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Abstract: We report the clinical and genetic study of a primary hyperoxaluria type I (PH1) family with two sisters homozygous for p.Gly170Arg who are still asymptomatic at age 29 and 35, and two brothers, also homozygous for the same mutation, who are affected since age 27 and 30. The clear sex difference observed in this family and in others reported in the literature fits well with the prevalence of males over females in the Italian registry. In the KO model of PH1, only male mice develop renal stones, suggesting that the sex difference may affect both oxalate production and stone formation. A likely mechanism is the sex-related expression of glycolate oxidase shown in experimental animals. The stable isotope method recently developed by Huidekoper and van Woerden for in vivo assessment of the endogenous oxalate production could help to clarify the issue in humans.

Arsenic is one of the most toxic elements in natural waters since prolonged exposure to this metalloid can cause chronic damage to health. Its removal from groundwater remains one of the greatest environmental challenges to be addressed nowadays. Here, we present core–satellite hybrid nanostructures formed by plasmonic gold satellites supported onto magnetic iron oxide cores for sunlight-driven remediation of arsenic-containing water. Our experimental results show that the gold nanoparticles catalyze the oxidation of arsenic to much less toxic species and that – upon illumination – the generated heat and hot carriers further enhance the reaction rate. The iron oxides act as an arsenic adsorbent, enabling the complete removal of the catalysts and the adsorbed oxidized arsenic species through a magnet. We quantified the different catalytic contributions, showing that the plasmonic one is of the same order as the surface one. This work highlights the synergy between plasmonic catalysts and iron oxides for light-assisted water remediation.

In this work, we combine experiments and molecular simulations to unveil the hidden allosteric propensity of a thermophilic malate dehydrogenase protein (MDH). We provide evidence that, at its working temperature, the nonallosteric MDH takes a compact structure because of internal dewetting and reorganizes the active state toward functional conformations similar to its homologous allosteric LDHs. Moreover, a single-point mutation confers on the MDH a cooperative behavior that mimics an allosteric LDH. Our work not only demonstrates that thermophilic MDHs use temperature as an external parameter to regulate its functionality in a similar way allosteric LDHs use substrates/cofactors binding but also shows that the scaffold of MDHs possesses an intrinsic and hidden allosteric potentiality.

Upconversion is a common process in lanthanides-based materials in which absorption of multiple low energy photons result in a high energy one. The emission spectrum is frequently tuned by changing the composition of the material. However, a commonly overlooked aspect is the non-linear power dependence which can influence the spectral and temporal properties of the emission. Moreover, as upconverting materials have been shown to increase the output current density in photovoltaic cells when used as spectral converters, the complete power profile is required to calculate the improved efficiency and needs to be incorporated in the design process.

Objective: Tilmicosin is a macrolide antibiotic utilized in veterinary medicine in the pharmaceutical form of a 25% propylene-glycol solution (Micotil 300[R]). This preparation is cardiotoxic and potentially fatal for humans. We describe a case of intentional intramuscular self-injection of Micotil 300[R], in which the toxicokinetics of tilmicosin was investigated. Case report: A 41-year-old, 53 kg woman with a history of previous attempted suicides, self-injected 2 mL of Micotil 300[R] into her left gluteal muscle. Seventy-five minutes later she was admitted to the Emergency Department with vomiting, severe cardiovascular collapse (systolic blood pressure: 40 mmHg) and bradycardia (heart rate: 50/minute) with QT prolongation (0.44 seconds). Immediately transferred to the Critical Care Unit, she was treated with dopamine, dobutamine, oxygen and massive vascular filling according to the value of central venous pressure. Hemodynamic status improved rapidly, but bradycardia and ECG alterations lasted 2 days. After recovery, the patient confirmed the injection of exactly 2 mL of Micotil 300[R]. Toxicological analysis were performed by high performance liquid chromatography. Tilmicosin concentration was determined in the pharmaceutical solution (296 mg/mL), as well as in blood and urine (sequential samples were taken at 1.5, 3.75, 5.75, 9.75, 13.75, 19.75, 25.75, 33.75, 41.75, 49.75, 73.75 hours after the injection). The estimated total injected amount was 592 mg. The highest tilmicosin serum concentration (2.5 [micro]g/mL) was found at 1.5 hours post-injection. In the following hours, a two phase exponential decay was found according to the following equation: y([micro]g/mL) = 4.54 [e.sup.-0.3x(hours)] + 0.2 [e.sup.1.6x(hours)]. Tilmicosin serum washout time was 49.75 hours (0.09 [micro]g/mL). The antibiotic was detected in urine until 33.75 hours post-injection. The total amount eliminated in urine was 13.56 mg (2.29% of the injected dose). Tilmicosin was not detected in the gastric aspirate at admission. Conclusion: To our knowledge, this is the first description of tilmicosin toxicokinetics in humans. Clinical examination of the injection site and toxicological investigation confirmed the intramuscular route of poisoning. Additionally, this case shows that an intensive symptomatic treatment is effective to counteract the cardiac failure related to as high as 11 mg/kg. Zoppellari R(1), Locatelli C(2), Brunaldi V(3), Marchi M(1), Bianconi M(1), Zanotti C(4), Avato FA(3), Zatelli R(1) (1) Department of Anaesthesia and Critical Care, S. Anna Hospital, Ferrara (2) National Toxicology Information Centre, Maugeri Foundation IRCCS, Pavia (3) Institute of Legal Medicine and Insurances, University of Ferrara (4) Emergency Department, S. Anna Hospital, Ferrara, Italy

The possibility of employing the Total Reflection X-ray fluorescence (TXRF) technique for the analysis of some derivatives of petroleum crude oil (Petrol, Diesel oil, Fuel oil), is demonstrated with the help of certified standards (NIST, ENEL, ICIP). The quantitative analysis is conducted via an internal standard method. Some problems about elements volatility (S in Diesel oil and Pb in Petrol) are solved to permit an accurate quantitative simultaneous determination of the elements (from Z = 13 to Z = 90 with a detection limit in the range from ppb to ppm) present in the samples of petroleum derivatives. The analyses are conducted with a new Total Reflection X-ray spectrometer (TX 2000 supplied by Ital Structures)

Les abcès pulmonaires peuvent être présents dès le diagnostic de cancer pulmonaire, ou en être une complication. Il n’existe que peu de consensus concernant la prise en charge thérapeutique de ces tumeurs abcédées. La prise en charge de ces patients peut devenir très délicate, opposant l’instauration d’une chimiothérapie anti-infectieuse et la poursuite du traitement anti-cancéreux.

