Treatment of [Ph3EMe][I] with [NaN(SiMe3)2] affords the ylides [Ph3E=CH2] (E = As, 1As; P, 1P). For 1As this overcomes prior difficulties in the synthesis of this classical arsonium-ylide that have historically impeded its wider study. The structure of 1As has now been determined, 45 years after it was first convincingly isolated, and compared to 1P, confirming the long-proposed hypothesis of increasing pyramidalisation of the ylide-carbon, highlighting the increasing dominance of E+-C- dipolar resonance form (sp3-C) over the E=C ene p-bonded form (sp2-C), as group 15 is descended. The uranium(IV)-cyclometallate complex [UN(CH2CH2NSiPri3)2(CH2CH2SiPri2CH(Me)CH2)] reacts with 1As and 1P by a-proton abstraction to give [U(TrenTIPS)(CHEPh3)] (TrenTIPS = N(CH2CH2NSiPri3)3; E = As, 2As; P, 2P), where 2As is an unprecedented structurally characterised arsonium-carbene complex. The short U-C distances and obtuse U-C-E angles suggest significant U=C double bond character. A shorter U-C distance is found for 2As than 2P, consistent with increased uranium- and reduced pnictonium-stabilisation of the carbene as group 15 is descended, which is supported by quantum chemical calculations.Context Learning technologies are ubiquitous in medical schools implemented in anticipation of more effective, active and authentic learning and teaching. Such thinking appears to be an instance of solutionism. The evidence is that academics' adoption of learning technologies is often limited in scale and scope and frequently fails to transform their teaching practices. Methods This paper aims to provide a contextualised analysis of considerations pertinent to the adoption of learning technologies by teaching staff. We contextualise a framework for understanding adoption of learning technologies in higher education to medical education. Conclusions We identify multiple precursors that predict individual patterns of adoption, illuminating factors related to the technology, the individual staff member charged with adoption and the working environment. We offer conceptual clarity to the vexed issue of learning technology adoption and provide evidence explaining why, despite their widely promulgated potential, learning technologies do not offer an easy route to the transformation of medical education.Xanthelasma are localized accumulation of lipid deposits on the eyelids. Lesions are typically asymptomatic and treatment is often sought for cosmetic purposes. Unfortunately, there is paucity of strong evidence in the literature for the effective treatment of normolipidaemic xanthelasmas. Lasers have been used in the management of xanthelasma and in this article the experience with ultrapulsed CO2 laser is discussed with efficacy, complications and risk of recurrence explained.Herein an efficient Pd-catalyzed asymmetric allylic substitution cascade of both (E)- and (Z)-but-2-ene-1,4-diyl dimethyl dicarbonates with α-substituted cyano ketones is described for the preparation of chiral 2,3-dihydrofurans in up to 97% yield with 98% ee. A suggested steric control process has been proposed to illustrate the differences in enantioselectivity between the reactions of (E)- and (Z)-allyl substrates. The cascade reaction could be conducted on a gram-scale, and the resulting product allows for several transformations.The rising costs of new medicinal products are a challenge to the economic sustainability of national healthcare systems in ensuring patients' access to therapies. European Union (EU) and US legislators have provided regulatory pathways aimed at simplifying Marketing Authorization (MA) applications for new medicinal products in cases when safety and efficacy profiles can be derived from the data of already-marketed products. In this review, we discuss the different regulatory pathways towards the MA of new medicinal products containing old drug substances and intended to improve the therapeutic value of a treatment, to obtain a new therapeutic indication (drug repositioning), or to ensure the same therapeutic value of a reference product at lower costs.SLC30A8 encodes the zinc transporter ZnT8. SLC30A8 haploinsufficiency protects against type 2 diabetes (T2D), suggesting that ZnT8 inhibitors may prevent T2D. We show here that, while adult chow fed Slc30a8 haploinsufficient and knockout (KO) mice have normal glucose tolerance, they are protected against diet-induced obesity (DIO), resulting in improved glucose tolerance. We hypothesize that this protection against DIO may represent one mechanism whereby SLC30A8 haploinsufficiency protects against T2D in humans and that, while SLC30A8 is predominantly expressed in pancreatic islet beta cells, this may involve a role for ZnT8 in extra-pancreatic tissues. Consistent with this latter concept we show in humans, using electronic health record-derived phenotype analyses, that the 'C' allele of the non-synonymous rs13266634 single nucleotide polymorphism, which confers a gain of ZnT8 function, is associated not only with increased T2D risk and blood glucose but also but also increased risk for hemolytic anemia and decreased mean corpuscular hemoglobin (MCH). In Slc30a8 KO mice MCH was unchanged but reticulocytes, platelets and lymphocytes were elevated. Both young and adult Slc30a8 KO mice exhibit delayed rise in insulin after glucose injection but only the former exhibit increased basal insulin clearance and impaired glucose tolerance. Young Slc30a8 KO mice also exhibit elevated pancreatic G6pc2 gene expression, potentially mediated by decreased islet zinc levels. These data indicate that the absence of ZnT8 results in a transient impairment in some aspects of metabolism during development. These observations in humans and mice suggest the potential for negative effects associated with T2D prevention using ZnT8 inhibitors.Fluoride facilitates the remineralization of dental hard tissues and affects bacterial activities. Therefore, it is extensively used as an anti-caries agent in clinical practice and daily life. Although some studies focused on understanding Streptococcus mutans' response to fluoride, the mechanism regulating intrinsic fluoride tolerance is not yet clear. Since the TetR family of transcription factors is associated with multidrug resistance, our aim was to evaluate whether they are related to fluoride tolerance in S. mutans. A mutant library including each S. mutans TetR gene was constructed and the transcription factor fluoride related transcriptional regulator (FrtR) was identified. The in-frame deletion of the S. mutans frtR gene resulted in decreased cell viability under fluoride in both the planktonic state and single-/dual-species biofilms.  https://www.selleckchem.com/products/terephthalic-acid.html  This in-frame frtR mutant was used for RNA-sequencing and the fluoride related permease gene (frtP) was found as 1 of the downstream genes directly regulated by FrtR.