Controlled surface initiated polymerization of N-isopropylacrylamide from polycaprolactone substrates for regulating cell attachment and detachment

Poly(ε-caprolactone) (PCL) substrates were modified with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brushes to direct and control cellular attachment and detachment. Prior to brush growth, the surface of PCL was activated by a diamine to allow for initiator coupling. Infrared spectra taken before and after cell culturing demonstrated the covalently attached nature of the PNIPAM brushes. PCL is a biocompatible polymer and to prove that the modifications described above did not change this characteristic property, a cell attachment/detachment study was carried out. The modified substrates showed a lower cell attachment when compared to PCL alone and to PCL films modified with the initiator. The possibility to detach the cells in the form of a sheet was proved using PNIPAM-modified PCL films by lowering the temperature to 25 °C. No relevant detachment was shown by the unmodified or by the initiator modified surfaces. This confirmed that the detachment was temperature dependent and not connected to other factors such as polymer swelling. These functionalized polymeric films can find applications as smart cell culture systems in regenerative medicine applications

Relaxation of spherical systems with long-range interactions: a numerical investigation

The process of relaxation of a system of particles interacting with long-range forces is relevant to many areas of Physics. For obvious reasons, in Stellar Dynamics much attention has been paid to the case of 1/r^2 force law. However, recently the interest in alternative gravities emerged, and significant differences with respect to Newtonian gravity have been found in relaxation phenomena. Here we begin to explore this matter further, by using a numerical model of spherical shells interacting with an 1/r^alpha force law obeying the superposition principle. We find that the virialization and phase-mixing times depend on the exponent alpha, with small values of alpha corresponding to longer relaxation times, similarly to what happens when comparing for N-body simulations in classical gravity and in Modified Newtonian Dynamics.Comment: 6 pages, 3 figures, accepted in the International Journal of Bifurcation and Chao

Prevalence and pharmacologic management of familial hypercholesterolemia in an unselected contemporary cohort of patients with stable coronary artery disease

INTRODUCTION: Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) associated with premature cardiovascular disease. METHODS: Using the data from the START (STable Coronary Artery Diseases RegisTry) study, a nationwide, prospective survey on patients with stable coronary artery disease (CAD), we described prevalence and lipid lowering strategies commonly employed in these patients. The study population was divided into "definite/probable FH," defined as a Dutch Lipid Clinic Network (DLCN) score ≥6, "possible FH" with DLCN 3-5, and "unlikely FH" in presence of a DLCN <3. RESULTS: Among the 4030 patients with the DLCN score available, 132 (3.3%) were classified as FH (2.3% with definite/probable and 1.0% with possible FH) and 3898 (96.7%) had unlikely FH. Patients with both definite/probable and possible FH were younger compared to patients not presenting FH. Mean on-treatment LDL-C levels were 107.8 ± 41.5, 84.4 ± 40.9, and 85.8 ± 32.3 (P < 0.0001) and a target of ≤70 mg/dL was reached in 10.9%, 30.0%, and 22.0% (P < 0.0001) of patents with definite/probable, possible FH, and unlikely FH, respectively. Statin therapy was prescribed in 85 (92.4%) patients with definite/probable FH, in 38 (95.0%) with possible FH, and in 3621 (92.9%) with unlikely FH (P = 0.86). The association of statin and ezetimibe, in absence of other lipid-lowering therapy, was more frequently used in patients with definite/probable FH compared to patients without FH (31.5% vs 17.5% vs 9.5%; P < 0.0001). CONCLUSIONS: In this large cohort of consecutive patients with stable CAD, FH was highly prevalent and generally undertreated with lipid lowering therapies

On the vacuum of the minimal nonsupersymmetric SO(10) unification

We study a class of nonsupersymmetric SO(10) grand unified scenarios where the first stage of the symmetry breaking is driven by the vacuum expectation values of the 45-dimensional adjoint representation. Three decade old results claim that such a Higgs setting may lead exclusively to the flipped SU(5) x U(1) intermediate stage. We show that this conclusion is actually an artifact of the tree level potential. The study of the accidental global symmetries emerging in various limits of the scalar potential offers a simple understanding of the tree level result and a rationale for the drastic impact of quantum corrections. We scrutinize in detail the simplest and paradigmatic case of the 45_{H} + 16_{H} Higgs sector triggering the breaking of SO(10) to the standard electroweak model. We show that the minimization of the one-loop effective potential allows for intermediate SU(4)_C x SU(2)_L x U(1)_R and SU(3)_c x SU(2)_L x SU(2)_R x U(1)_{B-L} symmetric stages as well. These are the options favoured by gauge unification. Our results, that apply whenever the SO(10) breaking is triggered by , open the path for hunting the simplest realistic scenario of nonsupersymmetric SO(10) grand unification.Comment: 22 pages, 1 figure. Refs added. To appear in Phys. Rev.