Background: GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the central nervous system, which are involved in the regulation of feeding behavior. GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways. Aim:Aim of this study was to investigate whether GPR7gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects. Subjects and methods:The coding region of GPR7were sequenced in 150 obese patients and 100 normal-weight unrelated controls. Functional studies of the allelic variants were performed. Results:One genetic GPR7 variant was found (Tyr135Phe — rs33977775) in obese subjects (13.3%) and lean control (25%). Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW-mediated capacity to inhibit forskolin-induced cAMP production. Conclusions:Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population. As indicated by in vitroand in silicostudies, this variant is unlikely to cause a functional derangement of the receptor.

The aims of this study were 1) to investigate the potential application of near-infrared spectroscopy (NIRS) to predict intramuscular fat (IMF) and fatty acid (FA) composition of individual meat samples, 2) to estimate heritability of IMF and FA NIRS-based predictions, and 3) to assess the statistical relevance of the genetic background of such predictions by using the Bayes factor (BF) procedure. Young Piemontese bulls (n = 1,298) were raised and fattened on 124 farms, and slaughtered at the same commercial abattoir. Intramuscular fat content and FA composition were analyzed on a random subset of 148 samples of minced and homogenized longissimus thoracis muscle. Near-infrared spectroscopy spectra were collected on all samples (n = 1,298) in reflectance mode between 1,100 and 2,498 nm (every 2 nm) using fresh minced meat samples. Calibration models developed from the random subset of 148 samples were used to predict IMF and FA contents of the remaining 1,150 samples. Intramuscular fat content and FA predictions were analyzed under a Bayesian univariate animal linear models, and the statistical relevance of heritability estimates was assessed through BF; the model with polygenic additive effects was favored when BF > 1. In general, satisfactory results (R2> 0.60) were obtained for 6 out of the 8 major FA (C14:0, C:16:0, C16:1, C18:0, C18:1n-9 cis/trans, and C18:1n-11 trans), 6 out of the 19 minor FA (C10:0, C12:0, C17:0, C17:1, C18:2 cis-9,trans-11, and C20:2), and the total SFA, MUFA, and PUFA. Bayes factors between models with and without a genetic component provided values greater than 1 for IMF, C14:0, C16:0, C18:1n-9 cis/trans, C17:0, C17:1, C20:2, SFA, MUFA, and PUFA. The greatest BF was reached by C20:2 (BF >10), suggesting strong evidence of genetic determinism, whereas IMF, C18:1n-9 cis/trans, C17:0, C17:1, MUFA, and PUFA showed substantial evidence favoring the numerator model (3.16 < BF < 10). Point estimates of heritabilities for FA predicted by NIRS were low to moderate (0.07 to 0.21). Results support that NIRS is a useful technique to satisfactorily predict some FA of meat. The existence of an important genetic determinism affecting FA profile has been confirmed, suggesting that FA composition of meat can be genetically modified.

The aims of this study were 1) to investigate the potential application of near-infrared spectroscopy (NIRS) to predict beef quality (BQ) traits, 2) to assess genetic variations of BQ measures and their predictions obtained by NIRS, and 3) to infer the genetic relationship between measures of BQ and their predictions. Young Piedmontese bulls (n = 1,230) were raised and fattened on 124 farms and slaughtered at the same commercial abattoir. The BQ traits evaluated were shear force (SF, kg), cooking loss (CL, %), drip loss (DL, %), lightness (L*), redness (a*), yellowness (b*), saturation index (SI), and hue angle. Near-infrared spectra were collected using a Foss NIRSystems 5000 instrument over a spectral range of 1,100 to 2,498 nm every 2 nm, in reflectance mode. After editing, prediction models were developed on a calibration subset (n = 268) using partial least squares regressions, followed by application of these models to the validation subset (n = 940). Estimations of (co)variance for measures of BQ and NIRS-based predictions were obtained through a set of bivariate Bayesian analyses on the validation subset. Near-infrared predictions were satisfactory for measurements of L* (R2= 0.64), a* (R2= 0.68), hue angle (R2= 0.81), and saturation index (R2= 0.59), but not for b*, DL, CL, and SF. The loss of additive genetic variance of predicted vs. measured L*, a*, DL, CL, and SF was generally high and was similar to the loss of residual variance, being a function of the calibration parameter R2. As a consequence, estimated heritabilities of measures and predictions of BQ were similar for traits with high calibration R2values. Genetic correlations between BQ measures and predictions were high for all color traits and DL, and were greater than the corresponding phenotypic correlations, whereas both the phenotypic and genetic correlations for SF and CL were nil. Results suggest that NIRS-based predictions for color features and DL may be used as indicator traits to improve meat quality of the Piedmontese breed.

Recently, it has been reported that longer expansions of the polyalanine tract of the ARXgene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARXgene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARXis involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations. © 2010 Wiley‐Liss, Inc.

