Structural expression of exo-anomeric effect

Structural signatures for exo--anomeric effect have been extracted from the archetypal methyl--$\beta$--D--xyloside using broadband Fourier transform microwave spectroscopy combined with laser ablation. Spectrum analysis allows the determination of a set of rotational constants, which has been unequivocally attributed to conformer cc--$\beta$-$^{4}$C$_{1}$ g-, corresponding to the global minimum of the potential energy surface, where the aglycon residue (CH$_{3}$) orientation contributes towards maximization of the exo-anomeric effect. Further analysis allowed the determination of the r$_{s}$ structure, based on the detection of eleven isotopologues - derived from the presence of six $^{13}$C and five $^{18}$O atoms - observed in their natural abundances. The observed glycosidic C$_{1}$-O$_{1}$ bond length decrease (1.38 \AA) can be interpreted in terms of the exo--anomeric effect. As such, the exo--anomeric effect presents itself as one of the main driving forces controlling the shape of many biologically important oligosaccharides

H-bonding networks in sugar alcohols: identifying glucophores?

The conformational behaviour of sorbitol and dulcitol has been investigated for the first time using a combination of chirped pulse Fourier transform microwave spectroscopy (CP-FTMW) coupled with a laser ablation (LA) source. The observed conformers have been found to be overstabilised by cooperative networks of intramolecular hydrogen bonds between vicinal hydroxyl groups stretching throughout the whole molecule. A common structural signature - involving hydroxyl groups in the H-bond - has been characterized and ascribed to the glucophore's AH and B sites in accordance with Shallenberger’s old proposal.\footnote{R.~S.~Shallenberger, T.~E.~Acree, \textit{Nature,} \textbf{1967}, \textit{216}, 480-482}$^{,}$\footnote{R.~S.~Shallenberger, T.~E.~Acree, C.~Y.~Lee, \textit{Nature,} \textbf{1969}, \textit{221}, 555-556

Stakeholder Forum activities

The Deliverable 5.4.2 (Stakeholder Forums activities) is conceived as a report to inform about activities carried out in the Stakeholder Fora. It is conceived as a dynamic document, following progresses in the Stakeholder Forum organization and set up and reporting relevant achievements. It is substantially divided into three sections: The first one, represented by the Executive Summary and the Introduction, is not expected to change during the project life, at least in its core elements; The second one, represented by activities carried out in the Stakeholder Fora (Chapter 1), as general information on specific events, summarizing relevant activities performed in specific events, is supposed to change and be enlarged during the project life, so to provide updates on the activities carried out in Task 5.4.2 – Stakeholder Forum Activities. Next Actions: in Chapter 2 an overview is done on the activities planned to organize the next Stakeholder Fora. Annex 1 presents the Dissemination material to be presented at the General Stakeholder Fora. Annex 2 shows the Dissemination material presented during the TeleFOT First General Stakeholder Forum

The Role of Oestrogen Receptor Beta (ERβ) in the Aetiology and Treatment of Type 2 Diabetes Mellitus

Introduction: Challenges facing the treatment of type 2 diabetes necessitate the search for agents which act via alternative pathways to provide better therapeutic outcomes. Recently, an increasing body of evidence implicates the activation of oestrogen receptors (ERα and ERβ) in the development and treatment of underlying conditions in type 2 diabetes. This article summarizes available evidence for the involvement of oestrogen receptors in insulin secretion, insulin resistance as well as glucose uptake and highlights the potential of ERβ as a therapeutic target. Background: Recent studies indicate an association between the activation of each of the isoforms of ER and recent findings indicate that ERβ shows promise as a potential target for antidiabetic drugs. In vitro and in vivo studies in receptor knockout mice indicate beneficial actions of selective agonists of ERβ receptor and underscore its therapeutic potential. Conclusion: Studies are needed to further elucidate the exact mechanism underlying the role of ERβ activation as a therapeutic approach in the management of type 2 diabetes

Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7–9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies

Determinants and Differences in Satisfaction with the Inhaler Among Patients with Asthma or COPD

