Circulating myokines IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity

24 p.Objective: To examine the effects of a time-matched endurance versus concurrent training on circulating IL-6, IL-13, IL-15, IL-15Ra, FGF21 levels in postmenopausal women with obesity, and to determine these myokines response to endurance training pre- and postmenopause. Methods: Thirty-five sedentary postmenopausal women with obesity were randomly divided into endurance training (EN1, N=10), concurrent training (CON, N=13) or no training group (CT, N=12). Additionally, twelve sedentary premenopausal women with obesity were added to an endurance training group (EN2, N=12). Participants took part in a 12-week supervised intervention, performing 3 sessions/week of 60 min/session. Before and after the interventions, body composition and fitness were assessed, and blood samples obtained to measure serum myokines levels. Results: Total fat mass decreased in all exercised groups (CON,-5.2%; EN1,-5.3%; EN2,-5.6%). In postmenopausal women, serum IL-6, IL-15 and IL-15Ra decreased after training (P<0.01), finding a pronounced reduction in IL-6 (-42% vs. -16%) and IL-15 (- 50% vs. -31%) when comparing EN1 to CON (P<0.05). Serum FGF21 was only reduced in the EN1 (-27%; P=0.012). While EN1 and EN2 comparison, reported differences for IL-15R? concentration (-28% vs. -40%; P=0.023). Finally, in EN2, the delta change of fat mass and IL-6, IL-15 and IL-15R? were associated (r=0.605; r=0.546; r=0.515; P<0.05). IL-13 showed undetected concentrations. Conclusions: Circulating IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity. Endurance training promotes a higher reduction of these myokines, potentially activating their intricate immune and fat mass regulation roles in postmenopausal women with obesity.Universidad de Alcal

Centro Universitario de la Defensa de Madrid (CUD-ACD): nuevo paradigma de la formación del médico-militar

Es evidente, que con la aparición del Centro Universitario de la Defensa (CUD) se ha abierto un modelo diferente y moderno en la formación de los nuevos oficiales médicos que han de salvaguardar el futuro de la Sanidad Militar. El CUD es un centro de enseñanza perteneciente al Ministerio de Defensa que ejerce su control desde la Dirección General de Reclutamiento y Enseñanza Militar (DIGEREM), que está adscrito a la Universidad de Alcalá y que tiene por objetivo la formación de los estudiantes en el Grado de Medicina al mismo tiempo que realizan su formación castrense bajo el régimen de la Academia Central de la Defensa (ACD). La forma de acceso a esta formación, es a través de la oferta anual de empleo público. Existen dos formas de acceso: Acceso directo (aspirantes procedentes de Bachillerato) y Acceso por promoción interna, enfocada al ingreso por cambio de cuerpo (aspirantes que ya pertenecen a las Fuerzas Armadas a través de los Ejércitos y de la Armada) y por cambio de escala (aspirantes que provienen de la escala de enfermería militar). Como Oferta de Empleo Público que es, el acceso directo se realiza mediante concurso oposición en la que la fase de concurso es la nota de las pruebas de acceso a la Universidad y la oposición consiste en una prueba de inglés, unas pruebas físicas y un test psicotécnico y reconocimiento médico. El Plan de estudios para el Grado de Medicina es el aprobado para la Universidad de Alcalá (UAH) y el profesorado que imparte docencia en el CUD, es el mismo que lo hace en la Facultad de Medicina y Ciencias de la Salud de la UAH. El número de alumnos admitidos durante estos seis cursos de andadura del CUD-ACD ha oscilado entre 20 y 30 dependiendo de la promoción y la nota de corte ha oscilado entre 11,73 y 12,69. En cuanto a la paridad, las cifras han rondado entre el 40% y el 60% a favor del ingreso de varones, salvo en este último curso, en el que, por primera vez, el ingreso de mujeres ha superado al de hombres (16/14 respectivamente). El resultado medido en forma de rendimiento académico ha sido muy satisfactorio durante estos años obteniéndose medias por curso que oscilan entre 7,04 y 7,81 y un porcentaje de aprobados en cada curso de alrededor del 90%. Podemos concluir que la creación del CUD-ACD ha revolucionado la formación de los médicos –militares y que los resultados obtenidos validan este nuevo modelo.It is evident that with the appearance of the University Center of Defense (CUD) has opened a different and modern model in the training of new medical officers who must safeguard the future of the Military Health. The CUD is a teaching center belonging to the Ministry of Defense that exercises its control from the General Directorate of Recruitment and Military Education (DIGEREM), which is attached to the University of Alcala and which aims to train students in the Degree in Medicine at the same time that they carry out their military training under the regime of the Central Academy of Defense (ACD). The form of access to this training is through the annual offer of public employment. There are two forms of access: Direct access (applicants coming from the Baccalaureate) and Access by internal promotion, focused on the income for change of military corps (candidates who already belong to the Armed Forces through the Armies and the Navy) and for change of military scale (aspirants who come from the scale of military nursing). As a Public Employment Offer that is, the direct access is made through an open competition in which the contest phase is the university entrance exams and the exam consists of an English test, a physical test and a psycho-technical test and a medical examination. The curriculum for the Degree in Medicine is approved for the University of Alcalá (UAH) and the teaching staff that teaches in the CUD, is the same as it does in the Faculty of Medicine and Health Sciences of the UAH. The number of students admitted during these six courses of the CUD-ACD has ranged between 20 and 30 depending on the promotion and the minimum qualification of income has ranged between 11.73 and 12.69. The ratio between the number of men and women entering the CUD, has been 40% for women and 60% for men, except in this last year, in which, for the first time, the income of women has exceeded of men (16/14 respectively). The academic performance has been very satisfactory during these years, obtaining average grades per course that range between 7.04 and 7.81 and a passing percentage in each course of approximately 90%. We can conclude that the creation of the CUD-ACD has revolutionized the training of military doctors and that the results obtained validate this new model.