The aim of the study was to infer (co)variance components for daily milk yield, fat and protein contents, and somatic cell score (SCS) in Burlina cattle (a local breed in northeast Italy). Data consisted of 13576 monthly test-day records of 666 cows (parities 1 to 8) collected in 10 herds between 1999 and 2009. Repeatability animal models were implemented using Bayesian methods. Flat priors were assumed for systematic effects of herd test date, days in milk, and parity, as well as for permanent environmental, genetic, and residual effects. On average, Burlina cows produced 17.0 kg of milk per day, with 3.66 and 3.33% of fat and protein, respectively, and 358000 cells per mL of milk. Marginal posterior medians (highest posterior density of 95%) of heritability were 0.18 (0.09–0.28), 0.28 (0.21–0.36), 0.35 (0.25–0.49), and 0.05 (0.01–0.11) for milk yield, fat content, protein content, and SCS, respectively. Marginal posterior medians of genetic correlations between the traits were low and a 95% Bayesian confidence region included zero, with the exception of the genetic correlation between fat and protein contents. Despite the low number of animals in the population, results suggest that genetic variance for production and quality traits exists in Burlina cattle.

The amyloid cascade hypothesis sustains that beta-amyloid (A) is the main pathogenetic factor of Alzheimers Disease (AD). Although the direct and indirect neurotoxic role of A are unchallenged, recent findings suggest that the peptide may have so far unforeseen physiological roles. In this regard, the observations showing the ability of A to exert synaptic activities in absence of neurotoxicity are very intriguing. In particular, the peptide is able to affect synaptic transmission of different neurotransmitter systems in key brain areas that regulate executive and cognitive functions, an observation that points A as a new neuromodulator. However, in a pathological context, A may drive functional alterations of several neurotransmitter systems in the early phases of the disease, in turn producing subtle cognitive and behavioural disturbances in addition and before the well known neurodegenerative events. On the other hand, advancing age is the most significant risk factor for the development of AD. In fact, during aging increased A levels have been reported. Moreover, several neurotransmitter systems undergo age-related changes in parallel to a decline of cognitive functions. However, the putative neuromodulatory role of A in the context of aging is nowadays unknown. For these reasons, future studies about the spectrum of action of A (brain areas and neurotransmitter systems affected) are particularly interesting since may suggest new therapeutic targets in order to sustain those functions which may be altered during aging.

The amyloid cascade hypothesis sustains that beta-amyloid (Aβ) is the main pathogenetic factor of Alzheimer's Disease (AD). Although the direct and indirect neurotoxic role of Aβ are unchallenged, recent findings suggest that the peptide may have so far unforeseen physiological roles. In this regard, the observations showing the ability of Aβ to exert synaptic activities in absence of neurotoxicity are very intriguing. In particular, the peptide is able to affect synaptic transmission of different neurotransmitter systems in key brain areas that regulate executive and cognitive functions, an observation that points Aβ as a new neuromodulator. However, in a pathological context, Aβ may drive functional alterations of several neurotransmitter systems in the early phases of the disease, in turn producing subtle cognitive and behavioural disturbances in addition and before the well known neurodegenerative events. On the other hand, advancing age is the most significant risk factor for the development of AD. In fact, during aging increased Aβ levels have been reported. Moreover, several neurotransmitter systems undergo age-related changes in parallel to a decline of cognitive functions. However, the putative neuromodulatory role of Aβ in the context of aging is nowadays unknown. For these reasons, future studies about the spectrum of action of Aβ (brain areas and neurotransmitter systems affected) are particularly interesting since may suggest new therapeutic targets in order to sustain those functions which may be altered during aging.

The genetic variability and presence of population substructures in 4 native Northern Italian sheep breeds, Alpagota, Brogna, Foza, and Lamon, undergoing in situ conservation, and 1 widespread Italian breed, Bergamasca, were studied by investigating 19 microsatellite markers. The breeds showed considerable genetic variability in terms of number of alleles and heterozygosity, with the exception of Alpagota, which was the least variable (0.607). Nevertheless, a significant deficit of heterozygotes was observed in each breed due to rather increased levels of inbreeding or to the presence of population substructures, probably caused by increased genetic variation in the founder populations. The analyses evidenced clear genetic differentiation (FST= 0.085), reduced levels of admixture, and presence of private alleles among the breeds, confirming their genetic uniqueness. In particular, according to Reynolds genetic distances, Alpagota was the most differentiated, perhaps because it had been bred mostly in a rather isolated area. Loss of any of the investigated breeds would result in a loss of genetic diversity ranging from 0.5 to 1.6% of the total observed gene diversity. Results supported the decision to safeguard these breeds as important reservoirs of genetic diversity and suggested breeding and mating practices to maintain variability and to overcome within-breed substructures.

