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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as a major liver disease worldwide. Bile acid dysregulation has been suggested to be a key feature in its pathogenesis and progression. AIMS: To characterize the relationship between bile acid levels and NAFLD on the population level. METHODS: A cross-sectional study in Guatemala was conducted in 2016 to examine the prevalence of NAFLD. Participants (n=415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the Fatty Liver Index. The levels of 15 circulating bile acids were determined by LC-MS/MS. Adjusted prevalence odds ratios (POR(adj)) and 95%CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD. RESULTS: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (POR(adj T3 vs T1)=1.85), taurocholic acid (TCA) (POR(adj T3 vs T1)=2.45) and taurochenodeoxycholic acid (TCDCA) (POR(adj T3 vs T1)=2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (POR(adj T3 vs T1)=1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (POR(adj T3 vs T1)=1.81). CONCLUSIONS: The bile acid levels of persons with, and without, NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e., GCA, TCA) and the secondary bile acids that derive from CA (i.e., DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signaling mediated by the bile acids.

The Healthy Food Environment Policy Index (Food-EPI) aims to assess the extent of implementation of recommended food environment policies by governments compared with international best practices and prioritize actions to fill implementation gaps. The Food-EPI was applied in 11 countries across six regions (2015-2018). National public health nutrition panels (n = 11-101 experts) rated the extent of implementation of 47 policy and infrastructure support good practice indicators by their government(s) against best practices, using an evidence document verified by government officials. Experts identified and prioritized actions to address implementation gaps. The proportion of indicators at "very low if any," "low," "medium," and "high" implementation, overall Food-EPI scores, and priority action areas were compared across countries. Inter-rater reliability was good (GwetAC2 = 0.6-0.8). Chile had the highest proportion of policies (13%) rated at "high" implementation, while Guatemala had the highest proportion of policies (83%) rated at "very low if any" implementation. The overall Food-EPI score was "medium" for Australia, England, Chile, and Singapore, while "very low if any" for Guatemala. Policy areas most frequently prioritized included taxes on unhealthy foods, restricting unhealthy food promotion and front-of-pack labelling. The Food-EPI was found to be a robust tool and process to benchmark governments' progress to create healthy food environments.

Restricting children's exposures to marketing of unhealthy foods and beverages is a global obesity prevention priority. Monitoring marketing exposures supports informed policymaking. This study presents a global overview of children's television advertising exposure to healthy and unhealthy products. Twenty-two countries contributed data, captured between 2008 and 2017. Advertisements were coded for the nature of foods and beverages, using the 2015 World Health Organization (WHO) Europe Nutrient Profile Model (should be permitted/not-permitted to be advertised). Peak viewing times were defined as the top five hour timeslots for children. On average, there were four times more advertisements for foods/beverages that should not be permitted than for permitted foods/beverages. The frequency of food/beverages advertisements that should not be permitted per hour was higher during peak viewing times compared with other times (P

Tg2576 mice are widely used to study amyloid-dependent synaptic dysfunction related to Alzheimer's disease. However, conflicting data have been reported for these mice with regard to basal transmission as well as the in vitro correlate of memory, long-term potentiation (LTP). Some studies show clear impairments, whereas others report no deficiency. The present study uses hippocampal slices from 3-, 10-, and 15-month-old wild-type (WT) and Tg2576 mice to evaluate synaptic function in each group, including experiments to investigate basal synaptic transmission, short- and long-term plasticity by inducing paired-pulse facilitation, and both early and late LTP. We show that synaptic function remains intact in hippocampal slices from Tg2576 mice at 3 months of age. However, both early and late LTP decline progressively during aging in these mice. This deterioration of synaptic plasticity starts affecting early LTP, ultimately leading to the abolishment of both forms of LTP in 15-month-old animals. In comparison, WT littermates display normal synaptic parameters during aging. Additional pharmacological investigation into the involvement of NMDA receptors and L-type voltage-gated calcium channels in LTP suggests a distinct mechanism of induction among age groups, demonstrating that both early and late LTP are differentially affected by these channels in Tg2576 mice during aging.

Phosphodiesterase (PDE) inhibitors are currently considered promising therapeutic targets for treatment of cognitive impairment in diseases such as Schizophrenia and Alzheimer's disease. Inhibitors of PDE2A and PDE9A have emerged as potential candidates shown to improve synaptic plasticity and memory function in animals. However, the functional relevance of their putative different localization in the neuron is not understood. Thus, this study aims at elucidating potential presynaptic effects of PDE2A inhibition in comparison to the inhibition of PDE9A. For this purpose, we used paired-pulse facilitation (PPF), a model of short-term synaptic plasticity related to presynaptic function. First, we performed a series of experiments to validate the model in acute rat hippocampal slices using several reference substances including calcium channel blockers, glutamatergic receptor antagonists, and GPCR agonists. Second, we analysed the effect of PDE2A and PDE9A inhibition and their role regulating the influence that the second messengers cAMP and cGMP exert on basal transmission. Our results show that the interplay between the adenylyl cyclase activator forskolin, the soluble guanylyl cyclase activator BAY 41-8543 and the PDE2A inhibitor PF-999 reveals a primarily presynaptic mechanism of action of PDE2A inhibition. On the contrary, inhibition of PDE9A did not alter PPF under similar conditions. In conclusion, these data provide new evidence supporting a role of PDE2A modulating short-term synaptic plasticity. Moreover, this function of PDE2A is suggested to rely on an active modulation of the cAMP hydrolysis as a response to changes in cGMP levels at the presynaptic level.

The industrial production of high manganese steel melts with approx. 10–30 wt% Mn makes high demands on the utilized Mn-bearing alloying agents in terms of chemical composition and cost-efficiency. Conventional Mn-bearing alloying agents are reviewed in this regard. A modified process route has been conceived for pyrometallurgical winning of special silicomanganese grades tailored for high manganese steelmaking. For each individual process step, namely manganese slag production, silicomanganese production, and optional desiliconization of silicomanganese, results of lab-scale experiments are discussed.

Biege- und Querkrafttrager mit rechteckigem oder I-formigem Querschnitt sind im Stahlbau hinlanglich bekannt, jedoch ist bei der Ausbildung der Tragerstege und -gurte aus modernen CFK-Verbund-Laminaten eine angepasste Strukturmodellbildung erforderlich, um den Besonderheiten des im Allgemeinen anisotropen Leichtbauwerkstoffes CFK adaquat Rechnung zu tragen. Im Rahmen des von der Deutschen Forschungsgemeinschaft geforderten Projekts “Grose, hochbelastbare Biegetrager aus Faser-Kunststoff-Verbunden“ sind angepasste Balkentheorien hoherer Ordnung formuliert und implementiert worden, die auf einer recht allgemeinen Kinematik mit segmentweise verschiebungsbasierten Ansatzen fur die Tragerstege und -flansche basieren. Den Besonderheiten unterschiedlichster Laminat-Lagenaufbauten kann damit adaquat Rechnung getragen werden. In vielen Fallen konnen damit die Trager-Deformationen und Beanspruchungen sogar in geschlossen-analytischer Weise gewonnen werden, ansonsten ist eine wenigstens semi-analytische Beschreibung moglich. Dies ist insbesondere im Hinblick auf Parameterstudien und die gezielte Trageroptimierung von grosem Vorteil. Highly loaded CFRP-beams: Adapted higher-order beam theories. Load carrying beam structures with rectangular or I-shaped cross-sections are very common in steel constructions, but in the case of webs and flanges made of modern CFRP composite laminates an adapted new structural modeling is required in order to take into account the peculiarities of the typically anisotropic light weight material CFRP. In the framework of the joint project “Large high-strength fiber-reinforced polymer beams”, funded by the German Research Foundation, adapted higher-order beam theories have been formulated and implemented on the basis of rather general kinematical assumptions with segment-wise displacement representations for the webs and the flanges. Herewith the peculiarities of very different laminate layups can be taken into account properly. In many cases the beam deformations and stresses even can be given in a closed-form analytical manner, otherwise at least a semi-analytical description is possible. In particular in regard of parameter studies and in regard of a well-aimed beam optimization this is a big advantage.

