Fracture resistance of cement-retained and screw-cement-retained milled posterior crowns with screw-access hole preparations before and after firing: An in vitro study.

STATEMENT OF PROBLEM: When a cement-retained lithium disilicate crown needs to be removed, perforation is needed to reach the abutment screw. How this process affects its strength is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the fracture strength of milled lithium disilicate implant crowns with screw-access holes created before and after the firing stages. MATERIAL AND METHODS: Nine implant replicas with stock abutments were embedded in acrylic resin. Forty-five lithium disilicate (IPS e.max CAD) crowns were designed, milled, and divided into groups. The control group had no screw access, the blue state group had the screw access created in the intermediate phase of the ceramic, and the postfiring group had the screw access created after firing. The crowns were cemented with a self-adhesive resin cement, placed in an incubator for 24 hours and then thermocycled. The screw-access holes were sealed with composite resin. The crowns were loaded to failure with a universal testing machine using a 1- mm-diameter ball at a crosshead speed of 0.5 mm/min and a 5-kN cell load. Data were analyzed by ANOVA and the Tukey post hoc test (α=.05). RESULTS: Screw-access holes created before and after firing stages had a significant effect on the fracture resistance of lithium disilicate crowns (P=.002). No difference in fracture resistance was observed between the control group and the blue state group (P>.05), while the fracture resistance of the postfiring group was significantly lower than that of the control group and the blue state group (P<.05). CONCLUSIONS: The fracture strength of lithium disilicate crowns was not affected by a screw-access hole created during the blue state of the ceramic followed by repair with composite resin. Creating a screw-access hole after firing the ceramic reduced fracture strength.

Pioglitazone increases PGC1-α signaling within chronically ischemic myocardium.

The peroxisome proliferator-activated receptor (PPAR)-γ drug pioglitazone (PIO) has been shown to protect tissue against oxidant stress. In a swine model of chronic myocardial ischemia, we tested whether PIO increases PGC1-α signaling and the expression of mitochondrial antioxidant peptides. Eighteen pigs underwent a thoracotomy with placement of a fixed constrictor around the LAD artery. At 8 weeks, diet was supplemented with either PIO (3 mg/kg) or placebo for 4 weeks. Regional myocardial function and blood flow were determined at the time of the terminal study. PGC1-α expression was quantified from nuclear membranes by gels and respiration, oxidant stress markers and proteomics by iTRAQ were determined from isolated mitochondria. In the chronically ischemic LAD region, wall thickening from the PIO and control groups was 42 ± 6 and 45 ± 5 %, respectively (NS) with no intergroup differences in basal blood flow (0.72 ± 0.04 versus 0.74 ± 0.04 ml/min g, respectively; NS). In the PIO group, the expression of nuclear bound PGC1-α was higher (11.3 ± 2.6 versus 4.4 ± 1.4 AU; P < 0.05) and the content of mitochondrial antioxidant peptides including superoxide dismutase 2, aldose reductase, glutathione S-transferase and thioredoxin reductase were greater than controls. Although isolated mitochondria from the PIO group showed lower state 3 respiration (102 ± 13 versus 161 ± 22 nmol/min mg; P < 0.05), no differences in oxidant stress were noted by protein carbonyl (1.7 ± 0.7 versus 1.1 ± 0.1 nmol/mg). Chronic pioglitazone does not reduce regional myocardial blood flow or function in a swine model of chronic myocardial ischemia, but may have an important role in increasing expression of antioxidant proteins through PGC1-α signaling.

Expression of uncoupling protein-2 remains increased within hibernating myocardium despite successful coronary artery bypass grafting at 4 wk post-revascularization.

