Publications by authors named "Mark Turner"

374 Publications

The Induction with Foley OR Misoprostol (INFORM) Study dataset. A dataset of 602 women with hypertensive disease in pregnancy, in India, randomised to either Foley catheter or oral misoprostol for induction of labour.

BMC Res Notes 2021 Sep 10;14(1):355. Epub 2021 Sep 10.

University of Liverpool and Liverpool Women's Hospital for Liverpool Health Partners, Crown Street, Liverpool, L8 7SS, UK.

Objectives: Induction of labour (IOL), or starting labour artificially, can be a lifesaving intervention for pregnant women and their babies, and rates are rising significantly globally. As rates increase, it becomes increasingly important to fully evaluate all available data, especially that from low income settings where the potential benefits and harms are greater. The goal of this paper is to describe the datasets collected as part of the Induction with Foley OR Misoprostol (INFORM) Study, a randomised trial comparing two of the recommended methods of cervical ripening for labour induction, oral misoprostol and Foley catheter, in women being induced for hypertension in pregnancy, at two sites in India during 2013-15.

Data Description: This dataset includes comprehensive data on 602 women who underwent IOL for hypertensive disorders in pregnancy. Women were randomly assigned to cervical ripening with oral misoprostol or a transcervical Foley catheter in two government hospitals in India. The main dataset has 367 variables including monitoring during the induction of labour, medications administered, timing and mode of delivery, measures of neonatal morbidity and mortality, maternal mortality and morbidity, maternal satisfaction and health economic data. The dataset is anonymised and available on ReShare.
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http://dx.doi.org/10.1186/s13104-021-05772-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434713PMC
September 2021

WHO essential medicines for children 2011-2019: age-appropriateness of enteral formulations.

Arch Dis Child 2021 Sep 3. Epub 2021 Sep 3.

Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.

Introduction: The WHO Essential Medicine List for children (EMLc) is used for promoting access to medicines. The age-appropriateness of enteral (oral and rectal) formulations for children depend on their adaptability/flexibility to allow age-related or weight-related doses to be administered/prescribed and the child's ability to swallow, as appropriate. There is scant information on the age-appropriateness of essential enteral medicines for children.

Objective: To evaluate the age-appropriateness of enteral essential medicines.

Materials And Methods: Age-appropriateness of all enteral formulations indicated and recommended in the EMLc 3rd to 7th (2011-2019) editions were determined by assessing swallowability and/or dose adaptability for children under 12 years, stratified into five age groups.

Results: Enteral formulations in the EMLc were more age-appropriate for older children aged 6-11 years than for younger children. In the 3rd edition, for older children, 77%, n=342, of formulations were age-appropriate. For younger children, age-appropriateness decreased with age group: 34% in those aged 3-5 years, 30% in those aged 1-2 years, 22% among those aged 28 days to 11 months and 15% in those aged 0-27 days. Overall, similar proportions were found for the 7th edition. In contrast, the majority of medicines in the 7th list were age-appropriate in targeted diseases like HIV and tuberculosis.

Conclusion: Most recommended enteral essential medicines in EMLc 2011 and 2019 were not age-appropriate for children <6 years. Medicines which are not age-appropriate must be manipulated before administration, leading to potential issues of safety and efficacy. Evaluation of the age-appropriateness of formulations for medicines to be included in EMLc could improve access to better medicines for children in the future.
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http://dx.doi.org/10.1136/archdischild-2021-321831DOI Listing
September 2021

Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress.

Free Radic Biol Med 2021 Aug 27;175:65-79. Epub 2021 Aug 27.

Centre for Diabetes, Chronic Diseases and Ageing, School of Science and Technology, Nottingham Trent University, Clifton, Nottingham, NG11 8NS, UK. Electronic address:

Type 2 diabetes is characterised by failure to control glucose homeostasis, with numerous diabetic complications attributable to the resulting exposure of cells and tissues to chronic elevated concentrations of glucose and fatty acids. This, in part, results from formation of advanced glycation and advanced lipidation end-products that are able to modify protein, lipid, or DNA structure, and disrupt normal cellular function. Herein we used mass spectrometry to identify proteins modified by two such adduction events in serum of individuals with obesity, type 2 diabetes, and gestational diabetes, along with similar analyses of human and mouse skeletal muscle cells and mouse pancreatic islets exposed to glucolipotoxic stress. We also report that carnosine, a histidine containing dipeptide, prevented 65-90% of 4-hydroxynonenal and 3-nitrotyrosine adduction events, and that this in turn preserved mitochondrial function and protected stimulus-secretion coupling in cells exposed to metabolic stress. Carnosine therefore offers significant therapeutic potential against metabolic diseases.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.08.233DOI Listing
August 2021

Early Impact of SARS-CoV-2 on Pediatric Clinical Research: A Pan-European and Canadian Snapshot in Time.

J Pediatr 2021 Aug 23. Epub 2021 Aug 23.

Université de Tours, INSERM, N2C UMR 1069, 37032 Tours, France; French Clinical Research Infrastructure Network (F-CRIN) - PEDSTART.

Objective: To capture the early effects of the SARS-CoV-2 pandemic on pediatric clinical research.

Study Design: Pediatric clinical research networks from 20 countries and 50 of their affiliated research sites completed two surveys over one month from early May to early June 2020. Networks liaised with their affiliated sites and contributed to the interpretation of results through pan-European group discussions. Based on SARS-CoV-2 first detection dates, countries formed one early and one late detecting cluster. We tested the hypothesis that this clustering influenced clinical research.

