X-ray photoemission spectroscopy investigation of the interaction between 4-mercaptopyridine and the anatase TiO2 surface.

In polymer-metal oxide hybrid solar cells, an extremely careful engineering of the interface is required to ensure good device performances. Recently, very promising results have been obtained by functionalizing titanium dioxide (TiO2) by means of 4-mercaptopyridine (4-MPy) molecules, showing the beneficial effect of these molecules on the interface morphology. This study investigates the nature of the interaction of 4-MPy molecules with the TiO2 surface by means of X-ray photoemission spectroscopy. In order to mimic the device processing conditions, our analysis is carried out on molecules adsorbed from solution on a nanocrystalline surface. According to our analysis, 4-MPy molecules (C5H5NS) are likely bound with the oxide through the nitrogen atom. The bonding precedes either via a covalent interaction with Lewis surface sites, or via hydrogen mediation, possibly in the form of hydrogen bonds. Interestingly, in the latter case, we also observe strong changes in the spectroscopic features attributed to the thiol group.

Peripheral neuropathy in late-onset Krabbe disease: report of three cases.

Late-onset Krabbe disease may have variable misleading clinical manifestations and be a puzzling problem for physicians. We report clinical and peripheral nerve studies of three patients with adult-onset Krabbe disease. Two cases had a predominantly spastic paraparesis; in one case, the symptoms mimicked a cerebrovascular disorder. Predominantly, demyelinating neuropathy was observed in one case and axonal neuropathy in two cases. In all cases, no typical intracytoplasmic inclusions were found. These observations suggest that peripheral neuropathy in adult-onset Krabbe disease has variable clinical and pathological characteristics, different from those described in the classic form.

The relationship between ambient particulate matter and respiratory mortality: a multi-city study in Italy.

The association of air pollutants with natural and respiratory mortality has been consistently reported. However, several aspects of the relationship between particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM(10)) and respiratory mortality require further investigation. The aim of the present study was to assess the PM(10)-respiratory mortality association in Italy and examine potentially susceptible groups. All deaths from natural (n=276,205) and respiratory (n=19,629) causes among subjects aged ≥ 35 yrs in 10 northern, central and southern Italian cities in 2001-2005 were included in the study. Pollution data for PM(10), nitrogen dioxide and ozone were also obtained. A time-stratified case-crossover analysis was carried out. Different cumulative lags were selected to analyse immediate, delayed, prolonged and best-time effects of air pollution. The shape of the exposure-response curve was analysed. Age, sex, chronic conditions and death site were investigated as potential effect modifiers. We found a 2.29% (95% CI 1.03-3.58%) increase in respiratory mortality at 0-3 days lag. The increase in respiratory mortality was higher in summer (7.57%). The exposure-response curve had a linear shape without any threshold. Sex and chronic diseases modified the relationship between particular matter (PM) and respiratory mortality. The effect of PM on respiratory mortality was stronger and more persistent than that on natural mortality. Females and chronic disease sufferers were more likely to die of a respiratory disease caused by air pollution than males and healthy people.

Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy of 25 patients with brain tumor.

Formalin fixation under conditions that adversely affected the quality of the DNA, or indeterminant assay, or extensive tumor necrosis can compromise the genetic analysis of a brain bioptic sample. The success of DNA extraction and Methyl Guanine Methyl Transferase (MGMT) promoter methylation testing could be improved by freezing of fresh tumor tissue at the moment of biopsy. To ensure an increased concentration of the DNA samples the withdrawal should be performed in an area with high probability of neoplastic cells. From May 2007 to January 2011 fifty-two frameless neuronavigation brain needle biopsy were performed at the Neurosurgery Unit of the "Arcispedale Santa Maria Nuova" City Hospital of Reggio Emilia. The "image-guided" neuronavigated protocol sampling provided withdrawal specimens highly correlated with neuroimaging characteristics of the lesions. In this study the Authors report the genetic analysis on 24 cases of freezing fresh tissue from brain needle bioptic sample starting from July 2008. The molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction on fresh or cryopreserved needle bioptic tissue. The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in eleven patients, including a brain infection. The diagnostic yield of brain biopsy could be increased by the neuronavigated trajectories and the intraoperative frozen sections. In the future the availability of the molecular-genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment. The MGMT promoter status analysis on needle bioptic fresh tissue could be available also for that patient not eligible for surgical remotion of the tumor.

Detection of IDH1 mutations and the status of MGMT promoter on intraoperative fresh tissue section from frameless neuronavigation needle biopsy. Analysis on 17 patients with brain glial tumor ineligible for craniotomy and tumor resection.

It is well known that primary and secondary glioblastomas are histologically largely indistinguishable. Therefore, the detection of IDH1 mutations or the status of the MGMT promoter on a simple bioptic sample could be one of major diagnostic and prognostic importance for glial patients that complements clinical criteria for distinguishing secondary from primary glioblastomas and to predict a more favourable prognosis. Currently, biopsy is the method of choice to obtain tissue from intracranial lesions with uncertain neurodiagnostic findings or in deep locations, with a minimal invasive approach. The needle biopsy with frameless neuronavigation could provide a sampling with elevated diagnostic yield and high concentration of DNA, due to the "image-guided" computer assisted technique of needle insertion through the most neurodiagnostic representative tumor area. The freezing of fresh tumor tissue at biopsy could greatly improve the success of DNA extraction. The concentration of the DNA samples can also improved from a withdrawal in an area with high probability of neoplastic cells. The present study reports the results of 17 patients who had undergone frameless image-guided intracranial needle biopsy from April 2008 until July 2010 at Neurosurgery Unit of the "Arcispedale Santa Maria Nuova" of Reggio Emilia. For these patients the molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction and the screening of mutations in IDH1 e IDH2 genes was performer by polymerase chain reaction (PCR) and direct sequencing on fresh or cryopreserved needle bioptic tissue.

Comparison of two behavior management techniques used during mandibular block anesthesia among preschool children: a randomized clinical trial.

PURPOSE: To compare the Tell-Show-Do Technique (TSD-T) with Hiding Dental-Needle Technique (HDN-T) based on children's anxiety, pain, and behavior during first-time mandibular block anesthesia. METHODS: A total of 52 children aged 3-5 years who had never received dental anesthesia and had at least one mandibular primary molar requiring extraction or pulpal therapy were included in the study. Children were randomly allocated into two groups: G1: TSD-T (n = 26) and G2: HDN-T (n = 26). This study included two sessions: intervention session (baseline) and control session (7 days after intervention). Facial Image Scale and Wong-Baker Pain Scale were used to evaluate anxiety and pain levels, respectively. Frankl Behavior Scale was used to assess children's behavior. RESULTS: Anxiety and pain levels were not statistically significant between G1 and G2 groups (p > 0.05). Similar results were observed for children's behavior rating (p > 0.05). Higher pain level was associated with younger children (rate ratios (RR) = 0.41; p = 0.016) and negative behavior (RR = 1.11; p < 0.001). On the other hand, in within-groups comparisons, there was a statistical difference in anxiety levels between intervention session and control session (p = 0.032) in G2. CONCLUSIONS: Even though there are no differences in the efficacy of TSD-T compared to HDN-T during first-time mandibular block anesthesia in preschool children in terms of children's anxiety, pain, and behavior, children from the HDN-T group can show reduced dental anxiety levels in the control sessions.

Glomerular filtration rate is associated with trabecular bone score in patients with type 2 diabetes mellitus.

AIMS: The present study aimed to evaluate the trabecular and cortical bone components using Trabecular Bone Score (TBS) and its association with estimated-Glomerular Filtration Rate (e-GFR) in T2DM patients. METHODS: An assessment both of bone mineral density (BMD) and vertebral bone microarchitecture was performed in all patients using TBS iNsight® software version 3.0.2.0. Furthermore, the total population was divided into two groups based on the value of the eGFR (eGFR < o > at 60 ml/min/1.73 m2). RESULTS: TBS value was lower in patients with low e-GFR than that in patients with higher e-GFR (1.246 ± 0.125 vs 1.337 ± 0.115, respectively, p = 0.013 adjusted by gender and age) while there was no difference in total BMD value between two groups. In the multivariate model taking into account several possible confounders, such as age, gender, duration of diabetes, BMI, LDL cholesterol, serum calcium and HbA1c, the correlation between e-GFR and TBS remained significant (p: 0.046). CONCLUSIONS: In individuals with T2DM and reduced kidney function, TBS provides information independent of BMD, age and gender. TBS may be a useful additional tool to predict fracture risk in this unique population.

Chronic progressive external ophthalmoplegia: a new heteroplasmic tRNA(Leu(CUN)) mutation of mitochondrial DNA.

