We test the hypothesis that, being clients not fully informed on the expected benefit from fulfilling the disputes and being incentives of lawyers not aligned to those of their clients, the demand ...for legal disputes in Italy is induced. This hypothesis finds empirical support for a sample of Italian legal districts.
ABSTRACT
Noonan syndrome (NS) is a relatively common developmental disorder with a pleomorphic phenotype. Mutations causing NS alter genes encoding proteins involved in the RAS‐MAPK pathway. We and ...others identified Casitas B‐lineage lymphoma proto‐oncogene (CBL), which encodes an E3‐ubiquitin ligase acting as a tumor suppressor in myeloid malignancies, as a disease gene underlying a condition clinically related to NS. Here, we further explored the spectrum of germline CBL mutations and their associated phenotype. CBL mutation scanning performed on 349 affected subjects with features overlapping NS and no mutation in NS genes allowed the identification of five different variants with pathological significance. Among them, two splice‐site changes, one in‐frame deletion, and one missense mutation affected the RING domain and/or the adjacent linker region, overlapping cancer‐associated defects. A novel nonsense mutation generating a v‐Cbl‐like protein able to enhance signal flow through RAS was also identified. Genotype–phenotype correlation analysis performed on available records indicated that germline CBL mutations cause a variable phenotype characterized by a relatively high frequency of neurological features, predisposition to juvenile myelomonocytic leukemia, and low prevalence of cardiac defects, reduced growth, and cryptorchidism. Finally, we excluded a major contribution of two additional members of the CBL family, CBLB and CBLC, to NS and related disorders.
Germline mutations in CBL cause a leukemia‐prone disorder clinically related to Noonan syndrome. Here, we explored the spectrum of CBL mutationsand their associated phenotype. Five different mutations are identified, including a novel nonsense change generating a v‐Cbl‐like protein able to enhance signaling through RAS. Genotype‐phenotype correlation analysis indicate that germline CBL mutations cause a variable phenotype characterized by a relatively high frequency of neurological features, predisposition to JMML, and low prevalence of cardiac defects and reduced growth.
Purpose
The management of tandem extracranial internal carotid artery and intracranial large vessel occlusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) has been ...under-investigated. We sought to investigate outcomes of AIS patients with tandem occlusion (TO) treated with carotid artery stenting (CAS) compared to those not treated with CAS (no-CAS) during EVT.
Methods
We performed a cohort study using data from AIS patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Outcomes were 3 months’ mortality, functional outcome, complete and successful recanalization, any intracranial hemorrhage, parenchymal hematoma and symptomatic intracerebral hemorrhage.
Results
Among 466 AIS patients with TO, CAS patients were 122 and no-CAS patients were 226 (118 excluded). After adjustment for unbalanced variables, CAS was associated with a lower rate of 3 months’ mortality (OR 0.407, 95% CI 0.171–0.969,
p
= 0.042). After adjustment for pre-defined variables, CAS was associated with a lower rate of 3 months’ mortality (aOR 0.430, 95% CI 0.187–0.989,
p
= 0.047) and a higher rate of complete recanalization (aOR 1.986, 95% CI 1.121–3.518,
p
= 0.019), successful recanalization (aOR 2.433, 95% CI 1.263–4.686,
p
= 0.008) and parenchymal hematoma (aOR 2.876, 95% CI 1.173–7.050,
p
= 0.021). CAS was associated with lower 3 months mortality (OR 0.373, 95% CI 0.141–0.982,
p
= 0.046) and higher rates of successful recanalization (OR 2.082, 95% CI 1.099–3.942,
p
= 0.024) after adjustment for variables associated with 3 months’ mortality and successful recanalization, respectively.
Conclusions
Among AIS patients with TO, CAS during EVT was associated with a higher rate of successful reperfusion and a lower rate of 3 months’ mortality.
