Hybrid cyclic α/β-peptides, in which one or more β-amino acids are incorporated into the backbone, are gaining increasing interest as potential therapeutics, thanks to their ability to achieve ...enhanced binding affinities for a biological target through pre-organization in solution. The in silico prediction of their three dimensional structure through strategies such as MD simulations would substantially advance the rational design process. However, whether the molecular mechanics force fields are accurate in sampling highly constrained cyclopeptides containing β-amino acids remains to be verified. Here, we present a systematic assessment of the ability of 8 widely used force fields to reproduce 79 NMR observables (including chemical shifts and 3J scalar couplings) on five cyclic α/β-peptides that contain the integrin recognition motif isoDGR. Most of the investigated force fields, which include force fields from AMBER, OPLS, CHARMM and GROMOS families, display very good agreement with experimental 3J(HN,Hα), suggesting that MD simulations could be an appropriate tool in the rational design of therapeutic cyclic α-peptides. However, for NMR observables directly related to β-amino acids, we observed a poor agreement with experiments and a remarkable dependence of our evaluation on the choice of Karplus parameters. The force field weaknesses herein unveiled might constitute a source of inspiration for further force field optimization.
Acupuncture, both auricular and somatic, is a widely adopted and well-tolerated treatment for preoperative anxiety. The aim of our study was to compare the effectiveness of acupuncture with ...pharmacological treatment in reducing preoperative anxiety in patients undergoing cholecystectomy or TEP.
We randomized 120 patients in a control group PT (where patients underwent pharmacological treatment with Midazolam) and in an acupuncture group (here patients received somatic acupuncture SA and auricular acupuncture AA). Anxiety reduction was measured by intraoperative consumption of Propofol and Fentanyl and preoperatively by the Italian Version of the State-Trait Anxiety Inventory questionnaire (STAI).
Propofol consumption in the somatic (SA) and auricular (AA) acupuncture groups was found to be lower compared to patients that did not receive any treatment. SA and AA patients required less Propofol than the PT group (p=0.0019 and p=0.0016 respectively) and patients that underwent SA treatment used less Fentanyl than the PT group (p=0.002). No difference was measured when comparing SA to AA (p=0.15) and AA to PT (p=0.16).
Acupuncture is a safe and well-tolerated procedure that reduces preoperative anxiety. Both somatic and auricular acupuncture are more effective than pharmacological treatment in the intraoperative period. AA is easier to implement than SA.
Abstract
The aim is to make available in Italian a tool for measuring the system thinking skills of students aged between 10 and 14 years. The System Thinking Assessment (STA), developed and ...validated in Greek for students in Cyprus, has been translated, adapted and digitized so that it can be used as a small- and large-scale survey method in Italy. Two fifth-grade elementary school classes, a total of 43 students, were chosen as pilot classes for the administration of the test. This allowed us to determine the timeline for administering it in an average time of 30 minutes. To assess the difficulty of the test connected with the age group, an analysis of the item difficulty and discrimination index was made. This, together with the comments asked to the participants, led to the conclusion that the STA is suitable and usable for Italian 10-year-old students and can be used for the construction of a pathway connected with system thinking.
Objective and Background
To evaluate the association between periodontal disease, tooth loss and coronary heart disease (CHD). There is still controversy about the relationship between periodontal ...disease and tooth loss with vessel obstruction assessed using coronary angiography.
Material and Methods
This cross‐sectional study included 195 patients that underwent coronary angiography and presented with at least six teeth. Patients were classified into three categories of coronary obstruction severity: absence; one or more vessels with ≤ 50% obstruction; and one or more vessels with ≥ 50% obstruction. The extent of coronary obstruction was dichotomized into 0 and ≥ 1 affected vessels. A periodontist blinded to patient CHD status conducted a full mouth examination to determine mean clinical attachment loss, mean periodontal probing depth and tooth loss. Multiple logistic regression models were applied adjusting for age, gender, hypertension, smoking, body mass index, low‐density lipoprotein cholesterol and C‐reactive protein.
Results
Most patients were males (62.1%) older than 60 years (50.8%), and 61% of them had CHD. Mean periodontal probing depth, clinical attachment loss and tooth loss were 2.64 ± 0.72 mm, 4.40 ± 1.31 mm and 12.50 ± 6.98 teeth respectively. In the multivariable models, tooth loss was significantly associated with a higher chance of having at least one obstructed vessel (odds ratio = 1.04; 95% confidence interval 1.01–1.09) and with vessel obstruction ≥ 50% (odds ratio = 1.06; 95% confidence interval 1.01–1.11). No significant associations were found between periodontal variables and vessel obstruction.