BACKGROUND: We have previously shown that mitochondrial uncoupling protein-2 (UCP-2) is increased in a swine model of hibernating myocardium (HM). Although UCP-2 reduces oxidant stress, it can promote inefficiency of the electron transport chain. In this study, we tested whether UCP-2 remains increased in revascularized HM (RHM) after coronary artery bypass grafting (CABG). METHODS: Seven swine underwent thoracotomy with placement of a constrictor on the left anterior descending artery (LAD). Twelve weeks later, a left internal mammary artery graft was placed on the distal LAD. Four weeks post-CABG, computed tomography angiography documented patent grafts and function. At the terminal study, blood flow to the LAD and remote territories were assessed during high dose dobutamine and mitochondria isolated from both regions for analysis. Comparisons were made to a group of swine with HM who underwent constrictor placement without bypass grafting (n = 4). RESULTS: During dobutamine infusion, RHM demonstrated lower blood flows (2.44 ± 0.23 versus 3.43 ± 0.30 mL/min/g; P < 0.05) and reduced wall thickening (33 ± 9% versus 52 ± 13%; P < 0.05) compared with remote regions. RHM had lower respiratory control indices (3.7 ± 0.3 versus 4.3 ± 0.4; P < 0.05) with persistently increased UCP-2 content. CONCLUSIONS: Despite patent grafts, RHM demonstrates a submaximal response to dobutamine infusion and increased mitochondrial UCP-2 expression. These data support the notion that recovery of the mitochondria in RHM is delayed early post-CABG and may contribute to impaired oxygen consumption and contractile reserve during catecholamine challenges.

Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.

Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (P<0.05). Despite reduced regional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport.

Students from a Public School in the South of Chile with Better Physical Fitness Markers Have Higher Performance in Executive Functions Tests-Cross-Sectional Study.

In the past few years, the level of physical fitness in children has decreased globally. According to the SIMCE test carried out in 2015, 45% of 8th year students in Chile were overweight. Moreover, international studies have shown that being overweight is associated with the development of chronic illnesses, negatively affecting cognitive mechanisms and processes. Nevertheless, there is little to no evidence that analyzes the relationship between physical fitness and executive functions in students, at a national level. The aim was to analyze the relationship between cardiorespiratory, musculoskeletal, and motor fitness, and performance in an executive functions test, in students from a public school in the south of Chile. A qualitative, descriptive -correlational, non-experimental, and cross-sectional approach was used. In total, 100 students between 9 and 12 and 11 months of age from a public school in the south of Chile completed the physical fitness assessments through the ALPHA fitness test, and 81 students completed the executive function assessments through the ENFEN test. It was evidenced that students who achieved a longer duration of time and a later stage in the Course Navette test, more centimeters in the standing broad jump (SBJ) test, and a shorter duration in the 4 × 10 shuttle run obtained a better score in the gray trail test. Additionally, students who presented a stronger dominant handgrip scored higher in the colored trail tests. We conclude that students who show a higher level of physical fitness also present a better development of executive functions such as working memory and inhibitory control. In addition, these results suggest physical condition is a factor to consider for better cognitive and school performance.

How to perform the one-step conservative surgery for placenta accreta spectrum move by move.

BACKGROUND: There are 3 treatment options for placenta accreta spectrum: cesarean delivery with hysterectomy, expectant management, and uterine-sparing surgical techniques. One-step conservative surgery is the most extensively described conservative surgical technique, and it has extensive evidence supporting its usefulness; however, few groups apply it, most likely because of the misconception that it is a complex procedure that requires extensive training and is applicable to only a few patients. OBJECTIVE: This study aimed to evaluate the clinical outcomes of patients undergoing one-step conservative surgery in 4 placenta accreta spectrum reference hospitals and provided detailed steps for successfully applying this type of surgery. STUDY DESIGN: This was a multicenter, descriptive, prospective study that described the outcomes of patients with placenta accreta spectrum treated in 4 reference hospitals for this condition. The patients were divided into those managed with one-step conservative surgery and those managed with cesarean delivery and hysterectomy. RESULTS: Overall, 75 patients were included. One-step conservative surgery was possible in 85.3% of placenta accreta spectrum cases (64 patients). Intraoperative staging and placenta accreta spectrum topographic classification allowed for the selection of one-step conservative surgery candidates. The clinical outcomes of the 2 groups were similar, except for the frequency of transfusions (81.8% in the cesarean delivery and hysterectomy group vs 67.2% in the one-step conservative surgery group) and vascular interventions (27.3% in the cesarean delivery and hysterectomy group vs 4.7% in the one-step conservative surgery group), which were both higher in patients who underwent hysterectomy. In addition, the operation time was shorter in the one-step conservative surgery group (164.4 minutes vs 216.5 minutes). CONCLUSION: One-step conservative surgery is a valid procedure in most patients with placenta accreta spectrum. It is an applicable technique even in scenarios with limited resources. However, its safe application requires knowledge of the topographic classification and the application of intraoperative staging.

Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning.

