Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of adrenal steroidogenesis. Disorders in steroid 21‐hydroxylation account for over 95% of patients with CAH. ...Clinically, the 21‐hydroxylase deficiency has been classified in a broad spectrum of clinical forms, ranging from severe or classical, to mild late onset or non‐classical.
Known allelic variants in the disease causing CYP21A2 gene are spread among different sources. Until recently, most variants reported have been identified in the clinical setting, which presumably bias described variants to pathogenic ones, as those found in the CYPAlleles database. Nevertheless, a large number of variants are being described in massive genome projects, many of which are found in dbSNP, but lack functional implications and/or their phenotypic effect. In this work, we gathered a total of 1,340 GVs in the CYP21A2 gene, from which 899 variants were unique and 230 have an effect on human health, and compiled all this information in an integrated database. We also connected CYP21A2 sequence information to phenotypic effects for all available mutations, including double mutants in cis. Data compiled in the present work could help physicians in the genetic counseling of families affected with 21‐hydroxylase deficiency.
Disorders in steroid 21‐hydroxylation account for over 95% of patients with Congenital Adrenal Hyperplasia. We gathered a total of 899 unique genetic variants (GVs) from publicly available databases and publications for the disease causing CYP21A2 gene. From these GVs, 230 could be associated with an effect on human health. We also connected CYP21A2 sequence information to phenotypic effects for all available mutations and compiled them in an integrated database.
Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white ...adipose tissue (WAT) of 8-week-old male and female mouse offspring.
C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR.
Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (
< 0.05), exaggerated adipocyte hyperplasia (
< 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (
< 0.05) and the mRNA expression of
(
< 0.05). These changes were not observed in female Ob-Met offspring.
Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.
•The phenolic composition of 25 varieties of roselle (Hs) was determined.•A total of 7 new compounds were tentatively characterized in Hs extracts.•The Hs extracts exhibited potent antioxidant and ...antimicrobial activities.•Roselle varieties were classified based on their anthocyanin content.
This study reports the phytochemical profile (phenolics, flavonoids and anthocyanins), the antioxidant capacity and the antibacterial activity of the ethanolic extracts of a collection of 25 Mexican Hibiscus sabdariffa (Hs) varieties with different calyx color intensities, from green–yellow to deep red, cultivated in the same condition. A great variety of phenolic compounds were identified in the different extracts using HPLC-DAD-ESI-TOF-MS, mainly phenolic acids, flavonoids, and anthocyanidin, some of which have been described for the first time. The total phenolic, flavonoid and anthocyanidin contents showed great variation in the different Hs extracts, ranging from 2400±300 to 10,000±400mg gallic acid equivalents (GAE)/100g dry calyx (dc), from 419±2 to 2260±70mg quercetin/100g dc, and from 0 to 4408mg/100g dc with different ratios of delphinidin:cyanidin, respectively. Furthermore, the antioxidant capacity determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay presented the same behavior, with values that varied from 27.4±0.3 to 112±8mol equivalent trolox/g dc. In addition, the antibacterial activity of the HS extracts was assayed against Gram-negative (Escherichia coli, Salmonella enteritidis) and Gram-positive (Staphylococcus aureus, Micrococcus luteus) microorganisms, demonstrating that the ethanol extracts were effective against all the bacterial strains tested, showing a greater effect against Gram-positive bacteria. Finally, a multivariate analysis for the classification of the Hs varieties has been carried out based on the anthocyanidin content. The results reported in this paper shows for the first time antibacterial and phytochemistry diversity of the different varieties of Hs, which highlights the importance of a correct description of Hs materials used in research papers.
A new method for noise filtering in images that follow a Rician model-with particular attention to magnetic resonance imaging-is proposed. To that end, we have derived a (novel) closed-form solution ...of the linear minimum mean square error (LMMSE) estimator for this distribution. Additionally, a set of methods that automatically estimate the noise power are developed. These methods use information of the sample distribution of local statistics of the image, such as the local variance, the local mean, and the local mean square value. Accordingly, the dynamic estimation of noise leads to a recursive version of the LMMSE, which shows a good performance in both noise cleaning and feature preservation. This paper also includes the derivation of the probability density function of several local sample statistics for the Rayleigh and Rician model, upon which the estimators are built.
We developed a quantitative microbiological risk assessment (QMRA) of haemolytic uremic syndrome (HUS) associated with Shiga toxin-producing Escherichia coli (STEC)-contaminated beef (intact beef ...cuts, ground beef and commercial hamburgers) in children under 15 years of age from Argentina. The QMRA was used to characterize STEC prevalence and concentration levels in each product through the Argentinean beef supply chain, including cattle primary production, cattle transport, processing and storage in the abattoir, retail and home preparation, and consumption. Median HUS probability from beef cut, ground beef and commercial hamburger consumption was <10-15, 5.4x10-8 and 3.5x10-8, respectively. The expected average annual number of HUS cases was 0, 28 and 4, respectively. Risk of infection and HUS probability were sensitive to the type of abattoir, the application or not of Hazard Analysis and Critical Control Points (HACCP) for STEC (HACCP-STEC), stx prevalence in carcasses and trimmings, storage conditions from the abattoir to retailers and home, the joint consumption of salads and beef products, and cooking preference. The QMRA results showed that the probability of HUS was higher if beef cuts (1.7x) and ground beef (1.2x) were from carcasses provided by abattoirs not applying HACCP-STEC. Thus, the use of a single sanitary standard that included the application of HACCP-STEC in all Argentinean abattoirs would greatly reduce HUS incidence. The average number of annual HUS cases estimated by the QMRA (n = 32) would explain about 10.0% of cases in children under 15 years per year in Argentina. Since other routes of contamination can be involved, including those not related to food, further research on the beef production chain, other food chains, person-to-person transmission and outbreak studies should be conducted to reduce the impact of HUS on the child population of Argentina.
This paper develops a computational framework with unfitted meshes to solve linear piezoelectricity and flexoelectricity electromechanical boundary value problems including strain gradient elasticity ...at infinitesimal strains. The high-order nature of the coupled PDE system is addressed by a sufficiently smooth hierarchical B-spline approximation on a background Cartesian mesh. The domain of interest is embedded into the background mesh and discretized in an unfitted fashion. The immersed boundary approach allows us to use B-splines on arbitrary domain shapes, regardless of their geometrical complexity, and could be directly extended, for instance, to shape and topology optimization. The domain boundary is represented by NURBS, and exactly integrated by means of the NEFEM mapping. Local adaptivity is achieved by hierarchical refinement of B-spline basis, which are efficiently evaluated and integrated thanks to their piecewise polynomial definition. Nitsche’s formulation is derived to weakly enforce essential boundary conditions, accounting also for the non-local conditions on the non-smooth portions of the domain boundary (i.e. edges in 3D or corners in 2D) arising from Mindlin’s strain gradient elasticity theory. Boundary conditions modeling sensing electrodes are formulated and enforced following the same approach. Optimal error convergence rates are reported using high-order B-spline approximations. The method is verified against available analytical solutions and well-known benchmarks from the literature.
•Flexoelectricity is simulated with unprecedented generality and efficiency.•Nitsche’s method is developed for higher-order electromechanics.•Optimal convergence in non-trivial geometries is achieved.•Design and optimization of electromechanical devices with general geometries is enabled.
