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Abstract: In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca2+ levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca2+-activated K+-channel (BKCa) is activated by raised intracellular Ca2+ and voltage and typically hyperpolarizes the cell membrane. Whether BKCa is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BKCa in human and hamster testes and then used a highly specific toxin, the BKCa blocker iberiotoxin (IbTx), to experimentally dissect a role of BKCa. Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BKCa becomes strongly detectable in Leydig cells only after they acquire the ability to produce androgens. Using purified Leydig cells from adult hamsters, membrane potential changes in response to hCG were monitored. HCG hyperpolarized the cell membrane, which was prevented by the selective BKCa blocker IbTx. Steroidogenic acute regulatory (StAR) mRNA expression and testosterone production were not affected by IbTx under basal conditions but markedly increased when hCG, in submaximal and maximal concentration or when db-cAMP was added to the incubation media. A blocker of KV4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BKCa as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BKCa in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms. [Copyright &y& Elsevier]

Abstract: This paper introduces an enhancement of a cellular automata (CA) model by integrating system dynamics (SD) to incorporate household dynamics and housing decisions as driving forces of residential development. CA macro-models used to simulate the quantitative land-use change (LUC) for urban areas are, thus far, lacking profound dynamics driven by demographic change. The model presented in this paper focuses on household dynamics according to the concept of the second demographic transition (SDT), applying aging and population shrinkage to simulate respective effects on residential choice and the resulting LUC. Such a perspective becomes especially important for urban areas exhibiting growth and shrinkage simultaneously, as currently seen in cities in Europe and in the U.S. To analyze this simultaneity in detail, we implement the residential land use CA model Metronamica and apply it to Berlin’s metropolitan region, which was selected as a typical example that displays contrasting growth and shrinkage processes. The pre-implemented macro-model has been replaced with our new SD model H2DCA (Household Decision Dynamics for Cellular Automata). For the simulation, we used empirical census data, economic data, data on residential satisfaction and numerous types of geo-information representing land-use zoning, accessibility and suitability for the time span 1990–2008. A comparison of a null model (NM) and H2DCA provides a very satisfying reproduction of land-use patterns reflected by kappa coefficient values. The causal relation of LUC drivers is considerably improved by sophisticated housing choice-feedback mechanisms. Although specific residential land-use classes exhibit shrinkage, others expand. Due to the detailed residential land-use classification, current re-urbanization processes could also be simulated. [Copyright &y& Elsevier]

Objective: To examine the association between montelukast prescription and neuropsychiatric events in children with asthma.Study Design: A matched, nested case-control design was used to identify cases and controls from a cohort of children aged 5-18 years with physician-diagnosed asthma from 2004 to 2015, in Ontario, Canada, prescribed an asthma maintenance medication. Cases were children with a hospitalization or emergency department visit for a neuropsychiatric event. Cases were matched to up to 4 controls on birth year, year of asthma diagnosis, and sex. The exposures were dispensed prescriptions for montelukast (yes/no) and number of dispensed montelukast prescriptions in the year before the index date. Conditional logistic regression was used to measure the unadjusted OR and aOR and 95% CIs for montelukast prescription and neuropsychiatric events. Covariates in the adjusted model included sociodemographic factors and measures of asthma severity.Results: In total, 898 cases with a neuropsychiatric event and 3497 matched controls were included. Children who experienced a new-onset neuropsychiatric event had nearly 2 times the odds of having been prescribed montelukast, compared with controls (OR 1.91, 95% CI 1.15-3.18; P = .01). Most cases presented for anxiety (48.6%) and/or sleep disturbance (26.1%).Conclusions: Children with asthma who experienced a new-onset neuropsychiatric event had nearly twice the odds of having been prescribed montelukast in the year before their event. Clinicians should be aware of the association between montelukast and neuropsychiatric events in children with asthma, to inform prescribing practices and clinical follow-up. [ABSTRACT FROM AUTHOR]

We observed that peritubular myoid cells in the human testis are immunoreactive for angiotensin II (AngII) receptors (AT1R) and explored AngII actions in cultured human testicular peritubular cells (HTPCs). In response to AngII they contracted within minutes. The AT1R-blocker losartan blocked contraction, implying involvement of AngII and AT1R in intratesticular sperm transport. AngII also significantly increased IL-6 mRNA levels and IL-6 secretion within hours and losartan again prevented this action. This suggests involvement in inflammatory processes, which may play a role in male infertility. AngII can be generated locally by mast cell (MC)-derived chymase (CHY), which cleaves AngI. In testicular biopsies from infertile men we found abundant MCs, which express CHY, within the wall of seminiferous tubules. In contrast, CHY-positive MCs are hardly found in normal human testis. Testicular inflammatory events may fuel processes resulting in impaired spermatogenesis. Therefore therapeutic interference with MCs, CHY or AT1R might be novel options in male infertility. [ABSTRACT FROM AUTHOR]

Abstract: Multilayered zirconia toughened alumina (ZTA) and c-zirconia coatings were prepared using electron beam physical vapour deposition (EB-PVD). Characterizations of the morphology and chemical composition of the deposited coatings were performed using scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD). Scratch resistance, nano-indentation and bending strength were used for the evaluation of the mechanical properties. X-ray diffraction of the top ceramic TBC surface showed that it consists entirely of cubic ZrO2 phase. The energy-dispersive X-ray spectroscopy analysis (EDS) showed that α-Al2O3 is the only oxide phase present at the interface, while SEM indicated the presence of columnar c-ZrO2 as the only phase of the top coat. Delamination over a large region was observed in the case of double layer (ZTA) coating. In contrast, the multilayered (ZTA1+ZTA2+c-Z) coating showed neither delamination nor cracking. The hardness and scratch measurements showed that the top coat c-ZrO2 layer is harder than the ZTA layers. The thermal conductivity of the multilayer coatings was estimated using the theoretical density and thermal conductivity values of zirconia toughened alumina (ZTA) and cubic-zirconia (c-ZrO2) together with their experimentally measured data. [Copyright &y& Elsevier]