Analysing GCN4 Translational Control in Yeast by Stochastic Chemical Kinetics Modelling and Simulation

Peer reviewedPublisher PD

Low-cost eye phantom for stereophotogrammetry-based optic nerve head topographical 3D imaging

Glaucoma is the second leading cause of blindness globally. Stereophotogrammetry-based optic nerve head topographical imaging systems could potentially allow for objective glaucoma assessment in settings where technologies such as optical coherence tomography and the Heidelberg Retinal Tomograph are prohibitively expensive. In the development of such systems, eye phantoms are invaluable tools for both system calibration and performance evaluation. Eye phantoms developed for this purpose need to replicate the optical configuration of the eye, the related causes of measurement artefacts, and give the possibility to present to the imaging system the targets required for system calibration. The phantoms in the literature that show promise of meeting these requirements rely on custom lenses to be fabricated, making them very costly. Here, we propose a low-cost eye phantom comprising a vacuum formed cornea and commercially available stock bi-convex lens, that is optically similar to a gold-standard reference wide-angle schematic eye model and meets all the compliance and configurability requirements for use with stereo-photogrammetry-based ONH topographical imaging systems. Moreover, its modular design, being fabricated largely from 3D-printed components, lends itself to modification for other applications. The use of the phantom is successfully demonstrated in an ONH imager

Cold- and light-induced changes in the transcriptome of wheat leading to phase transition from vegetative to reproductive growth

<p>Abstract</p> <p>Background</p> <p>For plants to flower at the appropriate time, they must be able to perceive and respond to various internal and external cues. Wheat is generally a long-day plant that will go through phase transition from vegetative to floral growth as days are lengthening in spring and early summer. In addition to this response to day-length, wheat cultivars may be classified as either winter or spring varieties depending on whether they require to be exposed to an extended period of cold in order to become competent to flower. Using a growth regime to mimic the conditions that occur during a typical winter in Britain, and a microarray approach to determine changes in gene expression over time, we have surveyed the genes of the major pathways involved in floral transition. We have paid particular attention to wheat orthologues and functional equivalents of genes involved in the phase transition in <it>Arabidopsis</it>. We also surveyed all the MADS-box genes that could be identified as such on the Affymetrix genechip wheat genome array.</p> <p>Results</p> <p>We observed novel responses of several genes thought to be of major importance in vernalisation-induced phase transition, and identified several MADS-box genes that might play an important role in the onset of flowering. In addition, we saw responses in genes of the Gibberellin pathway that would indicate that this pathway also has some role to play in phase transition.</p> <p>Conclusion</p> <p>Phase transition in wheat is more complex than previously reported, and there is evidence that day-length has an influence on genes that were once thought to respond exclusively to an extended period of cold.</p

Radial artery access site complications during cardiac procedures, clinical implications and potential solutions : the role of nitric oxide

Supported by the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme.Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery, as this is safer than the femoral approach. However, despite improvements in technology and techniques, complications can occur. The most common complication, arterial spasm, can cause intense pain and, in some cases, procedural failure. The incidence of spasm is dependent on several variables, including operator experience, artery size, and equipment used. An anti-spasmolytic cocktail can be applied to reduce spasm, which usually includes an exogenous nitric oxide (NO) donor (glyceryl trinitrate). NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention. However, systemic administration can result in unwanted side-effects, such as hypotension. A method that adopts local delivery of NO might be advantageous. This review article describes the mechanisms involved in radial artery spasm, discusses the advantages and disadvantages of current strategies to reduce spasm, and highlight the potential of NO-loaded nanoporous materials for use in this setting.Publisher PDFPeer reviewe

Maternal benzodiazepines and z-drugs use during pregnancy and adverse birth and neurodevelopmental outcomes in offspring: a population-based cohort study

