Just Drink a Glass of Water? Effects of Bicarbonate-Sulfate-Calcium-Magnesium Water on the Gut-Liver Axis

Background and Aim: Fonte Essenziale (R) water is a bicarbonate-sulfate-calcium-magnesium water, low in sodium, recognized by the Italian health care system in hydropinotherapy and hepatobiliary dyspepsia therapy. We wanted to explore its effects on the gut-liver axis and microbiota in non-alcoholic fatty liver disease patients.Patients and Methods: We considered enrollment for 70 patients, of which four were excluded. We finally enrolled 55 patients with ultrasound-documented steatosis (SPs+) and 11 patients without it (SPs-). They then drank 400 ml of water for 6 months in the morning on an empty stomach. Routine hematochemical and metabolic parameters, oxidative stress parameters, gastrointestinal hormone levels, and fecal parameters of the gut microbiota were evaluated at three different assessment times, at baseline (T0), after 6 months (T6), and after a further 6 months of water washout (T12). We lost, in follow-up, 4 (T6) and 22 (T12) patients.Results: Between T0-T6, we observed a significant Futuin A and Selenoprotein A decrease and a GLP-1 and PYY increase in SPs+ and the same for Futuin A and GLP-1 in SPs-. Effects were lost at T12. In SPs+, between T0-T12 and T6-12, a significant reduction in Blautia was observed; between T0-T12, a reduction of Collinsella unc. was observed; and between T0-T12 and T6-12, an increase in Subdoligranulum and Dorea was observed. None of the bacterial strains we analyzed varied significantly in the SPs- population.Conclusion: These results indicate beneficial effects of water on gastrointestinal hormones and hence on the gut-liver axis in the period in which subjects drank water both in SPs- and in SPs+

New silibinin glyco-conjugates: Synthesis and evaluation of antioxidant properties

New silibinin glyco-conjugates have been synthesized by efficient method and in short time. Exploiting our solution phase strategy, several structurally diverse silibinin glyco-conjugates (gluco, manno, galacto, and lacto-) were successfully realized in very good yields and in short time. In preliminary study to evaluate their antioxidant and neuroprotective activities new derivatives were subjected to DPPH free radical scavenging assay and the Xanthine oxidase (XO) inhibition models assay. Irrespective of the sugar moiety examined, new glyco-conjugates are more than 50 times water-soluble of silibinin. In the other hand they exhibit a radical scavenging activities slightly higher than to silibinin and XO inhibition at least as silibinin. (C) 2014 Elsevier Ltd. All rights reserved

numerical simulation of liquid bio fuel combustion in an egr equipped micro gas turbine

This paper focuses the attention to the possibility of a correct combustion close to the flameless regime, even in the presence of lower calorific value fuels like those that can be found with high concentrations in the bio-mass derived ones. In addition, the authors pay attention to the nitric oxide control by means of an optimal choice of the pilot injector location. The authors follow their previous experiences in the search of feasible modifications to an existing lean-premixed combustor for a definite pollutant abatement from a micro-gas turbine

Helicobacter pylori Up-regulates Cyclooxygenase-2 mRNA Expression and Prostaglandin E2 Synthesis in MKN 28 Gastric Mucosal Cells in Vitro

Helicobacter pylori has been suggested to play a role in the development of gastric carcinoma in humans. Also, mounting evidence indicates that cyclooxygenase-2 overexpression is associated with gastrointestinal carcinogenesis. We studied the effect of H. pylori on the expression and activity of cyclooxygenase-1 and cyclooxygenase-2 in MKN 28 gastric mucosal cells. H. pylori did not affect cyclooxygenase-1 expression, whereas cyclooxygenase-2 mRNA levels increased by 5-fold at 24 h after incubation of MKN 28 cells with broth culture filtrates or bacterial suspensions from wild-type H. pylori strain. Also, H. pylori caused a 3-fold increase in the release of prostaglandin E2, the main product of cyclooxygenase activity. This effect was specifically related to H. pylori because it was not observed with Escherichia coli and was independent of VacA, CagA, or ammonia. H. pylori isogenic mutants specifically lacking picA or picB, which are responsible for cytokine production by gastric cells, were less effective in the up-regulation of cyclooxygenase-2 mRNA expression and in the stimulation of prostaglandin E2 release compared with the parental wild-type strain. This study suggests that development of gastric carcinoma associated with H. pylori infection may depend on the activation of cyclooxygenase-2-related events

Regorafenib in combination with silybin as a novel potential strategy for the treatment of metastatic colorectal cancer

Regorafenib, an oral multikinase inhibitor, has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients that have progressed after all standard therapies. However, novel strategies to improve tolerability and enhance anti-cancer efficacy are needed

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Déu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience. Trial registration: NCT02561416. Registered 23 September 201

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Deu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience

Rationale and Design of the PARTHENOPE Trial: A Two-by-Two Factorial Comparison of Polymer-Free vs. Biodegradable-Polymer Drug-Eluting Stents and Personalized vs. Standard Duration of Dual Antiplatelet Therapy in All-Comers Undergoing PCI.

BACKGROUND Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 13 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the non-inferiority between stents with respect to a device-oriented composite endpoint of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI