Quantitative Structure-Activity Relationship Modeling of the Amplex Ultrared Assay to Predict Thyroperoxidase Inhibitory Activity.

The thyroid system plays a major role in the regulation of several physiological processes. The dysregulation of the thyroid system caused by the interference of xenobiotics and contaminants may bring to pathologies like hyper- and hypothyroidism and it has been recently correlated with adverse outcomes leading to cancer, obesity, diabetes and neurodevelopmental disorders. Thyroid disruption can occur at several levels. For example, the inhibition of thyroperoxidase (TPO) enzyme, which catalyses the synthesis of thyroid hormones, may cause dysfunctions related to hypothyroidism. The inhibition of the TPO enzyme can occur as a consequence of prolonged exposure to chemical compounds, for this reason it is of utmost importance to identify alternative methods to evaluate the large amount of pollutants and other chemicals that may pose a potential hazard to the human health. In this work, quantitative structure-activity relationship (QSAR) models to predict the TPO inhibitory potential of chemicals are presented. Models are developed by means of several machine learning and data selection approaches, and are based on data obtained in vitro with the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay. Balancing methods and feature selection are applied during model development. Models are rigorously evaluated through internal and external validation. Based on validation results, two models based on Balanced Random Forest (BRF) and K-Nearest Neighbours (KNN) algorithms were selected for a further validation phase, that leads predictive performance (BA = 0.76-0.78 on external data) that is comparable with the reported experimental variability of the AUR-TPO assay (BA ∼0.70). Finally, a consensus between the two models was proposed (BA = 0.82). Based on the predictive performance, these models can be considered suitable for toxicity screening of environmental chemicals.

A design strategy to match the band gap of periodic and aperiodic metamaterials.

The focus of this paper is on elastic metamaterials characterised by the presence of wide sub-wavelength band gap. In most cases, such mechanical property is strictly connected to the periodic repetition of the unit cell. Nonetheless, the strict periodicity requirement could represent a drawback. In this paper, we present a design strategy for aperiodic elastic metamaterials in order to achieve the same performances as for the periodic counterparts. This is done by exploiting the concept of separation of modes for different building blocks, arranged in aperiodic fashion. A theoretical explanation is provided, as well as numerical simulations; the concept is validated by means of a set of experimental tests on prototypes that are realized via additive manufacturing.

Low frequency 3D ultra-wide vibration attenuation via elastic metamaterial.

The design of innovative metamaterials with robust and reliable performances is attracting increasing interest in the scientific community because of their unique properties and for their unexplored potential. In particular, dynamical properties of periodic structures are widely studied specifically for their bandgap opening characteristic, which enables the design of structures with unprecedented dynamical behaviour. In the present work an ultra-wide three-dimensional bandgap is presented, with extremely low frequency range of operation. Numerical simulations and analytical models are proposed to prove the claimed properties, together with experiments carried out on a prototype built by means of additive manufacturing.

3D auxetic single material periodic structure with ultra-wide tunable bandgap.

The design and the combination of innovative metamaterials are attracting increasing interest in the scientific community because of their unique properties that go beyond the ones of natural materials. In particular, auxetic materials and phononic crystals are widely studied for their negative Poisson's ratio and their bandgap opening properties, respectively. In this work, auxeticity and phononic crystals bandgap properties are properly combined to obtain a single phase periodic structure with a tridimensional wide tunable bandgap. When an external tensile load is applied to the structure, the auxetic unit cells change their configurations by exploiting the negative Poisson's ratio and this results in the tuning, either hardening or softening, of the frequencies of the modes limiting the 3D bandgap. Moreover, the expansion of the unit cell in all the directions, due to the auxeticity property, guarantees a fully 3D bandgap tunability of the proposed structure. Numerical simulations and analytical models are proposed to prove the claimed properties. The first experimental evidence of the tunability of a wide 3D bandgap is then shown thanks to the fabrication of a prototype by means of additive manufacturing.

The reconstruction of the spheno-orbital region using latissimus dorsi flap and costal graft.