We sequenced all genes of mitochondrial tRNAs of a patient with chronic progressive external ophthalmoplegia with 5% ragged red fibres and 15% COX-negative fibres but without macrorearrangements of mitochondrial DNA (mtDNA). Direct sequencing showed a novel heteroplasmic G>A substitution in position 12316 of tRNA(Leu(CUN)) gene. This change destroys a highly conserved G-C base coupling in tRNA TpsiC branch. By RFLP analysis we could demonstrate different degrees of heteroplasmy in different patient's tissues. This alteration, absent in a population of 110 patients with different encephalomyopathies, can be considered pathogenic: it is the tenth tRNA(Leu(CUN)) pathogenic mutation described up to date.

Long term effect of air pollution on incident hospital admissions: Results from the Italian Longitudinal Study within LIFE MED HISS project.

BACKGROUND: The LIFE MED HISS project aims at setting up a surveillance system on the long term effects of air pollution on health, using data from National Health Interview Surveys and other currently available sources of information in most European countries. Few studies assessed the long term effect of air pollution on hospital admissions in European cohorts. OBJECTIVE: The objective of this paper is to estimate the long term effect of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) on first-ever (incident) cause-specific hospitalizations in Italy. METHODS: We used data from the Italian Longitudinal Study (ILS), a cohort study based on the 1999-2000 National Health Interview Survey (NHIS), followed up for hospitalization (2001-2008) at individual level. The survey contains information on crucial potential confounders: occupational/educational/marital status, body mass index (BMI), smoking habit and physical activity. Annual mean exposure to PM2.5 and NO2 was assigned starting from simulated gridded data at spatial resolution of 4 × 4 km2 firstly integrated with data from monitoring stations and then up-scaled at municipality level. Statistical analyses were conducted using Cox proportional hazard models with robust variance estimator. RESULTS: For each cause of hospitalization we estimated the hazard ratios (HRs) adjusted for confounders with 95% Confidence Interval (CI) related to a 10 µg/m3 increase in pollutants. For PM2.5 and NO2, respectively, we found positive associations for circulatory system diseases [1.05(1.03-1.06); 1.05(1.03-1.07)], myocardial infarction [1.15(1.12-1.18); 1.15(1.12-1.18)], lung cancer [1.18(1.10-1.26); 1.20(1.12-1.28)], kidney cancer [1.24(1.11-1.29); 1.20(1.07-1.33)], all cancers (but lung) [1.06(1.04-1.08); 1.06(1.04-1.08)] and Low Respiratory Tract Infections (LRTI) [1.07 (1.04-1.11); 1.05 (1.02-1.08)]. DISCUSSION: Our results add new evidence on the effects of air pollution on first-ever (incident) hospitalizations, both in urban and rural areas. We demonstrated the feasibility of a low-cost monitoring system based on available data.

DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function.

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration.

Mould/dampness exposure at home is associated with respiratory disorders in Italian children and adolescents: the SIDRIA-2 Study.

AIMS: To report on the relation between home mould and/or dampness exposure and respiratory disorders in a large sample of children and adolescents in Italy, accounting for age at time of exposure. METHODS: 20,016 children (mean age 7 years) and 13,266 adolescents (mean age 13 years) completed questionnaires on indoor exposures and respiratory symptoms/diseases. Statistical analyses were adjusted for sex, age, questionnaire's compiler, area of residence, season of interview, parental educational status, family history of asthma, rhinitis, eczema, chronic obstructive pulmonary disease, presence of gas water heaters, passive smoking, pets, and active smoking (only for adolescents). Population attributable risk % (PAR) was also computed. RESULTS: Asthma was more strongly related to only early than to only current exposure, both in children (OR 1.80, 95% CI 1.41 to 2.30) and adolescents (OR 1.89, 95% CI 1.38 to 2.59). The same result was found for rhino-conjunctivitis (OR 1.46, 95% CI 1.17 to 1.82), in children, and for wheeze among adolescents (OR 1.56, 95% CI 1.15 to 2.11). In children, wheeze (OR 1.98, 95% CI 1.47 to 2.66) and eczema (OR 1.44, 95% CI 1.09 to 1.91) were more strongly related to mould/dampness when exposed both early and currently; the same occurred in adolescents for rhino-conjunctivitis (1.78, 95% CI 1.30 to 2.45). Although persistent cough/phlegm was significantly related to mould/dampness exposure in children, regardless of exposure timing, no significant association between mould/dampness exposure and eczema or cough/phlegm was found among adolescents. PAR estimates were higher for only early than only current exposures. Avoiding early only exposure would abate wheeze by 6%, asthma or cough/phlegm by 7%, rhino-conjunctivitis in children by 4%, and in adolescents, asthma by 6%, and wheeze by 4%. CONCLUSIONS: Respiratory disorders such as wheeze and asthma can often be explained by exposure to home mould/dampness, especially early in life. The association seems more evident in children than in adolescents. These findings may suggest the need for environmental prevention strategies.