Results: Research sites were first impacted by the pandemic in mid-March 2020 (03/16 ±10 days, the same date as lockdown initiation, P = .99). From first impact up until early June, site initiation and feasibility analysis processes were affected for ˃50% of the sites. Staff were redirected to COVID-19 research for 44% of the sites and 75.5% of sites were involved in pediatric COVID-19 research (only 6.3% reported COVID cases in their other pediatric trials). Mitigations were used, but differently between the early and late detecting country clusters and between countries with and without a pediatric COVID-19 research taskforce. Positive effects include the development of teleworking capacities.

Conclusions: Through this collaborative effort from pediatric research networks, we found that pediatric trials were affected and conducted with a range of unequally applied mitigations across countries during the pandemic. The global impact might be greater than captured. In a context where clinical research is increasingly multinational, this report reveals the importance of collaboration between National Networks.
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http://dx.doi.org/10.1016/j.jpeds.2021.08.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381618PMC
August 2021

Anti-cancer actions of carnosine and the restoration of normal cellular homeostasis.

Biochim Biophys Acta Mol Cell Res 2021 Oct 10;1868(11):119117. Epub 2021 Aug 10.

Aston Research Centre for Healthy Ageing, Aston University, Birmingham B4 7ET, UK.

Carnosine is a naturally occurring dipeptide found in meat. Alternatively it can be formed through synthesis from the amino acids, β-alanine and L-histidine. Carnosine has long been advocated for use as an anti-oxidant and anti-glycating agent to facilitate healthy ageing, and there have also been reports of it having anti-proliferative effects that have beneficial actions against the development of a number of different cancers. Carnosine is able to undertake multiple molecular processes, and it's mechanism of action therefore remains controversial - both in healthy tissues and those associated with cancer or metabolic diseases. Here we review current understanding of its mechanistic role in different physiological contexts, and how this relates to cancer. Carnosine turns over rapidly in the body due to the presence of both serum and tissue carnosinase enzymes however, so its use as a dietary supplement would require ingestion of multiple daily doses. Strategies are therefore being developed that are based upon either resistance of carnosine analogs to enzymatic turnover, or else β-alanine supplementation, and the development of these potential therapeutic agents is discussed.
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http://dx.doi.org/10.1016/j.bbamcr.2021.119117DOI Listing
October 2021

Effect of Carnosine or β-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis.

Adv Nutr 2021 Jul 31. Epub 2021 Jul 31.

Sport, Health, and Performance Enhancement (SHAPE) Research Centre, Musculoskeletal Physiology Research Group, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.

There is growing evidence that supplementation with carnosine, or its rate-limiting precursor β-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or β-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. We performed a systematic search of 6 electronic databases up to 31 December 2020. Primary outcomes were changes in 1) fasting glucose, 2) glycated hemoglobin (HbA1c), and 3) 2-h glucose following a glucose-tolerance test. A set of additional outcomes included fasting insulin and homeostatic model assessment of β-cell function (HOMA-β) and insulin resistance (HOMA-IR). We assessed risk of bias using the Cochrane risk of bias (RoB) 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) RoB (animal studies) tools; and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty. We used Bayesian hierarchical random-effects models, with informative priors for human data and noninformative priors for animal data. Inferences were made on posterior samples generated by Hamiltonian Markov Chain Monte Carlo using 90% credible intervals (90% CrI) and calculated probabilities. Twenty studies (n = 4 human, n = 16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-β, and HOMA-IR). The model provides evidence that supplementation decreases fasting glucose [humans: mean difference (MD)0.5 = -0.95 mmol · L-1 (90% CrI: -2.1, 0.08); rodent: MD0.5 = -2.26 mmol · L-1 (90% CrI: -4.03, -0.44)], HbA1c [humans: MD0.5 = -0.91% (90% CrI: -1.46, -0.39); rodents: MD0.5 = -1.05% (90% CrI: -1.64, -0.52)], HOMA-IR [humans: standardized mean difference (SMD)0.5 = -0.41 (90% CrI: -0.82, -0.07); rodents: SMD0.5 = -0.63 (90% CrI: -1.98, 0.65)], and fasting insulin [humans: SMD0.5 = -0.41 (90% CrI: -0.77, -0.07)]. GRADE assessment showed our certainty in the effect estimate of each outcome to be moderate (human outcomes) or very low (rodent outcomes). Supplementation with carnosine or β-alanine may reduce fasting glucose, HbA1c, and HOMA-IR in humans and rodents, and fasting insulin in humans; both compounds show potential as therapeutics to improve glycemic control and insulin resistance. This review was registered at PROSPERO as CRD42020191588.
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http://dx.doi.org/10.1093/advances/nmab087DOI Listing
July 2021

Oral Misoprostol alone versus oral misoprostol followed by oxytocin for labour induction in women with hypertension in pregnancy (MOLI): protocol for a randomised controlled trial.

BMC Pregnancy Childbirth 2021 Jul 29;21(1):537. Epub 2021 Jul 29.

Department of Women's and Children's Health, Liverpool Women's Hospital, University of Liverpool, Crown Street, Liverpool, L8 7SS, UK.

Background: Every year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion if ongoing stimulation is required. However, some studies have shown that oral misoprostol can be continued into active labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have never been directly compared.

Methods: This pragmatic, open-label, randomised trial will compare a misoprostol alone labour induction protocol with the standard misoprostol plus oxytocin protocol in three Indian hospitals. The study will recruit 520 pregnant women being induced for hypertensive disease in pregnancy and requiring augmentation after membrane rupture. Participants will be randomised to receive either further oral misoprostol 25mcg every 2 h, or titrated intravenous oxytocin. The primary outcome will be caesarean birth. Secondary outcomes will assess the efficacy of the induction process, maternal and fetal/neonatal complications and patient acceptability. This protocol (version 1.04) adheres to the SPIRIT checklist. A cost-effectiveness analysis, situational analysis and formal qualitative assessment of women's experience are also planned.

