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The downstream signaling of the interleukin-7 (IL-7) receptor (IL-7R) plays important physiological and pathological roles, including the differentiation of lymphoid cells and proliferation of acute lymphoblastic leukemia cells. Gain-of-function mutations in the IL-7Rα chain, the specific component of the receptor for IL-7, result in constitutive, IL-7-independent signaling and trigger acute lymphoblastic leukemia. Here, we show that the loss of the phosphoinositide 5-phosphatase INPP5K is associated with increased levels of the INPP5K substrate phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) and causes an altered dynamic structure of the IL-7 receptor. We discovered that the IL-7Rα chain contains a very conserved positively charged polybasic amino acid sequence in its cytoplasmic juxtamembrane region; this region establish stronger ionic interactions with negatively charged PtdIns(4,5)P2 in the absence of INPP5K, freezing the IL-7Rα chain structure. This dynamic structural alteration causes defects in IL-7R signaling, culminating in decreased expressions of EBF1 and PAX5 transcription factors, in microdomain formation, cytoskeletal reorganization, and bone marrow B-cell differentiation. Similar alterations after the reduced INPP5K expression also affected mutated, constitutively activated IL-7Rα chains that trigger leukemia development, leading to reduced cell proliferation. Altogether, our results indicate that the lipid 5-phosphatase INPP5K hydrolyzes PtdIns(4,5)P2, allowing the requisite conformational changes of the IL-7Rα chain for optimal signaling.
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Interleucina-7 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Interleucina-7/genética , Interleucina-7/metabolismo , Fosfatidilinositol 4,5-Difosfato , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/metabolismo , Transducción de Señal/genéticaRESUMEN
Bird populations are declining globally. Wind and solar energy can reduce emissions of fossil fuels that drive anthropogenic climate change, yet renewable-energy production represents a potential threat to bird species. Surveys to assess potential effects at renewable-energy facilities are exclusively local, and the geographic extent encompassed by birds killed at these facilities is largely unknown, which creates challenges for minimizing and mitigating the population-level and cumulative effects of these fatalities. We performed geospatial analyses of stable hydrogen isotope data obtained from feathers of 871 individuals of 24 bird species found dead at solar- and wind-energy facilities in California (USA). Most species had individuals with a mix of origins, ranging from 23% to 98% nonlocal. Mean minimum distances to areas of likely origin for nonlocal individuals were as close as 97 to >1250 km, and these minimum distances were larger for species found at solar-energy facilities in deserts than at wind-energy facilities in grasslands (Cohen's d = 6.5). Fatalities were drawn from an estimated 30-100% of species' desingated ranges, and this percentage was significantly smaller for species with large ranges found at wind facilities (Pearson's r = -0.67). Temporal patterns in the geographic origin of fatalities suggested that migratory movements and nonmigratory movements, such as dispersal and nomadism, influence exposure to fatality risk for these birds. Our results illustrate the power of using stable isotope data to assess the geographic extent of renewable-energy fatalities on birds. As the buildout of renewable-energy facilities continues, accurate assessment of the geographic footprint of wildlife fatalities can be used to inform compensatory mitigation for their population-level and cumulative effects.
