Adding dynamics to the Human Connectome Project with MEG.

The Human Connectome Project (HCP) seeks to map the structural and functional connections between network elements in the human brain. Magnetoencephalography (MEG) provides a temporally rich source of information on brain network dynamics and represents one source of functional connectivity data to be provided by the HCP. High quality MEG data will be collected from 50 twin pairs both in the resting state and during performance of motor, working memory and language tasks. These data will be available to the general community. Additionally, using the cortical parcellation scheme common to all imaging modalities, the HCP will provide processing pipelines for calculating connection matrices as a function of time and frequency. Together with structural and functional data generated using magnetic resonance imaging methods, these data represent a unique opportunity to investigate brain network connectivity in a large cohort of normal adult human subjects. The analysis pipeline software and the dynamic connectivity matrices that it generates will all be made freely available to the research community.

Intestinal perforation after surgical treatment for incisional hernia: iatrogenic or idiopathic?

Intestinal perforation (IP) is a life-threatening gastroenterological condition requiring urgent surgical care, which may present itself as an uncommon complication following incisional hernia repair surgery, most often because of iatrogenic traumatism occurring during the procedure. However, we report a case where a spontaneous onset can be hypothesised. A 60-years-old patient underwent repair of an abdominal laparocele, through rectus abdominis muscle plasty, 5 years after development of an incisional hernia due to exploratory laparotomy for the treatment of acute appendicitis. Xipho-pubic scar was excised and umbilicus and supra-umbilical hernia sac dissected, a linear median incision was performed along the sub-umbilical linea alba, reaching preperitoneal plane to assess any intestinal loop adherence to the abdominal wall. After limited viscerolysis, abdominal wall defect was corrected by 'rectus abdominis muscle plasty' and umbilicus reconstruction by Santanelli technique. Postoperative course was uneventful until Day 29, with sudden onset of epigastric pain, fever and bulge. Sixty cubic centimeter pus was drained percutaneously and cavity was rinsed with a 50% H2O2 and H2O V-V solution until draining clear fluid. Symptoms recurred two days later, while during rinsing presented dyspnoea. X-Ray and CT scan diagnosed IP, and she underwent under emergency an exploratory laparotomy, leading to right hemicolectomy extended to last ileal loops and middle third of the transverse, right monolateral salpingo-ovariectomy and a temporary ileostomy by general surgeon. Twenty-three days later an ileostomy reversal surgery was performed and 8 days after she was discharged. At latest follow-up patient showed fair conditions, complaining abdominal pain and diarrhoea, attributable to the extensive intestinal resection. IP following incisional hernia repair, is reported as uncommon and early postoperative complication. In our case, the previous regular postoperative course with late onset lead us to hypothesise a possible idiopathic etiopathogenesis, because of a strangulation followed by gangrene and abscess formation, which might begin before the incisional hernia repair and unnoticed at the time surgery was performed.

Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.

Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.

Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

VRAM-pedicled island flap for the coverage of an exposed prosthetic vascular graft in the suprapubic area.

The exposure of prosthetic vascular graft is a dangerous complication in revascularization procedures. In this case report, we describe a successful coverage of an exposed prosthetic femorofemoral vascular graft in the suprapubic area, with a vertical rectus abdominis myocutaneous (VRAM) island flap.

A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis.

BACKGROUND AND PURPOSE: Endothelium-derived NO is formed from L-arginine by endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because several studies have indicated that NO plays a key role in the development of the atherosclerotic process, we investigated whether common variants in the eNOS gene are associated with an increased risk of plaque on carotid arteries. METHODS: We studied 375 subjects attending the hypertension center of our institution to be screened for arterial hypertension. The examined subjects were classified according to the presence of carotid plaques (intima-media thickness >/=1.5 mm), and 2 intronic (CA and 27-bp repeats) polymorphisms and 1 exonic (Glu298Asp) polymorphism of the eNOS gene were explored. RESULTS: Only the Glu298Asp polymorphism of eNOS was associated with the presence of carotid plaques (P:<0.05). In particular, there was an excess of homozygotes for the Asp298 variant among subjects with carotid plaques, whereas the number of subjects who had the Glu298 allele in exon 7 of the eNOS gene was equally distributed in both study groups. Interestingly, the risk of having carotid plaques was increased approximately 3 times in subjects who were homozygotic for the Asp298 variant compared with subjects who were homozygotic for the Glu298 variant and was independent of the other common risk factors (age, blood pressure, and smoking). CONCLUSIONS: Homozygosity for Asp298, a common variant of the eNOS gene, is an independent risk factor for carotid atherosclerosis in this study population.

Opposite effects of L-arginine and nitroglycerin on cerebral blood velocity: nitric oxide precursors and cerebral blood velocity.