A novel controlled drug-delivery system for growth hormone applied to healing skin wounds in diabetic rats

Controlled release systems for drugs, hormones and growth factors can be particularly useful in tissue repair processes. These systems act as a biodegradable support containing the substance to be delivered, allowing their gradual release. In the past years, the local application of growth factors has acquired special relevance as a therapeutic option for use in subjects who show de cient tissue scarring, the hormone dose being the limiting factor for its success. In this study, the in vitro biocompatibility of a copolymer formed by vinylpyrrolidone and 2-hydroxyethyl methacrylate, used as an administration vehicle for hGH, was evaluated. The system was then tested in vivo in terms of its capacity for healing incisional wounds in healthy and diabetic rats. For the in vitro studies, polymer and hormone degradation rates were determined, and polymer biocompatibility was evaluated in broblast cultures. In the in vivo experiments, an incision was made in the back of the animals, and polymers discs with/ without hGH, were introduced in the aperture. Morphological, immunohistochemical and morphometric evaluations were performed on wound tissue specimens 3¿10 days after surgery. In vitro, the polymer was found to be biodegradable and showed no toxic effects on broblasts, the hormone being slowly released to the culture medium. In untreated diabetic rats, a delayed skin scarring and cell response were observed, compared to that noted in healthy animals. Skin closure, keratinisationand brosis occurred earlier in the presence of the polymer-hGH system. The use of this co-polymer as an administrationvehicle for hGH improves the wound scarring process in the pathological setting of diabetes

Improved Connective Integration of a Degradable 3D-Nano-Apatite/Agarose Scaffold Subcutaneaosly Implanted in a Rat Model

