Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy

Abstract: Information about heart failure with reduced ejection fraction (HFrEF) in women and the potential effects of aging in the female heart is scarce. We investigated the vulnerability to develop HFrEF in female elderly mice compared to young animals, as well as potential differences in reverse remodeling. First, HF was induced by isoproterenol infusion (30 mg/kg/day, 28 days) in young (10-week-old) and elderly (22-month-old) female mice. In a second set of animals, mice underwent isoproterenol infusion followed by no treatment during 28 additional days. Cardiac remodeling was assessed by echocardiography, histology and gene expression of collagen-I and collagen-III. Following isoproterenol infusion, elderly mice developed similar HFrEF features compared to young animals, except for greater cell hypertrophy and tissue fibrosis. After beta-adrenergic withdrawal, young female mice experienced complete reversal of the HFrEF phenotype. Conversely, reversed remodeling was impaired in elderly animals, with no significant recovery of LV ejection fraction, cardiomyocyte hypertrophy and collagen deposition. In conclusion, chronic isoproterenol infusion is a valid HF model for elderly and young female mice and induces a similar HF phenotype in both. Elderly animals, unlike young, show impaired reverse remodeling, with persistent tissue fibrosis and cardiac dysfunction even after beta-adrenergic withdrawal

A Phase I-II multicenter trial with Avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients; GEMCAD 1602 study

[Background]: Immune check-point blockade (ICB) has shown clinical beneft in mismatch repair-defcient/microsatellite instability high metastatic colorectal cancer (mCRC) but not in mismatch repair-profcient/microsatellite stable patients. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB as this combination has the potential to achieve synergistic efects. [Methods]: This was a Phase I/II multicentric study with translational sub-studies, to evaluate the safety, pharmacodynamics and anti-tumor efects of Avelumab plus ADC vaccine in heavily pre-treated MSS mCRC patients. Primary objective was to determine the maximum tolerated dose and the efcacy of the combination. The primary end-point was 40% progressionfree survival at 6 months with a 2 Simon Stage. [Results]: A total of 28 patients were screened and 19 pts were included. Combined therapy was safe and well tolerated. An interim analysis (Simon design frst-stage) recommended early termination because only 2/19 (11%) patients were disease free at 6 months. Median PFS was 3.1 months [2.1–5.3 months] and overall survival was 12.2 months [3.2–23.2 months]. Stimulation of immune system was observed in vitro but not clinically. The evaluation of basal RNA-seq noted signifcant changes between pre and post-therapy liver biopsies related to lipid metabolism and transport, infammation and oxidative stress pathways. [Conclusions]: The combination of Avelumab plus ADC vaccine is safe and well tolerated but exhibited modest clinical activity. Our study describes, for the frst-time, a de novo post-therapy metabolic rewiring, that could represent novel immunotherapyinduced tumor vulnerabilities.The study was funded by grants from the FIS PI17/00732 from Instituto de Salud Carlos III, Premi Fi de Residència Emili Letang from Hospital Clínic Barcelona, Plan Nacional de I + D (PID-107139RB-C21 to DB-R and PID2020-115051RB-I00 to MC) and Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD). The study was funded with Grants from Catalan Agency for Management of University and Research Grants (AGAUR) (2014-SGR-474, 2017-SGR-1174 and 2017-SGR-1033), Fundació la Marató de TV3 (201330.10), Instituto de Salud Carlos III (PI13/01728 and PI19/00740) and Fundacion Olga Torres (Modalitat A. 2019/2020) to JM. IMMETCOLS signature is under patent protection (EP21382772.8.) This research was financially supported by GEMCAD and (OR Avelumab was provided) by Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: https://doi.org/10.13039/100009945) and Pfizer

Tuning Single-Molecule Conductance in Metalloporphyrin-Based Wires via Supramolecular Interactions.

