American Registry of Ambulatory or acutely decompensated heart failure (AMERICCAASS Registry): First 1000 patients.

BACKGROUND: About 80% of cardiovascular diseases (including heart failure [HF]) occur in low-income and developing countries. However, most clinical trials are conducted in developed countries. HYPOTHESIS: The American Registry of Ambulatory or Acutely Decompensated Heart Failure (AMERICCAASS) aims to describe the sociodemographic characteristics of HF, comorbidities, clinical presentation, and pharmacological management of patients with ambulatory or acutely decompensated HF in America. METHODOLOGY: Descriptive, observational, prospective, and multicenter registry, which includes patients >18 years with HF in an outpatient or hospital setting. Collected information is stored in the REDCap electronic platform. Quantitative variables are defined according to the normality of the variable using the Shapiro-Wilk test. RESULTS: This analysis includes data from the first 1000 patients recruited. 63.5% were men, the median age of 66 years (interquartile range 56.7-75.4), and 77.6% of the patients were older than 55 years old. The percentage of use of the four pharmacological pillars at the time of recruitment was 70.7% for beta-blockers (BB), 77.4% for angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB II)/angiotensin receptor-neprilysin inhibitor (ARNI), 56.8% for mineralocorticoid receptor antagonists (MRA), and 30.7% for sodium-glucose cotransporter type-2 inhibitors (SGLT2i). The main cause of decompensation in hospitalized patients was HF progression (64.4%), and the predominant hemodynamic profile was wet-warm (68.3%). CONCLUSIONS: AMERICCAASS is the first continental registry to include hospitalized or outpatient patients with HF. Regarding optimal medical therapy, approximately a quarter of the patients still need to receive BB and ACEI/ARB/ARNI, less than half do not receive MRA, and more than two-thirds do not receive SGLT2i.

Galectin-3 contributes to acute cardiac dysfunction and toxicity by increasing oxidative stress and fibrosis in doxorubicin-treated mice.

BACKGROUND: Doxorubicin (DOX) leads to cardiovascular toxicity through direct cardiomyocyte injury and inflammation. We aimed to study the role of Galectin-3 (Gal-3), a ß-galactosidase binding lectin associated with inflammation and fibrosis in DOX-induced acute cardiotoxicity in mice. METHODS: Male C57 and Gal-3 knockout (KO) mice were given a single dose of DOX (15 mg/kg, i.p) or placebo. Serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and cardiac thiobarbituric acid-reactive substance (TBARS) were measured at 3 days to assess cardiac injury and oxidative stress. Cardiac remodeling and function were studied by echocardiography and catheterization at 7 days. Myocardial fibrosis was quantified in picrosirius red stained slices. RESULTS: Absence of Gal-3 tended to reduce the mortality after DOX. DOX significantly increased CPK, LDH, AST and TBARS while treated Gal-3 KO mice showed reduced injury and oxidative stress. After 7 days, adverse remodeling, fibrosis and dysfunction in treated-C57 mice were severely affected while those effects were prevented by absence of Gal-3. CONCLUSION: In summary, genetic deletion of Gal-3 prevented cardiac damage, adverse remodeling and dysfunction, associated with reduced cardiac oxidative stress and fibrosis. Understanding the contribution of GAL-3 to doxorubicin-induced cardiac toxicity reinforces its potential use as a therapeutic target in patients with several cancer types.

Patterns of morphological variation and ecological correlates in the skull of vipers (Serpentes: Viperidae).

The skull of vipers is a highly kinetic anatomical structure involved in envenomating and consuming of prey. Morphological knowledge about the viperid skull is based on studies on some groups of species, but information on its variation within the whole family and its functional morphology is still scarce. In this study, we aimed to explore variation in skull morphology among species of the three subfamilies of Viperidae, and test whether that variation correlates with macrohabitat and diet. We performed quantitative analyses of the viperid skull based on broad taxonomic sampling and two methodological approaches: linear and geometric morphometrics. The results of both approaches showed that much of the variation lies in differences of shape and relative size of the premaxilla, the nasals, the frontals, and the parietals. The results indicated that phylogeny and size influence the shape of the skull, but we also found evidence of morphological differentiation between arboreal and terrestrial species and in species with mammal specialist diet. Our findings imply that, besides evolutionary allometry and phylogenetic signal, demands of particular diets coupled with use of certain habitats have in part shaped morphological evolution of the viperid skull.

