The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

MicroRNA Cross-Involvement in Acne Vulgaris and Hidradenitis Suppurativa: A Literature Review

Acne Vulgaris (AV) and Hidradenitis suppurativa (HS) are common chronic inflammatory skin conditions that affect the follicular units that often coexist or are involved in differential diagnoses. Inflammation in both these diseases may result from shared pathways, which may partially explain their frequent coexistence. MicroRNAs (miRNAs) are a class of endogenous, short, non-protein coding, gene-silencing or promoting RNAs that may promote various inflammatory diseases. This narrative review investigates the current knowledge regarding miRNAs and their link to AV and HS. The aim is to examine the role of these molecules in the pathogenesis of AV and HS and to identify possible common miRNAs that could explain the similar characteristics of these two diseases. Five miRNA (miR-155 miR-223-, miR-21, and miRNA-146a) levels were found to be altered in both HS and AV. These miRNAs are related to pathogenetic aspects common to both pathologies, such as the regulation of the innate immune response, regulation of the Th1/Th17 axis, and fibrosis processes that induce scar formation. This review provides a starting point for further studies aimed at investigating the role of miRNAs in AV and HS for their possible use as diagnostic-therapeutic targets.     

EU regional development policy and territorial capital: A systemic approach

The territorial capital of regions is an important determinant of growth, but also of the impact of EU Cohesion Policy. First, because it can act as a filter, enhancing the impact of regional policies. Second, the latter can help building territorial capital which, in turn, will foster regional development. This work analyses the medium and long-run relationship between the territorial capital of EU NUTS 3 regions and Cohesion Policy using data from the programming period 2000–2006. Results point out complementarities between different territorial assets of regions and the impact of EU regional policy: Cohesion Policy effectiveness is higher when investments are focused on the assets complementary to those already abundant in the region.     

Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.     

Waste‐Free Electrochemical Oxidation of Alcohols in Water

We describe a new sol‐gel molecular electrode made of a thin layer of organosilica doped with the nitroxyl radical TEMPO (2,2,6,6‐tetramethylpiperidine‐1‐oxyl) electrodeposited on the surface of an ITO‐coated glass and its employment as a selective and versatile oxidation catalyst in the electrochemical conversion of different alcohols to carbonyl compounds. Environmentally friendly water or a water/acetonitrile mixture buffered with bicarbonate is used as solvent. The electrode is highly stable and it can be reused for a prolonged period of time allowing easy separation from the products.     

Reactive Compatibilizer Precursors for LDPE/PA6 Blends, 4

Summary: The effectiveness of some thermoplastic elastomers grafted with maleic anhydride (MA) or with glycidyl methacrylate (GMA) as compatibilizer precursors (CPs) for blends of low density polyethylene (LDPE) with polyamide‐6 (PA) has been studied. The CPs were produced by grafting different amounts of MA or GMA onto a styrene‐block‐(ethylene‐co‐1‐butene)‐block‐styrene copolymer (SEBS) (KRATON G 1652), either in the melt or in solution. A commercially available SEBS‐g‐MA copolymer with 1.7 wt.‐% MA (KRATON FG 1901X) was also used. The effect of the MA concentration and of other characteristics of the SEBS‐g‐MA CPs was also studied. The specific interactions between the CPs and the blends components were investigated through characterizations of the binary LDPE/CP and PA/CP blends, in the whole composition range. It was demonstrated that the SEBS‐g‐GMA copolymers display poor compatibilizing effectiveness due to cross‐linking resulting from reactions of the epoxy rings of these CPs with both the amine and the carboxyl end groups of PA. On the contrary, the compatibilizing efficiency of the MA‐grafted elastomers, as revealed by the thermal properties and the morphology of the compatibilized blends, was shown to be excellent. The results of this study confirm that the anhydride functional groups possess considerably higher efficiency, for the reactive compatibilization of LDPE/PA blends, than those of the ethylene‐acrylic acid and ethylene‐glycidyl methacrylate copolymers investigated in previous works.

SEM micrograph of the 75/25 LD08/PA blend (with 2 phr SEBSMA1).     

Modulation of Aβ42 Aggregation Kinetics and Pathway by Low-Molecular-Weight Inhibitors

The aggregation of amyloid-β 42 (Aβ42) is directly related to the pathogenesis of Alzheimer's disease. Here, we have investigated the early stages of the aggregation process, during which most of the cytotoxic species are formed. Aβ42 aggregation kinetics, characterized by the quantification of Aβ42 monomer consumption, were tracked by real-time solution NMR spectroscopy (RT-NMR) allowing the impact that low-molecular-weight (LMW) inhibitors and modulators exert on the aggregation process to be analysed. Distinct differences in the Aβ42 kinetic profiles were apparent and were further investigated kinetically and structurally by using thioflavin T (ThT) and transmission electron microscopy (TEM), respectively. LMW inhibitors were shown to have a differential impact on early-state aggregation. Insight provided here could direct future therapeutic design based on kinetic profiling of the process of fibril formation.     

Identification of Hck Inhibitors As Hits for the Development of Antileukemia and Anti‐HIV Agents

Hematopoietic cell kinase (Hck) is a member of the Src family of non‐receptor protein tyrosine kinases. High levels of Hck are associated with drug resistance in chronic myeloid leukemia. Furthermore, Hck activity has been connected with HIV‐1. Herein, structure‐based drug design efforts were aimed at identifying novel Hck inhibitors. First, an in‐house library of pyrazolo[3,4‐d]pyrimidine derivatives, which were previously shown to be dual Abl and c‐Src inhibitors, was analyzed by docking studies within the ATP binding site of Hck to select the best candidates to be tested in a cell‐free assay. Next, the same computational protocol was applied to screen a database of commercially available compounds. As a result, most of the selected compounds were found active against Hck, with K_i values ranging from 0.14 to 18.4 μM , confirming the suitability of the computational approach adopted. Furthermore, selected compounds showed an interesting antiproliferative activity profile against the human leukemia cell line KU‐812, and one compound was found to block HIV‐1 replication at sub‐toxic concentrations.