Summary The significance of serum bile acids as indicators of liver damages was investigated in minipigs carrying permanent venous catheters. Thioacetamide was applied as a model substance known to cause acute liver damages. Intraperitoneal application of this compound led to dose-dependent increases of the bile acid concentrations of the serum. The lowest thioacetamide concentration used, 10 mg/kg body weight, did not alter the serum bile acid concentration measured before feeding, whereas after feeding it caused a significant increase. Measurements at the same time of the enzymatic activities of lactic dehydrogenase, aminotransferases, alkaline phosphatase, and γ-glutamyltranspeptidase did not reveal any correlation. The conclusion drawn is that, under the conditions employed, serum bile acids can be regarded as sensitive indicators of acute liver damage in the minipig. Zusammenfassung Die Bedeutung der Serumgallensaurekonzentration als Indikator von Leberschaden beim Minischwein Unter Verwendung von Minischweinen, denen ein Venendauerkatheter implantiert wurde, wurde die Bedeutung der Serumgallensauren als Indikator von Leberschaden untersucht. Als Modellsubstanz wurde Thioacetamid appliziert, das akute Leberschaden verursacht. Die intraperitoneale Verabreichung dieses Stoffes fuhrte zu dosisabhangigen Konzentrationserhohungen der Serumgallensauren. Bei der niedrigsten verwendeten Thioacetamidkonzentration von 10 mg/kg KGW zeigten die vor der Futterung gemessenen Werte keine Veranderungen, wahrend nach der Futteraufnahme signifikante Erhohungen der Serumgallensauren zu beobachten waren. Gleichzeitige Bestimmungen von Serumenzymaktivitaten wie Laktatdehydrogenase, Aminotransferasen, alkalische Phosphatase und γ-Glutamyltranspeptidase ergaben keinerlei Korrelationen im Vergleich zu den Serumgallensauren. Daraus wird geschlossen, das Serumgallensauren unter den angegebenen Bedingungen als sensitiver Indikator von akuten Leberschaden angesehen werden konnen. Resume Signification de la concentration de l'acide cholique du serum comme indicateur de lesions hepatiques chez le porc miniature La signification de l'acide cholique du serum somme indicateur de lesions hepatiques a ete examinee sur des porcs miniatures chez lesquels un catheter veineux permanent avait ete pose. On a applique du thioacetamide comme substance temoin qui provoque des lesions hepatiques aigues. L'application intraperitoneale de cette substance declenche des elevations de concentration de l'acide cholique serique en fonction de la dose. Les valeurs mesurees avant le repas n'ont montre aucun changement avec la concentration la plus basse de thioacetamide de 10 mg/kg de poids alors que l'on a observe des augmentations significatives de l'acide cholique serique apres le repas. Des determinations simultanees d'activites enzymatiques seriques telles que lactate-dehydrogenase, aminotransferases, phosphatase alcaline et γ-glutamyltranspeptidase n'ont donne aucune correlation avec l'acide cholique serique. On a conclu que l'acide cholique serique dans les conditions indiquees pouvait etre considere comme un indicateur plus sensible des lesions hepatiques aigues. Resumen La significacion de la concentracion de acidos biliares sericos como indicador de lesiones hepaticas en el cerdo miniatura Utilizando cerdos miniatura, a los cuales se habia implantado un cateter venoso permanente, se estudio la significacion de los acidos biliares sericos como indicador de lesiones hepaticas. Como substancia modelo se aplico tioacetamida, la cual ocasiona lesiones hepaticas agudas. La administracion intraperitoneal de esta substancia conducia a aumentos en la concentracion, dependientes de la dosificacion, de los acidos biliares sericos. En la concentracion mas baja utilizada de 10 mg/kg peso vivo de tioacetamida no se mostraban modificaciones en los valores medidos antes de la alimentacion, mientras que despues de la ingestion de alimentos se observaron aumentos significantes de los acidos biliares sericos. Las mediciones simultaneas de las actividades de enzimas sericas, tales como lactato-dehidrogenasa, aminotransferasas, fosfatasa alcalina y γ-glutamiltranspeptidasa no acusaron ninguna clase de correlaciones en comparacion con los acidos biliares sericos. De aqui se saca en conclusion que los acidos biliares sericos se podrian considerar, bajo las condiciones indicadas, como indicador sensible de las lesiones hepaticas agudas en el minicerdo.

Introduction: Stunting (ST) and anemia (AN) have declined but are still high in some regions and subpopulations and overweight and obesity (OW/OB) have increased at alarming rates; therefore, under...

(3-Methyl-3-benzoborepin) chromium tricarbonyl was obtained by treating the free ligand with tris-(acetonitrile) chromium tricarbonyl in refluxing tetrahydrofuran. Red crystals of the complex C 14 H 11 BCrO 3 form in the P2 1 /n space group

In the present study the pharmacokinetics of chloramphenicol were investigated in bovine plasma and saliva. The method of detection of chloramphenicol, a radio-immunoassay, requires only small sample volumes, no further clean-up, and a large number of samples can be processed simultaneously. This enabled the collection of a larger number of samples over a longer period of time than in previous studies. The intention was to obtain a complete pharmacokinetic profile of chloramphenicol, to evaluate it according to common open-compartment models, and to compare it with the results of previous studies. The radio-immunoassay results were confirmed by analysing a number of samples distributed over the concentration range of interest by a gas-chromatographic method with electron-capture detection. The suitability of saliva was evaluated as a possible means of monitoring compliance with the ban on chloramphenicol in the Federal Republic of Germany in milk-producing animals.

For many cases of beam structures such as composite beams with box or I cross-sections, shear forces can not be neglected and it is necessary to take shear deformation into account. Therefore, a higher-order theory for composite beams is developed. The cross-section of the beams can be divided into webs and flanges, both are assumed to have different symmetric layups with balanced angles. The axial displacement representation is chosen to be of second-order for the flanges and of third-order for the webs. There is no transverse contraction allowed. All parts of a cross-section are assumed to have the same deflection in vertical direction. The geometric coupling of the flanges and webs is ensured by corresponding constraints. Based on the introduced kinematic representation, the principle of minimum potential energy is used to derive the respective differential equations. These governing equations are solved in a completely closed-form analytical manner. This way, a closed-form description of the whole beam behavior is achieved. In particular, all resultant local in-plane stresses can be obtained directly. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)

A higher-order theory is developed for composite box beams with rectangular, closed cross-sections. Each cross-section is therefore divided into two flanges and webs. Displacement representations are chosen for each part separately. The in-plane kinematics is 2nd order for the flanges and even 3rd order for the webs. The kinematics of the four parts is interconnected with the help of geometric coupling. All in-plane stress components can be obtained directly by using a reduced stiffness matrix for each single layer. The layups of the laminates for the flanges and webs are independent from each other. Only a symmetric layup with balanced angles is necessary. The determined differential equation system of 2nd order including four independent functions can be solved completely in a closed-form analytical manner. As an actual example a cantilever beam under combined bending moment and transverse force is considered. The results obtained by this new theory are compared with the results of a FEM-model with a very fine shell element discretization. (© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)