An Experimental Model of Myocardial Infarction for Studying Cardiac Repair and Remodeling in Knockout Mice.

Cardiovascular disease is the most prevalent cause of death in Western countries, with acute myocardial infarction (MI) being the most prevalent form. This paper describes a protocol for studying the role of galectin 3 (Gal-3) in the temporal evolution of cardiac healing and remodeling in an experimental animal model of MI. The procedures described include an experimental model of MI with a permanent coronary ligature in male C57BL/6J (control) and Gal-3 knockout (KO) mice, an echocardiography procedure to study cardiac remodeling and systolic function in vivo, a histological evaluation of interstitial myocardial fibrosis with picrosirius red-stained and rhodamine-conjugated lectin-stained sections for studying myocyte hypertrophy by the cross-sectional area (MCSA), and the quantification of infarct size and cardiac remodeling (scar thinning, septum thickness, and expansion index) by planimetry in slices stained with Masson's trichrome and triphenyl tetrazolium chloride. Gal-3 KO mice with MI showed disrupted cardiac remodeling and an increase in the scar thinning ratio and the expansion index. At the onset of MI, myocardial function and cardiac remodeling were also severely affected. At 4 weeks post MI, the natural evolution of fibrosis in infarcted Gal-3 KO mice was also affected. In summary, the experimental model of MI is a suitable model for studying the temporal evolution of cardiac repair and remodeling in mice with the genetic deletion of Gal-3 and other animal models. The lack of Gal-3 affects the dynamics of cardiac repair and disrupts the evolution of cardiac remodeling and function after MI.

Heart Failure After ST-Elevation Myocardial Infarction: Beyond Left Ventricular Adverse Remodeling.

ST-segment elevation myocardial infarction (STEMI) remains a significant source of morbidity and mortality worldwide. Despite advances in treatment leading to a significant reduction in the early complications and in-hospital mortality, a significant proportion of STEMI survivors develop heart failure (HF) at follow-up. The classic paradigm of HF after STEMI is one characterized by left ventricular adverse remodeling (LVAR) and encompasses the process of regional and global structural and functional changes that occur in the heart as a consequence of loss of viable myocardium, increased wall stress and neurohormonal activation, and results in HF with reduced ejection fraction (HFrEF). More recently, however, with further improvements in the treatment of STEMI the incidence and entity of LVAR appear to be largely reduced, yet the risk for HF following STEMI is not abolished and remains substantial, identifying a new paradigm by which patients with STEMI present with HF and preserved EF (HFpEF) characterized by reduction of diastolic or systolic reserve independent of LVAR.

Unraveling the role of galectin-3 in cardiac pathology and physiology.

Galectin-3 (Gal-3) is a carbohydrate-binding protein with multiple functions. Gal-3 regulates cell growth, proliferation, and apoptosis by orchestrating cell-cell and cell-matrix interactions. It is implicated in the development and progression of cardiovascular disease, and its expression is increased in patients with heart failure. In atherosclerosis, Gal-3 promotes monocyte recruitment to the arterial wall boosting inflammation and atheroma. In acute myocardial infarction (AMI), the expression of Gal-3 increases in infarcted and remote zones from the beginning of AMI, and plays a critical role in macrophage infiltration, differentiation to M1 phenotype, inflammation and interstitial fibrosis through collagen synthesis. Genetic deficiency of Gal-3 delays wound healing, impairs cardiac remodeling and function after AMI. On the contrary, Gal-3 deficiency shows opposite results with improved remodeling and function in other cardiomyopathies and in hypertension. Pharmacologic inhibition with non-selective inhibitors is also protective in cardiac disease. Finally, we recently showed that Gal-3 participates in normal aging. However, genetic absence of Gal-3 in aged mice exacerbates pathological hypertrophy and increases fibrosis, as opposed to reduced fibrosis shown in cardiac disease. Despite some gaps in understanding its precise mechanisms of action, Gal-3 represents a potential therapeutic target for the treatment of cardiovascular diseases and the management of cardiac aging. In this review, we summarize the current knowledge regarding the role of Gal-3 in the pathophysiology of heart failure, atherosclerosis, hypertension, myocarditis, and ischemic heart disease. Furthermore, we describe the physiological role of Gal-3 in cardiac aging.

Patterns of morphological variation and ecological correlates in the skull of vipers (Serpentes: Viperidae)

The skull of vipers is a highly kinetic anatomical structure involved in envenomating and consuming of prey. Morphological knowledge about the viperid skull is based on studies on some groups of species, but information on its variation within the whole family and its functional morphology is still scarce. In this study, we aimed to explore variation in skull morphology among species of the three subfamilies of Viperidae, and test whether that variation correlates with macrohabitat and diet. We performed quantitative analyses of the viperid skull based on broad taxonomic sampling and two methodological approaches: linear and geometric morphometrics. The results of both approaches showed that much of the variation lies in differences of shape and relative size of the premaxilla, the nasals, the frontals, and the parietals. The results indicated that phylogeny and size influence the shape of the skull, but we also found evidence of morphological differentiation between arboreal and terrestrial species and in species with mammal specialist diet. Our findings imply that, besides evolutionary allometry and phylogenetic signal, demands of particular diets coupled with use of certain habitats have in part shaped morphological evolution of the viperid skull.

Resistencia, re-existencia y juvenicidio: tres metáforas para comprender la Colombia del levantamiento popular / Resistance, re-existence and youthcide: three metaphors for understanding the popular uprising in Colombia / Resistência, re-existência e juvenilicídio: três metáforas para entender a Colômbia da revolta popular

Resumen (analítico) El artículo analiza las modalidades de resistencia y re-existencia producidas en el contexto del levantamiento popular de 2021, en sus relaciones con el juvenicidio. Metodológicamente, se optó por el análisis de narrativas de experiencias de jóvenes de tres ciudades, así como el análisis de un corpus de imágenes relacionado con estos acontecimientos. En resultados, la categoría salir del cerco evidenció que el levantamiento está imbricado con el juvenicidio, desde la precarización y la violencia estatal en pandemia y la existencia de opresiones cruzadas. En la categoría subvertir, se observó la presencia de estrategias de confrontación y deslegitimación simbólica al sistema dominante. En la categoría estéticas populares sobresalen la autorrepresentación y la curación simbólica. La categoría educación popular evidenció la implementación de prácticas fomentadoras del interaprendizaje y la cocreación para buenos vivires.

Abstract (analytical) This article analyzes the modalities of resistance and re-existence that occurred in the context of the Colombian popular uprising in 2021 and relates them with the practice of youthcide. At a methodological level, the article analyses narratives of experiences of young people from three cities, as well as a corpus of images related to the popular uprising. The results identify a category of getting off the fence, which shows that the uprising is related to acts of youthcide. The protests were a response to precariousness and state violence during pandemic, as well as the existence of multiple forms of oppression of the youth population. In the subversion category, confrontation strategies and symbolic delegitimization of the dominant system were observed. In the popular aesthetic category, self-representation and symbolic healing were evident. In the popular education category, the implementation of practices that promote mutual learning and co-creation for good living were identified.

Resumo (analítico) O artigo analisa as modalidades de resistência e reexistência ocorridas durante a revolta popular de 2021, em suas relações com a juvenilicídio. Metodologicamente, utilizou-se a análise de narrativas de experiências de jovens de três cidades, bem como a análise de imagens relacionadas a esses eventos. Nos resultados, a categoria de sair da cerca mostrou que a revolta está entrelaçada com a juvenilicídio, a partir do aprofundamento da precariedade e da violência estatal e para-estatal. Na categoria subverter, observou-se a implementação de estratégias de enfrentamento e deslegitimação simbólica do sistema dominante. Na categoria estética popular, destacam-se a autorrepresentação e a cura simbólica. E na categoria educação popular foram desveladas práticas que promovem o aprendizado mútuo para o bem viver.

