• Global predictions of primary soil salinization under changing climate in the 21st century

      Hassani, Amirhossein; orcid: 0000-0002-6470-0490; email: ahas@nilu.no; Azapagic, Adisa; orcid: 0000-0003-2380-918X; email: adisa.azapagic@manchester.ac.uk; Shokri, Nima; orcid: 0000-0001-6799-4888; email: nima.shokri@tuhh.de (Nature Publishing Group UK, 2021-11-18)
      Abstract: Soil salinization has become one of the major environmental and socioeconomic issues globally and this is expected to be exacerbated further with projected climatic change. Determining how climate change influences the dynamics of naturally-occurring soil salinization has scarcely been addressed due to highly complex processes influencing salinization. This paper sets out to address this long-standing challenge by developing data-driven models capable of predicting primary (naturally-occurring) soil salinity and its variations in the world’s drylands up to the year 2100 under changing climate. Analysis of the future predictions made here identifies the dryland areas of South America, southern and western Australia, Mexico, southwest United States, and South Africa as the salinization hotspots. Conversely, we project a decrease in the soil salinity of the drylands in the northwest United States, the Horn of Africa, Eastern Europe, Turkmenistan, and west Kazakhstan in response to climate change over the same period.
    • Tomographic mapping of the hidden dimension in quasi-particle interference

      Marques, C. A.; orcid: 0000-0002-3804-096X; Bahramy, M. S.; orcid: 0000-0001-9024-6335; email: m.saeed.bahramy@manchester.ac.uk; Trainer, C.; Marković, I.; Watson, M. D.; orcid: 0000-0002-0737-2814; Mazzola, F.; Rajan, A.; orcid: 0000-0001-5356-3032; Raub, T. D.; orcid: 0000-0003-4513-2245; King, P. D. C.; orcid: 0000-0002-6523-9034; Wahl, P.; orcid: 0000-0002-8635-1519; email: wahl@st-andrews.ac.uk (Nature Publishing Group UK, 2021-11-18)
      Abstract: Quasiparticle interference (QPI) imaging is well established to study the low-energy electronic structure in strongly correlated electron materials with unrivalled energy resolution. Yet, being a surface-sensitive technique, the interpretation of QPI only works well for anisotropic materials, where the dispersion in the direction perpendicular to the surface can be neglected and the quasiparticle interference is dominated by a quasi-2D electronic structure. Here, we explore QPI imaging of galena, a material with an electronic structure that does not exhibit pronounced anisotropy. We find that the quasiparticle interference signal is dominated by scattering vectors which are parallel to the surface plane however originate from bias-dependent cuts of the 3D electronic structure. We develop a formalism for the theoretical description of the QPI signal and demonstrate how this quasiparticle tomography can be used to obtain information about the 3D electronic structure and orbital character of the bands.
    • Selected Derivatives of Erythromycin B- In Silico and Anti-Malarial Studies

      Bhadra, Pranab K.; email: bhadra.pranab@gmail.com; Magwaza, Rachael N.; email: rachael.magwaza@manchester.ac.uk; Nirmalan, Niroshini; email: n.j.nirmalan@salford.ac.uk; Freeman, Sally; orcid: 0000-0002-3831-9151; email: Sally.Freeman@manchester.ac.uk; Barber, Jill; orcid: 0000-0002-5424-0291; email: Jill.Barber@manchester.ac.uk; Arsic, Biljana; orcid: 0000-0002-1248-5864; email: ba432@ymail.com (MDPI, 2021-11-18)
      Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their in silico molecular docking into segments of the exit tunnel of the apicoplast ribosome from Plasmodium falciparum. This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of P. falciparum for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of P. falciparum with low micro-molar IC50 values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC50 of 68.6 µM, d-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of P. falciparum. Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with in silico constructed segment from the exit tunnel from the apicoplast of P. falciparum is the reason for their weak in vitro anti-malarial activities.
    • Generation and Characterization of the Drosophila melanogaster paralytic Gene Knock-Out as a Model for Dravet Syndrome

