Results of medium seventeen years' follow-up after laparoscopic choledochotomy for ductal stones

INTRODUCTION: In a previously published article the authors reported the long-term follow-up results in 138 consecutive patients with gallstones and common bile duct (CBD) stones who underwent laparoscopic transverse choledochotomy (TC) with T-tube biliary drainage and laparoscopic cholecystectomy (LC). Aim of this study is to evaluate the results at up to 23 years of follow-up in the same series. METHODS: One hundred twenty-one patients are the object of the present study. Patients were evaluated by clinical visit, blood assay, and abdominal ultrasound. Symptomatic patients underwent cholangio-MRI, followed by endoscopic retrograde cholangiopancreatography (ERCP) as required. RESULTS: Out of 121 patients, 61 elderly patients died from unrelated causes. Fourteen patients were lost to follow-up. In the 46 remaining patients, ductal stone recurrence occurred in one case (2,1%) successfully managed by ERCP with endoscopic sphincterotomy. At a mean follow-up of 17.1 years no other patients showed signs of bile stasis and no patient showed any imaging evidence of CBD stricture at the site of choledochotomy. CONCLUSIONS: Laparoscopic transverse choledochotomy with routine T-tube biliary drainage during LC has proven to be safe and effective at up to 23 years of follow-up, with no evidence of CBD stricture when the procedure is performed with a correct technique

Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series

Cardiomyopathy associated with dystrophinopathies [Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-dCM) and cardiomyopathy of Duchenne/Becker (DMD/BMD) carriers] is an increasing recognized manifestation of these neuromuscular disorders and notably contributes to their morbidity and mortality. Dystrophinopathic cardiomyopathy (DCM) is the result of the dystrophin protein deficiency at the myocardium level, parallel to the deficiency occurring at the skeletal muscle level. It begins as a "presymptomatic" stage in the first decade of life and evolves in a stepwise manner toward pictures of overt cardiomyopathy (hypertrophic stage, arrhythmogenic stage and dilated cardiomyopathy). The final stage caused by the extensive loss of cardiomyocytes results in an irreversible cardiac failure, characterized by frequent episodes of acute congestive heart failure (CHF), despite a correct pharmacological treatment. The picture of a severe dilated cardiomyopathy with intractable heart failure is typical of BMD, XL-dCM and cardiomyopathy of DMD/BMD carriers, while it is less frequently observed in patients with DMD. Heart transplantation (HT) is the only curative therapy for patients with dystrophinopathic end-stage heart failure who remain symptomatic despite an optimal medical therapy. However, no definitive figures exist in literature concerning the number of patients with DCM transplanted, and their outcome. This overview is to summarize the clinical outcomes so far published on the topic, to report the personal series of dystrophinopathic patients receiving heart transplantation and finally to provide evidence that heart transplantation is a safe and effective treatment for selected patients with end-stage DCM

Physics-Informed Extreme Theory of Functional Connections Applied to Data-Driven Parameters Discovery of Epidemiological Compartmental Models

In this work we apply a novel, accurate, fast, and robust physics-informed neural network framework for data-driven parameters discovery of problems modeled via parametric ordinary differential equations (ODEs) called the Extreme Theory of Functional Connections (X-TFC). The proposed method merges two recently developed frameworks for solving problems involving parametric DEs, 1) the Theory of Functional Connections (TFC) and 2) the Physics-Informed Neural Networks (PINN). In particular, this work focuses on the capability of X-TFC in solving inverse problems to estimate the parameters governing the epidemiological compartmental models via a deterministic approach. The epidemiological compartmental models treated in this work are Susceptible-Infectious-Recovered (SIR), Susceptible-Exposed-Infectious-Recovered (SEIR), and Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIR). The results show the low computational times, the high accuracy and effectiveness of the X-TFC method in performing data-driven parameters discovery of systems modeled via parametric ODEs using unperturbed and perturbed data

Thermally-Reconfigurable Quantum Photonic Circuits at Telecom Wavelength by Femtosecond Laser Micromachining

