Notes

Computational insights in the recognized inhibitors of man dissolvable epoxide hydrolase.
Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers' attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers' attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Epidemiological studies have suggested a link between vitamin D deficiency and increased risk for nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms have remained unclear. Here, using both clinical samples and experimental rodent models along with several biochemical approaches, we explored the specific effects and mechanisms of vitamin D deficiency in NAFLD pathology. Serum vitamin D levels were significantly lower in individuals with NAFLD and in high-fat diet (HFD)-fed mice than in healthy controls and chow-fed mice, respectively. Vitamin D supplementation ameliorated HFD-induced hepatic steatosis and insulin resistance in mice. Hepatic expression of vitamin D receptor (VDR) was up-regulated in three models of NAFLD, including HFD-fed mice, methionine/choline-deficient diet (MCD)-fed mice, and genetically obese (ob/ob) mice. Liver-specific VDR deletion significantly exacerbated HFD- or MCD-induced hepatic steatosis and insulin resistance and also diminished the protective effect of vitamin D supplementation on NAFLD. Mechanistic experiments revealed that VDR interacted with hepatocyte nuclear factor 4 α (HNF4α) and that overexpression of HNF4α improved HFD-induced NAFLD and metabolic abnormalities in liver-specific VDR-knockout mice. These results suggest that vitamin D ameliorates NAFLD and metabolic abnormalities by activating hepatic VDR, leading to its interaction with HNF4α. Our findings highlight a potential value of using vitamin D for preventing and managing NAFLD by targeting VDR. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Two-photon imaging studies in mouse primary visual cortex (V1) consistently report that around half of the neurons respond to oriented grating stimuli. However, in cats and primates, nearly all neurons respond to such stimuli. Here we show that mouse V1 responsiveness and selectivity strongly depends on neuronal depth. Moving from superficial layer 2 down to layer 4, the percentage of visually responsive neurons nearly doubled, ultimately reaching levels similar to what is seen in other species. Over this span, the amplitude of neuronal responses also doubled. Moreover, stimulus selectivity was also modulated, not only with depth but also with response amplitude. Specifically, we found that orientation and direction selectivity were greater in stronger responding neurons, but orientation selectivity decreased with depth whereas direction selectivity increased. Importantly, these depth-dependent trends were found not just between layer 2/3 and layer four but at different depths within layer 2/3 itself. Thus, neuronal depth is an important factor to consider when pooling neurons for population analyses. Furthermore, the inability to drive the majority of cells in superficial layer 2/3 of mouse V1 with grating stimuli indicates that there may be fundamental differences in the micro-circuitry and role of V1 between rodents and other mammals.Significance Statement Studies frequently pool responses of neurons from different cortical depths in population analyses. Here we show that population neuronal response characteristics in mouse primary visual cortex vary dramatically across depth planes separated by just 50 μm. We also demonstrate that the stimulus selectivity of neuronal responses varies with both cortical depth and the response amplitude of neurons. These findings highlight the importance of considering cell depth and response amplitude as important factors contributing to the overall characteristics of neurons in sensory cortex. Copyright © 2020 O’Herron et al.BACKGROUND Intravenous chemotherapy (IVC) remains an important globe salvage therapy for retinoblastoma. https://www.selleckchem.com/products/mcc950-sodium-salt.html METHODS Evaluation of long-term globe salvage at 5, 10, 15 and 20 years following frontline IVC for retinoblastoma. RESULTS Of 994 eyes, comparison by International Classification of Retinoblastoma group (A vs B vs C vs D vs E) revealed more advanced group with older mean age at presentation (8 vs 7 vs 10 vs 11 vs 15 months, p less then 0.001). By clinical features, more advanced group demonstrated greater mean tumour diameter (3.2 vs 6.8 vs 9.4 vs 14.3 vs 16.4, p less then 0.001) and thickness (2.0 vs 3.7 vs 4.4 vs 7.3 vs 9.3, p less then 0.001), and greater frequency of vitreous seeds ≥1 quadrant (0% vs 0% vs 44% vs 42% vs 57%, p less then 0.001) and subretinal seeds (0% vs 0% vs 22% vs 65% vs 54%, p less then 0.001). By outcomes, less advanced group demonstrated greater tumour control (without need for enucleation or external beam radiotherapy (EBRT)) by year 2 (96% vs 91% vs 91% vs 71% vs 32%, p less then 0.001), and with minimal change up to 20 years. In order to achieve globe salvage, additional intra-arterial chemotherapy (IAC) or plaque radiotherapy was employed by year 2 (5% vs 26% vs 28% vs 27% vs 19%, p less then 0.001), with little further need up to 20 years. Pinealoblastoma (2%), metastasis (2%) and death (1%) were infrequent. CONCLUSION Frontline IVC (plus additional IAC and/or plaque radiotherapy) for retinoblastoma provided complete tumour control for groups A (96%), B (91%), C (91%), D (71%) and E (32%), avoiding enucleation or EBRT and was lasting for up to 20 years. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
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