The Role of Manganese in \u3cem\u3eStreptococcus sanguinis\u3c/em\u3e

Streptococcus sanguinis is primarily associated with oral health as a commensal bacterium. As an opportunistic pathogen, S. sanguinis is capable of colonizing heart valve vegetations, leading to the disease infective endocarditis. Previous studies from our lab have identified the high-affinity manganese transporter SsaACB as important for endocarditis virulence. The impact that manganese depletion has on S. sanguinis had never been evaluated and a secondary manganese transporter has not been identified. Thus, we employed the use of a fermentor to control large-scale growth over time and depleted manganese in an ΔssaACB mutant using a metal chelator, EDTA. The changes in the transcriptome and metabolome of these cells were measured and it was demonstrated that multiple systems were affected. Many of these systems were linked to carbon catabolite repression through CcpA. We found that levels of the glycolytic metabolite fructose-1,6-bisphosphate, a mediator of CcpA-dependent repression, were increased in manganese-depleted cells despite no change in glucose levels. We also evaluated the impact of low pH on the ΔssaACB mutant and found that growth was reduced at pH 6.2. The same pH did not affect the growth of the wild-type SK36 strain. Analysis of both strains in fermentor-grown cultures revealed that reducing the pH affected the manganese levels of cells and again influenced the transcription of multiple systems. Finally, we identified and characterized the secondary manganese transporter, here named TmpA. Here we report that TmpA transports manganese and contributes to endocarditis virulence in several strains of S. sanguinis. We confirmed that manganese is critical for growth and virulence of S. sanguinis and is intricately tied to many systems through its impact on glycolysis. These findings lay the groundwork for future drug development studies targeting either one or both manganese transporters to prevent endocarditis caused by S. sanguinis and related species

Effect of Short Periods of Normobaric Hyperoxia on Local Brain Tissue Oxygenation & Cerebrospinal Fluid Oxidative Stress Markers in Severe Traumatic Brain Injury

Preliminary evidence suggests that PbtO2 values of ¡Ü 15 mm Hg may be suggestive of brain tissue hypoxia. Accordingly, many neurotrauma intensive care units attempt to maintain the PbtO2 ¡Ý 20 mm Hg based on the belief that this intervention will increase availability of oxygen in the brain for metabolism, and will avoid periods of brain tissue hypoxia with a 5 mm Hg buffer range. In clinical practice, one approach to managing a low PbtO2 (< 20 torr) is to increase the delivered fraction of inspired oxygen (FiO2). It remains unclear whether this therapy has risks as it also has the potential to increase oxidative stress. To determine if short periods of normobaric hyperoxia (2h) affect oxidative stress markers and antioxidant defenses, cerebrospinal fluid (CSF) was assessed in adults [n=11, (9 male, 2 female), mean age 26¡À1.8 yrs], with severe TBI (Glasgow Coma Scale score 6¡À1.4) before, during, and after a FiO2=1.0 challenge. Markers of oxidative stress including lipid peroxidation (F2-isoprostane [ELISA]) and protein oxidation (protein sulfhydryls [fluorescence]) and markers of antioxidant defenses including total antioxidant reserve (AOR) [chemiluminescence] and glutathione [fluorescence] were evaluated in CSF. Physiological parameters, [intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), PbtO2, arterial oxygen content (pO2)] were assessed at the same time points, using a 30 minute average prior to each FiO2 change. Mean (¡ÀSD) PbtO2 and PaO2 levels significantly changed for each time point, [before 27.3¡À7.4, 173.1¡À51.4; during 93.9¡À58.1, 385.5¡À108.3; and after 29.3¡À13.0, 171.8¡À45.1] a FiO2 challenge, (p=.04; .01), respectively. Oxidative stress markers, antioxidant reserve defenses and physiological parameters did not significantly change for any time period. These preliminary findings suggest that brief periods of normobaric hyperoxia improve oxygen levels without producing local oxidative stress in brain tissue. Additional studies are required to examine extended periods of normobaric hyperoxia and application of treatment during periods of critical PbtO2 levels

