Ultrasonography validation for early alteration of diaphragm echodensity and function in the mdx mouse model of Duchenne muscular dystrophy

The mdx mouse model of Duchenne muscular dystrophy is characterized by functional and structural alterations of the diaphragm since early stages of pathology, closely resembling patients’ condition. In recent years, ultrasonography has been proposed as a useful longitudinal non-invasive technique to assess mdx diaphragm dysfunction and evaluate drug efficacy over time. To date, only a few preclinical studies have been conducted. Therefore, an independent validation of this method by different laboratories is needed to increase results reliability and reduce biases. Here, we performed diaphragm ultrasonography in 3- and 6-month-old mdx mice, the preferred age-window for pharmacology studies. The alteration of diaphragm function over time was measured as diaphragm ultrasound movement amplitude. At the same time points, a first-time assessment of diaphragm echodensity was performed, as an experimental index of progressive loss of contractile tissue. A parallel evaluation of other in vivo and ex vivo dystrophy-relevant readouts was carried out. Both 3- and 6-month-old mdx mice showed a significant decrease in diaphragm amplitude compared to wild type (wt) mice. This index was well-correlated either with in vivo running performance or ex vivo isometric tetanic force of isolated diaphragm. In addition, diaphragms from 6-month-old dystrophic mice were also highly susceptible to eccentric contraction ex vivo. Importantly, we disclosed an age-dependent increase in echodensity in mdx mice not observed in wt animals, which was independent from abdominal wall thickness. This was accompanied by a notable increase of pro-fibrotic TGF-β1 levels in the mdx diaphragm and of non-muscle tissue amount in diaphragm sections stained by hematoxylin & eosin. Our findings corroborate the usefulness of diaphragm ultrasonography in preclinical drug studies as a powerful tool to monitor mdx pathology progression since early stages

Peyronie's disease development and management in diabetic men

Background: Peyronie's disease (PD) is a fibrosing disorder of the penis resulting in plaque formation and penile deformity that negatively affect sexual and psychosocial function of patients. A multifactorial etiology of PD is assumed with diabetes mellitus (DM) being a potential risk factor. Objectives: The aim of this narrative review was to investigate diabetes role in PD pathophysiology, diagnosis, and treatment. Materials and methods: A non-systematic narrative review of original articles, meta-analyses, and randomized trials was conducted, including articles in the pre-clinical setting to support relevant findings. Results: Diabetes is one of the most common comorbidity observed in PD patients, with a prevalence of about 11% and a strong association with erectile dysfunction (ED). DM is associated with both a higher risk of developing PD and has also an impact on the outcomes of PD's treatments. Discussion: Evidence from literature underlines that metabolic alterations typical of DM are pivotal factors in the development of PD and resistance to its medical treatment. Conclusion: The role of DM in development of PD is still debated, while its role in PD development is not completely clear, there is a clear impact of DM on PD treatment outcomes

Association between metabolic syndrome, obesity, diabetes mellitus and oncological outcomes of bladder cancer. A systematic review

Metabolic syndrome is a cluster of several metabolic abnormalities, its prevalence is increasing worldwide. To summarize the most recent evidence regarding the relationship between metabolic syndrome, its components and the oncological outcomes in bladder cancer patients, a National Center for Biotechnology Information PubMed search for relevant articles either published or e-published up to March 2014 was carried out by combining the following Patient population, Intervention, Comparison, Outcome terms: metabolic syndrome, obesity, body mass index, hyperglycemia, insulin resistance, diabetes, hypertension, dyslipidemia, bladder cancer, risk, mortality, cancer specific survival, disease recurrence and progression. Metabolic syndrome is a complex, highly prevalent disorder, and central obesity, insulin resistance, dyslipidemia and hypertension are its main components. Published findings would suggest that metabolic syndrome per se might be associated with an increased risk of bladder cancer in male patients, but it did not seem to confer a risk of worse prognosis. Considering the primary components of metabolic syndrome (hypertension, obesity and dyslipidemia), available data are uncertain, and it is no possible to reach a conclusion yet on either a direct or an indirect association with bladder cancer risk and prognosis. Only with regard to type 2 diabetes mellitus, available data would suggest a potential negative correlation. However, as the evaluation of bladder cancer risk and prognosis in patients with metabolic disorders is certainly complex, further studies are urgently required to better assess the actual role of these metabolic disorders

Deep Energy Retrofit of Residential Buildings in the Mediterranean Area: The MedZEB Approach

