RNA-Templated Peptide Bond Formation Promotes L-Homochirality.

The world in which we live is homochiral. The ribose units that form the backbone of DNA and RNA are all D-configured and the encoded amino acids that comprise the proteins of all living species feature an all-L-configuration at the α-carbon atoms. The homochirality of α-amino acids is essential for folding of the peptides into well-defined and functional 3D structures and the homochirality of D-ribose is crucial for helix formation and base-pairing. The question of why nature uses only encoded L-α-amino acids is not understood. Herein, we show that an RNA-peptide world, in which peptides grow on RNAs constructed from D-ribose, leads to the self-selection of homo-L-peptides, which provides a possible explanation for the homo-D-ribose and homo-L-amino acid combination seen in nature.

Loading of Amino Acids onto RNA in a Putative RNA-Peptide World.

RNA is a molecule that can both store genetic information and perform catalytic reactions. This observed dualism places RNA into the limelight of concepts about the origin of life. The RNA world concept argues that life started from self-replicating RNA molecules, which evolved toward increasingly complex structures. Recently, we demonstrated that RNA, with the help of conserved non-canonical nucleosides, which are also putative relics of an early RNA world, had the ability to grow peptides covalently connected to RNA nucleobases, creating RNA-peptide chimeras. It is conceivable that such molecules, which combined the information-coding properties of RNA with the catalytic potential of amino acid side chains, were once the structures from which life emerged. Herein, we report prebiotic chemistry that enabled the loading of both nucleosides and RNAs with amino acids as the first step toward RNA-based peptide synthesis in a putative RNA-peptide world.

Diseño de un Programa Virtual en Archivística e Inteligencia de Negocios para la Universidad de La Salle, Bogotá-Colombia / Design of a Virtual Program in Archiving and Business Intelligence for Universidad de La Salle, Bogotá, Colombia

Se presenta la propuesta de diseño de un Programa Virtual en Archivística e Inteligencia de Negocios para la Universidad de La Salle, de Bogotá-Colombia. Dicha propuesta se asume como un ejercicio curricular disruptivo, debido a que se pretende generar articulaciones entre los conocimientos y las prácticas típicamente archivísticas-informacionales-organizacionales con el conocimiento, métodos y técnicas de la inteligencia de negocios y, con ello, formar un profesional desde un enfoque que potencie el carácter estratégico de la toma de decisiones en todo tipo de instituciones, en conexión con las necesidades socio-productivas. La comparación de programas de pregrado, el análisis de tendencias conceptuales y metódicas de ambos campos, la caracterización de la demanda académico-profesional para la modalidad virtual y los criterios técnico-curriculares-normativos del Ministerio de Educación Nacional de Colombia, así como los lineamientos de la Universidad de La Salle fueron los elementos sustantivos de la metodología. Los principales resultados se traducen en el perfil profesional por competencias, resultados de aprendizaje, plan de estudios y aspectos de la gestión curricular del programa que se propone. Como conclusión se enfatiza en lo disruptivo como el elemento transversal que debe guiar el diseño y planeación de programas académicos en Ciencias de la Información, los cuales deben ofrecer alternativas que estén en sintonía con las demandas sociales, configuradas a partir de las transformaciones producidas por las tecnologías digitales, en articulación con procesos analíticos de alto valor agregado en las organizaciones(AU)

A design proposal of Virtual Program in Archiving and Business Intelligence is presented for Universidad de La Salle, in Bogotá, Colombia. Said proposal is assumed as a disruptive curricular exercise, since it is intended to generate articulations between typically archival-informational-organizational knowledge and practices with the knowledge, methods and techniques of business intelligence and, with this, training a professional from an approach that enhances the strategic nature of decision-making in all kinds of institutions, in connection with socio-productive needs. The comparison of undergraduate programs, the analysis of conceptual and methodical trends of both fields, the characterization of the academic-professional demand for the virtual modality and the technical-curricular-regulatory criteria of Colombia National Ministry of Education, as well as the guidelines from the Universidad de La Salle were the major methodological elements. The main results are translated into the professional profile by competencies, learning outcomes, study plan and aspects of the curricular management of the proposed program. In conclusion, disruption is emphasized as the transversal element that must guide designing and planning academic programs in Information Sciences, which must offer alternatives that are in tune with social demands, shaped from the transformations produced by the digital technologies, in coordination with analytical processes of high added value in organizations(AU)

A prebiotically plausible scenario of an RNA-peptide world.