Altered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated during subsequent ischemia. Fourteen pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD artery, each separated by 2 minutes reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by iTRAQ(®) and respiration by an oxygen electrode. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during sustained low-flow ischemia. Compared with SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased expression of UCP-2, Complex IV (cytochrome c oxidase) and Complex V (ATPase) proteins. In comparison with SHAM pigs during in vivo conditions, transmural energetics in SWOP hearts, as estimated by the free energy of ATP hydrolysis (ΔG(0)), were similar at baseline but had decreased by the end of low-flow ischemia (-57.0 ± 2.1 versus -51.1 ± 1.4 kJ/mol; P < 0.05). In conclusion, within isolated mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert with enhanced Complex IV and V proteins, imparts a favorable energetic state during low-flow ischemia. These data support the notion that mitochondrial adaptations that may reduce oxidant damage do not reduce the overall efficiency of energetics during sustained oxygen deprivation.

Association between the Physical Activity Behavioral Profile and Sedentary Time with Subjective Well-Being and Mental Health in Chilean University Students during the COVID-19 Pandemic.

OBJECTIVE: To analyze the association between the behavioral profile of physical activity and sedentary time with subjective well-being and mental health in university students during the COVID-19 pandemic in Chile. METHODS: Cross-sectional study in a voluntary sample of 469 university students (22.4 ± 0.19 years; 66% women). According to students' self-reports of physical activity and sedentary time, four behavioral profiles were created to investigate their association with subjective well-being and mental health using one-factor ANOVA that was adjusted to a multifactorial model. RESULTS: The physically inactive and sedentary behavior profile presents the lowest levels of subjective well-being (p < 0.001), positive affective experiences (p < 0.001) and general mental health (p = 0.001). When adjusting for confounding variables, it was observed that the physically active and non-sedentary profile was associated with better general mental health (p < 0.01) in contrast to those who are physically active and sedentary. CONCLUSIONS: Chilean university students with a physically inactive and sedentary profile during the pandemic presented worse well-being and mental health, with a sedentary lifestyle being one of the variables that most affects the mental health of these students. Therefore, measures should be implemented to encourage this population to maintain adequate levels of physical activity and reduce sedentary times.

The role of ion channels in hypoxic pulmonary vasoconstriction.

Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism by which localized flow of blood in small resistance pulmonary arteries is matched to alveolar ventilation. This chapter discusses the role of several potassium and calcium channels in HPV, both in enhancing calcium influx into smooth muscle cells (SMCs) and in stimulating the release of calcium from the sarcoplasmic reticulum, thus increasing cytosolic calcium. The increase in calcium sensitivity caused by hypoxia is reviewed in Chapter 19. Particular attention is paid to the activity of the L-type calcium channels which increase calcium influx as a result of membrane depolarization and also increase calcium influx at any given membrane potential in response to hypoxia. In addition, activation of the L-type calcium channel may, in the absence of any calcium influx, cause calcium release from the sarcoplasmic reticulum. Many of these mechanisms have been reported to be involved in both HPV and in normoxic contraction of the ductus arteriosus.

[Clonal expansion and genomic characterization of the human T-cell lymphotropic virus type I during the integration process in adult T-cell leukemia/lymphoma]. / Expansión clónica y caracterización genómica del proceso de integración del virus linfotrópico humano tipo I en la leucemia/linfoma de células T en adultos.

INTRODUCTION: Although the integration of human T-cell lymphotropic virus type I into the T-cells is not a random process, the mechanistic details are not understood. OBJECTIVES: The characteristics of the flanking host chromatin were evaluated at the integration sites in adult T-cell leukaemia/lymphoma (ATLL) patients infected with the virus. MATERIALS AND METHODS: From seven leukemic Colombian patients positive for the human T-cell lymphotropic virus type I (HTLV-I), lymphocyte DNA samples were extracted and amplified by inverse polymerase chain reaction (IPCR). Clonal expansion and human genome nucleotide composition in an extension of 50 bp was determined. To establish the characteristics of the human genome flanking provirus, 61 IPCR sequences from Colombian and Japanese ATLL patients, were analyzed in silico to obtain insights about the genomic structure, functions and nature of associated chromatin. RESULTS: The clonal expansion of cell clones was predominantly oligoclonal. From 61 IPCR sequences, 155 alignments with homology higher than 95% (e-value < 0.05) were screened. Seventy-five percent of those sequences corresponded to non coding elements that include repetitive and non-repetitive DNA. Fifty percent of the proviral integrations were associated with chromosomes of A and B groups. Viral DNA integration tended to favor exons of genes that replicated early, controlled the cell cycle, or were involved in signal transduction. CONCLUSIONS: The results indicated that HTLV-I integration was preferentially directed towards genomic environments with high C:G content, and toward genes that replicate early, regulate cell cycle or involved with signal transduction.

