Benzazepinas azólicas mediante activaciones C-H catalizadas por metales de transición

En los últimos años, la activación de enlaces C-H se ha convertido en una poderosa herramienta sintética para acceder a heterociclos nitrogenados benzofusionados de tamaño medio. Uno de los esqueletos nitrogenados más relevante es el de siete eslabones, como son las benzazepinas y las benzodiazepinas, ya que están presentes en una gran variedad de compuestos biológicamente activos y en agentes terapeúticos. En esta tesis doctoral se abordan dos nuevas aproximaciones sintéticas a los núcleos de 1,3-benzodiazepinas y de 2-benzazepinas mediante procesos de activación C-H con grupos directores di- y trinitrogenados y alquinos catalizados por complejos organometálicos de Rh(III) y Pd(II), respectivamente

Rh(III)-Catalyzed [5+2] Oxidative Annulation of Cyclic Arylguanidines and Alkynes to 1,3-Benzodiazepines. A Striking Mechanistic Proposal from DFT

NOTICE: This is the peer reviewed version of the following article: Martínez-Yáñez, N., Suárez, J., Cajaraville, A., Varela, J. A., Saá, C. (2019). Rh(III)-Catalyzed [5+2] Oxidative Annulation of Cyclic Arylguanidines and Alkynes to 1,3-Benzodiazepines. A Striking Mechanistic Proposal from DFT. Org. Lett. 21, 6, 1779-1783. [doi: 10.1021/acs.orglett.9b00354]. This article may be used for non-commercial purposes in accordance with American Chemical Society Terms and Conditions for self-archivingA novel and mild Rh(III)-catalyzed [5+2] oxidative annulation between cyclic arylguanidines and alkynes efficiently affords 1,3-benzodiazepines (pentacyclic guanidines). The use of O2 as the sole oxidant in place commonly used metal oxidants such as AgOAc clearly improves the efficiency of the oxidative annulation process. The mechanism of the cycloaddition most likely involves the formation of an eight-membered rhodacycle. DFT calculations support a striking mechanistic proposal for the [5+2] oxidative annulation.This work has received financial support from MINECO (projects CTQ2014-59015R, CTQ2017-87939R and ORFEO-CINQA network CTQ2016-81797-REDC), the Xunta de Galicia (project GRC2014/032, ED431C 2018/04 and Centro singular de investigación de Galicia accreditation 2016–2019, ED431G/09) and the European Union (European Regional Development Fund - ERDF). N. M.-Y. thanks MINECO and Xunta de Galicia for a predoctoral contractS

Palladium-Catalyzed [5 + 2] Rollover Annulation of 1-Benzylpyrazoles with Alkynes: A Direct Entry to Tricyclic 2-Benzazepines

The first Pd-catalyzed [5 + 2] rollover annulation of 1-benzylpyrazoles with alkynes to assemble 10H-benzo[e]pyrazolo[1,5-a]azepines (tricyclic 2-benzazepines) has been developed. The rollover annulation implies a twofold C–H activation of aryl and heteroaryl Csp2–H bonds (C–H/C–H) of 1-benzylpyrazoles (five-atom partners) and alkynes to give the [5 + 2] annulated compounds.We acknowledge financial support from MICINN (Project PID2020-118048GB-I00 and ORFEO−CINQA Network RED2018-102387-T), the Xunta de Galicia (Project ED431C 2022/27 and Centro Singular de Investigación de Galicia Accreditation 2019−2022, ED431G 2019/03), and the European Union (European Regional Development Fund). A.S.-L. thanks MICINN for a predoctoral contract.S

Study of Different Personalised Dietary Plans on Eating Behaviour, Body Image and Mood in Young Female Professional Handball Players: A Randomised Controlled Trial

Low energy availability may precede or be caused by cognitive disturbances in professional athletes. Related psychological problems include disordered eating patterns, body shape preoccupation, depression or anxiety. The objective of this research was to evaluate the effects of different personalised dietary plans on psychological factors in young professional female handball players with low energy availability. This 12-week randomised clinical trial involved 21 female players aged 22 ± 4 years, 172.0 ± 5.4 cm and 68.4 ± 6.7 kg divided into three groups (FD: free diet; MD: Mediterranean diet; HAD: high antioxidant diet). Eating behaviour (Eating Attitude Test, EAT-26: diet, bulimia and oral control subscales), body image (Body Shape Questionnaire, BSQ) and mood state (Profile of Mode State, POMS: tension, vigour, anger, depression, fatigue) were assessed. All participants showed low energy availability (<30 kcal/lean mass per day). The different plans showed no significant differences between them but significant differences over time within groups for the variables: body image, Tension, Vigour and Depression (p < 0.05). Eating behaviour improved slightly but did not show statistically significant changes. Following an adequate nutritional planning for athletes seems to improve the mood and body perception of young female handball players. A longer intervention period is required to assess the differences between diets and improvement of other parameters.The author L.M-A. has received funding from the Ministry of Universities for University Teacher Training (FPU20/02136)

