Whole-Brain Propagation Delays in Multiple Sclerosis, a Combined Tractography-Magnetoencephalography Study.

Two structurally connected brain regions are more likely to interact, with the lengths of the structural bundles, their widths, myelination, and the topology of the structural connectome influencing the timing of the interactions. We introduce an in vivo approach for measuring functional delays across the whole brain in humans (of either sex) using magneto/electroencephalography (MEG/EEG) and integrating them with the structural bundles. The resulting topochronic map of the functional delays/velocities shows that larger bundles have faster velocities. We estimated the topochronic map in multiple sclerosis patients, who have damaged myelin sheaths, and controls, demonstrating greater delays in patients across the network and that structurally lesioned tracts were slowed down more than unaffected ones. We provide a novel framework for estimating functional transmission delays in vivo at the single-subject and single-tract level.SIGNIFICANCE STATEMENT This article provides a straightforward way to estimate patient-specific delays and conduction velocities in the CNS, at the individual level, in healthy and diseased subjects. To do so, it uses a principled way to merge magnetoencephalography (MEG)/electroencephalography (EEG) and tractography.

Visuospatial working memory abilities in children analyzed by the bricks game task (BGT).

The study of the development of visuospatial memory processes is useful for devising personalized educational interventions as well as for understanding the changes in cognitive functioning in an era characterized by technological progress. The present research is aimed at investigating spatial working memory ability in children that attended the first three years of primary school by means of the Brick Game Task (BGT), a novel visuospatial working memory test. BGT is a small-scale ecological test inspired by behavioral walking tasks with nine white bricks in different spatial configurations as well as to Corsi Block-Tapping test.228 Italian children (121 F; mean age: 7.22 ± 1.18) were assigned to three groups based on the primary school class attended: Group 1 (N = 85; 40 F; mean age 6.18 ± .5), Group 2 (N = 61; 36 F; mean age 7.2 ± .83), and Group 3 (N = 82; 44 F; mean age 8.32 ± .94). All participants were asked to complete the Digit Span test, the Corsi Block-Tapping test, and to explore the three spatial configurations of the BGT with the form of Matrix, M-BGT, Cluster, CL-BGT, Cross, CR-BGT.MANOVA revealed a main significant effect for Group (F12,434 = 15.06; p < .0001) indicating that the group of older obtained a better global executive performance than 1 and 2 groups. Multiple linear regression indicated that Corsi Block-Tapping test performance and Age significantly predicted the M-BGT score. Moreover, Corsi Block-Tapping test and Digit Span significantly predicted the CL-BGT performance, showing how a higher score results in a better CL- BGT performance. Finally, Corsi Block-Tapping test, Digit Span, and Age were positively associated with the CR- BGT performance. The present findings evidenced that novel BGT is a sensible visuospatial working memory task suggesting thus its use to assess the children's executive performance in ecological way. These results open to the development of personalized educational interventions.

"The influence of auditory stimulation on whole body variability in healthy older adults during gait".

Acoustic stimulation appears to be a promising strategy in reducing the risk of falling in older adults, demonstrating effectiveness in improving stability. However, its impact on movement variability, another crucial indicator of fall risk, seems to be limited. This study aims to assess movement variability during walking in a cohort of healthy older adults exposed to three different frequencies of acoustic stimulation (90%, 100% and 110% of each subject's average cadence). Using a systemic approach based on network theory, which considers the intricate relationships between all body segments, we constructed connectivity matrices composed of nodes, represented by bony landmarks, and edges, consisting of the standardised covariance of accelerations between each pair of nodes. By introducing a new metric called Similarity Score (S-score), we quantified the ability of each individual to repeat the same motor pattern at each gait cycle under different experimental conditions. The study revealed that rhythmic auditory stimulation (RAS) at 100% and 90% of the mean cadence significantly increased the S-scores compared to the baseline. These results highlight the effects of RAS in increasing gait repeatability in healthy older adults, with a focus on global kinematics.

The virtual multiple sclerosis patient.