Extensión geográfica de las poblaciones de aves afectadas por desarrollos de energía renovable Resumen Las poblaciones mundiales de aves están en declive. Las energías solar y eólica pueden reducir las emisiones de combustibles fósiles que causan el cambio climático, aunque la producción de energías renovables representa una amenaza potencial para las aves. Los censos para evaluar los efectos potenciales en los centros de energía renovable son exclusivamente locales y se sabe poco sobre la extensión geográfica representada por las aves que mueren en estas instalaciones, lo que plantea obstáculos para mitigar los efectos acumulativos y de nivel poblacional de estas muertes. Realizamos análisis geoespaciales con datos del isótopo de hidrógeno estable obtenido de las plumas de 871 ejemplares de 24 especies de aves que fueron hallados muertos en los centros de energía solar y eólica en California, EE.UU. La mayoría de las especies contó con ejemplares de orígenes mixtos, con un rango del 23% al 98% no local. La media de la distancia mínima a las áreas de probable origen de los ejemplares no locales varía entre los 97 hasta > 1,250 km. Estas distancias mínimas fueron mayores para las especies encontradas en los centros de energía solar situadas en desiertos que para las especies encontradas en los centros de energía eólica localizadas en pastizales (d de Cohen = 6.5). Las muertes representan un 30100% de la extensión de las especies. Este porcentaje fue significativamente menor para las especies con extensiones amplias encontradas en instalaciones eólicas (r de Pearson = 0.67). Los patrones temporales en el origen geográfico de las muertes sugieren que los movimientos migratorios y no migratorios, como la dispersión y el nomadismo, influyen en la exposición de estas aves al riesgo de muerte. Nuestros resultados demuestran la utilidad de los isótopos estables para evaluar el alcance geográfico de las muertes de aves asociadas a energías renovables. Con el progresivo aumento de instalaciones de energía renovable, una evaluación precisa de la huella geográfica de la mortandad de fauna salvaje podrá guiar la mitigación compensatoria de sus efectos acumulativos y de nivel poblacional.
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Conservación de los Recursos Naturales , Energía Renovable , Animales , Aves , Isótopos , VientoRESUMEN
Computer-aided design and computer-aided manufacturing (CAD-CAM) technologies have been integrated into the dental digital workflow. However, pretreatment virtual veneer preparations and the digital design and manufacturing of guided preparation and cementation templates has not yet been incorporated into the clinical routine. This article presents a novel protocol for digitally guided veneer rehabilitation by following the esthetic integration area concept, facilitating precise control over tooth structure removal and obviating the need for interim restorations.
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Rasa3 is a GTPase activating protein of the GAP1 family which targets R-Ras and Rap1. Although catalytic inactivation or deletion of Rasa3 in mice leads to severe hemorrhages and embryonic lethality, the biological function and cellular location of Rasa3 underlying these defects remains unknown. Here, using a combination of loss of function studies in mouse and zebrafish as well as in vitro cell biology approaches, we identify a key role for Rasa3 in endothelial cells and vascular lumen integrity. Specific ablation of Rasa3 in the mouse endothelium, but not in megakaryocytes and platelets, lead to embryonic bleeding and death at mid-gestation, recapitulating the phenotype observed in full Rasa3 knock-out mice. Reduced plexus/sprouts formation and vascular lumenization defects were observed when Rasa3 was specifically inactivated in mouse endothelial cells at the postnatal or adult stages. Similar results were obtained in zebrafish after decreasing Rasa3 expression. In vitro, depletion of Rasa3 in cultured endothelial cells increased ß1 integrin activation and cell adhesion to extracellular matrix components, decreased cell migration and blocked tubulogenesis. During migration, these Rasa3-depleted cells exhibited larger and more mature adhesions resulting from a perturbed dynamics of adhesion assembly and disassembly which significantly increased their life time. These defects were due to a hyperactivation of the Rap1 GTPase and blockade of FAK/Src signaling. Finally, Rasa3-depleted cells showed reduced turnover of VE-cadherin-based adhesions resulting in more stable endothelial cell-cell adhesion and decreased endothelial permeability. Altogether, our results indicate that Rasa3 is a critical regulator of Rap1 in endothelial cells which controls adhesions properties and vascular lumen integrity; its specific endothelial cell inactivation results in occluded blood vessels, hemorrhages and early embryonic death in mouse, mimicking thus the Rasa3-/- mouse phenotype.