The RNA world concept1 is one of the most fundamental pillars of the origin of life theory2-4. It predicts that life evolved from increasingly complex self-replicating RNA molecules1,2,4. The question of how this RNA world then advanced to the next stage, in which proteins became the catalysts of life and RNA reduced its function predominantly to information storage, is one of the most mysterious chicken-and-egg conundrums in evolution3-5. Here we show that non-canonical RNA bases, which are found today in transfer and ribosomal RNAs6,7, and which are considered to be relics of the RNA world8-12, are able to establish peptide synthesis directly on RNA. The discovered chemistry creates complex peptide-decorated RNA chimeric molecules, which suggests the early existence of an RNA-peptide world13 from which ribosomal peptide synthesis14 may have emerged15,16. The ability to grow peptides on RNA with the help of non-canonical vestige nucleosides offers the possibility of an early co-evolution of covalently connected RNAs and peptides13,17,18, which then could have dissociated at a higher level of sophistication to create the dualistic nucleic acid-protein world that is the hallmark of all life on Earth.

Percepción de la salud por adultos mayores que realizan actividad física en un parque público de Cali, Colombia / Perception of health by older adults who perform physical activity in a public park in Cali, Colombia / Percepção da saúde pelos idosos que realizam atividade física num parque público em Cali, Colômbia

Resumen Objetivo: Comprender la percepción que sobre la salud tienen los adultos mayores que realizan actividad física en un parque público de Cali, Colombia. Metodología: Se llevó a cabo un estudio de caso cualitativo, con enfoque fenomenológico. El grupo de estudio estuvo conformado por siete adultos que realizan actividad física en el parque, seleccionados por muestreo propositivo por conveniencia. La técnica utilizada fue la entrevista en profundidad. Resultados: Se encontró que la percepción que sobre la salud tienen los adultos mayores es positiva y está relacionada con la independencia, la autonomía, el poder valerse por sí mismos, sentirse útiles y relacionarse con otras personas. Conclusión: La actividad física es utilizada por el adulto mayor para conservar la salud y como un pretexto para interactuar con sus pares, utilizar el tiempo libre y desarrollar tareas en pro de su comunidad

Abstract Objective: To understand the perception of health by older adults who perform physical activity in a public park in Cali, Colombia. Methodology: A qualitative case study was carried out with a phenomenological approach. The study group was made up of seven adults who perform physical activity in the park, selected by convenience and purposeful sampling. The technique used was the in-depth interview. Results: It was found that the perception that older adults have about health is positive and is related to independence, autonomy, being able to fend for themselves, feeling useful, and interacting with other people. Conclusion: Physical activity is used by the elderly to maintain health and as a pretext to interact with their peers, use their free time, and undertake tasks in favor of their community.

Resumo Objetivo: Compreender a percepção que os idosos que realizam atividade física num parque público em Cali, Colômbia, têm sobre a saúde. Metodologia: Foi realizada uma pesquisa qualitativa com análise fenomenológica. O grupo de estudo foi formado por sete adultos que realizam atividade física no parque, selecionados por amostragem propositiva por conveniência. A técnica utilizada foi entrevista em profundidade. Resultados: Encontrou-se que a percepção que os idosos têm sobre a saúde é positiva e está relacionada com a independência, a autonomia, o poder de se defenderem por si mesmos, sentirem-se úteis e relacionar-se com outras pessoas. Conclusão: A atividade física é usada pelo idoso para conservar a saúde e como um pretexto para interagir com seus pares, utilizar o tempo livre e desenvolver tarefas em prol da sua comunidade.