In this work, we evaluate the tissue response and tolerance to a designed 3D porous scaffold composed of nanocrystalline carbonate-hydroxyapatite and agarose as a preliminary step in bone repair and regeneration. These scaffolds were subcutaneously implanted into rats, which were sacrificed at different times. CD4þ, CD8þ and ED1þ cells were evaluated as measurements of inflammatory reaction and tolerance. We observed some inflammatory response early after subcutaneous implantation. The 3D interconnected porosity increased scaffold integration via the formation of granulation tissue and the generation of a fibrous capsule around the scaffold. The capsule is initially formed by collagen which progressively invades the scaffold, creating a network that supports the settlement of connective tissue and generating a compact structure. The timing of the appearance of CD4þ and CD8þ cell populations is in agreement with the resolved inflammatory response. The appearance of macrophage activity evidences a slow and gradual degradation activity. Degradation started with the agarose component of the scaffold, but the nano-apatite was kept intact for up to 30 days. Therefore, this apatite/agarose scaffold showed a high capacity for integration by a connective network that stabilizes the scaffold and results in slow nano-apatite degradation. The fundamental properties of the scaffold would provide mechanical support and facilitate bone mobilization, which is of great importance in the masticatory system or large bones

Lipidomic profiling of chorionic villi in the placentas of women with chronic venous disease

Background: Chronic venous disease (CVD) is a prevalent lower limb venous pathology that especially affects women, who also show an increased risk of this disease during pregnancy. Studies have shown significant structural changes in the placentas of women with CVD and several markers of tissue damage have been also described. Patients and Methods: To try to understand the different placental pathologies, research efforts have focused on examining metabolomic profiles as indicators of the repercussions of these vascular disorders. This study examines changes produced in the metabolomic profiles of chorionic villi in the placentas of women with CVD. In a study population of 12 pregnant women, 6 with and 6 without CVD, we compared through mass spectroscopy coupled to ultra-high performance liquid chromatography (UHPLC-MS), 240 metabolites in chorionic villus samples. Results: This study is the first to detect in the placental villi of pregnant women with CVD, modifications in lysophosphatidylcholines and amino acids along with diminished levels of other lipids such as triglycerides, sphingomyelins, and non-esterified omega 9 fatty acids, suggesting a role of these abnormalities in the pathogenesis of CVD. Conclusions: Our findings are a starting point for future studies designed to examine the impacts of CVD on maternal and fetal well-bein

Newborns of Mothers with Venous Disease during Pregnancy Show Increased Levels of Lipid Peroxidation and Markers of Oxidative Stress and Hypoxia in the Umbilical Cord

The study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (grant no. Estatal de I + D + I 2013–2016) and co-financed by the European Development Regional Fund “A way to achieve Europe” and B2017/BMD-3804 MITIC-CM (Comunidad de Madrid), and Halekulani S.L.Chronic venous disease (CVD) encompasses a set of disorders of the venous system that have a high prevalence in Western societies and are associated with significant sociohealth costs. Pregnancy is a period in which different hormonal and haemodynamic changes occur that lead to significant changes in the cardiovascular system, increasing the risk of developing venous problems, especially during the third trimester of gestation. In turn, CVD involves a series of local and systemic alterations that can have negative repercussions in pregnancy. In this context, the role of oxidative stress in the pathophysiology of this condition has been shown to significantly affect other vascular structures during pregnancy, such as the placenta. However, the effects of oxidative stress on the umbilical cord in women with CVD have not yet been fully elucidated. Thus, the objective of this study was to analyse the gene and protein expression of the enzymes NOX-1, NOX-2 and iNOS, which are involved in the production of reactive oxygen and nitrogen species, respectively. Similarly, the presence of hypoxia-inducible factor 1-alpha (HIF-1α) in the umbilical cord in women with CVD was compared to that of pregnant control women, and the levels of the lipid peroxidation marker malonyldialdehyde (MDA) in cord tissue and blood was also analysed. Our results support a significant increase in the enzymes NOX-1, NOX-2 and iNOS and HIF-1α and MDA in the umbilical cord tissue and blood of women with CVD. For the first time, our work demonstrates an increase in oxidative stress and cellular damage in the umbilical cords of pregnant women who develop this condition, deepening the understanding of the consequences of CVD during pregnancy.Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEUnión EuropeaComunidad de MadridInstituto de Salud Carlos IIIHalekulanipu

Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-kappa B response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level

