Evidence for detrimental cross interactions between reactive oxygen and nitrogen species in Leber's hereditary optic neuropathy cells

Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber’s hereditary optic neuropathy (LHON) patients.We report that peripheral blood mononuclear cells (PBMCs), derived froma female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment

New insights on partial trisomy 3q syndrome: de novo 3q27.1-q29 duplication in a newborn with pre and postnatal overgrowth and assisted reproductive conception

Background. Duplications of the long arm of chromosome 3 are rare, and associated to a well-defined contiguous gene syndrome known as partial trisomy 3q syndrome. It has been first described in 1966 by Falek et al., and since then around 100 patients have been reported. Clinical manifestations include characteristic facial dysmorphic features, microcephaly, hirsutism, congenital heart disease, genitourinary anomalies, hand and feet abnormalities, growth disturbances and intellectual disability. Most of cases are due to unbalanced translocations, inherited from a parent carrying a balanced aberration (reciprocal translocation or inversion), and rarely the genomic anomaly arises de novo. Very few studies report on the prenatal identification of such rearrangements. Case presentation. Hereby, we report on a newborn with a rare pure duplication of the long arm of chromosome 3. Noninvasive prenatal test (cell free fetal DNA analysis on maternal blood), performed for advanced parental age and use of assisted reproductive technique, evidenced a partial 3q trisomy. Then, invasive cytogenetic (standard and molecular) investigations, carried out through amniocentesis, confirmed and defined a 3q27.1-q29 duplication spanning 10.9 Mb, and including about 80 genes. Our patient showed clinical findings (typical facial dysmorphic features, esotropia, short neck, atrial septal defect, hepatomegaly, mild motor delay) compatible with partial trisomy 3q syndrome diagnosis, in addition to pre- and postnatal overgrowth. Conclusions. Advanced parental age increases the probability of chromosomal and/or genomic anomalies, while ART that of epigenomic defects. Both conditions, thus, deserve more careful prenatal monitoring and screening/diagnostic investigations. Among the latter, cell free fetal DNA testing can detect large segmental aneuploidies, along with chromosomal abnormalities. It identified in our patient a wide 3q rearrangement, then confirmed and defined through invasive molecular cytogenetic analysis. Neonatologists and pediatricians must be aware of the potential risks associated to duplication syndromes. Therefore, they should offer to affected subjects an adequate management and early and careful follow-up. These may be able to guarantee to patients satisfactory growth and development profiles, prevent and/or limit neurodevelopmental disorders, and timely recognition of complications

Electrocardiographic and other noninvasive hemodynamic markers in decompensated CHF patients

cutely decompensated chronic heart failure (adCHF) is among the most important causes of in-hospital mortality. R-wave peak time (RpT) or delayed intrinsicoid deflection was proposed as a risk marker of sudden cardiac death and heart failure decompensation. Authors want to verify if QR interval or RpT, obtained from 12-lead standard ECG and during 5-min ECG recordings (II lead), could be useful to identify adCHF. At hospital admission, patients underwent 5-min ECG recordings, obtaining mean and standard deviation (SD) of the following ECG intervals: QR, QRS, QT, JT, and T peak–T end (Te). The RpT from a standard ECG was calculated. Patients were grouped by the age-stratified Januzzi NT-proBNP cut-off. A total of 140 patients with suspected adCHF were enrolled: 87 (mean age 83 ± 10, M/F 38/49) with and 53 (mean age: 83 ± 9, M/F: 23/30) without adCHF. V5-, V6- (p < 0.05) RpT, and QRSD, QRSSD, QTSD, JTSD, and TeSD p < 0.001 were significantly higher in the adCHF group. Multivariable logistic regression analysis demonstrated that the mean of QT (p < 0.05) and Te (p < 0.05) were the most reliable markers of in-hospital mortality. V6 RpT was directly related to NT-proBNP (r: 0.26, p < 0.001) and inversely related to a left ventricular ejection fraction (r: 0.38, p < 0.001). The intrinsicoid deflection time (obtained from V5-6 and QRSD) could be used as a possible marker of adCHF

Modello di capacità e valutazione delle prestazioni per le rotatorie a turbina.

L’evoluzione più recente delle intersezioni a rotatoria si è indirizzata verso schemi cosiddetti a turbina (turborotatorie) con l’obiettivo di garantire condizioni di sicurezza più elevate rispetto agli schemi tradizionali. I pochi esempi di realizzazione delle rotatorie a turbina non hanno tuttavia finora consentito di sviluppare metodi di analisi delle condizioni operative e modelli di capacità che possano vantare una validazione attraverso osservazioni di campo. In ogni caso, l’approccio teorico allo studio funzionale delle turborotatorie presenta aspetti decisamente più complessi di quelli delle rotatorie convenzionali sia a causa delle traiettorie dei flussi in ingresso (costretti ad immettersi in corsie fisicamente separate) sia per la configurazione a turbina della carreggiata anulare e del regime delle precedenze che si stabilisce all’ingresso in rotatoria. Ne risultano profondamente modificati, rispetto alle rotatorie convenzionali, gli schemi di conflitto tra flusso entrante e flusso di contrasto e, di conseguenza, i modelli di capacità applicabili e gli stessi criteri per la valutazione delle prestazioni dell’intersezione. A partire da queste considerazioni, tenuto conto dello stato delle conoscenze, nella presente memoria si propone un criterio di valutazione della capacità delle turborotatorie basato su alcune formulazioni esistenti per le intersezioni regolate dal segnale di precedenza, per le quali è possibile far riferimento alla teoria del gap acceptance. Pur con i limiti di una trattazione esclusivamente teorica, i principali obiettivi dell’approccio seguito sono: i) determinare il dominio di convenienza (in termini capacitivi) delle rotatorie con configurazione a turbina rispetto a quelle convenzionali; ii) valutare indici prestazionali (ritardi, lunghezze delle code e livelli di servizio) più aderenti al reale funzionamento delle turborotatori