The importance of integrated quantum photonics in the telecom band resides on the possibility of interfacing with the optical network infrastructure developed for classical communications. In this framework, femtosecond laser written integrated photonic circuits, already assessed for quantum information experiments in the 800 nm wavelength range, have great potentials. In fact these circuits, written in glass, can be perfectly mode-matched at telecom wavelength to the in/out coupling fibers, which is a key requirement for a low-loss processing node in future quantum optical networks. In addition, for several applications quantum photonic devices will also need to be dynamically reconfigurable. Here we experimentally demonstrate the high performance of femtosecond laser written photonic circuits for quantum experiments in the telecom band and we show the use of thermal shifters, also fabricated by the same femtosecond laser, to accurately tune them. State-of-the-art manipulation of single and two-photon states is demonstrated, with fringe visibilities greater than 95%. This opens the way to the realization of reconfigurable quantum photonic circuits on this technological platform

APE1 polymorphic variants cause persistent genomic stress and affect cancer cell proliferation

Apurinic/apyrimidinic endonuclease 1 (APE1) is the main mammalian AP-endonuclease responsible for the repair of endogenous DNA damage through the base excision repair (BER) pathway. Molecular epidemiological studies have identified several genetic variants associated with human diseases, but a well-defined functional connection between mutations in APE1 and disease development is lacking. In order to understand the biological consequences of APE1 genetic mutations, we examined the molecular and cellular consequences of the selective expression of four non-synonymous APE1 variants (L104R, R237C, D148E and D283G) in human cells. We found that D283G, L104R and R237C variants have reduced endonuclease activity and impaired ability to associate with XRCC1 and DNA polymerase \u3b2, which are enzymes acting downstream of APE1 in the BER pathway. Complementation experiments performed in cells, where endogenous APE1 had been silenced by shRNA, showed that the expression of these variants resulted in increased phosphorylation of histone H2Ax and augmented levels of poly(ADP-ribosyl)ated (PAR) proteins. Persistent activation of DNA damage response markers was accompanied by growth defects likely due to combined apoptotic and autophagic processes. These phenotypes were observed in the absence of exogenous stressors, suggesting that chronic replication stress elicited by the BER defect may lead to a chronic activation of the DNA damage response. Hence, our data reinforce the concept that non-synonymous APE1 variants present in the human population may act as cancer susceptibility alleles

Growth Factor Receptor-bound Protein 2 Interaction with the Tyrosine-phosphorylated Tail of Amyloid β Precursor Protein Is Mediated by Its Src Homology 2 Domain

The sequential processing of the familial disease gene product amyloid beta precursor protein (AbetaPP) by beta- and gamma-secretases generates amyloid beta, which is considered to be the pathogenic factor of Alzheimer's disease, and the AID peptide (AbetaPP intracellular domain). The AID peptide acts as a positive regulator of apoptosis and modulates transcription and calcium release. To gain clues about the molecular mechanisms regulating the function of AbetaPP and AID, proteins interacting with the AID region of AbetaPP have been isolated using the yeast two-hybrid system. Recent evidence indicates that AbetaPP undergoes post-translational modification events in the AID region and that phosphorylation might regulate its affinity for interacting proteins. To test this possibility and to uncover AbetaPP-binding partners whose interaction depends on AbetaPP phosphorylation, we used a proteomic approach. Here we describe a protein, growth factor receptor-bound protein 2 (Grb2), that specifically binds AbetaPP, phosphorylated in Tyr(682). Furthermore, we show that this interaction is direct and that Grb2 binds to phospho-AbetaPP via its Src homology 2 region. Together with the evidence that Grb2 is in complex with AbetaPP in human brains and that these complexes are augmented in brains from Alzheimer's cases, our data indicate that Grb2 may mediate some biological and possibly pathological AbetaPP-AID function

Model-Based Control of Torque and Nitrogen Oxide Emissions in a Euro {VI} 3.0 L Diesel Engine through Rapid Prototyping

