Increased p53 gene dosage reduces neointimal thickening induced by mechanical injury but has no effect on native atherosclerosis

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The definitive publisher-authenticated version Cardiovasc Res. 75 (4):803-12. is available online at: http://cardiovascres.oxfordjournals.org/cgi/content/full/75/4/803OBJECTIVE: The tumor suppressor p53 regulates cell proliferation and apoptosis, two key processes in the pathogenesis of occlusive vascular disease. Here, we examined the consequences of heightening p53 function on neointimal lesion formation in the setting of atherosclerosis and mechanical injury. METHODS: (1) Immunohistopathological characterization of neointimal lesions in atherosclerosis-prone apolipoprotein E-null mice with normal p53 gene dosage (apoEKO) and carrying a p53 transgene (Super-p53/apoE-KO); (2) molecular studies in macrophages and smooth muscle cells (SMCs) obtained from these mice. RESULTS: The p53 transgene conferred p53 gain-of-function in cultured cells and mice. In vitro, survival of irradiated Super-p53 macrophages and femoral SMCs was reduced, but only Super-p53 SMCs exhibited attenuated proliferation. In vivo, whereas the size of spontaneously formed and diet-induced aortic atheromas was undistinguishable in apoE-KO and Super-p53/apoE-KO mice, the latter exhibited attenuated neointimal thickening in mechanically-injured femoral artery. In both models, neither apoptosis nor cell proliferation were affected by additional p53 gene dosage when examined in established neointimal lesions. However, at 2 days after mechanical injury when neointimal lesions were not formed yet, cell proliferation was significantly attenuated within medial SMCs of Super-p53/apoEKO mice. CONCLUSION: Heightening p53 function has differential effects on in vitro proliferation of macrophages (unaffected) versus SMCs (reduced), and on native atherosclerosis (unaffected) versus mechanically-induced neointimal thickening (reduced) in apoE-KO mice. The protective effect of p53 in mechanically-injured femoral artery coincided with limited medial SMC proliferation at early time points preceding neointima formation, but neither medial nor neointimal cell proliferation was affected in vessels with established occlusive lesions. These findings corroborate p53 gain-of-function as a promising therapeutic strategy to limit post-angioplasty restenosis but not native atherosclerosis.Work financed by grants from Ministerio de Sanidad y Consumo/Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares, RECAVA), from the Regional Government of Valencia (GV04B-288) and from Ministerio de Educación y Ciencia and the European Regional Development Fund (SAF2004-03057). S.M.S.-G. and J.M.G received salary support from Instituto de Salud Carlos III, and J.J.F. from CSIC-I3P predoctoral fellowship program cosponsored by the European Social Fund.Peer reviewe

Cyclometalated Iminophosphorane Gold(III) and Platinum(II) Complexes. A Highly Permeable Cationic Platinum(II) Compound with Promising Anticancer Properties

New organometallic gold(III) and platinum(II) complexes containing iminophosphorane ligands are described. Most of them are more cytotoxic to a number of human cancer cell lines than cisplatin. Cationic Pt(II) derivatives 4 and 5, which differ only in the anion, Hg2Cl62– or PF6– respectively, display almost identical IC50 values in the sub-micromolar range (25–335-fold more active than cisplatin on these cell lines). The gold compounds induced mainly caspase-independent cell death, as previously reported for related cycloaurated compounds containing IM ligands. Cycloplatinated compounds 3, 4, and 5 can also activate alternative caspase-independent mechanisms of death. However, at short incubation times cell death seems to be mainly caspase dependent, suggesting that the main mechanism of cell death for these compounds is apoptosis. Mercury-free compound 5 does not interact with plasmid (pBR322) DNA or with calf thymus DNA. Permeability studies of 5 by two different assays, in vitro Caco-2 monolayers and a rat perfusion model, have revealed a high permeability profile for this compound (comparable to that of metoprolol or caffeine) and an estimated oral fraction absorbed of 100%, which potentially makes it a good candidate for oral administration

High seroprevalence against SARS-CoV-2 among faculty of medicine and health sciences personnel and students of the University of Alcalá, Spain: contributing factors

Purpose: Seroprevalence against SARS-CoV-2 within university systems is poorly studied, making evidence-based discussions of educational system reopening difficult. Moreover, few studies evaluate how antibodies against SARS-CoV-2 are maintained over time. We assessed serological response against the SARS-CoV-2 virus among our university students and staff. Patients and Methods: In this prospective cohort study, seroprevalence was determined in 705 randomly selected volunteers, members of the Faculty of Medicine and Health Sciences of the University of Alcala, using a chemiluminescent Siemens&apos; SARS-CoV-2 immunoassay for total antibodies. Positive samples were tested for IgG and IgM/IgA using VIRCLIA (R) MONOTEST (Vircell). A first analysis took place during June 2020, and in those testing positive, a determination of secondary outcomes was performed in November 2020. Results: A total of 130 subjects showed anti-SARS-CoV-2 antibodies (18.5%, 95% CI, 15.8-21.5%). Of these, IgM/IgA was positive in 27 and indeterminate in 19; IgG was positive in 118, indeterminate in 1. After 23 weeks, among 102 volunteers remeasured, IgG became undetectable in 6. Presence of antibodies was associated, in multivariable logistic regression, with exposure to infected patients (31.3%) [OR 1.84, 95% CI, 1.14-2.96; P = 0.012], presence of COVID-19 symptoms (52.4%) [OR 6.88, 95% CI, 4.28-11.06; P < 0.001], and confirmed earlier infection (82.9%) [OR 11.87, 95% CI, 4.26-33.07; P < 0.001]. Conclusions: The faculty of medicine and health sciences personnel and students of our university showed a high infection rate for SARS-CoV-2 during 2020 associated with providing clinical care to infected patients. This emphasizes the importance of the performance of continuous surveillance methods of the most exposed health personnel, including health science students

Efficacy of prompted voiding for reversing urinary incontinence in older adults hospitalized in a functional recovery unit: Study protocol

Aims: To assess the efficacy of a prompted voiding programme for restoring urinary continence at discharge in hospitalized older adults who presented with reversible urinary incontinence (UI) on admission to a functional recovery unit (FRU). To assess the maintenance of the outcomes achieved after hospitalization. To identify modifiable and unmodifiable factors associated with the success of the prompted voiding programme. Design: Quasi-experimental, pre-/post-intervention study without a control group. Methods: Participants were aged 65 and over with a history of reversible UI in the previous year who had been admitted to a FRU and were on a prompted voiding programme throughout their hospitalization period. The sample consisted of 221 participants. A non-probabilistic sampling method, in order of recruitment after signing the informed consent form, was used. The primary outcomes were UI assessed at discharge and 1 month, 3 months and 6 months after discharge. Funding was granted in July 2019 by the Spain Health Research Fund (PI19/00168, Ministry of Health). The proposal was approved by the Spanish Research Ethics Committee. Discussion: The prompted voiding programme described can reverse UI or decrease the frequency and amount of urine loss in hospitalized older adults. Impact: Urinary incontinence is highly prevalent in hospitalized older adults. There is a need for care aimed at prevention, recovery and symptom control. Prompted voiding is a therapy provided by the nursing team during hospitalization and can also be provided by family caregivers at home after receiving proper training by the nursing team. Prompted voiding will enhance the health, functional ability and quality of life of older adults with UI, resulting in the reduction of associated healthcare costs and the risk of developing complicationsThis study has been funded by Instituto de Salud Carlos III through the project “PI19/00168” (Co-funded by European Regional Development Fund/ European Social Fund “A way to make Europe”/“Investing in your future”

