Physical performance and quality of life in older adults: Is there any association between them and potential drug interactions in Polymedicated Octogenarians?

Producción CientíficaOlder adults are at increased risk of several cytochrome P450 (CYP) drug interactions that can result in drug toxicity, reduced pharmacological effect, and adverse drug reactions. This study aimed to assess the prevalence of potential CYP interactions referring to the most clinically relevant drugs and exploring the relationship between them and quality of life and physical performance in Spanish octogenarians. Institutionalized and community-dwelling octogenarians (n = 102) treated at three primary care centers, were recruited by a research nurse. Anthropometric measurements, chronic diseases, prescribed drugs, quality of life, physical performance, mobility skills, hand grip strength and cognitive status data were collected. Potential CYP drug-drug interactions (DDIs) were selected referring to the main CYP implicated in their metabolism. The 72.2% of recruited octogenarians presented potentially inappropriate CYP inhibitor-substrate or CYP inductor-substrate combinations. Analyzing the EuroQol Visual Analogue scale (EQ-VAS) results, patients with a potential CYP DDI perceived worse health status than patients without it (p = 0.004). In addition, patients with a potential CYP DDI presented worse exercise capacity, kinesthetic abilities, or mobility than those who didn’t present a potential interaction (p = 0.01, p = 0.047, and p = 0.02, respectively). To investigate and control factors associated with loss of muscle strength and poor quality of life, polypharmacy and DDIs could help institutions in the management of physical frailty.Fundación Científica Caja Rural de Soria (project 00200200227

Home parenteral nutrition registry in Spain for the year 2010: NADYA-SENPE group

Objetivos: Comunicar los datos del Registro del Grupo NADYA SENPE de Nutrición Parenteral Domiciliaria NPD en España del año 2010. Material y métodos: Estudio descriptivo de la base de datos del Registro de ámbito nacional de NPD del grupo NADYA-SENPE (1 de enero de 2010 al 31 de diciembre de 2010). Para el cálculo de prevalencias se utilizó los últimos datos publicados por el Instituto Nacional de Estadística. Resultados: Se registraron 148 pacientes procedentes de 23 hospitales, 86 mujeres (58,11%) y 9 niños (6,08%). La edad media de los 139 pacientes adultos fue de 53,06 ± 15,41 años. La duración media de la NPD fue de 316,97 días/paciente. El diagnóstico más frecuente en los niños (menores de 14 años) fue intestino corto traumático con 5 casos (55,55%) y en los adultos la neoplasia en tratamiento paliativo 29 (19,59%). El motivo de la indicación de la NPD fue el síndrome de intestino corto en 74 ocasiones (47%). La vía de acceso más frecuentemente registrada fue el catéter tunelizado en 36 (22,78%) casos seguido del reservorio en 13 (8,23%) y otras vías en 3 ocasiones (1,90%). Se registraron 23 infecciones relacionadas con el catéter (82,14%), lo que representa 0,49/1000 días de NP y todas ellas ocurrieron en los adultos. A lo largo del año finalizaron 24 episodios de NPD, la causa más frecuente fue el paso a la vía oral en 12 episodios (50%). Se registró que los pacientes tenían una actividad normal en 70 episodios de NPD (44,30%) con una total autonomía en 88 de episodios (55,69%). Se identificaron 39 (24,68%) posibles candidatos para trasplante intestinal. Conclusiones: El número de pacientes registrados es discretamente inferior al del año anterior, aunque el número de hospitales participantes es el mismo. La complicación más frecuente sigue siendo la infección relacionada con el catéter aunque ha disminuido su incidencia respecto a años anteriores, presentándose la tasa más baja desde la creación del registro. Las diferencias en la participación en el registro observadas por Comunidades Autónomas lleva a plantear el desarrollo de estrategias de implementación del registro. Se observa un aumento progresivo de la duración de los días de NPD a lo largo de los años que hace pensar en la cronicidad de algunos pacientes, pero nos obliga a estudiar la existencia de un posible factor de confusión, en el caso de que existiera un olvido de cierre de algún episodio por lo que se hace necesario actualizar el registro con sistemas de alertas periódicas que faciliten la revisión de los pacientes incluidos y optimice la validez del registroObjectives: To report the Group Registry NADYASENPE data about home parenteral nutrition (HPN) in Spain in 2010. Material and methods: A descriptive study of the database of the national registry of HPN of NADYA-SENPE (December 10, 2009 to December 10, 2010). For the calculation of prevalence the latest data published by the Institute National Statistics Office (01/01/2009) was used. Results: There were registered 148 patients from 23 hospitals, 86 women (58.11%) and 9 children (6.08%). The average age of the 139 patients older than 14 years was 53.06 ± 15.41 years. The average duration of HPN was 316.97 days/patient. The most common diagnosis in those younger than 14 years was short bowel traumatic with 5 cases (55.55%) and in those older than 14 years, palliative care cancer with 29 cases (19.59%). The reason for the indication for HPN was short bowel syndrome in 74 cases (47%). The access via most frequently recorded was tunneled catheter in 36 cases (22.78%) followed by implanted port-catheters in 13 cases (8.23%) and other pathways in 3 cases (1.90%). There were 23 catheterrelated infections (82.14%) which represented 0.49 /1,000 days of PN, all of which occurred in cases older than 14 years. During the year 24 episodes of HPN ended, the most frequent cause was the transition to oral nutrition in 12 episodes (50%). It was reported that patients had a normal activity in 70 episodes of HPN (44.30%) with complete autonomy in 88 episodes (55.69%). Some patients 39 (24.68%) were potential candidates for intestinal transplantation. Conclusions: The number of registered patients is slightly lower than the previous year, although the number of participating hospitals is the same. The most frequent complication remains catheter-related infection but its incidence has decreased from previous years, presenting the lowest rate since the creation of the record. Differences in participation in the registry observed in the Autonomous Communities causes the development of implementation strategies. There is a gradual increase in day length of HPN over the years, which suggests the chronic treatments of some patients and obliges to study the existence of a possible confounding factor, in case there is an oversight of closing an episode. Therefore, it is necessary to update the registry with warning systems that facilitate periodic review of the patients and optimize the validity of registratio