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Permeabilidad Capilar/genética , Adhesión Celular/genética , Células Endoteliales/fisiología , Endotelio Vascular/metabolismo , Proteínas Activadoras de GTPasa/fisiología , Proteínas de Unión al GTP rap1/fisiología , Animales , Animales Modificados Genéticamente , Células Cultivadas , Embrión de Mamíferos , Embrión no Mamífero , Femenino , Proteínas Activadoras de GTPasa/genética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Megacariocitos/fisiología , Ratones , Ratones Noqueados , Transducción de Señal , Pez Cebra , Proteínas de Unión al GTP rap1/genéticaRESUMEN
BACKGROUND: Patients with advanced chronic kidney disease (CKD) exhibit higher prevalence of coronary artery calcification (CaC) than general population. CaC has been proposed as a risk factor for mortality in end-stage CKD, but most studies in the field are based on short-term follow-up. METHODS: We conducted a cohort, 10-year prospective longitudinal study of consecutive cases referred to the renal unit. A non-enhanced multislice coronary computed tomography was performed at baseline. CaC was assessed by Agatston method. Patients were stratified according to their CaC score: severe calcification group (CaCs< 400 HU) and mild-moderate calcification group (CaCs≥400 HU). The overall and cardiovascular (CV) mortality, CV events, and factors potentially associated with CaC development were recorded. RESULTS: 137 patients with advanced CKD were enrolled and provided consent. Overall mortality rate was 58%; 40% due to CV events. The rate of overall mortality in the severe calcification group was 75%, and 30% in the low calcification group, whereas the rate of CV mortality was 35% vs. 6%, respectively (p < 0.001). The severe calcification group was older, had higher prevalence of type 2 diabetes mellitus, former cardiologic events, and lower albumin serum levels than the mild-moderate calcification group. In a multivariate Cox model, severe CaC was a significant predictor of CV mortality (HR 5.01; 95%CI 1.28 to 19.6, p = 0.02). CONCLUSIONS: Among advanced CKD, there was a significantly increase of CV mortality in patients with severe CaCs during a 10-year follow-up period. CaCs could be a useful prognostic tool to predict CV mortality risk in CKD patients.
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Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Calcificación Vascular/diagnóstico , Calcificación Vascular/mortalidad , Anciano , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/sangre , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Valor Predictivo de las Pruebas , Estudios Prospectivos , Insuficiencia Renal Crónica/sangre , Factores de Tiempo , Calcificación Vascular/sangreRESUMEN
Lead is toxic to humans and wildlife. Most studies of lead exposure of raptors focus on the winter, non-breeding season when they scavenge heavily. We evaluated blood lead concentrations (BLCs) of red-shouldered hawks (Buteo lineatus) during the non-scavenging season in the eastern United States. BLCs of 53 of 70 hawks were above the limit of detection ([Formula: see text] = 9.25 µg/dL ± 19.81; ± SD). Adult hawks had higher BLCs ([Formula: see text] = 12.86 µg/dL ± 24.72) than did nestlings ([Formula: see text] = 3.25 µg/dL ± 2.62; p ≤ 0.001, χ2 = 13.2). There was no difference in BLCs of adult hawks among physiographic provinces but there were differences between urban and non-urban settings (p = 0.04, χ2 = 4.2). Soils and invertebrate hawk prey also had quantifiable lead concentrations. Our work shows that red-shouldered hawks are exposed to lead when not scavenging, and suggests pathways by which these birds may be exposed.
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Cruzamiento , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/sangre , Halcones/sangre , Plomo/sangre , Animales , Animales Salvajes , Región de los Apalaches , Estaciones del Año , Estados UnidosRESUMEN
The role of nonfictional and fictional media in suicide contagion has been well established, ostensibly beginning with the publication of Goethe's The Sorrows of Young Werther in 1774. In recent decades, the emergence of several new forms of media (e.g. websites, social media, blogs, smartphone applications) has revolutionized the communication and social interaction paradigms. This article reviews "the Werther effect" (or suicide contagion related to media), special populations who are more influential or susceptible, current media reporting guidelines and their effectiveness, and the latest research on new media and its effect on suicide and suicide contagion. The aim is to update recommendations on how to mitigate the potential negative effects of both traditional and new media on suicidal behavior and suicide contagion.