To minimize complications in skull base surgery, it is necessary to separate intracranial structures from the upper aerodigestive tract with well-vascularized tissue. The majority of defects can be reconstructed using local flaps using pericranium, galea, or temporalis muscle. However, there are conditions that affect the suitability of the previously mentioned flaps, for example, previous surgical procedures or radiotherapy. Local flaps may also be inadequate to reconstruct particularly large defects. Extensive bony demolitions produce aesthetic deformities that need accurate reconstructions. Orbital wall defects have to be reconstructed to avoid complications such as the transmission of cerebral pulsation, bulbar dystopias, diplopia, and ophthalmoplegia. The microvascular latissimus dorsi flap is ideal in all these cases, and the use of a costal graft allows simultaneous reconstruction of bony defects. From January 2000 to January 2008, 17 patients have undergone surgical ablation of the spheno-orbital region and reconstruction with latissimus dorsi flap and costal grafts. The flap survival rate was 100%. One patient required revision of the venous anastomosis. No cerebrospinal fluid leak or intracranial infections have been detected. The only complications registered were dystopias in 6 patients and diplopia in 4; all of these spontaneously resolved within 2 months. The microvascular latissimus dorsi flap with costal graft is an effective method for the reconstruction of the spheno-orbital region when local flaps are not indicated. It has a negligible donor-site morbidity, an ideal vascular pedicle, and an easy harvesting technique. The costal graft allows the simultaneous reconstruction of the orbital walls, giving good results.

Cyclic nucleotide phosphodiesterase activity in stem cells of human periodontal ligament (PDL-MSCs) before and after osteogenic induction.

OBJECTIVE: The aim of this work was to evaluate both the level of endogenous cyclic nucleotides cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cAMP) and phosphodiesterase activity in mesenchymal stem cells (MSCs) before and during the osteogenic induction. STUDY DESIGN: Samples were organized into control (nondifferentiated) and test groups which were analyzed at 3 different time points: 1, 2, and 4 weeks. Periodontal ligament MSCs were isolated and then expanded in an MSCM medium while cyclic nucleotide levels and phosphodiesterase activity were assessed. RESULTS: cAMP and cGMP levels were markedly higher in the first week than in the following stages. Similarly, PDE activity increased during the first week and reached the peak in the second week. CONCLUSIONS: This work validates that cAMP, cGMP, and PDE activities are important factors in the first phase of the osteogenic induction of a human stem cell.

Long-term outcome in children with chronic hepatitis B: a 24-year observation period.

BACKGROUND: Chronic hepatitis B seems to manifest as mild disease in children and young adults. However, data regarding the long-term course of hepatitis B in untreated and interferon-treated children are still scarce. This study investigates the long-term outcome of disease in a large series of untreated and treated children with hepatitis B virus (HBV) infection. METHODS: Clinical, biochemical, virological, and histological features were evaluated in children (age range, 2-18 years) with chronic HBV infection who did not have concomitant chronic systemic diseases other than HBV infection and who were admitted to the liver unit in the Department of Pediatrics at University "Frederico II" (Naples, Italy) during the period 1981-2005. RESULTS: One hundred eight consecutive patients observed for up to 24 years were studied. During the observation period, 67 children remained untreated, and 41 were treated with interferon-alpha. After a median period of observation of 12.1 years (range, 5-23 years), hepatitis B early antigen loss and serum HBV DNA clearance occurred in 43 untreated patients (69.3%) who were hepatitis B early antigen positive at study entry and in 33 treated children (80%; the P value is not statistically significant). In addition, 6 untreated patients (9.7%) and 4 treated patients (9.7%) became anti-HBs [corrected] positive at the end of the follow-up period. Histological assessment, evaluated for 57 children, showed mild-to-moderate disease in 91.2% of cases of HBV infection. No patient developed end-stage liver disease or hepatocellular carcinoma. CONCLUSIONS: Children with chronic HBV infection are symptom free, with morphologically mild liver disease. Considering that the overall long-term outcomes did not differ between treated and untreated patients, the real impact of therapy on the long-term course of HBV infection remains to be established. Additional studies are needed to confirm our conclusions.

Influence of electrolyte composition on the electroosmotic flow and electrophoretic mobility of proteins and peptides.

The influence of electrolyte composition on the electroosmotic flow and peptide/protein migration behavior in capillary zone electrophoresis, either with bare fused-silica or polyacrylamide-coated capillaries, has been investigated. The examined electrolyte solutions consist of buffers tailored for controlling the protonic equilibrium over a wide pH range and effective at masking the active adsorption sites of the capillaries for proteins and peptides. Such buffers are composed of the aliphatic oligoamine triethylentetramine (TETA), in combination with either a monoprotic or a polyprotic acid. The drastic variations in the electroosmotic flow and the inhibition of untoward interactions of basic proteins with the capillary wall observed over a wide pH range were associated with the specific adsorption of TETA ions at the interface between the capillary wall and the electrolyte solution. Modifications of the migration behavior of basic proteins and closely related peptides observed using different buffer anions, such as perchlorate, phosphate and citrate, in combination with TETA may be the result of selective interactions of these counter-ions with the analytes.