Review: Towards the next-generation models of the rumen microbiome for enhancing predictive power and guiding sustainable production strategies.

The rumen ecosystem harbours a galaxy of microbes working in syntrophy to carry out a metabolic cascade of hydrolytic and fermentative reactions. This fermentation process allows ruminants to harvest nutrients from a wide range of feedstuff otherwise inaccessible to the host. The interconnection between the ruminant and its rumen microbiota shapes key animal phenotypes such as feed efficiency and methane emissions and suggests the potential of reducing methane emissions and enhancing feed conversion into animal products by manipulating the rumen microbiota. Whilst significant technological progress in omics techniques has increased our knowledge of the rumen microbiota and its genome (microbiome), translating omics knowledge into effective microbial manipulation strategies remains a great challenge. This challenge can be addressed by modelling approaches integrating causality principles and thus going beyond current correlation-based approaches applied to analyse rumen microbial genomic data. However, existing rumen models are not yet adapted to capitalise on microbial genomic information. This gap between the rumen microbiota available omics data and the way microbial metabolism is represented in the existing rumen models needs to be filled to enhance rumen understanding and produce better predictive models with capabilities for guiding nutritional strategies. To fill this gap, the integration of computational biology tools and mathematical modelling frameworks is needed to translate the information of the metabolic potential of the rumen microbes (inferred from their genomes) into a mathematical object. In this paper, we aim to discuss the potential use of two modelling approaches for the integration of microbial genomic information into dynamic models. The first modelling approach explores the theory of state observers to integrate microbial time series data into rumen fermentation models. The second approach is based on the genome-scale network reconstructions of rumen microbes. For a given microorganism, the network reconstruction produces a stoichiometry matrix of the metabolism. This matrix is the core of the so-called genome-scale metabolic models which can be exploited by a plethora of methods comprised within the constraint-based reconstruction and analysis approaches. We will discuss how these methods can be used to produce the next-generation models of the rumen microbiome.

Performance Comparison of Different Flat Plate Solar Collectors by Means of the Entropy Generation Rate Using Computational Fluid Dynamics.

In this work, a numerical analysis of three different flat plate solar collectors was conducted using their entropy generation rates. Specifically, the Computational Fluid Dynamics (CFD) technique was used to compare the detailed performance of conventional and zigzag tube geometries of flat plate solar collectors (FPCs) in terms of their entropy generation rates. The effects of fluid viscosity, heat transfer, and heat loss of the flat plate solar collectors were considered for the local and global entropy generation rate analyses. Variations on the inlet volumetric flow rate of the FPCs from 1.0 to 9.0 L/min were simulated under the average solar radiation for one year in the state of Guanajuato, Mexico. The results illustrate and discuss the temperatures, pressures, and global entropy generation rates for volumetric flow variations. The velocity, temperature, and pressure distributions and the maps of the local entropy generation rates inside the collectors are presented and analyzed for the case with a flow rate of 3.0 L/min. These results demonstrate that the zigzag geometries achieved higher outlet temperatures and greater entropy generation rates than the conventional geometry for all the volumetric flow rates considered.

Assessment of dependence potential and abuse liability of Δ8-tetrahydrocannabinol in mice.

Delta-8-tetrahydrocannabinol (Δ8-THC) is a psychotropic cannabinoid produced in low quantities in the cannabis plant. Refinements in production techniques, paired with the availability of inexpensive cannabidiol substrate, have resulted in Δ8-THC being widely marketed as a quasi-legal, purportedly milder alternative to Δ9-THC. Yet, little research has probed the behavioral and physiological effects of repeated Δ8-THC use. The present study aimed to evaluate the effects of acute and repeated exposure to Δ8-THC. We hypothesized that Δ8-THC produces effects similar to Δ9-THC, including signs of drug tolerance and dependence. Adult male and female C57BL/6J mice were treated acutely with Δ8-THC (6.25-100 mg/kg, i.p.) or vehicle and tested in the tetrad battery to quantify cannabimimetic effects (i.e., catalepsy, antinociception, hypothermia, immobility) as compared with a non-selective synthetic cannabinoid (WIN 55,212-2) and Δ9-THC. As previously reported, Δ8-THC (≥12.5 mg/kg) induced cannabimimetic effects. Pretreatment with the CB1 receptor-selective antagonist rimonabant (3 mg/kg, i.p.) blocked each of these effects. In addition, repeated administration of Δ8-THC (50 mg/kg, s.c.) produced tolerance, as well as cross-tolerance to WIN 55,212-2 (10 mg/kg, s.c.) in tetrad, consistent with downregulated CB1 receptor function. Behavioral signs of physical dependence in the somatic signs, tail suspension, and marble burying assays were also observed following rimonabant-precipitated withdrawal from Δ8-THC (≥10 mg/kg BID for 6 days). Lastly, Δ8-THC produced Δ9-THC-like discriminative stimulus effects in both male and female mice. Together, these findings demonstrate that Δ8-THC produces qualitatively similar effects to Δ9-THC, including risk of drug dependence and abuse liability.

