COL2A1 gene mutations: mechanisms of spondyloepiphyseal dysplasia congenita

The COL2A1 gene consists of 54 exons spanning over 31.5 kb and encodes for type II collagen. Type II collagen is the main component of hyaline cartilage extracellular matrix, nucleus pulposus of intervertebral discus, vitreous humor of the eye and inner ear structure. Molecular defects in COL2A1 gene cause a wide variety of rare autosomal-dominant conditions known as type II collagenopathies. A clear genotype–phenotype relationship is not yet known. However, some correlations are described. Spondyloephyseal dysplasia congenita was suggested for a short-trunk dwarfing condition affecting primarily the vertebrae and the proximal epiphyses of the long bones

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. Introduction The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. Methods This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Results Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. Conclusions This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs

Perturbation Theory and Control in Classical or Quantum Mechanics by an Inversion Formula

We consider a perturbation of an ``integrable'' Hamiltonian and give an expression for the canonical or unitary transformation which ``simplifies'' this perturbed system. The problem is to invert a functional defined on the Lie- algebra of observables. We give a bound for the perturbation in order to solve this inversion. And apply this result to a particular case of the control theory, as a first example, and to the ``quantum adiabatic transformation'', as another example.Comment: Version 8.0. 26 pages, Latex2e, final version published in J. Phys.

Intravitreal injection of Ozurdex(®) implant in patients with persistent diabetic macular edema, with six-month follow-up

AIM: To evaluate the efficacy of intravitreal dexamethasone injections in diabetic macular edema (DME). METHODS: A 700 μg slow-release intravitreal dexamethasone implant (Ozurdex®) was placed in the vitreal cavity of 17 patients (19 eyes) affected with persistent DME. Best corrected visual acuity (BCVA) was assessed through Early Treatment Diabetic Retinopathy Study (ETDRS). Central macular thickness (CMT) was measured by spectral-domain optical coherence tomography. BCVA and CMT examinations were carried out at baseline (T0) and repeated after three days, one month (T1), three months (T3), four months (T4), and six months (T6) post injection. RESULTS: Dexamethasone implant induced an improvement in ETDRS at T1, T3, T4, and T6 post injection. CMT was reduced at T1, T3, and T4, while at T6, CMT values were not statistically different from baseline. No complications were observed during the follow-up. CONCLUSION: Our data suggest that dexamethasone implant is effective in reducing DME symptoms within a six-month frame

Drug-eluting Microspheres Compared to Conventional Transarterial Chemoembolization as First Line Treatment for Unresectable Hepatocellular Carcinoma: A Single-center Retrospective Cost-utility Analysis

Purpose: To assess the cost-utility of initial treatment with drug-eluting microspheres (DEM) transarterial chemoembolization (TACE) versus conventional (C)-TACE in patients with hepatocellular carcinoma considering the perspective of a Local Healthcare Authority in Italy. Materials and methods: The economic evaluation is based on a retrospective single-center study and individual patients' data whose details have been previously reported. The impact of initial treatment with DEM-TACE or C-TACE on disease progression, mortality, and direct health costs over a lifetime horizon were simulated and compared in terms of incremental cost-utility ratio expressed as costs per quality adjusted life years (QALY). Costs included direct health costs related to the first chemoembolization procedure and all subsequent follow-up costs associated with health care resources used for disease management. Probabilistic (PSA) sensitivity analysis was used to assess the robustness of the results. Results: A total of 101 patients in each treatment group were considered. All over the time-horizon median costs were €3,145.14 and €2,158.32 in the DEM-TACE and C-TACE group, respectively (p &lt; 0.001); while mean costs were € 24,619 and € 17,001, respectively (p &lt; 0.001). The ICUR was 6,461.86 €/QALY when using median costs derived from the study population as input for the health-economic evaluation and 49,932.15 €/QALY when the mean costs were considered. Results from PSA highlighted that using median costs DEM-TACE was always cost-effective, while using mean costs, it was preferable only 24.7% of times. Conclusions: The higher prices of DEMs are counterbalanced by the positive impact on QALY

Single-Photon Single-Flux Coupled Detectors

In this work, we present a novel device that is a combination of a superconducting nanowire single-photon detector and a superconducting multi-level memory. We show that these devices can be used to count the number of detections through single-photon to single-flux conversion. Electrical characterization of the memory properties demonstrates single-flux quantum (SFQ) separated states. Optical measurements using attenuated laser pulses with different mean photon number, pulse energies and repetition rates are shown to differentiate single-photon detection from other possible phenomena, such as multi-photon detection and thermal activation. Finally, different geometries and material stacks to improve device performance, as well as arraying methods are discussed

A discussion of possible approaches to the integration of thermochemical storage systems in concentrating solar power plants

One of the most interesting perspectives for the development of concentrated solar power (CSP) is the storage of solar energy on a seasonal basis, intending to exploit the summer solar radiation in excess and use it in the winter months, thus stabilizing the yearly production and increasing the capacity factor of the plant. By using materials subject to reversible chemical reactions, and thus storing the thermal energy in the form of chemical energy, thermochemical storage systems can potentially serve to this purpose. The present work focuses on the identification of possible integration solutions between CSP plants and thermochemical systems for long-term energy storage, particularly for high-temperature systems such as central receiver plants. The analysis is restricted to storage systems potentially compatible with temperatures ranging from 700 to 1000 ◦C and using gases as heat transfer fluids. On the basis of the solar plant specifications, suitable reactive systems are identified and the process interfaces for the integration of solar plant/storage system/power block are discussed. The main operating conditions of the storage unit are defined for each considered case through process simulation