Modification of chiral dimethyl tartrate through transesterification : immobilisation on POSS and enantioselectivity reversion in Sharpless asymmetric epoxidation

Modification of dimethyl tartrate has been investigated through transesterification with aminoalcohols to provide reactive functionalities for the covalent bonding of chiral tartrate to polyhedral oligomeric silsesquioxanes. The transesterification of dimethyl tartrate has been widely studied by means of using different catalytic systems and reaction conditions. Through the proper selection of both, the catalytic system and the reaction conditions, it is possible to achieve the mono- or the bis-substituted tartrate derivative as sole products. All the intermediate chiral tartrate-derived ligands were successfully used in the homogeneous enantioselective epoxidation of allylic alcohols providing moderate enantiomeric excess over the products. Attached amine groups have been used to support the modified tartrate ligands onto a haloaryl-functionalized silsesquioxane moiety. This final chiral tartrate ligand displays enantioselectivity reversion in the asymmetric epoxidation of allylic alcohols with regards to the starting dimethyl tartrate ligand, having both molecules them the same chiral sign. However, the POSS-containing ligand can be easily recovered in almost quantitative yield and reused in asymmetric epoxidation reactions. In addition, recovered silsesquioxane-pendant ligand, though displaying decreasing catalytic activity in recycling epoxidation tests, showed very stable enantioselective behavior

Randomised, controlled trial of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers : PRESSURE (pressure relieving support surfaces) trial

Objective To compare whether differences exist between alternating pressure overlays and alternating pressure mattresses in the development of new pressure ulcers, healing of existing pressure ulcers, and patient acceptability. Design Pragmatic, open, multicentre, randomised controlled trial. Setting 11 hospitals in six NHS trusts. Participants 1972 people admitted to hospital as acute or elective patients. Interventions Participants were randomised to an alternating pressure mattress (n = 982) of- an alternating pressure overlay (n = 990). Main outcome measures The proportion of participants developing a new pressure ulcer of grade 2 or worse; time to development of new pressure ulcers; proportions of participants developing a new ulcer within 30 days; healing of existing pressure ulcers; and patient acceptability Results Intention to treat analysis found no difference in the proportions of participants developing a new pressure ulcer of grade 2 or worse (10.7% overlay patients, 10.3% mattress patients; difference 0.4%, 95% confidence interval - 23% to 3.1%, P = 0.75). More overlay patients requested change owing to dissatisfaction (23.3%) than mattress patients (18.9%, P = 0.02). Conclusion No difference was found between alternating pressure mattresses and alternating pressure overlays in the proportion of people who develop a pressure ulcer

Exercise Interventions for Improving Flexibility in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis

[ES] Background and objectives: People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility levels in this population have been linked to postural problems and muscular pain. Therefore, the purpose of this study was to conduct a systematic review and a meta-analysis aimed at identifying the characteristics and methodological quality of investigations studying the effects of exercise interventions on the flexibility levels of people with MS. Materials and Methods: Three electronic databases (MEDLINE/PubMed, SPORTDiscus and Scopus) were systematically searched up to May 2019 for intervention studies focused on the effects of exercise on the flexibility levels of people with MS. A meta-analysis, including randomized controlled trials (RCT), which reported information regarding the effects of exercise on flexibility, was also conducted. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database, and the Quality Assessment Tool for Before–After Studies, with no control group. The quality of the information reported, regarding the programs conducted, was assessed by means of the Consensus on Exercise Reporting Template (CERT) scale. Results: Seven studies, four RCTs and three uncontrolled investigations were finally selected. The methodological quality of the RCTs was considered “poor” in one study, and “good” and “excellent” in two studies and one investigation, respectively. The three uncontrolled studies showed a methodological quality between “fair” and “poor”. Following the CERT scale, four studies were graded as “high” and three as “low”. Findings from the meta-analysis indicated no significant effects on hamstring flexibility, or the range of motion in the hips, knees or ankles. Conclusions: There is preliminary evidence from individual studies which indicates that people with MS can improve their lower limb flexibility following participation in physical exercise programs, but the meta-analysis did not confirm these findings

Integration of Dirac-Jacobi structures

We study precontact groupoids whose infinitesimal counterparts are Dirac-Jacobi structures. These geometric objects generalize contact groupoids. We also explain the relationship between precontact groupoids and homogeneous presymplectic groupoids. Finally, we present some examples of precontact groupoids.Comment: 10 pages. Brief changes in the introduction. References update

Ditopic receptors containing urea groups for solvent extraction of Cu(II) salts

[Abstract] The ditopic receptor L3 [1-(2-((7-(4-(tert-butyl)benzyl)-1,4,7,10-tetraazacyclododecan-1-yl)methyl)phenyl)-3-(3-nitrophenyl)urea] containing a macrocyclic cyclen unit for Cu(II)-coordination and a urea moiety for anion binding was designed for recognition of metal salts. The X-ray structure of [CuL3(SO4)] shows that the sulfate anion is involved in cooperative binding via coordination to the metal ion and hydrogen-bonding to the urea unit. This behaviour is similar to that observed for the related receptor L1 [1-(2-((bis(pyridin-2-ylmethyl)amino)methyl)phenyl)-3-(3-nitrophenyl)urea], which forms a dimeric [CuL1(μ-SO4)]2 structure in the solid state. In contrast, the single crystal X-ray structure of [ZnL3(NO3)2] contains a 1 : 2 complex (metal : anion) where one anion coordinates to the metal and the other is hydrogen-bonded to the urea group. Spectrophotometric titrations performed for the [CuL3(OSMe2)]2+ complex indicate that this system is able to bind a wide range of anions with an affinity sequence: MeCO2− > Cl− > H2PO4− > Br− > NO2− > HSO4− > NO3−. Lipophilic analogues of L1 and L3 extract CuSO4 and CuCl2 from water into chloroform with high selectivity over the corresponding Co(II), Ni(II) and Zn(II) salts.Xunta de Galicia; EM 2012/088Xunta de Galicia; CN-2012/01

Exercise Interventions for Improving Flexibility in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background and objectives: People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility levels in this population have been linked to postural problems and muscular pain. Therefore, the purpose of this study was to conduct a systematic review and a meta-analysis aimed at identifying the characteristics and methodological quality of investigations studying the effects of exercise interventions on the flexibility levels of people with MS. Materials and Methods: Three electronic databases (MEDLINE/PubMed, SPORTDiscus and Scopus) were systematically searched up to May 2019 for intervention studies focused on the effects of exercise on the flexibility levels of people with MS. A meta-analysis, including randomized controlled trials (RCT), which reported information regarding the effects of exercise on flexibility, was also conducted. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database, and the Quality Assessment Tool for Before–After Studies, with no control group. The quality of the information reported, regarding the programs conducted, was assessed by means of the Consensus on Exercise Reporting Template (CERT) scale. Results: Seven studies, four RCTs and three uncontrolled investigations were finally selected. The methodological quality of the RCTs was considered “poor” in one study, and “good” and “excellent” in two studies and one investigation, respectively. The three uncontrolled studies showed a methodological quality between “fair” and “poor”. Following the CERT scale, four studies were graded as “high” and three as “low”. Findings from the meta-analysis indicated no significant effects on hamstring flexibility, or the range of motion in the hips, knees or ankles. Conclusions: There is preliminary evidence from individual studies which indicates that people with MS can improve their lower limb flexibility following participation in physical exercise programs, but the meta-analysis did not confirm these findings.post-print1388 K

DIRECT EFFECTS OF METFORMIN ON PI3K AND RAS SIGNALING IN ENDOMETRIAL CANCER

Metformin has antiproliferative effects through the activation of AMPK and has gained interest as an antineoplastic agent in several cancer types, although studies in endometrial cancer (EC) are limited. The aims of this project were to evaluate pathways targeted by metformin in EC, investigate mechanisms by which metformin exerts its antiproliferative effects, and explore rational combination therapies with other targeted agents. Three EC cell lines were used to evaluate metformin’s effect on cell proliferation, PI3K and Ras-MAPK signaling, and apoptosis. A xenograft mouse model was also used to evaluate the effects of metformin treatment on in vivo tumor growth. These preliminary studies demonstrated that K-Ras mutant cell lines exhibited a decreased proliferative rate, reduced tumor growth, and increased apoptosis in response to metformin compared to K-Ras wild-type cells. To test the hypothesis that mutant K-Ras may predict response to metformin, murine EC cells with loss of PTEN and expressing mutant K-RasG12D were transfected to re-express PTEN or have K-Ras silenced using siRNA. While PTEN expression did not alter response to metformin, cells in which K-Ras was silenced displayed reduced sensitivity to metformin. Mislocalization of K-Ras to the cytoplasm is associated with decreased signaling and induction of apoptosis. Metformin’s effect on K-Ras localization was analyzed by confocal microscopy in cells expressing oncogenic GFP-K-RasG12V. Metformin demonstrated concentration-dependent mislocalization of K-Ras to the cytoplasm. Mislocalization of K-Ras to the cytoplasm was confirmed in K-Ras mutant EC cells (Hec1A) by cell fractionation in response to metformin 1 and 5 mM (p=0.008 and p=0.004). This effect appears to be AMPK-independent as combined treatment with Compound C, an AMPK inhibitor, did not alter K-Ras localization. Furthermore, treatment of EC cells with metformin in combination with PI3K inhibitors resulted in a significant decrease in proliferation than either agent or metformin alone. While metformin exerts antineoplastic effects by activation of AMPK and decreased PI3K signaling, our data suggest that metformin may also disrupt localization of K-Ras and hence its signaling in an AMPK-independent manner. This has important implications in defining patients who may benefit from metformin in combination with other targeted agents, such as mTOR inhibitors

Impact of COVID-19 Pandemic on University Students' Physical Activity Levels: An Early Systematic Review

[EN] Purpose: This systematic review aimed to analyze the impact that the COVID-19 lockdown had on the amount of physical activity performed by university students. Materials and Methods: A systematic electronic search for studies providing information regarding physical activity levels pre and during COVID-19 pandemic in university students was performed up to 20th October 2020 in the databases Cochrane Library, PubMed, SPORTDiscus, and Web of Science. The risk of bias of external validity quality of included studies was assessed by means of those the Newcastle-Ottawa Scale (NOS). The quality of the evidence for main outcomes was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results and Conclusions: A total of 10 studies were selected. Physical activity levels were assessed by means of questionnaires (10 studies) and accelerometer (1 study). Risk of bias was regarded as low and high in six and four investigations, respectively. The quality of evidence was downgraded to low. A significant reduction of physical activity levels were observed in 9 studies. Compared to pre-lockdown values, five studies showed a reduction of light/mild physical activity (walking) between 32.5 and 365.5%, while seven studies revealed a reduction of high/vigorous physical activity between 2.9 and 52.8%. Walking, moderate, vigorous, and total physical activity levels have been reduced during the COVID-19 pandemic confinements in university students of different countries. Despite of the reductions, those who met the current minimum PA recommendations before the lockdown generally met the recommendations also during the confinements

Theoretical Analysis of SPH in Simulating Free-surface Viscous flows

A theoretical analysis on the performance, close to a free surface, of the most used SPH formulations for Newtonian viscous terms is carried out in this paper. After an introduction of the SPH formalism, the SPH expressions for the viscous term in the momentum equation are analyzed in their continuous form. Using a Taylor expansion, a reformulation of those expressions is undertaken which allows to characterize the behavior of the viscous term close to the free surface. Under specific flow conditions, we show that the viscous term close to the free surface is singular when the spatial resolution is increased. This problem is in essence related to the incompleteness of the kernel function close to the free surface and appears for all the formulations considered. In order to assess the impact of such singular behavior, an analysis of the global energy dissipation is carried out, which shows that such a free-surface singularity vanishes when the integral quantities are considered. Not with standing that, not all the SPH viscous formulas allow the correct evaluation of the energy dissipation rate and, consequently, they may lead to an inaccurate modelling of viscous free-surface flows

Effects of exercise training on obesity‐related parameters in people with intellectual disabilities: systematic review and meta‐analysis

.Background: Efforts to synthesise existing knowledge concerning the effects of exercise interventions on obesity (i.e. changes in body weight and composition) have been made, but scientific evidence in this matter is still limited. This systematic review and meta-analysis aims to identify and critically analyse the best available evidence regarding the use of physical exercise as a strategy to attenuate obesity through its effects on adiposity-related anthropometric parameters in people with intellectual disability (ID). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a literature search was performed using PubMed, Scopus, SPORTDiscus, CINAHL and the Cochrane Library through specific keywords up to July 2020. The search adhered to the population, intervention, comparison and outcome strategy. Randomised controlled trials addressing the effects of the exercise intervention on adiposity-related anthropometric parameters (body mass index, waist circumference, waist–hip ratio, fat percentage or body weight) in children, adolescents and adults with ID were included. The methodological quality of the studies found was evaluated through the PEDro scale. Results: A total of nine investigations with children and/or adolescents (10–19 years) and 10 investigations with adults (18–70 years) were selected, mostly experiencing mild and moderate ID. Methodological quality was fair in 13 of these publications, good in five and excellent in one. Seventeen trials reported comparable baseline and post-intervention data for the intervention and control groups and were included in the meta-analysis. In nine studies, the intervention group performed a cardiovascular training programme. Five papers described a combined training programme. Two trials executed whole-body vibration training programmes, and one publication proposed balance training as the primary intervention. According to the meta-analysis results, the reviewed studies proposed exercise modalities that, in comparison with the activities performed by the participants' in the respective control groups, did not have a greater impact on the variables assessed. Conclusions: While physical exercise can contribute to adiposity-related anthropometric parameters in people with mild and moderate ID, these findings show that exercise alone is not sufficient to manage obesity in this population. Multicomponent interventions appear to be the best choice when they incorporate dietary deficit, physical activity increase and behaviour change strategies. Finding the most effective modality of physical exercise can only aid weight loss interventions. Future research would benefit from comparing the effects of different exercise modalities within the framework of a multicomponent weight management intervention.S