Role of lymphocyte co-stimulation pathways and extracellular vesicles in cardiovascular damage of chronic uremic patients and new therapeutic strategies

Introduction: Chronic kidney disease (CKD) is characterized by high cardiovascular (CV) risk and the RISCAVID study identified a correlation between CV risk and blood levels of sCD40L in uremia. Moreover, sCD40L correlates with osteoblastic differentiation of vascular smooth muscle cells (VSMC) and endothelial cells (EC) inflammation. In addition, CKD-related extracellular vesicles (EVs) express CD40L and polymethylmethacrylate (PMMA) dialyzer could reduce not only uremic toxins as indoxyl sulfate (IS), but also sCD40L and EVs by adsorption. Aim of the study: 1) identify a sCD40L predictive value for major cardiovascular events (MACE) in uremia, 2) assess the sCD40L role, 3) compare the efficacy of PMMA vs polysulfone (PS) in sCD40L and other molecule removal, and 4) perform CKD-EV characterization and analysis of their role CKD vascular damage. Patients and methods: In 201 dialysis patients from 6 Italian dialysis Centers, we assessed sCD40L and MACE during the follow-up. 48 high CV risk patients started 9 months randomized doublecrossover study (treatment with PMMA or PS). We assessed SCD40L and biochemical parameters every 3 months. We evaluated sCD40L/IS mass removal and sCD40L effects on EC and VSMC in vitro. We characterized CKD-EVs and evaluate their role incubating EC and VSMC in vitro. Results: sCD40L cut-off of 7,8 ng/mL was the best predictor of MACE and PMMA was more efficient in reducing hepcidin, sCD40L and IS. PMMA decreased ROS production, monocyte adhesion and osteoblastic differentiation. CKD-EVs expressed CD40L and other inflammation markers, were internalized by EC and VSMC and modulated osteoblastic differentiation. Conclusions: sCD40L predicts MACE in CKD patients and PMMA is able to remove this molecule. sCD40L is not only a marker of CKD-CV damage, but also a mediator of progression. sCD40L and IS reduction could therefore have an impact on CKD-CV risk and CKD-EVs could also be considered true uremic toxins and effective mediators of damage

Prediction of IVF cycle success with antimullerian hormone levels

BACKGROUND: Current estimates indicate approximately 6.7% of women in the US are infertile. Infertility can arise from many different conditions and can be both attributed to male and female factors. In women, measures of ovarian reserve such as AMH level or FSH level on day three of the menstrual cycle can be used to predict reproductive success. In conjunction with additional tests and lifestyle screening, these values help to guide the course of treatment, with some patients moving eventually to in vitro fertilization. In vitro fertilization therapy is cost-prohibitive if the patient does not have insurance coverage, an issue for the majority of patients across the United States. AIMS: To evaluate the correlation between cycle number, age, and AMH level with achieving a successful live birth through a statistical analysis of over 50,000 cycles of in vitro fertilization. Methods: Data was obtained from Practice Highway, a company that owns the electronic medical record (EMR) program eIVF, used by over 140 reproductive endocrinology practices across the country. The database provided a total of 88 variables and 138,526 IVF cycle observations ranging from 01/01/2005 to 09/09/2015. A thorough review of available literature was performed to determine the need for the correlations analyzed in this paper. Utilizing this information in conjunction with the scope of this paper, the number of variables was reduced to four. Linear regression and multivariate regression was performed on the four main study variables to identify possible correlations. Results: The results of our study indicate that there is not a strong correlational relationship between the variables analyzed. There was not a significant correlation between age and whether a live birth was achieved. As expected, the strongest relationship identified through our study is the decrease in AMH as age increases. Conclusions: Our study results indicate that there is no correlation between AMH and live birth, suggesting that this biomarker alone is insufficient to be used by physicians as a means of advising patients on IVF success. Additionally, measures such as number of cycles completed and age at cycle start can be useful when counseling patients on their probability of success with assisted reproductive technologies

Merging 1D and 3D genomic information: Challenges in modelling and validation

Genome organization in eukaryotes during interphase stems from the delicate balance between non-random correlations present in the DNA polynucleotide linear sequence and the physico/chemical reactions which shape continuously the form and structure of DNA and chromatin inside the nucleus of the cell. It is now clear that these mechanisms have a key role in important processes like gene regulation, yet the detailed ways they act simultaneously and, eventually, come to influence each other even across very different length-scales remain largely unexplored. In this paper, we recapitulate some of the main results concerning gene regulatory and physical mechanisms, in relation to the information encoded in the 1D sequence and the 3D folding structure of DNA. In particular, we stress how reciprocal crossfeeding between 1D and 3D models may provide original insight into how these complex processes work and influence each other. This article is part of a Special Issue entitled: Transcriptional Profiles and Regulatory Gene Networks edited by Dr. Dr. Federico Manuel Giorgi and Dr. Shaun Mahony

Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene

Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor agonists or antagonists in a tissue-specific manner. This article reviews lasofoxifene, a new-generation SERM that has completed phase III development for the prevention and treatment of osteoporosis in postmenopausal women. Consistent with preclinical observations, this new SERM demonstrated improved skeletal efficacy over raloxifene and at an oral dose of 0.5 mg/day was effective in the prevention of both vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. At the same dosage, lasofoxifene treatment also reduced estrogen receptor-positive breast cancer risk and the occurrence of vaginal atrophy, but, like the other SERMs, was associated with hot flushes and an increased risk of venous thromboembolic events. With its increased efficacy on the prevention of nonvertebral fractures than current available SERMs and its positive effects on the vagina, this new compound may represent an alternative and cost-effective therapy for osteoporosis in postmenopausal women

Aromatase Activity and Bone Loss in Men

Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen precursors into estrogens. This enzyme is encoded by the CYP19A1 gene located at chromosome 15q21.2, that is, expressed in ovary and testis, but also in many extraglandular sites such as the placenta, brain, adipose tissue, and bone. The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target issues including bone. Importantly, extraglandular aromatization of circulating androgen precursors is the major source of estrogen in men. Clinical and experimental evidences clearly indicate that aromatase activity and estrogen production are necessary for longitudinal bone growth, the attainment of peak bone mass, pubertal growth spurt, epiphyseal closure, and normal bone remodeling in young individuals. Moreover, with aging, individual differences in aromatase activity may significantly affect bone loss and fracture risk in men

Hospitalidad en la dimensión religiosa en la romería Nuestra Señora de Caravaggio, Farroupilha/RS, Brasil

La presente propuesta tiene como objetivo describir algunas acciones que ocurren en la Romería al Santuario Nuestra Señora de Caravaggio en el municipio de Farroupilha/RS, a la luz de la hospitalidad religiosa ofrecida por los sectores de la Iglesia a los peregrinos. El estudio se vale de aparato conceptual acerca de la hospitalidad y religiosidad en el turismo religioso y tiene como referencia básica estudios de Boff, Baptista, Lashley, Grassi, Correia y de documentos de la Iglesia Católica. La investigación es de naturaleza cualitativa y las entrevistas se realizaron con representantes de la Iglesia que actúan o actuaron en el Santuario en el período de la romería. Los cuestionamientos buscan apurar la percepción del concepto de hospitalidad de la Iglesia. Los resultados apuntan a un empeño de la Iglesia en atender la demanda de servicios esenciales y promover y ampliar la dinámica de la hospitalidad. La romería es un fenómeno relevante que desplaza a miles de peregrinos que regresan al lugar anualmente y fortalecen la devoción hacia la Santa, estimulando el turismo religioso.Este artigo tem como objetivo descrever algumas ações que ocorrem na romaria ao Santuário Nossa Senhora de Caravaggio no município de Farroupilha, RS, à luz da hospitalidade religiosa oferecida pelos membros da Igreja aos peregrinos. O estudo vale-se de aparato conceitual acerca da hospitalidade e religiosidade no turismo religioso e tem como referência básica os estudos de Boff, Baptista, Lashley, Grassi, Correia e de documentos da Igreja Católica. A pesquisa é de natureza qualitativa e suas entrevistas foram realizadas com representantes da Igreja que atuam ou atuaram no santuário no período da romaria. Os questionamentos buscam apurar a percepção do conceito de hospitalidade da Igreja. Os resultados apontam para um empenho da Igreja em atender a demanda de serviços essenciais e promover e ampliar a dinâmica da hospitalidade. A romaria é um fenômeno relevante que desloca milhares de peregrinos que retornam ao local anualmente e fortalecem a devoção em relação à Santa, estimulando o turismo religioso.This proposal is intended to describe some actions that take place during the Pilgrimage to the Shrine of Our Lady of Caravaggio, in the town of Farroupilha, RS, in the light of the religious hospitality that is offered to pilgrims by sectors of the Church. The study uses the conceptual apparatus of hospitality and religiosity in religious tourism, whose basic reference sources are the studies of Boff, Baptista, Lashley, Grassi, Correia and documents of the Catholic Church. The research is qualitative and the interviews have been conducted with representatives of the Church, who work or used to work in the Shrine during the pilgrimage. The questions seek to determine what the perception of the concept Church hospitality is. The results indicate that the Church is committed to meeting the demands for essential services, in addition to promoting and expanding the dynamics of hospitality. The pilgrimage is a relevant phenomenon that draws thousands of pilgrims who return to the site every year, thus strengthening the devotion to the Saint and stimulating religious tourism

Um Novo Lenho Gimnospérmico da Formação Rio Bonito, SC, Brasil - Aterradoxylon solidum gen. et sp.nov.