Generation of oxidants by hypoxic human pulmonary and coronary smooth-muscle cells.

BACKGROUND: Pulmonary vasoconstriction in response to hypoxia is unusual inasmuch as local exposure of nonpulmonary vasculature to hypoxia results in vasodilation. It has been suggested that pulmonary artery smooth-muscle cells may relax in response to intracellular generation of reactive oxygen species (ROS) and that the production of ROS decreases under hypoxia. However, other workers report increased ROS production in human pulmonary artery smooth-muscle cells (HPASMC) during hypoxia. METHODS: Using dihydrodichlorofluorescein diacetate, dihydroethidium, and Amplex Red (Molecular Probes; Eugene, OR), we estimated ROS generation by confluent primary cultures of HPASMC and human coronary artery smooth-muscle cells (HCASMC) under normoxia (20%) and acute hypoxia (5%). RESULTS: All three assay systems showed that HPASMC production of ROS is decreased under hypoxia and to a greater extent than the decrease in ROS production by HCASMC. A substantially greater percentage of normoxic ROS production by HPASMC is mitochondrial (> 60%) compared to HCASMC (< 30%). CONCLUSIONS: These results support the conclusion that ROS generation decreases, rather than increases, in HPASMC during hypoxia. However, as ROS production also decreases in HCASMC during hypoxia, the reason for the opposite change in vascular tone is not yet apparent.

Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults.

The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.

Role of store-operated calcium channels and calcium sensitization in normoxic contraction of the ductus arteriosus.

BACKGROUND: At birth, the increase in oxygen causes contraction of the ductus arteriosus, thus diverting blood flow to the lungs. Although this contraction is modulated by substances such as endothelin and dilator prostaglandins, normoxic contraction is an intrinsic property of ductus smooth muscle. Normoxic inhibition of potassium channels causes membrane depolarization and calcium entry through L-type calcium channels. However, the studies reported here show that after inhibition of this pathway there is still substantial normoxic contraction, indicating the involvement of additional mechanisms. METHODS AND RESULTS: Using ductus ring experiments, calcium imaging, reverse-transcription polymerase chain reaction, Western blot, and cellular electrophysiology, we find that this depolarization-independent contraction is caused by release of calcium from the IP3-sensitive store in the sarcoplasmic reticulum, by subsequent calcium entry through store-operated channels, and by increased calcium sensitization of actin-myosin filaments, involving Rho-kinase. CONCLUSIONS: Much of the normoxic contraction of the ductus arteriosus at birth is related to calcium entry through store-operated channels, encoded by the transient receptor potential superfamily of genes, and to increased calcium sensitization. A clearer understanding of the mechanisms involved in normoxic contraction of the ductus will permit the development of better therapy to close the patent ductus arteriosus, which constitutes approximately 10% of all congenital heart disease and is especially common in premature infants.

Interplay between dengue virus and Toll-like receptors, RIG-I/MDA5 and microRNAs: Implications for pathogenesis.

A growing body of evidence has demonstrated the role of components of innate immunity, including Toll-like receptors (TLRs), the retinoic acid-inducible gene I/melanoma-differentiation factor 5 (RIG-I/MDA5) and microRNAs (miRNAs) in the recognition of dengue virus (DENV) or its components by infected cells. TLR3, TLR7/8 and RIG-I/MDA5 sense genomic RNA or dsRNA, the product of an intermediate step of DENV replication, activating intracellular pathways leading to the production of antiviral effectors, including interferon and pro-inflammatory cytokines. Recognition by TLR2 and TLR4 also promotes the activation of other intracellular pathways and alters viral replication in an interferon-independent manner. It was also recently demonstrated that cellular miRNAs, a class of post-transcriptional regulatory small RNAs, can affect replication. To accomplish this, miRNAs bind either directly to viral RNA, through base-pair complementarity affecting translation, or indirectly through virus-mediated changes in host protein expression in the viral life cycle. There is also evidence that certain miRNAs can recognize or be recognized by TLRs and RIG-I/MDA5, resulting in alteration of the innate immune response. In this review, we summarize our present knowledge of DENV-host factor interactions, emphasizing the role of TLRs, RIG-I/MDA5 and miRNAs and their possible connection with pathogenesis. Our discussion is based on recent reports suggesting how these different innate immune components might be activated to induce an antiviral response, and how DENV has developed mechanisms to manipulate or evade these antiviral activities.