Conversion of existing roundabouts into turbo-roundabouts: case studies from real world, Journal of Civil Engineering and Architecture 6(8)

Compared with roundabouts the main advantages of turbo-roundabouts are the reduction in the number of potential conflicting points and the lower speed of vehicles through the intersection; they both can improve road safety conditions at the junction. Moreover, the physical delimitation among lanes limits the side-by-side accident risk. These aspects make turbo-roundabouts more appropriate than roundabouts when a higher level of safety has to be guaranteed, particularly in presence of relevant pedestrian and two-wheels traffic volumes. The present paper has three main objectives : 1) to discuss general design criteria and functional principles of turbo roundabouts; 2) to give the geometric design principles of the central island and circulating lanes; 3) to present three case studies from real world concerning the conversion of existing roundabouts into turbo roundabouts

EVALUATING CAPACITY AND EFFICIENCY OF TURBO-ROUNDABOUTS.

Recent evolution of roundabout design has been directed towards the so-called turbo-roundabout, with the aim of ensuring better safety conditions than those afforded by traditional schemes. The few turbo-roundabout installations so far implemented have not allowed sufficient research in order to analyze operational conditions and capacity models validated by field observations. In any case the theoretical approach to the functional study of turbo-roundabouts undoubtedly involves more complex aspects compared to typical roundabouts because of the paths of entering streams (constrained to get onto physically separated lanes), the “turbine” configuration of the circulatory carriageway, as well as the right-of-way regime imposed on entering traffic. So the conflicting schemes between entering and circulating flows appear highly modified. And so do, consequently, the capacity models and the criteria for evaluating performance which can be applied. Considering these points and the state-of-the-art knowledge on the subject, this paper proposes a criterion for evaluation of turbo-roundabouts capacity which is based on some previous models for unsignalized intersections (particularly roundabouts and Two-Way-Stop-Controlled intersections) and validly tested by the gap-acceptance theory. Though theoretical, the proposed approach has the following main objectives: i) determination of the advantage domain (in terms of capacity) of turbo-roundabouts compared with typical ones; ii) evaluation of performance indicators (delays, queue lengths and levels of service) more consistent with real operational conditions of turbo-roundabouts; iii) the possibility of establishing a homogeneous comparison between traffic performances at turbo-roundabouts and usual uncontrolled intersections

TURBO-ROUNDABOUT GENERAL DESIGN CRITERIA AND FUNCTIONAL PRINCIPLES: CASE STUDIES FROM REAL WORLD

Compared with usual roundabouts the main advantages of turbo-roundabouts are the reduction in the number of potential conflicting points and the lower speed of passing vehicles through the intersection; they both can improve road safety conditions at the junction. Also, the physical delimitation among lanes limits the side-by-side accident risk. These aspects make turbo-roundabouts more appropriate than roundabouts when a higher level of safety has to be guaranteed, particularly in presence of relevant pedestrian and two-wheels traffic volumes. In a previous paper authors proposed a theoretical approach to evaluate turbo-roundabouts capacity founded on gap acceptance theory. In particular, to model in a realistic way traffic conditions at turbo-roundabouts, simulations have been developed starting from behavioral parameters (critical gap and follow-up time) obtained by field observations on the few existing turbo roundabouts. The determination of the advantage domain (in terms of capacity) of turbo-roundabouts compared with typical ones and the way to value performance indicators (delays, queue lengths and levels of service) more consistent with real operational conditions of turbo roundabouts were also proposed. The present paper has three main objectives: 1. to discuss general design criteria and functional principles of turbo roundabouts; 2. to give the geometric design principles of the central island and circulating lanes; 3. to present three case studies from real world concerning the conversion of existing roundabouts into turbo roundabouts. Although results of the study cannot be generalized, by methodological point of view they can be useful to the practitioners and to the road administrations in decision making about the conversion of existing intersections

Entropy from Correlations in TIP4P Water

International audienceWe use molecular dynamics to compute the pair distribution function of liquid TIP4P water as a function of the intermolecular distance and of the five angles that are needed to specify the relative position and orientation of two water molecules. We also calculate the translational and orientational contributions to the two-body term in the multiparticle correlation expansion of the configurational entropy at three selected thermodynamic states, where we also test various approximations for the angular dependence of the pair distribution function. We finally compare the results obtained for the pair entropy of TIP4P water with the experimental values of the excess entropy of ordinary water