Discussion: Avoiding oxytocin and continuing low dose misoprostol into active labour may have a number of benefits for both women and the health care system. Misoprostol is heat stable, oral medication and thus easy to store, transport and administer; qualities particularly desirable in low resource settings. An oral medication protocol requires less equipment (e.g. electronic infusion pumps) and may free up health care providers to assist with other aspects of the woman's care. The simplicity of the protocol may also help to reduce human errors associated with the delivery of intravenous infusions. Finally, women may prefer to be mobile during labour and not restricted by an intravenous infusion. There is a need, therefore, to assess whether augmentation using oral misoprostol is superior clinically and economically to the standard protocol of intravenous oxytocin.

Trial Registration: Clinical Trials.gov, NCT03749902 , registered on 21 Nov 2018.
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http://dx.doi.org/10.1186/s12884-021-04009-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320158PMC
July 2021

Setting up a pragmatic clinical trial in a low-resource setting: A qualitative assessment of GoLBeT, a trial of podoconiosis management in Northern Ethiopia.

PLoS Negl Trop Dis 2021 Jul 28;15(7):e0009582. Epub 2021 Jul 28.

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.

Background: Clinical trials are often perceived as being expensive, difficult and beyond the capacity of healthcare workers in low-resource settings. However, in order to improve healthcare coverage, the World Health Organization (WHO) World Health Report 2013 stated that all countries need to become generators as well as recipients of data. This study is a methodological examination of the steps and processes involved in setting up the Gojjam Lymphoedema Best Practice Trial (GoLBeT; ISRCTN67805210), a highly pragmatic clinical trial conducted in northern Ethiopia. Challenges to the trial and strategies used to deal with them were explored, together with the reasons for delays.

Methodology And Principal Findings: Qualitative research methods were used to analyse emails and reports from the period between trial inception and recruitment. This analysis was complemented by interviews with key informants from the trial operational team. The Global Health Research Process Map was used as a framework against which to compare the steps involved in setting up the trial. A mini-group discussion was conducted with the trial operational team after study completion for reflection and further recommendations. This study showed that the key areas of difficulty in setting up and planning this trial were: the study design, that is, deciding on the study endpoint, where and how best to measure it, and assuring statistical power; recruitment and appropriate training of staff; planning for data quality; and gaining regulatory approvals. Collaboration, for example with statisticians, the trial steering committee, the study monitors, and members of the local community was essential to successfully setting up the trial.

Conclusions And Significance: Lessons learnt from this trial might guide others planning pragmatic trials in settings where research is not common, allowing them to anticipate possible challenges and address them through trial design, planning and operational delivery. We also hope that this example might encourage similar pragmatic studies to be undertaken. Such studies are rarely undertaken or locally led, but are an accessible and efficient way to drive improved outcomes in public health.
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http://dx.doi.org/10.1371/journal.pntd.0009582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370641PMC
July 2021

Transcatheter Aortic Valve Implantation in Severe Native Pure Aortic Regurgitation Following Endocarditis With Large Vegetation.

JACC Case Rep 2021 Jun 16;3(6):859-863. Epub 2021 Jun 16.

Cardiology Department, Bristol Heart Institute, Bristol, United Kingdom.

We present the case of a 76-year-old man with recently treated infective endocarditis and severe residual native pure aortic regurgitation that was causing recurrent pulmonary edema. In view of his prohibitive surgical risk, he underwent transcatheter aortic valve implant with an excellent clinical outcome. ().
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http://dx.doi.org/10.1016/j.jaccas.2021.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311271PMC
June 2021

Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper.

Br J Clin Pharmacol 2021 Jun 27. Epub 2021 Jun 27.

Department of Development and Regeneration, KU Leuven, Leuven, Belgium.

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease- and/or target organ-specific examples. Identifying and testing PD targets and effects in special populations, and application of age- and/or population-specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD-related as well as drug safety-related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development.
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http://dx.doi.org/10.1111/bcp.14958DOI Listing
June 2021

Pharmacogenetics to Avoid Loss of Hearing (PALOH) trial: a protocol for a prospective observational implementation trial.

BMJ Open 2021 06 16;11(6):e044457. Epub 2021 Jun 16.

Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.

Introduction: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss.

Methods And Analysis: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice.

Ethics And Dissemination: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study.

Trial Registration Number: ISRCTN13704894.

Protocol Version: V 1.3.
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http://dx.doi.org/10.1136/bmjopen-2020-044457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211036PMC
June 2021

Invited review: Characterization of new probiotics from dairy and nondairy products-Insights into acid tolerance, bile metabolism and tolerance, and adhesion capability.

J Dairy Sci 2021 Aug 30;104(8):8363-8379. Epub 2021 Apr 30.

Food and Nutritional Science, School of Biological Sciences, the University of Hong Kong, Pokfulam Road, Hong Kong 999077, P.R. China.

The selection of potential probiotic strains that possess the physiological capacity of performing successfully in the gastrointestinal tract (GIT) is a critical challenge. Probiotic microorganisms must tolerate the deleterious effects of various stresses to survive passage and function in the human GIT. Adhesion to the intestinal mucosa is also an important aspect. Recently, numerous studies have been performed concerning the selection and evaluation of novel probiotic microorganisms, mainly probiotic bacteria isolated from dairy and nondairy products. Therefore, it would be crucial to critically review the assessment methods employed to select the potential probiotics. This article aims to review and discuss the recent approaches, methods used for the selection, and outcomes of the evaluation of novel probiotic strains with the main purpose of supporting future probiotic microbial assessment studies. The findings and approaches used for assessing acid tolerance, bile metabolism and tolerance, and adhesion capability are the focus of this review. In addition, probiotic bile deconjugation and bile salt hydrolysis are explored. The selection of a new probiotic strain has mainly been based on the in vitro tolerance of physiologically related stresses including low pH and bile, to ensure that the potential probiotic microorganism can survive the harsh conditions of the GIT. However, the varied experimental conditions used in these studies (different types of media, bile, pH, and incubation time) hamper the comparison of the results of these investigations. Therefore, standardization of experimental conditions for characterizing and selecting probiotics is warranted.
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http://dx.doi.org/10.3168/jds.2021-20398DOI Listing
August 2021

Recommendations by the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA) Working Group on preparedness of clinical trials about paediatric medicines process.

