Clinical spectum of tuberculous optic neuropathy

Purpose Tuberculous optic neuropathy may follow infection with Mycobacterium tuberculosis or administration of the bacille Calmette–Guerin. However, this condition is not well described in the ophthalmic literature. Methods Ophthalmologists, identified through professional electronic networks or previous publications, collected standardized clinical data relating to 62 eyes of 49 patients who they had managed with tuberculous optic neuropathy. Results Tuberculous optic neuropathy was most commonly manifested as papillitis (51.6 %), neuroretinitis (14.5 %), and optic nerve tubercle (11.3 %). Uveitis was an additional ocular morbidity in 88.7 % of eyes. In 36.7 % of patients, extraocular tuberculosis was present. The majority of patients (69.4 %) had resided in and/or traveled to an endemic area. Although initial visual acuity was 20/50 or worse in 62.9 % of 62 eyes, 76.7 % of 60 eyes followed for a median of 12 months achieved visual acuities of 20/40 or better. Visual field defects were reported for 46.8 % of eyes, but these defects recovered in 63.2 % of 19 eyes with follow-up. Conclusion Visual recovery from tuberculous optic neuropathy is common, if the diagnosis is recognized and appropriate treatment is instituted. A tuberculous etiology should be considered when evaluating optic neuropathy in persons from endemic areas.Research to Prevent Blindness (unrestricted grant to Casey Eye Institute) provided partial support for this work

Food and nutrition security discursive frames in the context of the Spanish economic crisis

[EN] The recent economic crisis in Spain has provoked a number of food and nutrition security (FNS) impacts that have fuelled a fragmented landscape of food-related debates, although these have not taken the form of a coherent and allembracing public discussion on national food security. This paper is an inductive analysis of such debates, mostly based on media coverage, in an attempt to disentangle the different discourse frames on FNS in Spain, and the role played by the economic crisis in the shaping and underpinning of such frames. For this purpose a frame matrix was constructed, paying particular attention to the stakeholders governance claims in order to confront frame-specific problems. Results show how stakeholders have used elements of the crisis to underpin or reinterpret their core arguments. In addition, governance claims have concentrated on the malfunctioning of the food chain, mostly due to unequal bargaining power, and the way this could be putting at risk crucial components of the food system and future FNS. Also, the short-termism of most stakeholders approaches obscures the long run threats to the Spanish food system.This research is part of the project "Assessment of the impact of global drivers of change on Europe's food security" (TRANSMANGO), granted by the EU under 7th Framework Programme, theme KBBE.2013.2.5-01, Grant agreement no: 613532. Authors gratefully appreciate the comments and suggestions made by the three anonymous reviewers and the editors of the Journal.OOrtiz Miranda, D.; Moreno Pérez, OM.; Arnalte Alegre, EV. (2016). Food and nutrition security discursive frames in the context of the Spanish economic crisis. Food Security. 8(3):665-677. https://doi.org/10.1007/s12571-016-0574-xS66567783Antentas, J. M., & Vivas, E. (2014). 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Bonn: ZEF.Sáez-Almendros, S., Obrador, B., Bach-Faig, A., & Serra-Majem, L. (2013). Environmental footprints of Mediterranean versus Western dietary patterns: beyond the health benefits of the Mediterranean diet. Environmental Health, 12, 118.Shepherd, B. (2012). Thinking critically about food security. Security Dialogue, 43(3), 195–212.Sineiro, F. (2012). Situación actual, retos y perspectivas del vacuno de leche. Available at http://www.eumedia.es/portales/files/documentos/2-FSineiro.pdf . Accessed 19 Nov 2015.Van Gorp, B. (2007). The constructionist approach to framing: bringing culture back. Journal of Communication, 57, 60–78.Van Gorp, B., & van der Goot, M. J. (2012). Sustainable food and agriculture: Stakeholder’s frames. Communication, Culture & Critique, 5, 127–148.Vidal, R., Moliner, E., Pikula, A., Mena-Nieto, A., & Ortega, A. (2015). Comparison of the carbon footprint of different patient diets in a Spanish hospital. Journal of Health Services Research & Policy, 20(1), 39–44

A systematic review and meta-analysis to determine the contribution of mr imaging to the diagnosis of foetal brain abnormalities In Utero.