Nitric oxide (NO), a gaseous molecule synthesized in the arteriolar endothelium from the amino acid L-arginine (L-arg), has been identified as the previously described Endothelium-Derived Relaxing Factor (EDRF): nitroderivatives such as nitroglycerin are known to induce vasodilation via NO release. The aim of this study was to evaluate by Transcranial Doppler (TCD) monitoring any changes in cerebral hemodynamics induced by both the infusion of L-arg and the sublingual administration of nitroglycerin in 20 healthy subjects. L-arg infusion induced a significant increase in blood velocity compared to the baseline value (mean +/- S.D. percent change = 18 +/- 8.71; p<0.0001 ) and a slight but significant decrease in Pulsatility Index. By contrast, nitroglycerin was able to cause a significant decrease in blood velocity (mean +/- S.D. percent change = 24.8 +/- 7.68; p<0.0001), while leaving Pulsatility Index unchanged. These data suggest that L-arg and nitroglycerin, both hypothesized to use NO as the final product at the vascular level, result in opposite blood velocity patterns within the cerebral circulation. This may be due to the particular type of artery and/or to the local endothelial environment whereby the released NO may act.

Raman characterization of single-walled nanotubes of various diameters obtained by catalytic disproportionation of CO.

Single-walled carbon nanotubes prepared by disproportionation of CO over Co-Mo/SiO2 catalysts have been characterized by Raman spectroscopy, using several excitation energies. By varying the reaction temperature, different ranges of nanotube diameter were obtained. The average diameter of a single-walled nanotube produced at 750 degrees C was 0.9 nm, while it increased up to about 1.5 nm when the synthesis was conducted at 950 degrees C. The analysis of the Raman spectra obtained with a range of laser excitation energies not only gives a definite description of the single-walled nanotubes diameters but also helps differentiate the metallic or semiconducting character of the samples. This analysis can be done by comparing the experimental data with calculated gap energies as a function of nanotube diameter as well as comparing the relative intensity of bands centered at 50-60 cm-1 lower than the tangential G mode. The analysis of this feature, which can be fitted with a Breit-Wigner-Fano line, offers a method for distinguishing between metallic and semiconducting single-walled carbon nanotubes.

[The effects of plasma cholesterol reduction on vasoconstriction due to sympathetic activation in patients with moderate primary hypercholesterolemia]. / Effetti della riduzione del colesterolo plasmatico sulla vasoconstrizione da attivazione simpatica in pazienti con ipercolesterolemia primaria moderata.

Recent studies have demonstrated that hypercholesterolemia is one of the major factor involved in the progression of coronary heart disease and that the reduction in plasma cholesterol reduces mortality for cardiovascular events. Indeed, recent experimental studies have demonstrated alterations in vascular reactivity in atherosclerosis. The aim of this study was to evaluate in patients with primary hypercholesterolemia the consequences of an effective of chronic treatment with inhibitor of HMG-CoA reductase on vascular responsiveness to cold pressure test. We observed a significant reduction in total plasma cholesterol during the study that was accompanied by a significant decrease in the response of peripheral vascular resistances to cold pressure test (55 +/- 4% vs 73 +/- 5% p < 0.01). There was also a significant relationship between the reduction of total cholesterol and the response of vascular resistance to the cold pressure test (r = 0.853, p < 0.05). Our results demonstrate that the reduction in total plasma cholesterol may influence the haemodynamic response induced by the activation of the sympathetic system.

[Effects of antihypertensive treatment on carotid vascular changes]. / Effetti del trattamento antipertensivo sulle alterazioni vascolari del distretto carotideo.

The carotid artery is one of the most important sites in the progression of atherosclerotic lesions. Atherosclerosis is known to be determined by a variety of factors, among which arterial hypertension is one of the most important. Blood pressure control by antihypertensive treatment is thus of great benefit in management of atherosclerosis, particularly in view of the direct action of some classes of antihypertensive agents on atheromatous lesions. Today, modern diagnostic technique allow a non-invasive examination of the artery wall (B-mode ultrasound and pulsed-Doppler), so that early detection of structural and functional alterations is possible. In order to evaluate the efficacy of the long term blood pressure reduction in the progression and/or in the regression of cardiovascular structural abnormalities, we studied intima-media thickness and arterial compliance during one-year antihypertensive treatment with a new calcium-antagonist, lacidipine, or a diuretic hydrochlorothiazide. In both groups we observed a comparable blood pressure reduction (lacidipine: from 166 +/- 5/100 +/- 1 to 142 +/- 4/88 +/- 2 mmHg; hydrochlorothiazide: from 154 +/- 5/102 +/- 2 to 140 +/- 4/88 +/- mmHg; both p < 0.01). On the contrary, only in patients treated with lacidipine did we obtain a significant improvement in carotid blood flow (383 +/- 16 vs 411 +/- 16 ml/min p <) and in arterial compliance (0.8 +/- 0.1 vs 1.2 +/- 0.2 cm/dyne p < 0.01). Indeed, we observed a different behaviour of the intima-media thickness in the two groups (lacidipine: 1.11 +/- 1.4 vs 1.13 +/- 1.5 mm n.s.; hydrochlorothiazide: 1.15 +/- 0.15 vs 1.21 +/- 0.17 mm p < 0.06). Our results demonstrate that an effective antihypertensive treatment with calcium antagonists may influence the progression of carotid vascular abnormalities.

