A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

The hexameric resorcin[4]arene capsule as a self-assembled organocatalyst promotes a series of reactions like the carbonyl–ene cyclization of (S)-citronellal preferentially to isopulegol, the water elimination from 1,1-diphenylethanol, the isomerization of α-pinene and β-pinene preferentially to limonene and minor amounts of camphene. The role of the supramolecular catalyst consists in promoting the protonation of the substrates leading to the formation of cationic intermediates that are stabilized within the cavity with consequent peculiar features in terms of acceleration and product selectivity. In all cases the catalytic activity displayed by the hexameric capsule is remarkable if compared to many other strong Brønsted or Lewis acid

Substrate Selectivity Imparted by Self‐Assembled Molecular Containers and Catalysts

Recent trends in catalysis are devoted to mimicking some peculiar features of enzymes like site selectivity, through functional group recognition, and substrate selectivity, through recognition of the entire surface of the substrate. The latter is a specific feature of enzymes that is seldomly present in homogeneous catalysis. Supramolecular catalysis, thanks to the self-assembly of simple subunits, enables the creation of cavities and surfaces whose confinement effects drive the preferential binding of a substrate among others with consequent substrate selectivity. The topic is an emerging field that exploits recognition phenomena to discriminate the reagents based on their size and shape. This review deals this cutting-edge field of research covering examples of supramolecular self-assembled molecular containers and catalysts operating in organic as well as aqueous media, with special emphasis for catalytic systems dealing with direct competitive experiments involving two or more substrates.Substrate selectivity is the property of catalysts like enzymes to pick up one substrate among many others in solution. To implement substrate selectivity in artificial homogeneous catalysts, an emerging approach in homogeneous catalysis consists in exploiting self-assembled nano-catalysts and nanocontainers. The confinement effects provide supramolecular substrate recognition before the catalytic step. This review covers recent achievements in this challenging field of research.imag

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C - both symptomatic and asymptomatic - have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment

Preliminary Study on the Effect of a Night Shift on Blood Pressure and Clock Gene Expression

Night shift work has been found to be associated with a higher risk of cardiovascular and cerebrovascular disease. One of the underlying mechanisms seems to be that shift work promotes hypertension, but results have been variable. This cross-sectional study was carried out in a group of internists with the aim of performing a paired analysis of 24 h blood pressure in the same physicians working a day shift and then a night shift, and a paired analysis of clock gene expression after a night of rest and a night of work. Each participant wore an ambulatory blood pressure monitor (ABPM) twice. The first time was for a 24 h period that included a 12 h day shift (08.00–20.00) and a night of rest. The second time was for a 30 h period that included a day of rest, a night shift (20.00–08.00), and a subsequent period of rest (08.00–14.00). Subjects underwent fasting blood sampling twice: after the night of rest and after the night shift. Night shift work significantly increased night systolic blood pressure (SBP), night diastolic blood pressure (DBP), and heart rate (HR) and decreased their respective nocturnal decline. Clock gene expression increased after the night shift. There was a direct association between night blood pressure and clock gene expression. Night shifts lead to an increase in blood pressure, non-dipping status, and circadian rhythm misalignment. Blood pressure is associated with clock genes and circadian rhythm misalignement

Is there a place for nutritional supplements in the treatment of idiopathic male infertility?

Objective: Infertility affects 15% of couples in fertile age. Male factor is a cause of infertility in almost half of cases, mainly due to oligoasthenoteratozoospermia (OAT). The purpose of this study is to review the effects of nutritional supplements as medical treatment for idiopathic male infertility. Material and methods: A Pub Med and Medline review of the published studies utilizing nutritional supplements for the treatment of male infertility has been performed. Results: Clinical trials on Vitamin E, Vitamin A, Vitamin C. Arginine, Carnitine, N-Acetyl-Carnitine, Glutathione, Coenzyme Q10, Selenium and Zinc were reviewed. Although there is a wide variability in selected population, dose regimen and final outcomes, nutritional supplements both alone and in combination seems to be able to improve semen parameters (sperm count, sperm motility and morphology) and pregnancy rate in infertile men. Conclusions: There are rising evidences from published randomized trials and systematic review suggesting that nutritional supplementation may improve semen parameters and the likelihood of pregnancy in men affected by OAT. This improvement, however, is not consistent and there is a wide variation in the treatment regimens used. Well designed and adequately powered RCTs are needed to better clarify the role of nutritional supplements as treatment for male infertility

