Lycopersicon esculentum lectin: an effective and versatile endothelial marker of normal and tumoral blood vessels in the central nervous system

The binding of Lycopersicon esculentum lectin (LEA) to the vascular endothelium was studied in the central nervous system of rat, mouse and guinea pig at different developmental ages, and in a gliosarcoma model. Our observations showed that LEA consistently stained the entire vascular tree in the spinal cord and in the brain of all animal species at all developmental ages investigated. In the tumor model, the staining of the vascular network was very reproducible, enabled an easy identification of vascular profiles and displayed a higher efficiency when compared to two other commonly used vascular marker (EHS laminin and PECAM-1). Moreover, our results showed that LEA staining was comparable in both vibratome and paraffin sections and could be easily combined with other markers in double labeling experiments. These observations indicate that LEA staining may represent an effective and versatile endothelial marker for the study of the vasculature of the central nervous system in different animal species and experimental conditions

Out-of-hospital helmet CPAP in acute respiratory failure reduces mortality: a study led by nurses

Background and Aim. Acute respiratory failure (ARF) is a condition that must be treated as quickly as possible. Continuous Positive Airway Pressure (CPAP) is a common method used to treat ARF in hospital. The main objective of our study was to investigate the effect of CPAP prior to admission to the emergency room, on the reduction of endotracheal intubation, in-hospital mortality and on the length of stay in hospital (HLOS). Methods. A prospective, observational (non-randomised) study with a historical control group. Data from 3 groups of patients with ARF, irrespective of cause, was collected: pre-hospital CPAP (PHCPAP) group, i.e. 35 patients treated with a helmet CPAP in the ambulance, by trained nurses (mean age, years 80.1±7.9 SD; 14 males); hospital CPAP (HCPAP) group, i.e. 46 patients treated with helmet CPAP in the hospital emergency room (mean age 78.6±6.9 SD; 27 males), and a historical control group of 125 patients treated with medical therapy only (mean age 76.7±5.5 SD; 52 males). CPAP was delivered via a helmet interface. Results. Compared with standard medical therapy, helmet CPAP (pre and in-hospital) reduced mortality by 77 % (p=0.005), while pre-hospital helmet CPAP reduced it by 94% (p=0.011), after adjustment for age, sex, severity of clinical conditions at entry and diagnosis upon admission. HLOS was reduced, compared with standard medical therapy, by 63.5% and by 66% (adjusting for age, sex, severity of clinical conditions at entry and diagnosis at admission) with helmet CPAP (pre and in-hospital) and with helmet CPAP in the ambulance, respectively (p<0.0001). Conclusions. Treating patients with ARF of any cause, with CPAP by trained nurses, before hospital admission, is safe, reduces mortality and the length of stay needed in hospital

Hypertension risk and clinical care in patients with bipolar disorder or schizophrenia; a systematic review and meta-analysis.

BACKGROUND: A higher cardiovascular morbidity and mortality has been observed in patients with bipolar disorder (BPD) or schizophrenia, partly due to an increased risk of hypertension (HTN), or a less effective care of it. This systematic review and meta-analysis, presents a critical appraisal and summary of the studies addressing the risk of HTN, or the differences in its care, for those with schizophrenia or BPD. METHODS: Prospective studies were searched in PubMed, Embase, PsycINFO, Scopus, and the Web of Science, from database inception to June 2017. A meta-analysis was undertaken to obtain pooled estimates of the risk of HTN. RESULTS: Five studies reporting the risk of HTN, and five studies presenting differences in its clinical care, were identified. An increased risk of HTN was observed for BPD patients, with an overall Incidence Rate Ratio 1.27(1.15-1.40). The pooled Incidence Rate Ratio of HTN for those with schizophrenia was 0.94 (0.75 - 1.14). A poorer care of HTN (lower rates of screening, prescription, and adherence) was reported in four studies of schizophrenia, and two of BPD patients, compared to people without these conditions. LIMITATIONS: reduced number of studies on risk and care of HTN on patients with BPD or schizophrenia. CONCLUSIONS: Limited evidence suggests that patients with BPD have a higher risk of HTN. Patients with schizophrenia and BPD receive poor care of HTN. Understanding the risk of HTN, and the differences in its care, is essential for clinicians to reduce the cardiovascular morbidity and overall mortality of these patients.Luis Ayerbe is funded by an NIHR Clinical Lectureship. Salma Ayis is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust and Kings College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Healt