[Carotid vascular structural changes and left ventricular hypertrophy]. / Alterazioni strutturali vascolari carotidee ed ipertrofia ventricolare sinistra.

In the literature there are few studies evaluating carotid vascular atherosclerotic involvement in patients with essential arterial hypertension. Nowadays with new non-invasive methodological methods, such as Doppler-echotomography, it is possible to evaluate accurately structural vascular and cardiac changes. In this study we evaluated the relationship between carotid vascular structural changes and cardiac left ventricular mass index in 15 normotensive subjects and in 15 patients with essential hypertension. We performed a B-mode echotomography (7.5 MHz) of a common carotid in order to measure the diameter of the vessel and intima-media wall thickness. In the same subjects we determined echocardiographic left ventricular mass index and we measured arterial pressure by sphygmomanometric method. There was no statistical significant difference in the two groups except that in systolic, diastolic and mean arterial pressure (96 +/- 2 vs 123 +/- 2 mmHg, p < 0.01), left ventricular mass index (102 +/- 3 vs 118 +/- 3 g/m2, p < 0.01) and in the common carotid intima media wall thickness (0.91 +/- 0.01 vs 2.23 +/- 0.02 mm). In the normotensive subject mean arterial pressure correlated significantly with age (r = 0.699) and with common carotid arterial diameter (r = 0.523) (both p < 0.05). In hypertensive patients, on the contrary, mean arterial pressure correlated with left ventricular mass index (r = 0.523), carotid arterial diameter (r = 0.627) and common carotid intima media wall thickness (r = 0.847). These results demonstrate that in hypertensive patients cardiac abnormalities accompanied vascular structural changes.

[The role of the blood viscosity and hematocrit value in acute stroke. Experimental considerations]. / Il ruolo della viscosità ematica e del valore ematocrito nello stroke acuto. Considerazioni sperimentali.

The link between blood viscosity, Ht and the onset of stroke is highlighted and reports in the literature are examined. On this basic, the paper proposes an experimental model of cerebral ischaemia in the rabbit as providing a better insight into this aspect which may be highly significant, particularly in the prevention of strokes.

Variable p-CREB expression depicts different asthma phenotypes.

BACKGROUND: Chromatin modification may play a role in inflammatory gene regulation in asthma. Cyclic adenosine mono-phosphate response element-binding protein (CREB), with the specific co-activator, the CREB-binding protein (CBP), contributes to the acetylation of chromatin and to the transcription of pro-inflammatory genes. OBJECTIVES: To evaluate the expression of CBP and of phospho-CREB (p-CREB) in bronchial biopsies and in peripheral blood mononuclear cells (PBMC) of controls (C), untreated (UA), inhaled steroid treated (ICS) and steroid-dependent asthmatic (SDA) patients. METHODS: We used immunohistochemistry in bronchial biopsies and western blot analysis and immunocytochemistry in PBMC. RESULTS: Cyclic adenosine mono-phosphate response element-binding protein expression, in the epithelium was similar in all groups, while p-CREB expression was increased in UA and in SDA in comparison with ICS and C subjects (C vs UA P = 0.002, C vs SDA P = 0.007), (ICS vs SDA P = 0.005), (ICS vs UA P = 0.001). Interestingly, also in the submucosa, p-CREB was increased in UA and SDA in comparison with ICS and C subjects (C vs UA P = 0.0004) (C vs SDA P < 0.0001) (ICS vs UA P = 0.002) (ICS vs SDA P < 0.0001) and positively correlated with leukocyte infiltration within the bronchi (CD45RB+ cells). Similar results were obtained with PBMC isolated from the same patient groups. Incubation of PBMC in vitro, with fluticasone propionate, decreased the p-CREB expression induced by cytokine activation (interferon-gamma, tumor necrosis factor-alpha). CONCLUSIONS: This study demonstrates that the expression of p-CREB is related, in asthma, to the persistent inflammation according to the disease severity. p-CREB expression can be modulated by glucocorticoids in responsive patients.

Seasonal patterns of hospital treatment for inflammatory bowel disease in Italy.