Empatia en estudiantes de medicina de la Universidad del Norte, Colombia. Comparación de dos grupos (2012 y 2015) / Empathy among medical students at Universidad del Norte, Colombia. Comparison of two groups (2012 and 2015)

Resumen Introducción. La empatía es un elemento importante en la relación médico-paciente, por lo que la formación en empatía de los estudiantes de medicina debe ser un objetivo permanente de los programas universitarios. Objetivo. Determinar si las actividades académicas de formación en empatía médica implementadas en la Universidad del Norte en 2013 produjeron cambios significativos en los estudiantes de medicina matriculados en 2015 respecto a los matriculados en 2012. Materiales y métodos. Estudio transversal realizado en 934 estudiantes de Medicina de la Universidad del norte (426 hombres y 508 mujeres) matriculados en 2015 a los que se les aplicó la versión en español de la escala de empatía médica de Jefferson. Por su parte, el grupo de comparación estuvo conformado por 345 estudiantes de medicina (106 hombres y 239 mujeres) matriculados en 2012 en la misma universidad. Se realizó un análisis de varianza (ANOVA) y se evaluaron las diferencias entre los años académicos y entre género, así como las interacciones entre estos dos factores. Resultados. Aunque en general no se encontraron diferencias significativas en las tres dimensiones evaluadas (p>0.05) para los dos grupos, sí se observaron diferencias significativas en las preguntas 4, 17 y 20, correspondientes a la dimensión Toma de perspectiva, y en la pregunta 6, correspondiente a la dimensión Ponerse en el lugar del otro (p<0.05), ya que las medias de puntaje fueron mayores en la cohorte de 2012. Conclusión. Las actividades de formación en empatía establecidas en el plan de estudios del programa de medicina no produjeron cambios significativos, por lo que es necesario evaluar y perfeccionar tanto los contenidos del currículo, como los procesos de enseñanza-aprendizaje relacionados con la formación en empatía del programa de Medicina de la Universidad del Norte (Barranquilla, Colombia).

Abstract Introduction: Empathy is an important component of the doctor-patient relationship, so the provision of empathy training to medical students must be a permanent goal of MD programs. Objective: To determine whether the academic medical empathy training activities implemented at Universidad del Norte in 2013 resulted in significant changes in medical students enrolled in 2015 compared to those enrolled in 2012. Materials and methods: Cross-sectional study conducted on 934 medical students (426 men and 508 women) enrolled at Universidad del Norte in 2015 who were administered the Spanish version of the Jefferson Scale of Empathy. The comparison group consisted of 345 medical students (106 men and 239 women) enrolled in 2012 at the same university. An analysis of variance (ANOVA) was performed and differences between academic years and between genders were evaluated, as well as the interactions between these two factors. Results: Although, in general, there were no significant differences between both groups in the three dimensions that were evaluated (p>0.05), statistically significant differences were observed in questions 4, 17 and 20, which are part of the Perspective Taking dimension, and in question 6, included in the Walking in Patient's Shoes dimension (p<0.05), since scores medias were higher in the 2012 cohort. Conclusions: The empathy training activities implemented in the medical program did not produce significant changes. Therefore, it is necessary to assess and improve both the contents and the teaching-learning processes related to empathy training in the medical program offered at Universidad del Norte.

Envelope sequence variation and phylogenetic relations of human T cell lymphotropic virus type 1 from endemic areas of Colombia.

The HTLV-1 envelope gene of 12 TSP/HAM patients from two endemic areas of southwest Colombia (Tumaco and Buenaventura) was amplified by nested PCR, sequenced, and compared with previously reported HTLV-1 envelope sequences from isolates worldwide. In general, the sequence divergences among all Colombian samples ranged from 0.1 to 1.6%. Some amino acid substitutions, referring to the ATK-1 prototype strain in the surface domain gp46 and in p21, were highly prevalent in southwest Colombia, suggesting a geographical clustering of mutations in the envelope gene. The phylogenetic analysis showed that the Colombian isolates belong to the HTLV-1a lineage with minor subgroups. The genetic distance between Colombian and Japanese isolates ranged from 0.1 to 1.8%; in comparison, the genetic distance between Colombian and Caribbean isolates ranged from 0.4 to 2.2%. Our results strongly suggest that the actual quasispecies populations in southwest Colombia have been generated by separate, differently timed introductions of virus.