      Tapia, Andrea; email: atapia@cipf.es; Giachello, Carlo N.; email: carlogiachello.cg@gmail.com; Palomino-Schätzlein, Martina; orcid: 0000-0001-7303-0743; email: mpalomino@cipf.es; Baines, Richard A.; orcid: 0000-0001-8571-4376; email: Richard.Baines@manchester.ac.uk; Galindo, Máximo Ibo; orcid: 0000-0001-8448-9760; email: igalindo@cipf.es (MDPI, 2021-11-18)
      Dravet syndrome is a severe rare epileptic disease caused by mutations in the SCN1A gene coding for the Nav1.1 protein, a voltage-gated sodium channel alpha subunit. We have made a knock-out of the paralytic gene, the single Drosophila melanogaster gene encoding this type of protein, by homologous recombination. These flies showed a heat-induced seizing phenotype, and sudden death in long term seizures. In addition to seizures, neuromuscular alterations were observed in climbing, flight, and walking tests. Moreover, they also manifested some cognitive alterations, such as anxiety and problems in learning. Electrophysiological analyses from larval motor neurons showed a decrease in cell capacitance and membrane excitability, while persistent sodium current increased. To detect alterations in metabolism, we performed an NMR metabolomic profiling of heads, which revealed higher levels in some amino acids, succinate, and lactate; and also an increase in the abundance of GABA, which is the main neurotransmitter implicated in Dravet syndrome. All these changes in the paralytic knock-out flies indicate that this is a good model for epilepsy and specifically for Dravet syndrome. This model could be a new tool to understand the pathophysiology of the disease and to find biomarkers, genetic modifiers and new treatments.
    • Compliance of the fish outflow tract is altered by thermal acclimation through connective tissue remodelling

      Keen, Adam N.; Mackrill, John J.; orcid: 0000-0003-2473-129X; Gardner, Peter; Shiels, Holly A.; orcid: 0000-0001-5223-5205; email: holly.shiels@manchester.ac.uk (The Royal Society, 2021-11-17)
      To protect the gill capillaries from high systolic pulse pressure, the fish heart contains a compliant non-contractile chamber called the bulbus arteriosus which is part of the outflow tract (OFT) which extends from the ventricle to the ventral aorta. Thermal acclimation alters the form and function of the fish atria and ventricle to ensure appropriate cardiac output at different temperatures, but its impact on the OFT is unknown. Here we used ex vivo pressure–volume curves to demonstrate remodelling of passive stiffness in the rainbow trout (Oncorhynchus mykiss) bulbus arteriosus following more than eight weeks of thermal acclimation to 5, 10 and 18°C. We then combined novel, non-biased Fourier transform infrared spectroscopy with classic histological staining to show that changes in compliance were achieved by changes in tissue collagen-to-elastin ratio. In situ gelatin zymography and SDS-PAGE zymography revealed that collagen remodelling was underpinned, at least in part, by changes in activity and abundance of collagen degrading matrix metalloproteinases. Collectively, we provide the first indication of bulbus arteriosus thermal remodelling in a fish and suggest this remodelling ensures optimal blood flow and blood pressure in the OFT during temperature change.
    • Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer

      Schenk, Maximilian W.; Humphrey, Sam; Hossain, A. S. Md Mukarram; Revill, Mitchell; Pearsall, Sarah; Lallo, Alice; Brown, Stewart; Bratt, Samuel; Galvin, Melanie; Descamps, Tine; et al. (Nature Publishing Group UK, 2021-11-17)
      Abstract: Small cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) is recurrently upregulated in post-chemotherapy progression CDX models, which correlates with acquired chemoresistance. Expression and activation of sGC is regulated by Notch and nitric oxide (NO) signalling with downstream activation of protein kinase G. Genetic targeting of sGC or pharmacological inhibition of NO synthase re-sensitizes a chemoresistant CDX progression model in vivo, revealing this pathway as a mediator of chemoresistance and potential vulnerability of relapsed SCLC.
    • Sexually dimorphic patterns in maternal circulating microRNAs in pregnancies complicated by fetal growth restriction