Conclusion
Tooth loss was found to be a risk indicator for CHD.
The reliability and the accompanying fatigue law for solder joints are a challenge for the aerospace and defense industries. Due to the service loadings and the lifetime requirements, fatigue laws ...must take into account plastic and viscous damages for solder joint materials. This paper presents an innovative test bench developed for the fatigue analysis of assembled packages. Two failure criteria are discussed: the electrical criterion, based on the monitoring of electrical resistance, and the mechanical criteria, based on force magnitude. The monitoring of the electrical resistance is able to detect the failure of a single solder ball, which represents a failure for a functional component. The electrical failure is reached without significant change in the mechanical parameters and the electrical criterion is always reached before the mechanical failure. The electrical criterion can be used to define the limit for the calculation of stabilized values of the mechanical parameters. This work opens up a fatigue Design of Experiment in order to define, based on experimental results, a fatigue law for solder joint which takes into account creep-fatigue interaction.
•An innovative test bench has been developed for the fatigue analysis of assembled packages.•Fatigue shear tests at various force levels, temperatures and dwell times can be performed.•The monitoring of the electrical resistance is able to detect the failure of a single solder ball.•Cyclic mechanical parameters as plastic and creep displacements are computed in order to define a fatigue law.
The formation constants (log K 1) of lanthanide(III) (Ln) ions except for Pm(III) and the Y(III) cation have been measured with the ligand TPEN (N,N,N′,N′-tetra-2-picolylethylenediamine). These ...log K 1 values show a typical variation with ionic radius, with a local maximum at Sm(III) and a local minimum at Gd(III), with an overall increase in log K 1 from La(III) to Lu(III) as the ionic radius decreases. The log K 1 for the Y(III)/TPEN complex is much lower than expected from its ionic radius, while the literature log K 1 for Am(III) is much higher. The latter effect is thought to be due to greater covalence in the M–L (metal–ligand) bond than for Ln(III) ions: the low log K 1 for Y(III) is interpreted as being due to lower covalence. The f → f transitions in the Nd(III) and Pr(III) complexes were examined for effects that might indicate the participation of f orbitals in M–L bonding. The intensity of the f → f transitions in the Nd(III)/TPEN complex was greatly increased compared to that of the Nd3+ aqua ion, which appeared to be due to additional sharp peaks, possibly parity forbidden transitions where parity rules were broken by covalence in the M–L bond. The Pr(III)/TPEN complex showed that all of the f → f transitions shifted to longer wavelengths by some 5 nm, with modest increases in intensity. The effects seen in the f → f transitions of Nd(III) and Pr(III) with TPEN with its six nitrogen donors were present to a much smaller extent in the EDTA and other complexes with fewer nitrogen donors. The changes in the f → f transitions of the TPEN complexes of Er(III) and Ho(III) were small, suggesting a smaller contribution of f orbitals to M–L bonding in these heavier Ln(III) ions. The intense Laporte allowed f → d transitions in Ce(III) complexes show large shifts to longer wavelengths as complexes of, for example, EDTA with increasing numbers of nitrogen donors, suggesting the participation of both f and d orbitals, or either, in M–L bonding. The nature of M–L bonding in M(III)/TPEN complexes was further investigated via density functional theory calculations.
Abstract Rett syndrome is a neurodevelopmental disease accompanied by complex, disabling symptoms, including breathing symptoms. Because Rett syndrome is caused by mutations in the transcriptional ...repressor methyl-CpG-binding protein 2 (MeCP2), Mecp2 -deficient mice have been generated as experimental model. Males of Mecp2 -deficient mice ( Mecp2 −/ y ) breathe normally at birth but show abnormal respiratory responses to hypoxia and hypercapnia from postnatal day 25 (P25). After P30, Mecp2 −/ y mice develop breathing symptoms reminiscent of Rett syndrome, aggravating until premature death at around P60. Using plethysmography, we analyzed the sighs and the post-sigh breathing pattern of unrestrained wild type male mice (WT) and Mecp2 −/ y mice from P15 to P60. Sighs are spontaneous large inspirations known to prevent lung atelectasis and to improve alveolar oxygenation. However, Mecp2 −/ y mice show early abnormalities of post-sigh breathing, with long-lasting post-sigh apnoeas, reduced tidal volume when eupnoea resumes and lack of post-sigh bradypnoea which develop from P15, aggravate with age and possibly contribute to breathing symptoms to come.