Normative Autonomy and Normative Co-ordination: Declarative Power, Representation, and Mandate

In this paper we provide a formal analysis of the idea of normative co-ordination. We argue that this idea is based on the assumption that agents can achieve flexible co-ordination by conferring normative positions to other agents. These positions include duties, permissions, and powers. In particular, we explain the idea of declarative power, which consists in the capacity of the power-holder of creating normative positions, involving other agents, simply by "proclaiming" such positions. In addition, we account also for the concepts of representation, namely the representative's capacity of acting in the name of his principal, and of mandate, which is the mandatee's duty to act as the mandator has requested. Finally, we show how the framework can be applied to represent the contract-net protocol. Some brief remarks on future research and applications conclude this contribution

Training fisico ed attivazione piastrinica in pazienti con claudicatio intermittens: effetti in condizioni di riposo e dopo induzione di ischemia.

Training is a documented effective treatment in patients affected from paripheral arterial disease. Platelet activation plays a pivoltal role in atherosclerosis progression and cardiovascular events. In ischemic heart disease, platelet activation is reduced by aerobic traning, while strenuous execise is associated with enhanced activation. Few data can be found for patients with peripheral arterial disease on training. We aimed to evaluate the effects of aerobic training on platelet activation and oxidative stress at rest and after maximal walking exercise. 18 patients with claudication were enrolled and underwent a 15 days aerobic training period (cycling and treadmill exercise under maximal walking capacity). Platelet function (PAF 100, P selectin) and oxidative stress (malondialdehyde) were analyzed at rest and after maximal treadmill test, at the beginning and at the end of the period. At the end of training absolute walking distance increased, malondialdehyde significantly decreased, P-selectin decreased and epinephrine platelet activation improved. Maximal treadmill test increased ADP platelet activation, while it decrease at the end of training. Aerobic supervised training in patients with peripheral arterial disease improves platelets aggregation, oxidative stress and platelets aggregation during ischemia. These data support and help explaining the benefit of training in atherosclerosis

Out-of-hospital helmet CPAP in acute respiratory failure reduces mortality: a study led by nurses

Background and Aim. Acute respiratory failure (ARF) is a condition that must be treated as quickly as possible. Continuous Positive Airway Pressure (CPAP) is a common method used to treat ARF in hospital. The main objective of our study was to investigate the effect of CPAP prior to admission to the emergency room, on the reduction of endotracheal intubation, in-hospital mortality and on the length of stay in hospital (HLOS). Methods. A prospective, observational (non-randomised) study with a historical control group. Data from 3 groups of patients with ARF, irrespective of cause, was collected: pre-hospital CPAP (PHCPAP) group, i.e. 35 patients treated with a helmet CPAP in the ambulance, by trained nurses (mean age, years 80.1±7.9 SD; 14 males); hospital CPAP (HCPAP) group, i.e. 46 patients treated with helmet CPAP in the hospital emergency room (mean age 78.6±6.9 SD; 27 males), and a historical control group of 125 patients treated with medical therapy only (mean age 76.7±5.5 SD; 52 males). CPAP was delivered via a helmet interface. Results. Compared with standard medical therapy, helmet CPAP (pre and in-hospital) reduced mortality by 77 % (p=0.005), while pre-hospital helmet CPAP reduced it by 94% (p=0.011), after adjustment for age, sex, severity of clinical conditions at entry and diagnosis upon admission. HLOS was reduced, compared with standard medical therapy, by 63.5% and by 66% (adjusting for age, sex, severity of clinical conditions at entry and diagnosis at admission) with helmet CPAP (pre and in-hospital) and with helmet CPAP in the ambulance, respectively (p<0.0001). Conclusions. Treating patients with ARF of any cause, with CPAP by trained nurses, before hospital admission, is safe, reduces mortality and the length of stay needed in hospital