Il mare che e... Un intervento psicosociale sui giovani autori di reato di Palermo

I progetti di intervento sui minori autori di reato possono creare un utile servizio ad un adeguato percorso rieducativo dei beneficiari, mirato ad una crescita personale e ad un incremento di responsabilit\ue0. Infatti le azioni proposte dai progetti non solo possono creare una rete tra istituzioni e privato-sociale atta a supportare l'intervento della giustizia minorile, ma hanno anche la capacit\ue0 di contribuire alla riduzione del rischio di recidiva e alla promozione del reinserimento sociale dei giovani coinvolti. Questi i presupposti per i quali due associazioni di volontariato e sportive del palermitano, con la supervisione dell'Universit\ue0 degli studi della citt\ue0, per l'estate 2015 hanno proposto all\u2019Istituto Penale per i Minorenni "Malaspina" un progetto avente come strumento lo snorkeling, escursione subacquea che si pratica in acque di bassa profondit\ue0, e come obiettivo quello di favorire l'integrazione sociale dei beneficiari (5 giovani) contrapponendosi alla discriminazione e, ancora, di incrementare nuove capacit\ue0 d'analisi dei processi di sfida e di confronto. Il mare, scenario del progetto, ha ulteriormente stimolato lo sviluppo e la consapevolezza sia delle potenzialit\ue0 del singolo sia delle opportunit\ue0 offerte dal territorio. L'esito positivo del progetto ha esortato alla sua conferma per gli anni successivi e al coinvolgimento di altre associazioni e di altri minori e giovani adulti dell'istituto. L'evento pubblico conclusivo, finalizzato alla conoscenza e alla diffusione dell'iniziativa, ha inoltre contribuito a sensibilizzare i presenti all' esperienza detentiva dei minori e dei giovani adulti ed esortato alla riflessione sul possibile cambiamento degli autori di reato

Observation of the rare decay B+ -> K+π0π0 and measurement of the quasi-two-body contributions B+ -> K*(892)+π0, B+ -> f0(980)K+, and B+ -> χc0K+

We report an analysis of charmless hadronic decays of charged B mesons to the final state K(+) pi(0)pi(0), using a data sample of (470.9 +/- 2.8) x 10(6) B (B) over bar events collected with the BABAR detector at the Y(4S) resonance. We observe an excess of signal events, with a significance above 10 standard deviations including systematic uncertainties, and measure the branching fraction and CP asymmetry to be B(B(+) -> K(+) pi(0)pi(0)) = (16.2 +/- 1.2 +/- 1.5) x 10(-6) and A(CP)(B(+) -> K(+) pi(0)pi(0)) = -0.06 +/- 0.06 +/- 0.04, where the uncertainties are statistical and systematic, respectively. Additionally, we study the contributions of the B(+) -> K*(892)(+) pi(0), B(+) -> f(0)(980)K(+), and B(+) -> chi(c0)K(+) quasi-two-body decays. We report the world's best measurements of the branching fraction and CP asymmetry of the B(+) -> K(+) pi(0)pi(0) and B(+) -> K(+)(892)(+) pi(0) channels

First observation of the charmless decay B+ -> K+π0π0 and study of the Dalitz plot structure