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Medios de Comunicación de Masas , Medios de Comunicación Sociales , Ideación Suicida , Intento de Suicidio/psicología , Comunicación , Humanos , Relaciones InterpersonalesRESUMEN
Defensins play an important role in plant defense against fungal pathogens. The plant defensin, MtDef4, inhibits growth of the ascomycete fungi, Neurospora crassa and Fusarium graminearum, at micromolar concentrations. We have reported that MtDef4 is transported into the cytoplasm of these fungi and exerts its antifungal activity on intracellular targets. Here, we have investigated whether the antifungal mechanisms of MtDef4 are conserved in these fungi. We show that N. crassa and F. graminearum respond differently to MtDef4 challenge. Membrane permeabilization is required for the antifungal activity of MtDef4 against F. graminearum but not against N. crassa. We find that MtDef4 is targeted to different subcellular compartments in each fungus. Internalization of MtDef4 in N. crassa is energy-dependent and involves endocytosis. By contrast, MtDef4 appears to translocate into F. graminearum autonomously using a partially energy-dependent pathway. MtDef4 has been shown to bind to the phospholipid phosphatidic acid (PA). We provide evidence that the plasma membrane localized phospholipase D, involved in the biosynthesis of PA, is needed for entry of this defensin in N. crassa, but not in F. graminearum. To our knowledge, this is the first example of a defensin which inhibits the growth of two ascomycete fungi via different mechanisms.
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Antifúngicos/metabolismo , Defensinas/metabolismo , Endocitosis/fisiología , Fusarium/crecimiento & desarrollo , Neurospora crassa/crecimiento & desarrollo , Transporte Biológico Activo/efectos de los fármacos , Transporte Biológico Activo/fisiología , Brefeldino A/farmacología , Permeabilidad de la Membrana Celular/fisiología , Endocitosis/efectos de los fármacos , Filipina/farmacología , Ácidos Fosfatidicos/química , Fosfolipasa D/química , Fosfolipasa D/genética , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/metabolismo , Plantas/microbiología , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/crecimiento & desarrolloRESUMEN
Rasa3 is a GTPase activating protein of the GAP1 family which targets Ras and Rap1. Ubiquitous Rasa3 catalytic inactivation in mouse results in early embryonic lethality. Here, we show that Rasa3 catalytic inactivation in mouse hematopoietic cells results in a lethal syndrome characterized by severe defects during megakaryopoiesis, thrombocytopenia and a predisposition to develop preleukemia. The main objective of this study was to define the cellular and the molecular mechanisms of terminal megakaryopoiesis alterations. We found that Rasa3 catalytic inactivation altered megakaryocyte development, adherence, migration, actin cytoskeleton organization and differentiation into proplatelet forming megakaryocytes. These megakaryocyte alterations were associated with an increased active Rap1 level and a constitutive integrin activation. Thus, these mice presented a severe thrombocytopenia, bleeding and anemia associated with an increased percentage of megakaryocytes in the bone marrow, bone marrow fibrosis, extramedular hematopoiesis, splenomegaly and premature death. Altogether, our results indicate that Rasa3 catalytic activity controls Rap1 activation and integrin signaling during megakaryocyte differentiation in mouse.
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Plaquetas/metabolismo , Proteínas Activadoras de GTPasa/genética , Hematopoyesis/genética , Proteínas de Unión a Telómeros/genética , Animales , Plaquetas/citología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Diferenciación Celular/genética , Fémur/metabolismo , Fémur/patología , Citometría de Flujo , Proteínas Activadoras de GTPasa/antagonistas & inhibidores , Proteínas Activadoras de GTPasa/metabolismo , Integrinas/genética , Megacariocitos/metabolismo , Megacariocitos/patología , Ratones , Complejo Shelterina , Transducción de Señal/genética , Bazo/metabolismo , Bazo/patología , Proteínas de Unión a Telómeros/metabolismoAsunto(s)
COVID-19 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Niño , Humanos , México/epidemiología , Pandemias , SARS-CoV-2RESUMEN
Snail2 is a zinc finger transcription factor involved in driving epithelial to mesenchymal transitions. Snail2 null mice are viable, but display defects in melanogenesis, gametogenesis and hematopoiesis, and are markedly radiosensitive. Here, using mouse genetics, we have studied the contributions of Snail2 to epidermal homeostasis and skin carcinogenesis. Snail2 (-/-) mice presented a defective epidermal terminal differentiation and, unexpectedly, an increase in number, size and malignancy of tumor lesions when subjected to the two-stage mouse skin chemical carcinogenesis protocol, compared with controls. Additionally, tumor lesions from Snail2 (-/-) mice presented a high inflammatory component with an elevated percentage of myeloid precursors in tumor lesions that was further increased in the presence of the anti-inflammatory agent dexamethasone. In vitro studies in Snail2 null keratinocytes showed that loss of Snail2 leads to a decrease in proliferation indicating a non-cell autonomous role for Snail2 in the skin carcinogenic response observed in vivo. Bone marrow (BM) cross-reconstitution assays between Snail2 wild-type and null mice showed that Snail2 absence in the hematopoietic system fully reproduces the tumor behavior of the Snail2 null mice and triggers the accumulation of myeloid precursors in the BM, blood and tumor lesions. These results indicate a new role for Snail2 in preventing myeloid precursors recruitment impairing skin chemical carcinogenesis progression.
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Inflamación/patología , Queratinocitos/patología , Células Progenitoras Mieloides/patología , Neoplasias Experimentales/patología , Neoplasias Cutáneas/patología , Factores de Transcripción/fisiología , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Apoptosis , Western Blotting , Carcinógenos/toxicidad , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Hematopoyesis , Técnicas para Inmunoenzimas , Inflamación/inducido químicamente , Inflamación/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células Progenitoras Mieloides/efectos de los fármacos , Células Progenitoras Mieloides/metabolismo , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/metabolismo , Factores de Transcripción de la Familia SnailRESUMEN
Snail1 (Snail) and Snail2 (Slug) are transcription factors that share a similar DNA binding structure of four and five C2H2 zinc finger motifs (ZF), respectively. Both factors bind specifically to a subset of E-box motifs (E2-box: CAGGTG/CACCTG) in target promoters like the E-cadherin promoter and are key mediators of epithelial-to-mesenchymal transition (EMT). However, there are differences in the biological actions, in binding affinities to E-cadherin promoter, and in the target genes of Snail1 and Snail2, although the molecular bases are presently unknown. In particular, the role of each Snail1 and Snail2 ZF in the binding to E-boxes and in EMT induction has not been previously explored. We have approached this question by modeling Snail1 and Snail2 protein-DNA interactions and through mutational and functional assays of different ZFs. Results show that Snail1 efficient repression and binding to human and mouse E-cadherin promoter as well as EMT-inducing ability require intact ZF1 and ZF2, while for Snail2, either ZF3 or ZF4 is essential for those functions. Furthermore, the differential distribution of E2-boxes in mouse and human E-cadherin promoters also contributes to the differential Snail factor activity. These data indicate a non-equivalent role of Snail1 and Snail2 ZFs in gene repression, contributing to the elucidation of the molecular differences between these important EMT regulators.
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Cadherinas/genética , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción/genética , Animales , Secuencia de Bases , Western Blotting , Línea Celular , ADN/química , ADN/genética , ADN/metabolismo , Regulación de la Expresión Génica , Células HEK293 , Humanos , Ratones , Microscopía Confocal , Modelos Moleculares , Mutación , Conformación de Ácido Nucleico , Regiones Promotoras Genéticas/genética , Unión Proteica , Estructura Terciaria de Proteína , Factores de Transcripción de la Familia Snail , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Dedos de Zinc/genéticaRESUMEN
OBJECTIVE: Determine the frequency of assaults on health workers and characterize aspects that deepen understanding and development of prevention strategies. METHODS: A voluntary and confidential electronic survey was conducted through the IntraMed website, a social network of health professionals. Frequency of verbal and physical assaults was analyzed along with their association with demographic variables, occupation, career, specialty, potential consequences, perception of insecurity in the workplace, and proposals to reduce them. RESULTS: A total of 19 967 surveys were analyzed, of which 13 323 (66.7%) described assaults. Assaults were physical in 11.3% of cases, and 73.4% occurred in public institutions, mainly in emergency areas. Delay in care and lack of resources were the most frequent triggers. Alcohol or drug intoxication was reported in 13.8% of aggressors, altered mental status from another cause or psychiatric illness in 13.9%, and no detected impairment of mental faculties in 63%. Of professionals attacked, 16.9% reported sequelae, 7.9% of which were physical, and 28% were temporarily unable to work. Insecurity in the workplace was described by 46.6% of respondents, who suggested various measures to reduce it, chief among them, community education CONCLUSIONS: Verbal and physical violence toward health workers was frequent, resulting in work-related, mental, and even physical sequelae. This study contributes information that could be used to develop strategies aimed at prevention and control of assaults.
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Atención a la Salud , Personal de Salud , Humanos , Encuestas y Cuestionarios , Violencia/prevención & controlRESUMEN
Tolerance to abiotic stresses by microorganisms require of appropriate signalling and regulatory pathways. Calcineurin phosphatases mediate calcium-dependent signalling pathways which are widely distributed among phylogeny. In Saccharomyces cerevisiae, calcineurin mediates the post-translational modification of downstream effectors, most of them transcription factors, being the best-characterized calcineurin-regulated zinc-finger factor 1, Crz1p. Here we study the signalling process of CrzA, a filamentous fungal Crz orthologue, in response to calcium and ambient-pH alkalinization. In Aspergillus nidulans resting cells CrzA locates in the cytoplasm being excluded from nuclei. CrzA is a phospho-protein and upon calcium, manganese or alkaline-pH stresses, accumulates in nuclei in a calcineurin-dependent manner. Functional analysis of CrzA defined the presence of a nuclear-export and two nuclear-localization signals as well as a PSINVE sequence that constitutes the major calcineurin-docking domain. First 450 amino acids of CrzA contain these functional motifs and in this region is where phosphorylated residues locate. Different phosphorylation steps are identified in CrzA and activities of casein kinase 1 homologue, CkiA, and of glycogen synthase kinase-3ß, identified for the first time here as GskA, are involved. The phospho-signalling process and nucleocytoplasmic trafficking of CrzA shows similarities to those described in yeast for Crz1p homologues and of NFATs in mammals.
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Aspergillus nidulans/citología , Calcio/metabolismo , Proteínas Fúngicas/metabolismo , Procesamiento Proteico-Postraduccional , Transporte Activo de Núcleo Celular , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Calcineurina/metabolismo , Proteínas Fúngicas/genética , Eliminación de Gen , Regulación Fúngica de la Expresión Génica , Concentración de Iones de Hidrógeno , Mutagénesis Sitio-Dirigida , Señales de Localización Nuclear , Fosforilación , Regiones Promotoras Genéticas , Elementos Reguladores de la TranscripciónRESUMEN
Classically, aldosterone actions are associated with the stability of the effective circulating volume and with blood pressure control, while parathormone actions are linked to bone mineral metabolism, calcium, and phosphate homeostasis. Nevertheless, the relationship between these two hormonal axes surpasses these areas. A bidirectional interrelation between calcium-phosphorus metabolism and blood pressure control can lead to alterations in both. This can have significant implications for the evolution and treatment of patients. To illustrate this relationship, we present two clinical cases that demonstrate the pathophysiology involved.).
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Optimal hypertension care and control at population level significantly reduces cardiovascular morbidity and mortality. The study objective was to measure the gaps in the diagnosis, care, and control of hypertension in residents of an urban community in Quito, Ecuador. A cross-sectional population-based study with a sample of 2160 persons was performed using a survey and direct blood pressure measurement. Logistical regression models were used for analyzing factors associated with the gaps, expressed as percentages. The prevalence of hypertension was 17.6% [CI 95% 17.3-17.9%]. The diagnosis gap was 6.1% [CI 95% 5.9-6.2%] among the entire population and 34.5% [CI 95% 33.7-35.3%] among persons with hypertension. No access gaps were detected; whereas the follow-up gap was 22.7% [CI 95% 21.8-23.6%] and control gap reached 43.5% [CI 95% 42.6-44.2%]. Results indicated that being male, older than 64 years, an employee, without health insurance, and not perceiving a need for healthcare, increased the risk of experiencing these gaps. Data showed appropriate access to health services and high coverage in the diagnosis was due to the application of a community and family healthcare model. Notwithstanding, we found significant gaps in the follow-up and control of hypertensive patients, especially among older males, which should warrant the attention of the Ministry of Health.
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Hipertensión , Determinación de la Presión Sanguínea , Estudios Transversales , Ecuador/epidemiología , Femenino , Humanos , Renta , MasculinoRESUMEN
The enzyme spermine oxidase (SMOX) is involved in polyamine catabolism and converts spermine to spermidine. The enzymatic reaction generates reactive hydrogen peroxide and aldehydes as by-products that can damage DNA and other biomolecules. Increased expression of SMOX is frequently found in lung, prostate, colon, stomach and liver cancer models, and the enzyme also appears to play a role in neuronal dysfunction and vascular retinopathy. Because of growing evidence that links SMOX activity with DNA damage, inflammation, and carcinogenesis, the enzyme has come into view as a potential drug target. A major challenge in cancer research is the lack of characterization of antibodies used for identification of target proteins. To overcome this limitation, we generated a panel of high-affinity rabbit monoclonal antibodies against various SMOX epitopes and selected antibodies for use in immunoblotting, SMOX quantification assays, immunofluorescence microscopy and immunohistochemistry. Immunohistochemistry analysis with the antibody SMAB10 in normal and transformed tissues confirms that SMOX is upregulated in several different cancers. Together, the panel of antibodies generated herein adds to the toolbox of high-quality reagents to study SMOX biology and to facilitate SMOX drug development.
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Antineoplásicos Inmunológicos , Neoplasias , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH , Anticuerpos Monoclonales , Humanos , Inmunohistoquímica , Masculino , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Espermina/metabolismo , Poliamino OxidasaRESUMEN
We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.
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COVID-19 , Glomerulonefritis , Nefritis , Anticuerpos Anticitoplasma de Neutrófilos , COVID-19/complicaciones , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/terapia , Humanos , Masculino , SARS-CoV-2RESUMEN
Human papillomavirus (HPV) is one of the most common causes of sexually transmitted diseases, and the main etiology of cervical cancer. This study was aimed to assess type-specific cervical HPV prevalence and their association with HPV-specific antibodies in a cohort of female university students. HPV genotyping was performed by amplifying and sequencing a fragment of the L1 protein. A BLAST search was performed to identify HPV types. HPV-specific IgG antibodies were measured by ELISA in serum samples. A total of 129 women participated, with an average age of 21.75 years. The prevalence of vaginal HPV infection was 74.42%. The most predominant high-risk HPV types were 18 (13.95%), 31 (10.85%), and 16 (9.3%). We found that early age at coitarche and a higher number of sexual partners were significantly associated with a high prevalence of HPV infection. In addition to sexual behavior, we observed that the presence of serum-specific IgG antibodies against HPV can impact the prevalence of the virus. Seropositivity to HPV-16 and HPV-18 was associated with a lower prevalence of HPV-16, but not for other HPV types. Of note, there was a lower proportion of HPV-specific seropositivity in women who had the presence of the same HPV type in a cervical specimen, suggesting an immunoregulatory mechanism associated with the viral infection. In conclusion, the prevalence of HPV in university women was higher than expected and it was associated with early age of sexual debut, an increasing number of sexual partners, and a low proportion of HPV seropositivity.
Asunto(s)
Infecciones por Papillomavirus , Adulto , Anticuerpos Antivirales , ADN Viral/análisis , Femenino , Humanos , Inmunoglobulina G , México/epidemiología , Papillomaviridae , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos , Estudiantes , Universidades , Adulto JovenRESUMEN
Lead poisoning occurs worldwide in populations of predatory birds, but exposure rates and population impacts are known only from regional studies. We evaluated the lead exposure of 1210 bald and golden eagles from 38 US states across North America, including 620 live eagles. We detected unexpectedly high frequencies of lead poisoning of eagles, both chronic (46 to 47% of bald and golden eagles, as measured in bone) and acute (27 to 33% of bald eagles and 7 to 35% of golden eagles, as measured in liver, blood, and feathers). Frequency of lead poisoning was influenced by age and, for bald eagles, by region and season. Continent-wide demographic modeling suggests that poisoning at this level suppresses population growth rates for bald eagles by 3.8% (95% confidence interval: 2.5%, 5.4%) and for golden eagles by 0.8% (0.7%, 0.9%). Lead poisoning is an underappreciated but important constraint on continent-wide populations of these iconic protected species.