Nature has developed amazing supramolecular constructs to deliver outstanding charge transport capabilities using metalloporphyrin-based supramolecular stacks.1 Here we are incorporating simple, naturally inspired supramolecular interactions via the axial complexation of metalloporphyrins into the formation of a single-molecule wire in a nanoscale gap to dissect the resulting electron pathways through the final chemical adduct. We observe that small structural changes in the axial coordinating linkers result in dramatic changes in the transport properties through the metalloporphyrin-based wire. The increased flexibility of a pyridine-4-yl-methanethiol ligand due to an extra methyl group as compared to a more rigid mercaptopyridine linker allows the former to adopt an unexpected highly conductive stacked structure between the two junction electrodes and the metalloporphyrin ring. DFT calculations reveal a molecular junction structure composed of a shifted stack of the three molecular backbones; the two pyridine ligands sandwiching the metalloporphyrin ring, which is stabilized by a combination of the porphyrin metal center coordinating the pyridinic N and the pyridine/porphyrin overlapping. Contrarily, the more rigid 4-mercaptopyridine ligand presents a more expected octahedral coordination of the metalloporphyrin metal center, leading to much lower conductance. Furthermore, we show that a mechanical forced imposed along the molecular wire axis results in a variety of more extended supramolecular structures between the pyridine linkers and the porphyrin ring spanning the tunneling gap and scoring relatively high conductance values. This works sets an example of the use of supramolecular chemistry in the construction of efficient molecular conduits towards the development of supramolecular electronics, a concept already exploited in natural organisms

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis

This research was funded by the Spanish National Research Council (CSIC), project no. 202080E231, and the Agreement with the University of Barcelona and the University of Granada (Official State Gazette 311, on 27 November 2020).Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.Spanish National Research Council (CSIC), project no. 202080E231Agreement with the University of Barcelona and the University of Granad

Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses

Objective: The aim of this study was to identify the risk factors associated with fragility fracture (FF) development in glucocorticoid (GC)-treated patients. Methods: 127 patients (aged 62±18 years, 63% women) on GC-treatment (mean dose 14.5±14.1 mg/day and duration 47.7±69 months) were included. The clinical data collected included bone metabolism study (including gonadal axis), GC-treatment, disease activity, dual-energy X-ray absorptiometry analysis (evaluating densitometric osteoporosis (OP) and trabecular bone score (TBS) degraded microarchitecture values (DMA)), X-ray (assessing vertebral fractures (VF)), FRAX risk (GC-adjusted) and previous FF. Results: 17% of the patients had VF, 28% FF (VF and/or non-VF), 29% OP and 52% DMA. Patients with VF received more GC boluses (57.1% vs 29.5%, p=0.03), were older (68±13 vs 60±19 years, p=0.02), postmenopausal (100% vs 67%, p=0.02), had low testosterone levels (57% vs 11%, p=0.02), lower TBS values (1.119±0.03 vs 1.237±0.013, p100, p=0.01) and having received GC boluses (OR 3.45; 95% CI 1.04 to 12.15, p=0.01) were the main factors related to VF. Hypogonadism (OR 7.03; 95% CI 1.47 to 38.37, p=0.01) and FRAX >20 (OR 7.08; 95% CI 1.28 to 53.71, p=0.02) were factors related to FF. Conclusion: Hypogonadism is the principal risk factor for developing fractures in GC-treated men and women, whereas receiving GC boluses is a major factor for VF. These results indicate the importance of evaluating the gonadal axis in these patients

Early-Career Coordinated Distributed Experiments: Empowerment Through Collaboration

