 5% CO2 inhalation while performing a passive motor paradigm. Together with BP and EtCO2, a gate signal to represent the effect of stimulation was used as input to a multivariate autoregressive‐moving average model to calculate their separate effects on CBFv. Hypercapnia led to a depression of dynamic CA at rest and during stimulation in both hemispheres (P, The influence of hypercapnia on dynamic cerebral autoregulation (CA), CO2 vasoreactivity (CVR), and neurovascular coupling (NVC) was described based on a single recording during motor stimulation coupled to a new multivariate modeling approach. Hypercapnia led to a depression of CA at rest and during stimulation in both hemispheres as well as impairment of the NVC response. Neither hypercapnia nor the passive motor stimulation influenced CVR. Dynamic CA was not influenced by the motor paradigm during normocapnia. The stability of CVR during these maneuvers and the lack of influence of stimulation on dynamic CA are novel findings which deserve further investigation.

PD EIO could mark a turning point in the development of “European criminal procedure.” The Proposal will obtain evidence in cross-border cases and is particularly suitable for investigations on the subject of international organized crime. From the long gestation period and the contents of the Proposal emerges, however, the difficulty of making a balance between the investigation of crimes and the guarantees of the individuals involved. The use of collected of evidence from different legal systems is often an overly neglected aspect. Doubt surrounds the regulation of banking instruments, the rules on wiretapping, and all provisions for undercover investigations.

Objective Cerebral vasomotor reactivity (VMR) and coherence of resting state electroencephalographic (EEG) rhythms are impaired in Alzheimer's disease (AD) patients. Here we tested the hypothesis that these two variables could be related. Methods We investigated VMR and coherence of resting state EEG rhythms in nine normal elderly (Nold) and in 10 amnesic mild cognitive impairment (MCI) subjects. Resting state eyes-closed EEG data were recorded at baseline pre-CO 2 (ambient air, 2min), during 7% CO 2 /air mixture inhalation (hypercapnia, 90s) and post-CO 2 (ambient air, 2min) conditions. Simultaneous frontal bilateral near-infrared spectroscopy (NIRS) was performed to assess VMR by cortical oxy- and deoxy-haemoglobin concentration changes. EEG coherence across all electrodes was computed at delta (2–4Hz), theta (4–8Hz), alpha 1 (8–10.5Hz), alpha 2 (10.5–13Hz), beta 1 (13–20Hz), beta 2 (20–30Hz) and gamma (30–40Hz) bands. Results In Nold subjects, ‘total coherence' of EEG across all frequency bands and electrode pairs decreased during hypercapnia, with full recovery during post-CO 2 . Total coherence resulted lower in pre-CO 2 and post-CO 2 and presented poor reactivity during CO 2 inhalation in MCI patients compared with Nold subjects. Hypercapnia increased oxy-haemoglobin and decreased deoxy-haemoglobin concentrations in both groups. Furthermore, the extent of changes in these variables during CO 2 challenge was correlated with the EEG coherence, as a reflection of neurovascular coupling. Conclusions Hypercapnia induced normal frontal VMR that was detected by NIRS in both Nold and amnesic MCI groups, while it produced a reactivity of global functional coupling of resting state EEG rhythms only in the Nold group. Significance In amnesic MCI patients, global EEG functional coupling is basically low in amplitude and does not react to hypercapnia.

Regulatory interventions and the application of lessons from outcomes together with the renewed value of human rights in criminal proceedings demonstrate that the fight against organized crime at the European level requires constant attention to the balance between individual rights on the one hand and the need for an effective investigation on the other.

Cerebral vasomotor reactivity (CVR) represents the capability of cerebral vessels to modify their caliber in response to a stimulus. Impaired CVR is associated with an increased risk for ischemic events in patients with carotid disease. Endothelial dysfunction is considered an important pathogenic factor for atherosclerosis and can be noninvasively assessed by flow-mediated vasodilation (FMD) evaluation. We aimed to evaluate both CVR and FMD in patients without histories of vascular disease in order to define a possible correlation. FMD was measured as brachial artery flow and diameter changes induced by transient ischemia. CVR to hypercapnia was assessed in all subjects by means of a breath-holding test and, in 20 subjects, by an additional CO(2) inhalation test. In 30 healthy volunteers (60% women, mean age 56 ± 6 years), CVR and FMD did not appear to be correlated (p = 0.444). A strong association between CO(2)-induced CVR and breath-holding index was observed (p < 0.001). CVR and FMD represent 2 different modalities that evaluate vasomotor function. According to our data, they did not appear to correlate, probably due to physiologic differences between cerebral and peripheral vascular districts and the vasodilatory stimulus used. The carbon dioxide-induced CVR and breath-holding index appeared to be significantly associated.

Background and Purpose— Cerebral vasomotor reactivity (VMR) is a capability of cerebral vessels to dilate in response to hypercapnia. Transcranial direct current stimulation (tDCS) effects on cerebral hemodynamics have been poorly studied. Methods and Results— Ten healthy subjects underwent anodal/cathodal tDCS on the left motor cortex. Before and after tDCS, VMR assessment by transcranial Doppler and an electrocardiogram were performed. Normalized low-frequency band power of heart rate variability and its reactivity from basal to VMR condition (LFN react ) were estimated as relative markers of sympathetic activation. tDCS exerted a polarity-specific effect on both VMR ( P =0.0001) and LFN react ( P =0.001). Anodal tDCS decreased VMR by 3.4%/mm Hg CO 2 bilaterally and increased LFN react , whereas cathodal tDCS increased VMR by 0.8%/mm Hg CO 2 bilaterally and reduced LFN react . Conclusions— Cerebral VMR is modified by tDCS. Based on the consensual changes with heart rate variability, we can hypothesize that the sympathetic nervous system could modulate the bihemispheric modification of VMR. Further studies are needed to confirm this hypothesis.

Objective Repetitive Transcranial Magnetic Stimulation (rTMS) has been recently employed as a therapeutic strategy for stroke, although its effects on cerebral hemodynamics has been poorly investigated. This study aims to examine the impact of high frequency rTMS on cerebral vasomotor reactivity (VMR). Methods Twenty-nine healthy subjects were randomly assigned to real (19) or sham 17-Hz rTMS, applied on primary motor cortex (M1) of the dominant hemisphere. All subjects underwent Transcranial Doppler of the middle cerebral arteries to evaluate mean flow velocity and VMR before ( T 0 ) and within 10min ( T 1 ) following rTMS. Four subjects underwent further VMR evaluations at 2 ( T 2 ), 5 ( T 3 ) and 24h ( T 4 ) after rTMS. As a control condition, 10 subjects underwent real (5) or sham rTMS on calcarine cortex. In addition, five acute stroke patients underwent five daily rTMS sessions on the affected hemisphere mimicking a therapeutic trial. Results Following real rTMS on M1 ( p =0.002) and calcarine cortex ( p T 0 in both hemispheres, while no change was observed after sham rTMS ( p >0.6). VMR tended to remain lower than T 0 until T 3. Cerebral VMR decreased independently of the stimulated side also in the patients' group. Conclusions High frequency rTMS reduces cerebral VMR, possibly as a secondary effect on autonomic control of cerebral hemodynamics. Significance The effect of rTMS on cerebral hemodynamics should be carefully considered before proceeding toward a therapeutic application in stroke patients.

to the editor: We are grateful to Dr. Willie ([6][1]) for his letter, which is a welcome contribution to the debate on the complex interaction between cerebrovascular regulatory mechanisms, namely neurovascular coupling (NVC), cerebral autoregulation (CA), and CO2 vasoreactivity (CO2-VR). A