Results for the first measurement of the inclusive branching and CP asymmetry of the charmless 3-body decay B+ -> K+π0π0 are presented. The analysis uses a data sample with an integrated luminosity of 429.0 fb−1, recorded by the BABAR detector at the PEP-II asymmetric B Factory. This sample corresponds to 470.9 ± 2.8 million BB pairs. Measurements of the branching fractions (B) and CP asymmetries (ACP) of some of the intermediate resonances in the K+π0π0 Dalitz plot are also presented. The results are summarised here: # B (B+ -> K+π0π0) = (16.2 ± 1.2 ± 1.4) × 10−6 # B (B+ -> K*(892)+π0;K*0(892) -> K+π0) = (2.72 ± 0.50 ± 0.34) × 10−6 # B (B+ -> f0(980)K+; f0(980) -> π0π0) = (2.77 ± 0.56 ± 0.43) × 10−6 # B (B+ -> Xc0K+; Xc0 -> π0π0) = (0.51 ± 0.22 ± 0.09) # ACP (B+ -> K+π0π0) = (−6 ± 6 ± 4)% # ACP (B+ -> K*(892)+π0) = (−4 ± 26 ± 4)% # ACP (B+ -> f0(980)K+) = (17 ± 18 ± 4)% # ACP (B+ -> Xc0K+) = (−89 ± 37 ± 4)

Examination of coalescence as the origin of nuclei in hadronic collisions

The origin of weakly bound nuclear clusters in hadronic collisions is a key question to be addressed by heavy-ion collision (HIC) experiments. The measured yields of clusters are approximately consistent with expectations from phenomenological statistical hadronization models (SHMs), but a theoretical understanding of the dynamics of cluster formation prior to kinetic freeze-out is lacking. The competing model is nuclear coalescence, which attributes cluster formation to the effect of final state interactions (FSI) during the propagation of the nuclei from kinetic freeze-out to the observer. This phenomenon is closely related to the effect of FSI in imprinting femtoscopic correlations between continuum pairs of particles at small relative momentum difference. We give a concise theoretical derivation of the coalescence-correlation relation, predicting nuclear cluster spectra from femtoscopic measurements. We review the fact that coalescence derives from a relativistic Bethe-Salpeter equation, and recall how effective quantum mechanics controls the dynamics of cluster particles that are nonrelativistic in the cluster center-of-mass frame. We demonstrate that the coalescence-correlation relation is roughly consistent with the observed cluster spectra in systems ranging from PbPb to pPb and pp collisions. Paying special attention to nuclear wave functions, we derive the coalescence prediction for the hypertriton and show that it, too, is roughly consistent with the data. Our work motivates a combined experimental programme addressing femtoscopy and cluster production under a unified framework. Upcoming pp, pPb, and peripheral PbPb data analyzed within such a program could stringently test coalescence as the origin of clusters

A techno-economic approach for decision-making in metal additive manufacturing: metal extrusion versus single and multiple laser powder bed fusion

This work presents a decision-making methodology that allows the merging of quantitative and qualitative decision variables for selecting the optimal metal Additive Manufacturing (AM) technology. The approach is applied on two competing technologies in the field of metal AM industry, i.e., the metal extrusion AM process (metal FFF) and the Laser Powder Bed Fusion process (LPBF) with single and multiple lasers, which represent the benchmark solution currently on the market. A comprehensive techno-economical comparison is presented where the two processes are analysed in terms of process capabilities (quality, easiness of use, setup time, range of possible materials, etc.) and costs, considering two different production scenarios and different parts’ geometries. In the first scenario, the AM system is assumed to be dedicated to one single part production while in this second scenario, the AM system is assumed to be saturated, as devoted to producing a wide mix of part types. For each scenario, two different part types made of 17–4 PH stainless steel are considered as a reference to investigate the effect of shape complexity, part size and production times to select the best technology when metal FFF and LPBF must be considered. The first part type refers to an extrusion die, to represent typical shapes of interest in the tooling industry, while the second part type is an impeller which can be used in many different industrial sectors, ranging from oil and gas to aerospace. In order to include quantitative and qualitative criteria, a decision-making model based on Analytic Hierarchy Process (AHP) is proposed as the enabler tool for decision making. The proposed approach allows to determine the most effective solution depending on the different production configurations and part types and can be used as a guideline and extended to include other technologies in the field of metal AM. On the other side, the critical discussion of the criteria selected, and the results achieved allow to highlight the pros and cons of the competing technologies, thus defining the existing limits to define directions for future research