Este artículo contiene 7 páginas, 1 tabla, 3 figuras.Coordinated distributed experiments (CDEs) enable the study of large-scale ecological patterns in geographically dispersed areas, while simultaneously providing broad academic and personal benefits for the participants. However, the effective involvement of early-career researchers (ECRs) presents major challenges. Here, we analyze the benefits and challenges of the first CDE exclusively led and conducted by ECRs (i.e. ECR-CDE), which sets a baseline for similar CDEs, and we provide recommendations for successful CDE execution. ECR-CDEs achieve most of the outcomes identified in conventional CDEs as well as extensive benefits for the young cohort of researchers, including: (i) receiving scientific credit, (ii) peer-training in new concepts and methods, (iii) developing leadership and communication skills, (iv) promoting a peer network among ECRs, and (v) building on individual engagement and independence. We also discuss the challenges of ECR-CDEs, which are mainly derived from the lack of independence and instability of the participants, and we suggest mechanisms to address them, such as resource re-allocation and communication strategies. We conclude that ECR-CDEs can be a relevant tool to empower ECRs across disciplines by fostering their training, networking and personal well-being.The authors were supported by the following founding: NC the support of the Beatriu de Pinós postdoctoral program of the Government of Catalonia’s Secretariat for Universities and Research of the Ministry of Economy and Knowledge (BP2016- 00215), EE by a predoctoral grant from the Basque Government (2014-2017), AB by a Generalitat de Catalunya—Beatriu de Pinós (BP-00385-2016), AMG-F by a predoctoral research grant (BES-2013-065770) from the Spanish Ministry of Economy and Competitiveness, MAr by a postdoctoral grant from the Basque Government, MIA by a Juan de la Cierva postdoctoral grant (FJCI-2015-26192), PR-L by a Margalida Comas postdoctoral contract (PD/031/2018) funded by the Government of the Balearic Islands and the European Social Fund, AP by a Ramón Areces Foundation Postdoctoral Scholarship, and AL by a Kempe Foundation stipend. DOMIPEX project was founded by the First Call of Collaborative Projects among Young Researchers of the Iberian Association of Limnology (AIL; 2013-2015).Peer reviewe

La gestió de casos en la pràctica infermera

Infermer gestor de casos; pràctica infermera; Atenció sanitàriaEnfermero gestor de casos, Práctica enfermera; Atención sanitariaNurse Case Manager; Nurse practitioner; Health careAquest document proposa recomanacions bàsiques, des de la pràctica infermera, sobre la metodologia de gestió de casos i exposa per on pot discórrer aquesta pràctica assistencial, alhora que emfatitza la coordinació com a eix vertebrador de la continuïtat assistencial de la persona que presenta una situació de complexitat clínica i social. Els elements fonamentals d’aquesta metodologia es basen en la continuïtat assistencial d’infermeria i de treball social, i en l’establiment de circuits que garanteixin el traspàs d’informació entre nivells o entre sectors,que tenen com a precursor el programa Prealt.Documento que propone recomendaciones básicas, des de la práctica enfermera, sobre la metodología de gestión de casos y expone por dónde puede discurrir esta práctica asistencial, al mismo tiempo que enfatiza la coordinación como eje vertebrador de la continuidad asistencial de la persona que presenta una situación de complejidad clínica y social. Los elementos fundamentales de esta metodología se basan en la continuidad asistencial de enfermería y de trabajo social, y en el establecimiento de circuitos que garantizan el traspaso de información entre niveles o entre sectores, que tienen como a percusor el programa Prealt

Determinants and Differences in Satisfaction with the Inhaler Among Patients with Asthma or COPD

Satisfaction with the inhaler is an important determinant of treatment adherence in patients with asthma and chronic obstructive pulmonary disease (COPD). However, few studies have compared these 2 groups to identify the factors associated with satisfaction with the inhaler. To assess and compare satisfaction with the inhaler in patients with asthma or COPD and to determine the variables associated with high inhaler satisfaction. A multicenter, cross-sectional study of 816 patients (406 with asthma and 410 with COPD) was conducted. Satisfaction was assessed with the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. All participants completed the Test of Adherence to Inhalers and either the Asthma Control Test (ACT) or the COPD Assessment Test (CAT). Overall, the asthma group was significantly more satisfied with the inhaler (mean [standard deviation] FSI-10 scores: 44.1 [6.5] vs 42.0 [7.7]; P <.001) and more satisfied on most (7 of 10; 70%) items. Patients with asthma were significantly more satisfied with the inhaler regardless of the adherence level or the type of nonadherence pattern. Younger age, good disease control (ACT ≥20 or CAT ≤10), previous inhaler training, and absence of unwitting nonadherence were all independently and significantly associated with high inhaler satisfaction. Age, disease control, and training in inhalation technique all play a more significant role than the specific diagnosis in explaining satisfaction with the device in patients with asthma and COPD. These findings underscore the need to provide better training and more active monitoring of the inhalation technique to improve patient satisfaction, treatment adherence, and clinical outcomes