Multiple sclerosis (MS) diagnosis typically involves assessing clinical symptoms, MRI findings, and ruling out alternative explanations. While myelin damage broadly affects conduction speeds, traditional tests focus on specific white-matter tracts, which may not reflect overall impairment accurately. In this study, we integrate diffusion tensor immaging (DTI) and magnetoencephalography (MEG) data into individualized virtual brain models to estimate conduction velocities for MS patients and controls. Using Bayesian inference, we demonstrated a causal link between empirical spectral changes and inferred slower conduction velocities in patients. Remarkably, these velocities proved superior predictors of clinical disability compared to structural damage. Our findings underscore a nuanced relationship between conduction delays and large-scale brain dynamics, suggesting that individualized velocity alterations at the whole-brain level contribute causatively to clinical outcomes in MS.

Dynamical interactions reconfigure the gradient of cortical timescales.

The functional organization of the brain is usually presented with a back-to-front gradient of timescales, reflecting regional specialization with sensory areas (back) processing information faster than associative areas (front), which perform information integration. However, cognitive processes require not only local information processing but also coordinated activity across regions. Using magnetoencephalography recordings, we find that the functional connectivity at the edge level (between two regions) is also characterized by a back-to-front gradient of timescales following that of the regional gradient. Unexpectedly, we demonstrate a reverse front-to-back gradient when nonlocal interactions are prominent. Thus, the timescales are dynamic and can switch between back-to-front and front-to-back patterns.

Frontal Behavioural Inventory in the differential diagnosis of dementia.

OBJECTIVE: To evaluate diagnostic properties of the Frontal Behavioural Inventory (FBI) in patients suffering from different forms of dementia. METHODS: The FBI was administered with other psychometric tests investigating cognitive performances and behavioral scales to the caregivers of 35 patients with the frontal variant of frontotemporal dementia (fv-FTD), 22 patients with Alzheimer's disease (AD) and 15 with vascular dementia (VaD). All patients were comparable for degree of dementia severity and level of executive impairment. RESULTS: The FBI showed high concurrent validity, internal consistency and good inter-rater and test-retest reliability. The discriminant validity was also very high. A new FBI cut-off score of 23 gave 97% sensitivity and 95% specificity in distinguishing fv-FTD from non-FTD patients. Conversely, the Neuropsychiatic Inventory (NPI) score was unable to differentiate fv-FTD from AD. CONCLUSIONS: The FBI is a neurobehavioral tool suitable to distinguish fv-FTD from other forms of dementia also when data from cognitive testing or other behavioral scales fail to support the differential diagnosis.

Influence of age and menopausal status on pathologic and biologic features of breast cancer.

The distribution of the main prognostic factors in different age groups was evaluated in 1226 patients operated on for primary breast cancer, in order to identify those influenced by age and/or menopausal status. Patients were divided into the following groups: 1) 40 years of age and under; 2) premenopausal over 40 years of age; 3) postmenopausal under 75 years of age and 4) 75 years of age and over. Our findings showed that the youngest patients had the worst prognostic pattern, which improves as age increases and is the best in patients over 75 years of age. Some of the parameters investigated (tumour size, histologic and nuclear grade, tumour infiltrating lymphocytes, p53 and Ki 67) were found to be influenced by age, some (necrosis and oestrogen receptors) were influenced by menopausal status and/or age, some (vascular invasion, ploidy, S-phase and progesterone receptors) showed significant differences in different age groups but there was no consistent relation with patient age or menopausal status, and others (node status, ErbB2/Neu and Cathepsin D) were not influenced by age or menopause.