Caracterización epidemiológica de pacientes con miopatía inflamatoria en un hospital de cuarto nivel en Cali, Colombia / Epidemiological characterization of patients with inflammatory myopathy in a fourth level hospital in Cali, Colombia

Introducción: Las miopatías inflamatorias idiopáticas (MII) constituyen un grupo heterogéneo de enfermedades que comprometen la musculatura esquelética y se manifiestan por debilidad y signos inflamatorios en la biopsia muscular. El objetivo de este estudio es hacer una caracterización epidemiológica de una cohorte de pacientes con MII en una población del suroccidente colombiano. Metodología: De forma retrospectiva, se revisaron las historias clínicas de pacientes con diagnóstico de MII que fueron tratados en un hospital de cuarto nivel de complejidad en Cali, Colombia, entre el 2011 y el 2017. Se recolectaron variables demográficas, clínicas, serológicas y de tratamiento. Resultados: Se identificaron 72 pacientes con MII, mayoritariamente mujeres (n = 54, 75%). La media de edad al inicio de los síntomas fue de 37,11 ± 19,18 años. Las principales MII fueron dermatomiositis (DM) y polimiositis, las cuales se presentaron en 35 (48,6%) y 25 pacientes (34,7%), respectivamente. Veintiocho pacientes (38,8%) presentaban enfermedad autoinmune asociada, siendo el lupus eritematoso sistémico la más frecuente, al presentarse en7 (9,72%) pacientes. La biopsia de músculo se realizó en 25 pacientes (34,7%), mientras que28 (38,8%) tenían anticuerpos antinucleares positivos. La mediana de la creatinfosfoquinasa fue de 877,5 mg/dL (163,5-4.358,3). Sesenta y siete pacientes (93,1%) fueron tratados con glucocorticoides y 18 (25%) con rituximab (RTX) como monoterapia o combinado con otro fármaco inmunosupresor. Conclusiones: La DM es la condición clínica más frecuente, es común en mujeres y se presenta en la cuarta década de vida. Los tratamientos con los que más se obtuvo mejoría clínica fueron los glucocorticoides, seguidos del RTX en monoterapia o combinado con otros inmunosupresores.

Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases characterised by skeletal muscle involvement, manifested by weakness and inflammatory signs in the muscle biopsy. The objective of this article is to describe the clinical, laboratory, and treatment features of a cohort of patients with IIM in southwest Colombia. Methods: A retrospective review was conducted on the medical records of patients diagnosed with IIM treated at a fourth-level complexity hospital in Cali, Colombia, from 2011 to 2017. Demographic, clinical, serological, and treatment data were collected. Results: A total of 72 patients with IIM were identified, mostly women (n = 54,75%). The mean age at onset of symptoms was 37.11 ± 19.18 years. The main subtypes of IIM were dermatomyositis (DM) and polymyositis, occurring in 35 patients (48.6%) and 25 patients (34.7%), respectively. Twenty-eight patients (38.8%) had associated autoimmune disease, with syste mic lupus erythematosus being the most frequent in 7 (9.72%) patients. Muscle biopsy was performed in 25 patients (34.7%), while 28 (38.8%) had positive antinuclear antibodies. The median creatine phosphokinase was 877.5 mg/dL (163.5-4358.3). Sixty-seven patients (93.1%) were treated with glucocorticoids, and 18 (25%) patients were treated with rituximab (RTX) as monotherapy or combined with another immunosuppressant drug. Conclusions: DM is the most frequent subtype of IIM, being common in women and occurring in the fourth decade of life. The most used treatments were glucocorticoids, followed by RTX monotherapy, or combined with other immunosuppressants.