Organitzacions saludables: fem salut, fem ioga

Organitzacions saludables; Ioga; Salut públicaOrganizaciones saludables; Yoga; Salud públicaHealthy organizations; Yoga; Public healthAmb l’objectiu de dissenyar un programa fonamentat en la promoció d’organitzacions saludables a través d’una intervenció específica de ioga, es va crear la Comunitat de Pràctica (CoP) Fem salut, fem ioga. Perquè una organització esdevingui saludable ha de permetre als treballadors conciliar la vida laboral amb la familiar, promoure horaris raonables, difondre la cura de la salut amb l’exemple, facilitar un bon ambient laboral i fer prevaldre el treball en equip inter i multidisciplinari i la cooperació per assolir les fites establertes, en alineació amb els objectius de l’empresa. També ha d’animar els treballadors a participar en obres socials i fer educació en salut, tant per als empleats com per als grups amb què es relaciona. Una de les maneres més habituals de promocionar una organització saludable és crear programes adreçats als treballadors que continguin accions concretes, com pot ser, per exemple, la implementació d’un programa de pràctica de ioga. Les malalties causades pels entorns laborals acostumen a estar relacionades amb problemes osteoarticulars (cervicàlgies, lumbàlgies...) i amb la gestió de l’estrès5,6. La pràctica del ioga pot ajudar a prevenir aquest tipus de problemes o a minimitzar-ne els efectes. Com a resultat final es va definir, implementar i avaluar una intervenció pilot de ioga a l’entorn laboral (en aquest cas, institucions governamentals) per a fomentar organitzacions saludables.Con el objetivo de diseñar un programa fundamentado en la promoción de organizaciones saludables a través de una intervención específica de yoga, se creó la Comunidad de Práctica (CoP) Hacemos salud, hacemos yoga. Para que una organización sea saludable debe permitir a los trabajadores conciliar la vida laboral con la familiar, promover horarios razonables, difundir el cuidado de la salud con el ejemplo, facilitar un buen ambiente laboral y primar el trabajo en equipo inter y multidisciplinar y la cooperación para alcanzar las metas establecidas, en alineación con los objetivos de la empresa. También debe animar a los trabajadores a participar en obras sociales y hacer educación en salud, tanto para los empleados como para los grupos con los que se relaciona. Una de las formas más habituales de promocionar una organización saludable es crear programas dirigidos a los trabajadores que contengan acciones concretas, como puede ser, por ejemplo, la implementación de un programa de práctica de yoga. Las enfermedades causadas por los entornos laborales suelen estar relacionadas con problemas osteoarticulares (cervicalgias, lumbalgias...) y con la gestión del estrés5,6. La práctica del yoga puede ayudar a prevenir este tipo de problemas o minimizar sus efectos. Como resultado final se definió, implementó y evaluó una intervención piloto de yoga en el entorno laboral (en este caso, instituciones gubernamentales) para fomentar organizaciones saludables.In order to design a program based on the promotion of organizations health through a specific yoga intervention, the Community of Practice (CoP) We do health, we do yoga. For an organization to be healthy, it must allow workers to reconcile work and family life, promote reasonable hours, disseminate health care by example, facilitate a good work environment, and prioritize inter and multidisciplinary teamwork and cooperation. to achieve the established goals, in alignment with the objectives of the company. It should also encourage workers to participate in social projects and health education, both for employees and for the groups with which they are related. One of the most common ways to promote a healthy organization is to create programs aimed at workers that contain specific actions, such as, for example, the implementation of a yoga practice program. Illnesses caused by work environments are usually related to osteoarticular problems (neck pain, low back pain...) and stress management5,6. The practice of yoga can help prevent these types of problems or minimize their effects. As a final result, a pilot yoga intervention was defined, implemented and evaluated in the work environment (in this case, government institutions) to promote healthy organizations