Introduction: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. / Objective: To evaluate whether gestational benzodiazepines and/or z-drugs exposure is associated with adverse birth and neurodevelopmental outcomes. / Methods: A population-based cohort including mother-child pairs from 2001–2018 in Hong Kong was analysed to compared gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression. Sibling-matched analyses and negative control analyses were applied. / Results: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95%CI=0.97–1.25) for preterm birth and 1.03 (95%CI=0.76–1.39) for small for gestational age while the weighted hazard ratio (wHR) was 1.40 (95%CI=1.13–1.73) for ASD and 1.15 (95%CI=0.94–1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR=0.84, 95%CI=0.66–1.06; small for gestational age: wOR=1.02, 95%CI=0.50–2.09; ASD: wHR=1.10, 95%CI=0.70–1.72; ADHD: wHR=1.04, 95%CI=0.57–1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. / Conclusions: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against that of untreated anxiety and sleep problems

Maternal Benzodiazepines and Z-Drugs Use during Pregnancy and Adverse Birth and Neurodevelopmental Outcomes in Offspring:A Population-Based Cohort Study

Introduction: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. Objective: The aim of the study was to evaluate whether gestational benzodiazepine and/or z-drug exposure is associated with adverse birth and neurodevelopmental outcomes. Methods: A population-based cohort including mother-child pairs from 2001 to 2018 in Hong Kong was analysed to compare gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression with a 95% confidence interval (CI). Sibling-matched analyses and negative control analyses were applied. Results: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95% CI = 0.97-1.25) for preterm birth and 1.03 (95% CI = 0.76-1.39) for small for gestational age, while the weighted hazard ratio (wHR) was 1.40 (95% CI = 1.13-1.73) for ASD and 1.15 (95% CI = 0.94-1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR = 0.84, 95% CI = 0.66-1.06; small for gestational age: wOR = 1.02, 95% CI = 0.50-2.09; ASD: wHR = 1.10, 95% CI = 0.70-1.72; ADHD: wHR = 1.04, 95% CI = 0.57-1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. Conclusions: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against those of untreated anxiety and sleep problems.</p

3D reconstruction of the optic nerve head of a phantom eye from images obtained using a slit lamp fitted with low cost add-ons

Early detection and treatment are key in limiting vision loss from glaucoma, the second leading cause of blindness worldwide. The alteration of the optic nerve head’s (ONH) morphology, detectable early in the condition, is a key clinical indicator. The current gold standard is subjective observation through a slit lamp. If quantitative diagnostic devices to extract the topography of the ONH could be made objective and affordable, it could mean task shifting glaucoma diagnostics from specialist to primary/community care. A potentially cost-effective solution is to apply digital 3D reconstruction to stereo images obtained through a slit lamp, a mainstay of eye diagnostics, present in practically all ophthalmology and optometry practices. This works shows ONH reconstruction in an eye phantom through a common slit lamp fitted with extremely inexpensive cameras. Quantitative reconstructions, in close agreement with ground truths, were obtained

Synthetic stereo images of the optic disc from the CORD dataset

Advancement of techniques for 3D reconstruction of the optic disc could lead to affordable objective detection of glaucoma. Applying computer stereo vision techniques to image pairs is particularly promising. More data, along with the stereo camera calibration parameters and ground truths required for validation, could aid development. This work presents a method to generate, using a virtual environment, synthetic stereo images of optic discs from images in the CORD database and obtain the corresponding stereo camera calibration parameters and ground truths. Our own reconstruction technique was tested using data created using this environment and quantitatively validated

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring:population based cohort study

textabstractObjective To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Design Population based cohort study. Setting Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. Participants 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Main outcome measure Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Results Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). Conclusions The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously

Treatment with Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) and the Risk of All-Cause Poisoning in Children and Adolescents:A Self-Controlled Case Series Study

BACKGROUND: Children and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning. METHODS: Patients aged 5–18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods). RESULTS: 42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33–5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06–4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males. CONCLUSIONS: The risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40263-021-00824-x