      Baker, Bernadette C.; orcid: 0000-0003-0048-0465; email: bernadette.baker@manchester.ac.uk; Lui, Sylvia; Lorne, Isabel; Heazell, Alexander E. P.; Forbes, Karen; email: K.A.Forbes@leeds.ac.uk; Jones, Rebecca L. (BioMed Central, 2021-11-17)
      Abstract: Background: Current methods fail to accurately predict women at greatest risk of developing fetal growth restriction (FGR) or related adverse outcomes, including stillbirth. Sexual dimorphism in these adverse pregnancy outcomes is well documented as are sex-specific differences in gene and protein expression in the placenta. Circulating maternal serum microRNAs (miRNAs) offer potential as biomarkers that may also be informative of underlying pathology. We hypothesised that FGR would be associated with an altered miRNA profile and would differ depending on fetal sex. Methods: miRNA expression profiles were assessed in maternal serum (> 36 weeks’ gestation) from women delivering a severely FGR infant (defined as an individualised birthweight centile (IBC) < 3rd) and matched control participants (AGA; IBC = 20–80th), using miRNA arrays. qPCR was performed using specific miRNA primers in an expanded cohort of patients with IBC < 5th (n = 15 males, n = 16 females/group). Maternal serum human placental lactogen (hPL) was used as a proxy to determine if serum miRNAs were related to placental dysfunction. In silico analyses were performed to predict the potential functions of altered miRNAs. Results: Initial analyses revealed 11 miRNAs were altered in maternal serum from FGR pregnancies. In silico analyses revealed all 11 altered miRNAs were located in a network of genes that regulate placental function. Subsequent analysis demonstrated four miRNAs showed sexually dimorphic patterns. miR-28-5p was reduced in FGR pregnancies (p < 0.01) only when there was a female offspring and miR-301a-3p was only reduced in FGR pregnancies with a male fetus (p < 0.05). miR-454-3p was decreased in FGR pregnancies (p < 0.05) regardless of fetal sex but was only positively correlated to hPL when the fetus was female. Conversely, miR-29c-3p was correlated to maternal hPL only when the fetus was male. Target genes for sexually dimorphic miRNAs reveal potential functional roles in the placenta including angiogenesis, placental growth, nutrient transport and apoptosis. Conclusions: These studies have identified sexually dimorphic patterns for miRNAs in maternal serum in FGR. These miRNAs may have potential as non-invasive biomarkers for FGR and associated placental dysfunction. Further studies to determine if these miRNAs have potential functional roles in the placenta may provide greater understanding of the pathogenesis of placental dysfunction and the differing susceptibility of male and female fetuses to adverse in utero conditions.
    • Quantitative Magnetic Resonance Imaging in Perianal Crohn’s Disease at 1.5 and 3.0 T: A Feasibility Study

      Alyami, Ali; email: aalmansour@jazanu.edu.sa; Hoad, Caroline L.; orcid: 0000-0001-5483-1027; email: Caroline.L.Hoad@nottingham.ac.uk; Tench, Christopher; email: Christopher.Tench@nottingham.ac.uk; Bannur, Uday; email: uday.bannur@nuh.nhs.uk; Clarke, Christopher; orcid: 0000-0002-8092-9877; email: christopher.clarke@nuh.nhs.uk; Latief, Khalid; email: khalid.latief@nuh.nhs.uk; Argyriou, Konstantinos; orcid: 0000-0002-2026-9678; email: kosnar2@yahoo.gr; Lobo, Alan; email: alan.lobo@nhs.net; Lung, Philip; email: philliplung@nhs.net; Baldwin-Cleland, Rachel; email: r.baldwin@nhs.net; et al. (MDPI, 2021-11-17)
      Perianal Crohn’s Disease (pCD) is a common manifestation of Crohn’s Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn’s Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.
    • On prediction of aided behavioural measures using speech auditory brainstem responses and decision trees

