• Influence of curing modes on thermal stability, hardness development and network integrity of dual-cure resin cements.

      Aldhafyan, Mohammed; Silikas, Nikolaos; email: nick.silikas@manchester.ac.uk; Watts, David C; email: david.watts@manchester.ac.uk (2021-09-27)
      To explore the effect of different curing modes of conventional and self-adhesive dual-cure resin cements on their rates of thermal decomposition, hardness development and network integrity. Five self-adhesive (PANAVIA SA, RelyX Universal Resin, RelyX Unicem 2, Bifix SE and SpeedCEM Plus) and three conventional (PANAVIA V5, Nexus Third Generation and RelyX Ultimate Universal) dual-cure resin cements were investigated. Thermal decomposition stages, initial onset temperatures, the maximum rate of mass-loss and the filler mass-fraction of each resin cement were analysed by thermogravimetric analysis (TGA). Surface hardness was measured at 1h post-cure and after 24h of dry storage at 37°C. The relative network integrities were estimated from reductions in hardness after 168h of water storage. Data were analysed via one-way ANOVA, Tukey post-hoc tests and paired/independent sample t-tests (a=0.05). No difference was apparent between TGA data for self-cured and light-cured specimens. Numerical differentiation of mass-loss versus temperature showed either single or multiple peaks. For the set of 8 cements, the maximum rate of mass-loss (%/°C) correlated negatively with residual mass at 600°C. All dry-stored cements increased in hardness from 1 to 24h, ranging from 20.4% to 52.6% for light-cure mode and from 41.3% to 112.6% for self-cure. After 168h water storage, the hardness of cements decreased: by 18.5%-36.2% for light-cured and by 9.8%-17.9% for self-cured. Overall, surface hardness was greater for light-cured cements. The initial onset temperature (IOT) of thermal decomposition correlated negatively with the hardness decrease produced by water-storage: r =0.77 for light-cure and r =0.88 for self-cure. This provided the basis for a relative scale of composite network integrity, probably reflecting differences in cross-link density. Light-curing, where possible, remains beneficial to the hardness and related properties of dual-cure resin cements. Combination of TG analysis and solvent softening experiments give an indication of relative network integrity - between materials - and their relative cross-link densities. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]
    • Information content best characterises the hemispheric selectivity of the inferior parietal lobe: a meta-analysis

      Gray, Oliver; email: oliver.gray@manchester.ac.uk; Fry, Lewis; Montaldi, Daniela (Nature Publishing Group UK, 2020-09-15)
      Abstract: Our understanding of the inferior parietal lobe (IPL) remains challenged by inconsistencies between neuroimaging and neuropsychological perspectives. To date, others assume that hemispheric specialisation of the IPL is linked with the type of processing; attention processing in the right hemisphere; memory retrieval and semantic judgement in the left hemisphere. Here, we provide compelling evidence associating the type of information being processed with the recruitment of each hemisphere’s IPL. In a meta-analysis, we classify 121 previous fMRI reports of IPL activity arising from episodic memory retrieval, according to the type of information that characterises each fMRI contrast. We demonstrate that the left IPL is more consistently associated with retrieval of the semantic (95% of eligible contrasts) than perceptual aspects of memory (83%). In contrast, the right IPL is more consistently associated with the retrieval of perceptual (97%), than semantic aspects of memory (43%). This work revises assumptions of how the IPL contributes to healthy cognition and has major implications for IPL-related neuropsychological deficits.
    • Information literacy

      Fiander, Wendy; University of Chester (SAGE, 2011)
      This book chapter discusses the importance of developing information literacy skills in healthcare students.
    • Inhibition of Wnt signalling by Notch via two distinct mechanisms.

      Acar, Ahmet; email: acara@metu.edu.tr; Hidalgo-Sastre, Ana; Leverentz, Michael K; Mills, Christopher G; Woodcock, Simon; Baron, Martin; Collu, Giovanna M; Brennan, Keith; email: keith.brennan@manchester.ac.uk (2021-04-27)
      Notch and Wnt are two essential signalling pathways that help to shape animals during development and to sustain adult tissue homeostasis. Although they are often active at the same time within a tissue, they typically have opposing effects on cell fate decisions. In fact, crosstalk between the two pathways is important in generating the great diversity of cell types that we find in metazoans. Several different mechanisms have been proposed that allow Notch to limit Wnt signalling, driving a Notch-ON/Wnt-OFF state. Here we explore these different mechanisms in human cells and demonstrate two distinct mechanisms by which Notch itself, can limit the transcriptional activity of β-catenin. At the membrane, independently of DSL ligands, Notch1 can antagonise β-catenin activity through an endocytic mechanism that requires its interaction with Deltex and sequesters β-catenin into the membrane fraction. Within the nucleus, the intracellular domain of Notch1 can also limit β-catenin induced transcription through the formation of a complex that requires its interaction with RBPjκ. We believe these mechanisms contribute to the robustness of cell-fate decisions by sharpening the distinction between opposing Notch/Wnt responses.
    • Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients

      Wulandari, Laksmi; Hamidah, Berliana; Pakpahan, Cennikon; Damayanti, Nevy Shinta; Kurniati, Neneng Dewi; Adiatmaja, Christophorus Oetama; Wigianita, Monica Rizky; Soedarsono; Husada, Dominicus; Tinduh, Damayanti; et al. (BioMed Central, 2021-05-17)
      Abstract: Background: Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host’s response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. Results: We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. Conclusion: Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.
    • Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients.

      Wulandari, Laksmi; Hamidah, Berliana; Pakpahan, Cennikon; Damayanti, Nevy Shinta; Kurniati, Neneng Dewi; Adiatmaja, Christophorus Oetama; Wigianita, Monica Rizky; Soedarsono; Husada, Dominicus; Tinduh, Damayanti; et al. (2021-05-17)
      Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.
    • Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients.

      Wulandari, Laksmi; Hamidah, Berliana; Pakpahan, Cennikon; Damayanti, Nevy Shinta; Kurniati, Neneng Dewi; Adiatmaja, Christophorus Oetama; Wigianita, Monica Rizky; Soedarsono; Husada, Dominicus; Tinduh, Damayanti; et al. (2021-05-17)
      <h4>Background</h4>Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load.<h4>Results</h4>We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19.<h4>Conclusion</h4>Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.
    • Insights into Public Perceptions of Earthship Buildings as Alternative Homes

      Booth, Colin A.; orcid: 0000-0003-4410-0129; email: colin.booth@uwe.ac.uk; Rasheed, Sona; email: sonamoghal@hotmail.co.uk; Mahamadu, Abdul-Majeed; email: abdul.mahamadu@uwe.ac.uk; Horry, Rosemary; email: r.e.horry@derby.ac.uk; Manu, Patrick; orcid: 0000-0001-7766-8824; email: patrick.manu@manchester.ac.uk; Awuah, Kwasi Gyau Baffour; orcid: 0000-0001-7927-7528; email: k.a.b.gyau@salford.ac.uk; Aboagye-Nimo, Emmanuel; orcid: 0000-0002-7651-744X; email: e.aboagye-nimo2@brighton.ac.uk; Georgakis, Panagiotis; orcid: 0000-0002-3200-997X; email: p.georgakis@wlv.ac.uk (MDPI, 2021-08-25)
      Sustainable futures necessitate a concomitant requirement for both sustainable buildings and sustainable behaviours under one roof. The defining principles behind Earthship buildings are to promote the use of local, recycled, waste, natural and renewable materials in their construction, for the adoption of a passive solar design for internal heating/cooling, collection of rainwater as a potable water supply, and encourage the onsite recycling of used water for plants to aid food production. However, despite growth in Earthship buildings constructed across many countries of the world, their appeal has not yet made a noticeable contribution to mainstream housing. Therefore, this study is the first to attempt to explore public perceptions towards the benefits and barriers of Earthship buildings as a means of understanding their demand by potential home builders/owners. Opinions were sought through questionnaire surveys completed by visitors to the Brighton Earthship building. Results reveal that the public believe that the reclamation of rainwater and greywater, renewable energy consumption and use of recycled materials included in the design/build are the major benefits of Earthship buildings, whilst the opportunity for a modern living style in a conservative lifestyle/setting, having a building that is cheaper than an ordinary home and the possibility of living totally off grid are considered the least beneficial reasons for building Earthship homes. Results also reveal that the public believe acquiring necessary permits/permissions to build may be more complicated, securing financial support (mortgage/loan) may be more challenging, and identifying/attaining suitable building plots are major barriers of Earthship buildings, whilst the futuristic/alternative building design, being built from waste materials and being entirely dependent on renewable resources (rainfall/wind/sunshine) are considered the least important barriers to building Earthship homes. Notwithstanding the participants included in this study already having an interest in Earthship buildings/lifestyles, it is concluded that the general public deem the general principles of Earthships as an acceptable choice of building/living but it is the formal means of building or buying an Earthship home that is the greatest hurdle against the uptake of Earthship buildings. Therefore, if sustainable futures are to be realized, it is proposed that a shift away from traditional house building towards Earthship building will require the involvement of all stakeholders immersed in the building process (architects, planners, builders, investors, lawyers) to path an easier journey for Earthship buildings and sustainable living.
    • Insights into the 9 December 2019 eruption of Whakaari/White Island from analysis of TROPOMI SO

      Burton, Mike; orcid: 0000-0003-3779-4812; email: mike.burton@manchester.ac.uk; Hayer, Catherine; orcid: 0000-0001-5734-0549; Miller, Craig; orcid: 0000-0001-8499-0352; Christenson, Bruce (2021-06-18)
      Small, phreatic explosions from volcanic hydrothermal systems pose a substantial proximal hazard on volcanoes, which can be popular tourist sites, creating casualty risks in case of eruption. Volcano monitoring of gas emissions provides insights into when explosions are likely to happen and unravel processes driving eruptions. Here, we report SO flux and plume height data retrieved from TROPOMI satellite imagery before, during, and after the 9 December 2019 eruption of Whakaari/White Island volcano, New Zealand, which resulted in 22 fatalities and numerous injuries. We show that SO was detected without explosive activity on separate days before and after the explosion, and that fluxes increased from 10 to 45 kg/s ~40 min before the explosion itself. High temporal resolution gas monitoring from space can provide key insights into magmatic degassing processes globally, aiding understanding of eruption precursors and complementing ground-based monitoring. [Abstract copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).]
    • Insights into the 9 December 2019 eruption of Whakaari/White Island from analysis of TROPOMI SO<sub>2</sub> imagery.

      Burton, Mike; orcid: 0000-0003-3779-4812; email: mike.burton@manchester.ac.uk; Hayer, Catherine; orcid: 0000-0001-5734-0549; Miller, Craig; orcid: 0000-0001-8499-0352; Christenson, Bruce (2021-06-18)
      Small, phreatic explosions from volcanic hydrothermal systems pose a substantial proximal hazard on volcanoes, which can be popular tourist sites, creating casualty risks in case of eruption. Volcano monitoring of gas emissions provides insights into when explosions are likely to happen and unravel processes driving eruptions. Here, we report SO<sub>2</sub> flux and plume height data retrieved from TROPOMI satellite imagery before, during, and after the 9 December 2019 eruption of Whakaari/White Island volcano, New Zealand, which resulted in 22 fatalities and numerous injuries. We show that SO<sub>2</sub> was detected without explosive activity on separate days before and after the explosion, and that fluxes increased from 10 to 45 kg/s ~40 min before the explosion itself. High temporal resolution gas monitoring from space can provide key insights into magmatic degassing processes globally, aiding understanding of eruption precursors and complementing ground-based monitoring.
    • Insulin protects acinar cells during pancreatitis by preserving glycolytic ATP supply to calcium pumps