Publicado en : Green Energy and TechnologyMediterranean deep retrofit markets are characterized by common barriers and bottlenecks, which barely have been identified as shared challenges, and this has led to a lack of dedicated solutions and to a substantial delay in achieving the 2020 EU policy targets. This situation is addressed by the H2020 HAPPEN project by proposing a new MedZEB approach characterized by the following features: Holistic, i.e., aimed at integrating the most relevant aspects of the retrofitting supply chain;Transparent, i.e., aimed at putting on the market novel tools for enhancing investors’ trust;Adaptive, i.e., aimed at enhancing “added values” of the retrofitting such as flexibility, well-being, etc. Having arrived at its midpoint, HAPPEN has produced an advanced version of its main outputs, among which are: the HAPPEN cost-optimal technical solutions, developed according to a step-by-step logic;the HAPPEN financial solution, fully integrated with the step-by-step logic, and aimed at funding the retrofitting process by relying on the energy savings achieved;the MedZEB protocol conceived as a guarantee scheme for the achievement of retrofit targets;the HAPPEN platform, an assisted digital marketplace aimed at matching demand and offer according to a one-stop-shop logic, at defragmenting the retrofit value chain, and at supporting actors with dedicated tools. These outputs have been developed also thanks to an extensive living laboratory and pilot-building program, carried out within ten pilot sites across seven EU Med countries; this has made it possible for a large engagement of potential users, which resulted in the ideation of the HAPPEN program, an overall framework aimed at integrating project outputs into an exploitable renovation procedure powered by the HAPPEN platform. This paper describes the first simulation of such a procedure in its entirety based on a real case study. After characterizing the building according to the HAPPEN reference buildings and climates lists, a step-by-step cost-optimal package of solutions was calculated, followed by the application of the HAPPEN financial solution, and by the draft issue of the MedZEB protocol. Results provide the first evidence of the effectiveness of the MedZEB approach in potentially unlocking the deep retrofit market in the Med area, with special attention to the possibility of funding the interventions by relying on the economies generated by the energy savings achieved. Further, the project activities will be aimed at co-creating, together with relevant stakeholders, a go-to-market strategy for the HAPPEN program.Horizonte 2020 (Unión Europea) 78507

Quantum Phases of Dipolar Bosons in Bilayer Geometry

We investigate the quantum phases of hard-core dipolar bosons confined to a square lattice in a bilayer geometry. Using exact theoretical techniques, we discuss the many-body effects resulting from pairing of particles across layers at finite density, including a novel pair supersolid phase, superfluid and solid phases. These results are of direct relevance to experiments with polar molecules and atoms with large magnetic dipole moments trapped in optical lattices.Comment: 7 pages, 5 figure

Effect of Doublon-Holon Binding on Mott transition---Variational Monte Carlo Study of Two-Dimensional Bose Hubbard Models

To understand the mechanism of Mott transitions in case of no magnetic influence, superfluid-insulator (Mott) transitions in the S=0 Bose Hubbard model at unit filling are studied on the square and triangular lattices, using a variational Monte Carlo method. In trial many-body wave functions, we introduce various types of attractive correlation factors between a doubly-occupied site (doublon, D) and an empty site (holon, H), which play a central role for Mott transitions, in addition to the onsite repulsive (Gutzwiller) factor. By optimizing distance-dependent parameters, we study various properties of this type of wave functions. With a hint from the Mott transition arising in a completely D-H bound state, we propose an improved picture of Mott transitions, by introducing two characteristic length scales, the D-H binding length $\xi_{\rm dh}$ and the minimum D-D exclusion length $\xi_{\rm dd}$. Generally, a Mott transition occurs when $\xi_{\rm dh}$ becomes comparable to $\xi_{\rm dd}$. In the conductive (superfluid) state, domains of D-H pairs overlap with each other ($\xi_{\rm dh}>\xi_{\rm dd}$); thereby D and H can propagate independently as density carriers by successively exchanging the partners. In contrast, intersite repulsive Jastrow (D-D and H-H) factors have little importance for the Mott transition.Comment: 16 pages, 22 figures, submitted to J. Phys. Soc. Jp

Evaluation of potential synergistic action of a combined treatment with alpha-methyl-prednisolone and taurine on the mdx mouse model of Duchenne muscular dystrophy

Aims: Glucocorticoids are the sole drugs clinically used in Duchenne muscular dystrophy, in spite of the relevant side effects. Combination of glucocorticoids with synergistic drugs may be one strategy to lower doses and control side effects, meanwhile providing wider control of the complex pathology. This study is a preclinical evaluation of the effect of a combined treatment of amethyl-prednisolone (PDN) with taurine, a safe aminoacid with positive effects on some pathology-related events. Methods: PDN (1 mg/kg/day i.p.) and taurine (1 g/kg/day orally) were administered either alone or in combination, for 4-8 weeks to male dystrophic mdx mice chronically exercised on a treadmill. Effects were assessed in vivo and ex vivo with a variety of methodological approaches. Results: In vivo, each treatment significantly increased fore limb strength, a marked synergistic effect being observed with the combination PDN + taurine. Ex vivo, PDN + taurine completely restored the mechanical threshold, an electrophysiological index of calcium homeostasis, of extensor digitorum longus myofibres and the benefit was greater than for PDN alone. In parallel, the overactivity of voltage-independent cation channels in dystrophic myofibres was reduced. No effects were observed on plasma levels of creatine kinase, while lactate dehydrogenase was decreased by taurine and, to a minor extent, by PDN + taurine. A similar histology profile was observed in PDN and PDN + taurine-treated muscles. PDN + taurine significantly increased taurine level in fast-twitch muscle and brain, by high-pressure liquid chromatography analysis. Conclusions: The combination PDN + taurine has additive actions on in vivo and ex vivo functional end points, with less evident advantages on histopathology and biochemical markers of the disease

