Comparison of Physical and Chemical Properties of Green and Brown Brazilian Propolis Collected in Minas Gerais, Brazil.

Among the 13 types of propolis classified in Brazil according to their physicochemical properties, green propolis and brown propolis are the most commonly found and used. In this work, a comparison of the physicochemical properties of green and brown propolis produced in Minas Gerais, Brazil was performed according to the methodology established by the Brazilian legislation. And, the content of 9 bioactive compounds in the samples was determined by RP-HPLC. GrProp showed a higher content of pinocembrin, artepillin C and baccharin, and a higher quantity of total flavonoids, in comparison with BrwProp. The mechanical mass content in both types of propolis was above the limit established by legislation. However, the other physicochemical parameters were within the limits. The chemical composition, especially the flavonoid content and the free radical (DPPH) scavenger property confer to both types of propolis a promising pharmacological activity.

First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study.

Objectives To evaluate the first trimester maternal biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM). Methods The study was a case-control study of healthy women with singleton pregnancies at the first trimester carried out at the Obstetrics and Gynecology Unit, Clinica Davila, Santiago, Chile. After obtaining informed consent, peripheral blood samples of pregnant women under 14 weeks of gestation were collected. At 24-28 weeks of pregnancy, women were classified as GDM (n=16) or controls (n=80) based on the results of a 75-g oral glucose tolerance test (OGTT). In all women, we measured concentrations of fasting blood glucose, insulin, glycated hemoglobin, uric acid, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), sex hormone-binding globulin (SHBG), adiponectin, tissue plasminogen activator (t-PA), leptin and placental growth factor (PGF). Results The GDM group displayed an increased median concentration of cholesterol (P=0.04), triglycerides (P=0.003), insulin (P=0.003), t-PA (P=0.0088) and homeostatic model assessment (HOMA) (P=0.003) and an increased mean concentration of LDL (P=0.009) when compared to the control group. The receiver operating characteristic (ROC) curve for significant variables achieved an area under the curve (AUC) of 0.870, a sensitivity of 81.4% and a specificity of 80.0%. The OGTT was positive for GDM according to the IADPSG (International Diabetes in Pregnancy Study Group) criteria. Conclusion Women who subsequently developed GDM showed higher levels of blood-borne biomarkers during the first trimester, compared to women who did not develop GDM. These data warrant validation in a larger cohort.

The Effect of Leadership Interventions on Staff Nurse Job Enjoyment and Leadership Perception.

Nurse managers (NMs) influence retention and job satisfaction, although many facilities lack NM training programs. A program examined staff nurse perceptions after their NMs participated in leadership training. NMs with limited training may find it more challenging to positively affect their nurses' job satisfaction and retention. This program evaluation suggests that nurse executive investment in and support of the NM role yield positive benefits for the NM leader and their staff.

Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens.

Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the reduction of pGE owing to dysregulation of AIRE, we assessed the expression of AIRE and of several peripheral tissue-restricted Ag genes by quantitative PCR in thymus samples from 19 DS subjects and 21 euploid controls. Strikingly, despite the 21 trisomy, AIRE expression was significantly reduced by 2-fold in DS thymuses compared with controls, which was also confirmed by fluorescent microscopy. Allele-specific quantification of intrathymic AIRE showed that despite its lower expression, the three copies are expressed. More importantly, decreased expression of AIRE was accompanied by a reduction of pGE because expression of tissue-restricted Ags, CHRNA1, GAD1, PLP1, KLK3, SAG, TG, and TSHR, was reduced. Of interest, thyroid dysfunction (10 cases of hypothyroidism and 1 of Graves disease) developed in 11 of 19 (57.9%) of the DS individuals and in none of the 21 controls. The thymuses of these DS individuals contained significantly lower levels of AIRE and thyroglobulin, to which tolerance is typically lost in autoimmune thyroiditis leading to hypothyroidism. Our findings provide strong evidence for the fundamental role of AIRE and pGE, namely, central tolerance, in the predisposition to autoimmunity of DS individuals.