Clinical presentation and prevalence of spontaneous bacterial peritonitis in patients with cryptogenic cirrhosis and features of metabolic syndrome.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis. The prevalence and clinical relevance that spontaneous bacterial peritonitis may have in complicating ascites due to NASH-related cirrhosis have yet to be defined. METHODS: Among 611 cases of cirrhosis-associated ascites, 45 patients with cryptogenic cirrhosis were retrospectively identified. Of these, 36 patients and a control group of subjects with viral- associated ascites were followed up and compared in a case control study. Information on the onset of ascites, with or without spontaneous bacterial peritonitis, history of risk factors for multimetabolic syndrome, and serological and ascitic laboratory data were compared between groups. RESULTS: Spontaneous bacterial peritonitis occurred significantly more often in patients with cryptogenic cirrhosis than in equally symptomatic viral controls. The prevalence of obesity, diabetes and spontaneous bacterial peritonitis was significantly higher in patients with cryptogenic cirrhosis. Although liver function was similar in both groups, cryptogenic cirrhosis patients had lower aminotransferase levels. Multivariate analysis identified diabetes, juvenile obesity and spontaneous bacterial peritonitis as independent factors associated with ascites due to cryptogenic cirrhosis. CONCLUSIONS: Features suggestive of NASH are more frequently observed in patients with ascites and cryptogenic cirrhosis than in age- and sex-matched ascitic patients with well-defined viral etiology. Ascites may be a presenting symptom of NASH-related cirrhosis, and affected patients have a twofold greater risk of spontaneous bacterial peritonitis.

Outpatient surgery of varices of the lower limbs: experience of 2,568 cases at four universities.

Outpatient surgery of varices of the lower limbs is currently considered a viable alternative to traditional surgery with hospitalization. This paper reports the experience of 4 university groups (Padua, Modena, Verona, Milan), where outpatient treatment has been used since 1987. From June 1987 to June 1992, 2,568 lower limb varices were treated in this way. Different techniques of anaesthesia were used (local infiltration, combined local and general, general, subarachnoid). In all cases, crossectomy was combined with short or long saphenous stripping. There were no intra- or perioperative deaths, and only limited morbidity. Postoperative hospitalization was required in only 2 cases: for hemorrhaging of the inguinal wound in one case, and headache 2 days after spinal anaesthesia in the other. In 2 separate samples of 100 patients, 88 and 89 indicated satisfaction with the surgical treatment. In conclusion, outpatient surgery of varices can be based on the same techniques as in-patients treatment. The risks of surgery and anaesthesia in specialised centres are very limited, with scope for a variety of anaesthetic techniques according to facilities available. Patients satisfaction is high.

Steady state pharmacokinetics of idebenone in patients with moderate hepatic impairment.

The kinetics of idebenone (45 mg twice daily p.o.) in 6 Caucasian chronic hepatopathic patients without portal hypertension were studied. The pharmacokinetic parameters were evaluated both for single (day 1) and multiple (day 10) administrations. These 6 patients showed a first order bi-compartimental kinetic curve for idebenone and for its metabolites, superimposable on the curves obtained from healthy volunteers. The C(max) parameters, tmax and bioavailability confirm the absence of accumulation. On day 12, 48 h after the last administration (performed on day 10), there was no evidence of residual drug. One of these patients was being treated with diuretics (chlorthalidone) and with perfusion fluids, including 5% glucose, and no interference was shown between the two drugs. There is no evidence of any particular side effect or alteration of the haematochemical parameters that could be thought to be drug related. This study confirms that idebenone at the dose of 90 mg/day p.o. administered to hepatopathic patients does not cause accumulation or toxicity.

Steady-state pharmacokinetics of idebenone in patients with moderate renal impairment.

Idebenone (45 mg twice daily) was administered to 7 patients with moderate renal impairment (creatinine clearance 21-40 ml/min) for 10 days. Standard pharmacokinetic parameters were computed on day 1 (single administration) and on day 10. On day 1 the mean of the maximum plasma concentration values (C(max)) was 364 ng/ml (standard deviation (S.D.) 100); time to C(max) (t(max)) was in the range of 1-2 h for 6 patients and 12 h for the remaining patient: the mean was 3 h (S.D. 3.99); the mean area under the plasma concentration vs. time curve (AUC) was 3005 ng h/ml (S.D. 1152). On day 10 the mean C(max) was 531 ng/ml (S.D. 355.3), the mean t(max) was 0.07 h (S.D. 0.19), the mean AUC was 3167 ng/ml (S.D. 2944) and the mean elimination half-life (t(1/2)) was 4.9 h (S.D. 1.1). Idebenone metabolites (QS-4, QS-6 and QS-10) showed a kinetic profile similar to the parent compound, with pharmacokinetic parameters comparable to idebenone for QS-4 and lower than idebenone for QS-6 and QS-10. Idebenone was metabolized and easily excreted and no accumulation was observed for the compound and its metabolites. No significant modification of the biohumoral indexes and vital signs and no adverse reactions were observed.

