Clonal Composition of Human Adrenocortical Neoplasms

The mechanisms of tumorigenesis of adrenocortical neoplasms are still not understood. Tumor formation may be the result of spontaneous transformation of adrenocortical cells by somatic mutations. Another factor stimulating adrenocortical cell growth and potentially associated with formation of adrenal adenomas and, less frequently, carcinomas is the chronic elevation of proopiomelanocortin-derived peptides in diseases like ACTH-dependent Cushing's syndrome and congenital adrenal hyperplasia. To further investigate the pathogenesis of adrenocortical neoplasms, we studied the clonal composition of such tumors using X-chromosome inactivation analysis of the highly polymorphic region Xcen-Xp11.4 with the hybridization probe M27ß, which maps to a variable number of tandem repeats on the X-chromsome. In addition, polymerase chain reaction amplification of a phosphoglycerokinase gene polymorphism was performed. After DNA extraction from tumorous adrenal tissue and normal leukocytes in parallel, the active X-chromosome of each sample was digested with the methylation-sensitive restriction enzyme HpaII. A second digestion with an appropriate restriction enzyme revealed the polymorphism of the region Xcen-Xp11.4 and the phosphoglycerokinase locus. Whereas in normal polyclonal tissue both the paternal and maternal alleles are detected, a monoclonal tumor shows only one of the parental alleles. A total of 21 female patients with adrenal lesions were analyzed; 17 turned out to be heterozygous for at least one of the loci. Our results were as follows: diffuse (n = 4) and nodular (n = 1) adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome, polyclonal pattern; adrenocortical adenomas (n = 8), monoclonal (n = 7), as well as polyclonal (n = 1); adrenal carcinomas (n = 3), monoclonal pattern. One metastasis of an adrenocortical carcinoma showed a pattern most likely due to tumor-associated loss of methylation. In the special case of a patient with bilateral ACTH-independent macronodular hyperplasia, diffuse hyperplastic areas and a small nodule showed a polyclonal pattern, whereas a large nodule was monoclonal. We conclude that most adrenal adenomas and carcinomas are monoclonal, whereas diffuse and nodular adrenal hyperplasias are polyclonal. The clonal composition of ACTH-independent massive macronodular hyperplasia seems to be heterogeneous, consisting of polyclonal and monoclonal areas

Climate change and food security: health impacts in developed countries.

BACKGROUND: Anthropogenic climate change will affect global food production, with uncertain consequences for human health in developed countries. OBJECTIVES: We investigated the potential impact of climate change on food security (nutrition and food safety) and the implications for human health in developed countries. METHODS: Expert input and structured literature searches were conducted and synthesized to produce overall assessments of the likely impacts of climate change on global food production and recommendations for future research and policy changes. RESULTS: Increasing food prices may lower the nutritional quality of dietary intakes, exacerbate obesity, and amplify health inequalities. Altered conditions for food production may result in emerging pathogens, new crop and livestock species, and altered use of pesticides and veterinary medicines, and affect the main transfer mechanisms through which contaminants move from the environment into food. All these have implications for food safety and the nutritional content of food. Climate change mitigation may increase consumption of foods whose production reduces greenhouse gas emissions. Impacts may include reduced red meat consumption (with positive effects on saturated fat, but negative impacts on zinc and iron intake) and reduced winter fruit and vegetable consumption. Developed countries have complex structures in place that may be used to adapt to the food safety consequences of climate change, although their effectiveness will vary between countries, and the ability to respond to nutritional challenges is less certain. CONCLUSIONS: Climate change will have notable impacts upon nutrition and food safety in developed countries, but further research is necessary to accurately quantify these impacts. Uncertainty about future impacts, coupled with evidence that climate change may lead to more variable food quality, emphasizes the need to maintain and strengthen existing structures and policies to regulate food production, monitor food quality and safety, and respond to nutritional and safety issues that arise

What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review

© 2014 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. Methods: A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Results: Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Conclusions: Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.The Canadian Institute of Health Research (CIHR) Drug Safety and Effectiveness Network (Funding reference number – 116573)

Water

Meta-analysis can be a powerful tool for demonstrating the applicability of a concept beyond the context of individual clinical trials and observational studies, including exploration of effects across different subgroups. Meta-analysis avoids Simpson's paradox, in which a consistent effect in constituent trials is reversed when results are simply pooled. Meta-analysis in critical care medicine is made more complicated, however, by the heterogeneous nature of critically ill patients and the contexts within which they are treated. Failure to properly adjust for this heterogeneity risks missing important subgroup effects in, for example, the interaction of treatment with varying levels of baseline risk. When subgroups are defined by characteristics that vary within constituent trials (such as age) rather than features constant within each trial (such as drug dose), there is the additional risk of incorrect conclusions due to the ecological fallacy. The present review explains these problems and the strategies by which they are overcome

Intelligent driver profiling system for cars – a basic concept

Many industries have been transformed by the provision of service solutions characterised by personalisation and customisation - most dramatically the development of the iPhone. Personalisation and customisation stand to make an impact on cars and mobility in comparable ways. The automobile industry has a major role to play in this change, with moves towards electric vehicles, auton-omous cars, and car sharing as a service. These developments are likely to bring disruptive changes to the business of car manufacturers as well as to drivers. However, in the automobile industry, both the user's preferences and demands and also safety issues need to be confronted since the frequent use of different makes and models of cars, implied by car sharing, entails several risks due to variations in car controls depending on the manufacturer. Two constituencies, in particular, are likely to experience even more difficulties than they already do at present, namely older people and those with capability variations. To overcome these challenges, and as a means to empower a wide car user base, the paper here presents a basic concept of an intelligent driver profiling system for cars: the sys-tem would enable various car characteristics to be tailored according to individual driver-dependent profiles. It is intended that wherever possible the system will personalise the characteristics of individual car components; where this is not possible, however, an initial customisation will be performed

Benefícios do ômega 3 na prevenção de doença cardiovascular: Revisão integrativa de literatura

Introduction: Omega-3 polyunsaturated fatty acids such as alpha-linolenic acid (ALA), a fat found in plant foods, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both found in fish, have been considered relevant substances for the maintenance of health, so that supplementation is being considered relevant for the reduction of cardiovascular risks. Objective: To identify and analyze the scientific evidence available in the literature on the contribution of omega 3 in the prevention and treatment of cardiovascular disease. Materials and Methods: Integrative literature review, with deference to materials published in the Scielo and PubMed databases, which considered as inclusion criteria articles published in the last 5 years, available in full, in English, Spanish, and Portuguese, which addressed the proposed theme; the exclusion criteria were editorials, letters to the editor, review studies, theses, dissertations, and duplicate articles that did not correspond to the theme. Results: Based on the aforementioned scientific evidence, the body's omega-3 indices are relevant to identify possible cardiovascular risk, so it can therefore be used as an objective for treatment when there is a possible risk for these manifestations. This risk factor can be modified by taking EPA and DHA. The standard 1 g/day dose of EPA and DHA recommended by cardiac societies is, however, probably far from ideal for everyone, as not only this standard dose but also diet, individual genetic history, body mass index, calorie intake and disposal, and other factors all together probably determine a person's level of omega-3 fatty acids. Therefore, it is suggested that the omega-3 index acts not only as a risk factor for cardiovascular disease, but that other contexts allied to the patient's lifestyle should be considered. Conclusion: Diet or supplementation of these nutrients may result in cardiovascular and other types of benefits to society as a whole

The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity

Background: We characterized the biologic effects of a novel small molecule STAT3 pathway inhibitor that is derived from the natural product curcumin. We hypothesized this lead compound would specifically inhibit the STAT3 signaling pathway to induce apoptosis in melanoma cells. Results: FLLL32 specifically reduced STAT3 phosphorylation at Tyr705 (pSTAT3) and induced apoptosis at micromolar amounts in human melanoma cell lines and primary melanoma cultures as determined by annexin V/propidium iodide staining and immunoblot analysis. FLLL32 treatment reduced expression of STAT3-target genes, induced caspase-dependent apoptosis, and reduced mitochondrial membrane potential. FLLL32 displayed specificity for STAT3 over other homologous STAT proteins. In contrast to other STAT3 pathway inhibitors (WP1066, JSI-124, Stattic), FLLL32 did not abrogate IFN-γ-induced pSTAT1 or downstream STAT1-mediated gene expression as determined by Real Time PCR. In addition, FLLL32 did not adversely affect the function or viability of immune cells from normal donors. In peripheral blood mononuclear cells (PBMCs), FLLL32 inhibited IL-6-induced pSTAT3 but did not reduce signaling in response to immunostimulatory cytokines (IFN-γ, IL 2). Treatment of PBMCs or natural killer (NK) cells with FLLL32 also did not decrease viability or granzyme b and IFN-γ production when cultured with K562 targets as compared to vehicle (DMSO). Conclusions: These data suggest that FLLL32 represents a lead compound that could serve as a platform for further optimization to develop improved STAT3 specific inhibitors for melanoma therapy

Detección de patrones aberrantes en pruebas tipo test: Una aplicación en el Grado en Psicología de la Universidad de Barcelona

Las pruebas con ítems de respuesta múltiple son una práctica habitual en el contexto universitario. Los patrones de respuesta incoherentes, denominados Patrones Atípicos de Respuesta (PAR), aparecen cuando las respuestas correctas e incorrectas a los ítems no siguen el patrón esperado, i.e., acertar los ítems más fáciles y fallar los más difíciles. Este estudio pretende identificar los PAR en una prueba tipo test de la asignatura Psicometría del Grado en Psicología de la Universidad de Barcelona y explorar su relación con el rendimiento académico. Un total de 214 alumnos matriculados durante el curso 2018-2019 respondieron a una prueba tipo test de 20 ítems. Se calcularon cuatro índices de detección y se identificaron 13 PAR (6,1%), con más presencia en estudiantes con una calificación superior. La detección de PAR debería contribuir a la mejora de los sistemas de evaluación y del proceso de aprendizaje de los alumnos

European Society of Cardiology quality indicators update for the care and outcomes of adults with heart failure. The Heart Failure Association of the ESC.

AIMS: To update the European Society of Cardiology (ESC) quality indicators (QIs) for the evaluation of the care and outcomes of adults with heart failure. METHODS AND RESULTS: The Working Group comprised experts in heart failure including members of the ESC Clinical Practice Guidelines Task Force for heart failure, members of the Heart Failure Association, and a patient representative. We followed the ESC methodology for QI development. The 2023 focused guideline update was reviewed to assess the suitability of the recommendations with strongest association with benefit and harm against the ESC criteria for QIs. All the new proposed QIs were individually graded by each panellist via online questionnaires for both validity and feasibility. The existing heart failure QIs also underwent voting to 'keep', 'remove' or 'modify'. Five domains of care for the management of heart failure were identified: (1) structural QIs, (2) patient assessment, (3) initial treatment, (4) therapy optimization, and (5) patient health-related quality of life. In total, 14 'main' and 3 'secondary' QIs were selected across the five domains. CONCLUSION: This document provides an update of the previously published ESC QIs for heart failure to ensure that these measures are aligned with contemporary evidence. The QIs may be used to quantify adherence to clinical practice as recommended in guidelines to improve the care and outcomes of patients with heart failure