Plasma Letrozole Concentrations in Postmenopausal Women With Breast Cancer Are Associated With CYP2A6 Genetic Variants, Body Mass Index, and Age

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109858/1/cptclpt2011174.pd

Closing a gap in tropical forest biomass estimation : taking crown mass variation into account in pantropical allometries

Accurately monitoring tropical forest carbon stocks is a challenge that remains outstanding. Allometric models that consider tree diameter, height and wood density as predictors are currently used in most tropical forest carbon studies. In particular, a pantropical biomass model has been widely used for approximately a decade, and its most recent version will certainly constitute a reference model in the coming years. However, this reference model shows a systematic bias towards the largest trees. Because large trees are key drivers of forest carbon stocks and dynamics, understanding the origin and the consequences of this bias is of utmost concern. In this study, we compiled a unique tree mass data set of 673 trees destructively sampled in five tropical countries (101 trees > 100 cm in diameter) and an original data set of 130 forest plots (1 ha) from central Africa to quantify the prediction error of biomass allometric models at the individual and plot levels when explicitly taking crown mass variations into account or not doing so. We first showed that the proportion of crown to total tree aboveground biomass is highly variable among trees, ranging from 3 to 88 %. This proportion was constant on average for trees = 45 Mg. This increase coincided with a progressive deviation between the pantropical biomass model estimations and actual tree mass. Taking a crown mass proxy into account in a newly developed model consistently removed the bias observed for large trees (> 1 Mg) and reduced the range of plot- level error (in %) from [-23; 16] to [0; 10]. The disproportionally higher allocation of large trees to crown mass may thus explain the bias observed recently in the reference pantropical model. This bias leads to far- from- negligible, but often overlooked, systematic errors at the plot level and may be easily corrected by taking a crown mass proxy for the largest trees in a stand into account, thus suggesting that the accuracy of forest carbon estimates can be significantly improved at a minimal cost

Gender disparities in pulmonary hypertension at a tertiary centre in Cameroon

Background. Pulmonary hypertension (PH) is a potent cause of heart failure and has been little investigated in the African setting.Objective. To investigate the effects of gender on the clinical presentation, echocardiographic features and outcomes of patients with PH in Douala, Cameroon.Methods. A prospective cohort study was conducted from March 2012 to December 2013 as part of the Pan African Pulmonary Hypertension Cohort study. PH was diagnosed by echocardiography and defined as a right ventricular systolic pressure >35 mmHg in the absence of acute right heart failure. Patients were followed up for a maximum of 12 months for primary endpoint mortality.Results. In total, 130 patients with PH were recruited; 71 (54.6%) were women. The median age was 59.2 years for men and 58.3 years for women (p=0.76). Active smoking and alcohol use were more frequent in men than women (both p<0.001), but women had greater exposure to indoor cooking fumes than men (p<0.001). Previous tuberculosis infection (11.3% v. 1.7%) and S3 gallop rhythm (30.9% v. 11.9%) were more common in women (both p<0.03). Women had a significantly higher mean systolic blood pressure (134 mmHg v. 125 mmHg; p=0.04) and pulse pressure (53.8 mmHg v. 44.9 mmHg; p=0.01) and a lower mean haemoglobin concentration (10.4 g/dL v. 12.4 g/dL; p<0.05) compared with men. Echocardiographic left ventricular (LV) systolic dysfunction was more frequent in men: mean LV ejection fraction 42.6% v. 51.5% (p=0.01) and mean fractional shortening 21.4% v. 28.6% (p=0.01). The overall mortality rate was 20.3%, and rates were similar in the two groups (Kaplan-Meier log rank 1.1; p=0.30).Conclusions. Despite differences in baseline characteristics including cardiovascular risk factors, mortality rates on follow-up were similar in men and women in this study. However, these different baseline characteristics probably suggest differences in the pathogenesis of PH in men and women in our setting that need further investigation.

Exemestane may be less detrimental than letrozole to bone health in women homozygous for the UGT2B17*2 gene deletion

Purpose: UGT2B17 gene deletion (UGT2B17*2) has been reported to affect bone health as well as the pharmacokinetics of aromatase inhibitor (AI) drugs such as exemestane. The goal of this study was to assess associations between UGT2B17 gene deletion and bone health prior to and after 24 months of AI treatment in postmenopausal women with hormone receptor positive (HR+) breast cancer. Methods: Bone health in women with HR+ breast cancer enrolled on the prospective randomized Exemestane and Letrozole Pharmacogenetics (ELPh) trial was determined by measuring bone turnover markers (BTM) and bone mineral density (BMD) pre-treatment and after 3 BTM and 24 BMD months of treatment with either the steroidal AI exemestane or the nonsteroidal AI letrozole. DNA samples were genotyped for UGT2B17*2. Results: Of the 455 subjects included in the analyses, 244 (53.6%) carried at least one copy of UGT2B17*2. UGT2B17*2 was associated with lower pre-treatment BMD at the hip (P = 0.01) and spine (P = 0.0076). Letrozole treatment was associated with a greater decrease in BMD of the hip (P = 0.03) and spine (P = 0.03) than exemestane. UGT2B17 genotype was not associated with changes in BMD from 24 months of AI treatment, though in UGT2B17*2 homozygous patients, there was a trend toward greater decreases in BMD of the spine from treatment with letrozole compared with exemestane (P = 0.05). Conclusion: UGT2B17*2 may be associated with lower baseline BMD in women with HR+ breast cancer. Exemestane is less detrimental to bone health than letrozole in postmenopausal women treated with AI, and this effect may be confined to patients carrying UGT2B17*2, though this finding requires independent validation

Ethnoknowledge of medicinal and mystical plants used by healers in Juazeiro do Norte, Ceará, Northeast Brazil

154-166The aim of this study was to investigate the use of medicinal plants by healers in Juazeiro do Norte, Northeast Brazil, as well as to understand their role in prayer/healing practices. 30 residents from 20 neighborhoods, 18 urban neighborhoods and 2 randomly selected rural locations, were interviewed using a sample method known as "snowball", with two pilot interviews being initially conducted, where for greater method reliability and for the analysis of the importance attributed to the plants by the respondents, a calculation to determine their Relative Importance (RI) index was used. The results indicate the use of 60 species distributed across 34 families. The most representative families were: Fabaceae (7), Lamiaceae (6) and Asteraceae (5), where 10 species (eight exotic and two native) obtained a Relative Importance (RI>1): Ruta graveolens L. (1.47), Vernonia condensata Baker (1.47), Piper aduncun L. (1.44), Mentha spicata L. (1.33), Myracrodruon urundeuva Allemão (1.3), Psidium guajava L. (1.19), Hymenaea stignocarpa Mart. ex. Hayne (1.15), Lippia alba (Mil.) (1.11), Leonotis nepetaefolia (L.) R. Br. (1.08) and Cymbopogon citratus (D.C.) Stapf (1.01). The aforementioned species are acquired from backyards (50%), open markets (33.3%) or from surrounding scrubs (16.6%). Indications included usage for 11 body systems, with 36 species (60%) being indicated for the treatment of the digestive system and 15 (25%) for the treatment of diseases of the female reproductive system. Nine species (15%) were indicated for ritualistic purposes (prayer/healing). With this, the importance of the Healer figure in several municipal districts was observed, a tradition that remains alive, despite the need for greater transmission and assimilation to upcoming generations

Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy

<div><p>There is strong evidence from human and animal models that exposure to maternal hyperglycemia during <i>in utero</i> development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified <i>ex vivo</i> using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7±23.3 vs. STZ 153.2±24.6, mean±SEM, <i>p</i>&lt;0.01) and ureteric tree length (control 33.1±2.6 mm vs. STZ 17.6±2.7 mm, <i>p</i> = 0.001) vs. controls. At E18.5, fetal growth restriction was still present in offspring of STZ dams and a deficit in nephron endowment was observed (control 1246.2±64.9 vs. STZ 822.4±74.0, <i>p&lt;</i>0.001). Kidney malformations in the form of duplex ureter and hydroureter were a common observation (26%) in embryos of diabetic pregnancy compared with controls (0%). Maternal insulin treatment from E13.5 normalised maternal glycaemia but did not normalise fetal weight nor prevent the nephron deficit. The detrimental effect of hyperglycemia on ureteric branching morphogenesis and, in turn, nephron endowment in the growth-restricted fetus highlights the importance of glycemic control in early gestation and during the initial stages of renal development.</p> </div

Resistance of African tropical forests to an extreme climate anomaly.

The responses of tropical forests to environmental change are critical uncertainties in predicting the future impacts of climate change. The positive phase of the 2015-2016 El Niño Southern Oscillation resulted in unprecedented heat and low precipitation in the tropics with substantial impacts on the global carbon cycle. The role of African tropical forests is uncertain as their responses to short-term drought and temperature anomalies have yet to be determined using on-the-ground measurements. African tropical forests may be particularly sensitive because they exist in relatively dry conditions compared with Amazonian or Asian forests, or they may be more resistant because of an abundance of drought-adapted species. Here, we report responses of structurally intact old-growth lowland tropical forests inventoried within the African Tropical Rainforest Observatory Network (AfriTRON). We use 100 long-term inventory plots from six countries each measured at least twice prior to and once following the 2015-2016 El Niño event. These plots experienced the highest temperatures and driest conditions on record. The record temperature did not significantly reduce carbon gains from tree growth or significantly increase carbon losses from tree mortality, but the record drought did significantly decrease net carbon uptake. Overall, the long-term biomass increase of these forests was reduced due to the El Niño event, but these plots remained a live biomass carbon sink (0.51 ± 0.40 Mg C ha-1 y-1) despite extreme environmental conditions. Our analyses, while limited to African tropical forests, suggest they may be more resistant to climatic extremes than Amazonian and Asian forests

Leveraging Signatures of Plant Functional Strategies in Wood Density Profiles of African Trees to Correct Mass Estimations From Terrestrial Laser Data

peer reviewedWood density (WD) relates to important tree functions such as stem mechanics and resistance against pathogens. This functional trait can exhibit high intraindividual variability both radially and vertically. With the rise of LiDAR-based methodologies allowing nondestructive tree volume estimations, failing to account for WD variations related to tree function and biomass investment strategies may lead to large systematic bias in AGB estimations. Here, we use a unique destructive dataset from 822 trees belonging to 51 phylogenetically dispersed tree species harvested across forest types in Central Africa to determine vertical gradients in WD from the stump to the branch tips, how these gradients relate to regeneration guilds and their implications for AGB estimations. We find that decreasing WD from the tree base to the branch tips is characteristic of shade-tolerant species, while light-demanding and pioneer species exhibit stationary or increasing vertical trends. Across all species, the WD range is narrower in tree crowns than at the tree base, reflecting more similar physiological and mechanical constraints in the canopy. Vertical gradients in WD induce significant bias (10%) in AGB estimates when using database-derived species-average WD data. However, the correlation between the vertical gradients and basal WD allows the derivation of general correction models. With the ongoing development of remote sensing products providing 3D information for entire trees and forest stands, our findings indicate promising ways to improve greenhouse gas accounting in tropical countries and advance our understanding of adaptive strategies allowing trees to grow and survive in dense rainforests. © 2020, The Author(s)

Restriction associated DNA-genotyping at multiple spatial scales in Arabidopsis lyrata reveals signatures of pathogen-mediated selection

Background: Genome scans based on outlier analyses have revolutionized detection of genes involved in adaptive processes, but reports of some forms of selection, such as balancing selection, are still limited. It is unclear whether high throughput genotyping approaches for identification of single nucleotide polymorphisms have sufficient power to detect modes of selection expected to result in reduced genetic differentiation among populations. In this study, we used Arabidopsis lyrata to investigate whether signatures of balancing selection can be detected based on genomic smoothing of Restriction Associated DNA sequencing (RAD-seq) data. We compared how different sampling approaches (both within and between subspecies) and different background levels of polymorphism (inbreeding or outcrossing populations) affected the ability to detect genomic regions showing key signatures of balancing selection, specifically elevated polymorphism, reduced differentiation and shifts towards intermediate allele frequencies. We then tested whether candidate genes associated with disease resistance (R-gene analogs) were detected more frequently in these regions compared to other regions of the genome. Results: We found that genomic regions showing elevated polymorphism contained a significantly higher density of R-gene analogs predicted to be under pathogen-mediated selection than regions of non-elevated polymorphism, and that many of these also showed evidence for an intermediate site-frequency spectrum based on Tajima’s D. However, we found few genomic regions that showed both elevated polymorphism and reduced FST among populations, despite strong background levels of genetic differentiation among populations. This suggests either insufficient power to detect the reduced population structure predicted for genes under balancing selection using sparsely distributed RAD markers, or that other forms of diversifying selection are more common for the R-gene analogs tested. Conclusions: Genome scans based on a small number of individuals sampled from a wide range of populations were sufficient to confirm the relative scarcity of signatures of balancing selection across the genome, but also identified new potential disease resistance candidates within genomic regions showing signatures of balancing selection that would be strong candidates for further sequencing efforts