Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.

BACKGROUND: Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the anti-leukaemic effect of CNB. METHODS: Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo. RESULTS: We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARP-mediated apoptosis which was further confirmed with the translocation of AIF to the nucleus observed in WIN-treated cells. Nicotinamide prevented WIN-related apoptosis, indicating NAD+ depletion. Finally, WIN altered glycolytic enzymes levels as well as the activity of G6PDH. These effects are reversed through PARP1 inhibition. CONCLUSIONS: WIN-55 exerts an antileukemic effect through Parthanatos, leading to translocation of AIF to the nucleus and depletion of NAD+, which are reversed through PARP1 inhibition. It also induces metabolic disruptions. These effects are not observed in normal HSC.

A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Comparative 16S rRNA gene sequencing study of subgingival microbiota of healthy subjects and patients with periodontitis from four different countries.

AIM: To investigate the differences between the subgingival microbiota of healthy subjects (HS) and periodontitis patients (PP) from four different countries through a metagenomic approach. MATERIALS AND METHODS: Subgingival samples were obtained from subjects from four different countries. Microbial composition was analysed through high-throughput sequencing of the V3-V4 region of the 16S rRNA gene. The country of origin, diagnosis and clinical and demographic variables of the subjects were used to analyse the microbial profiles. RESULTS: In total, 506 subgingival samples were analysed: 196 from HS and 310 from patients with periodontitis. Differences in richness, diversity and microbial composition were observed when comparing samples pertaining to different countries of origin and different subject diagnoses. Clinical variables, such as bleeding on probing, did not significantly affect the bacterial composition of the samples. A highly conserved core of microbiota associated with periodontitis was detected, while the microbiota associated with periodontally HS was much more diverse. CONCLUSIONS: Periodontal diagnosis of the subjects was the main variable explaining the composition of the microbiota in the subgingival niche. Nevertheless, the country of origin also had a significant impact on the microbiota and is therefore an important factor to consider when describing subgingival bacterial communities.

Proteome alterations during clonal isolation of established human pancreatic cancer cell lines.

Clonal isolation is an integral step of numerous workflows in genome editing and cell engineering. It comprises the isolation of a single progenitor cell from a defined cell line population with subsequent expansion to obtain a monoclonal cell population. This process is associated with transient loss of cell-cell contacts and absence of a multicellular microenvironment. Previous studies have revealed transcriptomic changes upon clonal isolation with cell line specific extent. Since transcriptome alterations are only partially reflected on the proteome level, we sought to investigate the impact of clonal isolation on the cellular proteome to a depth of > 6000 proteins in three established pancreatic cancer cell lines. We show that clonal isolation does have an impact on the cellular proteome, however, with cell line specific extent, affecting different biological processes, and also depending on the isolation method. We demonstrate a different impact of clonal isolation on mesenchymal- and epithelial-derived cell lines mainly affecting cell proliferation, metabolism, cell adhesion and cellular stress. The results bear relevance to the field of genomic editing and cell engineering and highlight the need to consider the impact of clonal isolation when interpreting data stemming from experiments that include this step.

Phosphate-Arsenic Interactions in Halophilic Microorganisms of the Microbial Mat from Laguna Tebenquiche: from the Microenvironment to the Genomes.

Arsenic (As) is a metalloid present in the earth's crust and widely distributed in the environment. Due to its high concentrations in the Andean valleys and its chemical similarity with phosphorus (P), its biological role in Andean Microbial Ecosystems (AMEs) has begun to be studied. The AMEs are home to extremophilic microbial communities that form microbial mats, evaporites, and microbialites inhabiting Andean lakes, puquios, or salt flats. In this work, we characterize the biological role of As and the effect of phosphate in AMEs from the Laguna Tebenquiche (Atacama Desert, Chile). Using micro X-ray fluorescence, the distribution of As in microbial mat samples was mapped. Taxonomic and inferred functional profiles were obtained from enriched cultures of microbial mats incubated under As stress and different phosphate conditions. Additionally, representative microorganisms highly resistant to As and able to grow under low phosphate concentration were isolated and studied physiologically. Finally, the genomes of the isolated Salicola sp. and Halorubrum sp. were sequenced to analyze genes related to both phosphate metabolism and As resistance. The results revealed As as a key component of the microbial mat ecosystem: (i) As was distributed across all sections of the microbial mat and represented a significant weight percentage of the mat (0.17 %) in comparison with P (0.40%); (ii) Low phosphate concentration drastically changed the microbial community in microbial mat samples incubated under high salinity and high As concentrations; (iii) Archaea and Bacteria isolated from the microbial mat were highly resistant to arsenate (up to 500 mM), even under low phosphate concentration; (iv) The genomes of the two isolates were predicted to contain key genes in As metabolism (aioAB and arsC/acr3) and the genes predicted to encode the phosphate-specific transport operon (pstSCAB-phoU) are next to the arsC gene, suggesting a functional relationship between these two elements.