Genetic Deletion of Galectin-3 Exacerbates Age-Related Myocardial Hypertrophy and Fibrosis in Mice.

BACKGROUND/AIMS: Aging is accompanied by progressive and adverse cardiac remodeling characterized by myocardial hypertrophy, fibrosis, and dysfunction. We previously reported that galectin-3 (Gal-3) is a critical regulator of inflammation and fibrosis associated with hypertensive heart disease and myocardial infarction. Nevertheless, the role and mechanism of Gal-3 in age-related cardiac remodeling have not been previously investigated. We hypothesized that Gal-3 plays a critical role in cardiac aging and that its deficiency exacerbates the underlying mechanisms of myocardial hypertrophy and fibrosis. METHODS: Male C57BL/6 (control) (n=24) and Gal-3 knockout (KO) (n=29) mice were studied at 24 months of age to evaluate the role of Gal-3 in cardiac aging. We assessed 1) survival rate; 2) systolic blood pressure (SBP) by plethysmography; 3) myocardial hypertrophy, apoptosis, and fibrosis by quantification of histological and immunohistochemical analysis; 4) cardiac expression of angiotensin (Ang) II, Ang (1-7) by Radioimmunoassay; 5) transforming growth factor-ß (TGF-ß), sirtuin (SIRT) 1, SIRT 7 and metalloproteinase 9 (MMP-9) by RT-qPCR and 6) ventricular remodeling and function by echocardiography. RESULTS: We found that aged Gal-3 KO mice had a lower survival rate and exhibited exacerbated myocardial hypertrophy and fibrosis without changes in SBP. Similarly, myocardial apoptosis and MMP-9 mRNA expression was significantly increased in the hearts of Gal-3 KO mice compared to controls. Additionally, cardiac Ang II and TGF-ß expression were higher in aged Gal-3 KO mice while SIRT1 and SIRT7 expression were reduced. CONCLUSION: Our findings strongly suggest that Gal-3 is involved in age-related cardiac remodeling by regulating critical mechanisms associated with the development of pathological hypertrophy. The gene deletion of Gal-3 reduced the lifespan and markedly increased age-dependent mechanisms of myocardial hypertrophy, apoptosis, and fibrosis, including Ang-II, TGF-ß, and MMP-9. At the same time, there was diminished cardiac-specific expression of SIRT1 and SIRT7, which are extensively implicated in delaying age-dependent cardiomyopathies.

"The Triptan's Hangover": A Multicentric Cross-sectional Observational Study of the Adverse Events of Triptans in Patients With Migraine.

ABSTRACT: The emergence of triptans represented a breakthrough in the treatment of migraine, but in clinical practice, patients describe symptoms that resemble those of a hangover after taking them. We propose the use of the Hangover Symptoms Scale (HSS) to evaluate this syndrome in patients that take triptans, which may help identify patients at higher risk of presenting these adverse effects that may interfere with therapeutic compliance.A cross-sectional observational pilot study with prospective data collection through a clinical-demographic questionnaire and the HSS was carried out on patients with migraine treated in headache units in 3 tertiary hospitals in Madrid.Sixty-six patients were included in the study. The median HSS was 4 and all symptoms were present in at least 15% of the patients, with difficulty to concentrate being the most frequent (57.6%). No significant differences were found between the presence of a higher HSS score and the sociodemographic characteristics of the patient or his migraine. The presence of aura was associated with a higher percentage of trembling (P = 0.029) and fatigue (nonvisual, polymodal auras; P = 0.017).According to our study, triptans are responsible for a set of symptoms overlapping with those that occur during a hangover. Therefore, we propose that the HSS could be a useful tool for the evaluation and quantification of these effects in patients receiving triptans. In addition, we found that clinical features could be more frequently associated with the appearance of these adverse effects that, however, are not related to any particular patient profile.

Application of a novel microscopic technique for quantifying CA125 binding to circulating mononuclear cells in longitudinal specimens during treatment for ovarian cancer.