Arch Dis Child 2021 Apr 15. Epub 2021 Apr 15.

Institute if Life Course and Medical Sciences, Liverpool Health Partners, University of Liverpool, Liverpool, UK

Conduct of clinical trials in babies, children and young people is often hindered by issues that could have been foreseen before the trial opened; that is, some clinical trials are often underprepared. In order to identify a good approach to trial preparedness, the European Network of Paediatric Research at the European Medicines Agency formed a working group. The Working Group included representation from regulators, industry, academics, paediatric clinical research networks and parents.The Working Group consulted widely about how to prepare for paediatric clinical trials. The Group's detailed recommendations have been published (https://www.ema.europa.eu/en/documents/other/preparedness-medicines-clinical-trials-paediatrics-recommendations-enpr-ema-working-group-trial_en.pdf).This paper is a summary of the key recommendations including the following: start early, preferably in parallel to designing the medicine's development plan and individual protocols; identify the rationale and clinical need; listen to the perspectives of children and families, and of patient advocacy groups; identify how many people will be eligible for the trial; identify the resources needed, such as clinical facilities (including play therapy) and out-of-pocket expenditure by participants and their families; use all available data to estimate what is possible; present information about preparedness in a structured way; deploy proportionate resources to support the preparation of trials.A well-prepared, well-designed trial is likely to require fewer changes during its course, be run in a shorter time frame and achieve expected objectives.
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http://dx.doi.org/10.1136/archdischild-2020-321433DOI Listing
April 2021

Cyclic di-AMP Oversight of Counter-Ion Osmolyte Pools Impacts Intrinsic Cefuroxime Resistance in Lactococcus lactis.

mBio 2021 04 8;12(2). Epub 2021 Apr 8.

School of Agriculture and Food Sciences, University of Queensland, Brisbane, Queensland, Australia

The broadly conserved cyclic di-AMP (c-di-AMP) is a conditionally essential bacterial second messenger. The pool of c-di-AMP is fine-tuned through diadenylate cyclase and phosphodiesterase activities, and direct binding of c-di-AMP to proteins and riboswitches allows the regulation of a broad spectrum of cellular processes. c-di-AMP has a significant impact on intrinsic β-lactam antibiotic resistance in Gram-positive bacteria; however, the reason for this is currently unclear. In this work, genetic studies revealed that suppressor mutations that decrease the activity of the potassium (K) importer KupB or the glutamine importer GlnPQ restore cefuroxime (CEF) resistance in diadenylate cyclase () mutants of Metabolite analyses showed that glutamine is imported by GlnPQ and then rapidly converted to glutamate, and GlnPQ mutations or c-di-AMP negatively affects the pools of the most abundant free amino acids (glutamate and aspartate) during growth. In a high-c-di-AMP mutant, GlnPQ activity could be increased by raising the internal K level through the overexpression of a c-di-AMP-insensitive KupB variant. These results demonstrate that c-di-AMP reduces GlnPQ activity and, therefore, the level of the major free anions in through its inhibition of K import. Excessive ion accumulation in mutants results in greater spontaneous cell lysis under hypotonic conditions, while CEF-resistant suppressors exhibit reduced cell lysis and lower osmoresistance. This work demonstrates that the overaccumulation of major counter-ion osmolyte pools in c-di-AMP-defective mutants of causes cefuroxime sensitivity. The bacterial second messenger cyclic di-AMP (c-di-AMP) is a global regulator of potassium homeostasis and compatible solute uptake in many Gram-positive bacteria, making it essential for osmoregulation. The role that c-di-AMP plays in β-lactam resistance, however, is unclear despite being first identified a decade ago. Here, we demonstrate that the overaccumulation of potassium or free amino acids leads to cefuroxime sensitivity in mutants partially defective in c-di-AMP synthesis. It was shown that c-di-AMP negatively affects the levels of the most abundant free amino acids (glutamate and aspartate) in Regulation of these major free anions was found to occur via the glutamine transporter GlnPQ, whose activity increased in response to intracellular potassium levels, which are under c-di-AMP control. Evidence is also presented showing that they are major osmolytes that enhance osmoresistance and cell lysis. The regulatory reach of c-di-AMP can be extended to include the main free anions in bacteria.
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http://dx.doi.org/10.1128/mBio.00324-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092236PMC
April 2021

Physiological and pathophysiological concentrations of fatty acids induce lipid droplet accumulation and impair functional performance of tissue engineered skeletal muscle.

J Cell Physiol 2021 Oct 19;236(10):7033-7044. Epub 2021 Mar 19.

School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK.

Fatty acids (FA) exert physiological and pathophysiological effects leading to changes in skeletal muscle metabolism and function, however, in vitro models to investigate these changes are limited. These experiments sought to establish the effects of physiological and pathophysiological concentrations of exogenous FA upon the function of tissue engineered skeletal muscle (TESkM). Cultured initially for 14 days, C2C12 TESkM was exposed to FA-free bovine serum albumin alone or conjugated to a FA mixture (oleic, palmitic, linoleic, and α-linoleic acids [OPLA] [ratio 45:30:24:1%]) at different concentrations (200 or 800 µM) for an additional 4 days. Subsequently, TESkM morphology, functional capacity, gene expression and insulin signaling were analyzed. There was a dose response increase in the number and size of lipid droplets within the TESkM (p < .05). Exposure to exogenous FA increased the messenger RNA expression of genes involved in lipid storage (perilipin 2 [p < .05]) and metabolism (pyruvate dehydrogenase lipoamide kinase isozyme 4 [p < .01]) in a dose dependent manner. TESkM force production was reduced (tetanic and single twitch) (p < .05) and increases in transcription of type I slow twitch fiber isoform, myosin heavy chain 7, were observed when cultured with 200 µM OPLA compared to control (p < .01). Four days of OPLA exposure results in lipid accumulation in TESkM which in turn results in changes in muscle function and metabolism; thus, providing insight ito the functional and mechanistic changes of TESkM in response to exogenous FA.
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http://dx.doi.org/10.1002/jcp.30365DOI Listing
October 2021

Cyclic nucleotide phosphodiesterase inhibitors as therapeutic interventions for cystic fibrosis.