[Presentation of a new instrument for the prolonged monitoring (24 hrs.) of endoesophageal pH, based on microprocessor technologies]. / Presentazione di un nuovo strumento per il monitoraggio prolungato (24 ore) del pH endoesofageo, basato su tecnologie a microprocessori.

Prolonged monitoring of oesophageal pH is the most sensitive test for GOR. An ideal instrument for this test should be simple, reliable and inexpensive. It should enable the patient to live a normal life, even at home, allows rapid analysis of the data, and monitors other parameters at the same time (intragastric pH). An instrument with these features has been devised at Padua University Surgical Clinic. It uses NSC 800 microprocessor technology and has a 32 K C-MOS memory. The examination can be programmed (patient code, date, start and end times, sampling duration and time). Postural changes are automatically recorded. Subjective symptoms are signalled by the patient through an alphanumeric keyboard. ROM software at the end of the test is employed for automatic processing according to Johnson and De Meester's parameters. Proxima is also made for a serial output to a larger-capacity computer and an analogue output compatible with a Beckman paper printer.

[Epidemiologic findings in esophageal cancer in the Veneto region]. / Rilievi epidemiologici sul cancro esofageo nella Regione Veneto.

The results of an epidemiological study using the case-control method on 150 oesophageal cancer cases, observed at the IIIrd Surgical Department in Padua and on 150 controls are presented. The results show that alcohol an maize flour (corn meal) are two aetiopathogenetic factors of verified statistical significance in oesophageal carcinoma in the Veneto population. This confirms other studies among populations with a high risk of oesophageal cancer.

[Echo-sclerotherapy in the management of varices of the lower extremities]. / La sclerosi ecoguidata nel trattamento delle varici degli arti inferiori.

Sclerotherapy has been used with satisfactory results, for several years in the treatment of varicose veins. Nevertheless sometimes sclerosis can be incomplete because of the morphology of lower limbs or because the varicose disease is not clinically evident. In addition, sclerotherapy can give rise to severe complications due to intrarterial or extraluminal injections. In order to exceed this limits, some authors suggested to use a new technique, the echosclerotherapy, which was presented for the first time in Strasburg 1989 by Knight and Vin. Echosclerotherapy is a good help for traditional sclerotherapy, especially when it is applied in the sclerosis of the short saphenous veins, of perforating veins or in unfavourable anatomical situations. From May to November 1993 at the Second Surgical Department of Padua University, 31 patients, 29 women and 3 men, have been treated by echosclerotherapy. 25 patients had great saphenous varicose veins; 3 patients had varices due to perforating veins of the popliteal fossa and 3 patients varices due to Hunter perforating veins. In 48.4% of cases we obtained a complete sclerosis of the vessel; in 38.7% a stump remained near the sapheno-femoral junction of about two centimeters; in one case the treatment was not completed and in one case remained a stump of ten centimeters. Only in two cases Echosclerotherapy was not able to obtain sclerosis. None of the patients had major complications and nobody had deep vein thrombosis. If we consider our results altogether we can say that in 87% of cases we had good results.(ABSTRACT TRUNCATED AT 250 WORDS)

[Blood tumor markers in patients with lung cancer]. / Marcatori tumorali sierici in pazienti con cancro del polmone.