Marijuana use in young mothers and adverse pregnancy outcomes: a retrospective cohort study.

OBJECTIVE: To evaluate the association between marijuana use and a composite adverse pregnancy outcome using biological sampling. DESIGN: Retrospective cohort study. SETTING: Single tertiary center. POPULATION: Young women (13-22 years old) with singleton, non-anomalous pregnancies delivered from September 2011 to May 2017. METHODS: Exposure was defined as marijuana detected on universal urine toxicology testing or by self-report. Multivariable logistic regression modelling was used to estimate the effect of any marijuana use on the primary composite outcome. The effect of marijuana exposure was also estimated for self-reported use, toxicology-detected use, and multiple use detected by toxicology. MAIN OUTCOME MEASURE: The primary composite outcome included spontaneous preterm birth, hypertensive disorders of pregnancy, stillbirth, or small for gestational age. RESULTS: Of 1206 pregnant young women, 17.5% (n = 211) used marijuana. Among the women who used marijuana, 8.5% (n = 18) were identified by self-report alone, 63% (n = 133) by urine toxicology alone, and 28.4% (n = 60) by both. Urine toxicology testing results were available for 1092 (90.5%) births. The composite outcome occurred more frequently in pregnancies exposed to marijuana (46 versus 34%, P < 0.001). This remained significant after adjusting for race/ethnicity and tobacco in the multivariable model (adjusted OR 1.50, 95% CI 1.09-2.05). When marijuana exposure was defined by self-report only, the association with adverse pregnancy outcome became non-significant (adjusted OR 1.01, 95% CI 0.62-1.64). CONCLUSION: In a population of young women with nearly universal biological sampling, marijuana exposure was associated with adverse pregnancy outcomes. The heterogeneity of findings in existing studies evaluating the impact of marijuana on mothers and neonates may result from the incomplete ascertainment of exposure. TWEETABLE ABSTRACT: Marijuana use, as detected by universal urine testing, was associated with a composite adverse pregnancy outcome among young mothers.

Combined pollution of copper nanoparticles and atrazine in soil: Effects on dissipation of the pesticide and on microbiological community profiles.

Copper nanoparticles (NCu) have been proposed as an antimicrobial agent in agriculture. Therefore, NCu may interact with numerous pollutants including pesticides. Little is known about the combined effects of NCu and pesticides in soil. This study aimed at assessing the impact of NCu combined with the herbicide atrazine (ATZ) on soil. We focused on assessing the adsorption and dissipation of ATZ in the presence of NCu and the changes in microbial community profiles. First, ATZ adsorption isotherms (described using the Freundlich equation) were evaluated. After that, soil samples were spiked with NCu (40-60 nm) at 0.05 and 0.15% w/w and ATZ (3 mg a.i kg-1) and incubated for 30 days. The results showed that ATZ adsorption is favored by the presence of NCu. On the other hand, NCu at 0.15% w/w caused a significant decrease in ATZ dissipation, increasing its half-life from 6 to 37 days. Microbial community profiles (bacteria, fungi and nitrifying bacteria) remained relatively stable throughout the evaluated period. Therefore, our findings suggest that NCu can increase the persistence of ATZ in soil, which may be mostly associated to physical-chemical interaction with soil particles more than a microbial impact.

Expanding the plasmonic response of bimetallic nanoparticles by laser seeding.

This work explores a cost-effective route to enhance the tuning range of the optical response of metal nanostructures on substrates beyond the ranges that are achievable through the nanostructure dimensions, composition or dewetting processes. The new route (laser seeding) uses single nanosecond laser pulses to induce dewetting in regions of a metal layer deposited on a glass substrate followed by the deposition of a second metal layer, both layers being deposited by pulsed laser deposition. In order to show the possibilities of this new route, we have chosen that the two metals were different, namely Ag and Au. The comparison of the optical response of these regions to those that were laser irradiated after deposition of the second metal layer shows that while nanoalloyed nanoparticles (NPs) are formed in the latter case, the NPs produced in the former case have a heterogeneous structure. The interface between the two metals is either sharp or a narrow region where they have mixed depending on the laser fluence used. While the nanoalloyed NPs exhibit a single, narrow surface plasmon resonance (SPR), the heterogeneous NPs show broader SPRs that peak in the near infrared and depending on conditions exhibit even two clear SPRs. The laser seeding approach in the conditions used in this work allows for the expansion of the tuning range of the color to the blue-green region, i.e. beyond the region that can be achieved through nanoalloyed NPs (yellow-red region). In addition, the results presented foresee the laser seeding route as a means to produce round and almost isolated NPs in an enhanced range of diameters.

Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone.

The developmental effects of NMP are well studied in Sprague-Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose-response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose-response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose-response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively.

Alterations in the antioxidant defense system in prepubertal children with a history of extrauterine growth restriction.

PURPOSE: The role of oxidative stress is well known in the pathogenesis of acquired malnutrition. Intrauterine growth restriction has been associated with an imbalance in oxidative stress/antioxidant system. Therefore, early postnatal environment and, consequently, extrauterine growth restriction might be associated with alterations in the antioxidant defense system, even in the prepubertal stage. METHODS: This is a descriptive, analytical, and observational case-control study. The study included two groups; 38 Caucasian prepubertal children born prematurely and with a history of extrauterine growth restriction as the case group, and 123 gender- and age-matched controls. Plasma exogenous antioxidant (retinol, ß-carotene, and α-tocopherol) concentrations were measured by HPLC; antioxidant enzyme activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were determined in lysed erythrocytes by spectrophotometric techniques. RESULTS: Catalase and glutathione peroxidase concentrations were significantly lower in extrauterine growth restriction children than in controls (P < 0.001). Lower plasma retinol concentrations were found in the case group (P = 0.029), while concentrations of ß-carotene and α-tocopherol were higher (P < 0.001) in extrauterine growth restriction prepubertal children as compared with controls. After correction by gestational age, birth weight, and length, statistically significant differences were also found, except for retinol. CONCLUSIONS: Prepubertal children with a history of extrauterine growth restriction present alterations in their antioxidant defense system. Knowing these alterations may be important in establishing pharmacological and nutritional treatments as this situation might be associated with higher metabolic disorders in adulthood.

Desafíos de la investigación en nutrición comunitaria / Challenges of research in community nutrition

La investigación en nutrición comunitaria orientada a la participación social debe ser interdisciplinaria, con el apoyo de agentes externos a la comunidad para promover el proceso de participación activa y de investigación, logrando mejorar la calidad de vida y la seguridad alimentaria. Muchos estudios han indicado el valor de las asociaciones: comunidad con instituciones académicas, públicas y privadas que han brindado la oportunidad de desempeñar su rol protagonista como conductores en el proceso metodológico de la investigación y en la ejecución y evaluación de programas. Igualmente, es necesaria la participación del propio Estado, que apoye el proceso para el éxito de la investigación. La Escuela de Nutrición y Dietética de la Universidad de los Andes ha logrado experiencias satisfactorias en la investigación comunitaria, por citar algunas de ellas tenemos “Las agendas papa y plátano”, con la participación de 6 facultades y entes gubernamentales. Empleando la metodología participación-acción se fomentó la participación activa, la integración y la organización comunitaria. El desafío es además de la participación activa de la comunidad, el enfoque interdisciplinario del problema y, por otra parte, involucrar a las instituciones públicas y privadas en las políticas y estrategias a seguir por las comunidades en la solución de los problemas(AU)

Community nutrition social participation-oriented research should be interdisciplinary, with the support of agents external to the community to promote the active participation and research process and improve the quality of life, and food security. Many studies have indicated the value of partnerships: community with academic, public and private institutions that have provided the opportunity to play its role, as in the methodological dietétiresearch process and the implementation and evaluation of programmes. The participation of the State to support the process to the success of the research is also needed. The school of Nutrition and dietetics at Universidad de los Andes has achieved successful experiences in community research, such as “Las agendas papa y plátano” (The Agendas Pope and banana) with the participation of six faculties and governmental bodies. Using the methodology participation - action, which allowed to encourage active participation, integration and community organization. The challenge is the interdisciplinary approach to the problem and the active participation of the community and by involving public and private institutions in the policies and strategies followed by communities in solving problems(AU)

Inhibition of Trypanosoma cruzi hexokinase by bisphosphonates.

Hexokinase is the first enzyme involved in glycolysis in most organisms, including the etiological agents of Chagas disease (Trypanosoma cruzi) and African sleeping sickness (Trypanosoma brucei). The T. cruzi enzyme is unusual since, unlike the human enzyme, it is inhibited by inorganic diphosphate (PPi). Here, we show that non-hydrolyzable analogues of PPi, bisphosphonates, are potent inhibitors of T. cruzi hexokinase (TcHK). We determined the activity of 42 bisphosphonates against TcHK, and the IC(50) values were used to construct pharmacophore and comparative molecular similarity indices analysis (CoMSIA) models for enzyme inhibition. Both models revealed the importance of electrostatic, hydrophobic, and steric interactions, and the IC(50) values for 17 active compounds were predicted with an average error of 2.4x by using the CoMSIA models. The compound most active against T. cruzi hexokinase was found to have a 2.2 microM IC(50) versus the clinically relevant intracellular amastigote form of T. cruzi, but only a approximately 1-2 mM IC(50) versus Dictyostelium discoideum and a human cell line, indicating selective activity versus T. cruzi.