Pharmacol Ther 2021 Aug 1;224:107826. Epub 2021 Mar 1.

Department of Physiology, McGill University, Montreal, QC, Canada; Cystic Fibrosis Translational Research Centre, McGill University, Montreal, QC, Canada.

Cystic Fibrosis (CF) lung disease results from mutations in the CFTR anion channel that reduce anion and fluid secretion by airway epithelia. Impaired secretion compromises airway innate defence mechanisms and leads to bacterial colonization, excessive inflammation and tissue damage; thus, restoration of CFTR function is the goal of many CF therapies. CFTR channels are activated by cyclic nucleotide-dependent protein kinases. The second messengers 3'5'-cAMP and 3'5'-cGMP are hydrolysed by a large family of cyclic nucleotide phosphodiesterases that provide subcellular spatial and temporal control of cyclic nucleotide-dependent signalling. Selective inhibition of these enzymes elevates cyclic nucleotide levels, leading to activation of CFTR and other downstream effectors. Here we examine members of the PDE family that are likely to regulate CFTR-dependent ion and fluid secretion in the airways and discuss other actions of PDE inhibitors that can influence cyclic nucleotide-regulated mucociliary transport, inflammation and bronchodilation. Finally, we review PDE inhibitors and the potential benefits they could provide as CF therapeutics.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107826DOI Listing
August 2021

Association of Patient Mental Health Status With the Level of Agreement Between Patient and Physician Ratings of Psoriasis Severity.

JAMA Dermatol 2021 04;157(4):413-420

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Importance: The emerging paradigm of treat-to-target in psoriasis requires accurate monitoring of treatment response. The commonly used physician global assessment tool does not capture the patient's perception of their disease. Patient assessments facilitate shared decision-making and foster patient-centered care; however, recent research reports a discordance between patient- and physician-reported psoriasis severity. Understanding the factors underlying this discordance may improve treatment satisfaction and disease outcomes.

Objectives: To evaluate the discordance between patient- and physician-reported measures of psoriasis severity and assess the association with patient mental health status.

Design, Setting, And Participants: A cohort study using repeated cross-sectional analysis of real-world longitudinal data was conducted at a large specialist psoriasis service serving London and Southeast England. A total of 502 patients attending the psoriasis service between May 12, 2016, and November 1, 2018, were included. Data analysis was conducted July 22 to October 22, 2019.

Main Outcomes And Measures: Psoriasis severity was assessed on each visit with identical 5-point physician and patient global assessment scales (clear/nearly clear, mild, moderate, severe, and very severe). Each patient completed validated self-report screens for depression and anxiety on each visit.

Results: Longitudinal data from 502 individuals with psoriasis (1985 total observations) were available. A total of 339 patients (68%) were men, 396 (79%) were White, mean (SD) age was 47 (13) years, and 197 patients (39%) had concurrent psoriatic arthritis, 43 (9%) screened positive for depression, and 49 (10%) screened positive for anxiety. There was discordance between physician and patient measures of disease severity in 768 of 1985 office appointments (39%); on 511 visits (26%) patients rated their psoriasis as less severe and on 257 visits (13%) patients rated their psoriasis as more severe compared with their physician. Individuals who screened positive for depression or anxiety were more likely to overestimate their psoriasis severity compared with their physician (relative risk ratio: depression, 2.7; 95% CI, 1.6-4.5; anxiety, 2.1; 95% CI, 1.3-3.4). These findings remained statistically significant after adjustment for age, ethnicity, sex, body mass index, smoking, number of comorbidities, treatment modality, and presence of psoriatic arthritis.

Conclusions And Relevance: The findings of this cohort study suggest that discordance between patient and physician assessments of psoriasis severity is associated with patients' mental health status. Recognition of anxiety and depression in individuals with psoriasis appears to be important when interpreting patient-reported outcome measures and informing appropriate treatment decisions.
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http://dx.doi.org/10.1001/jamadermatol.2020.5844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931137PMC
April 2021

Comparison between cage and free-range egg production on microbial composition, diversity and the presence of Salmonella enterica.

Food Microbiol 2021 Aug 3;97:103754. Epub 2021 Feb 3.

CSIRO Agriculture and Food, Coopers Plains, Queensland, Australia.

The microbial composition of the food production environment plays an important role in food safety and quality. This study employed both 16 S rRNA gene sequencing technology and culture-based techniques to investigate the bacterial microbiota of an egg production facility comprising of both free-range and conventional cage housing systems. The study also aimed to detect the presence of Salmonella enterica and determine whether its presence was positively or negatively associated with other taxa. Our findings revealed that microbiota profiles of free-range and cage houses differ considerably in relation to the relative abundance and diversity with a number of taxa unique to each system and to individual sampling sites within sheds. Core to each housing system were known inhabitants of the poultry gastrointestinal tracts, Romboutsia and Turicibacter, as well as common spoilage bacteria. Generally, free-range samples contained fewer taxa and were dominated by Staphylococcus equorum, differentiating them from the cage samples. Salmonella enterica was significantly associated with the presence of a taxa belonging to the Carnobacteriaceae family. The results of this study demonstrate that the diversity and composition of the microbiota is highly variable across egg layer housing systems, which could have implications for productivity, food safety and spoilage.
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http://dx.doi.org/10.1016/j.fm.2021.103754DOI Listing
August 2021

The conect4children (c4c) Consortium: Potential for Improving European Clinical Research into Medicines for Children.

Pharmaceut Med 2021 03 4;35(2):71-79. Epub 2021 Feb 4.

Division of Pediatric Infectious Diseases, Department of Woman's and Child's Health, University of Padua, Padua, Italy.

The need for information about new and existing drugs used in children was recognized in the European Union (EU) with the implementation of the Paediatric Regulation in 2007. In 2017, the 10-year review of the Paediatric Regulation identified barriers to the conduct of clinical trials, including delays in setting up and completing paediatric trials. Across Europe, the difficulties with clinical research are compounded by variation within countries and between countries. Ethics and regulatory review have national specificities. This paper describes the Collaborative Network for European Clinical Trials for Children (conect4children, c4c), which addresses selected difficulties in the design and conduct of paediatric clinical trials. c4c is a time-limited public-private consortium funded by the Innovative Medicines Initiative (IMI2). The elements of c4c are as follows: expert advice providing input on study design and/or paediatric development programmes (including patient involvement activities); a network of sites following harmonised procedures coordinated by National Hubs and a single point of contact for Europe; a facility for education and training for sites and trial teams; and support for managing data used by the network and a common paediatric data dictionary. c4c does not sponsor trials. c4c is taking a phased approach with careful piloting through industry and non-industry studies intended to demonstrate the viability of the network (proof-of-viability studies). c4c uses a co-design approach involving industry and academics within a clearly defined scope. A sustainable, successor organization open to all potential service users will be open for business before the end of IMI2 funding in 2024.
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http://dx.doi.org/10.1007/s40290-020-00373-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979601PMC
March 2021

Survival relative to pacemaker status after transcatheter aortic valve implantation.

Catheter Cardiovasc Interv 2021 Sep 27;98(3):E444-E452. Epub 2021 Jan 27.

Sussex Cardiac Center, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.

Objectives: To determine whether a permanent pacemaker (PPM) in situ can enhance survival after transcatheter aortic valve implantation (TAVI), in a predominantly inoperable or high risk cohort.

Background: New conduction disturbances are the most frequent complication of TAVI, often necessitating PPM implantation before hospital discharge.

Methods: We performed an observational cohort analysis of the UK TAVI registry (2007-2015). Primary and secondary endpoints were 30-day post-discharge all-cause mortality and long-term survival, respectively.

Results: Of 8,651 procedures, 6,815 complete datasets were analyzed. A PPM at hospital discharge, irrespective of when implantation occurred (PPM 1.68% [22/1309] vs. no PPM 1.47% [81/5506], odds ratio [OR] 1.14, 95% confidence interval [CI] 0.71-1.84; p = .58), or a PPM implanted peri- or post-TAVI only (PPM 1.44% [11/763] vs. no PPM 1.47% [81/5506], OR 0.98 [0.51-1.85]; p = .95) did not significantly reduce the primary endpoint. Patients with a PPM at discharge were older, male, had right bundle branch block at baseline, were more likely to have received a first-generation self-expandable prosthesis and had experienced more peri- and post-procedural complications including bailout valve-in-valve rescue, bleeding and acute kidney injury. A Cox proportional hazards model demonstrated significantly reduced long-term survival in all those with a PPM, irrespective of implantation timing (hazard ratio [HR] 1.14 [1.02-1.26]; p = .019) and those receiving a PPM only at the time of TAVI (HR 1.15 [1.02-1.31]; p = .032). The reasons underlying this observation warrant further investigation.

Conclusions: A PPM did not confer a survival advantage in the first 30 days after hospital discharge following TAVI.
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http://dx.doi.org/10.1002/ccd.29498DOI Listing
September 2021

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome: two-year outcomes.

J Matern Fetal Neonatal Med 2020 Dec 20:1-5. Epub 2020 Dec 20.

University Children's Hospital, University of Würzburg, Würzburg, Germany.

Objective: To assess at 24 months corrected age (CA) the neurological, respiratory, and general health status of children born prematurely from 27 to 33 weeks' gestation who were treated in a first-in-human study with a new fully synthetic surfactant (CHF5633) enriched with SP-B and SP-C proteins.

Outcome Measures: Children were assessed using Bayley Scales of Infant Development (BSID), with a score below normal defined as BSID-II Mental Development Index score <70, or BSID-III cognitive composite score <85. In addition, a health status questionnaire was used to check for functional disability including respiratory problems and related treatments, sensory and neurodevelopment assessments, communication skills as well as the number of hospitalizations.

Results: 35 of 39 survivors had a neurodevelopmental assessment, 24 infants being evaluated by Bayley's Scales and 11 by health status questionnaires only. 23 children had scores within normal limits and one had BSID-III <85. The remaining 11 were judged clinically to have normal development. Health status questionnaires detected only issues that would normally be expected in preterm-born children.

Conclusions: This assessment offers reassurance that treatment with CHF5633 surfactant was not associated with adverse neurodevelopmental, respiratory, or health outcomes by two years corrected age.
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http://dx.doi.org/10.1080/14767058.2020.1863363DOI Listing
December 2020

Updates on understanding of probiotic lactic acid bacteria responses to environmental stresses and highlights on proteomic analyses.

Compr Rev Food Sci Food Saf 2020 05 14;19(3):1110-1124. Epub 2020 Apr 14.

Department of Food, Nutrition and Health, College of Food and Agriculture, United Arab Emirates University (UAEU), Al Ain, 15551, UAE.