Correlation between Maternal Characteristics during Early Pregnancy, Fetal Growth Rate and Newborn Weight in Healthy Pregnancies.

BACKGROUND: The objective of this study was to evaluate the association between maternal characteristics in early pregnancy and fetal growth (FG) and birth weight (BW). METHODS: A prospective cohort study was performed in unselected pregnant women who attended an ultrasound evaluation at 11-14 weeks of pregnancy. Medical history, biochemical blood tests, biophysical variables and fetal weight at 20-25 and 30-36 weeks as well as the BW were assessed. Bivariate and multivariate linear models were constructed. RESULTS: In all, 543 patients with normal pregnancy and labor were selected. The multiple regression analysis showed a statistically significant association between maternal body mass index (BMI) in early pregnancy and the uterine artery pulsatility index (UtAPI) in the first trimester with BW (p < 0.0008) and with the ratio of fetal growth between the second and third trimesters (p < 0.0001). No correlation was found between these variables and first trimester levels of hemoglobin or glycemia. CONCLUSION: Maternal first trimester BMI and UtAPI correlate with the rate of intrauterine FG and with the BW. This evidence highlights the influence of maternal first trimester variables on fetuses with normal growth and the potential role of these variables in fetal programming.

[Tree above-ground biomass allometries for carbon stocks estimation in the Caribbean mangroves in Colombia]. / Ecuaciones alométricas de biomasa aérea para la estimación de los contenidos de carbono en manglares del Caribe Colombiano.

The distribution of carbon in "Blue Carbon" ecosystems such as mangroves is little known, when compared with the highly known terrestrial forests, despite its particular and recognized high productivity and carbon storage capacity. The objective of this study was to analyze the above ground biomass (AGB) of the species Rhizophora mangle and Avicennia germinans from the Marine Protected Area of Distrito de Manejo Integrado (DMI), Cispatá-Tinajones-La Balsa, Caribbean Colombian coast. With official authorization, we harvested and studied 30 individuals of each species, and built allometric models in order to estimate AGB. Our AGB results indicated that the studied mangrove forests of the DMI Colombian Caribbean was of 129.69 ± 20.24 Mg/ha, equivalent to 64.85 ± 10.12 MgC/ha. The DMI has an area of 8 570.9 ha in mangrove forests, and we estimated that the total carbon potential stored was about 555 795.93 Mg C. The equations generated in this study can be considered as an alternative for the assessment of carbon stocks in AGB of mangrove forests in Colombia; as other available AGB allometric models do not discriminate mangrove forests, despite being particular ecosystems. They can be used for analysis at a more detailed scale and are considered useful to determine the carbon storage potential of mangrove forests, as a country alternative to support forest conservation and emission reduction strategies. In general, the potential of carbon storage from Colombian Caribbean mangrove forests is important and could promote the country leadership of the "blue carbon" stored.

Prediction of gestational diabetes early in pregnancy: targeting the long-term complications.

Gestational diabetes (GD), defined as carbohydrate intolerance with onset or first recognition during pregnancy, has a prevalence of 7% and is a growing problem worldwide. Infants born to mothers with GD are more likely to be large for gestational age, incur traumatic birth injury, require a stay in the intensive care unit and develop postnatal metabolic disturbances. As the worldwide epidemic of obesity worsens, more women are entering pregnancy with metabolic alterations and preexisting insulin resistance, which is heightened by the hormonal milieu of pregnancy. The Hyperglycemia Adverse Pregnancy Outcome (HAPO) study has clearly shown that GD-related complications correlate with glycemic control. We will review the current understanding of the physiology of GD and the screening and treatment guidelines that are commonly utilized in clinical care. In addition, we will discuss the need for development of multiparametric models combining maternal clinical risk factors and biomarkers early in pregnancy to better stratify and predict risk of GD-related complications and offer targeted intervention.

