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The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia, edema, and gynecomastia by inhibiting steroid synthesis and metabolism. Mechanisms underlying pseudohyperaldosteronism include inhibition of adrenal 11β-hydroxylase cytochrome-P450 (CYP) 11B1 and 17α-hydroxylase (CYP17A1) as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazoles have been developed. This study employed H295R adrenocortical cells and enzyme activity assays to assess the potential risk of oteseconazole and two other tetrazoles, VT-1598 and quilseconazole, to inhibit adrenal steroidogenesis or 11β-HSD2. Steroidomic footprint analyses of H295R cell supernatants using untargeted liquid-chromatography-high-resolution mass-spectrometry (LC-HRMS) indicated overall patterns common to oteseconazole, quilseconazole and itraconazole, as well as similarities between VT-1598 and isavuconazole. Additionally, more specific features of the steroid signatures were observed. Targeted quantification of nine adrenal steroids in supernatants from treated H295R cells revealed an overall inhibition of adrenal steroidogenesis by the three tetrazoles, itraconazole and isavuconazole, providing an explanation for their similar steroidomic pattern. Applying recombinant enzymes indicated that this effect is not due to direct inhibition of steroidogenic enzymes because no or only weak inhibition could be observed. Moreover, oteseconazole and the two other tetrazoles did not inhibit 11β-HSD2, suggesting that they do not pose a risk of pseudohyperaldosteronism. Furthermore, oteseconazole did not alter steroid concentrations in a recent clinical study. Nevertheless, follow-up studies should assess the mechanism underlying the observed overall steroidogenesis inhibition by tetrazoles, itraconazole and isavuconazole, and whether concentrations achievable in a subgroup of susceptible patients might cause adrenal insufficiency and hyperplasia.

When it comes to parasitic absorption in thin-film silicon solar cells, most studies focus on one electrode only, most of the time the substrate (in n-i-p configuration) or superstrate (in p-i-n configuration). We investigate here simultaneously the influence of the absorption in both front and back electrodes on the current density of tandem micromorph solar cells in p-i-n configuration. We compare four possible combinations of front and back electrodes with two different doping levels, but identical sheet resistance and identical light-scattering properties. In the infrared part of the spectrum, parasitic absorption in the front or back electrode is shown to have a similar effect on the current generation in the cell, which is confirmed by modeling. By combining highly transparent front and back ZnO electrodes and high-quality silicon layers, a micromorph device with a stabilized efficiency of 11.75% is obtained.

Abstract Background The expectations of patients for managing pain induced by exercise and mobilization (PIEM) have seldom been investigated. We identified the views of patients and care providers regarding pain management induced by exercise and mobilization during physical therapy programs. Methods We performed a qualitative study based on semi-structured interviews with a stratified sample of 12 patients (7 women) and 14 care providers (6 women): 4 general practitioners [GPs], 1 rheumatologist, 1 physical medicine physician, 1 geriatrician, 2 orthopedic surgeons, and 5 physical therapists. Results Patients and care providers have differing views on PIEM in the overall management of the state of disease. Patients' descriptions of PIEM were polymorphic, and they experienced it as decreased health-related quality of life. The impact of PIEM was complex, and patient views were sometimes ambivalent, ranging from denial of symptoms to discontinuation of therapy. Care providers agreed that PIEM is generally not integrated in management strategies. Care providers more often emphasized the positive and less often the negative dimensions of PIEM than did patients. However, the consequences of PIEM cited included worsened patient clinical condition, fears about physical therapy, rejection of the physical therapist and refusal of care. PIEM follow-up is not optimal and is characterized by poor transmission of information. Patients expected education on how better to prevent stress and anxiety generated by pain, education on mobilization, and adaptations of physical therapy programs according to pain intensity. Conclusion PIEM management could be optimized by alerting care providers to the situation, improving communication among care providers, and providing education to patients and care providers.