BACKGROUND: Measurement of serum CA125, an antigenic fragment of human mucin 16 (MUC16), is used to monitor the clinical progression of epithelial ovarian cancer (EOC). However, rather than simply a passive marker reflecting tumor burden, MUC16 may have a more active role by binding to immune cells and altering their tumor response. We developed a research tool to measure MUC16-binding to the surfaces of peripheral blood mononuclear cell (PBMC) subtypes and tested its research value using specimens collected serially from a woman being treated for high grade serous EOC. METHODS: Cryopreserved PBMCs were mixed with anti-CA125 antibody-labeled plasmonic gold nanoparticles (PNPs) to detect cell surface MUC16-binding along with fluorescent stains to identify B cells, NK cells, NK-T cells, T cells, and monocytes. From 3D darkfield images, a computer algorithm was applied to enumerate PNP-binding and fluorescence microscopy to identify cell lineage. Average MUC16-binding was determined by fitting a Poisson distribution to PNP-counts across similar cell types. MUC16-binding to cell types was correlated with treatment details, CA125 levels, and complete blood count (CBC) data. RESULTS: Over a 21-month period, monocytes had the highest level of MUC16-binding which was positively correlated with serum CA125 and inversely correlated with circulating monocyte and lymphocyte counts. Fluctuations of PNP-binding to NK cells were associated temporally with types of chemotherapy and surgical events. Levels of MUC16 bound to NK cells were positively correlated with levels of MUC16 bound to T and NK-T cells and inversely correlated with circulating platelets. CONCLUSIONS: Assessment of MUC16-binding among cryopreserved PBMC cell types can be accomplished using darkfield and fluorescence microscopy. Correlations observed between level of binding by cell type with serum CA125, CBC data, and treatment details suggest that the new techniques may offer novel insights into EOC's clinical course.

What is new in computer vision and artificial intelligence in medical image analysis applications.

Computer vision and artificial intelligence applications in medicine are becoming increasingly important day by day, especially in the field of image technology. In this paper we cover different artificial intelligence advances that tackle some of the most important worldwide medical problems such as cardiology, cancer, dermatology, neurodegenerative disorders, respiratory problems, and gastroenterology. We show how both areas have resulted in a large variety of methods that range from enhancement, detection, segmentation and characterizations of anatomical structures and lesions to complete systems that automatically identify and classify several diseases in order to aid clinical diagnosis and treatment. Different imaging modalities such as computer tomography, magnetic resonance, radiography, ultrasound, dermoscopy and microscopy offer multiple opportunities to build automatic systems that help medical diagnosis, taking advantage of their own physical nature. However, these imaging modalities also impose important limitations to the design of automatic image analysis systems for diagnosis aid due to their inherent characteristics such as signal to noise ratio, contrast and resolutions in time, space and wavelength. Finally, we discuss future trends and challenges that computer vision and artificial intelligence must face in the coming years in order to build systems that are able to solve more complex problems that assist medical diagnosis.

Impacto de la pandemia por COVID-19 en la población pediátrica con apendicitis aguda: experiencia en un hospital general de tercer nivel / Impact of the COVID-19 pandemic on the pediatric population with acute appendicitis: Experience at a general, tertiary care hospital

Introducción. La apendicitis constituye la principal causa de abdomen agudo quirúrgico en pediatría. Durante la pandemia por COVID-19, se replantearon las estrategias de manejo ydisminuyeron las consultas en las guardias, lo que podría asociarse a diagnósticos tardíos y complicaciones. El objetivo de este estudio fue analizar el impacto de la pandemia en los niños con apendicitis aguda. Métodos. Estudio analítico retrospectivocomparativo de pacientes pediátricos conapendicitis aguda durante los cinco meses del confinamiento por COVID-19 versus los meses equivalentes del año previo. Se analizaron la incidencia, la clínica, el estadio, el abordajequirúrgico y las complicaciones. Resultados. Los casos totales de apendicitisse redujeron un 25 % (n = 67 versus n = 50 en 2020). El tiempo medio hasta la consulta fue de 24 horas en ambos períodos (p = 0,989). La incidencia de peritonitis fue del 44 % (n = 22) versus el 37 % (n = 22) (p = 0,22) en 2019. No se evidenció diferencia en los estadios deenfermedad de acuerdo con lo informado en los partes quirúrgicos. En 2019, todas las cirugías se realizaron por vía laparoscópica; en 2020, solo un42 % (n = 21). La incidencia de complicaciones fue del 6 %, contra 7,5 % en el período previo (p = 0,75). Un paciente fue COVID-19 positivo. Conclusión. A pesar de la reducción en el númerode casos de apendicitis, no se evidenció una demora en la consulta en nuestra población. El mayor impacto se asoció a la readecuación del manejo, evitando el abordaje laparoscópico para reducir la diseminación del virus.

Introduction. Appendicitis is the leading cause of surgical acute abdomen in pediatrics. During the COVID-19 pandemic, management strategies were reassessed and the number of visits to the emergency department dropped down, which may be associated with delayed diagnoses and complications. The objective of this study was to analyze the impact of the pandemic on children with acute appendicitis. Methods. Analytical, retrospective, comparative study of pediatric patients with acute appendicitis in the 5 months of COVID-19 lockdown versus the same period in the previous year. Incidence, clinical data, stage, surgical approach, and complications were analyzed. Results. The total number of appendicitis cases went down by 25 % (n = 67 versus n = 50 in 2020). The mean time to consultation was 24 hours in both periods (p = 0.989). The incidence of peritonitis was 44 % (n = 22) versus 37 % (n = 22) (p = 0.22) in 2019. No differences were  observed in terms of appendicitis stage based on surgery reports. In 2019, all surgeries were laparoscopic; while in 2020, only 42 % (n = 21). The incidence of complications was 6 % versus 7.5 % in the previous period (p = 0.75). One patient was COVID-19 positive. Conclusion. Although in our population the number of appendicitis cases dropped down, consultation was not delayed. The greater impact was associated with the reformulation of management strategies, in which the laparoscopic approach is avoided to reduce virus transmission.

Impact of the COVID-19 pandemic on the pediatric population with acute appendicitis: Experience at a general, tertiary care hospital. / Impacto de la pandemia por COVID-19 en la población pediátrica con apendicitis aguda: experiencia en un hospital general de tercer nivel.

INTRODUCTION: Appendicitis is the leading cause of surgical acute abdomen in pediatrics. During the COVID-19 pandemic, management strategies were reassessed and the number of visits to the emergency department dropped down, which may be associated with delayed diagnoses and complications. The objective of this study was to analyze the impact of the pandemic on children with acute appendicitis. METHODS: Analytical, retrospective, comparative study of pediatric patients with acute appendicitis in the 5 months of COVID-19 lockdown versus the same period in the previous year. Incidence, clinical data, stage, surgical approach, and complications were analyzed. RESULTS: The total number of appendicitis cases went down by 25% (n = 67 versus n = 50 in 2020). The mean time to consultation was 24 hours in both periods (p = 0.989). The incidence of peritonitis was 44% (n = 22) versus 37% (n = 22) (p = 0.22) in 2019. No differences were observed in terms of appendicitis stage based on surgery reports. In 2019, all surgeries were laparoscopic; while in 2020, only 42% (n = 21). The incidence of complications was 6% versus 7.5% in the previous period (p = 0.75). One patient was COVID-19 positive. CONCLUSION: Although in our population the number of appendicitis cases dropped down, consultation was not delayed. The greater impact was associated with the reformulation of management strategies, in which the laparoscopic approach is avoided to reduce virus transmission.

Introducción. La apendicitis constituye la principal causa de abdomen agudo quirúrgico en pediatría. Durante la pandemia por COVID-19, se replantearon las estrategias de manejo y disminuyeron las consultas en las guardias, lo que podría asociarse a diagnósticos tardíos y complicaciones. El objetivo de este estudio fue analizar el impacto de la pandemia en los niños con apendicitis aguda. Métodos. Estudio analítico retrospectivo comparativo de pacientes pediátricos con apendicitis aguda durante los cinco meses del confinamiento por COVID-19 versus los meses equivalentes del año previo. Se analizaron la incidencia, la clínica, el estadio, el abordaje quirúrgico y las complicaciones. Resultados. Los casos totales de apendicitis se redujeron un 25% (n = 67 versus n = 50 en 2020). El tiempo medio hasta la consulta fue de 24 horas en ambos períodos (p = 0,989). La incidencia de peritonitis fue del 44% (n = 22) versus el 37% (n = 22) (p = 0,22) en 2019. No se evidenció diferencia en los estadios de enfermedad de acuerdo con lo informado en los partes quirúrgicos. En 2019, todas las cirugías se realizaron por vía laparoscópica; en 2020, solo un 42% (n = 21). La incidencia de complicaciones fue del 6%, contra 7,5% en el período previo (p = 0,75). Un paciente fue COVID-19 positivo. Conclusión. A pesar de la reducción en el número de casos de apendicitis, no se evidenció una demora en la consulta en nuestra población. El mayor impacto se asoció a la readecuación del manejo, evitando el abordaje laparoscópico para reducir la diseminación del virus.

Cardiac Natriuretic Peptide Profiles in Chronic Hypertension by Single or Sequentially Combined Renovascular and DOCA-Salt Treatments.

The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.

Stress-induced expression of IPT gene in transgenic wheat reduces grain yield penalty under drought.

BACKGROUND: The heterologous expression of isopentenyl transferase (IPT) under the transcriptional control of the senescence-associated receptor-like kinase (SARK) promoter delayed cellular senescence and, through it, increased drought tolerance in plants. To evaluate the effect of pSARK::IPT expression in bread wheat, six independent transgenic events were obtained through the biolistic method and evaluated transgene expression, phenology, grain yield and physiological biomass components in plants grown under both drought and well-irrigating conditions. Experiments were performed at different levels: (i) pots and (ii) microplots inside a biosafety greenhouse, as well as under (iii) field conditions. RESULTS: Two transgenic events, called TR1 and TR4, outperformed the wild-type control under drought conditions. Transgenic plants showed higher yield under both greenhouse and field conditions, which was positively correlated to grain number (given by more spikes and grains per spike) than wild type. Interestingly, this yield advantage of the transgenic events was observed under both drought and well-watered conditions. CONCLUSIONS: The results obtained allow us to conclude that the SARK promoter-regulated expression of the IPT gene in bread wheat not only reduced the yield penalty produced by water stress but also led to improved productivity under well-watered conditions.

Characterization of Cell-Bound CA125 on Immune Cell Subtypes of Ovarian Cancer Patients Using a Novel Imaging Platform.

MUC16, a sialomucin that contains the ovarian cancer biomarker CA125, binds at low abundance to leucocytes via the immune receptor, Siglec-9. Conventional fluorescence-based imaging techniques lack the sensitivity to assess this low-abundance event, prompting us to develop a novel "digital" optical cytometry technique for qualitative and quantitative assessment of CA125 binding to peripheral blood mononuclear cells (PBMC). Plasmonic nanoparticle labeled detection antibody allows assessment of CA125 at the near-single molecule level when bound to specific immune cell lineages that are simultaneously identified using multiparameter fluorescence imaging. Image analysis and deep learning were used to quantify CA125 per each cell lineage. PBMC from treatment naïve ovarian cancer patients (N = 14) showed higher cell surface abundance of CA125 on the aggregate PBMC population as well as on NK (p = 0.013), T (p < 0.001) and B cells (p = 0.024) compared to circulating lymphocytes of healthy donors (N = 7). Differences in CA125 binding to monocytes or NK-T cells between the two cohorts were not significant. There was no correlation between the PBMC-bound and serum levels of CA125, suggesting that these two compartments are not in stoichiometric equilibrium. Understanding where and how subset-specific cell-bound surface CA125 takes place may provide guidance towards a new diagnostic biomarker in ovarian cancer.

