Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer.

PURPOSE: To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas. METHODS: Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score). RESULTS: The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)). CONCLUSIONS: This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test.

Priority setting for health research: toward a management process for low and middle income countries (Working Paper 1)

This Working Paper documents the interactions of a ‘think tank’ consultation, initiated by COHRED, bringing together health research managers from Brazil, South Africa, The Netherlands, The Philippines, the private sector, the Pan American Health Organization (PAHO), the Global Forum for Health Research and COHRED. Its purpose was to better understand the issues countries face and their needs in moving priority setting forward as well as seeking advice from professionals on how COHRED can support them in managing a process of setting and measuring progress in health research priorities. Rather than having priorities ‘reviewed’ and ‘set’ through a workshop or national activity that produces a plan reflecting the situation at one point in time, the discussion in this think tank examined what process is needed so that national health research priorities are managed in a dynamic way, and are measured, updated and can evolve with the reality of the national, operational and political context. (...)

Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration.

All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other hand, proper development and functioning of the retina requires a precise balance between the processes of proliferation, differentiation and programmed cell death. The life-or-death decision seems to be the result of a complex balance between pro- and anti-apoptotic signals. It has been recently shown the efficacy of natural products to slow retinal degenerative process through different pathways. In this review, we assess the neuroprotective effect of two compounds used in the ancient pharmacopoeia. On one hand, it has been demonstrated that administration of the saffron constituent safranal to P23H rats, an animal model of retinitis pigmentosa, preserves photoreceptor morphology and number, the capillary network and the visual response. On the other hand, it has been shown that systemic administration of tauroursodeoxycholic acid (TUDCA), the major component of bear bile, to P23H rats preserves cone and rod structure and function, together with their contact with postsynaptic neurons. The neuroprotective effects of safranal and TUDCA make these compounds potentially useful for therapeutic applications in retinal degenerative diseases.

Gradual morphogenesis of retinal neurons in the peripheral retinal margin of adult monkeys and humans.

The adult mammalian retina has for long been considered to lack a neurogenerative capacity. However, retinal stem/progenitor cells, which can originate retinal neurons in vitro, have been recently reported in the ciliary body of adult mammals. Here we explored the possibility of retinal neurogenesis occurring in vivo in adult monkeys and humans. We found the presence of cells expressing molecular markers of neural and retinal progenitors in the nonlaminated retinal margin and ciliary body pars plana of mature primates. By means of immunohistochemistry and electron microscopy we also observed photoreceptors and other retinal cell types in different stages of morphological differentiation along the peripheral retinal margin. These findings allow us to extend to primates the idea of neurogenesis aimed at retinal cell turnover throughout life.

Alpha synuclein gene expression profile in the retina of vertebrates.

PURPOSE: Alpha-synuclein is a Parkinson's disease-linked protein of ubiquitous expression in the central nervous system. It has a proposed role in the modulation of neurotransmission and synaptic function. This study was aimed at analyzing expression of the alpha-synuclein gene in the normal retina, and characterizing its pattern of distribution in the different retinal cell types and layers in a variety of vertebrates, ranging from fish to humans. METHODS: Reverse transcriptase-polymerase chain reaction and immunoblotting were used to assess alpha-synuclein expression at both mRNA and protein levels. Its retinal distribution profile was characterized by immunohistochemical methods. With this purpose, retinal sections were analyzed under fluorescent confocal microscopy using specific antibodies against alpha-synuclein, alone and in double or triple combinations with a set of antibodies to molecular markers for the distinct retinal neuronal types. Also, synaptophysin was used as a marker for synaptic vesicles in the retina. RESULTS: Alpha-synuclein mRNA and protein were expressed by both retinal pigment epithelium (RPE) and neural retinal cells. The pattern of alpha-synuclein distribution in the retina was quite consistent across all vertebrate species examined. A strong immunoreactivity was found in the outer segments (OS) of photoreceptors and in their axon terminals (cone pedicles and rod spherules) in the outer plexiform layer (OPL) of the retina. Alpha-synuclein was also present in rod and cone bipolar cells, as well as in GABAergic and glycinergic amacrines, distributing along a complex plexus throughout the inner plexiform layer (IPL). Additionally, colocalization was found between alpha-synuclein and synaptophysin at presynaptic terminals of the retina. Alpha-synuclein-positive phagosome-like structures were observed in the cytoplasm of RPE cells. CONCLUSIONS: An involvement of alpha-synuclein can be postulated in neurotransmission at axon terminals of photoreceptors in the OPL, and at presynaptic endings of bipolar and amacrine cells in the IPL. As well, this protein could have a role in the function as well as the maintenance of photoreceptor OS. Alpha-synuclein contained in RPE cells should derive not only from protein expression by this cell type, but also from their phagocytosis of OS disc membranes.

Morphological impairments in retinal neurons of the scotopic visual pathway in a monkey model of Parkinson's disease.

Physiological abnormalities resulting from death of dopaminergic neurons of the central nervous system in Parkinson's disease also extend to the retina, resulting in impaired visual functions. In both parkinsonian patients and animal models, low levels of dopamine and loss of dopaminergic cells in the retina have been reported. However, the morphology and connectivity of their postsynaptic neurons, the amacrine cells, have not been analyzed. Here we report, with macaques chronically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a model of Parkinson's disease, that morphological impairments in dopaminergic retinal neurons and their plexus in the inner retina are accompanied by an immunoreactivity decrease in gamma-aminobutyric acidergic and glycinergic amacrine cells. Especially deteriorated were AII amacrine cells, the main neuronal subtype postsynaptic to dopaminergic cells, which exhibited a marked loss of lobular appendages and dendritic processes. Concomitantly, electrical synapses among AII cells, as well as chemical synapses between these and rod bipolar cells, were highly deteriorated in parkinsonian monkeys. These results highlight that the scotopic visual pathway is severely impaired in the parkinsonian condition and provide a morphological basis for a number of abnormalities found in electrophysiological and psychophysical trials in Parkinson's disease patients and animal models.

Os desafios da integração regional para a pesquisa em sistemas e serviços de saúde.

Apresentação que trata do esforço nacional em criar, estruturar e transformar a pesquisa na área de saúde, de forma a se tornar uma ferramenta da integração regional. Expõe o panorama da saúde pública no Brasil a partir do ano 2000, abordando a necessidade de políticas de intervenção não só nacionais, mas também para o Mercosul. Propõe uma Agenda Nacional de Prioridades de Pesquisa em Saúde de forma a identificar o contexto de cada região, identificar temas de pesquisa, incentivar a participação de gestores e promover cada vez mais discussões com conferências municipais, regionais e estaduais de saúde. .