Evaluation of a novel low-cost disposable endoscope for visual assessment of the esophagus and stomach in an ex-vivo phantom model

Background and study aims Our academic lab has developed a novel, low-cost, disposable endoscope for assessment of the esophagus and stomach without need for large equipment or complex electronics. Usability and intuitiveness of the platform are unknown. Methods The novel endoscope (NE) consists of a high-definition camera, LED module, and three bellows. Compressed air actuates the bellows, producing camera/LED articulation. Insufflation and lens cleaning ports are present. Video can be displayed on any monitor. Total material costs less than $ 35 US. Five novices, five fellows, and five attendings performed five trials using a conventional endoscope and the NE on an upper tract phantom with six gastric landmarks marked. Outcomes included successful identification and time to landmarks; and intuitiveness (NASA task load index; user comments). Results All landmarks were successfully identified with both endoscopes for all trials (n = 900). Attendings and fellows were quicker with the conventional endoscope when compared to the NE (24.48 v 37.13s; P < 0.01). There was no significant time difference between platforms for novices (P = 0.16). All users found the NE intuitive with low mental and physical demand. Novices reported lower temporal demand and effort when using the NE. Conclusions The NE was easy to maneuver, intuitive, and successful at visualizing gastric landmarks. All users were pleased with the NE drive mechanism and were successful at visualizing the gastric landmarks in a clinically acceptable time. The novel platform has the potential to facilitate rapid, low-cost, diagnostic assessment of the esophagus and stomach in non-traditional settings – facilitating patient management decisions, minimizing encumbrance, and avoiding cross-contamination

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation

The North Wyke Farm Platform: effect of temperate grassland farming systems on soil moisture contents, runoff and associated water quality dynamics

This is the final version of the article. Available from Wiley via the DOI in this record.The North Wyke Farm Platform was established as a United Kingdom national capability for collaborative research, training and knowledge exchange in agro-environmental sciences. Its remit is to research agricultural productivity and ecosystem responses to different management practices for beef and sheep production in lowland grasslands. A system based on permanent pasture was implemented on three 21-ha farmlets to obtain baseline data on hydrology, nutrient cycling and productivity for 2 years. Since then two farmlets have been modified by either (i) planned reseeding with grasses that have been bred for enhanced sugar content or deep-rooting traits or (ii) sowing grass and legume mixtures to reduce nitrogen fertilizer inputs. The quantities of nutrients that enter, cycle within and leave the farmlets were evaluated with data recorded from sensor technologies coupled with more traditional field study methods. We demonstrate the potential of the farm platform approach with a case study in which we investigate the effects of the weather, field topography and farm management activity on surface runoff and associated pollutant or nutrient loss from soil. We have the opportunity to do a full nutrient cycling analysis, taking account of nutrient transformations in soil, and flows to water and losses to air. The NWFP monitoring system is unique in both scale and scope for a managed land-based capability that brings together several technologies that allow the effect of temperate grassland farming systems on soil moisture levels, runoff and associated water quality dynamics to be studied in detail. HIGHLIGHTS: Can meat production systems be developed that are productive yet minimize losses to the environment?The data are from an intensively instrumented capability, which is globally unique and topical.We use sensing technologies and surveys to show the effect of pasture renewal on nutrient losses.Platforms provide evidence of the effect of meteorology, topography and farm activity on nutrient loss.The North Wyke Farm Platform is a UK National Capability supported by the Biotechnology and Biological Sciences Research Council (BBSRC BB/J004308/1)

The merger that led to the formation of the Milky Way's inner stellar halo and thick disk