The aim of this study was to investigate the effect of different breeds and breed crosses on age (AC, d), BW (kg), price (PR, $/kg), and market value (MV, $/calf) of purebred and crossbred calves sold for veal and beef production. The Kovieh wholesale cattle organization (Bolzano, Italy) grouped calves from several dairy herds located in the Trentino-Südtirol region in Italy and sold them by public auctions. Data on AC, BW, PR, and MV from 96,458 calves were recorded from January 2003 to December 2007 and consisted of 4 pure breeds [2 dairy, Brown Swiss (BS) and Holstein-Friesian (HF); and 2 dual-purpose, Simmental (SI) and Alpine Grey (AG)], and 8 crossbreds by crosses of Limousin (LI) and Belgian Blue (BB) with the 4 dam breeds. Least squares means for AC, BW, PR, and MV were calculated for breeds and breed crosses with a model that included fixed effects of herd of birth, age (except for AC), sex, and breed of the calf, year and season of auction, and interactions between the main effects. The coefficients of determination of the models were 0.41, 0.51, 0.84, and 0.82 for AC, BW, PR, and MV, respectively. Sex, age, and breed were the most relevant sources of variation for BW (P< 0.001), whereas breed and sex were the most important sources of variation for AC, PR, and MV (P< 0.001). Also, PR and MV were significantly influenced (P< 0.01) by all the effects included in the model, except for season × age interaction in the case of MV. Market value of male was greater (P< 0.001) than that of female calves, with the exception of BS (−$28.76/calf) and HF (−$20.70/calf) purebred males. Dual-purpose purebred calves presented greater (P< 0.001) PR and MV than dairy purebreds (MV of $426.97/calf and $307.96/calf for SI and AG, and $256.24/calf and $275.65/calf for BS and HF, respectively). Calves from SI and AG dams had greater (P< 0.001) BW, PR, and MV than calves from BS and HF dams. Calves from SI cows had greater (P< 0.001) BW, PR, and MV than calves from AG cows. Crossbreeding with beef bulls increased (P< 0.001) BW, PR, and MV of calves from dairy and dual-purpose dams. Crossbreeding with BB bulls increased PR (+$2.58 ± 0.04/kg; P< 0.001) and MV (+$190.84 ± 3.62/calf; P< 0.001) of calves much more than LI. The use of beef bull semen on dairy herds resulted in an economic revenue from selling crossbred calves.

Environment‐sensitive Bragg reflectors are built using functional mesoporous thin films as building blocks. Tuning of optical properties is achieved by changing the composition or porosity of the slabs or the introduction of planar defects. Sorption or capillary condensation of molecules into the pore system results in a 10–40 nm photonic bandgap (PBG) shift. Organic functions added to the pore surface change the response, permitting tailoring of the selectivity towards small‐size molecules.

Hydration of a spherical micelles of C12E6 in solution is studied by molecular dynamics simulation. The interface is found to be separated in an inner part composed of water and hydrophobic and hydrophilic moieties and an outer part with hydrophilic moiety and water only. Hydration numbers in the inner and in the outer parts are in excellent agreement with experimental data from various different methods. Temperature dehydration occurs in the inner region only and is related to the presence of water molecules directly in contact with the hydrophobic core at low temperature.

The use of correlation analysis of photoacoustic signal changes during the sol-gel-aging evolution of titania sols prepared from the hydrolysis of titanium n-butoxide in alcoholic, aqueous, and micellar media which provide different initial conditions and different evolution pathways is proposed. The photoacoustic experiments were done either at constant temperature for monitoring the initial evolution of the system, or under heating at 2°Cċmin−1for monitoring molecular processes related to drying, sintering, and crystallization. Results obtained from photoacoustic measurements display higher sensibility when compared with those from differential thermal analysis (DTA) and thermogravimetric analysis (TGA). The evolution of these systems shows instabilities below and above gelation, as well as during thermal treatment. These stabilities are minimized when the thermal treatment is performed on gels aged several months, and can be associated to molecular rearrangements or oscillating chemical reactions. For all the systems studied, the sensitivity of the correlation analysis recovered from photoacoustic signals permits detection of a transition in the 100 to 150°C range.

BACKGROUND: Endothelial dysfunction and inflammation are present in both type 2 diabetes mellitus (T2DM) and obesity. In this paper we compared the role of weight loss and of glycaemic control in determining circulating levels of ICAM-1, endothelin-1 (ET-1), and E-selectin in patients with morbid (grade 3) obesity. METHODS AND RESULTS: ICAM-1, E-selectin, and ET-1 were higher in obese patients (n=96) than in lean controls (n=30); among obese patients, the three molecules were higher in T2DM patients (n=26) than in patients with normal (NGT, n=43) or impaired (IGT, n=27) glucose tolerance. Sixty-eight obese patients had a significant weight loss induced by bariatric surgery, and showed a significant decrease in blood glucose, HbA1c and all molecules, so that ICAM-1, E-selectin, and ET-1 were not different in NGT, IGT and T2DM patients, and in lean controls; in 13 patients with a small weight loss induced by diet, changes were not significant, in spite of a significant reduction in blood glucose and HbA1c. At stepwise regression, changes in ICAM-1, ET-1, and E-selectin significantly correlated only with change in body mass index. CONCLUSIONS: These data indicate that weight loss is more important than glycaemic control in regulating circulating levels of ICAM-1, ET-1, E-selectin in morbidly obese subjects.

Noise, vibration, and harshness (NVH) can be predominate brake noise described as roughness/judder, brake creep groan, and brake squeal, all of which are important issues and concerns for customer satisfaction in the automotive industry. Brake roughness and groan are low-frequency vibration and noise, while brake squeal is a high-frequency noise. These have been the challenging issues for engineers and researchers for many years due to their complex nature that involves multiple disciplines such as nonlinear dynamics, contact mechanics, and tribology or nanotribology. As in the body/chassis and power-train arena, laser metrology can be uniquely applied in brake NVH to shed light on this complex issue. Engineers can gain insight on NVH fundamental root causes and provide guidance for optimal design resolution. We provide some examples that illustrate the recent progress and novel applications of holographic interferometry, pulsed laser holographic interferometry, pulsed laser electronic speckle pattern interferometry, and laser Doppler vibrometry methodology to identify the root causes of brake concerns and verify engineering solutions. © 2003 Society of Photo-Optical Instrumentation Engineers.

In this paper, we present the structural and dynamic results of a 3.4 ns molecular dynamics simulation of a reaction center protein immersed in a micelle-like environment formed by a detergent, lauryl dimethyl amino oxide or LDAO, and hydrated by more than 6000 additional water molecules. The whole system, ≈40 000 atoms, was simulated using an all-atom force field with refined potential parameters developed by us to describe the protein cofactors and the detergent molecules. LDAO, inserted at the beginning of the run in a configuration far from equilibrium, rearranged forming a micelle attached to the hydrophobic regions of the protein. The micelle is a stable and dynamic structure over the whole trajectory and prevents the protein and the internal cofactors from contacts with water. Comparing our simulated system with the high-resolution crystallographic structure, the deviations of the backbone atoms are small, less than 1.8 Å after 3.4 ns, and the chromophore arrangement geometry is stable and close to X-ray for the whole simulation. Thus, our system constitutes a realistic model to investigate at an atomic level the role of the protein environment on the charge transfer processes taking place in this complex. Related to the functionality of this RC protein, we observe the isomerization of the tyr M210 which is directly coupled with the primary electron transfer. Concerning the branch functionality of the RC, we observe that the computed minimum distance between the chromophores on the L and M side has a different dynamic behavior and is smaller on average for transitions on the L side. This finding might have some bearing on the electron-transfer asymmetry of the primary charge transfer.

To evaluate the role of anticoagulation therapy in carotid stenting with filter devices, we compared the activated clotting times (ACT) to angiographic filter patency and to the materials found inside the filters.29 endovascular treatments with filter cerebral protection in 27 patients affected by symptomatic internal carotid stenosis > 70% were considered. Angiographic findings, ACT and histopathologic specimens were recorded and statistically correlated.Satisfactory dilatation of the stenosis was always achieved with a complication rate of 3%. During the procedure nine filters caused temporary flow impairment. Histopathologic examination demonstrated material inside the filters in 86% of cases but this material was fibrin alone in 38% and plaque debris in 48%. Significant statistical correlation (p = 0.009) was found between low activated clotting time and occlusion of the filter.Distal protection filters can collect plaque fragments occurring during carotid stenting. A significant proportion of the debris found in the filters consisted of thrombotic material. Monitoring of heparin anticoagulation is recommended to prevent filter occlusion.

The sol to gel evolution of titania based systems in AOT (sodium 2-etil-hexil sulfosuccinate) reverse micelles is monitored by the fluorescence anisotropy of molecular probes located in the different phases of the system. In contrast with processes in homogeneous systems, hydrolysis and condensation reactions occur in different time windows. The obtained results allow to describe the location of the hydrolysis, the reorganisation of the surfactant and to predict the formation of precipitates.

Background: There are now a variety of methods to assess body fat distribution, anthropometric (waist circumference and waist/hip W/H ratio), computed tomography (CT), and ultrasound (US) measurements, with CT considered as the reference method. Bariatric surgery leads to a significant and usually durable weight loss in morbidly obese patients; when assessing its results, it is of interest to measure changes of total fat tissue and of body fat distribution. Methods: In this study, we compared anthropometric, US, and CT measurements of body fat distribution under basal conditions and 1 year after laparoscopic adjustable gastric banding (LAGB); 120 morbidly obese patients were considered at baseline, and 40 patients were re-evaluated 1 year after LAGB. Results: Thickness of visceral and subcutaneous fat measured through CT and US methods was superimposable both under basal conditions and 1 year after LAGB, and the highest correlation was found between CT and US data on visceral fat, followed by CT and US data on subcutaneous fat; a fair correlation was also found between CT and US data on visceral fat and waist circumference. Conclusion:We suggest that evaluation of body fat distribution is accomplished by US instead of CT measurement, because of its lower cost and low exposure risk. Waist circumference stands as a reasonable surrogate of both methods, while W/H ratio is poorly correlated with other measures of body fat distribution.

The sol to gel evolution of systems based on the hydrolysis of titanium n-butoxide, Ti(OBuⁿ)4, in 1-butanol was investigated by monitoring the changes of the radiative and nonradiative electronic excited state processes of embedded dyes (cresyl violet and 4-(dicyanomethylene)-2-methyl-6(p-dimethylaminostyryl)-4H-pyran). Fluorescence anisotropy experiments (FA) allow determination of changes in the microviscosity of the medium surrounding the fluorophore through the sol−gel evolution. The increase of the anisotropy parameter, 〈r〉, is explained in terms of solvent confinement in cavities enclosed within cross-linked polymeric chains. The acoustic signal recorded in laser-induced optoacoustics experiments (LIOAS) is attenuated as the system loses fluidity, with a minimum at tg, thus providing an alternative method for determining the gelation point. In addition, within the theoretical approach of percolation theory, the exponent of the viscosity power law is obtained from the attenuation of the sound wave. Although both FA and LIOAS provide information on the degree of cross-linking between polymeric chains, there is a clear difference between the behavior of the macroscopic shear viscosity determined by LIOAS and the local friction or microviscosity obtained from FA.

Summary: The metabasites of Montiggiu Nieddu occur as a lenticular body in the Hercynian migmatite complex of NE Sardinia and consist of two major lithological associations: ultramafic amphibolites and plagioclase-banded amphibolites, which are genetically related by processes of cumulate differentiation of an original tholeiitic magma. The ultramafic amphibolites consist of relics of igneous phases (anorthite, olivine, orthopyroxene, and clinopyroxene) and metamorphic minerals (orthopyroxene, clinopyroxene, plagioclase, garnet, chlorite, and amphibole) in variable proportions. Based on the distribution of the relics of igneous minerals three main compositional layers (A, B, C) have been identified in the ultramafic amphibolites. The plagioclase-banded amphibolites consist of dark-green and white bands made up of plagioclase, amphibole, garnet, and rare pyroxene in variable proportions. No relics of magmatic minerals were observed. The trace element patterns of the Montiggiu Nieddu metabasites are characterised by selective enrichment of incompatible elements of low ionic potential, such as Sr, Rb, Ba, and Th, and low abundance of K, Cr, Ni, and elements of high ionic potential (from Ta to Yb), which define a relatively flat trend similar to MORB composition. Ti, Y, and heavy rare earth elements are all positively correlated with Zr. This correlation suggests that no significant transport of these elements took place during metamorphism. The metabasites of Montiggiu Nieddu are characterised by low Ti, Ti/V, and Ti/Zr content, low rare earth and high-field strength element concentrations, and moderate selective enrichment in large-ion lithophile elements. They also show geochemical features similar to those of supra subduction zone tholeiites. The CaO-MgO diagram displays a segmented trend, which provides powerful evidence in favour of crystal-liquid separation during magmatic evolution.

An analysis of structural properties of the tryptophan−histidine (TRP−HIS) pair in vacuo and in various solvents (water, dimethyl sulfoxide, methanol, and carbon tetrachloride) has been done using classical molecular dynamics simulations with atomistic potential models for both solute and solvent molecules. The potential of mean force (PMF) was determined as a function of the TRP centroid−HIS centroid distance and of the angle between the ring planes. We show that T-shaped structures are favored in nonpolar solvents, whereas they are completely destabilized in solvents forming strong hydrogen bonds. Amphiphilic solvents such as methanol and dimethyl sulfoxide destabilize both the T-shaped and stacked arrangements. The results are consistent with previous analysis on protein crystallographic databases, where the stacked structures are found mainly on the protein surface exposed to the solvent, while T-shaped arrangements are preferentially found in the hydrophobic protein core. Finally, comparison of explicit solvent molecular simulation data and continuum solvent model results emphasizes the importance of microsolvation phenomena in shaping the potential of mean force for tryptophan−histidine interactions.

Background. In Alport syndrome (AS) impaired production and/or assembly of col IV α-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV α-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS.
Methods. GBM distribution of col IV α1-, α3-, and α5-chain was investigated by immunohistochemistry in 32 patients (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on the severity of ultrastructural findings, the biopsies were grouped in three (I-III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning, thickening, splitting, basket weaving of the lamina densa) were singularly evaluated using a semiquantitative scale (0-3).
Results. Col IV α1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IVα3- and α5-chains were observed: positive, negative, and α3(IV)-positive/α5(IV)-negative. By χ²-test, EM class III lesions and complete loss of α3(IV)- and α5(IV)-antigen were significantly more frequent (P&lt;0.05 and P&lt;0.01) in male patients, but no significant relation was observed between EM classes and immunohistochemical patterns. GBM alterations did not correlate with staining for α5(IV)-chain. Intensity of α3(IV)-chain staining, however, had a negative correlation (P&lt;0.05) with the severity of GBM basket weaving.
Conclusions. Our results suggest that the α3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of α3(IV)-chain in GBM could indicate a more severe renal disease in AS.

In Alport syndrome (AS) impaired production and/or assembly of col IV alpha-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV alpha-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS.

This paper is focused on the structural changes occurring in hydrated bovine pancreatic trypsin inhibitor (BPTI) at varying hydrostatic pressure. We have carried out a series of nanosecond constant pressure simulations of BPTI at increasing pressure employing two popular force fields, AMBER and CHARMM. Results concerning the hydrogen bonds lengths and distribution underline differences in the two force fields. Overall, CHARMM predicts a compression of the BPTI backbone hydrogen bond network, while AMBER computes a slight increase in the length of these bonds. Compared to the experimental NMR estimate of hydrogen bond shortening, CHARMM, and to a minor extent AMBER, follow the experimental trend in the β -sheet and helix H2 regions of BPTI. Notwithstanding, both force fields show a rather large overall deviation from NMR findings.

We apply density functional theory in the gradient-corrected local-density approximation to the determination of structural properties and harmonic vibrational modes of trehalose in the gas phase and in the monohydrate crystal. We analyze the local conformation and the relative strength of intra- and intermolecular hydrogen bonds, and we discuss the effects of the crystal environment on the molecular geometry and vibrational frequencies. The density functional results are used to assess the quality of a recent molecular mechanics model. This simplified scheme provides a fairly good description of ground-state geometries, while vibrational properties are only in qualitative agreement with those computed by the density functional method.

The CUSUM method is frequently used by epidemiologists for detecting a shift in the incidence of rare health events. An exact solution for a Poisson process has been proposed by other works, but potential applications have been limited by the fact that the size, the structure of the at‐risk population and the baseline rate may not be constant during the period of surveillance. Furthermore, for practical use tables of critical values are available only for some expected values and in any case less then 9. This paper proposes an approximate CUSUM procedure, based on the normal approximation to a Poisson process, which may be an efficient solution of the problems previously pointed out. Analyses of simulated and actual data sets illustrate the usefulness of the proposed procedure. An application to mortality data for respiratory diseases in a north Tuscany area, characterized by the presence of chemical plants, is showed. No shift in the mortality rate during the 1980–1989 period was detected compared with the 1970–1979 period, in contrast with the result obtained with the standard CUSUM method for a Poisson variate. Copyright © 1999 John Wiley & Sons, Ltd.

More and more citizens urge public health authorities to investigate reports of disease excess in their neighbourhood. These environmental concerns are legitimate and it is part of good public health practice to respond to these complaints. However, the methodological and practical problems are severe and a lot of controversy exists about the usefulness of these investigations. To clarify the possibilities and limitations in this situation, this paper proposes a typology of cluster studies. According to this framework, cluster response is distinguished from two other types of cluster studies: Cluster monitoring, screening proactively for clusters to act as an early warning system, and cluster research, scrutinizing clustering to generate and test aetiological hypotheses. To each of these three types of cluster studies corresponds a different public health context; respectively public health action, public health surveillance and public health research. Probably, part of the controversy mentioned stems from not acknowledging sufficiently the corresponding intrinsic differences in rationality and practical constraints. Cluster response is crisis management and not scientific research. In a relatively short time, an informed decision should be taken by a multidisciplinary team of experts using readily available information and knowledge. In accordance with this point of view, cluster reports should be handled stepwise and the role of statistics is to quantify a cluster exploring different points of view as an input to the decision process.

Attempts to reduce the multiplicity and variety of the range of indicators presently used to measure science and technology to lean patterns have so far proved unsuccessful.

We present a density-functional study of the paclitaxel, taxotere, baccatin III, epothilone-A, and discodermolide molecules in their gas phase. For each of these compounds we determine the geometry and the electronic structure of the ground state and of some isomers and analogues. We find that the central part of all these molecules is insensitive to changes in structure, orientation, and isomerization of its tail and is characterized by a rather large dipole that has similar orientation with respect to the molecular frame. These similarities extend also to the electronic structure. Our results provide an extended and consistent set of data to gauge classical force fields in view of the atomistic investigations of the interaction of these molecules with tubulin.

La patologia della colonna dell'anziano, intendendo arbitrariamente con questo termine soggetti di età superiore ai 60 anni, è costituita per lo più da lesioni degenerative osteo-disco-articolari, dalla osteoporosi e dalle sue complicanze.Dalla revisione di 1.000 esami di tomografia computerizzata della colonna in pazienti di età superiore a 60 anni gli Autori infatti hanno posto diagnosi in 808 casi di malattia degenerativa e di osteoporosi e in 192 casi hanno ritrovato altre patologie che, pur non essendo di esclusiva pertinenza dell'anziano, mostrano una netta predilezione per questa fascia di età. In 27 pazienti fu posta diagnosi di metastasi ed il dato, epidemiologicamente non significativo, è da porsi in relazione al carattere monospecialistico degli Istituti Ortopedici Rizzoli.In 93 casi fu posta diagnosi di tumore osseo primitivo benigno rappresentato dall'emangioma nelle sue varietà asintomatica e compressiva; i 43 casi di tumori ossei primitivi maligni sono da ascrivere in ordine decrescente al mieloma, al cordoma, ai linfomi e a rarissimi casi di emangioendotelioma. In 21 pazienti fu posta diagnosi di spondilodiscite e in 8 di malattia di Paget.Gli autori descrivono le caratteristiche clinico-radiologiche di queste lesioni enfatizzando il ruolo della tomografia computerizzata e della risonanza magnetica non solo nella individuazione e precisazione della lesione ma anche nel bilancio loco-regionale ed infine sottolineano la difficoltà della diagnosi differenziale tra metastasi, tumori primitivi maligni talora con le spondilodisciti e la malattia di Paget per cui spesso è indispensabile il ricorso alla biopsia TC-guidata.

Nel Servizio di Neuroradiologia dell'Ospedale Civile di Vicenza viene svolta attività terapeutica consistente in:1a)Biopsia stereotassica.Eseguita in particolare quando il paziente deve essere sottoposto a radioterapia tradizionale o radiochirurgia stereotassica. In quest'ultima evenienza, infatti le modalità di irradiazione (dose e dimensioni del campo) ed il risultato terapeutico sono influenzati dall'istotipo del tumore.1b)Radiochirurgia stereotassica delle lesioni espansive.Una volta stabiliti i parametri della lesione rispetto al casco stereotassico, il paziente viene trasferito in un acceleratore lineare tipo Mevatron da 6 MeV e sottoposto a radiochirurgia in un'unica seduta.Abbiamo eseguito la radiochirurgia stereotassica in 110 pazienti portatori di tumori cerebrali.1c)Radiochirurgia stereotassica delle malformazioni artero venose (MAV).Nella nostra esperienza, la radiochirurgia stereotassica deve essere limitata alle MAV, mentre risultati mediocri o addirittura peggioramento della situazione si ha nelle malformazioni tipo cavernomi o angiomi venosi. La nostra casistica consiste in 126 MAV.1d)Infissione di Radioisotopi in alcuni casi di glioma.Procedimento analogo a quello utilizzato nella biopsia stereotassica. Viene praticato in casi molto selezionati di neoplasie cerebrali primitive, quando è richieta una irradiazione prolungata con una esposizione limitata e ben definita nello spazio.2)Embolizzazione.In collaborazione con il reparto di Chirurgia Maxillo Facciale, dal 1973.Quasi tutti i nostri interventi sono condotti in anestesia locale, per via femorale, con catateri da 5 o 4 F o con catetere Tracker 18.Utilizziamo soltanto emboli solidi (gelfoam, dura madre, PVA, microspirali in platino). Abbiamo trattato complessivamente 136 pazienti affetti da malformazioni arteriose, artero-venose o venose e neoformazioni benigne o maligne, ipervascolarizzate.3)Chemonucleolisi e nucleotomia percutanea.Effettuata dapprima con il Discase e, dal febbraio 1990, con Lekopain.Abbiamo trattato 135 pazienti, nessuna complicazione. I risultati a distanza di 6 mesi, sono stati ottimi e buoni nel 78%.Per quanto riguarda a nucleotomia percutanea (Onik) abbiamo iniziato nell'agosto 1989. Abbiamo finora trattato 55 pazienti. A distanza di 6 mesi abbiamo riscontrato risultati ottimi e buoni nel 67% dei casi. Non abbiamo avuto nessuna complicazione.4)Biopsia vertebrale.Eseguita in anestesia locale. Abbiamo finora effettuato 35 casi.Sono stati ottenuti soddisfacenti risultati in 32 casi, 18 lesioni tumorali primitive o secondarie e 13 processi infettivi (tubercolosi, osteomielite, micosi). In 4 casi la biopsia non ha fornito la diagnosi.Nessuna complicazione.