Over the past years, a number of serum components have been confirmed as useful biological markers of lung cancer. Although none have been sensitive or specific enough to enable early diagnosis, they do seem to facilitate the monitoring and prediction of disease prognosis. We studied tumor markers in 66 patients with lung cancer: serum levels of ferritin, carcinoembryonic antigen (CEA), alpha-fetoprotein (alpha-FP); tissue polypeptide antigen (TPA), cytocheratin fragment 19, 21-1 (CYFRA 21-1) and carbohydrate antigen 125 (CA 125) levels were measured and correlated to tumor stage and histological type. Postulating a specificity of 95% versus benign diseases of the lung, we confirmed the following diagnostic sensitivity for the markers: ferritin = 39.3%; CEA = 42.4%; alpha-FP = 5.1%; TPA = 57.5%; CYFRA 21-1 = 65.1%; CA 125 = 46.9%. CYFRA 21-1 showed significantly higher sensitivity in non small cell lung cancer patients than in those with small cell lung cancer (Wilcoxon, p = 0.02). Moreover since survival time was significantly shorter in patients with high serum CYFRA 21-1, these levels seemed to be correlated with the prognosis.

[How to prevent saphenous nerve injury. A personal modified technique for the stripping of the long saphenous vein]. / Come prevenire le lesioni del nervo safeno. Una tecnica personale modificata per lo stripping della grande safena.

BACKGROUND: In literature the incidence of paresthesia caused by long stripping (LS) of the saphenous vein (SV) varies widely. Best results have been reported with the invagination technique by Van Der Stricht. However, this technique is associated with a high incidence of vein rupture and incomplete stripping. The aim of this study is to test a personal technique to avoid the SV rupture and to reduce the incidence of saphenous nerve injury. METHODS: Sixty-eight patients underwent LS of the SV from groin to ankle under monolateral spinal anesthesia on a one-day surgery basis using a personal technique combining external and invaginated saphenous stripping. All patients underwent a clinical re-evalutation 1, 3, 6, 12, 24 and 48 months after the operation. RESULTS: No intraoperative complications were recorded. Stripping of the long saphenous vein was complete in all cases without any rupture of the veins. Only one postoperative hematoma of the leg (1.5%) which was naturally reabsorbed, was recorded; four patients (5.9%) had transitory saphenous nerve injury. Permanent saphenous nerve damage was found in only one of 68 patients (1.5%). All the patients were discharged on the day of operation and we did not register any prolonged hospitalization. CONCLUSIONS: The result of our approach was a very low postoperative complication rate (1.5% of permanent neurological damage) without any rupture of the vein.

[Use of a latissimus dorsi myocutaneous flap in locally advanced breast cancer]. / L'uso del lembo miocutaneo di gran dorsale nel carcinoma mammario localmente avanzato.

Locally advanced breast cancer has a poor prognosis. Skin infiltration, ulceration and invasion of the chest wall, in the absence of distant metastases, worsen dramatically the quality of life. The Authors report 4 cases of one time wide resection and reconstruction using a pedicled myocutaneous flap of latissimus dorsi. This technique allowed good and rapid palliation of local symptoms.

Role of cytosolic calcium-dependent phospholipase A2 in Alzheimer's disease pathogenesis.

Phospholipases (PLA2s) are a superfamily of enzymes characterized by the ability to specifically hydrolyze the sn-2 ester bond of phospholipids generating arachidonic acid, utilized in inflammatory responses, and lysophospholipids involved in the control of cell membrane remodeling and fluidity. PLA2s have been so far considered a crucial element in the etiopathogenesis of several neurological diseases such as cerebral ischemia, multiple sclerosis, Parkinson's disease, and Alzheimer's disease (AD). In AD, the role of beta-amyloid (Aß) fragments is well established although still more elusive are the molecular events of the cascade that from the Aß accumulation leads to neurodegeneration with its clinical manifestations. However, it is well known that inflammation and alteration of lipid metabolism are common features of AD brains. Findings obtained from in vitro studies, animal models, and human brain imaging analysis point towards cPLA2 as a key molecule in the onset and maintenance of the neurodegenerative mechanism(s) of AD. In this review, we have focused on the molecular and biological evidence of the involvement of cPLA2s in the pathogenesis of AD. An insight into the molecular mechanism(s) underlying the action and the regulation of cPLA2 is of tremendous interest in the pharmaceutical and biotechnology industry in developing selective and potent inhibitors able to modulate the onset and/or the outcome of AD.