Stability study of MOF@IL composite materials

Abstract enviado al congresos 5th International Conference on Multifunctional, Hybrid and Nanomaterials (6-10 March 2017 | Lisbon, Portugal) y poster presentado en dicho congreso.Metal-organic frameworks (MOF) offer unique advantages for many applications due to their ordered structures, high thermal stability, tunable chemical functionality, ultra-high porosity and the availability of hundreds of well characterized structures.[1] On the other hand, Ionic Liquids (IL), which are ionic salts liquid at ambient conditions, have suitable properties for many applications, such as negligible volatility, non-flammability, high thermal and chemical stability, and high ionic conductivity. However, their liquid nature hinders their handling, making it necessary the use solid supports. [2] The insertion of ILs into MOFs has resulted in a new generation of materials with properties of both MOF and IL. [3] The studies of potential applications of MOF@IL composite materials are still very incipient, but they point out that the properties of MOFs could be improved by the insertion of ILs.[4] In order to know whether MOF@IL could be used as new materials it is necessary to study their stability, both thermal and chemical. In this work, three MOFs were selected, CuBTC, ZIF-8 and MOF-74,[5] to produce MOF@IL with two ILs, [BMIM][BF4] and [EMIM][BF4]. Themogravimetry was used to determine the thermal stability of the composites, as well as, to quantify the IL content before and after the leakeage tests both in water and toluene. Other characterization techniques, such as, IR spectroscopy and X-ray powder diffraction were used. The insertion of ILs was successful for CuBTC and ZIF-8, but not for MOF-74. The thermal stability of the MOF@IL is related to the interactions established between thet MOF and the IL. However, the chemical stability of the composites in water and toluene depend on that of the MOFs and, consequently, a poor stability is observed for CuBTC@IL in water. The use of these new materials is, therefore, determined by the stability of the MOFs acting as host structures.Ministerio de Economía y Competitividad: MAT2013-42092-R Gobierno Vasco: IT-630-13 Dpto. desarrollo economico y competitividad (GV), programa ELKARTEK: ACTIMAT KK-2015/00094 y LISOL KK-2016/0009

Relación índice de masa corporal, complexión y riesgo metabólico en familiares de estudiantes de Nutriología

Introduction: Anthropometric assessment is a reliable method in the early detection of chronic non-communicable diseases, with an increasing prevalence in the face of an increasingly older, sedentary population with an unhealthy lifestyle. Objective: To identify in the family of students of the degree in Nutrition, from the University of Sciences and Arts of Chiapas, the body mass index, waist hip and complexion, relating them to metabolic risk. Material and method: Descriptive, cross-sectional study, sample of 48 relatives of undergraduate students in Nutrition, aged 19 to 59 years, variables weight, height, waist, hip and wrist circumferences, determination of body mass index, waist-hip and complexion. With descriptive statistical analysis. Results: The predominant body mass index was normal, 63.8% had a large complexion according to wrist circumference. 46.8% with presence of android obesity, waist-hip ratio in women 27.6%, men 19.1%; relationship between body mass index and height/wrist index with a significant difference p≤0.05* in all anthropometric variables. Conclusions: The study population showed a large complexion, short stature, and android obesity, evidenced by the greater accumulation of fat in the upper segment, representing a greater risk of cardiovascular and metabolic diseases, which implies greater care in lifestyle.Introducción: La valoración antropométrica método confiable en la detección temprana de enfermedades crónicas no transmisibles, con prevalencia en aumento ante una población cada vez más envejecida, sedentaria y estilo de vida no saludable. Objetivo: Identificar en la familia de estudiantes de la licenciatura en Nutriología, de Universidad de Ciencias y Artes de Chiapas, el índice de masa corporal, cintura cadera y complexión, relacionándolos con el riesgo metabólico. Material y Método: Estudio descriptivo, transversal, muestra de 48 familiares de estudiantes de licenciatura en Nutriología, edad de 19 a 59 años, variables peso, estatura, circunferencias de cintura, cadera y muñeca, determinación de índices de masa corporal, cintura-cadera y complexión. Con análisis estadísticos descriptivos.  Resultados: El índice de masa corporal predominante fue normal, 63.8% presentó complexión grande de acuerdo a circunferencia de muñeca. 46.8% con presencia de obesidad androide, índice cintura cadera en mujeres 27.6%, hombres 19.1%; relación índice de masa corporal e índice talla/muñeca con diferencia significancia p≤0.05* en todas las variables antropométricas. Conclusiones: la población de estudio dio muestra de complexión grande, estatura baja, obesidad androide, evidenciado por la mayor acumulación de grasa en el segmento superior, representando mayor riesgo a las enfermedades cardiovasculares y metabólicas, lo que implica mayor cuidado en el estilo de vida