GEMSS: grid-infrastructure for medical service provision.

OBJECTIVES: The European GEMSS Project is concerned with the creation of medical Grid service prototypes and their evaluation in a secure service-oriented infrastructure for distributed on demand/supercomputing. Key aspects of the GEMSS Grid middleware include negotiable QoS support for time-critical service provision, flexible support for business models, and security at all levels in order to ensure privacy of patient data as well as compliance to EU law. METHODS: The GEMSS Grid infrastructure is based on a service-oriented architecture and is being built on top of existing standard Grid and Web technologies. The GEMSS infrastructure offers a generic Grid service provision framework that hides the complexity of transforming existing applications into Grid services. For the development of client-side applications or portals, a pluggable component framework has been developed, providing developers with full control over business processes, service discovery, QoS negotiation, and workflow, while keeping their underlying implementation hidden from view. RESULTS: A first version of the GEMSS Grid infrastructure is operational and has been used for the set-up of a Grid test-bed deploying six medical Grid service prototypes including maxillo-facial surgery simulation, neuro-surgery support, radio-surgery planning, inhaled drug-delivery simulation, cardiovascular simulation and advanced image reconstruction. CONCLUSIONS: The GEMSS Grid infrastructure is based on standard Web Services technology with an anticipated future transition path towards the OGSA standard proposed by the Global Grid Forum. GEMSS demonstrates that the Grid can be used to provide medical practitioners and researchers with access to advanced simulation and image processing services for improved preoperative planning and near real-time surgical support.

Accelerated elimination from the circulation of homologous aged red blood cells in rats bearing anti-spectrin antibodies.

In order to analyse a possible role of anti-spectrin antibodies in the clearance of aged red blood cells (RBC), a homologous system was employed, whereby a population of aged RBC, obtained by hypertransfusion, was injected into rats bearing a high level of anti-spectrin antibodies, following immunization with spectrin. The aged RBC bound the anti-spectrin antibodies 'in vitro' and were eliminated from circulation in spectrin-treated rats at a faster rate than in control rats with naturally occurring antibodies. The analysis of the clearance curves revealed aged RBC of heterogeneous lifespans: two principal populations of short- and longer-living could be identified. In rats with anti-spectrin antibodies, the survival of the short-living population was further reduced. However, the similar kinetics of elimination of aged RBC in the two groups (with naturally-occurring and induced antibodies, respectively) suggest that anti-spectrin antibodies strengthened the intervention of the naturally-occurring ones. On the basis of these results, we assume that during their aging in circulation, RBC can accumulate surface alterations to make spectrin accessible to antibodies so that, in addition to anti-band 3 antibodies, anti-spectrin antibodies may contribute to their elimination.

Asymptomatic cores and paracrystalline mitochondrial inclusions in CADASIL.

Three siblings with genetically assessed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with core-like lesions and mitochondrial abnormalities in muscles are described. Involvement of the Ryanodine receptor 1 gene was excluded. In the current cases, the relation between molecular genetic lesion and muscle fiber abnormalities remains to be determined, but the Notch3 gene may influence mitochondrial metabolism.

Kinematic analysis of the reach to grasp movement in Parkinson's and Huntington's disease subjects.

This experiment investigates the kinematic characteristics of the reach to grasp movement of Parkinson's and Huntington's disease subjects under two different experimental conditions. In the first condition subjects were required to perform the movement at a normal speed, while in the second condition they were required to perform the movement as fast as possible. Results showed that the kinematic parameterization of movement in Parkinson's disease subjects did not differ from that of age-matched control subjects for both the normal and the fast condition. However, the performances of Huntington's disease subjects appeared to be different when compared to the other two groups. Differences were mainly related to Huntington's disease patients' inability to properly define the temporal features of the movements.

The metabolism of carbamazepine in humans: steric course of the enzymatic hydrolysis of the 10,11-epoxide.