The assembly process of our Galaxy can be retrieved using the motions and chemistry of individual stars. Chemo-dynamical studies of the nearby halo have long hinted at the presence of multiple components such as streams, clumps, duality and correlations between the stars' chemical abundances and orbital parameters. More recently, the analysis of two large stellar surveys have revealed the presence of a well-populated chemical elemental abundance sequence, of two distinct sequences in the colour-magnitude diagram, and of a prominent slightly retrograde kinematic structure all in the nearby halo, which may trace an important accretion event experienced by the Galaxy. Here report an analysis of the kinematics, chemistry, age and spatial distribution of stars in a relatively large volume around the Sun that are mainly linked to two major Galactic components, the thick disk and the stellar halo. We demonstrate that the inner halo is dominated by debris from an object which at infall was slightly more massive than the Small Magellanic Cloud, and which we refer to as Gaia-Enceladus. The stars originating in Gaia-Enceladus cover nearly the full sky, their motions reveal the presence of streams and slightly retrograde and elongated trajectories. Hundreds of RR Lyrae stars and thirteen globular clusters following a consistent age-metallicity relation can be associated to Gaia-Enceladus on the basis of their orbits. With an estimated 4:1 mass-ratio, the merger with Gaia-Enceladus must have led to the dynamical heating of the precursor of the Galactic thick disk and therefore contributed to the formation of this component approximately 10 Gyr ago. These findings are in line with simulations of galaxy formation, which predict that the inner stellar halo should be dominated by debris from just a few massive progenitors.Comment: 19 pages, 8 figures. Published in Nature in the issue of Nov. 1st, 2018. This is the authors' version before final edit

Morris dancers, matriarchs and paperbacks:Doing the village in contemporary Britain

To call a place rural is to categorize it as a particular kind of place and, often, to presume that particular kinds of being innately occur there. Over the past 20 years, however, trends in British rural studies have problematized easy ascription; this article is an ethnographic contribution within those trends. If it is no longer adequate to read the rural as a container for being, then, as I contend here, rurality can be explored anew through doing. I draw upon David Matless’s (1994) frame of ‘doing the village’ representationally, and amplify it to include concepts of place as representational and relational. I thus use ‘doing’ to read the multiple ways in which diverse residents in a Northern England village engage with both their real locality and with nationally shared rural imaginings

Single Parenting and Child Behavior Problems in Kindergarten

Two waves of data from a sample of 89 poor and near-poor single black mothers and their preschool children were used to study the influences of parenting stress, physical discipline practices, and nonresident fathers’ relations with their children on behavior problems in kindergarten. The results indicate that higher levels of parent stress, more frequent spanking, and less frequent father–child contact at time 1 were associated with increased teacher-reported behavior problems at time 2. In addition, more frequent contact between nonresident biological fathers and their children moderated the negative effect of harsh discipline by mothers on subsequent child behavior problems. Specifically, when contact with the father was low, maternal spanking resulted in elevated levels of behavior problems; with average contact, this negative effect of spanking was muted; and with high contact, spanking was not associated with increased behavior problems in kindergarten. The implications of these findings for future research and policy are discussed

Low pre-exercise muscle glycogen availability offsets the effect of post-exercise cold water immersion in augmenting PGC-1α gene expression

We assessed the effects of post-exercise cold-water immersion (CWI) in modulating PGC-1α expression in response to exercise commenced with low muscle glycogen availability. In a randomized repeated-measures design, nine recreationally active males completed an acute two-legged high-intensity cycling protocol (8 x 5 min at 82.5% peak power output) followed by 10 minutes of two-legged post-exercise CWI (8°C) or control conditions (CON). During each trial, one limb commenced exercise with low (LOW: <300 mmol.kg-1 dw) or very low (VLOW: <150 mmol.kg-1 dw) pre-exercise glycogen concentration, achieved via completion of a one-legged glycogen depletion protocol undertaken the evening prior. Exercise increased (P<0.05) PGC-1α mRNA at 3 h post-exercise. Very low muscle glycogen attenuated the increase in PGC-1α mRNA expression compared with the LOW limbs in both the control (CON VLOW ~3.6-fold vs. CON LOW ~5.6-fold: P = 0.023, ES 1.22 Large) and CWI conditions (CWI VLOW ~2.4-fold vs. CWI LOW ~8.0 fold: P = 0.019, ES 1.43 Large). Furthermore, PGC-1α mRNA expression in the CWI-LOW trial was not significantly different to the CON LOW limb (P = 0.281, ES 0.67 Moderate). Data demonstrate that the previously reported effects of post-exercise CWI on PGC-1α expression (as regulated systemically via β-adrenergic mediated cell signalling) are offset in those conditions in which local stressors (i.e. high-intensity exercise and low muscle glycogen availability) have already sufficiently activated the AMPK- PGC-1α signaling axis. Additionally, data suggest that commencing exercise with very low muscle glycogen availability attenuates PGC-1α signaling