Probiotics are defined as live microorganisms that improve the health of the host when administered in adequate quantities. Nonetheless, probiotics encounter extreme environmental conditions during food processing or along the gastrointestinal tract. This review discusses different environmental stresses that affect probiotics during food preparation, storage, and along the alimentary canal, including high temperature, low temperature, low and alkaline pH, oxidative stress, high hydrostatic pressure, osmotic pressure, and starvation. The understanding of how probiotics deal with environmental stress and thrive provides useful information to guide the selection of the strains with enhanced performance in specific situations, in food processing or during gastrointestinal transit. In most cases, multiple biological functions are affected upon exposure of the cell to environmental stress. Sensing of sublethal environmental stress can allow for adaptation processes to occur, which can include alterations in the expression of specific proteins.
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http://dx.doi.org/10.1111/1541-4337.12554DOI Listing
May 2020

The effect of carnosine or β-alanine supplementation on markers of glycaemic control and insulin resistance in human and animal studies: a protocol for a systematic review and meta-analysis.

Syst Rev 2020 12 5;9(1):282. Epub 2020 Dec 5.

Sport, Health and Performance Enhancement (SHAPE) Research Centre, Musculoskeletal Physiology Research Group, School of Science and Technology, Nottingham Trent University, Nottingham, UK.

Background: Diabetes is a major public health issue and there is a need to develop low-cost, novel interventions to prevent or reduce disease progression. Growing evidence shows that supplementation with carnosine, or its rate-limiting precursor β-alanine, can ameliorate aspects of the metabolic dysregulation that occurs in diabetes. There is, however, a need to develop a better understanding of the magnitude of effect and the factors associated with positive outcomes. The purpose of this systematic review and meta-analysis is to evaluate the effect of carnosine or β-alanine supplementation on markers of glycaemic control and insulin resistance in humans and animals.

Methods: We will perform a systematic search for randomised and non-randomised controlled trials. Studies will be retrieved by searching electronic databases, clinical trial registers, author review, and cross-referencing. Primary outcomes include changes in (i) fasting glucose, (ii) glycated haemoglobin, and (iii) 2-h glucose following a glucose tolerance test. A set of additional outcomes includes other markers of glycaemic control and insulin resistance. Risk of bias (RoB) will be assessed using the Cochrane RoB 2.0 tool (human studies) and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) RoB tool (animal studies). Confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. All meta-analyses will be conducted within a Bayesian framework, providing a flexible modelling approach to account for uncertainty in model parameters and underlying structures within the data.

Discussion: By including all available human and animal data, we will provide the most comprehensive overview on the topic to date. The results will have implications for those working in prediabetes, diabetes, and metabolic health in general and may lead to the development of new treatment approaches.

Dissemination: Study results will be presented at a professional conference and published in a peer-reviewed journal.

Systematic Review Registration: CRD42020191588.
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http://dx.doi.org/10.1186/s13643-020-01539-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719243PMC
December 2020

The urgent need for research coordination to advance knowledge on COVID-19 in children.

Pediatr Res 2020 Nov 11. Epub 2020 Nov 11.

Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool Health Partners, Liverpool, UK.

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http://dx.doi.org/10.1038/s41390-020-01259-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656217PMC
November 2020

Study protocol: azithromycin therapy for chronic lung disease of prematurity (AZTEC) - a randomised, placebo-controlled trial of azithromycin for the prevention of chronic lung disease of prematurity in preterm infants.

BMJ Open 2020 10 6;10(10):e041528. Epub 2020 Oct 6.

Department of Child Health, School of Medicine, Cardiff University, Cardiff, United Kingdom

Introduction: Chronic lung disease of prematurity (CLD), also known as bronchopulmonary dysplasia (BPD), is a cause of significant respiratory morbidity in childhood and beyond. Coupled with lung immaturity, infections (especially by spp) are implicated in the pathogenesis of CLD through promotion of pulmonary inflammation. Azithromycin, which is a highly effective against spp also has potent anti-inflammatory properties. Thus, azithromycin therapy may improve respiratory outcomes by targeting infective and inflammatory pathways. Previous trials using macrolides have not been sufficiently powered to definitively assess CLD rates. To address this, the azithromycin therapy for chronic lung disease of prematurity (AZTEC) trial aims to determine if a 10-day early course of intravenous azithromycin improves rates of survival without CLD when compared with placebo with an appropriately powered study.

Methods And Analysis: 796 infants born at less than 30 weeks' gestational age who require at least 2 hours of continuous respiratory support within the first 72 hours following birth are being enrolled by neonatal units in the UK. They are being randomised to receive a double-blind, once daily dose of intravenous azithromycin (20 mg/kg for 3 days, followed by 10 mg/kg for a further 7 days), or placebo. CLD is being assessed at 36 weeks' PMA. Whether colonisation with spp prior to randomisation modifies the treatment effect of azithromycin compared with placebo will also be investigated. Secondary outcomes include necrotising enterocolitis, intraventricular/cerebral haemorrhage, retinopathy of prematurity and nosocomial infections, development of antibiotic resistance and adverse reactions will be monitored.

Ethics And Dissemination: Ethics permission has been granted by Wales Research Ethics Committee 2 (Ref 18/WA/0199), and regulatory permission by the Medicines and Healthcare Products Regulatory Agency (Clinical Trials Authorisation reference 21323/0050/001-0001). The study is registered on ISRCTN (ISRCTN11650227). The study is overseen by an independent Data Monitoring Committee and an independent Trial Steering Committee. We shall disseminate our findings via national and international peer-reviewed journals, and conferences. A summary of the findings will also be posted on the trial website.
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http://dx.doi.org/10.1136/bmjopen-2020-041528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539578PMC
October 2020

The Phosphodiesterase Inhibitor Ensifentrine Reduces Production of Proinflammatory Mediators in Well Differentiated Bronchial Epithelial Cells by Inhibiting PDE4.

