Radiation Produces Irreversible Chronic Dysfunction in the Submandibular Glands of the Rat

The exposure to high doses of ionizing radiation during radiotherapy results in severe morphological and functional alterations of the salivary glands, such as xerostomia. In the present study we investigated the chronic effect of a single radiation dose of 15 Gray (Gy) limited to head and neck on rat salivary gland function (salivary secretion and gland mass) and histology. Results indicate that norepinephrine (NE)-induced salivary secretion was reduced significantly at 30, 90, 180 and 365 days after the administration of a single dose of 15 Gy of ionizing radiation compared to non-irradiated animals. The maximal secretory response was reduced by 33% at 30 and 90 days post irradiation. Interestingly, a new fall in the salivary response to NE was observed at 180 days and was maintained at 365 days post irradiation, showing a 75% reduction in the maximal response. The functional fall of the salivary secretion observed at 180 days post irradiation was not only associated with a reduction of gland mass but also to an alteration of the epithelial architecture exhibiting a changed proportion of ducts and acini, loss of eosinophilic secretor granular material, and glandular vacuolization and fibrosis. On the basis of the presented results, we conclude that ionizing radiation produces irreversible and progressive alterations of submandibular gland (SMG) function and morphology that leads to a severe salivary hypo-function

Urinary Phthalate Metabolites in Relation to Preterm Birth in Mexico City

Background: Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a role. Objective: We investigated the relationship between phthalate exposure and preterm birth. Methods: Within a large Mexican birth cohort study, we compared third-trimester urinary phthalate metabolite concentrations in 30 women who delivered preterm (< 37 weeks of gestation) with those of 30 controls (≥ 37 weeks of gestation). Results: Concentrations of most of the metabolites were similar to those reported among U.S. females, although in the present study mono-n-butyl phthalate (MBP) concentrations were higher and monobenzyl phthalate (MBzP) concentrations lower. In a crude comparison before correcting for urinary dilution, geometric mean urinary concentrations were higher for the phthalate metabolites MBP, MBzP, mono(3-carboxylpropyl) phthalate, and four metabolites of di(2-ethyl-hexyl) phthalate among women who subsequently delivered preterm. These differences remained, but were somewhat lessened, after correction by specific gravity or creatinine. In multivariate logistic regression analysis adjusted for potential confounders, elevated odds of having phthalate metabolite concentrations above the median level were found. Conclusions: We found that phthalate exposure is prevalent among this group of pregnant women in Mexico and that some phthalates may be associated with preterm birth

Computerized ICU Data Management Pitfalls and Promises

journal articleBiomedical Informatic

Order-of-magnitude speedup for steady states and traveling waves via Stokes preconditioning in Channelflow and Openpipeflow

Steady states and traveling waves play a fundamental role in understanding hydrodynamic problems. Even when unstable, these states provide the bifurcation-theoretic explanation for the origin of the observed states. In turbulent wall-bounded shear flows, these states have been hypothesized to be saddle points organizing the trajectories within a chaotic attractor. These states must be computed with Newton's method or one of its generalizations, since time-integration cannot converge to unstable equilibria. The bottleneck is the solution of linear systems involving the Jacobian of the Navier-Stokes or Boussinesq equations. Originally such computations were carried out by constructing and directly inverting the Jacobian, but this is unfeasible for the matrices arising from three-dimensional hydrodynamic configurations in large domains. A popular method is to seek states that are invariant under numerical time integration. Surprisingly, equilibria may also be found by seeking flows that are invariant under a single very large Backwards-Euler Forwards-Euler timestep. We show that this method, called Stokes preconditioning, is 10 to 50 times faster at computing steady states in plane Couette flow and traveling waves in pipe flow. Moreover, it can be carried out using Channelflow (by Gibson) and Openpipeflow (by Willis) without any changes to these popular spectral codes. We explain the convergence rate as a function of the integration period and Reynolds number by computing the full spectra of the operators corresponding to the Jacobians of both methods.Comment: in Computational Modelling of Bifurcations and Instabilities in Fluid Dynamics, ed. Alexander Gelfgat (Springer, 2018

Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models

<p>Abstract</p> <p>Background</p> <p>Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism.</p> <p>Methods</p> <p>Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: <it>HFE </it>[hemochromatosis], <it>TF </it>[transferrin], and <it>ALAD </it>[δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data.</p> <p>Results</p> <p>Percentage of participants carrying at least one copy of <it>HFE C282Y</it>, <it>HFE H63D</it>, <it>TF P570S</it>, and <it>ALAD K59N </it>variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either <it>C282Y </it>or <it>H63D </it>allele in <it>HFE </it>gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) μg/l. Women with any <it>HFE </it>variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]). <it>TF </it>and <it>ALAD </it>variants were not significant predictors of blood manganese. In animal models, <it>Hfe</it>^-/-mice displayed a significant reduction in blood manganese compared with <it>Hfe</it>^+/+mice, replicating the altered manganese metabolism found in our human research.</p> <p>Conclusions</p> <p>Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.</p

Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics

Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that interact and dissociate the tubulin dimer. Here we show how TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO– present in TBCB, which is similar to the EEY/F-COO– element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated to microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

<i>KCNV2</i>-associated retinopathy:genotype-phenotype correlations-<i>KCNV2</i> study group report 3

Background/aims To investigate genotype–phenotype associations in patients with KCNV2 retinopathy.Methods Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared.Results Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants.Conclusions Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials

Consequences of a large-scale fragmentation experiment for Neotropical bats : disentangling the relative importance of local and landscape-scale effects

Context Habitat loss, fragmentation and degradation are widespread drivers of biodiversity decline. Understanding how habitat quality interacts with landscape context, and how they jointly affect species in human-modified landscapes, is of great importance for informing conservation and management. Objectives We used a whole-ecosystem manipulation experiment in the Brazilian Amazon to investigate the relative roles of local and landscape attributes in affecting bat assemblages at an interior-edge-matrix disturbance gradient. Methods We surveyed bats in 39 sites, comprising continuous forest (CF), fragments, forest edges and intervening secondary regrowth. For each site, we assessed vegetation structure (local-scale variable) and, for five focal scales, quantified habitat amount and four landscape configuration metrics. Results Smaller fragments, edges and regrowth sites had fewer species and higher levels of dominance than CF. Regardless of the landscape scale analysed, species richness and evenness were mostly related to the amount of forest cover. Vegetation structure and configurational metrics were important predictors of abundance, whereby the magnitude and direction of response to configurational metrics were scale-dependent. Responses were ensemble-specific with local-scale vegetation structure being more important for frugivorous than for gleaning animalivorous bats. Conclusions Our study indicates that scale-sensitive measures of landscape structure are needed for a more comprehensive understanding of the effects of fragmentation on tropical biota. Although forest fragments and regrowth habitats can be of conservation significance for tropical bats our results further emphasize that primary forest is of irreplaceable value, underlining that their conservation can only be achieved by the preservation of large expanses of pristine habitat