Screening for Mutations in Hereditary Cancer Susceptibility Genes in a Region with High Endogamy in Brazil.

Introduction Cancer is a multifactorial disease dependent on the influence of genetic and environmental factors. About 10% of cancers are associated with germline mutations, which predispose to a higher risk of developing cancer. Currently, the use of panels that identify susceptibility and/or association genes cancer has been increasingly used, both in clinical practice and in scientific research. Objective To investigate genetic mutations in patients with a profile for hereditary cancer in individuals from a region of northeast Brazil, where there is a high frequency of endogenous and consanguineous marriages. Methods A set of 17 genes ( BRCA1 , BRCA2 , APC , TP53 , PTEN , RET , VHL , RB1 , CDKN2 , CDH1 , CHEK2 , MLH1 , MSH2 , MSH6 , MUTYH , XPA , and XPC ) associated with cancer and hereditary syndromes were analyzed. Fifteen patients with a hereditary cancer profile were evaluated. Results The pathogenic variant found was c.1187G > A (p.Gly396Asp), rs36053993 in the MUTYH gene in a male patient diagnosed with melanoma at the age of 43 years and a family history for this tumor. This gene encodes an important enzyme related to DNA repair and has been associated with other types of cancer, this is the first report of an association with melanoma, the biological plausibility of this association is given once the MUTYH protein is expressed in the skin tissue and is responsible for repairing damage caused, for example, by sun exposure. Conclusion The results of this study suggest that this mutation may be important for the hereditary predisposition to melanoma, but a broader investigation of this mutation is needed.

Clinical perspective in relation to age in patients treated with thrombectomy for anterior circulation stroke in a stroke center in Colombia.

BACKGROUND AND AIMS: Endovascular treatment for cerebrovascular disease is accepted as a first-line option with level I evidence in patients with an early and late time of window of onset symptoms, and an additional option in patients who do not respond or with contraindications to systemic thrombolysis; nevertheless the efficacy and outcomes of some groups were not clear, one of them are patients aged 80 years and older, because they were excluded of the trials, so the evidence is controversial with significant heterogeneity, for that reason in our study, we decided to analyze the age in the patients treated in our stroke center, as a predictor of prognosis, and to provide a baseline for the establishment of personalized treatment plans. METHODS: Observational, retrospective study of patients that received endovascular treatment for cerebrovascular disease in a Colombian stroke center between 2016 and 2020, continuous and categorical variables were compared using the Student's t test and Chi-Square. To determine cut-off points in the variable against death and Rankin score variable on 90th day. RESULTS: In total, 108 patients were recruited, 35 of them were of 80 or more years, and the mean age was 72.7 years, we found age as a significant variable to predict the risk in the population over 80 years of age [RR 3.37 CI (95% 1.14-103) p = 0.029]. CONCLUSIONS: Age younger than 80 is a significant predictor for results and long-term outcomes in patients suffering from stroke, and in patients older than 80 years old a Thrombolysis in Cerebral Infarction score 2b-3 is a predictor of good outcomes. Further studies are needed to evaluate the relationship between intrahospital complications and long-term outcomes.

Content validity of the Post-Stroke Guidance and Follow-up Booklet.

OBJECTIVES: to provide sources of content validity evidence for the Post-Stroke Guidance and Follow-up Booklet. METHODS: a quantitative-qualitative approach, using two Delphi method and content analysis rounds. The Educational Content Validation Instrument in Health was sent to 53 independent judges. A Content Validity Index above 0.90 was considered. RESULTS: of the 14 nurses who participated, 64.3% have experience with stroke care, 35.7% with primary care and 64.3% with educational material production. In content analysis, judges' suggestions were stratified into four categories: material conformation, objectivity, accuracy and perception. Spelling changes were made to the images, addition of functionality scale, adequacy of technical terms and language. The Content Validity Index in the second round showed a concordance of 0.97. CONCLUSIONS: the booklet presented satisfactory content validity sources of evidence.