3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine

The current study reports on the manufacturing by rapid prototyping technique of three-dimensional (3D) scaffolds based on silicon substituted hydroxyapatite with Elastin-like Recombinamers (ELRs) functionalized surfaces. Silicon doped hydroxyapatite (Si-HA), with Ca-10(PO4)(5.7)(SiO4)(0.3)(OH)(1.7)h(0.3) nominal formula, was surface functionalized with two different types of polymers designed by genetic engineering: ELR-RGD that contain cell attachment specific sequences and ELR-SNA15/RGD with both hydroxyapatite and cells domains that interact with the inorganic phase and with the cells, respectively. These hybrid materials were subjected to in vitro assays in order to clarify if the ELRs coating improved the well-known biocompatible and bone regeneration properties of calcium phosphates materials. The in vitro tests showed that there was a total and homogeneous colonization of the 3D scaffolds by Bone marrow Mesenchymal Stromal Cells (BMSCs). In addition, the BMSCs were viable and able to proliferate and differentiate into osteoblasts. Statement of Significance Bone tissue engineering is an area of increasing interest because its main applications are directly related to the rising life expectancy of the population, which promotes higher rates of several bone pathologies, so innovative strategies are needed for bone tissue regeneration therapies. Here we use the rapid prototyping technology to allow moulding ceramic 3D scaffolds and we use different bio-polymers for the functionalization of their surfaces in order to enhance the biological response. Combining the ceramic material (silicon doped hydroxyapatite, Si-HA) and the Elastin like Recombinamers (ELRs) polymers with the presence of the integrin-mediate adhesion domain alone or in combination with SNAI 5 peptide that possess high affinity for hydroxyapatite, provided an improved Bone marrow Mesenchymal Stromal Cells (BMSCs) differentiation into osteoblastic linkage. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Women with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes

y. Psychosis is a hazardous and functionally disruptive psychiatric condition which may affect women in pregnancy, entailing negative consequences for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in pregnancy remain to be further elucidated. The placenta is a pivotal tissue with many functions in the gestational period, critically influencing the fate and development of pregnancy. Although detrimental alterations have been observed in women undergoing severe psychiatric disorders in pregnancy, there are little studies evaluating the consequences of suffering from a psychotic episode in the placental tissue In this work, we have evaluated the histopathological consequences of a first episode of psychosis in pregnancy (FE-PW; N=22) and compare them with healthy pregnant women (HC-PW; N=20) by using histological, immunohistochemical and gene expression techniques. Our results define that the placental tissue of FE-PW display an increase in the number of placental villi, bridges, syncytial knots and syncytial knots/villi. Besides, we have also observed an enhanced gene and protein expression in FE-PW of the hypoxic marker HIF-1α, together with the apoptotic markers BAX and Bcl-2. To our knowledge, this is the first study demonstrating significant histopathological changes in the placenta of women suffering a new-onset psychotic episode in pregnancy. Further studies should be aimed at deepening the knowledge about the pernicious effects of psychosis in the maternofetal tissues, as well as the potential implications of these alterations

The Use of Prebiotics from Pregnancy and Its Complications: Health for Mother and Offspring—A Narrative Review

Pregnancy involves a metabolic reprogramming that includes changes in the gut microbiota composition in women. Evidence shows that maternal dysbiosis is linked to neonatal dysbiosis, and this factor can determine health status in adulthood. Although there is little literature available on this topic, high heterogeneity is a limitation when examining nutritional interventions. Information has been gathered to contrast the benefits of prebiotic usage, specifically in pregnancy, in its possible complications and in newborns’ gut microbiota development. The objective pursued in this brief narrative review is to provide a clear summary of relevant content when searching with regard to the use of prebiotics in pregnancy, the effects in prenatal and postnatal periods, and to help in clinical decision-making in pregnancy management and lactation. A search has found that the nutritional status of the pregnant mother is key for the earliest microbial colonization in newborns, and thus intervention programs from pregnancy could assure better outcomes in both the mother and offspring. In this sense, prebiotics (administered to mothers who breastfeed or provided in formula milk) are feasible and cost-effective elements that can prevent allergies, colic, and other maladies in newborn