Transforming Growth Factor Beta 2 and Heme Oxygenase 1 Genes Are Risk Factors for the Cerebral Malaria Syndrome in Angolan Children

BACKGROUND: Cerebral malaria (CM) represents a severe outcome of the Plasmodium falciparum infection. Recent genetic studies have correlated human genes with severe malaria susceptibility, but there is little data on genetic variants that increase the risk of developing specific malaria clinical complications. Nevertheless, susceptibility to experimental CM in the mouse has been linked to host genes including Transforming Growth Factor Beta 2 (TGFB2) and Heme oxygenase-1 (HMOX1). Here, we tested whether those genes were governing the risk of progressing to CM in patients with severe malaria syndromes. METHODOLOGY/PRINCIPAL FINDINGS: We report that the clinical outcome of P. falciparum infection in a cohort of Angolan children (n = 430) correlated with nine TGFB2 SNPs that modify the risk of progression to CM as compared to other severe forms of malaria. This genetic effect was explained by two haplotypes harboring the CM-associated SNPs (Pcorrec. = 0.035 and 0.036). In addition, one HMOX1 haplotype composed of five CM-associated SNPs increased the risk of developing the CM syndrome (Pcorrec. = 0.002) and was under-transmitted to children with uncomplicated malaria (P = 0.036). Notably, the HMOX1-associated haplotype conferred increased HMOX1 mRNA expression in peripheral blood cells of CM patients (P = 0.012). CONCLUSIONS/SIGNIFICANCE: These results represent the first report on CM genetic risk factors in Angolan children and suggest the novel hypothesis that genetic variants of the TGFB2 and HMOX1 genes may contribute to confer a specific risk of developing the CM syndrome in patients with severe P. falciparum malaria. This work may provide motivation for future studies aiming to replicate our findings in larger populations and to confirm a role for these genes in determining the clinical course of malaria

Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study

<p>Abstract</p> <p>Background</p> <p>Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE) inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events.</p> <p>Methods</p> <p>We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala), catalase (CAT -21A/T), glutathione peroxidase 1 (GPx-1 Pro198Leu), ACE (I/D) and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135) to hydrogen peroxide (H₂O₂), and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H₂O₂at 250 μM and 1 mM).</p> <p>Results</p> <p>After treatment with H₂O₂at 250 μM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress.</p> <p>Conclusions</p> <p>The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.</p

Near-infrared fluorescence laparoscopy of the cystic duct and cystic artery: first experience with two new preclinical dyes in a pig model

Imaging techniques that enhance visualisation of the anatomy may help prevent bile duct injury. Near-Infrared Fluorescence Imaging is such a technique. Previous experiments with ICG have shown that illumination of the extra-hepatic bile ducts is feasible. Yet, there is room for improvement in the visualisation of the target as compared to the background. Experiments with IRDye(A (R)) 800CW show promising results. However, this dye is too expensive for routine clinical use. The aim of this study is to test the first applicability of two newly developed preclinical dyes regarding intraoperative imaging of the cystic duct and cystic artery, compared with IRDye(A (R)) 800CW.Laparoscopic cholecystectomy was performed in three pigs, using a laparoscopic fluorescence imaging system. Each pig received 6 mg of one of the fluorescent dyes (1 mg/mL; IRDye(A (R)) 800CW, IRDye(A (R)) 800BK or IRDye(A (R)) 800NOS) by intravenous injection. Intraoperative recognition of the biliary system and cystic artery was registered at set time points. All procedures were digitally recorded, and the target to background ratio (TBR) was determined to assess the fluorescence signal.With all three fluorescent dyes, the cystic artery was directly visualised. For the visualisation of the cystic duct, 15, 34 and 30 min were needed using IRDye(A (R)) 800BK, IRDye(A (R)) 800NOS and IRDye(A (R)) 800CW, respectively. The maximum TBR of the cystic duct was the highest with IRDye(A (R)) 800NOS (4.20) after 36 min, compared to 2.45 for IRDye(A (R)) 800BK and 2.15 for IRDye(A (R)) 800CW, both after 45 min. There were no adverse events.IRDye(A (R)) 800BK and IRDye(A (R)) 800NOS seem to be good alternatives for IRDye(A (R)) 800CW for the visualisation of the cystic duct and cystic artery in pigs.</p

Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests

Tropical forests face increasing climate risk1,2, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, Ψ50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk3–5, little is known about how these vary across Earth’s largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters Ψ50 and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both Ψ50 and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM50 forests. We propose that this may be associated with a growth–mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon6,7, with strong implications for the Amazon carbon sink

Diretrizes para cessação do tabagismo - 2008

Estas diretrizes constituem uma ferramenta atualizada e abrangente para auxiliar o profissional de saúde na abordagem do tabagista, recomendando atitudes baseadas em evidências clínicas como a melhor forma de conduzir cada caso. De forma reduzida e mais objetiva possível, o texto final foi agrupado em dois grandes itens: Avaliação e Tratamento. Os dois itens apresentam comentários e níveis de recomendação das referências utilizadas, bem como algumas propostas de abordagem, como por exemplo, redução de danos, em situações específicas ainda pouco exploradas, como recaídas, tabagismo passivo, tabagismo na categoria médica e uso de tabaco em ambientes específicos.These guidelines are an up-to-date and comprehensive tool to aid health professionals in treating smokers, recommending measures and strategies for managing each case based on clinical evidence. Written in a simplified and objective manner, the text is divided into two principal sections: Evaluation and Treatment. The sections both present comments on and levels of evidence represented by the references cited, as well as some proposals for the reduction of damage and for intervening in specific and still poorly explored situations, such as relapse, passive smoking, physician smoking, and tobacco use in specific environments

Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The pan-Amazonian HT dataset (Ψ 50, Ψ dry and HSM50) and branch wood density per species per site, as well as forest dynamic and climate data per plot presented in this study are available as a ForestPlots.net data package at https://forestplots.net/data-packages/Tavares-et-al-2023. Basal area weighted mean LMA is shown in Supplementary Table 2. Species stem wood density data were obtained from Global Wood Density database65,66. Species WDA data were extracted from ref. 45.Code availability: The codes to recreate the main analyses and the main figures presented in this study are available as a ForestPlots.net data package at https://forestplots.net/data-packages/Tavares-et-al-2023.Tropical forests face increasing climate risk, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, Ψ 50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk, little is known about how these vary across Earth’s largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters Ψ 50 and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both Ψ 50 and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM50 forests. We propose that this may be associated with a growth–mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon, with strong implications for the Amazon carbon sink