Study the Effect of Relative Energy Deficiency on Physiological and Physical Variables in Professional Women Athletes: A Randomized Controlled Trial

Energy deficits are often observed in athletes, especially in female athletes, due to the high expenditure of sport and strict diets. Low energy availability can cause serious health problems and affect sport performance. The aim of this study was to evaluate the effects of different personalized dietary plans on physiological and physical factors related to energy deficit syndrome in female professional handball players. Twenty-one professional female handball players, aged 22 ± 4 years, 172.0 ± 5.4 cm and 68.4 ± 6.7 kg, divided into three groups (FD: free diet; MD: Mediterranean diet; and AD: high antioxidant diet), participated in this 12-week randomized controlled trial. Energy expenditure through indirect calorimetry, energy availability, 7 day dietary intake analysis, blood pressure, cholesterol, menstrual function, body composition by both anthropometry and bioelectrical impedance, and strength performance were assessed. All participants showed low energy availability (< 30 kcal/lean mass per day); despite this, all had eumenorrhea. Significant improvements were found after the intervention in all components of body composition (p <0.05). In the remaining variables, despite slight improvements, none were significant neither over time nor between the different groups. Low energy availability has been observed in all professional female handball players, which may lead to serious consequences. A longer period of intervention is required to assess the differences between diets and improvements in other parameters.The author L.M-A. has received funding from the Ministry of Universities for University Teacher Training (FPU20/02136)

The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry

Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4(+) T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP(2)) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP(2) accumulation is increased in syntenin-1–depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP(2) production, and the dynamics of HIV-1 entry

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Ramadan Nutritional Strategy: Professional Soccer Player Case Study

The period of Ramadan induces changes in the usual eating patterns of individuals. During this period, Muslims must abstain from drinking and eating from dawn to dusk. Therefore, some research conducted on professional soccer players has observed that during and/or after Ramadan, performance, running speed, agility, dribbling speed, and endurance and/or skill performance in athletic events may be negatively affected by Ramadan intermittent fasting (RIF). The objective of this study was to analyze the influence of a dietary plan during RIF on performance and body composition in a professional soccer player. A 20-year-old elite player (86.0 kg, 188.5 cm) followed a dietary-nutritional plan with an isocaloric diet and was supplemented with glycerol. The athlete’s strength and power in the lower limbs was assessed by performing a countermovement jump (CMJ) and Abalakov vertical jump (ABK) before and after Ramadan. After nutritional planning, the patient’s body composition improved in terms of fat loss (6.61 to 5.70%) and muscle mass gain (50.26 to 51.50%). In addition, this translated into improvements in performance tests, both in the CMJ (36.72 to 40.00 cm) and ABK (39.16 to 49.34 cm). In conclusion, during a period of fasting, personalised nutritional planning and an appropriate supplementation and rest protocol can improve the body composition and performance of soccer players

Ingestion of Carbohydrate Solutions and Mouth Rinse on Mood and Perceptual Responses during Exercise in Triathletes

Triathlons are endurance events that include swimming, running, and cycling. Triathletes need to eat optimally during training and competitions to maximize their potential for success. The presence of carbohydrates in the mouth could activate regions in the brain to enhance athletic performance in exercise. Methods: This study examined the effects of glucose and mouthwash in ten male triathletes (age: 26.0 ± 8.7 years, height: 173.6 ± 10.4 cm, BMI 22.0 ± 1.7 kg/m2). The four oral test solutions included (A) Rinse with placebo, (B) Water + gel with placebo, (C) Rinse with 15% CH concentration, and (D) Water + gel with 15% CH concentration (25 g gel in 165 mL water). The Rate of Perceived Exertion (RPE), Sensation Scale (FS), Felt Arousal Scale (FAS), Profile of Mood States (POMS), blood glucose, sprints, and dietary habits were assessed in each subject. All preceded ingestion of the oral-based test solution during workouts. Results: RPE showed no significant differences for subjective perceptions. The same was observed for FS and sprints. FAS scores increased over time (p = 0.039) in all groups. POMS score increased significantly in group D (p = 0.041). There was no effect of time on plasma glucose levels (p = 0.737). As for correlations, positive correlations were observed between sprint and FAS variables (p = 0.011). Conclusions: It appears that CH intake correlates positively with mood, but in all other variables, there are no differences depending on the product