Ascorbic acid prevents cimetidine-induced decrease of serum hydrocortisone concentrations

Abstract A blind, parallel, prospective, clinical study was conducted to investigate the effect of ascorbic acid on human serum hydrocortisone concentrations which were decreased by the administration of cimetidine. The study population included 16 male adults scheduled for major abdominal vascular surgery. The study was conducted in surgical patients under anaesthesia, in which steroidogenesis was inhibited by cimetidine. The results showed a reduction in serum hydrocortisone concentrations in patients receiving a placebo. In patients receiving ascorbic acid, there was a significant increase in serum hydrocortisone concentration. This reflects the normal serum hydrocortisone profile for this operation and anaesthetic technique. Cimetidine can bind to cytochrome P-450 covering the active haem group, the cytochrome proves to be of vital importance for hydroxylation reactions, involved in human steroidogenesis. Serum hydrocortisone concentrations will decrease when cytochrome P-450 becomes blocked. Intravenous administration of ascorbic acid was supposed to cause relief for this decrease. The reasons are undetermined yet. This investigation proved that ascorbic acid can prevent cimetidine-induced decrease of human serum hydrocortisone concentrations

Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia.

Cell division is essential to expand, shape, and replenish epithelia. In the adult small intestine, cells from a common progenitor intermix with other lineages, whereas cell progeny in many other epithelia form contiguous patches. The mechanisms that generate these distinct patterns of progeny are poorly understood. Using light sheet and confocal imaging of intestinal organoids, we show that lineages intersperse during cytokinesis, when elongated interphase cells insert between apically displaced daughters. Reducing the cellular aspect ratio to minimize the height difference between interphase and mitotic cells disrupts interspersion, producing contiguous patches. Cellular aspect ratio is similarly a key parameter for division-coupled interspersion in the early mouse embryo, suggesting that this physical mechanism for patterning progeny may pertain to many mammalian epithelia. Our results reveal that the process of cytokinesis in elongated mammalian epithelia allows lineages to intermix and that cellular aspect ratio is a critical modulator of the progeny pattern

How do Students Test Software Units?

We gained insight into ideas and beliefs on testing of students who finished an introductory course on programming without any formal education on testing. We asked students to fill in a small survey, to do four exercises and to fill in a second survey. We interviewed eleven of these students in semi-structured interviews, to obtain more in-depth insight. The main outcome is that students do not test systematically, while most of them think they do test systematically. One of the misconceptions we found is that most students can only think of test cases based on programming code. Even if no code was provided (black-box testing), students try to come up with code to base their test cases on

Vaccine effectiveness against laboratory-confirmed influenza in Europe – Results from the DRIVE network during season 2018/19

The DRIVE project aims to establish a sustainable network to estimate brand-specific influenza vaccine effectiveness (IVE) annually. DRIVE is a public–private partnership launched in response to EMA guidance that requires effectiveness evaluation from manufacturers for all individual influenza vaccine brands every season. IVE studies are conducted by public partners in DRIVE. Private partners (vaccine manufacturers from the European Federation of Pharmaceutical Industries and Association (EFPIA)) provide written feedback moderated by an independent scientific committee. Test-negative design (TND) case-control studies (4 in primary care and five in hospital) were conducted in six countries in Europe during the 2018/19 season. Site-specific confounder-adjusted vaccine effectiveness (VE) estimates for any vaccine exposure were calculated by age group (<18 years (y), 18-64y and 65 + y) and pooled by setting (primary care, hospital) through random effects meta-analysis. In addition, one population-based cohort study was conducted in Finland. TND studies included 3339 cases and 6012 controls; seven vaccine brands were reported. For ages 65 + y, pooled VE against any influenza strain was estimated at 27% (95%CI 6–44) in hospital setting. Sample size was insufficient for meaningful IVE estimates in other age groups, in the primary care setting, or by vaccine brand. The population-based cohort study included 274,077 vaccinated and 494,337 unvaccinated person-years, two vaccine brands were reported. Brand-specific IVE was estimated for Fluenz Tetra (36% [95%CI 24–45]) for ages 2-6y, Vaxigrip Tetra (54% [43–62]) for ages 6 months to 6y, and Vaxigrip Tetra (30% [25–35]) for ages 65 + y. The results presented are from the second influenza season covered by the DRIVE network. While sample size from the pooled TND studies was still too low for precise (brand-specific) IVE estimates, the network has approximately doubled in size compared to the pilot season. Taking measures to increase sample size is an important focus of DRIVE for the coming years

Darolutamide does not interfere with OATP-mediated uptake of docetaxel

The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient-derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3-mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drug–drug interaction was identified

Darolutamide does not interfere with OATP-mediated uptake of docetaxel

The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient-derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3-mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drug–drug interaction was identified

Motmot, an open-source toolkit for realtime video acquisition and analysis

<p>Abstract</p> <p>Background</p> <p>Video cameras sense passively from a distance, offer a rich information stream, and provide intuitively meaningful raw data. Camera-based imaging has thus proven critical for many advances in neuroscience and biology, with applications ranging from cellular imaging of fluorescent dyes to tracking of whole-animal behavior at ecologically relevant spatial scales.</p> <p>Results</p> <p>Here we present 'Motmot': an open-source software suite for acquiring, displaying, saving, and analyzing digital video in real-time. At the highest level, Motmot is written in the Python computer language. The large amounts of data produced by digital cameras are handled by low-level, optimized functions, usually written in C. This high-level/low-level partitioning and use of select external libraries allow Motmot, with only modest complexity, to perform well as a core technology for many high-performance imaging tasks. In its current form, Motmot allows for: (1) image acquisition from a variety of camera interfaces (package motmot.cam_iface), (2) the display of these images with minimal latency and computer resources using wxPython and OpenGL (package motmot.wxglvideo), (3) saving images with no compression in a single-pass, low-CPU-use format (package motmot.FlyMovieFormat), (4) a pluggable framework for custom analysis of images in realtime and (5) firmware for an inexpensive USB device to synchronize image acquisition across multiple cameras, with analog input, or with other hardware devices (package motmot.fview_ext_trig). These capabilities are brought together in a graphical user interface, called 'FView', allowing an end user to easily view and save digital video without writing any code. One plugin for FView, 'FlyTrax', which tracks the movement of fruit flies in real-time, is included with Motmot, and is described to illustrate the capabilities of FView.</p> <p>Conclusion</p> <p>Motmot enables realtime image processing and display using the Python computer language. In addition to the provided complete applications, the architecture allows the user to write relatively simple plugins, which can accomplish a variety of computer vision tasks and be integrated within larger software systems. The software is available at <url>http://code.astraw.com/projects/motmot</url></p