Immunogenetics of an antigen identified in both sheep and cattle sera.

SUMMARYAlloimmunization in sheep revealed an antigen specificity B1 which is also to be found in cattle sera. The molecular weight of the protein carrying B1 was greater in sheep than in cattle, whilst in both cases its isoelectric point was at pH 6·2. The electrophoretic position of the antigen suggests that the molecule carrying B1 might be a β-globulin. Family studies indicated that in both species B1 was inherited in a simple Mendelian manner, as if it were a product of a dominant alleleB1at an autosomal locusB

Venous Pulse Wave Velocity variation in response to a simulated fluid challenge in healthy subjects

Purpose: The evaluation of a mini or simulated fluid challenge is still a complex and open issue in the clinical setting and it is of paramount significance for the fluid therapy optimization. We here investigated the capacity of a new hemodynamic parameter, the venous Pulse Wave Velocity (vPWV), to detect the effect of passive leg raising (PLR). Materials and methods: In 15 healthy volunteers (7 M, 8 F, age 26 ± 3) venous pressure pulses were elicited by pneumatic compressions of the left hand and proximally detected by ultrasound for calculation of the vPWV. We also non-invasively measured the basilic vein (BV) cross-sectional perimeter, and peripheral venous pressure (PVP). The PLR manoeuvre was performed twice to evaluate reliability of the assessment. Results: The PLR had an overall statistically significant effect on the entire set of variables (MANOVA, p < 0.05): vPWV increased from 2.11 ± 0.46 to 2.30 ± 0.47 m/s (p = 0.01; average increase: 10%). This effect was transient and dropped below 5% after about 3 min. A significant increase was also exhibited by BV size and PVP. In consecutive measurements vPWV showed little intra-subject variability (CoV = 8%) and good reliability (ICC = 0.87). Finally, the vPWV responses to the two PLRs exhibited good agreement (paired T-test: p = 0.96), and moderate reliability (ICC = 0.57). Conclusion: These results demonstrated that vPWV can be non-invasively, objectively and reliably measured in healthy subjects and that it is adequate to detect small pressure/volume variations, as induced by PLR-from-supine. These characteristics make it suitable for clinical applications

Why Local Party Leaders Don't Support Nominating Centrists

Would giving party leaders more influence in primary elections in the United States decrease elite polarization? Some scholars have argued that political party leaders tend to support centrist candidates in the hopes of winning general elections. In contrast, the authors argue that many local party leaders - especially Republicans - may not believe that centrists perform better in elections and therefore may not support nominating them. They test this argument using data from an original survey of 1,118 county-level party leaders. In experiments, they find that local party leaders most prefer nominating candidates who are similar to typical co-partisans, not centrists. Moreover, given the choice between a more centrist and more extreme candidate, they strongly prefer extremists: Democrats do so by about 2 to 1 and Republicans by 10 to 1. Likewise, in open-ended questions, Democratic Party leaders are twice as likely to say they look for extreme candidates relative to centrists; Republican Party leaders are five times as likely. Potentially driving these partisan differences, Republican leaders are especially likely to believe that extremists can win general elections and overestimate the electorate's conservatism by double digits

Assessment of myocardial extracellular volume on body computed tomography in breast cancer patients treated with anthracyclines

Background: Cancer treatment with anthracyclines may lead to an increased incidence of cardiac disease due to cardiotoxicity, as they may cause irreversible myocardial fibrosis. So far, the proposed methods for screening patients for cardiotoxicity have led to only limited success, while the analysis of myocardial extracellular volume (mECV) at cardiac magnetic resonance (CMR) has shown promising results, albeit requiring a dedicated exam. Recent studies have found strong correlations between mECV values obtained through computed tomography (CT), and those derived from CMR. Thus, our purpose was to evaluate the feasibility of estimating mECV on thoracic contrast-enhanced CT performed for staging or follow-up in breast cancer patients treated with anthracyclines, and, if feasible, to assess if a rise in mECV is associated with chemotherapy, and persistent over time. Methods: After ethics committee approval, female patients with breast cancer who had undergone at least 2 staging or follow-up CT examinations at our institution, one before and one shortly after the end of chemotherapy including anthracyclines were retrospectively evaluated. Patients without available haematocrit, with artefacts in CT images, or who had undergone radiation therapy of the left breast were excluded. Follow-up CT examinations at longer time intervals were also analysed, when available. mECV was calculated on scans obtained at 1, and 7 min after contrast injection. Results: Thirty-two female patients (aged 57\ub113 years) with pre-treatment haematocrit 38%\ub14%, and ejection fraction 64%\ub16% were analysed. Pre-treatment mECV was 27.0%\ub12.9% at 1 min, and 26.4%\ub13.8% at 7 min, similar to values reported for normal subjects in the literature. Post-treatment mECV (median interval: 89 days after treatment) was 31.1%\ub14.9%, and 30.0%\ub15.1%, respectively, values significantly higher than pre-treatment values at all times (P&lt;0.005). mECV at follow-up (median interval: 135 days after post-treatment CT) was 31.0%\ub14.5%, and 27.7%\ub13.7%, respectively, without significant differences (P&gt;0.548) when compared to post-treatment values. Conclusions: mECV values from contrast-enhanced CT scans could play a role in the assessment of myocardial condition in breast cancer patients undergoing anthracycline-based chemotherapy. CT-derived ECV could be an imaging biomarker for the monitoring of therapy-related cardiotoxicity, allowing for potential secondary prevention of cardiac damage, using data derived from an examination that could be already part of patients\u2019 clinical workflow

Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response

A Pig Model of Hemivascular Liver Occlusion for The Study of Ischemia-Reperfusion Injury: Use of an Infrared System for Detecting Ischemic Areas

Aim: Different animals are used as experimental models for the hepatic Ischemia- Reperfusion (IR) injury investigations and for each one of these animal models, many different surgical approaches have been performed. The aim of our study was to establish a new surgical pig model in which a hemi-liver is used to study the pathophysiology of hepatic IR injury. Contro-lateral hemi- liver is used as an internal control in the same animal. Methods: Liver ischemia was performed in six pigs by clamping the hepatic artery and vein and the portal vein to isolate the left hepatic lobe. Four hours of warm ischemia were followed by 4-hourrs of reperfusion. Biochemical and hematological analyses were performed throughout the experiments. Needle biopsies were obtained prior to ischemia and then hourly during the reperfusion for evaluation of tissue damage. To assess local temperature gradients on the liver surface a focal plane array detector camera was used. Results: Four hours ischemia induced mild signs of hepatic damage on the left ischemic lobe while more dramatic changes were evidenced after 2-hours reperfusion. Absence of tissue damage was detected on the right lobe. The liver functional test reached their maximum value at 2-4 hours after reperfusion. Conclusion: Our model is easy to perform, feasible and reproducible. This surgical model minimizes biases dependent on the individual response of different animals under the same conditions. In this IR model the new technology of an infrared thermocamera was used to control temperature changes and provide clinically important real-time information during surgery

Low-grade gliomas in patients with Noonan syndrome: case-based review of the literature

Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling