Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are responsible for a hereditary cancer syndrome characterized by high susceptibility to hemangioblastomas of the retina and central ...nervous system, pheochromocytomas, and renal cell carcinomas. In agreement with its role as a tumor suppressor, the vast majority of spontaneous clear cell carcinomas of the kidney present loss of heterozygosity at the VHL locus. Recently, it has been shown that VHL works as the substrate recognition component of an E3 ubiquitination complex that targets the hypoxia-inducible factor (HIF) for proteosomal degradation. Under normal oxygen tension, the half-life of HIF transcription factors is extremely short because of its high degradation rate by the proteasome, resulting in undetectable HIF activity in normal cells. However, in VHL-deficient tumor cells, the HIF transcriptional pathway is constitutively activated because of impaired ubiquitination of this transcription factor. To target VHL-deficient tumors, we have exploited this feature to develop a conditionally replicative adenovirus (Ad9xHRE1A), the replication of which is HIF dependent. In this new oncolytic adenovirus, the expression of the E1A gene is controlled by an optimized minimal promoter containing HIF recognition elements. Here, we show that the induction of the E1A gene, as well as the viral replication and cytolytic effect of Ad9xHRE1A, are dependent on HIF activity. As a consequence, this virus efficiently kills VHL-deficient cells both in vitro and in vivo, as well as cells growing under hypoxic conditions. These data suggest that Ad9xHRE1A could be used as a highly specific therapy for VHL-deficient cancers and probably many other tumors that show extensive hypoxic areas or increased HIF activity by genetic alterations other than VHL loss.
Borderline Personality Disorder (BPD) has been associated with an intensive use of health resources and a high economic burden.
The aim of this study is to analyze the use of mental healthcare ...resources by BPD patients, to identify the information gaps on BPD at the regional health databases and to describe specific indicators and patterns of care utilization by persons with BPD in order to guide evidence-informed policy planning in Catalonia (Spain).
A multi-level cross-design synthesis approach was applied following a mixed quantitative-qualitative analysis to estimate the regional service utilisation of patients with BPD. This framing analysis included estimates based on all available data on the use of services combined with prior expert knowledge gathered through a nominal group of key stakeholders in this field.
The estimated year prevalence of BPD was 0.7% but only 9.6% of all BPD patients in Catalonia had any contact with the health care system. Of those, less than half contacted mental health care. BPD represented 1.7% of the total care load in the community mental health centres. A significant information gap was identified in all the official databases and impeded their direct use for planning and resource allocation in BPD. Expert knowledge was required to estimate rates of care utilization at every level of care system (primary care, specialized outpatient care and hospital care). Nevertheless the high pattern of care utilization identified at the databases was accurate according to the experts.
Detection of BPD was lower than expected in the local, regional and national databases and registries of Catalonia. Local data was judged highly inaccurate by experts in comparison to data available on other mental disorders in the same databases.
Specific incentives should be implemented to improve the availability and accuracy of information on BPD at the regional databases. When present, BPD should be coded before other psychiatric disorders in clinical records and health databases. Mental health surveys and psychiatric epidemiological studies should specifically incorporate BPD in their inclusion criteria and further studies on the utilisation pattern of this disorder are needed, both locally and internationally.
This paper presents an overview of the work done so far related to the use of temperature sensors as performance monitors for RF and MMW circuits with the goal to implement built-in testing or ...self-calibration techniques. The strategy is to embed small temperature sensors on the same silicon die as the circuit under test, taking advantage of empty spaces in the layout. This paper reviews the physical principles, and presents examples that reveal how temperature sensors can be used as functional built-in testers serving to reduce testing costs and enhance yield as part of self-healing strategies.
Evidence strongly supports that to improve breastfeeding practices it is needed to strengthen actions of promotion, protection and support. To achieve this goal, it is necessary to establish a ...multisectoral national policy that includes elements such as design, implementation, monitoring and evaluation of programs and policies, funding research, advocacy to develop political willingness, and the promotion of breastfeeding from the national to municipal level, all coordinated by a central level. It is until now that Mexico has initiated a reform process to the establish a National Strategy for Breastfeeding Action. This strategy, is the result not only of the consistent scientific evidence on clear and strong benefits of breastfeeding on population health and the development of human capital, but also for the alarming data of deterioration of breastfeeding practices in the country. The comprehensive implementation of the National Strategy for Breastfeeding Action that includes the establishment of a national committee, intra- and inter-sectoral coordination of actions, setting clear goals and monitoring the International Code of Marketing of Breast-Milk Substitutes, is the awaiting responsibility of the public health agenda of the country.
Objective: Borderline personality disorder (BPD) is a common personality disorder, with a population prevalence of 1.4-5.9%, although the epidemiology of this disorder in primary care is ...insufficiently known. Our objective was to determine the registered prevalence of BPD in primary care databases and to study the demographic and clinical characteristics of these patients. Methods: We performed a cross-sectional study of the computerized databases of primary care clinical records. The target population consisted of all adults (> 16 years old) registered in the Catalan Health Institute (n = 4,764,729). Results: The prevalence of recorded BPD was 0.017%, and was higher in patients with other mental disorders, particularly substance-abuse disorders (0.161%). These patients had twice as many appointments with the general practitioner as the general population (8.1 vs. 4.4). Conclusion: The number of diagnoses of BPD recorded in primary care is extremely low, which contrasts with the available population-based data.Objetivo: El trastorno límite de la personalidad (TLP) es frecuente, con una prevalencia poblacional del 1,4% al 5,9%, aunque la epidemiología de este trastorno en atención primaria es escasamente conocida. Nuestro objetivo es determinar la prevalencia registrada de TLP en atención primaria y estudiar las características de estos pacientes. Métodos: Estudio transversal de las bases de datos informatizadas de las historias clínicas de atención primaria. La población diana son los adultos (>16 años) registrados en el Instituto Catalán de la Salud (n = 4.764.729). Resultados: La prevalencia de TLP registrada es del 0,017%, y es mayor en los pacientes con otros trastornos mentales, particularmente trastornos por abuso de sustancias (0,161%). Estos pacientes duplican las visitas al médico general de la población general (8,1 frente a 4,4). Conclusión: Los diagnósticos de TLP registrados en atención primaria son escasos, lo que contrasta con los datos poblacionales disponibles.
Electric fields have been highlighted as a smart reagent in nature's enzymatic machinery, as they can directly trigger or accelerate redox and/or non-redox chemical processes with stereo- and ...regio-specificity. In natural catalysis, controlled mass transport of chemical species in confined spaces is also key in facilitating the transport of reactants into the active reaction site. Despite the opportunities the above offers in developing strategies for a new, clean electrostatic catalysis exploiting oriented electric fields, research in this area has been mostly limited to theoretical and experimental studies at the level of single molecules or small molecular ensembles, where both the control over mass transport and scalability cannot be tested. Here, we quantify the electrostatic catalysis of a prototypical Huisgen cycloaddition in a large-area electrode surface and directly compare its performance to the traditional Cu(I)-catalyzed method of the same reaction. Mass diffusion control is achieved in a custom-built microfluidic cell, which enhances reagent transport towards the electrified reactive interface while avoiding both turbulent flow conditions and poor control of the convective mass transport. This unprecedented electrostatic continuous-flow microfluidic reactor is an example of an electric-field driven platform where clean large-scale electrostatic catalytic processes can be efficiently implemented and regulated.
La atelectasia crónica maxilar (ACM) es una enfermedad poco frecuente, que se caracteriza por una disminución de volumen del seno maxilar con retracción de una o más de sus paredes. El mecanismo ...causal parece ser una hipoventilación del seno maxilar por obstrucción del complejo ostiomeatal, que crea presión negativa y retracción de las paredes del seno.
Se presenta el caso de una niña de 14 años asintomática, que presentaba una imagen radiológica de opacidad en seno maxilar persistente a tratamiento. En la TC coronal se apreciaba una opacificación parcial del seno maxilar derecho, con desplazamiento lateral de la pared infundibular medial y retracción de la mucosa del meato medio, por lo que la paciente fue diagnosticada de ACM. El interés del caso radica en que se trata de una enfermedad poco conocida, que no debe confundirse con la sinusitis maxilar.
Chronic maxillary atelectasis (CMA) is an infrequent entity characterized by a persistent decrease in maxillary sinus volume due to inward bowing of one or more antral walls. The cause of CMA is probably maxillary sinus hypoventilation secondary to ostiomeatal complex obstruction. This creates negative pressure, leading to thinning of the sinus walls.
We report the case of a 14-year-old asymptomatic girl with an opacified maxillary sinus on radiology following unsuccessful antibiotic treatment. A coronal computed tomography scan showed partial right antral opacification, with a laterally malpositioned medial infundibular wall and fontanel retraction, and consequently CMA was diagnosed. The interest of this case lies in the infrequency of CMA and the need to distinguish it from maxillary sinusitis.
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