Identification of LOC101927355 as a Novel Biomarker for Preeclampsia.

Preeclampsia, a disorder with a heterogeneous physiopathology, can be attributed to maternal, fetal, and/or placental factors. Long non-coding RNAs (lncRNAs) refer to a class of non-coding RNAs, the essential regulators of biological processes; their differential expression has been associated with the pathogenesis of multiple diseases. The study aimed to identify lncRNAs, expressed in the placentas and plasma of patients who presented with preeclampsia, as potential putative biomarkers of the disease. In silico analysis was performed to determine lncRNAs differentially expressed in the placentas of patients with preeclampsia, using a previously published RNA-Seq dataset. Seven placentas and maternal plasma samples collected at delivery from preterm preeclamptic patients (≤37 gestational weeks of gestation), and controls were used to validate the expression of lncRNAs by qRT-PCR. Six lncRNAs were validated and differentially expressed (p < 0.05) in the preeclampsia and control placentas: UCA1 and HCG4 were found upregulated, and LOC101927355, LINC00551, PART1, and NRAD1 downregulated. Two of these lncRNAs, HCG4 and LOC101927355, were also detected in maternal plasma, the latter showing a significant decrease (p = 0.03) in preeclamptic patients compared to the control group. In silico analyses showed the cytoplasmic location of LOC101927355, which suggests a role in post-transcriptional gene regulation. The detection of LOC101927355 in the placenta and plasma opens new possibilities for understanding the pathogenesis of preeclampsia and for its potential use as a biomarker.

Improving Health Professions Students' Understanding of Interprofessional Roles Through Participation in a Patient Stabilization Simulation.

Objective. To teach interprofessional communication and teamwork skills to health professions students through a standardized patient simulation on acute patient stabilization and measure the impact on learners' perceptions of interprofessional collaboration.Methods. Medical and pharmacy students in their final year and post-licensure nurses in their initial six-month probationary period worked together to stabilize a simulated acutely ill standardized patient. Perceptions of IPE were assessed pre- and post-simulation using the Student Perceptions of Interprofessional Clinical Education-Revised Instrument, version 2 (SPICE-R2). Medical student participants' scores were compared to those of a concurrently enrolled cohort of medical students who did not participate in the simulation.Results. Eighty learners participated in the simulation and all completed pre and post SPICE-R2 assessments. Learners' perceptions increased significantly in all domains, including understanding of roles in collaborative practice, interprofessional teamwork and team-based practice, and patient outcomes from collaborative practice. Compared to the control cohort, participants' perceptions of team-based practice and the impact on patient outcomes improved significantly, while a statistically similar improvement in scores for understanding of roles and responsibilities was seen. The SPICE-R2 scores increased similarly among students in each profession. Repeat exposure to the simulation continued to improve perceptions but not as robustly as the initial simulation.Conclusion. This simulation changed learners' perceptions of how interprofessional collaboration affects patient care, which supports the incorporation of standardized patient-based interprofessional education even in the late-stage education of health professionals.

Increased Circulating Levels of Tissue-Type Plasminogen Activator Are Associated with the Risk of Spontaneous Abortion During the First Trimester of Pregnancy.