      editor: Menezes, Pedro de Lemos; Perugia, Emanuele; orcid: 0000-0002-4392-6933; email: emanuele.perugia@manchester.ac.uk; BinKhamis, Ghada; orcid: 0000-0002-7696-1073; Schlittenlacher, Josef; Kluk, Karolina; orcid: 0000-0003-3638-2787; email: karolina.kluk@manchester.ac.uk (Public Library of Science, 2021-11-16)
      Current clinical strategies to assess benefits from hearing aids (HAs) are based on self-reported questionnaires and speech-in-noise (SIN) tests; which require behavioural cooperation. Instead, objective measures based on Auditory Brainstem Responses (ABRs) to speech stimuli would not require the individuals’ cooperation. Here, we re-analysed an existing dataset to predict behavioural measures with speech-ABRs using regression trees. Ninety-two HA users completed a self-reported questionnaire (SSQ-Speech) and performed two aided SIN tests: sentences in noise (BKB-SIN) and vowel-consonant-vowels (VCV) in noise. Speech-ABRs were evoked by a 40 ms [da] and recorded in 2x2 conditions: aided vs. unaided and quiet vs. background noise. For each recording condition, two sets of features were extracted: 1) amplitudes and latencies of speech-ABR peaks, 2) amplitudes and latencies of speech-ABR F0 encoding. Two regression trees were fitted for each of the three behavioural measures with either feature set and age, digit-span forward and backward, and pure tone average (PTA) as possible predictors. The PTA was the only predictor in the SSQ-Speech trees. In the BKB-SIN trees, performance was predicted by the aided latency of peak F in quiet for participants with PTAs between 43 and 61 dB HL. In the VCV trees, performance was predicted by the aided F0 encoding latency and the aided amplitude of peak VA in quiet for participants with PTAs ≤ 47 dB HL. These findings indicate that PTA was more informative than any speech-ABR measure, as these were relevant only for a subset of the participants. Therefore, speech-ABRs evoked by a 40 ms [da] are not a clinical predictor of behavioural measures in HA users.
    • Synchronous uterine and bladder cancers detected in urine and vaginal samples by cytology

      Narine, Nadira; Rana, Durgesh; Shelton, David; Awad, Dina; O'Flynn, Helena; Jones, Eleanor R.; Ryan, Neil A. J.; Crosbie, Emma J.; orcid: 0000-0003-0284-8630; email: emma.crosbie@manchester.ac.uk (John Wiley & Sons, Inc., 2021-11-16)
      Abstract: Novel diagnostics for uterine cancer are urgently needed to reduce the burden of invasive testing for the majority of healthy women with postmenopausal bleeding. We have previously shown that uterine cancer cells can be detected by cytology in urine and vaginal samples with high diagnostic accuracy. Here, we demonstrate its potential to distinguish malignant cells of different aetiologies in the same urogenital biofluid sample according to their distinctive morphology and immunoprofiles. Synchronous tumours of the urogenital tract are uncommon but can cause diagnostic confusion, delays and poor outcomes. A 79‐year‐old woman presented to accident and emergency with postmenopausal bleeding. Voided urine and Delphi screener‐collected vaginal samples were assessed by cytology and immunocytochemistry. Two malignant cell populations with distinct morphology and immunophenotypes consistent with synchronous uterine and urothelial tumours were identified. Subsequent routine diagnostics confirmed concurrent uterine carcinosarcoma and high‐grade urothelial carcinoma of the bladder. This case demonstrates that cytology and adjunctive immunocytochemistry can simultaneously identify and phenotype cancers of different aetiologies from a single urogenital biofluid sample. This can help rationalise diagnostic pathways in complex, unusual cases of dual urogenital primaries.
    • Non-Alcoholic Fatty Liver Disease (NAFLD) and Potential Links to Depression, Anxiety, and Chronic Stress

      Shea, Sue; email: sue.shea@warwick.ac.uk; Lionis, Christos; orcid: 0000-0002-9324-2839; email: lionis@galinos.med.uoc.gr; Kite, Chris; orcid: 0000-0003-1342-274X; email: c.kite@chester.ac.uk; Atkinson, Lou; orcid: 0000-0003-1613-3791; email: l.atkinson1@aston.ac.uk; Chaggar, Surinderjeet S.; email: surinder.chaggar@nhs.net; Randeva, Harpal S.; email: harpal.randeva@uhcw.nhs.uk; Kyrou, Ioannis; email: ad6702@coventry.ac.uk (MDPI, 2021-11-16)
      Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.
    • Exploring the Frequency, Intensity, and Duration of Loneliness: A Latent Class Analysis of Data from the BBC Loneliness Experiment