First Assessment of the Impacts of the COVID-19 Pandemic on Global Marine Recreational Fisheries

This work is the result of an international research effort to determine the main impacts of the COVID-19 pandemic on marine recreational fishing. Changes were assessed on (1) access to fishing, derived from lockdowns and other mobility restrictions; (2) ecosystems, because of alterations in fishing intensity and human presence; (3) the blue economy, derived from alterations in the investments and expenses of the fishers; and (4) society, in relation to variations in fishers’ health and well-being. For this, a consultation with experts from 16 countries was carried out, as well as an international online survey aimed at recreational fishers, that included specific questions designed to capture fishers’ heterogeneity in relation to behavior, skills and know-how, and vital involvement. Fishers’ participation in the online survey (5,998 recreational fishers in 15 countries) was promoted through a marketing campaign. The sensitivity of the fishers’ clustering procedure, based on the captured heterogeneity, was evaluated by SIMPER analysis and by generalized linear models. Results from the expert consultation highlighted a worldwide reduction in marine recreational fishing activity. Lower human-driven pressures are expected to generate some benefits for marine ecosystems. However, experts also identified high negative impacts on the blue economy, as well as on fisher health and well-being because of the loss of recreational fishing opportunities. Most (98%) of the fishers who participated in the online survey were identified as advanced, showing a much higher degree of commitment to recreational fishing than basic fishers (2%). Advanced fishers were, in general, more pessimistic about the impacts of COVID-19, reporting higher reductions in physical activity and fish consumption, as well as poorer quality of night rest, foul mood, and raised more concerns about their health status. Controlled and safe access to marine recreational fisheries during pandemics would provide benefits to the health and well-being of people and reduce negative socioeconomic impacts, especially for vulnerable social groups.Versión del edito

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Imaging the photodissociation dynamics of the methyl radical from the 3s and 3pz Rydberg states