Human serum paraoxonase-1 (PON1) is thought to play a role in the favorable vascular effects of high-density lipoproteins, mainly through a reduction in low-density lipoprotein oxidation. Endothelial ...dysfunction, characterized by an impaired capacity of the arteries to dilate in response to a number of stimuli, represents the earliest stage of atherosclerosis. We performed the present study in 37 patients with peripheral arterial disease, with the aim of investigating the influence of PON1 Q192R polymorphism and activity on peripheral endothelial function, evaluated as brachial-artery flow-mediated vasodilation (FMV). Patients with the R allele (QR or RR genotype,
n
=
19) had significantly higher PON1 activity 408
U/mL (309–456) versus 180
U/mL (141–243),
p
<
0.001 and greater brachial FMV (5.7
±
3.9% versus 3.0
±
2.8%,
p
<
0.001) than those with Q allele (QQ genotype,
n
=
18). In the whole population, PON1 activity showed a direct relation to brachial FMV (
r
=
0.46,
p
=
0.004). In a multivariate linear regression analysis, the only independent predictors of brachial FMV were PON1 activity (
β
=
0.40,
p
=
0.008), brachial-artery diameter (
β
=
−0.39,
p
=
0.01) and male sex (
β
=
−0.27,
p
=
0.04).
These finding support the importance of PON1 activity as a modulating factor of the endothelial function.
Neutrinos are so far the most elusive known particles, and in the last decades many sophisticated experiments have been set up in order to clarify several questions about their intrinsic nature, in ...particular their masses, mass hierarchy, intrinsic nature of Majorana or Dirac particles. Evidence of the Neutrinoless Double-Beta Decay (NDBD) would prove that neutrinos are Majorana particles, thus improving the understanding of the universe itself. Besides the search for several large underground experiments for the direct experimental detection of NDBD, the NUMEN experiment proposes the investigation of a nuclear mechanism strongly linked to this decay: the Double Charge Exchange reactions (DCE). As such reactions share with the NDBD the same initial and final nuclear states, they could shed light on the determination of the Nuclear Matrix Elements (NMEs), which play a relevant role in the decay. The physics of DCE is described elsewhere in this issue, while the focus of this paper will be on the challenging experimental apparatus currently under construction in order to fulfil the requirements of the NUMEN experiment. The overall structure of the technological improvement to the cyclotron, along with the newly developed detection systems required for tracking and identifying the reaction products and their final excitation level are described.
The research carried out at the Istituto Nazionale di Ricerca Metrologica (formerly Istituto di Metrologia «G. Colonnetti») aiming to develop a transportable ballistic absolute gravimeter ended with ...a new version of the instrument, called the IMGC-02. It uses laser interferometry to measure the symmetrical free rising and falling motion of a test mass in the gravity field. Providing the same accuracy achieved with previous versions, the instrumental improvements mainly concern size, weight, data processing algorithms and operational simplicity. An uncertainty of 9 ?Gal (1 ?Gal=1×108 m·s?2) can be achieved within a single observation session, lasting about 12 h, while the time series of several observation sessions show a reproducibility of 4 ?Gal. At this level, gravity measurements provide useful information in Geophysics and Volcanology. A wide set of dynamic phenomena, i.e. seismicity and volcanic activity, can produce temporal gravity changes, often quite small, with an amplitude ranging from a few to hundreds of microgals. Therefore the IMGC absolute gravimeter has been employed since 1986 in surveying the Italian active volcanoes. A brief history of the gravimeter and the description of the new apparatus, together with the main results of ongoing applications in Geophysics and Volcanology are presented.
The study of nuclear cluster states bound by valence neutrons is a field of recent large interest. In particular, it is important to study the pre-formation of α-clusters in α-conjugate nuclei and ...the dynamical condensation of clusters during nuclear reactions 1–5. The NUCL–EX collaboration has recently initiated an experimental campaign of exclusive measurements of fusion–evaporation reactions with light nuclei as interacting partners. In collisions involving light systems, the low expected multiplicity of fragments increases the probability of achieving a quasi-complete reconstruction of the event. In particular the formation and decay modes of an excited 24Mg system have been studied through two different reactions, 12C (95 MeV)+ 12C and 14N (80.7 MeV)+ 10B, which have been used to produce fused systems with nearly the same mass and excitation energy (~60 MeV). In particular, even the de-excitation of the Hoyle state in 12C have been studied, both in peripheral (projectiles de-excitation) and in central collisions (six α-particles channel). Moreover, a research campaign studying pre-equilibrium emission of light charged particles and cluster properties of light and medium-mass nuclei has been carried out. For this purpose, a comparative study of the three nuclear systems 18O+28Si, 16O+30Si and 19F+27Al has been recently studied using the GARFIELD+RCo 4π setup 6. The experimental data are compared with the predictions of simulated events generated with the statistical models (GEMINI++ and HFl) and through dynamical models like Stochastic Mean Field (SMF) and Antisymmetrized Molecular Dynamics (AMD) and filtered with a software replica of our apparatus in order to take into account the experimental conditions.
