The quest for equity in Latin America: a comparative analysis of the health care reforms in Brazil and Colombia

<p>Abstract</p> <p>Introduction</p> <p>Brazil and Colombia have pursued extensive reforms of their health care systems in the last couple of decades. The purported goals of such reforms were to improve access, increase efficiency and reduce health inequities. Notwithstanding their common goals, each country sought a very different pathway to achieve them. While Brazil attempted to reestablish a greater level of State control through a public national health system, Colombia embraced market competition under an employer-based social insurance scheme. This work thus aims to shed some light onto why they pursued divergent strategies and what that has meant in terms of health outcomes.</p> <p>Methods</p> <p>A critical review of the literature concerning equity frameworks, as well as the health care reforms in Brazil and Colombia was conducted. Then, the shortfall inequality values of crude mortality rate, infant mortality rate, under-five mortality rate, and life expectancy for the period 1960-2005 were calculated for both countries. Subsequently, bivariate and multivariate linear regression analyses were performed and controlled for possibly confounding factors.</p> <p>Results</p> <p>When controlling for the underlying historical time trend, both countries appear to have experienced a deceleration of the pace of improvements in the years following the reforms, for all the variables analyzed. In the case of Colombia, some of the previous gains in under-five mortality rate and crude mortality rate were, in fact, reversed.</p> <p>Conclusions</p> <p>Neither reform seems to have had a decisive positive impact on the health outcomes analyzed for the defined time period of this research. This, in turn, may be a consequence of both internal characteristics of the respective reforms and external factors beyond the direct control of health reformers. Among the internal characteristics: underfunding, unbridled decentralization and inequitable access to care seem to have been the main constraints. Conversely, international economic adversities, high levels of rural and urban violence, along with entrenched income inequalities seem to have accounted for the highest burden among external factors.</p

On-sky results of the adaptive optics MACAO for the new IR-spectrograph CRIRES at VLT

The adaptive optics MACAO has been implemented in 6 focii of the VLT observatory, in three different flavors. We present in this paper the results obtained during the commissioning of the last of these units, MACAO-CRIRES. CRIRES is a high-resolution spectrograph, which efficiency will be improved by a factor two at least for point-sources observations with a NGS brighter than R=15. During the commissioning, Strehl exceeding 60% have been observed with fair seeing conditions, and a general description of the performance of this curvature adaptive optics system is done.Comment: SPIE conference 2006, Advances in adaptive optics, 12 pages, 11 figure

A Highly Sensitive Assay for Monitoring the Secretory Pathway and ER Stress

Background: The secretory pathway is a critical index of the capacity of cells to incorporate proteins into cellular membranes and secrete proteins into the extracellular space. Importantly it is disrupted in response to stress to the endoplasmic reticulum that can be induced by a variety of factors, including expression of mutant proteins and physiologic stress. Activation of the ER stress response is critical in the etiology of a number of diseases, such as diabetes and neurodegeneration, as well as cancer. We have developed a highly sensitive assay to monitor processing of proteins through the secretory pathway and endoplasmic reticulum (ER) stress in real-time based on the naturally secreted Gaussia luciferase (Gluc). Methodology/Principle Findings: An expression cassette for Gluc was delivered to cells, and its secretion was monitored by measuring luciferase activity in the conditioned medium. Gluc secretion was decreased down to 90% when these cells were treated with drugs that interfere with the secretory pathway at different steps. Fusing Gluc to a fluorescent protein allowed quantitation and visualization of the secretory pathway in real-time. Expression of this reporter protein did not itself elicit an ER stress response in cells; however, Gluc proved very sensitive at sensing this type of stress, which is associated with a temporary decrease in processing of proteins through the secretory pathway. The Gluc secretion assay was over 20,000-fold more sensitive as compared to the secreted alkaline phosphatase (SEAP), a well established assay for monitoring of protein processing and ER stress in mammalian cells. Conclusions/Significance: The Gluc assay provides a fast, quantitative and sensitive technique to monitor the secretory pathway and ER stress and its compatibility with high throughput screening will allow discovery of drugs for treatment of conditions in which the ER stress is generally induced

Constrained SUSY seesaws with a 125 GeV Higgs

Motivated by the ATLAS and CMS discovery of a Higgs-like boson with a mass around 125 GeV, and by the need of explaining neutrino masses, we analyse the three canonical SUSY versions of the seesaw mechanism (type I, II and III) with CMSSM boundary conditions. In type II and III cases, SUSY particles are lighter than in the CMSSM (or the constrained type I seesaw), for the same set of input parameters at the universality scale. Thus, to explain $m_{h^0} \simeq 125 GeV$ at low energies, one is forced into regions of parameter space with very large values of $m_0$, $M_{1/2}$ or $A_0$. We compare the squark and gluino masses allowed by the ATLAS and CMS ranges for $m_{h^0}$ (extracted from the 2011-2012 data), and discuss the possibility of distinguishing seesaw models in view of future results on SUSY searches. In particular, we briefly comment on the discovery potential of LHC upgrades, for squark/gluino mass ranges required by present Higgs mass constraints. A discrimination between different seesaw models cannot rely on the Higgs mass data alone, therefore we also take into account the MEG upper limit on BR$(\mu \to e \gamma)$ and show that, in some cases, this may help to restrict the SUSY parameter space, as well as to set complementary limits on the seesaw scale.Comment: 28 pages, 7 figures. v2: comments and references added. Final version to appear in JHE

Role of Chaperone Mediated Autophagy (CMA) in the Degradation of Misfolded N-CoR Protein in Non-Small Cell Lung Cancer (NSCLC) Cells

Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells

Don’t make me angry, you wouldn’t like me when I’m angry: volitional choices to act or inhibit are modulated by subliminal perception of emotional faces

Volitional action and self-control—feelings of acting according to one’s own intentions and in being control of one’s own actions—are fundamental aspects of human conscious experience. However, it is unknown whether high-level cognitive control mechanisms are affected by socially salient but nonconscious emotional cues. In this study, we manipulated free choice decisions to act or withhold an action by subliminally presenting emotional faces: In a novel version of the Go/NoGo paradigm, participants made speeded button-press responses to Go targets, withheld responses to NoGo targets, and made spontaneous, free choices to execute or withhold the response for Choice targets. Before each target, we presented emotional faces, backwards masked to render them nonconscious. In Intentional trials, subliminal angry faces made participants more likely to voluntarily withhold the action, whereas fearful and happy faces had no effects. In a second experiment, the faces were made supraliminal, which eliminated the effects of angry faces on volitional choices. A third experiment measured neural correlates of the effects of subliminal angry faces on intentional choice using EEG. After replicating the behavioural results found in Experiment 1, we identified a frontal-midline theta component—associated with cognitive control processes—which is present for volitional decisions, and is modulated by subliminal angry faces. This suggests a mechanism whereby subliminally presented “threat” stimuli affect conscious control processes. In summary, nonconscious perception of angry faces increases choices to inhibit, and subliminal influences on volitional action are deep seated and ecologically embedded

Preclinical Evidence Supporting Early Initiation of Citalopram Treatment in Machado-Joseph Disease

Spinocerebellar ataxias are dominantly inherited neurodegenerative disorders with no disease-modifying treatment. We previously identified the selective serotonin reuptake inhibitor citalopram as a safe and effective drug to be repurposed for Machado-Joseph disease. Pre-symptomatic treatment of transgenic (CMVMJD135) mice strikingly ameliorated mutant ataxin-3 (ATXN3) pathogenesis. Here, we asked whether citalopram treatment initiated at a post-symptomatic age would still show efficacy. We used a cohort of CMVMJD135 mice that shows increased phenotypic severity and faster disease progression (CMVMJD135hi) compared to the mice used in the first trial. Groups of hemizygous CMVMJD135hi mice were orally treated with citalopram. Behavior, protein analysis, and pathology assessment were performed blindly to treatment. Our results show that even when initiated after symptom onset, treatment of CMVMJD135hi mice with citalopram ameliorated motor coordination and balance, attenuating disease progression, albeit to a lesser extent than that seen with pre-symptomatic treatment initiation. There was no impact on ATXN3 aggregation, which contrasts with the robust reduction in ATXN3-positive inclusions observed in CMVMJD135 mice, when treated pre-symptomatically. Post-symptomatic treatment of CMVMJD135hi mice revealed, however, a limited neuroprotective effect by showing a tendency to repair cerebellar calbindin staining, and to increase the number of motor neurons and of NeuN-positive cells in certain brain regions. While supporting that early initiation of treatment with citalopram leads to a marked increase in efficacy, these results strengthen our previous observation that modulation of serotonergic signaling by citalopram is a promising therapeutic approach for Machado-Joseph disease even after symptom onset.European Regional Development Funds (FEDER), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER. This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to PM) and [EXPL/BIM-MEC/0239/2012] (to AT-C), by FCT through the project [POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to PM), by National Ataxia foundation (to PM and to AT-C), and by Ataxia UK (to PM). SE, SD-S, SO, and AT-C were supported by the FCT individual fellowships, SFRH/BD/78554/2011, SFRH/BD/78388/2011, PD/BD/127818/2016, and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa, and EU/FSEinfo:eu-repo/semantics/publishedVersio

Performance, feed utilization, and hepatic metabolic response of weaned juvenile Atlantic bluefin tuna (Thunnus thynnus L.): effects of dietary lipid level and source

The development of formulated diets and feeds is essential to increase production of farmed tuna species. There is limited knowledge of this topic, mainly on Pacific Bluefin tuna (Thunnus orientalis) in Japan, whereas no major attempts have been made with Atlantic Bluefin tuna (Thunnus thynnus; ABT). In the present study, two trials were performed using inert formulated diets as on-growing feeds for weaned ABT juvenile in order to establish adequate dietary levels of both lipid and omega-3 long-chain polyunsaturated fatty acids (LC-PUFA). In a first trial, ABT (initial weight = 2.9±0.9g) were fed for 10 days with either a commercial (Magokoro®, MGK) or two experimental feeds with two different lipid levels (15 or 20%) using krill oil (KO) as the single lipid source in order to estimate the suitable lipid content. Fish fed MGK displayed the highest growth, followed by 15KO, with no differences in fish survival. Thus, a lipid content of 15% was considered better than 20% for ABT juveniles. In the second trial, fish (initial weight = 3.3 ± 0.6g) were fed either MGK, 15KO or a feed containing 15% lipid with a combination (1:1, v/v) KO and rapeseed oil (RO) (15KORO). Fish fed 15KO and 15KORO showed the highest growth in terms of weight and fork length (including weight gain and SGR). Increasing dietary lipid level or adding RO to the feeds did not increase liver lipid content. The liver fatty acid profile largely reflected dietary intake confirming very limited LC-PUFA biosynthetic activity for this teleost species. In this respect, liver of fish fed 15KO and 20KO displayed the highest contents of docosahexaenoic acid (DHA). The hepatic expression of genes of lipid and fatty acid metabolism, transcription factors, and antioxidant enzymes was investigated with many of the genes showing regulation by both dietary lipid and LC-PUFA contents. The present study showed promising results that suggested ABT juveniles can be on grown on inert dry feeds that supported good fish growth and the accumulation of the health-promoting fatty acid DHA. Further studies are required in order to fully elucidate lipid and fatty acid requirements of this iconic species regarding dietary sources and production costs.En prensa1,52