16 years follow-up evaluation of immediate vs delayed vs. combined hormonal therapy on fertility of patients with cryptorchidism: results of a longitudinal cohort study

To investigate in a longitudinal cohort study, the best treatment to preserve fertility in cryptorchid subjects. Patients treated with immediate hormonal vs. delayed vs. combined (hormone plus surgery) therapy consecutively enrolled during the period 1987-1997, were evaluated

Coronary Angiography After Transcatheter Aortic Valve Replacement (TAVR) to Evaluate the Risk of Coronary Access Impairment After TAVR‐in‐TAVR

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Leukemia inhibitory factor protects cholangiocarcinoma cells from drug-induced apoptosis via a PI3K/AKT-dependent Mcl-1 activation

Cholangiocarcinoma is an aggressive, strongly chemoresistant liver malignancy. Leukemia inhibitory factor (LIF), an IL-6 family cytokine, promotes progression of various carcinomas. To investigate the role of LIF in cholangiocarcinoma, we evaluated the expression of LIF and its receptor (LIFR) in human samples. LIF secretion and LIFR expression were assessed in established and primary human cholangiocarcinoma cell lines. In cholangiocarcinoma cells, we tested LIF effects on proliferation, invasion, stem cell-like phenotype, chemotherapy-induced apoptosis (gemcitabine+cisplatin), expression levels of pro-apoptotic (Bax) and anti-apoptotic (Mcl-1) proteins, with/without PI3K inhibition, and of pSTAT3, pERK1/2, pAKT. LIF effect on chemotherapy-induced apoptosis was evaluated after LIFR silencing and Mcl-1 inactivation. Results show that LIF and LIFR expression were higher in neoplastic than in control cholangiocytes; LIF was also expressed by tumor stromal cells. LIF had no effects on cholangiocarcinoma cell proliferation, invasion, and stemness signatures, whilst it counteracted drug-induced apoptosis. Upon LIF stimulation, decreased apoptosis was associated with Mcl-1 and pAKT up-regulation and abolished by PI3K inhibition. LIFR silencing and Mcl-1 blockade restored drug-induced apoptosis. In conclusion, autocrine and paracrine LIF signaling promote chemoresistance in cholangiocarcinoma by up-regulating Mcl-1 via a novel STAT3- and MAPK-independent, PI3K/AKT-dependent pathway. Targeting LIF signaling may increase CCA responsiveness to chemotherapy

Two different mechanisms of stabilization of regular pi-stacks of radicals in switchable dithiazolyl-based materials

Materials based on regular π-stacks of planar organic radicals are intensively pursued by virtue of their technologically relevant properties. Yet, these π-stacks are commonly unstable against π-dimerization. In this computational study, we reveal that regular π-stacks of planar dithiazolyl radicals can be rendered stable, in some range of temperatures, via two different mechanisms. When the radicals of a π-stack are both longitudinally and latitudinally slipped with respect to each other, the corresponding regular π-stacked configuration is associated with a locally stable minimum in the potential energy surface of the system. Conversely, those regular π-stacks in which radicals are latitudinally slipped with respect to each other are stable as a result of a dynamic interconversion between two degenerate dimerized configurations. The existence of two stabilization mechanisms, which can be traced back to the bonding properties of isolated π-dimers, translates into two different ways of exploiting spin-Peierls-like transitions in switchable dithiazolyl-based materials