Del alteractivismo al estallido social: acción juvenil colectiva y conectiva (2011 y 2019) / From alteractivism to social outbreak: collective and connective youth action (2011 & 2019) / Da alterativismo ao surto social: ação coletiva e conectiva da juventude (2011 e 2019)

Resumen (analítico) En este artículo analizamos la participación de los jóvenes en los movimientos alteractivistas de 2011 y los estallidos sociales de 2019, quienes, al parecer, han sido protagonistas de nuevas formas de acción colectiva y conectiva. Desde el enfoque cualitativo de investigación y el método de análisis documental, se revisó un corpus de 61 documentos que comprenden literatura académica e información mediática sobre estos hechos. En los resultados se destacan: la redefinición ontológica y sociopolítica de la condición juvenil a partir de la acción colectiva; el tránsito de prácticas políticas antiglobalización a repertorios de acción colectiva más radicales que buscan resistir a la precariedad y la violencia; y acciones conectivas que transitan de estrategias de replicación a intercambios entre gestores de contenidos y audiencias, por medio de textos multimodales-performativos.

Abstract (analytical) In this article we analyze the participation of young people in the alteractivist movements of 2011 and the social outbreaks of 2019, who, apparently, have been protagonists of new forms of collective and connective action. From the qualitative research approach and the documentary method, we check a corpus of 61 documents about academic literature and media information. The results show: the ontological and sociopolitical redefinition of the youth condition based on collective action; the transition from anti-globalization political practices to more radical repertoires of collective action that seek to resist precariousness and violence; and connective actions that go from replication strategies to exchanges between content managers and audiences, through multimodal-performative texts.

Resumo (analítico) Neste artigo, analisamos a participação dos jovens nos movimentos alterativistas de 2011 e os surtos sociais de 2019, que, aparentemente, foram protagonistas de novas formas de ação coletiva e conectiva. A partir da abordagem qualitativa da pesquisa e do método de análise documental, foi revisado um corpus de 61 documentos que compõem a literatura acadêmica e informações midiáticas sobre esses eventos. Destacam-se os resultados: a redefinição ontológica e sociopolítica da condição juvenil a partir da ação coletiva; a transição das práticas políticas antiglobalização para repertórios mais radicais de ação coletiva que buscam resistir à precariedade e à violência; e ações conectivas que vão desde estratégias de replicação até trocas entre gestores de conteúdo e públicos, por meio de textos multimodal-performativos.

Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats.

ß-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional ß-blockers compared with other antihypertensive drugs. It is unknown whether third-generation ß-blockers share the limitations of traditional ß-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor ß (TGF-ß), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional ß-blockers must not be carried forward to third-generation ß-blockers.

Plasmonic Nanoparticle-Based Digital Cytometry to Quantify MUC16 Binding on the Surface of Leukocytes in Ovarian Cancer.

Although levels of the circulating ovarian cancer marker (CA125) can distinguish ovarian masses that are likely to be malignant and correlate with severity of disease, serum CA125 has not proved useful in general population screening. Recently, cell culture studies have indicated that MUC16 may bind to the Siglec-9 receptor on natural killer (NK) cells where it downregulates the cytotoxicity of NK cells, allowing ovarian cancer cells to evade immune surveillance. We present evidence that the presence of MUC16 can be locally visualized and imaged on the surface of peripheral blood mononuclear cells (PBMCs) in ovarian cancer via a novel "digital" cytometry technique that incorporates: (i) OC125 monoclonal antibody-conjugated gold nanoparticles as optical nanoprobes, (ii) a high contrast dark-field microscopy system to detect PBMC-bound gold nanoparticles, and (iii) a computational algorithm for automatic counting of these nanoparticles to estimate the quantity of surface-bound MUC16. The quantitative detection of our technique was successfully demonstrated by discriminating clones of the ovarian cancer cell line, OVCAR3, based on low, intermediate, and high expression levels of MUC16. Additionally, PBMC surface-bound MUC16 was tracked in an ovarian cancer patient over a 17 month period; the results suggest that the binding of MUC16 on the surface of immune cells may play an early indicator for recurrent metastasis 6 months before computational tomography-based clinical diagnosis. We also demonstrate that the levels of surface-bound MUC16 on PBMCs from five ovarian cancer patients were greater than those from five healthy controls.