Carbamazepine 10,11-oxide (1a,10b-dihydro-6H-dibenzo[b,f]oxireno[d]azepine-6-carboxamide), a key intermediate in carbamazepine metabolism, was found to be unusually resistant to enzymatic hydrolysis when incubated with microsomal and cytosolic fractions from rabbit, rat, and guinea pig livers. However, its hydrolysis product, trans-10,11-dihydro-10,11-dihydroxy-5H-dibenzo[b,f]azepine-5-carboxamide , was excreted, as previously reported, both in the free and in conjugated forms, as the main metabolite in the urine of humans under carbamazepine treatment. The free diol and that obtained after treatment with beta-glucuronidase/arylsulfatase were both found by Mosher's method to be formed in an enantiomeric excess of 80%, the prevalent enantiomer having the (-)-10S,11S absolute configuration, as determined by applying the CD exciton coupling method to its bis[p-(dimethylamino)benzoyl] ester. This finding confirms the pronounced enantioselectivity of the microsomal epoxide hydrolase toward meso and racemic substrates, but is in contrast with the prevalent formation of (R,R)-diols in most other known cases of enzymatic hydrolysis of epoxides. Preparatively useful syntheses of the racemic trans-10,11-dihydro-10,11-diol and of 9-(hydroxymethyl)-10-carbamoylacridan, another carbamazepine metabolite, are reported for the first time.

Binding of anti-spectrin antibodies to red blood cells and vesiculation in various in vivo and in vitro ageing conditions in the rat.

In this study, the binding of naturally occurring antibodies as well as of induced anti-spectrin antibodies to red blood cells (RBC), in relation with different ageing conditions, was investigated in the rat. RBC from aged animals, or from rats whose RBC were age-induced either by means of hypertransfusion (which blocks erythropoiesis) or by treatment with clodronate-containing liposomes (which reduces RBC removal from circulation), were used. Attainment of RBC ageing was demonstrated by MCV reduction and by an increase of both RBC density and 4.1a/4.1b RBC membrane protein ratio. The results demonstrate an augmented anti-spectrin antibody binding to RBC in relation with their ageing condition, especially when induced by hypertransfusion. The vesiculation process was also investigated and correlated with antibody binding: vesicles were found only in the plasma of clodronate-treated rats, whose RBC showed the lowest level of anti-spectrin antibody binding with respect to the other groups. In addition, RBC preserved in vitro in different media showed a binding of anti-spectrin antibody, which inversely correlated with the vesiculation process. On the whole, the latter results suggest a protective effect of vesicles towards IgG opsonization of aged RBC.

Ultrastructure and immunoreactivity of dystrophic axons indicate a different pathogenesis of Hallervorden-Spatz disease and infantile neuroaxonal dystrophy.

An immunohistochemical and ultrastructural analysis of dystrophic axons (DAs) in the brain and peripheral nerve of a patient with familial infantile neuroaxonal dystrophy (INAD) and in the brain of a patient with familial Hallervorden-Spatz Disease (HSD) revealed prevalent membrano-tubular or granulo-vesicular profiles with a graded pattern of evolution in INAD, while dense bodies, vesicles and amorphous material were present in HSD. DAs immunoreactivity with tai-protein and 200 kDa-neurofilament antibodies was stronger in HSD than in INAD. In both cases immunohistochemistry was positive for ubiquitin and negative for beta-tubulin and beta-amyloid. Distinct ultrastructural features and immunoreactivity pattern of cytoskeletal components suggest different pathogenetic mechanisms.

Atypical McLeod syndrome manifested as X-linked chorea-acanthocytosis, neuromyopathy and dilated cardiomyopathy: report of a family.

We report a family with three members affected by a typically X-linked McLeod syndrome. In the proband a very weak positivity for antigens of the Kell group was detected. His sister showed a normal antigenic pattern. We emphasize the prominent neurological picture characterized by a choreic syndrome with atrophy of the caudate nucleus on MRI, psychiatric disturbances, peripheral nerve and muscle biopsy findings indicating slight neuromuscular involvement, and cardiac abnormalities. The differential diagnosis is discussed.

Juvenile Leigh syndrome with protracted course presenting as chronic sensory motor neuropathy, ataxia, deafness and retinitis pigmentosa: a clinicopathological report.

We herein describe a male patient who died at 37 years of age, after having suffered from a slowly progressive syndrome of chronic sensory motor neuropathy, deafness, retinitis pigmentosa and ataxia. The neuropathological study showed symmetric areas of necrosis and demyelination affecting the cerebellum and brainstem. The type of lesion was consistent with the characteristics of Leigh Syndrome. On the basis of the histology of the lesions, we believe that they appeared only a few months before the death of the patient. We underline the atypical clinical picture and suggest that, in certain cases, brain MRI may not be a reliable diagnostic tool.