      Qualter, Pamela; orcid: 0000-0001-6114-3820; email: pamela.qualter@manchester.ac.uk; Petersen, Kimberly; orcid: 0000-0002-4941-6897; email: kimberley.petersen@manchester.ac.uk; Barreto, Manuela; orcid: 0000-0002-6973-7233; email: M.Barreto@exeter.ac.uk; Victor, Christina; email: Christina.Victor@brunel.ac.uk; Hammond, Claudia; email: claudia.hammond@bbc.co.uk; Arshad, Sana-Arub; email: arshad18@live.co.uk (MDPI, 2021-11-16)
      Almost all measures of loneliness have been developed without discussing how to best conceptualize and assess the severity of loneliness. In the current study, we adapted the four-item UCLA, so that it continued to measure frequency of loneliness, but also assessed intensity and duration, providing a measure of other aspects of loneliness severity. Using data from participants resident in the UK who completed the BBC Loneliness Experiment (N = 36,767; F = 69.6%) and Latent Class Profile Analyses, we identified four groups of people who scored high on loneliness on at least one of the three severity measures. Duration of loneliness often over months or years seemed to be particularly important in distinguishing groups. Further, group membership was predicted by important demographic and psychological variables. We discuss the findings in terms of implications for research and practice. We highlight the need to explore these profiles longitudinally to investigate how membership predicts later mental and physical health, and well-being.
    • Physical Activity, Mental Health and Wellbeing during the First COVID-19 Containment in New Zealand: A Cross-Sectional Study

      O’Brien, Wendy J.; orcid: 0000-0002-9123-3111; email: w.j.obrien@massey.ac.nz; Badenhorst, Claire E.; email: c.badenhorst@massey.ac.nz; Draper, Nick; email: nick.draper@canterbury.ac.nz; Basu, Arindam; orcid: 0000-0003-2326-2292; email: arindam.basu@canterbury.ac.nz; Elliot, Catherine A.; orcid: 0000-0001-5594-4699; email: catherine.elliot@lincoln.ac.nz; Hamlin, Michael J.; orcid: 0000-0001-7941-8554; email: michael.hamlin@lincoln.ac.nz; Batten, John; orcid: 0000-0001-7499-7817; email: John.Batten@winchester.ac.uk; Lambrick, Danielle; email: D.M.Lambrick@soton.ac.uk; Faulkner, James; orcid: 0000-0002-3704-6737; email: James.Faulkner@winchester.ac.uk (MDPI, 2021-11-16)
      Strategies implemented worldwide to contain COVID-19 outbreaks varied in severity across different countries, and established a new normal for work and school life (i.e., from home) for many people, reducing opportunities for physical activity. Positive relationships of physical activity with both mental and physical health are well recognised, and therefore the aim was to ascertain how New Zealand’s lockdown restrictions impacted physical activity, mental health and wellbeing. Participants (n = 4007; mean ± SD: age 46.5 ± 14.7 years, 72% female, 80.7% New Zealand European) completed (10–26 April 2020) an online amalgamated survey (Qualtrics): International Physical Activity Questionnaire: Short Form; Depression, Anxiety and Stress Scale-9; World Health Organisation-Five Well-Being Index; Stages of Change Scale. Positive dose–response relationships between physical activity levels and wellbeing scores were demonstrated for estimates that were unadjusted (moderate activity OR 3.79, CI 2.88–4.92; high activity OR 8.04, CI 6.07–10.7) and adjusted (confounding variables: age, gender, socioeconomic status, time sitting and co-morbidities) (moderate activity 1.57, CI 1.11–2.52; high activity 2.85, CI 1.97–4.14). The study results support previous research demonstrating beneficial effects of regular physical activity on mental health and wellbeing. Governments may use these results to promote meeting physical activity guidelines in order to protect mental health and wellbeing during the ongoing COVID-19 restrictions and future pandemics.
    • Developing a Complex Understanding of Physical Activity in Cardiometabolic Disease from Low-to-Middle-Income Countries—A Qualitative Systematic Review with Meta-Synthesis