We report our experience of needle biopsy over the past two and a half, viz. 395 cases. We find that the technique meets the needs of diagnosis and research very satisfactorily. We describes its advantages over open biopsy and recommend it in preference to the latter, provided that the necessary technical skill for processing the sample is available.

The possibility of interaction between neurotransmitter uptake mechanisms and presynaptic receptors regulating transmitter release was investigated using rat brain synaptosomes in superfusion. Various conditions were considered including: absence of substrate for the uptake with uptake potentially operative; absence of substrate and presence of uptake inhibitors; and uptake activated by added substrate, with or without uptake inhibitors. The release of [3H]-5-hydroxytryptamine ([3H]-5-HT) evoked by 15 mM KCl from cerebral cortex synaptosomes was inhibited by lysergic acid diethylamide. The 5-HT uptake inhibitors citalopram and chlorimipramine did not affect the inhibitory action of lysergic acid diethylamide. Clonidine decreased both the K+-evoked release of [3H]norepinephrine and that of [3H]-5-HT in cortical synaptosomes through the activation of presynaptic alpha-2 adrenoceptors. In superfusion conditions, the action of clonidine on [3H]norepinephrine release was not antagonized by the norepinephrine uptake inhibitors desipramine or cocaine; similarly, the inhibition of [3H]-5-HT release was unaffected when 5-HT uptake was blocked. The K+-evoked release of [3H]dopamine from striatal nerve terminals was potentiated by acetylcholine (ACh) through the activation of muscarinic presynaptic receptors. The action of ACh was not modified by the presence of nomifensine, a dopamine uptake inhibitor. Finally, in superfused cortical synaptosomes, the block of the high-affinity uptake of choline by hemicholinium-3 had no effect on the muscarinic autoreceptor-mediated inhibition of [3H]ACh release by ACh. Altogether the present results do not support the previously proposed idea that in nerve terminals a functional coupling may exist between uptake mechanisms and presynaptic receptors.

A 32-year-old female presented with progressive external ophthalmoplegia (PEO) and multisystem abnormalities, strikingly associated with myotonia and muscle hypertrophy. These two features were not found in her brother, who had a complex neuromuscular disorder complicating chronic PEO. In both subjects muscle biopsy revealed “ragged-red” fibres and myofibres containing glycogen granules, which were never bound by membranes. A severe demyelinating neuropathy was revealed by electrophysiological and morphological studies. Cranial CT scan showed extensive demyelination of the cerebral white matter. Genetic studies demonstrated that this familial syndrome is transmitted as an autosomal recessive trait.

The effects of acetylcholine (ACh) on the release of endogenous glutamic acid (GLU) and of [3H]ACh have been investigated comparatively in superfused rat hippocampal synaptosomes. Exogenous ACh added to the superfusion fluid inhibited the Ca++-dependent K+ (15 mM)-evoked release of GLU in a concentration-dependent manner (the maximal inhibition was about 50%). Carbachol and oxotremorine mimicked, although less potently, the action of ACh. The inhibition of GLU release caused by 10 microM ACh was antagonized by 0.1 microM atropine but not by 10 microM mecamylamine. It also was insensitive to the M-1 receptor antagonists pirenzepine or dicyclomine (both at 1 microM). In contrast, the novel M-2 muscarinic antagonist AF-DX 116 [(11-[(2-[diethylamino]methyl)-1-piperidinyl]acetyl)-5-11-dihydro-6 H-pyrido-[2-3-b][1,4]benzo-diazepine-6-one] was as potent as atropine in blocking the inhibition of GLU release brought about by ACh. The autoreceptor-mediated inhibition of [3H]ACh release observed in presence of ACh (10 microM) was totally antagonized by atropine (0.1 microM). It was insensitive to mecamylamine (10 microM), dicyclomine (1 microM) or pirenzepine (1 microM). However, it was much less sensitive to AF-DX 116 (80-100 times) than the cholinergic inhibition of GLU release. It is concluded that 1) the release of GLU in rat hippocampus can be inhibited through a muscarinic receptor and 2) this novel muscarinic receptor belongs to the M-2 subtype but it seems to differ pharmacologically from the M-2 autoreceptor.

An epidemiological investigation on Duchenne muscular dystrophy in Turin and its province has been carried out for the period 1955–1974. The incidence of the disease proved to be 24×10−5, and the prevalence 2.15×10−5. The mutation rate was 80×10−6. The data are compared with the literature. Segregation analysis on many families was performed in order to find the theoretical number of carrier among Duchenne mothers. The importance of epidemiology for genetic counselling is stressed.

La diagnosi differenziale tra lesione neoplastica primitiva benigna o maligna e metastasi solitaria nei pazienti con anamnesi oncologica negativa è estremamente difficoltosa ma rappresenta un'esigenza fondamentale per una corretta strategia terapeutica. Una revisione della casistica degli Istituti Ortopedici Rizzoli raccolta negli ultimi 4 anni, ha dimostrato che solo in 18 casi di pazienti di età compresa fra 50 e 80 anni si è posto il problema diagnostico differenziale menzionato e che esso, nonostante le informazioni ottenute con la RC, la TC e la RM, è stato risolto solo ricorrendo alla biopsia, o TC guidata o chirurgica.È stato possibile tuttavia rilevare, specie utilizzando la TC con mezzo di contrasto, alcune caratteristiche semeiologiche delle lesioni riscontrate (10 metastasi, 4 cordomi, 2 plasmocitomi, 1 linfoma e 1 emangiopericitoma) che consentono di formulare un orientamento diagnostico; la TC e la RM si sono mostrate in tutti i casi utili per realizzare una corretta stadiazione loco-regionale.