[Tuberculosis of ankle]. / Artritis tuberculosa de tobillo.

The authors present a case of tuberculous arthritis of ankle with sinovial fluid and sputum aspirate Lowenstein positive (M. tuberculosis) in a patient non inmunocomprometid and review the clinical, diagnosis and treatment aspects of this entity, and show the difficult diagnosis in cases of radiology normal or low suspect.

Artritis tuberculosa de tobillo / Tuberculosis of ankle

Se presenta un caso de tuberculosis articular de tobillo en un paciente no inmunocomprometido, confirmado bacteriológicamente mediante cultivo del líquido articular y se comentan los aspectos clínicos, diagnósticos y terapéuticos de esta entidad. Se señalan las dificultades diagnósticas especialmente en los casos en que no existe un alto índice de sospecha y cuando la radiología de tórax es normal, lo que ocurre en el 50 por ciento de los casos (AU)

Inhibition of glutamate carboxypeptidase II by phosphonamidothionate derivatives of glutamic acid.

A limited series of N-thiophosphonyl-glutamates were found to be inhibitors of the prostate-specific membrane antigen (PSMA) form of glutamate carboxypeptidase II. Comparative inhibitory profiles of an analogous O-thiophosphonyl-2-hydroxyglutarate revealed that the amido-linkage of the N-thiophosphonyl-glutamate provides a significant enhancement of inhibitory potency presumably due to significant hydrogen-bonding interactions with acceptor groups in the active-site of PSMA resulting in tighter binding. An analogous N-phosphonyl-glutamate exhibited significantly greater inhibitory potency than the parent N-thiophosphonyl-glutamate indicating that the sulfur ligand of the N-thiophosphonyl-glutamates is responsible for less favorable active-site interactions than oxygen, potentially due to steric crowding from the longer P-S bond or as a result of active-site metal substitution of Co(II) for Zn(II) arising from assay conditions.

Comparison between isotropic and nonisotropic dosimetry systems during intraperitoneal photodynamic therapy.

BACKGROUND AND OBJECTIVE: On-line monitoring of light fluence during intraperitoneal photodynamic therapy (IP PDT) is crucial for safe light delivery. A flat photodiode-based dosimetry system is compared with an isotropic detector-based system in patients undergoing IP PDT. STUDY DESIGN/MATERIALS AND METHODS: Flat photodiodes and spherical detectors were placed side by side in the abdomen, for simultaneous light dosimetry in 19 patients. Tissue phantom experiments were performed to provide a preliminary estimate of the tissue optical properties of the peritoneum. RESULTS: The conversion factor between systems for 630-nm light was found to be 1.7 +/- 0.12. The mu(eff) of the tissues in the abdomen is estimated to vary between 0.5 cm(-1) to 1.4 cm(-1) assuming a mu(s)' = 7 cm(-1). CONCLUSIONS: The measured conversion factor should allow for comparison of light fluences with future clinical protocols that use an isotropic-based detector system. Differences in the optical properties of the underlying tissues may contribute to the variability in light measurements.

Competitive inhibition of a glutamate carboxypeptidase by phosphonamidothionate derivatives of glutamic acid.

Several N-thiophosphonyl-glutamates were found to be potent competitive inhibitors of a zinc-dependent glutamyl hydrolase, carboxypeptidase G (CPG). Weak inhibition exhibited by an analogous N-phosphonyl-glutamate suggests that the enhanced potency of the phosphonamidothioates is due to the presence of their sulfur ligand and its favorable interactions with active site features, presumably zinc(II).

Evaluation of phosphorus-containing inhibitors of gamma-glutamyl hydrolase.

Several putative, phosphorus-containing inhibitors of gamma-glutamyl hydrolase were synthesized and evaluated for inhibitory activity. The phosphonamidoic acids were shown to be weak competitive inhibitors while both a phosphoramidate diester and a phosphonamidate ester were shown to be potent time-dependent inactivators, presumably through irreversible phosphorylation of an active site nucleophile.

Dissociation constants of carboxymethyloxysuccinic acid.

The dissociation constants of carboxymethyloxysuccinic acid (CMOS) have been measured at 25 degrees and an ionic strength of 0.1M in sodium perchlorate. The values found were: pK(1) = 2.52, pK(2) = 3.77 and pK(3) = 5.00. CMOS is thus seen to be rather stronger than its isomer citric acid.