Fijación percutánea para manejo de dedo en martillo. Estudio de Corte Transversal / Percutaneous internal fixation for mallet finger injuries. Cross-sectional study

Introducción El movimiento de los dedos es dado por un complejo mecanismo que combina tanto extensión como flexión. La alteración del mecanismo extensor en la zona descrita como I, produce una deformidad del dedo conocida como dedo en martillo. El cual puede tener manejo conservador o inclusive quirúrgico cuando está indicado. Materiales y Métodos Estudio observacional descriptivo de tipo corte transversal retrospectivo de pacientes intervenidos por lesión de dedo en martillo en la mano entre junio de 2017 y enero de 2018, operados por cirujanos del módulo de mano a partir de la técnica quirúrgica percutánea con pin transóseo. Resultados Con un total de 48 de pacientes, el 81,25% de los casos fueron hombres, entre los 31 y los 55 años, en su gran mayoría diestros, con mayor frecuencia de lesión de la mano derecha y en el 41,67% de los casos con compromiso del segundo dedo, seguido del tercer dedo (39,58%), secundario a un trauma contuso. Adicionalmente se reportó complicaciones en 2 pacientes (4,16%). Discusión El dedo en martillo es una lesión en su mayoría secundaria a un trauma contuso, de predominio en hombres y de la mano dominante, la cual puede recibir manejo conservador a partir del uso de una férula tipo stack o quirúrgico. Los resultados reportados en el presente estudio siguen los datos descritos por la literatura internacional, encontrándose de forma adicional, la presentación de múltiples comorbilidades y siendo rara la incidencia de la lesión en poblaciones jóvenes. La población atendida presenta características demográficas y relacionadas a la lesión similares a las reportadas en la literatura internacional.

Background The movement of the fingers is given by a complex mechanism that combines both extension and flexion. The alteration of the extensor mechanism at distal interphalangeal joint of the finger is known as mallet finger. Mallet finger can be managed either surgically or not surgically with external splints. Materials and methods A retrospective cross-sectional descriptive observational study was performed including patients diagnosed with mallet finger injury between June 2017 and January 2018 surgically treated with percutaneous internal fixation surgical technique using a transosseous pin. Results A total of 48 patients were included, 81.25% of the cases were men, between 31 and 55 years old, the vast majority right-handed, with a higher frequency of injury to the right hand. 41.67% of cases involved the second finger, followed by the third finger (39.58%), secondary to a blunt trauma. Additionally, complications were reported in 2 patients (4.16%). Discussion Mallet finger is an injury mostly secondary to a blunt trauma, predominantly in men and of the dominant hand, which can receive conservative management from the use of a stack-type or surgical splint. The results reported in the present study follow the data described in the international literature, additionally finding the presentation of multiple comorbidities and the incidence of injury in young populations being rare. The population treated presents demographic and injury-related characteristics similar to those reported in the international literature.

Novel fibronectin mutations and expansion of the phenotype in spondylometaphyseal dysplasia with "corner fractures".

Heterozygous pathogenic variants in the FN1 gene, encoding fibronectin (FN), have recently been shown to be associated with a skeletal disorder in some individuals affected by spondylometaphyseal dysplasia with "corner fractures" (SMD-CF). The most striking feature characterizing SMD-CF is irregularly shaped metaphyses giving the appearance of "corner fractures". An array of secondary features, including developmental coxa vara, ovoid vertebral bodies and severe scoliosis, may also be present. FN is an important extracellular matrix component for bone and cartilage development. Here we report five patients affected by this subtype of SMD-CF caused by five novel FN1 missense mutations: p.Cys123Tyr, p.Cys169Tyr, p.Cys213Tyr, p.Cys231Trp and p.Cys258Tyr. All individuals shared a substitution of a cysteine residue, disrupting disulfide bonds in the FN type-I assembly domains located in the N-terminal assembly region. The abnormal metaphyseal ossification and "corner fracture" appearances were the most remarkable clinical feature in these patients. In addition, generalized skeletal fragility with low-trauma bilateral femoral fractures was identified in one patient. Interestingly, the distal femoral changes in this patient healed with skeletal maturation. Our report expands the phenotypic and genetic spectrum of the FN1-related SMD-CF and emphasizes the importance of FN in bone formation and possibly also in the maintenance of bone strength.

Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration Manifesting as Acute Cerebellitis with Posterior Cranial Fossa Hypertension.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a rare complication of some malignant cancers. It is most commonly described in women with gynecologic or breast malignancies; however, there have been reports in other types of cancers. Symptoms include ataxia, dysarthria, and tremors, which could be the first manifestations of an underlying malignancy. CASE DESCRIPTION: A 50-year-old woman had an acute PCD with anti-Yo antibodies from an underlying breast invasive ductal carcinoma. She presented with intracranial hypertension in the posterior cranial fossa that required an emergent decompressive craniectomy. CONCLUSIONS: PCD is an uncommon disease that may manifest initially as posterior cranial fossa hypertension and subsequent acute hydrocephalus owing to diffuse cerebellar swelling. To our knowledge, this is the first described case of an anti-Yo PCD that has manifested as acute posterior cranial fossa hypertension owing to diffuse cerebellar edema. Early diagnosis and treatment should be pursued to improve long-term outcomes.

Incidental finding of persistent left superior vena cava after 'bubble study' verification of central venous catheter.

We report a case of a patient with septic shock who underwent central venous catheter placement in the left internal jugular vein, and a bedside ultrasound 'bubble study' revealed venous cannulation. A chest X-ray postprocedure revealed concern for arterial system catheterisation. However, the possibility of a persistent left superior vena cava was discussed and confirmed with a formal transthoracic echocardiogram and CT. This case demonstrates the importance of ultrasound-guided visualisation of anatomical structures in real time during central venous catheterisation. Other similar cases from the literature are briefly described.

Distribución de Aedes aegypti y Aedes albopictus en Guatemala 2016 / Distribution of Aedes aegypti and Aedes albopictus in Guatemala 2016

Los recientes brotes de zika y chikungunya en Guatemala, y el continuo padecimiento de dengue, hacen necesario generar preguntas respecto a la presencia de los vectores de arbovirus, Aedes aegypti y A. albopictus, en este país. Los reportes publicados previamente, señalan la presencia de estos vectores en cuatro departamentos de Guatemala. El objetivo de este estudio fue actualizar los reportes de A. aegypti y A. albopictus en Guatemala para informar con datos robustos a las agencias de salud. Se utilizaron datos del Programa de Enfermedades Transmitidas por Vectores del Ministerio de Salud Pública y Asistencia Social, que contiene principalmente información sobre la presencia de estadios larvales de los vectores. Los sitios de colecta de los mosquitos fueron validados usando herramientas de Sistemas de Información Geográfica, generando mapas de distribución de ambas especies de vectores en todo el país. Los resultados incluyen la presencia de A. aegypti en 21 departamentos y A. albopictus en 11. Aedes aegypti fue reportado en zonas bajas con tolerancias a altas temperaturas (32.3-34.8°C), mientras A. albopictus se reportó en zonas con mayor precipitación y en mayores altitudes (2,301 m). Se concluye en un notable incremento en la distribución de estas dos especies en Guatemala, basados en los informes del primer trimestre 2016 del Programa de Enfermedades Transmitidas por Vectores colectados en época seca. Se discuten la oportunidad de integrar a la academia con los programas actuales de vigilancia epidemiológica para abordar las necesidades de investigación de estos vectores a nivel nacional.

Recent outbreaks of zika and chikungunya in Guatemala, and the continued burden of dengue, make necessary to generate novel questions regarding the presence of arboviruses vectors, Aedes aegypti and A. albopictus, in this country. Reports published before this manuscript, indicated the presence of these vectors in four departments of Guatemala. The aim of this study was to update the reports of A. aegypti and A. albopictus in Guatemala to better inform health agencies. We used data from the Programa de Enfermedades Transmitidas por Vectores, which mainly contains information about the presence of larval stages of vectors. Sites of mosquito collection were validated using geographic information systems tools, generating maps of both vector species' occurrence across the country. The results include A. aegypti presence in 21 departments and A. albopictus in 11. Aedes aegypti was reported in lowlands with high temperature tolerance, while A. albopictus was reported in drier zones and in higher altitudes (2,301 m). We conclude a notable increase in the distribution of these two species in Guatemala, based on the reports of the first quarter of 2016 of the Program of Vector-borne Diseases collected during the dry season. We discuss the opportunity to integrate the academy with epidemiological surveillance programs to address theresearch needs of these vectors at the national level