OBJECTIVES: This systematic review was undertaken to define the diagnostic performance of in utero MR (iuMR) imaging when attempting to confirm, exclude or provide additional information compared with the information provided by prenatal ultrasound scans (USS) when there is a suspicion of foetal brain abnormality. METHODS: Electronic databases were searched as well as relevant journals and conference proceedings. Reference lists of applicable studies were also explored. Data extraction was conducted by two reviewers independently to identify relevant studies for inclusion in the review. Inclusion criteria were original research that reported the findings of prenatal USS and iuMR imaging and findings in terms of accuracy as judged by an outcome reference diagnosis for foetal brain abnormalities. RESULTS: 34 studies met the inclusion criteria which allowed diagnostic accuracy to be calculated in 959 cases, all of which had an outcome reference diagnosis determined by postnatal imaging, surgery or autopsy. iuMR imaging gave the correct diagnosis in 91 % which was an increase of 16 % above that achieved by USS alone. CONCLUSION: iuMR imaging makes a significant contribution to the diagnosis of foetal brain abnormalities, increasing the diagnostic accuracy achievable by USS alone. KEY POINTS: • Ultrasound is the primary modality for monitoring foetal brain development during pregnancy • iuMRI used together with ultrasound is more accurate for detecting foetal brain abnormalities • iuMR imaging is most helpful for detecting midline brain abnormalities • The moderate heterogeneity of reviewed studies may compromise findings

Exhaustive prediction of disease susceptibility to coding base changes in the human genome

<p>Abstract</p> <p>Background</p> <p>Single Nucleotide Polymorphisms (SNPs) are the most abundant form of genomic variation and can cause phenotypic differences between individuals, including diseases. Bases are subject to various levels of selection pressure, reflected in their inter-species conservation.</p> <p>Results</p> <p>We propose a method that is not dependant on transcription information to score each coding base in the human genome reflecting the disease probability associated with its mutation. Twelve factors likely to be associated with disease alleles were chosen as the input for a support vector machine prediction algorithm. The analysis yielded 83% sensitivity and 84% specificity in segregating disease like alleles as found in the Human Gene Mutation Database from non-disease like alleles as found in the Database of Single Nucleotide Polymorphisms. This algorithm was subsequently applied to each base within all known human genes, exhaustively confirming that interspecies conservation is the strongest factor for disease association. For each gene, the length normalized average disease potential score was calculated. Out of the 30 genes with the highest scores, 21 are directly associated with a disease. In contrast, out of the 30 genes with the lowest scores, only one is associated with a disease as found in published literature. The results strongly suggest that the highest scoring genes are enriched for those that might contribute to disease, if mutated.</p> <p>Conclusion</p> <p>This method provides valuable information to researchers to identify sensitive positions in genes that have a high disease probability, enabling them to optimize experimental designs and interpret data emerging from genetic and epidemiological studies.</p

Recommendations for increasing the use of HIV/AIDS resource allocation models

The article of record as published may be found at: http://dx.doi.org/10.1186/1471-2458-9-S1-S8Background: Resource allocation models have not had a substantial impact on HIV/AIDS resource allocation decisions in spite of the important, additional insights they may provide. In this paper, we highlight six difficulties often encountered in attempts to implement such models in policy settings; these are: model complexity, data requirements, multiple stakeholders, funding issues, and political and ethical considerations. We then make recommendations as to how each of these difficulties may be overcome. Results: To ensure that models can inform the actual decision, modellers should understand the environment in which decision-makers operate, including full knowledge of the stakeholders' key issues and requirements. HIV/AIDS resource allocation model formulations should be contextualized and sensitive to societal concerns and decision-makers' realities. Modellers should provide the required education and training materials in order for decision-makers to be reasonably well versed in understanding the capabilities, power and limitations of the model. Conclusion: This paper addresses the issue of knowledge translation from the established resource allocation modelling expertise in the academic realm to that of policymaking

Regulation of Tumor Suppressor p53 and HCT116 Cell Physiology by Histone Demethylase JMJD2D/KDM4D

JMJD2D, also known as KDM4D, is a histone demethylase that removes methyl moieties from lysine 9 on histone 3 and from lysine 26 on histone 1.4. Here, we demonstrate that JMJD2D forms a complex with the p53 tumor suppressor in vivo and interacts with the DNA binding domain of p53 in vitro. A luciferase reporter plasmid driven by the promoter of p21, a cell cycle inhibitor and prominent target gene of p53, was synergistically activated by p53 and JMJD2D, which was dependent on JMJD2D catalytic activity. Likewise, overexpression of JMJD2D induced p21 expression in U2OS osteosarcoma cells in the absence and presence of adriamycin, an agent that induces DNA damage. Furthermore, downregulation of JMJD2D inhibited cell proliferation in wild-type and even more so in p53−/− HCT116 colon cancer cells, suggesting that JMJD2D is a pro-proliferative molecule. JMJD2D depletion also induced more strongly apoptosis in p53−/− compared to wild-type HCT116 cells. Collectively, our results demonstrate that JMJD2D can stimulate cell proliferation and survival, suggesting that its inhibition may be helpful in the fight against cancer. Furthermore, our data imply that activation of p53 may represent a mechanism by which the pro-oncogenic functions of JMJD2D become dampened

Motion processing with wide-field neurons in the retino-tecto-rotundal pathway

The retino-tecto-rotundal pathway is the main visual pathway in non-mammalian vertebrates and has been found to be highly involved in visual processing. Despite the extensive receptive fields of tectal and rotundal wide-field neurons, pattern discrimination tasks suggest a system with high spatial resolution. In this paper, we address the problem of how global processing performed by motion-sensitive wide-field neurons can be brought into agreement with the concept of a local analysis of visual stimuli. As a solution to this problem, we propose a firing-rate model of the retino-tecto-rotundal pathway which describes how spatiotemporal information can be organized and retained by tectal and rotundal wide-field neurons while processing Fourier-based motion in absence of periodic receptive-field structures. The model incorporates anatomical and electrophysiological experimental data on tectal and rotundal neurons, and the basic response characteristics of tectal and rotundal neurons to moving stimuli are captured by the model cells. We show that local velocity estimates may be derived from rotundal-cell responses via superposition in a subsequent processing step. Experimentally testable predictions which are both specific and characteristic to the model are provided. Thus, a conclusive explanation can be given of how the retino-tecto-rotundal pathway enables the animal to detect and localize moving objects or to estimate its self-motion parameters

Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods

Is analysing the nitrogen use at the plant canopy level a matter of choosing the right optimization criterion?

Optimization theory in combination with canopy modeling is potentially a powerful tool for evaluating the adaptive significance of photosynthesis-related plant traits. Yet its successful application has been hampered by a lack of agreement on the appropriate optimization criterion. Here we review how models based on different types of optimization criteria have been used to analyze traits—particularly N reallocation and leaf area indices—that determine photosynthetic nitrogen-use efficiency at the canopy level. By far the most commonly used approach is static-plant simple optimization (SSO). Static-plant simple optimization makes two assumptions: (1) plant traits are considered to be optimal when they maximize whole-stand daily photosynthesis, ignoring competitive interactions between individuals; (2) it assumes static plants, ignoring canopy dynamics (production and loss of leaves, and the reallocation and uptake of nitrogen) and the respiration of nonphotosynthetic tissue. Recent studies have addressed either the former problem through the application of evolutionary game theory (EGT) or the latter by applying dynamic-plant simple optimization (DSO), and have made considerable progress in our understanding of plant photosynthetic traits. However, we argue that future model studies should focus on combining these two approaches. We also point out that field observations can fit predictions from two models based on very different optimization criteria. In order to enhance our understanding of the adaptive significance of photosynthesis-related plant traits, there is thus an urgent need for experiments that test underlying optimization criteria and competing hypotheses about underlying mechanisms of optimization