      Bruce, Jason I. E.; orcid: 0000-0002-4503-1981; email: jason.bruce@manchester.ac.uk; Sánchez-Alvarez, Rosa; Sans, Maria Dolors; orcid: 0000-0002-9271-2106; Sugden, Sarah A.; Qi, Nathan; James, Andrew D.; orcid: 0000-0002-2432-5948; Williams, John A. (Nature Publishing Group UK, 2021-07-19)
      Abstract: Acute pancreatitis (AP) is serious inflammatory disease of the pancreas. Accumulating evidence links diabetes with severity of AP, suggesting that endogenous insulin may be protective. We investigated this putative protective effect of insulin during cellular and in vivo models of AP in diabetic mice (Ins2Akita) and Pancreatic Acinar cell-specific Conditional Insulin Receptor Knock Out mice (PACIRKO). Caerulein and palmitoleic acid (POA)/ethanol-induced pancreatitis was more severe in both Ins2Akita and PACIRKO vs control mice, suggesting that endogenous insulin directly protects acinar cells in vivo. In isolated pancreatic acinar cells, insulin induced Akt-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) which upregulated glycolysis thereby preventing POA-induced ATP depletion, inhibition of the ATP-dependent plasma membrane Ca2+ ATPase (PMCA) and cytotoxic Ca2+ overload. These data provide the first mechanistic link between diabetes and severity of AP and suggest that phosphorylation of PFKFB2 may represent a potential therapeutic strategy for treatment of AP.
    • Insulin protects acinar cells during pancreatitis by preserving glycolytic ATP supply to calcium pumps.

      Bruce, Jason I E; orcid: 0000-0002-4503-1981; email: jason.bruce@manchester.ac.uk; Sánchez-Alvarez, Rosa; Sans, Maria Dolors; orcid: 0000-0002-9271-2106; Sugden, Sarah A; Qi, Nathan; James, Andrew D; orcid: 0000-0002-2432-5948; Williams, John A (2021-07-19)
      Acute pancreatitis (AP) is serious inflammatory disease of the pancreas. Accumulating evidence links diabetes with severity of AP, suggesting that endogenous insulin may be protective. We investigated this putative protective effect of insulin during cellular and in vivo models of AP in diabetic mice (Ins2<sup>Akita</sup>) and Pancreatic Acinar cell-specific Conditional Insulin Receptor Knock Out mice (PACIRKO). Caerulein and palmitoleic acid (POA)/ethanol-induced pancreatitis was more severe in both Ins2<sup>Akita</sup> and PACIRKO vs control mice, suggesting that endogenous insulin directly protects acinar cells in vivo. In isolated pancreatic acinar cells, insulin induced Akt-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) which upregulated glycolysis thereby preventing POA-induced ATP depletion, inhibition of the ATP-dependent plasma membrane Ca<sup>2+</sup> ATPase (PMCA) and cytotoxic Ca<sup>2+</sup> overload. These data provide the first mechanistic link between diabetes and severity of AP and suggest that phosphorylation of PFKFB2 may represent a potential therapeutic strategy for treatment of AP.
    • Insulin protects acinar cells during pancreatitis by preserving glycolytic ATP supply to calcium pumps.

      Bruce, Jason I E; orcid: 0000-0002-4503-1981; email: jason.bruce@manchester.ac.uk; Sánchez-Alvarez, Rosa; Sans, Maria Dolors; orcid: 0000-0002-9271-2106; Sugden, Sarah A; Qi, Nathan; James, Andrew D; orcid: 0000-0002-2432-5948; Williams, John A (2021-07-19)
      Acute pancreatitis (AP) is serious inflammatory disease of the pancreas. Accumulating evidence links diabetes with severity of AP, suggesting that endogenous insulin may be protective. We investigated this putative protective effect of insulin during cellular and in vivo models of AP in diabetic mice (Ins2 ) and Pancreatic Acinar cell-specific Conditional Insulin Receptor Knock Out mice (PACIRKO). Caerulein and palmitoleic acid (POA)/ethanol-induced pancreatitis was more severe in both Ins2 and PACIRKO vs control mice, suggesting that endogenous insulin directly protects acinar cells in vivo. In isolated pancreatic acinar cells, insulin induced Akt-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) which upregulated glycolysis thereby preventing POA-induced ATP depletion, inhibition of the ATP-dependent plasma membrane Ca ATPase (PMCA) and cytotoxic Ca overload. These data provide the first mechanistic link between diabetes and severity of AP and suggest that phosphorylation of PFKFB2 may represent a potential therapeutic strategy for treatment of AP. [Abstract copyright: © 2021. The Author(s).]
    • Integrated Cleaner Biocatalytic Process for Biodiesel Production from Crude Palm Oil Comparing to Refined Palm Oil