8 págs.; 6 figs.; 1 tab.The photodissociation dynamics of the methyl radical from the 3s and 3pz Rydberg states have been studied using the velocity map and slice ion imaging in combination with pump–probe nanosecond laser pulses. The reported translational energy and angular distributions of the H(2S) photofragment detected by (2+1) REMPI highlight different dissociation mechanisms for the 3s and 3pz Rydberg states. A narrow peak in the translational energy distribution and an anisotropic angular distribution characterize the fast 3s photodissociation, while for the 3pz state Boltzmann-type translational energy and isotropic angular distributions are found. High level ab initio calculations have been performed in order to elucidate the photodissociation mechanisms from the two Rydberg states and to rationalize the experimental results. The calculated potential energy curves highlight a typical predissociation mechanism for the 3s state, characterized by the coupling between the 3s Rydberg state and a valence repulsive state. On the other hand, the photodissociation on the 3pz state is initiated by a predissociation process due to the coupling between the 3pz Rydberg state and a valence repulsive state and constrained, later on, by two conical intersections that allow the system to relax to lower electronic states. Such a mechanism opens up different reaction pathways leading to CH2 photofragments in different electronic states and inducing a transfer of energy between translational and internal modes.S. M. P. acknowledges financial support from Campus de Excelencia Internacional Moncloa and LASING S. A. D. V. C. acknowledges a contract from MINECO under the Fondo de Garantıía Juvenil. A. Z. thanks the support from the European Research Council under the European Union’s 7th Framework Program (FP7/2007–2013)/ERC Grant agreement 610256 (NANOCOSMOS). M. G. G. is grateful to Spanish MINECO for a contract through Programa de Técnicos de Apoyo a Infraestructuras. This work has been financed by the Spanish MINECO (grants FIS2011- 29596-C02-01, CTQ2012-37404-C02-01, FIS2013-40626-P and CTQ2015-65033-P) and by COST Actions CM1401 and CM05. This research has been carried out within the Unidad Asociada Química Física Molecular between Departamento de Química Física of Universidad Complutense de Madrid (UCM) and Consejo Superior de Investigaciones Científicas (CSIC). The facilities provided by the Centro de Láseres Ultrarrápidos at UCM are acknowledged. The Centro de Supercomputación de Galicia (CESGA, Spain) and CTI (CSIC) are acknowledged for the use of their resources.Peer Reviewe

A velocity-map imaging study of methyl non-resonant multiphoton ionization from the photodissociation of CH3I in the A-band

Chemical reaction dynamics and, particularly, photodissociation in the gas phase are generally studied using pump-probe schemes where a first laser pulse induces the process under study and a second one detects the produced fragments. Providing an efficient detection of ro-vibrationally state-selected photofragments, the resonance enhanced multiphoton ionization (REMPI) technique is, without question, the most popular approach used for the probe step, while non-resonant multiphoton ionization (NRMPI) detection of the products is scarce. The main goal of this work is to test the sensitivity of the NRMPI technique to fragment vibrational distributions arising from molecular photodissociation processes. We revisit the well-known process of methyl iodide photodissociation in the A-band at around 280 nm, using the velocity-map imaging technique in conjunction with NRMPI of the methyl fragment. The detection wavelength, carefully selected to avoid any REMPI transition, was scanned between 325 and 335nm seeking correlations between the different observables-the product vibrational, translational and angular distributions-and the excitation wavelength of the probe laser pulse. The experimental results have been discussed on the base of quantum dynamics calculations of photofragment vibrational populations carried out on available ab initio potential-energy surfaces using a four-dimensional model.Peer Reviewe

CYP2D6 genotype and optimization of breast cancer treatment

A previous modeling analysis suggests that postmenopausal breast cancer women with wild-type CYP2D6 (non-CYP2D6*4-allele carriers) might actually have superior disease-free survival (DFS) outcomes when they take tamoxifen rather than an aromatase inhibitor (AI). The present study not only adjusts that original model by the comedication status of CYP2D6-inhibitors but also reconstructs a multiple-genotypebased model, so that an optimizing endocrine therapy for patients harboring wild-type CYP2D6 would be exactly determined. We created Markov models (a modified model and a reconstructed model) to determine whether tamoxifen or AIs maximized 5-year DFS for extensive-metabolizer patients. We also employed twoway sensitivity analyses to explore the impacts of hazard ratio (HR) of decreased metabolizers and frequency of each metabolizer on DFS by studying a range of estimates. In the comedication-adjusted model, the 5-year-DFS of tamoxifen-treated extensive-metabolizer patients was 84.7%, similar to or slightly superior to that for genotypically unselected patients receiving AIs (84.0%). Similarly, in the reconstructed model, the extensive-metabolizer patients also benefited more from tamoxifen than from AIs (5-year-DFS, 85.7% vs. 84.0%). Our reconstructed model with two parameters simplified the prediction of tamoxifen response and increased the reliability. Two-way sensitivity analyses demonstrated the robustness of these results. In conclusion, our modeling analyses indicate that among extensivemetabolizer patients, DFS outcomes of patients receiving tamoxifen are similar to even superior to those receiving AIs. The findings strongly suggest that postmenopausal patients who are concerned about the toxicity or cost of AIs could refer to the CYP2D6 genetic testing to pursue an optimal adjuvant endocrine treatment.9.386 JCR (2010) Q1, 9/185 Oncolog