Herein, novel rodlike CdTe@MPA-PDA particles based on polydopamine (PDA) loaded with CdTe quantum dots (QDs) capped with mercaptopropionic acid (CdTe@MPA QDs) with atypical chemical features are ...evaluated as a potential actuator for photothermal therapy and oxidative stress induction. Under mild conditions established for the safe and efficient use of lasers, temperature increases of 10.2 and 7.8 °C, photothermal conversion efficiencies of 37.7 and 26.2%, and specific absorption rates of 99 and 69 W/g were obtained for CdTe@MPA-PDA and traditional PDA particles in water, respectively. The particles were set to interact with the human breast adenocarcinoma cell line MDA-MB-231. A significant cellular uptake with the majority of particles colocalized into the lysosomes was obtained at a concentration of 100 μg/mL after 24 h. Additionally, CdTe@MPA-PDA and CdTe@MPA QDs showed significantly different internalization levels and loading kinetics profiles. For the first time, the thermal lens technique was used to demonstrate the stability of particle-like CdTe@MPA-PDA after heating at pH 7 and their migration within the heating region due to the thermodiffusion effect. However, under acidic pH-type lysosomes, a performance decrease in heating was observed, and the chemical feature of the particles was damaged as well. Besides, the internalized rodlike CdTe@MPA-PDA notably enhanced the induction of oxidative stress compared with PDA alone and CdTe@MPA QDs in MDA-MB-231 cells initiating apoptosis. Combining these effects suggests that after meticulous optimizations of the conditions, the CdTe@MPA-PDA particles could be used as a photothermal agent under mild conditions and short incubation time, allowing cytoplasmatic subcellular localization. On the other hand, the same particles act as cell killers by triggering reactive oxygen species after a longer incubation time and lysosomal subcellular localization due to the pH effect on the chemical morphology features of the CdTe@MPA-PDA particles.
Canines are one of the best biological detectors of energetic materials available; however, canine detection of explosives is impacted by a number of factors, including environmental conditions. The ...objectives of this study were: 1) determine how canine detection limits vary when both the canine and odorant are tested in varying temperature and humidity conditions (canine and odor interactive effects); and 2) determine if an acclimatization plan can improve detection limits in an adverse environmental condition. Eight working line canines were trained to detect four energetics: prill ammonium nitrate (AN), Composition 4 (C4), trinitrotoluene (TNT) and double base smokeless powder (SP). In Experiment 1, canines completed a 3-alternative forced choice 3-down-1-up staircase threshold assessment in five environmental conditions: 40°C and 70% relative humidity (RH), 40°C and 40% RH, 0°C and 90% RH, 0°C and 50% RH and 21°C and 50% RH. Canines showed a 3.5-fold detection limit increase (poorer detection) for C4 in 40°C and 70% RH compared to their detection limit at 21°C and 50% RH. In Experiment 2, the eight canines were split into two groups (n = 4), control and acclimation groups. The control group completed the threshold assessment for C4 at 21°C and 50% RH each day for 20 days, with 5 minutes of petting prior to testing. The acclimation group completed the same assessment daily starting at 21°C and 50% RH but temperature and RH were incremented daily over the course of 6 days to the 40°C and 70% RH condition. After the initial six days, the acclimation group completed daily assessments at 40°C and 70% RH condition for the remainder of the experiment. All acclimatization group canines started their session with 5 minutes of toy or food retrieves. Detection limits for C4 for all dogs were tested in 40°C and 70% RH on day 11 and day 22. The acclimatization plan improved detection limits in the 40°C and 70% RH condition for C4 compared to the non-acclimated group. In this set of experiments, canine detection limits for four explosive odorants were found to vary based on environmental condition and were mostly driven by impacts on the canine rather than odor availability. The acclimatization plan did result in lower detection limits (i.e., increased performance). Future work should determine what factor (exercise or environmental exposure) is more effective in acclimatization for odor detection work.
A new filtering method to remove Rician noise from magnetic resonance images is presented. This filter relies on a robust estimation of the standard deviation of the noise and combines local linear ...minimum mean square error filters and partial differential equations for MRI, as the speckle reducing anisotropic diffusion did for ultrasound images. The parameters of the filter are automatically chosen from the estimated noise. This property improves the convergence rate of the diffusion while preserving contours, leading to more robust and intuitive filtering. The partial derivative equation of the filter is extended to a new matrix diffusion filter which allows a coherent diffusion based on the local structure of the image and on the corresponding oriented local standard deviations. This new filter combines volumetric, planar, and linear components of the local image structure. The numerical scheme is explained and visual and quantitative results on simulated and real data sets are presented. In the experiments, the new filter leads to the best results.
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