In the present paper, a model-based controller of engine torque and engine-out Nitrogen oxide (NOx) emissions, which was previously developed and tested by means of offline simulations, has been validated on a FPT F1C 3.0 L diesel engine by means of rapid prototyping. With reference to the previous version, a new NOx model has been implemented to improve robustness in terms of NOx prediction. The experimental tests have confirmed the basic functionality of the controller in transient conditions, over different load ramps at fixed engine speeds, over which the average RMSE (Root Mean Square Error) values for the control of NOx emissions were of the order of 55-90 ppm, while the average RMSE values for the control of brake mean effective pressure (BMEP) were of the order of 0.25-0.39 bar. However, the test results also highlighted the need for further improvements, especially concerning the effect of the engine thermal state on the NOx emissions in transient operation. Moreover, several aspects, such as the check of the computational time, the impact of the controller on other pollutant emissions, or on the long-term engine operations, will have to be evaluated in future studies in view of the controller implementation on the engine control unit

H/V measurements as an effective tool for the reliable detection of landslide slip surfaces: Case studies of Castagnola (La Spezia, Italy) and Roccalbegna (Grosseto, Italy)

AbstractA variety of methods (detailed geomorphological surveys, geotechnical investigations, local instrumentation, satellite data, and radar interferometry) along with geophysical techniques may be used to investigate slope instabilities and to detect the inhomogeneities of materials as well as their properties, boundaries, and sliding surfaces. Of these techniques, the method based on seismic noise measurements allows abrupt changes in seismic impedance at landslide boundaries resulting from varying levels of seismic velocity and material density to be detected. Peaks of the Horizontal to Vertical Spectral Ratio have proven to serve as effective indicators of the resonance frequency of low-impedance surface layers. In this work, horizontal to vertical spectral ratio surveys of the Castagnola (La Spezia, Italy) and Roccalbegna (Grosseto, Italy) landslides were carried out. From roughly 100 single-station measurements made inside and outside the landslides at each site, we define a threshold number of single-station seismic noise measures beyond which information is redundant because the variation in reconstructed impedance contrast surfaces is not significant. This approach allows one to reliably retrieve the geometry of a landslide body, ultimately generating useful information for determining whether further measurements are needed to improve landslide body reconstruction

Cost of illness of spinal muscular atrophy (SMA) in Italy

The objective of this study was to estimate the indirect and direct non-health costs associated with spinal muscular atrophy (SMA), a disease that burdens the daily life of adults, children and their families in Italy. In order to develop the economic model, a multidisciplinary group of researchers was created to prepare and computerize a questionnaire, which was promoted by SMA families in collaboration with the Economic Evaluation and Heath Technology Assessment center at the University of Rome Tor Vergata. The analysis envisaged a first phase for implementing and validating the questionnaire by the multidisciplinary group. Subsequently, the questionnaire was computerized and sent out to be completed through all the association's distribution channels. The social channels and specific mailing lists were limited exclusively to SMA families. To achieve the sample number required by the research protocol, data collection began on January 8, 2018, and closed on April 15, 2018. Finally, all the data were analyzed using the economic model in order to estimate the average costs per patient.The questionnaire was able to identify a sample of 118 families (22.88% SMA I, 48.31% SMA II, 28.81% SMA III). The average age of the patients was 18.49 years (average age at diagnosis 2.88 years) with more females (55,08%) in the total respondents, taking into account a 4.24% rate of non-respondents. The economic model estimated an average annual cost per patient with SMA of €15.371,41 (€17.683,85 for SMA I, €15.974,78 for SMA II and €12.523,52 for SMA III). Of these costs, about 52% were attributable to indirect costs associated with caregivers, 15% for indirect costs associated with the patient and 4% for social security costs. A total of 17% was attributable to the direct costs incurred by the patient and 12% was attributable to the direct costs incurred by the Italian National Health Service (SSN).To our knowledge, this survey represents the first nationwide analysis estimating the costs incurred by families for the management of SMA. This study highlights the need for specific policies to support families who must live with the disease, not only from the standpoint of their compromised quality of life but also due to the significant economic burden imposed by the disease