Silicon heterojunction (SHJ) solar cell efficiencies are limited by parasitic absorption from the hydrogenated amorphous silicon (a-Si:H) front contact, but this may be mitigated by selecting an alternative carrier selective contact material with a wider band gap. When choosing such a material as the hole-selective contact ('p-layer'), the alignment of the material's valence band edge energy ( boldsymbol{E{text{VB}} ) with that of crystalline silicon (c-Si) is an important criterion, but several other material parameters can also influence the band bending at the contact interface. In this article, we simulate an (n)c-Si/(i)a-Si:H/p-layer interface to explore the influence of six materials parameters in a variable p-layer on the SHJ performance. We find a strong influence on the fill factor (FF) from thickness, doping, and boldsymbol{E{text{VB}} , and on V{text{OC} from the interfacial defect density; notably, optimal boldsymbol{E{text{VB}} is sim 0.1 eV higher than the valence band edge energy of a-Si:H. Multiparameter sensitivity analyses demonstrate how performance is simultaneously influenced by boldsymbol{E{text{VB} and doping; thus, both parameters should be optimized alongside one another. To assess the influence of these parameters experimentally, we grow p-type text{NiO}{x} as a test-case p-layer, which shows that FFs decrease with the oxygen content likely from the increased misalignment of boldsymbol{E{text{VB}} . Although modest efficiencies are achieved experimentally (>7%), what is important is that our model simulates performance trends. With these results, we apply a materials discovery pipeline to suggest new materials (e.g., ZnTe and BeTe) to try as p-layers in the SHJ. This combination of simulations, experiments, and materials discovery informs a better understanding of contact selection in SHJ cells.

Insects' host preferences are regulated by multiple factors whose interactions are only partly understood. Here we make use of an in-depth, untargeted metabolomic approach combining molecular networking (MN) and supervised Analysis of variance Multiblock Orthogonal Partial Least Squares (AMOPLS) to untangle egg-laying preferences of Drosophila suzukii, an invasive, highly polyphagous and destructive fruit pest originating from Southeast Asia. Based on behavioural experiments in the laboratory as well as field observation, we selected eight genetically related Vitis vinifera cultivars (e.g., Ancellotta, Galotta, Gamaret, Gamay, Gamay précoce, Garanoir, Mara and Reichensteiner) exhibiting significant differences in their susceptibility toward D. suzukii. The two most and the two least attractive red cultivars were chosen for further metabolomic analyses of their grape skins. The combination of MN and statistical AMOPLS findings with semi-quantitative detection information enabled us to identify flavonoids as interesting markers for differences in the attractiveness of the four studied grape cultivars towards D. suzukii. Overall, dihydroflavonols were accumulated in unattractive grape cultivars, while attractive grape cultivars were richer in flavonols. Crucially, both dihydroflavonols and flavonols were abundant metabolites in the semi-quantitative analysis of the extracted molecules from the grape skin. We discuss how these two flavonoid classes might influence the egglaying behaviour of D. suzukii females and how they could serve as potential markers for D. suzukii infestations in grapes that can be potentially extended to other fruits. We believe that our novel, integrated analytical approach could also be applied to the study of other biological relationships characterised by multiple evolving parameters. [ABSTRACT FROM AUTHOR]

Development of new device architectures and process technologies is of tremendous interest in crystalline silicon (c-Si) photovoltaics to drive enhanced performance and/or reduced processing cost. In this regard, an emerging concept with a high-efficiency potential is to employ low/high work function metal compounds or organic materials to form asymmetric electron and hole heterocontacts. This Letter demonstrates two important milestones in advancing this burgeoning concept. First, a high-performance, low-temperature, electron-selective heterocontact is developed, comprised of a surface passivating a-Si:H layer, a protective TiOx interlayer, and a low work function LiFx/Al outer electrode. This is combined with a MoOx hole-selective heterocontact to demonstrate a cell efficiency of 20.7%, the highest value for this cell class to date. Second, we show that this cell passes a standard stability test by maintaining >95% of its original performance after 1000 h of unencapsulated damp heat exposure, indicating its potential for longevity.