J Pharmacol Exp Ther 2020 12 4;375(3):414-429. Epub 2020 Oct 4.

Departments of Physiology (M.J.T., J.W.H.) and Pediatrics (N.D.) and Cystic Fibrosis Translational Research Centre (M.J.T., L.C.L., J.W.H), McGill University, Montréal, Québec, Canada; Pediatric Respiratory Medicine, Montreal Children's Hospital, Montréal, Québec, Canada (N.D., L.C.L.); Research Institute - McGill University Health Centre, Montréal, Québec, Canada (L.C.L., J.W.H.); Department of Internal, Respiratory Translational Laboratory, Respiratory and Critical Care Medicine, Philipps-University of Marburg, Marburg, Germany (N.D.); and Faculty of Medicine and Healthcare, al-Farabi Kazakh National University, Almaty, Kazakhstan (N.D.).

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel that impair airway salt and fluid secretion. Excessive release of proinflammatory cytokines and chemokines by CF bronchial epithelium during airway infection leads to chronic inflammation and a slow decline in lung function; thus, there is much interest in finding safe and effective treatments that reduce inflammation in CF. We showed previously that the cyclic nucleotide phosphodiesterase (PDE) inhibitor ensifentrine (RPL554; Verona Pharma) stimulates the channel function of CFTR mutants with abnormal gating and also those with defective trafficking that are partially rescued using a clinically approved corrector drug. PDE inhibitors also have known anti-inflammatory effects; therefore, we examined whether ensifentrine alters the production of proinflammatory cytokines in CF bronchial epithelial cells. Ensifentrine reduced the production of monocyte chemoattractant protein-1 and granulocyte monocyte colony-stimulating factor (GM-CSF) during challenge with interleukin-1 Comparing the effect of ensifentrine with milrinone and roflumilast, selective PDE3 and PDE4 inhibitors, respectively, demonstrated that the anti-inflammatory effect of ensifentrine was mainly due to inhibition of PDE4. Beneficial modulation of GM-CSF was further enhanced when ensifentrine was combined with low concentrations of the -adrenergic agonist isoproterenol or the corticosteroid dexamethasone. The results indicate that ensifentrine may have beneficial anti-inflammatory effects in CF airways particularly when used in combination with -adrenergic agonists or corticosteroids. SIGNIFICANCE STATEMENT: Airway inflammation that is disproportionate to the burden of chronic airway infection causes much of the pathology in the cystic fibrosis (CF) lung. We show here that ensifentrine beneficially modulates the release of proinflammatory factors in well differentiated CF bronchial epithelial cells that is further enhanced when combined with β-adrenergic agonists or low-concentration corticosteroids. The results encourage further clinical testing of ensifentrine, alone and in combination with β-adrenergic agonists or low-concentration corticosteroids, as a novel anti-inflammatory therapy for CF.
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http://dx.doi.org/10.1124/jpet.120.000080DOI Listing
December 2020

Modulation of Rab7a-mediated growth factor receptor trafficking inhibits islet beta cell apoptosis and autophagy under conditions of metabolic stress.

Sci Rep 2020 09 25;10(1):15741. Epub 2020 Sep 25.

Department of Biomolecular Sciences, Kingston University, Penrhyn Road, Kingston-upon-Thames, KT1 2EE, UK.

Regenerative medicine approaches to enhancing beta cell growth and survival represent potential treatments for diabetes. It is known that growth factors such as insulin, IGF-1 and HGF support beta cell growth and survival, but in people with type 2 diabetes the destructive effects of metabolic stress predominate and beta cell death or dysfunction occurs. In this study we explore the novel hypothesis that regulation of growth factor receptor trafficking can be used to promote islet beta cell survival. Growth factor signalling is dependent on the presence of cell surface receptors. Endosomal trafficking and subsequent recycling or degradation of these receptors is controlled by the Rab GTPase family of proteins. We show that Rab7a siRNA inhibition enhances IGF-1 and HGF signalling in beta cells and increases expression of the growth factor receptors IGF-1R and c-Met. Furthermore, Rab7a inhibition promotes beta cell growth and islet survival, and protects against activation of apoptosis and autophagy pathways under conditions of metabolic stress. This study therefore demonstrates that Rab7a-mediated trafficking of growth factor receptors controls beta cell survival. Pharmaceutical Rab7a inhibition may provide a means to promote beta cell survival in the context of metabolic stress and prevent the onset of type 2 diabetes.
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http://dx.doi.org/10.1038/s41598-020-72939-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519639PMC
September 2020

Isolation and Evaluation of Anti-Listeria Lactococcus lactis from Vegetal Sources.

Methods Mol Biol 2021 ;2220:243-257

School of Agriculture and Food Sciences, University of Queensland, Brisbane, QLD, Australia.

This chapter describes methods used to isolate, identify, and partially characterize lactic acid bacteria (LAB) which exhibit inhibitory activity against Listeria monocytogenes from foods. Vegetal (plant based) sources are rich in naturally occurring LAB and therefore provide an easily accessible source of strains with potential antimicrobial activity for use in food-processing applications. From our previous work, the majority of LAB with inhibitory activity against L. monocytogenes were identified as generally recognized as safe (GRAS) Lactococcus lactis. Although these bacteria are most commonly known for their role in industrial dairy fermentations, they are believed to have originally derived from natural plant-based habitats. These isolates with anti-Listeria activity were all found to carry the genes involved in the production of nisin, which is an approved food-grade preservative (E234). These isolates may find various applications for in situ production of nisin allowing control of L. monocytogenes in various fermented and non-fermented foods and other environments.
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http://dx.doi.org/10.1007/978-1-0716-0982-8_19DOI Listing
April 2021
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