Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Recommendation of RILEM Technical Committee 250-CSM: Test method for Textile Reinforced Mortar to substrate bond characterization

Textile Reinforced Mortar (TRM), also known as Fabric Reinforced Mortar or Fabric Reinforced Cementitious Matrix, composites are an emerging technology for the external repair and strengthening of existing structures. For most applications, the effectiveness of the TRM reinforcement relies on its bond performance. This recommendation identifies the best practice to characterize the bond behaviour of TRM. A shear bond test method is proposed to determine the peak axial stress (associated with the maximum load that can be transferred from the structural member to the externally bonded TRM reinforcement), the stress–slip relationship and the failure mode that controls the TRM-to-substrate load transfer capacity. Guidelines on specimen manufacturing, experimental setup, test execution, and determination of test results are provided.     

Halitosis and Helicobacter pylori: a possible relationship

With the aim of investigating a possible relationship between "objective" halitosis (established by sulfide levels in the breath) and Helicobacter pylori, we performed a study in 58 dyspeptic patients reported to suffer from "bad breath." Furthermore, we evaluated the effects on halitosis of eradication therapy (only for H. pylori-positive patients) and chlorhexidine antiseptic mouth rinses (in all patients). Sulfide compound assay indicated objective halitosis in 52/58 patients, 30 of whom were positive and 22 negative for H. pylori. In 19/30 eradication by double therapy provoked a decrease to below the cutoff value of sulfide levels in 15. In the other 11 of the 30 subjects, in whom H. pylori positivity persisted, halitosis parameters did not change. Chlorexidine reduced sulfides to below the cutoff value in 16/22 H. pylori-negative patients, but did not provoke any change in the 11 unsuccessfully treated H. pylori-positive subjects. In these, objective halitosis disappeared only after a successful eradication by triple therapy (9/11). Our results show a possible association between halitosis and H. pylori since bacterial eradication may resolve the symptom. Antiseptic mouthwashes may be effective only in absence of H. pylori, when halitosis may be due to oral putrefactive microbial activity. In a small number of subjects the cause and treatment of halitosis need to be clarified.     

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.     

Optimal-tuning PID control of adaptive materials for structural efficiency

The objective of this paper was solving the optimization problem of lightweight stiffened structures modelled as a two-dimensional domain in an efficient computational way. The underlying premise was that mass should be distributed in an efficient way, so as to use a minimum amount of material to accomplish the mechanical function. This premise was expressed as a global, multi-objective optimization problem in which stiffness and mass were conflicting objectives. Alternative local evolution rules were implemented to update mass density or Young’s modulus at each step of the iterative procedure. The solution of the structural optimization problem was accomplished by a novel automatic procedure consisting of two consecutive stages of control and optimization. In the first stage of Proportional Integral Derivative (PID) control gains were manually selected whereas in the second stage the finding of optimal values of control gains, target, and cost indices was allowed. In this study a bone-like material was adopted and a thin slab was analysed as a sample problem.