Spontaneous abortion is a common complication in early pregnancy, with an incidence of around 20%. Ultrasound scan and measurement of human chorionic gonadotropin are used to identify patients at risk of spontaneous abortion; however, there is a clinical need to find new biomarkers to prospectively identify patients before the onset of clinical symptoms. Here, we aim to investigate potential biomarkers of spontaneous abortion taken in the first clinical appointment of pregnancy. A case-control study was conducted based on a prospectively collected cohort in which cases and controls were retrospectively stratified based on pregnancy outcome: normal healthy pregnancies (controls = 33) and pregnancies that ended in spontaneous abortion (cases = 10). We evaluated extracellular vesicles isolated by precipitation with ExoQuick™ and protein concentrations of tissue plasminogen activator, leptin, and adiponectin measured by ELISA. The extracellular vesicles showed the typical morphology and membrane proteins: CD63, Alix, and Flotilin-1. The size distributions of the isolated extracellular vesicles were 112 ± 27 and 118 ± 28 nm in diameter for controls and spontaneous abortion, respectively, and the total amount of extracellular vesicles did not show any difference between controls and the spontaneous abortion group. The tissue plasminogen activator showed a significant difference (p = 0.0004) between both groups, although neither adiponectin nor leptin revealed significant changes, indicating that women who had spontaneous abortions have significantly higher levels of tissue plasminogen activator than women who had normal pregnancies.

The simultaneous presence of IL-1B and TNFA two-positions risk haplotypes enhances the susceptibility for celiac disease.

To assess the joint contribution of interleukin 1 beta (IL-1B) and tumor necrosis factor alpha (TNFalpha) to the genetic risk of developing celiac disease (CD), we analyzed four biallelic polymorphisms of TNFA and IL-1B genes in 228 patients and 244 healthy controls. The individual contribution of TNFA -308A and IL-1B -511C alleles was weak (OR 1.47 and 1.66, respectively) and was null for TNFA -238 A/G and IL-1B +3953 C/T single nucleotide polymorphisms (SNPs). Due to the potential linkage disequilibrium between TNFA, human leukocyte antigen (HLA) -DQA1 and HLA-DQB1 genes, only individuals carrying DQ2 antigen (DQ2-positive) were considered to perform haplotype analyses. Two-position risk haplotypes were first defined by the combined presence of -511C and +3953T alleles for IL-1B (OR 9.402) or -308A and -238A alleles for TNFA (OR 15.389). The TNFA/IL-1B combined haplotype-stratified association analysis showed that the simultaneous presence of TNFA risk and IL-1B non-risk haplotypes (OR 13.32) but not TNFA non-risk and IL-1B risk haplotypes (OR 0.71) is associated with CD. Interestingly, our data suggest that the coexistence of both risk haplotypes seems to work synergistically (OR 29.59), which enhances the risk of developing CD.

Content validity of the Post-Stroke Guidance and Follow-up Booklet / Validación de contenido del Cuaderno de Orientación y Seguimiento Post-Accidente Cerebrovascular / Validação de conteúdo da Caderneta de Orientação e Acompanhamento Pós-Acidente Vascular Cerebral

ABSTRACT Objectives: to provide sources of content validity evidence for the Post-Stroke Guidance and Follow-up Booklet. Methods: a quantitative-qualitative approach, using two Delphi method and content analysis rounds. The Educational Content Validation Instrument in Health was sent to 53 independent judges. A Content Validity Index above 0.90 was considered. Results: of the 14 nurses who participated, 64.3% have experience with stroke care, 35.7% with primary care and 64.3% with educational material production. In content analysis, judges' suggestions were stratified into four categories: material conformation, objectivity, accuracy and perception. Spelling changes were made to the images, addition of functionality scale, adequacy of technical terms and language. The Content Validity Index in the second round showed a concordance of 0.97. Conclusions: the booklet presented satisfactory content validity sources of evidence.

RESUMEN Objetivos: proporcionar fuentes de evidencia de validación de contenido para el Manual de Orientación y Seguimiento Post-Accidentes Cerebrovascular. Métodos: abordaje cuantitativo-cualitativo, utilizando dos rondas del método Delphi y análisis de contenido. El Instrumento de Validación de Contenido de Educación en Salud fue enviado a 53 jueces independientes. Se consideró un Índice de Validez de Contenido superior a 0,90. Resultados: de los 14 enfermeros que participaron, el 64,3% tiene experiencia en el cuidado del ictus, el 35,7% en la atención primaria y el 64,3% en la producción de material educativo. En el análisis de contenido, las sugerencias de los jueces fueron estratificadas en cuatro categorías: conformación, objetividad, precisión y percepción del material. Se realizaron cambios ortográficos a las imágenes, adición de escala de funcionalidad, adecuación de términos técnicos y lenguaje. El Índice de Validez de Contenido en la segunda ronda mostró una concordancia de 0,97. Conclusiones: la cartilla presentó fuentes de evidencia de validez de contenido satisfactorias.

RESUMO Objetivos: prover fontes de evidências de validação de conteúdo para a Caderneta de Orientação e Acompanhamento Pós-Acidente Vascular Cerebral. Métodos: abordagem quanti-qualitativa, utilizando duas rodadas do método Delphi e análise de conteúdo. O Instrumento de Validação de Conteúdo Educativo em Saúde foi enviado para 53 juízes independentes. Considerou-se um Índice de Validade de Conteúdo acima de 0,90. Resultados: dos 14 enfermeiros que participaram, 64,3% têm experiência com atendimento a Acidente Vascular Cerebral, 35,7% com atenção primária e 64,3% com produção de material educativo. Na análise de conteúdo, as sugestões dos juízes foram estratificadas em quatro categorias: conformação, objetividade, precisão e percepção do material. Foram realizadas alterações ortográficas nas imagens, adição de escala de funcionalidade, adequação de termos técnicos e linguagem. O Índice de Validade de Conteúdo na segunda rodada demonstrou concordância de 0,97. Conclusões: a caderneta apresentou fontes de evidências de validade de conteúdo satisfatórias.

Placental Exosomes as Early Biomarker of Preeclampsia: Potential Role of Exosomal MicroRNAs Across Gestation.

Context: There is a need to develop strategies for early prediction of patients who will develop preeclampsia (PE) to establish preventive strategies to reduce the prevalence and severity of the disease and their associated complications. Objective: The objective of this study was to investigate whether exosomes and their microRNA cargo present in maternal circulation can be used as early biomarker for PE. Design, Setting, Patients, and Interventions: A retrospective stratified study design was used to quantify total exosomes and placenta-derived exosomes present in maternal plasma of normal (n = 32 per time point) and PE (n = 15 per time point) pregnancies. Exosomes present in maternal circulation were determined by nanoparticle tracking analysis. An Illumina TruSeq® Small RNA Library Prep Kit was used to construct a small RNA library from exosomal RNA obtained from plasma samples. Results: In presymptomatic women, who subsequently developed PE, the concentration of total exosomes and placenta-derived exosomes in maternal plasma was significantly greater than those observed in controls, throughout pregnancy. The area under the receiver operating characteristic curves for total exosome and placenta-derived exosome concentrations were 0.745 ± 0.094 and 0.829 ± 0.077, respectively. In total, over 300 microRNAs were identified in exosomes across gestation, where hsa-miR-486-1-5p and hsa-miR-486-2-5p were identified as the candidate microRNAs. Conclusions: Although the role of exosomes during PE remains to be fully elucidated, we suggest that the concentration and content of exosomes may be of diagnostic utility for women at risk for developing PE.

Anjos da Guarda: ferramenta para o ensino médico / Anjos Da Guarda (Guardian Angels): Medical Teaching Tool

Resumo A verdadeira medicina combina conhecimento biotecnocientífico ao cuidado. No entanto, as escolas médicas têm dado maior ênfase ao conhecimento científico em detrimento da relação médico-paciente. Objetivos: Este relato tem como objetivo descrever a experiência de imersão vivida por quatro estudantes de medicina do sexto período nos meses de fevereiro e março de 2020. Método: Tal imersão deu-se em um projeto de ensino denominado Anjos da Guarda, o qual é usado como ferramenta de educação médica no Hospital Universitário Gaffrée e Guinle da Universidade Federal do Estado do Rio de Janeiro (HUGG-UNIRIO). Resultados: O Projeto Anjos da Guarda desenvolve o profissionalismo médico, a empatia e os fundamentos da medicina centrados na pessoa do paciente como parte do processo de cuidado, sem menosprezar a importância do conhecimento biotecnocientífico e do raciocínio clínico. Conclusão: A experiência possibilitou ganhos em aprendizado para os estudantes, além de contribuir com o sistema de saúde e de beneficiar os pacientes envolvidos.

Abstract Conventional medicine combines biotechnoscientific knowledge with care. However, medical schools have placed greater emphasis on scientific knowledge to the detriment of the doctor-patient relationship. Objectives: This report aims to describe the immersion experience lived by four sixth-term medical students during the months of February and March 2020. Method: Such immersion took place in a teaching project named Anjos da Guarda, which is used as a medical education tool at the Gaffrée e Guinle University Hospital of the Federal University of the State of Rio de Janeiro (HUGG-UNIRIO). Results: The Anjos da Guarda Project develops medical professionalism, empathy and the fundamentals of medicine centered on the patient as part of the care process, without underestimating the importance of biotechnoscientific knowledge and clinical reasoning. Conclusion: The experience enabled gains in learning for students, in addition to contributing to the health system and benefiting the patients involved.

Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation.

Although there is significant interest in elucidating the role of placenta-derived exosomes (PdEs) during pregnancy, the exosomal profile in pregnancies complicated by gestational diabetes mellitus (GDM) remains to be established. The aim of this study was to compare the gestational-age profile of PdEs in maternal plasma of GDM with normal pregnancies and to determine the effect of exosomes on cytokine release from human umbilical vein endothelial cells. A prospective cohort of patients was sampled at three time points during pregnancy for each patient (i.e., 11-14, 22-24, and 32-36 weeks' gestation). A retrospective stratified study design was used to quantify exosomes present in maternal plasma of normal (n = 13) and GDM (n = 7) pregnancies. Gestational age and pregnancy status were identified as significant factors contributing to variation in plasma exosome concentration (ANOVA, P < 0.05). Post hoc analyses established that PdE concentration increased during gestation in both normal and GDM pregnancies; however, the increase was significantly greater in GDM (∼2.2-fold, ∼1.5-fold, and ∼1.8-fold greater at each gestational age compared with normal pregnancies). Exosomes isolated from GDM pregnancies significantly increased the release of proinflammatory cytokines from endothelial cells. Although the role of exosomes during GDM remains to be fully elucidated, exosome profiles may be of diagnostic utility for screening asymptomatic populations.

Intranasal Administration of Type V Collagen Reduces Lung Carcinogenesis through Increasing Endothelial and Epithelial Apoptosis in a Urethane-Induced Lung Tumor Model.

Type V collagen (Col V) is a "minor" component of normal lung extracellular matrix, which is subjected to decreased and abnormal synthesis in human lung infiltrating adenocarcinoma. We previously reported that a direct link between low amounts of Col V and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis. Moreover, this collagen species was able to trigger DNA fragmentation and impair survival of neoplastic cells. In this study, we have extended our investigation with the aim to obtain further evidence that the death induced by Col V-treatment is of the caspase-9 apoptotic type. We used (1) optical and electron microscopy, (2) quantitation of TUNEL-labeled cells and (3) analysis of the expression levels of Col V and selected genes coding for apoptosis-linked factors, by conventional RT-PCR. BALB/c mice were injected intraperitoneally with 1.5 g/kg body weight of urethane. After urethane injection, the animals received intranasal administration of 20 µg/20 µl of Col V every day during 2 months. We report here that Col V treatment was able to determine significant increase in Col V protein and gene expression and in the percentage of TUNEL-positive cells, to up-regulate caspase-9, resulting in low growth of tumor cells. Our data validate chemical carcinogenesis as a suitable "in vivo" model for further and more detailed studies on the molecular mechanisms of the death response induced by Col V in lung infiltrating adenocarcinoma opening new strategies for treatment.