      Heine, Martin; orcid: 0000-0003-4131-2863; email: mheine@sun.ac.za; Badenhorst, Marelise; email: marelise.badenhorst@aut.ac.nz; van Zyl, Chanel; email: chanelkat90@gmail.com; de Melo Ghisi, Gabriela Lima; orcid: 0000-0001-7946-3718; email: Gabriela.MeloGhisi@uhn.ca; Babu, Abraham Samuel; orcid: 0000-0003-1084-0137; email: abraham.babu@manipal.edu; Buckley, John; email: j.buckley@chester.ac.uk; Serón, Pamela; orcid: 0000-0003-0190-8988; email: pamela.seron@ufrontera.cl; Turk-Adawi, Karam; email: kadawi@brandeis.edu; Derman, Wayne; email: ewderman@sun.ac.za (MDPI, 2021-11-15)
      Physical activity behaviour is complex, particularly in low-resource settings, while existing behavioural models of physical activity behaviour are often linear and deterministic. The objective of this review was to (i) synthesise the wide scope of factors that affect physical activity and thereby (ii) underpin the complexity of physical activity in low-resource settings through a qualitative meta-synthesis of studies conducted among patients with cardiometabolic disease living in low-to-middle income countries (LMIC). A total of 41 studies were included from 1200 unique citations (up to 15 March 2021). Using a hybrid form of content analysis, unique factors (n = 208) that inform physical activity were identified, and, through qualitative meta-synthesis, these codes were aggregated into categories (n = 61) and synthesised findings (n = 26). An additional five findings were added through deliberation within the review team. Collectively, the 31 synthesised findings highlight the complexity of physical activity behaviour, and the connectedness between person, social context, healthcare system, and built and natural environment. Existing behavioural and ecological models are inadequate in fully understanding physical activity participation in patients with cardiometabolic disease living in LMIC. Future research, building on complexity science and systems thinking, is needed to identify key mechanisms of action applicable to the local context.
    • Anomalous Stochastic Transport of Particles with Self-Reinforcement and Mittag–Leffler Distributed Rest Times

      Han, Daniel; orcid: 0000-0002-9088-1651; email: dhan@mrc-lmb.cam.ac.uk; Alexandrov, Dmitri V.; orcid: 0000-0002-6628-745X; email: dmitri.v.alexandrov@gmail.com; Gavrilova, Anna; email: anna.gavrilova@postgrad.manchester.ac.uk; Fedotov, Sergei; email: sergei.fedotov@manchester.ac.uk (MDPI, 2021-11-15)
      We introduce a persistent random walk model for the stochastic transport of particles involving self-reinforcement and a rest state with Mittag–Leffler distributed residence times. The model involves a system of hyperbolic partial differential equations with a non-local switching term described by the Riemann–Liouville derivative. From Monte Carlo simulations, we found that this model generates superdiffusion at intermediate times but reverts to subdiffusion in the long time asymptotic limit. To confirm this result, we derived the equation for the second moment and find that it is subdiffusive in the long time limit. Analyses of two simpler models are also included, which demonstrate the dominance of the Mittag–Leffler rest state leading to subdiffusion. The observation that transient superdiffusion occurs in an eventually subdiffusive system is a useful feature for applications in stochastic biological transport.
    • Real-World Outcomes of Glucose Sensor Use in Type 1 Diabetes—Findings from a Large UK Centre