      Muanruksa, Papasanee; email: m.papasanee@kkumail.com; Wongsirichot, Phavit; email: phavit.wongsirichot@manchester.ac.uk; Winterburn, James; email: james.winterburn@manchester.ac.uk; Kaewkannetra, Pakawadee; email: paknar@kku.ac.th (MDPI, 2021-06-15)
      An integrated cleaner biocatalyst process was performed for biodiesel production from crude palm oil (CPO) and refined palm oil (RPO). It was evaluated on process efficiency in terms of high purity of biodiesel as well as by-products without purification, less wastewater, less time consuming, and a simple downstream process. A first saponification step was carried out in both f CPO and RPO, a high purity of glycerol (86.25% and 87.5%) was achieved, respectively, while free fatty acids (FFASs) in soap were obtained after hexane extraction. High yields of FFASs were obtained from both CPO and RPO (98.83% and 90.94%). Subsequently, the FFAs were esterified to biodiesel by a biocatalyst of immobilized lipase. The highest biodiesel yields achieved were of 92.14% and 92.58% (CPO and RPO). Remarkably, biodiesel yields obtained from CPO and RPO achieved satisfactory values and the biocatalyst used could be reused for more than 16–17 cycles.
    • Integrating visual arts into post-diagnostic dementia support groups in Memory Services

      Ponsillo, Nick; orcid: 0000-0003-1030-8028; Boot, Julia; Jones, Katy (SAGE Publications, 2020-09-15)
    • Intelligent Condition Monitoring of Wind Power Systems: State of the Art Review

      Benbouzid; orcid: 0000-0002-4844-508X; email: Mohamed.Benbouzid@univ-brest.fr; Berghout; orcid: 0000-0003-4877-4200; email: t.berghout@univ-batna2.dz; Sarma; email: nursarma@duzce.edu.tr; Djurović; orcid: 0000-0001-7700-6492; email: Sinisa.Durovic@manchester.ac.uk; Wu; orcid: 0000-0002-9396-1673; email: y.wu31@lancaster.ac.uk; Ma; email: xiandong.ma@lancaster.ac.uk (MDPI, 2021-09-20)
      Modern wind turbines operate in continuously transient conditions, with varying speed, torque, and power based on the stochastic nature of the wind resource. This variability affects not only the operational performance of the wind power system, but can also affect its integrity under service conditions. Condition monitoring continues to play an important role in achieving reliable and economic operation of wind turbines. This paper reviews the current advances in wind turbine condition monitoring, ranging from conventional condition monitoring and signal processing tools to machine-learning-based condition monitoring and usage of big data mining for predictive maintenance. A systematic review is presented of signal-based and data-driven modeling methodologies using intelligent and machine learning approaches, with the view to providing a critical evaluation of the recent developments in this area, and their applications in diagnosis, prognosis, health assessment, and predictive maintenance of wind turbines and farms.
    • Inter-species interactions alter antibiotic efficacy in bacterial communities.

      Bottery, Michael J; orcid: 0000-0001-5790-1756; email: michael.bottery@manchester.ac.uk; Matthews, Jessica L; Wood, A Jamie; orcid: 0000-0002-6119-852X; Johansen, Helle Krogh; Pitchford, Jon W; Friman, Ville-Petri; orcid: 0000-0002-1592-157X (2021-10-09)
      The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members' susceptibility to antibiotics. Here we quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples. We demonstrate that multi-drug resistant Stenotrophomonas maltophilia can provide high levels of antibiotic protection to otherwise sensitive P. aeruginosa. Exposure protection to imipenem was provided by chromosomally encoded metallo-β-lactamase that detoxified the environment; protection was dependent upon S. maltophilia cell density and was provided by S. maltophilia strains isolated from CF sputum, increasing the MIC of P. aeruginosa by up to 16-fold. In contrast, the presence of S. maltophilia provided no protection against meropenem, another routinely used carbapenem. Mathematical ordinary differential equation modelling shows that the level of exposure protection provided against different carbapenems can be explained by differences in antibiotic efficacy and inactivation rate. Together, these findings reveal that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities. [Abstract copyright: © 2021. The Author(s).]
    • Interaction between Dietary Fat Intake and Metabolic Genetic Risk Score on 25-Hydroxyvitamin D Concentrations in a Turkish Adult Population

      Isgin-Atici, Kubra; orcid: 0000-0002-3088-8675; email: k.isginatici@gmail.com; Alathari, Buthaina E.; email: b.e.a.a.alathari@pgr.reading.ac.uk; Turan-Demirci, Busra; orcid: 0000-0001-5497-0887; email: busraturan@hacettepe.edu.tr; Sendur, Suleyman Nahit; email: snahitsendur@hotmail.com; Lay, Incilay; orcid: 0000-0002-1466-5746; email: lincilay@gmail.com; Ellahi, Basma; email: b.ellahi@chester.ac.uk; Alikasifoglu, Mehmet; email: kasif@hacettepe.edu.tr; Erbas, Tomris; orcid: 0000-0003-1377-9394; email: erbast@hacettepe.edu.tr; Buyuktuncer, Zehra; email: zbtuncer@hacettepe.edu.tr; Vimaleswaran, Karani Santhanakrishnan; orcid: 0000-0002-8485-8930; email: v.karani@reading.ac.uk (MDPI, 2022-01-17)
      Previous studies have pointed out a link between vitamin D status and metabolic traits, however, consistent evidence has not been provided yet. This cross-sectional study has used a nutrigenetic approach to investigate the interaction between metabolic-genetic risk score (GRS) and dietary intake on serum 25-hydroxyvitamin D [25(OH)D] concentrations in 396 unrelated Turkish adults, aged 24−50 years. Serum 25(OH)D concentration was significantly lower in those with a metabolic-GRS ≥ 1 risk allele than those with a metabolic-GRS 1 risk allele (p = 0.020). A significant interaction between metabolic-GRS and dietary fat intake (energy%) on serum 25(OH)D levels was identified (Pinteraction = 0.040). Participants carrying a metabolic-GRS ≥ 1 risk allele and consuming a high fat diet (≥38% of energy = 122.3 ± 52.51 g/day) had significantly lower serum 25(OH)D concentration (p = 0.006) in comparison to those consuming a low-fat diet (38% of energy = 82.5 ± 37.36 g/d). In conclusion, our study suggests a novel interaction between metabolic-GRS and dietary fat intake on serum 25(OH)D level, which emphasises that following the current dietary fat intake recommendation (35% total fat) could be important in reducing the prevalence of vitamin D deficiency in this Turkish population. Nevertheless, further larger studies are needed to verify this interaction, before implementing personalized dietary recommendations for the maintenance of optimal vitamin D status.
    • Interaction between Metformin, Folate and Vitamin B 12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies

      Owen, Manon D.; email: ummdo@leeds.ac.uk; Baker, Bernadette C.; orcid: 0000-0003-0048-0465; email: bernadette.baker@manchester.ac.uk; Scott, Eleanor M.; email: E.M.Scott@leeds.ac.uk; Forbes, Karen; orcid: 0000-0002-3745-1337; email: K.A.Forbes@leeds.ac.uk (MDPI, 2021-05-28)
      Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.