Generation of an induced pluripotent stem cell line, CSSi011-A (6534), from an Amyotrophic lateral sclerosis patient with heterozygous L145F mutation in SOD1 gene

Among the known causative genes of familial ALS, SOD1 mutation is one of the most common. It encodes for the ubiquitous detoxifying copper/zinc binding SOD1 enzyme, whose mutations selectively cause motor neuron death, although the mechanisms are not as yet clear. What is known is that mutant-mediated toxicity is not caused by loss of its detoxifying activity but by a gain-of-function. In order to better understand the pathogenic mechanisms of SOD1 mutation, a human induced pluripotent stem cell (hiPSC) line was generated from the somatic cells of a female patient carrying a missense variation in SOD1 (L145F)

Cyclooxygenase 2, toll-like receptor 4 and interleukin 1beta mRNA expression in atherosclerotic plaques of type 2 diabetic patients.

Objectives and design: Inflammation has a prominent role in the development of atherosclerosis. Type 2 diabetes could contribute to atherosclerosis development by promoting inflammation. This status might accelerate changes in intrinsic vascular wall cells and favor plaque formation. Cyclooxygenase 2 (COX-2) is highly expressed in atherosclerotic plaques. COX-2 gene expression is promoted through activation of toll-like receptor 4 (TLR4) and pro-inflammatory cytokine interleukin 1\u3b2 (IL1-\u3b2). Aim of this study is to investigate whether expression profiles of pro-inflammatory genes such as COX-2, TLR4 and IL1-\u3b2 in atherosclerotic plaques are altered in type 2 diabetes (T2D).Methods: Total RNA was isolated from plaques of atherosclerotic patients and expression of COX-2, TLR4, IL1-\u3b2 analyzed using real-time PCR. Histological analysis was performed on sections of the plaque to establish the degree of instability.Results: Statistically significant differences in mRNA expression of COX-2 and IL1-\u3b2 were found in plaques of T2D compared with non-T2D patients. A multi-variable linear regression model suggests that COX-2 mRNA expression is affected by T2D pathology and IL1-\u3b2 mRNA expression in atherosclerotic plaques.Conclusions: Our results support the hypothesis that T2D pathology contributes in vivo to increase the inflammatory process associated with the atherosclerotic plaque formation, as shown by an increment of COX-2 and IL1-\u3b2 mRNA expression

Allelic Origin of Protease-Sensitive and Protease-Resistant Prion Protein Isoforms in Gerstmann-Sträussler-Scheinker Disease with the P102L Mutation

Gerstmann-Sträussler-Scheinker (GSS) disease is a dominantly inherited prion disease associated with point mutations in the Prion Protein gene. The most frequent mutation associated with GSS involves a proline-to-leucine substitution at residue 102 of the prion protein, and is characterized by marked variability at clinical, pathological and molecular levels. Previous investigations of GSS P102L have shown that disease-associated pathological prion protein, or PrPSc, consists of two main conformers, which under exogenous proteolysis generates a core fragment of 21 kDa and an internal fragment of 8 kDa. Both conformers are detected in subjects with spongiform degeneration, whereas only the 8 kDa fragment is recovered in cases lacking spongiosis. Several studies have reported an exclusive derivation of protease-resistant PrPSc isoforms from the mutated allele; however, more recently, the propagation of protease-resistant wild-type PrPSc has been described. Here we analyze the molecular and pathological phenotype of six GSS P102L cases characterized by the presence of 21 and 8 kDa PrP fragments and two subjects with only the 8 kDa PrP fragment. Using sensitive protein separation techniques and Western blots with antibodies differentially recognizing wild-type and mutant PrP we observed a range of PrPSc allelic conformers, either resistant or sensitive to protease treatment in all investigated subjects. Additionally, tissue deposition of protease-sensitive wild-type PrPSc molecules was seen by conventional PrP immunohistochemistry and paraffin-embedded tissue blot. Our findings enlarge the spectrum of conformational allelic PrPSc quasispecies propagating in GSS P102L thus providing a molecular support to the spectrum of disease phenotypes, and, in addition, impact the diagnostic role of PrP immunohistochemistry in prion diseases