Magnetic viscoelastic behavior in a colloidal ferrofluid.

Based on the stochastic Langevin equation, we derived the total friction experienced by a tracer particle diffusing in thermally equilibrated colloidal magnetic fluids. This transport property leads to new expressions for its long-time diffusion coefficients, which satisfy an Einstein relation with the frictions of its translational and rotational Brownian motion. Further use of the nano-rheology theory allowed us to derive also the viscoelastic modulus of the colloid from such a property. The temporal relaxation of the viscoelasticity and transport coefficient turns out to be governed by the intermediate scattering function of the colloid. We derived an explicit formula for this evolution function within a hydrodynamic theory to include rotational degrees of freedom of the particles. In the limit of short frequencies, the viscous moduli render a new expression for the static viscosity. We found that its comparison with known experiments, at low and high concentration of ferroparticles in magnetite ferrofluids, is fair. However, comparing the predicted viscoelastic moduli with computer simulations as a function of frequency yields poor agreement.

Predicting poverty. Data mining approaches to the health and demographic surveillance system in Cuatro Santos, Nicaragua.

BACKGROUND: In order to further identify the needed interventions for continued poverty reduction in our study area Cuatro Santos, northern Nicaragua, we aimed to elucidate what predicts poverty, measured by the Unsatisfied Basic Need index. This analysis was done by using decision tree methodology applied to the Cuatro Santos health and demographic surveillance databases. METHODS: Using variables derived from the health and demographic surveillance update 2014, transferring individual data to the household level we used the decision tree framework Conditional Inference trees to predict the outcome "poverty" defined as two to four unsatisfied basic needs using the Unsatisfied Basic Need Index. We further validated the trees by applying Conditional random forest analyses in order to assess and rank the importance of predictors about their ability to explain the variation of the outcome "poverty." The majority of the Cuatro Santos households provided information and the included variables measured housing conditions, assets, and demographic experiences since the last update (5 yrs), earlier participation in interventions and food security during the last 4 weeks. RESULTS: Poverty was rare in households that have some assets and someone in the household that has a higher education than primary school. For these households participating in the intervention that installed piped water with water meter was most important, but also when excluding this variable, the resulting tree showed the same results. When assets were not taken into consideration, the importance of education was pronounced as a predictor for welfare. The results were further strengthened by the validation using Conditional random forest modeling showing the same variables being important as predicting the outcome in the CI tree analysis. As assets can be a result, rather than a predictor of more affluence our results in summary point specifically to the importance of education and participation in the water installation intervention as predictors for more affluence. CONCLUSION: Predictors of poverty are useful for directing interventions and in the Cuatro Santos area education seems most important to prioritize. Hopefully, the lessons learned can continue to develop the Cuatro Santos communities as well as development in similar poor rural settings around the world.

Antero-posterior mandibular position at different vertical levels for mandibular advancing device design.

INTRODUCTION: Mandibular Advancement Devices (MAD) have been reported to be an alternative treatment to CPAP in moderate to severe obstructive sleep apnea (OSA) cases. The design of MAD has a major influence on its success rate on the patient, and design features that have an influence on efficacy, tolerance, and compliance. The aim of this study was to determine the range of mandibular protrusion at different vertical points; 2, 5, 8 and 11 mm in a young adult population. METHODS: Fifty two students aged 19 to 23 years (mean 21.3 ± 1.7; 29 females and 23 males), with full permanent dentition participated in the study. The absolute range of maximal mandibular protrusion and retrusion was measured (mm) with the use of the George Gauge. Descriptive statistics, ANOVA and paired t-test using SPSS were used. RESULTS: Range of mandibular advancement was possible to be determined for the 4 levels of vertical opening with the gauges: 2 mm fork mean mandibular advance 13,10 mm ± 0.604; 5 mm mean 11.98 mm ± 1.075; 8 mm mean 11.20 mm ± 1.369; 11 mm mean 9.87 mm ± 1.886. No significant differences were found between class I, II, and III. CONCLUSIONS: There is an impact of increased inter-incisal distance of effective mandibular protrusion when constructing a MAD. As vertical dimension increases the mandible rotates posteriorly and places itself in a more retrusive location, and the range of mandibular advancement reduces (0.3 mm for every 1 mm of vertical increase).

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy.

AIM: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. METHODS: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. RESULTS: The series consisted of five men and three women with an average age of death of 58 years (52-65 years) and average disease duration of 9 years (3-14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876-1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). CONCLUSIONS: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

Bioactive chemical compounds in Eremurus persicus (Joub. & Spach) Boiss. essential oil and their health implications.

The genus Eremurus is native to Eastern Europe and temperate Asia. Particularly, Eremurus persicus (Joub. & Spach) Boiss. is highly valued in traditional foods and medicine. Scientific knowledge about E. persicus chemical composition and bioactivity is required. Therefore, the present study is aimed to determine the volatile composition of E. persicus essential oil (EO) by means of gas chromatography coupled to flame ionization/mass spectrometry detection. Moreover, the antioxidant, antimicrobial, anticancer, and acetylcholinesterase inhibitory activities of the EO were tested. Interestingly, the anti-dermatophyte potency was close to that of the drug griseofulvin, with minimum fungicidal concentration ranging between 0.7 and 4.5% depending on the fungi strain. The EO was also effective against hepatocellular carcinoma (Hep-G2) and breast adenocarcinoma (MCF-7) human cancer cell lines in a concentration (200-1500 ng/mL)-dependent manner, with a decrease of the cell viability up to 65% and 52%, respectively. The E. persicus EO was rich in terpenes and oxygenated terpene derivatives. Individually, limonene (16.25%), geranylgeraniol (15.23%), n-nonanal (9.48%), geranyl acetone (9.12%), benzene acetaldehyde (8.51%), linalool (7.93%), α-pinene (6.89%), and 1,8-cineol (5.22%) were the most abundant volatile compounds and could be chosen as analytical markers of this essential oil. In conclusion, our results suggested that this EO possesses a wide range of bioactive properties that could be useful in nutraceutical, functional foods and cosmeceutical formulations.

Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study.

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10(-7)) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

A glimpse of the endophytic bacterial diversity in roots of blackberry plants (Rubus fruticosus).

The aim of this study was to explore the diversity of culturable bacterial communities residing in blackberry plants (Rubus fruticosus). Bacterial endophytes were isolated from plant roots, and their 16S rDNA sequences were amplified and sequenced. Our results show that the roots of R. fruticosus exhibit low colony forming units of bacterial endophytes per gram of fresh tissue (6 x 102 ± 0.5 x 102). We identified 41 endophytic bacterial species in R. fruticosus by BLAST homology search and a subsequent phylogenetic analysis, belonging to the classes Actinobacteria, Bacilli, Alfaproteobacteria, Betaproteobacteria, and Gammaproteobacteria. Predominantly, genera belonging the Proteobacteria (Burkholderia, 29.4%; Herbaspirillum, 10.7%; Pseudomonas, 4.9%; and Dyella, 3.9%), Firmicutes (Bacillus, 42.1%), and Actinobacteria (two isolates showing high identity with the Streptomyces genus, 1.9%) divisions were identified. Fifty percent of the bacterial endophytes produced the phytohormone indole-acetic acid (IAA), eleven of which exhibited higher IAA production (>5.8 mg/mL) compared to the plant growth-promoting strain, Pseudomonas fluorescens UM270. Additionally, the endophytic isolates exhibited protease activity (22%), produced siderophores (26.4%), and demonstrated antagonistic action (>50% inhibition of mycelial growth) against the grey mold phytopathogen Botrytis cinerea (3.9%). These results suggested that field-grown R. fruticosus plants contain bacterial endophytes within their tissues with the potential to promote plant growth and display antagonism towards plant pathogens.

Genetic relationships among American donkey populations: insights into the process of colonization.

This study presents the first insights into the genetic diversity and structure of the American donkey metapopulation. The primary objectives were to detect the main structural features underlying variability among American donkey populations, identify boundaries between differentiated gene pools, and draw the main colonization pathways since the introduction of donkeys into America in the 15th century. A panel of 14 microsatellite markers was applied for genotyping 350 American donkeys from 13 countries. The genetic structure of this metapopulation was analysed using descriptive statistics and Bayesian model-based methods. These populations were then compared to a database containing information on 476 individuals from 11 European breeds to identify the most likely ancestral donor populations. Results showed the presence of two distinct genetic pools, with confluence of the two in Colombia. The southern pool showed a unique genetic signature subsequent to an older founder event, but lacked any significant influence of modern gene flow from Europe. The northern pool, conversely, may have retained more ancestral polymorphisms and/or have experienced modern gene flow from Spanish breeds. The Andalusian and, to a lesser extent, the Catalan breeds have left a more pronounced footprint in some of the American donkey populations analysed.

Prevention and control strategies for ticks and pathogen transmission.

Ticks and tick-borne pathogens have evolved together, resulting in a complex relationship in which the pathogen's life cycle is perfectly coordinated with the tick's feeding cycle, and the tick can harbour high pathogen levels without affecting its biology. Tick-borne diseases (TBDs) continue to emerge and/or spread, and pose an increasing threatto human and animal health. The disruptive impacts of global change have resulted in ecosystem instability and the future outcomes of management and control programmes for ticks and TBDs are difficult to predict. In particular, the selection of acaricide-resistant ticks has reduced the value of acaricides as a sole means of tick control. Vaccines provide an alternative control method, but the use of tick vaccines has not advanced since the first vaccines were registered in the early 1990s. An understanding of the complex molecular relationship between hosts, ticks and pathogens and the use of systems biology and vaccinomics approaches are needed to discover proteins with the relevant biological function in tick feeding, reproduction, development, immune response, the subversion of host immunity and pathogen transmission, all of which mediate tick and pathogen success. The same approaches will also be required to characterise candidate protective antigens and to validate vaccine formulations. Tick vaccines with a dual effect on tick infestations and pathogen transmission could reduce both tick infestations and their vector capacity for humans, animals and reservoir hosts. The development of integrated tick control strategies, including vaccines and synthetic and botanical acaricides, in combination with managing drug resistance and educating producers, should lead to the sustainable control of ticks and TBDs.

[Weight control behaviors in dieting adolescent girls and their relation to body dissatisfaction and obsession with thinness]. / Conductas de control de peso en mujeres adolescentes dietantes y su relación con insatisfacción corporal y obsesión por la delgadez.

INTRODUCTION: Obsession with thinness and body dissatisfaction can lead adolescents to follow unsupervised diets, which could result in risky weight control behaviors such as fasting, vomiting, use of diuretics and laxatives. The aim of the current study is to examine weight control behaviors in dieting adolescents and relate them to body dissatisfaction (BD) and obsession with thinness (OT). METHODS: A cross-sectional study was conducted on 439 adolescents from Valparaiso public schools to investigate risky weight control behaviors due to BD and OT scales from the Eating Disorders Inventory-2 (EDI-2), comparing restrained eaters and non-restrained eaters. RESULTS: A total of 43% adolescents had followed a weight loss diet without medical supervision. The dieters had higher BD and OT values. Moderate to severe food restriction, based on expert judgment, was observed in 29.6%, and differences in the presence and severity of purging behaviors were found between the 2 groups. CONCLUSIONS: One third of the adolescents studied followed diets without professional supervision and had higher BD and OT values, as well as risky weight control behaviors. Overweight and obese adolescents followed more restrictive diets and developed riskier weight control behaviors.

Influence of the IL17A locus in giant cell arteritis susceptibility.

OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Characterization of bacterial diversity associated with microbial mats, gypsum evaporites and carbonate microbialites in thalassic wetlands: Tebenquiche and La Brava, Salar de Atacama, Chile.

In this paper, we report the presence of sedimentary microbial ecosystems in wetlands of the Salar de Atacama. These laminated systems, which bind, trap and precipitate mineral include: microbial mats at Laguna Tebenquiche and Laguna La Brava, gypsum domes at Tebenquiche and carbonate microbialites at La Brava. Microbial diversity and key biogeochemical characteristics of both lakes (La Brava and Tebenquiche) and their various microbial ecosystems (non-lithifying mats, flat and domal microbialites) were determined. The composition and abundance of minerals ranged from trapped and bound halite in organic-rich non-lithifying mats to aragonite-dominated lithified flat microbialites and gypsum in lithified domal structures. Pyrosequencing of the V4 region of the 16s rDNA gene showed that Proteobacteria comprised a major phylum in all of the microbial ecosystems studied, with a marked lower abundance in the non-lithifying mats. A higher proportion of Bacteroidetes was present in Tebenquiche sediments compared to La Brava samples. The concentration of pigments, particularly that of Chlorophyll a, was higher in the Tebenquiche than in La Brava. Pigments typically associated with anoxygenic phototrophic bacteria were present in lower amounts. Organic-rich, non-lithifying microbial mats frequently formed snake-like, bulbous structures due to gas accumulation underneath the mat. We hypothesize that the lithified microbialites might have developed from these snake-like microbial mats following mineral precipitation in the surface layer, producing domes with endoevaporitic communities in Tebenquiche and carbonate platforms in La Brava. Whereas the potential role of microbes in carbonate platforms is well established, the contribution of endoevaporitic microbes to formation of gypsum domes needs further investigation.

Pulmonary overexpression of inhibitor κBα decreases the severity of ventilator-induced lung injury in a rat model.

BACKGROUND: Activation of the nuclear factor-κB (NF-κB) pathway is central to the pathogenesis of lung injury and inflammation. We determined whether targeted overexpression of inhibitor-κBα (IκBα) in the lung could decrease the severity of ventilator-induced lung injury (VILI). METHODS: Anaesthetized adult male Sprague-Dawley rats were randomly allocated to undergo intratracheal instillation of: (i) vehicle alone (surfactant, n=10); (ii) 1×10(10) adeno-associated virus encoding IκBα (AAV-IκBα, n=10); (iii) 5×10(10) AAV-IκBα (n=10); and (iv) 1×10(10) AAV-Null (n=5). This was followed by 4 h of injurious mechanical ventilation. Subsequent experiments examined the effect of IκBα overexpression in animals undergoing 'protective' mechanical ventilation. RESULTS: IκBα overexpression increased survival duration at both the lower [3.8 h (0.4)] and higher [3.6 h (0.7)] doses compared with vehicle [2.7 h (1.0)] or the null transgene [2.2 h (0.8)]. IκBα overexpression reduced the alveolar-arterial oxygen gradient (kPa) at both the lower [53 (21)] and higher [52 (19)] doses compared with vehicle [75 (8.5)] or the null transgene [70 (15)], decreased alveolar neutrophil infiltration, and reduced alveolar concentrations of interleukin (IL)-1ß and IL-10. The lower IκBα dose was as effective as the higher dose. IκBα overexpression had no effect in the setting of protective lung ventilation. CONCLUSIONS: Inhibition of pulmonary NF-κB activity by IκBα overexpression reduced the severity of VILI in a rat model.

The nutrition transition in the Venezuelan Amazonia: increased overweight and obesity with transculturation.

OBJECTIVES: Amerindians have a particularly high propensity to overweight and obesity as they change lifestyle and experience a nutrition transition. The aim of this study was to evaluate the effects of transculturation on nutritional status in three Amazonian Amerindian villages. METHODS: Nutritional status was assessed in 232 volunteers: 65 Yanomami from an isolated village and 167 Guahibo subjects from villages with intermediate and high levels of transculturation. RESULTS: There was a significant pattern of decreasing stunting and increasing overweight and obesity across the gradient of transculturation. From the jungle Yanomami to the intermediate and transculturated Guahibo, stunting was respectively 72, 55, and 39%, and children /adult overweight was 0, 3/44, and 15/89%. These anthropometric-based patterns were confirmed by bioimpedance vector analysis. CONCLUSIONS: Transculturation in these Amerindian populations is associated with an increase in overweight and obesity coexisting with undernourished children.