Satisfaction with the inhaler is an important determinant of treatment adherence in patients with asthma and chronic obstructive pulmonary disease (COPD). However, few studies have compared these 2 groups to identify the factors associated with satisfaction with the inhaler. To assess and compare satisfaction with the inhaler in patients with asthma or COPD and to determine the variables associated with high inhaler satisfaction. A multicenter, cross-sectional study of 816 patients (406 with asthma and 410 with COPD) was conducted. Satisfaction was assessed with the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. All participants completed the Test of Adherence to Inhalers and either the Asthma Control Test (ACT) or the COPD Assessment Test (CAT). Overall, the asthma group was significantly more satisfied with the inhaler (mean [standard deviation] FSI-10 scores: 44.1 [6.5] vs 42.0 [7.7]; P <.001) and more satisfied on most (7 of 10; 70%) items. Patients with asthma were significantly more satisfied with the inhaler regardless of the adherence level or the type of nonadherence pattern. Younger age, good disease control (ACT ≥20 or CAT ≤10), previous inhaler training, and absence of unwitting nonadherence were all independently and significantly associated with high inhaler satisfaction. Age, disease control, and training in inhalation technique all play a more significant role than the specific diagnosis in explaining satisfaction with the device in patients with asthma and COPD. These findings underscore the need to provide better training and more active monitoring of the inhalation technique to improve patient satisfaction, treatment adherence, and clinical outcomes

Effects on short term outcome of non-invasive ventilation use in the emergency department to treat patients with acute heart failure: A propensity score-based analysis of the EAHFE Registry

Objective: To assess the effects of non-invasive ventilation (NIV) in emergency department (ED) patients with acute heart failure (AHF) on short term outcomes. Methods: Patients from the EAHFE Registry (a multicenter, observational, multipurpose, cohort-designed database including consecutive AHF patients in 41 Spanish EDs) were grouped based on NIV treatment (NIV+ and NIV–groups). Using propensity score (PS) methodology, we identified two subgroups of patients matched by 38 covariates and compared regarding 30-day survival (primary outcome). Interaction was investigated for age, sex, ischemic cardiomyopathy, chronic obstructive pulmonary disease, AHF precipitated by an acute coronary syndrome (ACS), AHF classified as hypertensive or acute pulmonary edema (APE), and systolic blood pressure (SBP). Secondary outcomes were intensive care unit (ICU) admission; mechanical ventilation; in-hospital, 3-day and 7-day mortality; and prolonged hospitalization (>7 days). Results: Of 11, 152 patients from the EAHFE (age (SD): 80 (10) years; 55.5% women), 718 (6.4%) were NIV+ and had a higher 30-day mortality (HR = 2.229; 95%CI = 1.861–2.670) (p 85 years, p < 0.001), AHF associated with ACS (p = 0.045), and SBP < 100 mmHg (p < 0.001). No significant differences were found in the secondary endpoints except for more prolonged hospitalizations in NIV+ patients (OR = 1.445; 95%CI = 1.122–1.862) (p = 0.004). Conclusion: The use of NIV to treat AHF in ED is not associated with improved mortality outcomes and should be cautious in old patients and those with ACS and hypotension

Redefining Clostridioides difficile infection antibiotic response and clinical outcomes

With the approval and development of narrow-spectrum antibiotics for the treatment of Clostridioides difficile infection (CDI), the primary endpoint for treatment success of CDI antibiotic treatment trials has shifted from treatment response at end of therapy to sustained response 30 days after completed therapy. The current definition of a successful response to treatment (three or fewer unformed bowel movements [UBMs] per day for 1-2 days) has not been validated, does not reflect CDI management, and could impair assessments for successful treatment at 30 days. We propose new definitions to optimise trial design to assess sustained response. Primarily, we suggest that the initial response at the end of treatment be defined as (1) three or fewer UBMs per day, (2) a reduction in UBMs of more than 50% per day, (3) a decrease in stool volume of more than 75% for those with ostomy, or (4) attainment of bowel movements of Bristol Stool Form Scale types 1-4, on average, by day 2 after completion of primary CDI therapy (ie, assessed on day 11 and day 12 of a 10-day treatment course) and following an investigator determination that CDI treatment can be ceased.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc