Molecular Diversity from Longipinenes of Santolina viscosa Lag. through Acid Catalysis: Biocidal Activity.

The search for new compounds with biocidal potential was carried out, focusing on the longipinenes 1-7 from the plant species Santolina viscosa Lag. Compounds 1, 2, and 5 showed remarkable molecular diversity when treated in acidic reaction conditions. Protonic, Lewis, and heterogeneous compounds were used in the treatment. Three main models of reaction have been observed: isomerization of the double bond (8-10); rearrangements to longibornane-based skeleton (11-15) and ring-opening to himachalane-based skeleton (16-18). Secolongibornane aldehydes 23 and 24 were obtained after epoxide opening under the same reaction conditions. The elucidation of the structures of the new compounds was carried out using spectroscopic data and was supported by computational theoretical calculations of 13C NMR spectra. Additionally, high-resolution mass spectrometry and single-crystal X-ray diffraction analysis were employed for certain compounds. Natural longipinenes 4-7, methyl esters 1-3 of corresponding natural carboxylic acids and the isomerized and derivatives compounds 8-19 exhibit moderate to high insecticidal activity against R. padi and M. persicae insects. Longipinene 5 shows potent inhibition against the root growth of the plants L. perenne and L. sativa, as well as compound 2 on the leaves of L. perenne. Furthermore, significant ixocidal and nematicidal activity was found for this latter compound.

A randomized controlled mHealth trial that evaluates social comparison-oriented gamification to improve physical activity, sleep quantity, and quality of life in young adults.

INTRODUCTION: The integration of gamification in mHealth interventions presents a novel approach to enhance user engagement and health outcomes. This study aims to evaluate whether comparison-oriented gamification can effectively improve various aspects of health and well-being, including physical activity, sedentary behavior, sleep, and overall quality of life among young adults. METHODS: Potential 107 young adults (from 19 to 28 years old) participated in an 8-week trial. Participants were assigned to either a gamified mHealth intervention (LevantApp) with daily leaderboards and progress bars (n = 53, 26 % dropped-out), or a control condition without gamification (n = 52, 29 % dropped-out). Physical activity (number of steps, moderate and moderate-to-vigorous physical activity -MVPA-) and sleep quantity were measured objectively via accelerometry and subjectively using the International Physical Activity Questionnaire(IPAQ), Pittsburgh Sleep Quality Index(PSQI), Sedentary Behavior Questionnaire(SBQ), and Short Form Health Survey(SF-36). RESULTS: This mHealth intervention with social comparison-oriented gamification significantly improved moderate physical activity to a greater extent than the control group. Additionally, the intervention group showed improvements in the number of steps, moderate physical activity, sedentary time, emotional wellbeing, and social functioning. However, no significant group by time interaction was observed. No significant differences were observed in sleep quality or quantity. CONCLUSION: s: The LevantApp gamified mHealth intervention was effective in improving moderate physical activity, physical functioning, and role-emotional in young adults. No significant effects were found on step counts, MVPA or sleep, suggesting that while gamification can enhance specific aspects of physical activity and quality of life, its impact may vary across different outcomes.

Beta-blockers and renin-angiotensin system inhibitors for Takotsubo syndrome recurrence: a network meta-analysis.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute heart failure syndrome, featured by transient left ventricular systolic dysfunction. Recurrences of TTS are not infrequent and there is no standard preventive therapy. The aim of this study was to evaluate in a network meta-analysis if beta-blockers (BB) and ACE inhibitors/angiotensin receptor blockers (ACEi/ARBs), in combination or not, can effectively prevent TTS recurrences. METHODS: We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for clinical studies published between January 2010 and September 2022. We considered all those studies including patients receiving medical therapy with BB, ACEi/ARBs. The primary outcome was TTS recurrence. RESULTS: We identified 6 clinical studies encompassing a total of 3407 patients with TTS. At 40±10 months follow-up, TTS recurrence was reported in 160 (4.7%) out of 3407 patients. Mean age was 69.8±2 years and 394 patients (11.5%) out of 3407 were male. There were no differences in terms of TTS recurrence when comparing ACEi/ARBs versus control (OR 0.83; 95% CI 0.47 to 1.47, p=0.52); BB versus control (OR 1.01; 95% CI 0.63 to 1.61, p=0.96) and ACEi/ARBs versus BB (OR 0.88; 95% CI 0.51 to 1.53, p=0.65).Combination of BB and ACEi/ARBs was also not effective in reducing the risk of recurrence versus control (OR 0.91; 95% CI 0.58 to 1.43, p=0.68) vs ACEi/ARBs (OR 0.79; 95% CI 0.46 to 1.34, p=0.38)) and vs BB (OR 0.77; 95% CI 0.49 to 1.21, p=0.26). CONCLUSIONS: Our study did not find sufficient statistical evidence regarding combination therapy with BB and ACEi/ARBs in reduction of TTS recurrence.

Bioinspired Synthesis of Platensimycin from Natural ent-Kaurenoic Acids.

The biomimetic formal synthesis of the antibiotic platensimycin for the treatment of infection by multidrug-resistant bacteria was accomplished starting from either ent-kaurenoic acid or grandiflorenic acid, each of which is a natural compound available in multigram scale from its natural source. Apart from the natural origin of the selected precursors, the keys of the described approach are the long-distance functionalization of ent-kaurenoic acid at C11 and the efficient protocol for the A-ring degradation of the diterpene framework.

Polygenic risk of bone fractures in Spanish women with osteoporosis / Riesgo poligénico de fracturas óseas en mujeres españolas con osteoporosis

Background: osteoporosis is a highly polygenic trait characterized by low bone mineral density (BMD) and/or fragility frac-tures. Over the past decade, polygenic risk scores (PRS) are an emerging tool to try to predict the risk of complex disorderswith a genetic component.Objective: to analyze the capacity of different PRSs to predict osteoporosis in the Spanish population.Material and methods: our dataset consisted of two differentiated groups. The first group included osteoporosis casesdiagnosed and treated at the Marques de Valdecilla University Hospital (n = 304; 293 women) while the second groupconsisted of people from the overall Spanish population (n = 3199; 1458 women). Four previously generated PRSs werecompared with generalized linear models.Results: the osteoporosis group showed a significantly higher genetic risk compared to the control group in 3 PRSs (PRS-1p = 1e-7; PRS-2 p = 1.87e-15; PRS-3 p = 0.1477; PRS-4 p = 8.98e-9). In addition, in these PRSs, the individuals in the upperquartile of risk had a significantly higher risk of osteoporosis, compared to those individuals in the other quartiles (PRS-1OR, 1.83; PRS-2 OR, 2.11; PRS-3 OR, 0.96; PRS-4 OR, 1.72).Conclusions: in summary, the application of PRSs shows significant differences between the overall Spanish populationand patients with osteoporosis, which is suggestive of its utility within strategies for the identification of subjects at riskbased on clinical-genetic criteria.(AU)

Recommendations for living donor kidney transplantation.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Selectivity of Relative Humidity Using a CP Based on S-Block Metal Ions.

Herein, we present the syntheses of a novel coordination polymer (CP) based on the perylene-3,4,9,10-tetracarboxylate (pery) linkers and sodium metal ions. We have chosen sodium metal center with the aim of surmising the effect that the modification of the metal ion may have on the relative humidity (RH) experimental measurements of the material. We confirm the role of the ions in the functionalization of the deposited layer by modifying their selectivity towards moisture content, paving the way to the generation of sensitive and selective chemical sensors.

Diclofenac N-Derivatives as Therapeutic Agents with Anti-Inflammatory and Anti-Cancer Effect.

A series of diclofenac N-derivatives (2, 4, 6, 8c, 9c, 10a-c) were synthesized in order to test their anti-cancer and anti-inflammatory effects. The anticarcinogen activity has been assayed against three cancer cell lines: HT29, human colon cancer cells; Hep-G2, human hepatic cells; and B16-F10, murine melanoma cells. First, we determined the cytotoxicity of the different compounds, finding that the most effective compound was compound 8c against all cell lines and both compounds 4 and 6 in human Hep-G2 and HT29 cell lines. Compounds 4 and 8c were selected for the percentage of apoptosis determination, cell cycle distribution, and mitochondrial membrane potential measure because these products presented the lowest IC50 values in two of the three cancer cell lines assayed (B16-F10 and HepG2), and were two of the three products with lowest IC50 in HT29 cell line. Moreover, the percentages of apoptosis induction were determined for compounds 4 and 8c, showing that the highest values were between 30 to 60%. Next, the effects of these two compounds were observed on the cellular cycle, resulting in an increase in the cell population in G2/M cell cycle phase after treatment with product 8c, whereas compound 4 increased the cells in phase G0/G1, by possible differentiation process induction. Finally, to determine the possible apoptosis mechanism triggered by these compounds, mitochondrial potential was evaluated, indicating the possible activation of extrinsic apoptotic mechanism. On the other hand, we studied the anti-inflammatory effects of these diclofenac (DCF) derivatives on lipopolysaccharide (LPS) activated RAW 264.7 macrophages-monocytes murine cells by inhibition of nitric oxide (NO) production. As a first step, we determined the cytotoxicity of the synthesized compounds, as well as DCF, against these cells. Then, sub-cytotoxic concentrations were used to determine NO release at different incubation times. The greatest anti-inflammatory effect was observed for products 2, 4, 8c, 10a, 10b, and 9c at 20 µg·mL-1 concentration after 48 h of treatment, with inhibition of produced NO between 60 to 75%, and a concentration that reduces to the 50% the production of NO (IC50 NO) between 2.5 to 25 times lower than that of DCF. In this work, we synthesized and determined for the first time the anti-cancer and anti-inflammatory potential of eight diclofenac N-derivatives. In agreement with the recent evidences suggesting that inflammation may contribute to all states of tumorigenesis, the development of these new derivatives capable of inducing apoptosis and anti-inflammatory effects at very low concentrations represent new effective therapeutic strategies against these diseases.

Selective Extraction of Bioactive Phenylethanoids from Digitalis obscura.

Cardenolide-free extracts from Digitalis obscura showed significant antifeedant effects against the aphid Myzus persicae and this activity correlated with their phenylethanoid content. The content in phenylethanoids of Digitalis obscura has been studied. Maceration of the aerial parts of D. obscura was used for the selective extraction of the natural compound rengyolone (1) and the aglycone of cornoside (compound 3). Pure rengyolone (1) can be obtained from D. obscura in approximately 90% purity from fresh plant from the CHCl3 soluble fraction of the ethanolic extract (0.8% yield). The ethanol extraction of freshly collected D. obscura showed the presence of compound 3 as the only phenylethanoid. Compound 3 was proven to easily evolve to rengyolone. Due to this instability, and although its presence in plants has been previously reported, the spectroscopical data of 3 are reported herein for the first time. Selective mono-acetylation of compound of 3 led to the active natural compound hallerone (5). The aphid antifeedant (against Myzus persicae) and nematicidal (against root-knot nematode Meloidogyne javanica) activities of these compounds have been evaluated. Here we report for the first time on the aphid antifeedant effects of 1, 3, and 5. Additionally, the nematicidal activity of hallerone (5) is described here for the first time.

Synthesis of Cannabinoids: "In Water" and "On Water" Approaches: Influence of SDS Micelles.

We have proven that the biomimetic-like synthesis of cannabinoids from citral and the corresponding phenolic counterpart may well be carried out using water as a solvent. The influence of different additives such as surfactants was also analyzed. Rationalization of the reaction mode and regiochemistry of the processes were provided in terms of "on water" and "in water" reactions. The same reactions were conducted in organic media using Ga(III) salts as catalysts. Worthy of being underlined, an unprecedented formal [2+2+2] process was found to occur between two citral molecules and the corresponding phenolic species in both aqueous and organic environments. Computational studies were performed in order to gain a comprehensive mechanistic and energetic understanding of the different steps of this singular process. Finally, the influence of SDS micelles in the chemical behavior of olivetol and citral was also pursued using PGSE diffusion and NOESY NMR studies. These data permitted to tentatively propose the existence of a mixed micelle between olivetol and SDS assemblies.

Contrast-Enhanced Echocardiographic Measurement of Left Ventricular Wall Thickness in Hypertrophic Cardiomyopathy: Comparison with Standard Echocardiography and Cardiac Magnetic Resonance.

BACKGROUND: Left ventricular wall thickness (LVWT) measurement is key in the diagnostic and prognostic assessment of hypertrophic cardiomyopathy (HCM). Recent investigations have highlighted discrepancies in LVWT by cardiac magnetic resonance (CMR) and standard echocardiography (S-Echo) in this condition. The aim of this study was to elucidate the role of contrast-enhanced echocardiography (C-Echo) to optimize LVWT measurement in patients with HCM. METHODS: Fifty patients with HCM were prospectively enrolled, undergoing S-Echo, C-Echo, and CMR. Blinded LVWT measurements were performed according to a 16-segment left ventricular model using all three imaging techniques. Agreement between both echocardiographic modalities and CMR (as the reference technique) at the segmental level was tested using Bland-Altman analyses. Reproducibility on segmental measurements by S-Echo and C-Echo was also investigated. RESULTS: Patients' mean age was 47 ± 21 years, and 35 (70%) were men. Maximal mean LVWT by S-Echo (20.1 ± 3.8 mm) was greater than the values derived using C-Echo (17.6 ± 4.0 mm, P < .01) and CMR (17.7 ± 4.5 mm, P < .01), with no statistically significant difference between the latter two. Segmental Bland-Altman models demonstrated globally smaller bias and narrower 95% limits of agreement for C-Echo compared with S-Echo. Across all left ventricular segments, LVWT by C-Echo was 2.4 mm lower (range, 1.0-2.5 mm) than that derived by S-Echo, which accounted for a 25% intertechnique difference. Regarding maximal LVWT, the mean absolute difference between C-Echo and S-Echo was 3.0 ± 1.9 mm (range, 0.0-7.9 mm), which represented a 15% intertechnique change. Data analyses demonstrated globally less intra- and interobserver variability in segmental LVWT derived from C-Echo compared with S-Echo. CONCLUSIONS: C-Echo rendered LVWT measurements closer to those derived by the reference technique (CMR) and improved reproducibility compared with S-Echo. C-Echo represents a suitable tool for LVWT measurement in patients with HCM as an alternative to CMR whenever this is not available or possible.

Novel Insect Antifeedant and Ixodicidal Nootkatone Derivatives.

Naturally occurring nootkatone, with reported insecticidal and acaricidal properties, has been used as a lead to generate molecular diversity and, consequently, new insect antifeedant and ixodicidal compounds. A total of 22 derivatives were generated by subjecting this molecule to several reactions including dehydrogenation with the iodine/DMSO system, oxidation with SeO2, epoxidation with mCPBA, oxidation or carbon homologations of the α-carbonyl position with TMSOTf (trimethylsilyl trifluoromethanesulfonate) followed by Rubottom and Dess Martin periodane oxidations, condensation with formaldehyde using Yb(OTf)3 as catalyst and dehydroxilation using the Grieco protocol. The insect antifeedant (against Myzus persicae and Ropaloshysum padi) and ixodicidal (against the tick Hyalomma lusitanicum) activities of these compounds were tested. Compound 20 was the most active substance against M. persicae and R. padi, and twice more efficient than nootkatone in the antitick test.

Mimicking Halimane Synthases: Monitoring a Cascade of Cyclizations and Rearrangements from Epoxypolyprenes.

We have developed and rationalized a biomimetic transformation mimicking halimane synthases based on a Lewis acid-catalyzed cascade of cyclizations and rearrangements of epoxypolyprenes. Two rings, three stereogenic centers, and a new double bond were generated in a single chemical operation. Based on this cascade transformation, we achieved a unified strategy toward the stereoselective total syntheses of halimene-type terpenoids and analogues as a proof-of-concept study. This method has been applied to the rapid synthesis of diterpene isotuberculosinol, a virulence factor of Mycobacterium tuberculosis as a representative example.

Germacrone Derivatives as new Insecticidal and Acaricidal Compounds: A Structure-Activity Relationship.

Currently, the use of synthetic pesticides is the main method of plant protection applied in agri- and horticulture. However, its excessive use leads to the development of pesticide resistance, a contamination of the environment, toxicity to non-target organisms, and risks for human health. With the ultimate aim of contributing to the develop of a more sustainable pest management, we used the natural product germacrone (compound 1), reported to possess significant insecticidal activity, as starting material for the generation of molecular diversity (2-24). Some of the generated derivatives are natural compounds, such as 1,10-epoxygermacrone (2), 4,5-epoxygermacrone (3), gajutsulactone A (7), germacrol (11), isogermacrone (14), 9-hydroxyeudesma-3,7(11)dien-6-one (19), eudesma-4,7(11),dien-8-one (20), eudesma-3,7(11)-dien-8-one (21) and eudesma-4(15),7(11)-dien-8-one (22). Compounds, 7,11-9,10-diepoxigermacr-4,5-en-8-ol (17), 7,11-epoxieudesma-4,7(11)-dien-8-one (23) and 7,11-epoxieudesma-3,7(11)-dien-8-one (24) are described for the first time. The biocidal activity of most of these compounds was assayed against the tick Hyalomma lusitanicum. The acaricidal effects of compound 24 were four times higher than that of germacrone (1). Compound 2 is an insect antifeedant a thousand times more potent than germacrone against Rhopalosiphum padi, which makes this substance a promising selective antifeedant against this cereal pest.

Offensive Transitions in High-Performance Football: Differences Between UEFA Euro 2008 and UEFA Euro 2016.

Coaches, footballers and researchers agree that offensive transitions are one of the most important moments in football today. In a sport where defense over attack dominates, with low scores on the scoreboard, the importance of these actions from the offensive point of view becomes very important. Despite this, scientific literature is still very limited on this topic. Therefore, the objectives set out in the present investigation have been two: first, by means of a proportion analysis and the application of a chi-square test, it was intended to describe the possible differences between the offensive transitions made in the UEFA Euro 2008 and UEFA Euro 2016; then, through different multivariate analyzes based on logistic regression models, it was intended to know the possible differences among the proposed models. Using observational methodology as a methodological filter, 1,533 offensive transitions corresponding to the observation of the quarter final, semifinal, and final quarter of UEFA Euro 2008 and UEFA Euro 2016 have been analyzed. The results obtained have shown that offensive transitions between both championships have changed throughout both UEFA Euro, as well as some of the variables or behaviors associated with them (p < 0.05). The predictive models considered, although they have been developed from the same predictor variables, have also yielded different results for both championships, evidencing predictive differences among themselves. These results allow to corroborate that the offensive phase in high level football, specifically in what refers to moments of transition defense-attack, have evolved over these 8 years. At the applied level, the results of this research allow coaches to have current and contemporary information on these actions, potentially allowing them to improve their offensive performance during competition.

Structural abnormalities in hypertrophic cardiomyopathy beyond left ventricular hypertrophy by multimodality imaging evaluation.

BACKGROUND: Echocardiography- and cardiovascular magnetic resonance (CMR)-based studies have revealed a wide range of phenotypic manifestations in hypertrophic cardiomyopathy (HCM) apart from hypertrophy. This study sought to comprehensively describe a number of structural abnormalities in HCM beyond hypertrophy, by multimodality imaging. METHODS: A total of 100 HCM patients were prospectively enrolled, undergoing standard and contrast echocardiography, and CMR. Morphological characteristics involving mitral valve leaflets (MVL), subvalvular apparatus, and left ventricular cavity and wall were investigated. Seventy healthy volunteers served as control population. RESULTS: As assessed by echo, MVLs were longer in HCM patients than in controls (anterior method 1: 24[22,28] vs 19[18,20] mm, P < 0.01; anterior method 2: 27[24, 29] vs 21[19, 23] mm, P < 0.01; posterior: 15[12,19] vs 14[13,15] mm, P < 0.01). Abnormal chordal attachment to anterior MVL, anterior papillary muscle displacement, and accessory apical-basal muscle bundle were present in 42 (42%), 61 (61%), and 35 (35%) patients, respectively (P values vs controls <0.01); direct papillary muscle insertion into MVL and hypertrabeculation were found in two and five patients, respectively. Contrast echocardiography (n = 94) detected myocardial crypts in 15 patients (16%). Overall, 83% of HCM subjects had at least one of these phenotypic manifestations. Echocardiography and CMR agreement for MVL length was poor, while for structural characteristics was moderate to substantial (Cohen's Kappa: 0.53-1.00). Except for posterior MVL length and hypertrabeculation, the phenotypic characteristics studied had acceptable reproducibility by echocardiography and CMR. CONCLUSIONS: Structural abnormalities in HCM beyond hypertrophy are significantly common. Multimodality imaging approach to these HCM facets by echocardiography and CMR is feasible and desirable.