UNILATERAL SENSORINEURAL HEARING LOSS IN SCHOLASTIC AGE SUBJECTS: PSYCHOPEDAGOGICAL ASPECTS

The Authors want to assess a probable significant relation between the unilateral sensorineural hearing loss and some learning difficulties and language acquisitions, often found, through our observation, in impaired children. The Authors have examined a group of subjects in their scholastic age who have this kind of hearing loss and, through several dialogues with them, they have gathered some relevant data about the difficulties that children have at school, and drawn up a questionnaire

Using musculoskeletal models to estimate in vivo total knee replacement kinematics and loads: effect of differences between models

Total knee replacement (TKR) is one of the most performed orthopedic surgeries to treat knee joint diseases in the elderly population. Although the survivorship of knee implants may extend beyond two decades, the poor outcome rate remains considerable. A recent computational approach used to better understand failure modes and improve TKR outcomes is based on the combination of musculoskeletal (MSK) and finite element models. This combined multiscale modeling approach is a promising strategy in the field of computational biomechanics; however, some critical aspects need to be investigated. In particular, the identification and quantification of the uncertainties related to the boundary conditions used as inputs to the finite element model due to a different definition of the MSK model are crucial. Therefore, the aim of this study is to investigate this problem, which is relevant for the model credibility assessment process. Three different generic MSK models available in the OpenSim platform were used to simulate gait, based on the experimental data from the fifth edition of the “Grand Challenge Competitions to Predict in vivo Knee Loads.” The outputs of the MSK analyses were compared in terms of relative kinematics of the knee implant components and joint reaction (JR) forces and moments acting on the tibial insert. Additionally, the estimated knee JRs were compared with those measured by the instrumented knee implant so that the “global goodness of fit” was quantified for each model. Our results indicated that the different kinematic definitions of the knee joint and the muscle model implemented in the different MSK models influenced both the motion and the load history of the artificial joint. This study demonstrates the importance of examining the influence of the model assumptions on the output results and represents the first step for future studies that will investigate how the uncertainties in the MSK models propagate on disease-specific finite element model results

Surface activated chemical ionization - Electrospray mass spectrometry in the analysis of urinary thiodiglycolic acid

RATIONALE Thiodiglycolic acid (TDGA) is a urinary metabolite of the oxazaphosphorine class of chemotherapeutics, in particular of ifosfamide. Ifosfamide metabolism generates chloroacetaldehyde (CAA), a toxic compound associated with neurotoxicity, nephrotoxicity, urotoxicity and cardiotoxicity. CAA, in turn, interacts with cellular thiol groups leading to GSH depletion, cell death and generation of thiodiglycolic acid (TDGA), as a final product. TDGA is mainly excreted in the urine. The ability to accurately measure TDGA in urine, therefore, will be a useful way of monitoring the ifosfamide exposure during chemotherapy. METHODS TDGA in urine samples was measured with liquid chromatograpy coupled to mass spectrometry (LC-MS) by means of a novel Surface Activated Chemical Ionization - Electrospray (SACI-ESI) or a classical ESI ion source alone. RESULTS The SACI - ESI and ESI alone based methods for analysis of urinary TDGA were optimized and compared. A strong reduction in matrix effect together with enhanced quantification performances was obtained with the SACI \u2013 ESI when compared with the ESI. In particular, an increase in quantification precision (from 85 to 95%) and accuracy (from 59 to 90%) were observed, which allowed for optimal detection of TDGA. CONCLUSIONS The LC-SACI-ESI-MS approach provides a very sensitive and quantitative method for the analysis of TDGA. Thanks to sensitivity enhancement and matrix effect reduction, the SACI \u2013 ESI enables the use of a relatively low cost ion-trap mass spectrometer in the analysis of this toxicity biomarker in urine. Due to these characteristics, this approach would constitutes an invaluable tool in the clinical laboratory, for measuring TDGA and other toxicity related biomarkers of chemotherapy with proper sensitivity and accuracy