AIM: It is still debated whether clinical flare-ups of chronic inflammatory bowel disease follow a seasonal pattern, and the various reports are based on general practitioners' records or hospital discharge charts. There are, however, no specific figures for treatment in hospital gastroenterology units, which serve as a reference point for these disorders. This study was therefore designed to investigate whether there is a seasonal pattern in admissions for inflammatory intestinal disease in Italy, differing from what is generally known about gastrointestinal pathologies, since there are no nation-wide figures on the subject. METHODS: The RING (Ricerca Informatizzata in Gastroenterologia) project is an observational study collecting hospital discharge forms from 22 centers in Italy. RESULTS: From winter 2000 to autumn 2003, the 22 gastroenterology units participating in the RING project discharged 32,357 patients following ordinary hospital admissions. Of these, 2,856 (8.8%) had a main diagnosis of inflammatory bowel disease: 1,541 Crohn's disease, and 1,315 ulcerative colitis. No seasonal patterns were detected for either category, or when the analysis was done by age, sex and site of disease. CONCLUSIONS: The most serious flare-ups of inflammatory bowel disease, i.e. those requiring routine hospital treatment, do not appear to follow any seasonal pattern, regardless of the site of the disease or the patient's age or sex.

Biochemical interaction between effects of beclomethasone dipropionate and salbutamol or formoterol in sputum cells from mild to moderate asthmatics.

BACKGROUND: Several in vitro studies demonstrate that corticosteroids and long-acting beta(2) agonists may have a complementary and synergistic mode of action on the inflammatory processes in asthma. METHODS: Sputum was induced in 20 mild to moderate asthmatic patients and the induced sputum cells (ISC) were cultured with beclomethasone dipropionate (BDP) 10(-7) M, salbutamol 10(-8) M and formoterol 10(-8) M either alone or in combination, BDP plus salbutamol and BDP plus formoterol, for 24 h. We measured the levels of growth macrophages-colony stimulating factor (GM-CSF), released on activation normal T cells expressed and activated (RANTES) and interleukin-8 (IL-8), in the supernatant of stimulated cells by ELISA. Furthermore, we assessed nuclear translocation of glucocorticoid receptor (GR) and the expression of beta(2) receptor in ISC by immunofluorescence and RT-PCR, respectively. RESULTS: The release of GM-CSF, RANTES and IL-8 in ISC was significantly reduced by BDP plus salbutamol or formoterol as compared with either drug alone (P < 0.0001). beta(2) receptor expression was increased after 30 min of incubation with BDP and continued to increase over a time period of 4 h (P < 0.0001). Furthermore after 30 min of incubation, nuclear translocation of GR was greater with BDP plus salbutamol or formoterol than with any of the drugs alone (P < 0.0001). CONCLUSION: The present ex vivo study demonstrates a complementary mode of action between BDP and salbutamol or formoterol leading to an enhanced anti-inflammatory activity.

Probing the role of cysteine residues in glucosamine-1-phosphate acetyltransferase activity of the bifunctional GlmU protein from Escherichia coli: site-directed mutagenesis and characterization of the mutant enzymes.

The glucosamine-1-phosphate acetyltransferase activity but not the uridyltransferase activity of the bifunctional GlmU enzyme from Escherichia coli was lost when GlmU was stored in the absence of beta-mercaptoethanol or incubated with thiol-specific reagents. The enzyme was protected from inactivation in the presence of its substrate acetyl coenzyme A (acetyl-CoA), suggesting the presence of an essential cysteine residue in or near the active site of the acetyltransferase domain. To ascertain the role of cysteines in the structure and function of the enzyme, site-directed mutagenesis was performed to change each of the four cysteines to alanine, and plasmids were constructed for high-level overproduction and one-step purification of histidine-tagged proteins. Whereas the kinetic parameters of the bifunctional enzyme appeared unaffected by the C296A and C385A mutations, 1,350- and 8-fold decreases of acetyltransferase activity resulted from the C307A and C324A mutations, respectively. The Km values for acetyl-CoA and GlcN-1-P of mutant proteins were not modified, suggesting that none of the cysteines was involved in substrate binding. The uridyltransferase activities of wild-type and mutant GlmU proteins were similar. From these studies, the two cysteines Cys307 and Cys324 appeared important for acetyltransferase activity and seemed to be located in or near the active site.

[Recurrent organic abdominal pain. Psychosocial investigation]. / Dolori addominali ricorrenti su base organica. Indagine psicosociale.

This study has produced the following results. All the children with RAP show an excessive excitability and timidness, a strong insecurity and apprehension towards the society. The majority of the children show a strong dependence upon their relatives, they are not able to place themselves, as active subjects, in the present trality and to make plans for their future life (absence of interests and/or programmes about their autorealization). These children have a psychological maturity not corresponding to the physical one, even if there is no real strongly marked mental insufficiency. About 50% of the subjects have difficult relations with their siblings, friends and teachers, unlike the group examined (infact these difficulties are not seen).