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letter to the edito

Novel antiproliferative biphenyl nicotinamide: NMR metabolomic study of its effect on the MCF-7 cell in comparison with cisplatin and vinblastine

A 1H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel nicotinamide derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC50 value, were investigated, with respect to the controls (K), by the 1H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or S-adenosylmethionine (SAM) limitation

The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor.

Signaling pathways have a key role in driving the uncontrolled development of familial adenomatous polyposis (FAP)- associated and sporadic desmoid tumors (DTs). The relationship between the Wnt/b-catenin signaling pathway and DTs has been extensively studied, but no reliable biomarkers able to detect their histological subtype have been identified for the accurate diagnosis. In this study we studied the differences in miRNA expression between sporadic (20 patients) and FAP-associated DTs (7 patients) using microarray confirmed by quantitative PCR (qPCR). The analysis showed 19 dysregulated miRNAs. Among them miR-133b levels were significantly lower in FAP-associated DT than in sporadic DT. Therefore, two mRNAs, associated to miR-133b and β-catenin expression, the SIRT1 and ELAVL1were analyzed. The qPCR analysis showed that SIRT1 mRNA levels were significantly up-regulated in FAP-associated DT than in sporadic DT, whereas no differences in ELAVL1 expression was observed between these two DT types. In addition, a negative correlation was observed between miR-133b and SIRT1 in FAP-associated DTs, but not in sporadic DTs. The miR-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying progression of FAP-associated D

Probing High Frequency Noise with Macroscopic Resonant Tunneling

We have developed a method for extracting the high-frequency noise spectral density of an rf-SQUID flux qubit from macroscopic resonant tunneling (MRT) rate measurements. The extracted noise spectral density is consistent with that of an ohmic environment up to frequencies ~ 4 GHz. We have also derived an expression for the MRT lineshape expected for a noise spectral density consisting of such a broadband ohmic component and an additional strongly peaked low-frequency component. This hybrid model provides an excellent fit to experimental data across a range of tunneling amplitudes and temperatures

(1R,2R,3S,6aS,7R,8R,9S,12aS)-1,2,3,7,8,9-Hexahydroxy­perhydro­dipyrido[1,2-a:1′,2′-d]pyrazine-6,12-dione

The crystal structure of the title compound, C12H18N2O8, exists as O—H⋯O hydrogen-bonded layers of mol­ecules running parallel to the ab plane. Each mol­ecule is a donor and acceptor for six hydrogen bonds. The absolute stereochemistry was determined by the use of d-glucuronolactone as the starting material

Staple line reinforcement with nebulized cyanoacrylate glue in laparoscopic sleeve gastrectomy: A propensity score-matched study

Background: A dreaded complication of laparoscopic sleeve gastrectomy (LSG) is suture leak. The study aimed to assess the efficacy of the nebulized comonomer Glubran 2® (N-butyl-cyanoacrylate + metacrylosysolfolane) applied to the LSG staple line. Methods: A propensity-matched comparison analysis was conducted in 125 patients undergoing LSG between 2017 and 2019. Groups included those treated with Glubran® (group 1, n = 70) and those without Glubran® treatment (group 2, n = 55). Results: There were differences in the mean body mass index (44.4 vs 43 kg/m2; P < 0.05) between the groups. There was a non-significant increase in the operative time for group 1 compared with group 2 (97 ± 8 vs 93.8 ± 10.7 min; P = 0.07), with a greater amount of estimated blood loss (94.5 mL vs 87.8; P < 0.01). There were more severe complications in group 2 over group 1 cases (8 vs 0%; P < 0.05), although postoperative bleeding did not differ between the two groups (1.4 vs 5.4%). There were no postoperative leaks in group 1 patients, but there were two leaks in group 2 cases with an increased length of hospital stay in patients with a leak. Conclusion: Glubran® LSG support may reduce leak risk without increasing operating time

Effects of temporary sacral nerve stimulation on gastrointestinal motility and function in patients with chronic refractory slow-transit constipation

Background: The efficacy of sacral nerve stimulation (SNS) on patients with chronic refractory slow-transit constipation is controversial and its mechanism of action on gastrointestinal motility and transit is not fully understood. The aim of this study was to document the effects of temporary SNS on the gastrointestinal and biliary tract motility and on gastrointestinal transit in patients with refractory slow-transit constipation. Methods: This was a prospective interventional study. Patients with slow-transit chronic constipation, unresponsive to any conservative treatment, were enrolled between January 2013 and December 2018. Patients’ quality of life [patient assessment of constipation quality of life (PAC-QOL) questionnaire], constipation scores (Cleveland Clinic Constipation Score) colonic transit time (CTT), orocecal transit time (OCTT), gastric and gallbladder kinetics, together with the assessment of the autonomic nerve function were evaluated before and during temporary SNS. Results: 14 patients (12 females, median age 38 years, range 24–42 years) had temporary SNS. The Cleveland Clinic Constipation Score did not change compared to baseline (23 ± 3 vs 21.4; p = 070). The PAC-QOL did not improve significantly during the stimulation period. Gallbladder/stomach motility (half-emptying time) did not change significantly before and after SNS. OCTT was delayed at baseline, as compared to standard internal normal values, and did not change during SNS. CTT did not improve significantly, although in two patients it decreased substantially from 97 to 53 h, and from 100 to 65 h. Conclusions: Temporary SNS did not have any effect on upper/lower gastrointestinal motility and transit in patients with severe constipation