Oligometástasis en cáncer de mama: estrategias y perspectivas para el control local del tumor primario y de las metástasis

El cáncer de mama metastásico, identificado en el momento del diagnóstico o desarrollado tras transcurrir cierto tiempo desde la aparición de la enfermedad primaria, presenta una naturaleza heterogénea. Los resultados obtenidos gracias a los avances farmacológicos nos motivan a explorar la suplementación del tratamiento empleando técnicas de abordaje local. Esta revisión está dirigida a analizar la información disponible en la literatura sobre dos aspectos fundamentales en el cáncer de mama. Por un lado, el control del tumor primario, tanto en la mama como en los ganglios linfáticos locorregionales, y por otro, el control local de las metástasis en función de su localización en los casos de enfermedad oligometastásica. Las principales estrategias para llevar a cabo dicho control local son la cirugía, la radioterapia, incluyendo la radioterapia estereotáctica corporal o la radioterapia de haz externo, y la ablación por radiofrecuencia. Las evidencias discutidas señalan que, a la espera de más resultados procedentes de ensayos controlados aleatorios y de estudios específicos de la enfermedad, las pacientes con oligometástasis deben ser evaluadas por un equipo multidisciplinar. Las metástasis únicas podrían ser candidatas para tratamiento local, cada vez más eficiente, y esto, en combinación con los avances en la terapia sistémica, podría resultar en un mejor control de la enfermedad. Todas estas alternativas deberían presentarse a las pacientes con la finalidad de seleccionar un tratamiento personalizado, con base en la evidencia científica y en las características propias de su enfermedad, que presuponga un resultado más eficaz.Metastatic breast cancer, identified at the time of diagnosis or developed after a certain period since the onset of the primary disease, presents a heterogeneous nature. The results obtained through pharmacological advances encourage us to explore supplementing the treatment using local management techniques. This review aims to analyze the available literature on two fundamental aspects of breast cancer. On the one hand, the control of the primary tumor, both in the breast and in the locoregional lymph nodes, and on the other hand, the local control of metastases depending on their location in cases of oligometastatic disease. The main strategies for carrying out such local control are surgery, radiotherapy, including stereotactic body radiotherapy or external beam radiotherapy, and radiofrequency ablation. The evidence discussed indicates that, pending further results from randomized controlled trials and disease-specific studies, patients with oligometastasis should be evaluated by a multidisciplinary team. Single metastases could be candidates for local treatment, increasingly efficient, and this, in combination with advances in systemic therapy, could result in better disease control. All these alternatives should be presented to patients with the purpose of selecting a personalized treatment, based on scientific evidence and the unique characteristics of their disease, which presupposes a more effective outcome.AstraZenecaLillyPfizerRoch

Impact of different waves of COVID-19 on emergency medical services and out-of-hospital cardiopulmonary arrest in Madrid, Spain

Out-of-hospital cardiac arrest (OHCA) is one of the three leading causes of death in industrialized countries.[1,2] Some studies have described the impact of the first COVID-19 pandemic wave in terms of the number of cases and OHCA survival rates in various regions,[3-5] but few have addressed the relationship between the successive phases and how they affected OHCA.[6,7] The 14-d cumulative incidence peaked at more than 990 cases, with these rates remaining above 200 for an eight-month period between 15 March 2020 and 15 March 2021 in Madrid, Spain. The objectives of the current study were twofold. First, we sought to describe how the different waves in the first pandemic year aff ected the healthcare activity of the Spanish emergency medical services (EMS). Second, we compared effects of the pandemic year on OHCA care to those of the preceding non-pandemic year in terms of initiating cardiopulmonary resuscitation and survival in a community with a high incidence of COVID-19.post-print164 K