      Lee, Kyuhan; orcid: 0000-0002-9644-5017; email: kyuhan.lee@student.manchester.ac.uk; Gunasinghe, Shakthi; email: shakthi.gunasinghe@student.manchester.ac.uk; Chapman, Alyson; email: alyson.chapman@mft.nhs.uk; Findlow, Lynne A.; email: lynneann.findlow@mft.nhs.uk; Hyland, Jody; email: jody.hyland@mft.nhs.uk; Ohol, Sheetal; email: sheetal.ohol@mft.nhs.uk; Urwin, Andrea; email: andrea.urwin@mft.nhs.uk; Rutter, Martin K.; email: martin.rutter@mft.nhs.uk; Schofield, Jonathan; email: jonathan.schofield@mft.nhs.uk; Thabit, Hood; orcid: 0000-0001-6076-6997; email: hood.thabit@mft.nhs.uk; et al. (MDPI, 2021-11-15)
      Flash glucose monitoring (FGM) and real-time continuous glucose monitoring (RT-CGM) are increasingly used in clinical practice, with improvements in HbA1c and time in range (TIR) reported in clinical studies. We aimed to evaluate the impact of FGM and RT-CGM use on glycaemic outcomes in adults with type 1 diabetes (T1DM) under routine clinical care. We performed a retrospective data analysis from electronic outpatient records and proprietary web-based glucose monitoring platforms. We measured HbA1c (pre-sensor vs. on-sensor data) and sensor-based outcomes from the previous three months as per the international consensus on RT-CGM reporting guidelines. Amongst the 789 adults with T1DM, HbA1c level decreased from 61.0 (54.0, 71.0) mmol/mol to 57 (49, 65.8) mmol/mol in 561 people using FGM, and from 60.0 (50.0, 70.0) mmol/mol to 58.8 (50.3, 66.8) mmol/mol in 198 using RT-CGM (p 0.001 for both). We found that 23% of FGM users and 32% of RT-CGM users achieved a time-in-range (TIR) (3.9 to 10 mmol/L) of >70%. For time-below-range (TBR) 4 mmol/L, 70% of RT-CGM users and 58% of FGM users met international recommendations of 4%. Our data add to the growing body of evidence supporting the use of FGM and RT-CGM in T1DM.
    • Identifying Chemical Composition, Safety and Bioactivity of Thai Rice Grass Extract Drink in Cells and Animals

      Phimphilai, Suthaya; email: sphimphi@gmail.com; Koonyosying, Pimpisid; orcid: 0000-0002-6119-7009; email: pimpisid_m@hotmail.com; Hutachok, Nuntouchaporn; orcid: 0000-0003-3856-5309; email: thenuntouch@gmail.com; Kampoun, Tanyaluk; email: tanyalukkk@hotmail.com; Daw, Rufus; orcid: 0000-0003-1258-937X; email: rufus.daw@postgrad.manchester.ac.uk; Chaiyasut, Chaiyavat; email: chaiyavat@gmail.com; Prasartthong-osoth, Vanli; email: sukho.organicrice@gmail.com; Srichairatanakool, Somdet; orcid: 0000-0002-5706-8781; email: somdet.s@cmu.ac.th (MDPI, 2021-11-15)
      Rice grass has been reported to contain bioactive compounds that possess antioxidant and free-radical scavenging activities. We aimed to assess rice grass extract (RGE) drink by determining catechin content, free-radical scavenging and iron-binding properties, as well as toxicity in cells and animals. Young rice grass (Sukhothai-1 strain) was dried, extracted with hot water and lyophilized in a vacuum chamber. The resulting extract was reconstituted with deionized water (260 mg/40 mL) and served as Sukhothai-1 rice grass extract drink (ST1-RGE). HPLC results revealed at least eight phenolic compounds, for which the major catechins were catechin, epicatechin and epigallocatechin-3-gallate (EGCG) (2.71–3.57, 0.98–1.85 and 25.47–27.55 mg/40 mL serving, respectively). Elements (As, Cu, Pb, Sn and Zn) and aflatoxin (B1, B2, G1 and G2) contents did not exceed the relevant limits when compared with WHO guideline values. Importantly, ST1-RGE drink exerted radical-scavenging, iron-chelating and anti-lipid peroxidation properties in aqueous and biological environments in a concentration-dependent manner. The drink was not toxic to cells and animals. Thus, Sukhothai-1 rice grass product is an edible drink that is rich in catechins, particularly EGCG, and exhibited antioxidant, free radical scavenging and iron-binding/chelating properties. The product represents a functional drink that is capable of alleviating conditions of oxidative stress and iron overload.