Vegetation loss and the 2016 Oropouche fever outbreak in Peru

BACKGROUND Oropouche virus causes Oropouche fever, an arboviral disease transmitted mainly by midges of the genus Culicoides and Culex mosquitoes. Clinical presentation of Oropouche fever in humans includes fever, headache, rash, myalgia, and in rare cases spontaneous bleeding and aseptic meningitis. Landscape change has been proposed as a driver of Oropouche fever emergence. OBJECTIVE To investigate the landscape epidemiology of the Oropouche fever outbreak that began in April 2016 in Cusco, Peru. METHODS We used information of vegetation and multivariate spatial analyses including ecological niche modeling. Vegetation was characterised using16-day composite enhanced vegetation index (EVI) images at 500 m spatial resolution from the MODIS sensor carried by the Terra satellite. FINDINGS Cases were distributed across seven Peruvian districts in two provinces. La Concepcion was the province with most of the affected districts. EVI time series across 2000 to 2016 suggested a decline in the vegetation in sites with Oropouche fever cases before the epidemic. Our ecological niche modeling suggests that other areas in Junin, Apurimac, and Madre de Dios departments are at risk of Oropouche fever occurrence. MAIN CONCLUSIONS Our results may provide a guide for future fieldwork to test hypotheses regarding Oropouche fever emergence and habitat loss in tropical Latin America.

Posibles efectos adversos oculares de los bifosfonatos. Reporte de 2 casos / Possible ocular adverse effects attributable to bisphosphonate therapy: Two case reports

RESUMEN Los bifosfonatos se utilizan para el manejo de enfermedades con incremento de la resorción ósea como la osteoporosis, la enfermedad metastásica ósea y la hipercalcemia maligna, entre otras patologías. En los últimos años se ha reportado que el uso de bifosfonatos intravenosos como el zoledronato y el pamidronato pueden generar efectos adversos oculares, ocasionados por una reacción de fase aguda mediada por la interleucina-6 (IL-6) y factor de necrosis tumoral alfa (TNF-a). Se reportan 2 casos (una mujer de 71 años y un hombre de 67 años) que entre las 24 a 72 h después de recibir terapia con zoledronato presentaron una uveítis anterior.

ABSTRACT Bisphosphonates are used in the management of diseases characterized by an increase in bone resorption such as osteoporosis, metatasic bone disease, malignant hypercalcemia among others. It has been reported that the use of IV bisphosphonates as zoledronate and pamidronate generate ocular adverse effects by an acute phase reaction mediated by an increase of interleukin 6 (IL-6) and tumoral necrosis factor (TNF-a). We present 2 cases, a woman 71 years old and a 67 years old man that received therapy with bisphosphonates and 24 to 72hours later they presented an anterior uveitis.

Fatal respiratory disease due to a homozygous intronic ABCA3 mutation: a case report.

BACKGROUND: Pulmonary surfactant is a complex mixture of lipids and proteins. Mutations in surfactant protein-C, surfactant protein-D, and adenosine triphosphate-binding cassette subfamily A member 3 have been related to surfactant dysfunction and neonatal respiratory failure in full-term babies. Adenosine triphosphate-binding cassette subfamily A member 3 facilitates the transfer of lipids to lamellar bodies. We report the case of patient with a homozygous intronic ABCA3 mutation. CASE PRESENTATION: We describe a newborn full-term Colombian baby boy who was the son of non-consanguineous parents of mixed race ancestry (Mestizo), who was delivered with severe respiratory depression. Invasive treatment was unsuccessful and diagnosis was uncertain. Exons 4 and 5 of the SP-C gene showed heterozygous Thr138Asn polymorphism and homozygous Asn186Asn polymorphism respectively. At intron 25 at position -98 from exon 26 a homozygous C>T transition mutation was detected in ABCA3 gene. CONCLUSIONS: The clinical presentation and the histopathological findings of this case are consistent with a case of neonatal respiratory failure due to surfactant deficiency. Analysis of the five coding SP-C exons does not support surfactant deficiency. An analysis of the mutation IVS25-98 T was performed and a homozygous mutation responsible for our case's neonatal respiratory failure was detected. The findings suggest an autosomic recessive pattern of inheritance. Genetic counseling was provided and the relatives are now informed of the recurrence risks and treatment options.