Single-Atom Resolved Fluorescence Imaging of an Atomic Mott Insulator

The reliable detection of single quantum particles has revolutionized the field of quantum optics and quantum information processing. For several years, researchers have aspired to extend such detection possibilities to larger scale strongly correlated quantum systems, in order to record in-situ images of a quantum fluid in which each underlying quantum particle is detected. Here we report on fluorescence imaging of strongly interacting bosonic Mott insulators in an optical lattice with single-atom and single-site resolution. From our images, we fully reconstruct the atom distribution on the lattice and identify individual excitations with high fidelity. A comparison of the radial density and variance distributions with theory provides a precise in-situ temperature and entropy measurement from single images. We observe Mott-insulating plateaus with near zero entropy and clearly resolve the high entropy rings separating them although their width is of the order of only a single lattice site. Furthermore, we show how a Mott insulator melts for increasing temperatures due to a proliferation of local defects. Our experiments open a new avenue for the manipulation and analysis of strongly interacting quantum gases on a lattice, as well as for quantum information processing with ultracold atoms. Using the high spatial resolution, it is now possible to directly address individual lattice sites. One could, e.g., introduce local perturbations or access regions of high entropy, a crucial requirement for the implementation of novel cooling schemes for atoms on a lattice

Attitude towards active surveillance: A cross-sectional survey among patients with uroandrological disorders

Objectives We looked at subjective attitude towards active surveillance (AS) as the first option for cancer management in a cohort of patients seeking first medical help for uroandrological disorders prior to a formal discussion with a caregiver. Design Cross-sectional observational study. Setting Uroandrological outpatient clinic of a European academic centre. Participants Data of 1059 patients at their first access for uroandrological purposes from January 2014 to December 2016 were analysed. Intervention Patients were invited to complete a survey with closed questions investigating their attitude towards AS, prior to any clinical evaluation. Likewise, patients were invited to score the importance given to different aspects of personal life in the case of a cancer diagnosis, using a 10-point Likert scale. Primary and secondary outcomes measures The reported opinion towards AS management for cancer was assessed. Logistic regression analyses tested participants' sociodemographic characteristics associated with a positive opinion on AS. Results Positive, negative and doubtful attitudes towards AS were observed in 347 (33%), 331 (31%) and 381 (36%) patients, respectively. Female patients were more likely to report a negative attitude towards AS (38.7% vs 29.6%, p=0.04) while patients with previous parenthood more frequently reported a positive opinion on AS (37.2% vs 29.9%, p=0.005). Patient age emerged as the only predictor of a positive attitude towards AS (OR 1.03; 95% CI 1.01 to 1.04, p<0.001), with a 46% and 33% probability of being pro-AS for a patient aged 65 and 45 years, respectively. Conclusions One out of three patients would express positive feedbacks on AS in the unfortunate case of tumour diagnosis, only according to his/her baseline personal opinion and prior to any discussion with a cancer caregiver. The older the patient, the higher the probability of being compliant with a conservative management for cancer

Dynamical mean-field theory for bosons

We discuss the recently developed bosonic dynamical mean-field (B-DMFT) framework, which maps a bosonic lattice model onto the selfconsistent solution of a bosonic impurity model with coupling to a reservoir of normal and condensed bosons. The effective impurity action is derived in several ways: (i) as an approximation to the kinetic energy functional of the lattice problem, (ii) using a cavity approach, and (iii) by using an effective medium approach based on adding a one-loop correction to the selfconsistently defined condensate. To solve the impurity problem, we use a continuous-time Monte Carlo algorithm based on a sampling of a perturbation expansion in the hybridization functions and the condensate wave function. As applications of the formalism we present finite temperature B-DMFT phase diagrams for the bosonic Hubbard model on a 3d cubic and 2d square lattice, the condensate order parameter as a function of chemical potential, critical exponents for the condensate, the approach to the weakly interacting Bose gas regime for weak repulsions, and the kinetic energy as a function of temperature.Comment: 26 pages, 19 figure