The majority of clinical studies on endothelial progenitor cells (EPCs) focuses on the role of these cells in cardiovascular diseases and no systematic studies exist regarding their variations in ...healthy subjects. In order to define the burden of angiogenesis in physiological conditions we assessed the frequency of peripheral blood endothelial colonies (PB-ECs) and their relation with other factors possibly involved in their function such as high-sensitivity C-reactive protein (hs-CRP), endothelial cell-specific mitogen factor (VEGF) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in a highly selected healthy population. A PB sample was obtained from 37/47 healthy subjects (age 40.2+/-15.0yrs; M/F 15/22) without known cardiovascular risk factors. The serum level of hs-CRP, VEGF, TIMP-1, the frequency of PB-ECs by clonogenic assay, and the number of early EPCs and late EPCs by flow cytometry analysis were evaluated. PB-ECs were formed by 40.5% of studied subjects with a mean of 0.40+/-0.82 colonies/10(6) cells. The differences in the frequency of colony formation between genders were not statistically significant. The subjects with PB-ECs were characterized by higher values of hs-CRP, when compared with those not forming colonies, 0.276+/-0.230 vs 0.095+/-0.077 mg/l (p=0.003) respectively, and of VEGF, 328.3+/-162.9 vs 202.68+/-118.53 pg/ml (p=0.02). No significant differences were found in TIMP-1 values. The EPC clonogenic potential seems to be related to hs-CRP and VEGF levels even in healthy population supporting the concept that these mediators are involved in physiological ECs function.
A total of 775 consecutive patients who survived the first 24 hours after cardiac operation were prospectively studied to assess the prevalence, mortality rate, and main risk factors for development ...of new acute renal failure. Normal renal function before operation (serum creatinine level less than 1.5 mg/dl) was registered in 734 (94.7%) patients. Of these, 111 (15.1%) showed a postoperative renal complication including 84 (11.4%) classified as renal dysfunction (serum creatinine level between 1.5 and 2.5 mg/dl) and 27 (3.7%) as acute renal failure (serum creatinine level higher than 2.5 mg/dl). The mortality rate was 0.8% in normal patients, 9.5% in patients with renal dysfunction, and 44.4% when acute renal failure developed (p < 0.0001). Indeed, the renal impairment proved to be an independent predictor of mortality (p < 0.001), along with the infective (p < 0.001), gastrointestinal (p < 0.001), and cardiovascular (p < 0.05) complications. Multivariate analysis identified the following variables as independent risk factors for postoperative renal impairment: use of intraaortic balloon pump (p < 0.0001), need for deep hypothermic circulatory arrest (p < 0.005), low-output syndrome (p < 0.005), advanced age (p < 0.005), need for emergency operation (p < 0.025), and low urinary output during cardiopulmonary bypass (p < 0.05). The 41 patients (5.3%) with preoperative renal failure showed a significantly higher morbidity and mortality rate than those without renal complications before operation. We conclude that in patients undergoing cardiac operation without preexisting renal dysfunction the likelihood of severe renal complications is reasonably low, but the associated mortality remains high. A prominent role in the development of postoperative acute renal failure must be recognized for preoperative, intraoperative, and postoperative hemodynamic factors, whereas cardiopulmonary bypass seems to be of lesser importance in this respect.
ABSTRACT
Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are ...a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)‐6, IL‐10, IL‐1α, IL‐1 ra, interferon‐γ, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed‐suction drain was inserted in the wound below the fascia and removed on postoperative day 4. Wound fluid was collected on postoperative days 1–4 and the amount was recorded each time. Growth factors and cytokines production was evaluated as the whole amount produced over a 24‐hour period. In all patients, the amount of drain fluid from surgical wounds was more copious the first day after surgery, it decreased significantly afterward. The presence of all cytokines was highest on postoperative day 1, decreasing over the following days. More specifically, the production of IL‐1 ra, IL‐6, IL‐1α, and IL‐10 on postoperative day 1 fell sharply on postoperative days 3 and 4, whereas, after an initial reduction, interferon‐γ showed an increase from day 2 onward. Vascular endothelial‐derived growth factor production increased progressively after the operation reaching statistical significance only on day 4. As for basic fibroblast growth factor, it showed an opposite pattern: it was higher on postoperative day 1 decreasing thereafter. This analysis of cytokine and growth factor production in the drain fluid will lead us to a better evaluation of the events that follow a surgical wound and to a better understanding of the healing process.
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