The morphoanatomic study of a taphoflora from the Rio Bonito Formation, Pouso Redondo County, Santa Catarina State, Brazil, resulted in the determination of new gymnospermous genera, among them a fossil wood that, by being represented by 9 of the 25 samples studied, constitutes the second form with significant representation in the assemblage (36%). By virtue of the solid and heterocelular pith, the centrifugal differentiation of the primary vascular system and the large pits in the cross-field of the secondary vascular system, the wood in question is similar to the morfogenus Megaporoxylon KRÄUSEL, 1956 from the Permian of South Africa. However, the presence of singular characters, like the nature of the secretory system and the outline of pith as well as the configuration of the bordered pits on radial walls of the secondary xylem cells, evidences the necessity of its segregation in new taxon which is named Aterradoxylon solidum gen. et sp. nov

Método de estudo paleoanatômico aplicado à taxonomia de lenhos gimnospérmicos gondvânicos (Paleozóico Superior)

The terminology used in the paleoanatomical study of gymnospermous woods, proceeding from Carboniferous and Permian of Gondwana, is characterized by vagueness of criteria regarding the selection of the characteristics of taxonomic value. In this regard, a greater negligence is comparatively emphasized in relation to the pith than the other units that composed the stem and the lack of uniformity in the nomenclature used in primary and secondary xylem paleoanatomy. Such procedures have led to elaboration of incomplete generic and specific descriptions, to the difficulty of comparison between the specimens and, often, to the inadequate taxonomic. Thus, aiming at the definition of the features of taxonomic value and the standardization of terminology, a methodology based on proposition and discussion of the anatomical characteristics of the pith and primary and secondary xylem used to inter-taxa differentiation of the Gondwana gymnospermous woods is presented. Notes about the anatomy of the other units of stem, neighboring the secondary xylem, and illustrations of taxa that exhibit the characters considered are also presented.A terminologia utilizada no estudo paleoanatômico de lenhos gimnospérmicos, oriundos do Carbonífero e Permiano do Gondvana, se caracteriza pela imprecisão de critérios com respeito à seleção das características de valor taxonômico. Neste aspecto, salienta-se ainda maior negligência em relação à medula, do que às outras unidades que compõem o eustelo caulinar, e a ausência de uniformidade nomenclatural na paleoanatomia dos xilemas primário e secundário. Tais procedimentos têm conduzido a elaboração de descrições genéricas e específicas incompletas, a dificuldade na comparação entre os espécimes e, muitas vezes, a um posicionamento taxonômico inadequado dos mesmos. Visando a definição dos aspectos de valor taxonômico e a padronização da terminologia, é aqui apresentada uma metodologia de estudo baseada na proposição e discussão dos caracteres anatômicos dos corpos medular e lenhoso utilizados na diferenciação inter-taxa em lenhos gimnopérmicos gondvânicos. Notas sobre a anatomia das demais unidades do eustelo caulinar, adjacentes ao xilema secundário, e ilustrações dos táxons que exibem os caracteres considerados são também apresentadas

Contramolde medular em conexão orgânica com fragmento lenhoso de Retemedulloxylon da Formação Rio Bonito (Eopermiano da Bacia do Paraná), Santa Catarina, Brasil

This work records the occurrence of a pith cast connected with wood fragment in a fossil assemblage proceeding from Pouso Redondo County, Santa Catarina State, Brazil, in sediments from the Rio Bonito Formation, Eopermian of the Paraná Basin. The pith cast, cylindrical, is highly siliceous and unprovided of diagnosis impressions and tissular vestiges. The fragment, which has a half-cylindrical shape and a concavity along the longitudinal axis, is devoid of primary xylem and reveals a secondary xylem with few defined axial and radial systems. The anatomic characteristics of the secondary wood body indicate taxonomic affinity of the fossil wood with the most representative genus in the assemblage, increasing the establishing of relationships between the pith casts and the gondwanic taxa describe until the present, and suggest that the occurrence of these pith casts in the gondwanic sediments is probably because of environmental influences

Reavaliação taxonômica de lenhos das formações Irati e Serra Alta, Permiano da Bacia do Paraná , Brasil

Based on bibliographic and taxonomic revision of fossil woods from the Upper Permian of Paraná Basin, Brazil, three new combinations, Myelontordoxylon camposii (Mussa), Abietopitys articulata (Dohms) and Paulistoxylon iratiensis (Guerra-Sommer), are proposed and one species, Polysolenoxylon bortoluzzii Guerra, is considered invalid. Except for M. camposii, originated from the levels of Irati Formation in the State of São Paulo, all others came from the Serra Alta Formation in the State of Rio Grande do Sul. Based on the new combinations, amendments to the generic diagnosis of Myelontordoxylon Mussa and Abietopitys Kräusel and to the specific diagnosis of A. articulata (Dohms) are presented.Com base na bibliografia e na revisão taxonômica de lenhos fósseis do Eopermiano da Bacia do Paraná, Brasil, três novas combinações, Myelontordoxy lon camposii (Mussa), Abietopitys  articulata (Dohms) e Paulistoxylon iratiensis (Guerra-Sommer), são propostas e uma espécie, Polysolenoxylon bortoluzzii Guerra, é considerada inválida. Excetuando-se M. camposii, originária da Formação Irati no Estado de São Paulo, todas as demais são provenientes da Formação Serra Alta no Estado do Rio Grande do Sul. Com base nas novas combinações, apresentam-se emendas à diagnose genérica de Myelontordoxylon Mussa e à diagnose específica de A. articulata (Dohms)