Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues. Several studies have reported that in human SLE, there is an important role of the Type-I-interferons (INF) system suggested by the upregulation of INF-inducible genes observed in serial gene expression microarray studies. This review aims to describe the transduction pathways of Type-I-interferons, in particular INFα, and its immune-regulatory function in the pathogenesis of SLE and, in particular, in LN. In addition, recent novelties concerning biologic therapy in LN will be discussed.     

Improvement of glucose/insulin metabolism reduces hypertension in insulin-dependent diabetes mellitus recipients of kidney-pancreas transplantation

OBJECTIVE: The current guidelines recommend 1-wk triple therapy regimens for eradicating H. pylori infection. Until now, shorter regimens have scarcely been investigated. Azithromycin is a new generation macrolide antibiotic with unusual and favorable pharmacokinetics, and seems to be a very promising agent for innovative anti-H. pylori regimens. We assessed the efficacy and tolerability of a new 4-day low dose triple therapy in comparison with a well established 1-wk triple therapy in the treatment of Helicobacter pylori infection. METHODS: One hundred-sixty consecutive patients with biopsy-proven H. pylori infection were randomized to receive lansoprazole 30 mg b.i.d. on days 1-4, azithromycin 500 mg u.i.d. on days 2-4, and tinidazole 2000 mg u.i.d. on day 3 (LAT group), or 7 days of triple therapy of omeprazole 20 mg u.i.d., clarithromycin 250 mg b.i.d., and tinidazole 500 mg b.i.d. (OCT group). Patients with gastric or duodenal active ulcer received proton pump inhibitors for an additional 4 wk. H. pylori eradication was defined as negative of both rapid urease test and histology on biopsies taken from the gastric body and antrum at least 1 month after the end of treatment. RESULTS: Seven patients in the LAT group and four in the OCT group were lost to follow-up. No significant difference in either efficacy or tolerability was observed between the two regimens. Active ulcers healed in 97.8% of cases with LAT and in 100% of cases with OCT. The eradication rate was 80.8% in the LAT group and 85.5% in the OCT group, considering the per-protocol results, and 73.3% and 81.2%, respectively, considering the intention-to-treat results. Side effects occurred in one LAzT patient and in two OCT patients; they were mild and did not interfere with compliance. CONCLUSION: The new proposed ultrashort triple therapy, including lansoprazole, low dose azithromycin for 3 days, and a single dose of tinidazole, appears to be a very effective anti-H. pylori regimen, a simpler, cheaper, well-tolerated, and equally effective alternative to 1-wk triple therapy.     

Poly(lactic acid)-based biocomposites reinforced with kenaf fibers

Biodegradable thermoplastic-based composites reinforced with kenaf fibers were prepared and characterized. Poly(lactic acid) (PLA) was selected as polymeric matrix. To improve PLA/fibers adhesion, low amount of a proper reactive coupling agent, obtained by grafting maleic anhydride onto PLA, was added during matrix/fibers melt mixing. Compared with uncompatibilized composites, this compatibilization strategy induces a strong interfacial adhesion and a pronounced improvement of the mechanical properties. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Design and characterization of a diode-pumped, single longitudinal and transverse mode, intracavity-doubled cw Nd:YAG laser

We report on the experimental results of a diode-pumped, intracavity-doubled cw Nd:YAG laser, pumped by a 10-W fiber-coupled semiconductor laser at 808 nm and emitting as much as 600 mW in a stable single longitudinal mode and TEM(00) spatial mode. We discuss the main issues of the resonator design and the optimization of the intracavity second harmonic conversion by interpreting our results using simple models. Improvements for the current project are also discussed.     

A learn‐and‐construct framework for general mixed‐integer programming problems

In this paper, we propose a new framework for finding an initial feasible solution from a mixed‐integer programming (MIP) model. We call it learn‐and‐construct since it first exploits the structure of the model and its linear relaxation solution and then uses this knowledge to try to produce a feasible solution. In the learning phase, we use an unsupervised learning algorithm to cluster entities originating the MIP model. Such clusters are then used to decompose the original MIP in a number of easier sub‐MIPs that are solved by using a black box solver. Computational results on three well‐known problems show that our procedure is characterized by a success rate larger than both the feasibility pump heuristic and a state‐of‐the‐art MIP solver. Furthermore, our approach is more scalable and uses less computing time on average.     

Topology driven modeling: the IS metaphor

In order to define a new method for analyzing the immune system within the realm of Big Data, we bear on the metaphor provided by an extension of Parisi’s model, based on a mean field approach. The novelty is the multilinearity of the couplings in the configurational variables. This peculiarity allows us to compare the partition function \(Z\) with a particular functor of topological field theory—the generating function of the Betti numbers of the state manifold of the system—which contains the same global information of the system configurations and of the data set representing them. The comparison between the Betti numbers of the model and the real Betti numbers obtained from the topological analysis of phenomenological data, is expected to discover hidden n-ary relations among idiotypes and anti-idiotypes. The data topological analysis will select global features, reducible neither to a mere subgraph nor to a metric or vector space. How the immune system reacts, how it evolves, how it responds to stimuli is the result of an interaction that took place among many entities constrained in specific configurations which are relational. Within this metaphor, the proposed method turns out to be a global topological application of the S[B] paradigm for modeling complex systems.     

Chemical modification and structural rearrangements of polyketone‐based polymer membrane

Alternating polyketones constitute a very interesting class of polymers, which can be modified for the preparation of functional polymers. The chemical modification of polyketone using 1,2‐diaminopropane was used to prepare a conductive membrane. This paper is focused on the synthesis and structural rearrangements of polyamine for preparing anion‐exchange membranes by the solvent casting technique. According to the Paal‐Knorr mechanism, 1,4‐dicarbonyl of polyketone reacts with 1,2‐diaminopropane to form a pyrrole ring along the polyketone backbone. In addition, the so‐modified polyamines can undergo structural rearrangements to form N‐substituted pyrrole crosslinked with dihydropyridine units. The conversion degree and the N content are quite low. The pathway reactions have been proposed on the basis of ¹H‐NMR, ultraviolet–visible, and Fourier transform infrared results. Scanning electron microscopy, differential scanning calorimetry, and X‐ray diffraction techniques were used to study the morphological, thermal, and structural characteristics of the modified polyketone, as well as the correspondoing membrane. The experimental results indicated that the membrane is a potential candidate for energy conversion technology. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45485.