Oral platelet gel supernatant plus supportive medical treatment versus supportive medical treatment in the management of radiation-induced oral mucositis: a matched explorative active control trial by propensity analysis

OBJECTIVES:: In this active control trial, the rate of radio-induced WHO grade 3/4 oral mucositis and the change in quality of life, assessed by OMWQ-HN, were measured in subjects with head and neck cancer treated by platelet gel supernatant (PGS) and supportive medical treatment versus subjects treated by supportive medical treatment alone. MATERIALS AND METHODS:: Eighty patients with nonmetastatic head and neck cancer underwent curative or adjuvant radiotherapy. All patients underwent supportive medical treatment and/or PGS at the beginning and during radiotherapy. Sixteen patients received PGS in association with supportive medical treatment. To obtain 2 groups virtually randomized for important clinical characteristics subjects were matched, by propensity analysis, with a group of subjects (64 patients) treated with supportive medical treatment alone. RESULTS:: Subjects treated with standard supportive treatment experienced significant higher WHO grade 3/4 toxicity (55%; 35/64) than subjects treated by PGS (13%; 3/16). The reduced toxicity found in PGS group paralleled with the evidence that they developed later symptoms with respect to controls. The Cox proportional hazard model indicated that patients treated with standard supportive medical treatment experienced 2.7-fold increase (hazard ratio=2.7; 95% confidence interval, 1.3-5.7) in the occurrence of WHO grade 3/4 toxicity. PGS group significantly experienced higher quality of life than control groups as measured by OMWQ-HN. A significant decrease in the opioid analgesics usage was found in the PGS group. CONCLUSIONS:: These preliminary data should be interpreted with caution and could serve as a framework around which to design future trials

Synthesis and characterisation of a new benzamide-containing nitrobenzoxadiazole as a GSTP1-1 inhibitor endowed with high stability to metabolic hydrolysis

The antitumor agent 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (1) is a potent inhibitor of GSTP1-1, a glutathione S-transferase capable of inhibiting apoptosis by binding to JNK1 and TRAF2. We recently demonstrated that, unlike its parent compound, the benzoyl ester of 1 (compound 3) exhibits negligible reactivity towards GSH, and has a different mode of interaction with GSTP1-1. Unfortunately, 3 is susceptible to rapid metabolic hydrolysis. In an effort to improve the metabolic stability of 3, its ester group has been replaced by an amide, leading to N-(6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexyl)benzamide (4). Unlike 3, compound 4 was stable to human liver microsomal carboxylesterases, but retained the ability to disrupt the interaction between GSTP1-1 and TRAF2 regardless of GSH levels. Moreover, 4 exhibited both a higher stability in the presence of GSH and a greater cytotoxicity towards cultured A375 melanoma cells, in comparison with 1 and its analog 2. These findings suggest that 4 deserves further preclinical testing

Data of safety in a single-center alemtuzumab treated population

Alemtuzumab is approved for highly active MS and, in Europe, can be employed after other disease-modifying treatments (DMTs) as an escalation approach or first therapeutic option. The occurrence of secondary autoimmune adverse events and infections differs depending on the employed approach. In the manuscript entitled “Alemtuzumab treatment of multiple sclerosis in real-world clinical practice: report from a single Italian center” by di Ioia M. and collaborators, efficacy and safety data of alemtuzumab were evaluated in a real-world MS population. The aim of the article is to describe in detail the unexpected serious adverse events which occurred in this cohort during and after the administration of the alemtuzumab treatment. Adverse events were observed in 45,7% of the patients. These events were ranked as severe in 23% of the patients. We reported, in particular, cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E and noninfectious meningo-encephalomyelitis

Successful Fat Grafting in a Patient with Thromboangiitis Obliterans

Thromboangiitis obliterans, or Buerger disease, is a rare nonatherosclerotic segmental inflammatory vasculitis that generally affects young tobacco smokers. Although no surgical treatment is available, the most effective way to halt the disease's progress is smoking cessation. In this case report, a 29-year-old smoker showed up to emergency department with gangrene of his fifth left toe and extensive plantar ulceration. After investigative angiography, he was diagnosed with Buerger disease. On November 2017, he underwent fifth left toe amputation and hyperbaric therapy. Five months after amputation, the patient was rehospitalized because of surgical wound dehiscence, wide ulceration, and pain. He was treated with lipofilling using the Coleman technique. Two weeks after the fat grafting procedure, the patient suspended pain control medication, and after 2 months, the surgical wound was almost healed. Fat grafting (lipofilling) is mostly used in plastic surgery; it offers regenerative effects, with minimal discomfort for the patient. This case report demonstrates a successful alternative use of lipofilling for this unique condition and opens up new options for use of this technique in other fields

Dynamical charge density fluctuations pervading the phase diagram of a Cu-based high-Tc superconductor

Charge density waves are a common occurrence in all families of high critical temperature superconducting cuprates. Although consistently observed in the underdoped region of the phase diagram and at relatively low temperatures, it is still unclear to what extent they influence the unusual properties of these systems. Using resonant x-ray scattering we carefully determined the temperature dependence of charge density modulations in (Y,Nd)Ba$_2$Cu$_3$O$_{7-{\delta}}$ for three doping levels. We discovered short-range dynamical charge density fluctuations besides the previously known quasi-critical charge density waves. They persist up to well above the pseudogap temperature T*, are characterized by energies of few meV and pervade a large area of the phase diagram, so that they can play a key role in shaping the peculiar normal-state properties of cuprates.Comment: 34 pages, 4 figures, 11 supplementary figure