Activation of the EGFR/p38/JNK pathway by mitochondrial-derived hydrogen peroxide contributes to oxygen-induced contraction of ductus arteriosus.

UNLABELLED: Oxygen-induced contraction of the ductus arteriosus (DA) involves a mitochondrial oxygen sensor, which signals pO2 in the DA smooth muscle cell (DASMC) by increasing production of diffusible hydrogen peroxide (H2O2). H2O2 stimulates vasoconstriction by regulating ion channels and Rho kinase, leading to calcium influx and calcium sensitization. Because epidermal growth factor receptor (EGFR) signaling is also redox regulated and participates in oxygen sensing and vasoconstriction in other systems, we explored the role of the EGFR and its signaling cascade (p38 and c-Jun N-amino-terminal kinase (JNK)) in DA contraction. Experiments were performed in DA rings isolated from full-term New Zealand white rabbits and human DASMC. In human DASMCs, increasing pO2 from hypoxia to normoxia (40 to 100 mmHg) significantly increased cytosolic calcium, p < 0.01. This normoxic rise in intracellular calcium was mimicked by EGF and inhibited by EGFR siRNA. In DA rings, EGF caused contraction while the specific EGFR inhibitor (AG1478) and the tyrosine kinase inhibitors (genistein or tyrphostin A23) selectively attenuated oxygen-induced contraction (p < 0.01). Conversely, orthovanadate, a tyrosine phosphatase inhibitor known to activate EGFR signaling, caused dose-dependent contraction of hypoxic DA and superimposed increases in oxygen caused minimal additional contraction. Anisomycin, an activator of EGFR's downstream kinases, p38 and JNK, caused DA contraction; conversely, oxygen-induced DA contraction was blocked by inhibitors of p38 mitogen-activated protein kinases (MAPK) (SB203580) or JNK (JNK inhibitor II). O2-induced phosphorylation of EGFR occurred within 5 min of increasing pO2 and was inhibited by mitochondrial-targeted overexpression of catalase. AG1478 prevented the oxygen-induced p38 and JNK phosphorylation. In conclusion, O2-induced EGFR transactivation initiates p38/JNK-mediated increases in cytosolic calcium and contributes to DA contraction. The EGFR/p38/JNK pathway is regulated by mitochondrial redox signaling and is a promising therapeutic target for modulation of the patent ductus arteriosus. KEY MESSAGES: Oxygen activates epidermal growth factor receptor (EGFR) in ductus arteriosus (DA) smooth muscle cells. EGFR inhibition selectively attenuates O2-induced DA constriction. pO2-induced EGFR activation is mediated by mitochondrial-derived hydrogen peroxide. p38 MAPK and JNK mediated EGFR's effects on oxygen-induced DA contraction. Tyrosine kinases and phosphatases participate in oxygen sensing in the DA. The EGFR pathway offers new therapeutic targets to modulate patency of the ductus arteriosus.

Síndrome de Klippel Trenaunay Weber. Consideraciones sobre un caso clínico / Klippel-Trenaunay-Weber syndrome. Considerations on a clinical case

RESUMEN Se presenta el caso de gestante de 26 años de edad, afecta del síndrome Klippel Trenaunay Weber congénito, con su primer embarazo el cual concluyó a las 39 semanas, mediante cesárea, obteniéndose recién nacido de 3450 gramos, buen Apgar al nacer, con evolución satisfactoria para el binomio madre-hijo. Se revisó bibliografía universal sobre esta patología, resaltándose los riesgos potenciales para la madre y su producto. Aún cuando la frecuencia de aparición de esta entidad es rara, resulta importante su conocimiento para los profesionales que laboran, tanto en la atención primaria de salud, como en la atención secundaria (AU).

ABSTRACT The case of a 26-years-old woman is presented. She presented the Klippel-Trenaunay-Weber syndrome in her first pregnancy finished at the 39th week through caesarian section; the newborn was 3450 grams, with good Apgar at birth: the mother-child binomial had a satisfactory evolution. The universal bibliography on this disease was reviewed, highlighting the potential risk for mother and child. Even when the frequency of this entity is rare, it is important its knowledge for the professionals working in the primary health care as much as in the secondary health care (AU).