A second family with CATSHL syndrome: Confirmatory report of another unique FGFR3 syndrome.

Here we describe the second reported family with the CATSHL syndrome, a condition resulting from a unique mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. Our family confirms the consistent and unique phenotype of this condition, and the specificity of the mutation in FGFR3. The CATSHL syndrome appears to be an autosomal dominant disorder with full penetrance. © 2016 Wiley Periodicals, Inc.

Pre-existing and Postoperative Intimal Hyperplasia and Arteriovenous Fistula Outcomes.

BACKGROUND: The contribution of intimal hyperplasia (IH) to arteriovenous fistula (AVF) failure is uncertain. This observational study assessed the relationship between pre-existing, postoperative, and change in IH over time and AVF outcomes. STUDY DESIGN: Prospective cohort study with longitudinal assessment of IH at the time of AVF creation (pre-existing) and transposition (postoperative). Patients were followed up for up to 3.3 years. SETTING & PARTICIPANTS: 96 patients from a single center who underwent AVF surgery initially planned as a 2-stage procedure. Veins and AVF samples were collected from 66 and 86 patients, respectively. Matched-pair tissues were available from 56 of these patients. PREDICTORS: Pre-existing, postoperative, and change in IH over time. OUTCOMES: Anatomic maturation failure was defined as an AVF that never reached a diameter > 6mm. Primary unassisted patency was defined as the time elapsed from the second-stage surgery to the first intervention. MEASUREMENTS: Maximal intimal thickness in veins and AVFs and change in intimal thickness over time. RESULTS: Pre-existing IH (>0.05mm) was present in 98% of patients. In this group, the median intimal thickness increased 4.40-fold (IQR, 2.17- to 4.94-fold) between AVF creation and transposition. However, this change was not associated with pre-existing thickness (r(2)=0.002; P=0.7). Ten of 96 (10%) AVFs never achieved maturation, whereas 70% of vascular accesses remained patent at the end of the observational period. Postoperative IH was not associated with anatomic maturation failure using univariate logistic regression. Pre-existing, postoperative, and change in IH over time had no effects on primary unassisted patency. LIMITATIONS: The small number of patients from whom longitudinal tissue samples were available and low incidence of anatomic maturation failure, which decreased the statistical power to find associations between end points and IH. CONCLUSIONS: Pre-existing, postoperative, and change in IH over time were not associated with 2-stage AVF outcomes.

Oxidative stress induces early-onset apoptosis of vascular smooth muscle cells and neointima formation in response to injury.

The present study dissects the mechanisms underlying the rapid onset of apoptosis that precedes post injury vascular remodelling. Using the rat balloon injury model, we demonstrated that a significant number of arterial vascular smooth muscle cells (VSMC) undergo apoptosis at 90 min after the procedure. This apoptotic wave caused significant loss in media cellularity (>90%) over the next 3 h and was accompanied by a marked accumulation of oxidative stress by-products in the vascular wall. Early apoptotic VSMC were rich in p38 mitogen-activated protein kinase (MAPK) and the transcription factor c-Jun and secreted IL-6 and GRO/KC into the milieu as determined using multiplex bead assays. Neointima thickness increased steadily starting on day 3 as a result of pronounced repopulation of the media. A second apoptotic wave that was detected at 14 days after injury affected mostly the neointima and was insufficient to control hyperplasia. Suppression of reactive oxygen species (ROS) production using either the NAD(P)H oxidase inhibitor VAS2870 or pegylated superoxide dismutase (PEG-SOD) significantly decreased the number of apoptotic cells during the first apoptotic wave and showed a trend towards reduction in the neointima-to-media thickness ratio at 30 days post injury. These results indicate that oxidative stress in response to injury induces early-onset apoptosis of VSMC through the activation of redox-sensible MAPK pro-apoptotic pathways. This remodelling process leads to the local accumulation of inflammatory cytokines and repopulation of the media, which ultimately contribute to neointima formation.