Publications by authors named "Ian Johnson"

216 Publications

A Comparative Neuro-Histological Assessment of Gluteal Skin Thickness and Cutaneous Nociceptor Distribution in Horses and Humans.

Animals (Basel) 2020 Nov 11;10(11). Epub 2020 Nov 11.

Sydney School of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.

The current project aims to build on knowledge of the nociceptive capability of equine skin to detect superficial acute pain, particularly in comparison to human skin. Post-mortem samples of gluteal skin were taken from men ( = 5) and women ( = 5), thoroughbreds and thoroughbred types (mares, = 11; geldings, = 9). Only sections that contained epidermis and dermis through to the hypodermis were analysed. Epidermal depth, dermal depth and epidermal nerve counts were conducted by a veterinary pathologist. The results revealed no significant difference between the epidermal nerve counts of humans and horses ( = 0.051, = 0.960). There were no significant differences between epidermal thickness of humans (26.8 µm) and horses (31.6 µm) for reference (left side) samples ( = 0.117, = 0.908). The human dermis was significantly thinner than the horse dermis ( = -2.946, = 0.007). Epidermal samples were thicker on the right than on the left, but only significantly so for horses ( = 2.291, = 0.023), not for humans ( = 0.694, = 0.489). The thicker collagenous dermis of horse skin may afford some resilience versus external mechanical trauma, though as this is below the pain-detecting nerve endings, it is not considered protective from external cutaneous pain. The superficial pain-sensitive epidermal layer of horse skin is as richly innervated and is of equivalent thickness as human skin, demonstrating that humans and horses have the equivalent basic anatomic structures to detect cutaneous pain. This finding challenges assumptions about the physical capacity of horses to feel pain particularly in comparison to humans, and presents physical evidence to inform the discussion and debate regarding the ethics of whipping horses.
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http://dx.doi.org/10.3390/ani10112094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696388PMC
November 2020

Implications of Altered Endosome and Lysosome Biology in Space Environments.

Int J Mol Sci 2020 Nov 2;21(21). Epub 2020 Nov 2.

Department of Microgravity and Translational Regenerative Medicine, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, 39106 Magdeburg, Germany.

Space exploration poses multiple challenges for mankind, not only on a technical level but also to the entire physiology of the space traveller. The human system must adapt to several environmental stressors, microgravity being one of them. Lysosomes are ubiquitous to every cell and essential for their homeostasis, playing significant roles in the regulation of autophagy, immunity, and adaptation of the organism to changes in their environment, to name a few. Dysfunction of the lysosomal system leads to age-related diseases, for example bone loss, reduced immune response or cancer. As these conditions have been shown to be accelerated following exposure to microgravity, this review elucidates the lysosomal response to real and simulated microgravity. Microgravity activates the endo-lysosomal system, with resulting impacts on bone loss, muscle atrophy and stem cell differentiation. The investigation of lysosomal adaptation to microgravity can be beneficial in the search for new biomarkers or therapeutic approaches to several disease pathologies on earth as well as the potential to mitigate pathophysiology during spaceflight.
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http://dx.doi.org/10.3390/ijms21218205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663135PMC
November 2020

Enhanced charge storage of nanometric ζ-VO in Mg electrolytes.

Nanoscale 2020 Nov;12(43):22150-22160

Department of Chemistry, University College London, London WC1H 0AJ, UK.

V2O5 is of interest as a Mg intercalation electrode material for Mg batteries, both in its thermodynamically stable layered polymorph (α-V2O5) and in its metastable tunnel structure (ζ-V2O5). However, such oxide cathodes typically display poor Mg insertion/removal kinetics, with large voltage hysteresis. Herein, we report the synthesis and evaluation of nanosized (ca. 100 nm) ζ-V2O5 in Mg-ion cells, which displays significantly enhanced electrochemical kinetics compared to microsized ζ-V2O5. This effect results in a significant boost in stable discharge capacity (130 mA h g-1) compared to bulk ζ-V2O5 (70 mA h g-1), with reduced voltage hysteresis (1.0 V compared to 1.4 V). This study reveals significant advancements in the use of ζ-V2O5 for Mg-based energy storage and yields a better understanding of the kinetic limiting factors for reversible magnesiation reactions into such phases.
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http://dx.doi.org/10.1039/d0nr05060aDOI Listing
November 2020

Diet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiber.

Cancer Prev Res (Phila) 2020 Oct 28. Epub 2020 Oct 28.

Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.

Inflammation drives colorectal cancer development, and colorectal cancer risk is influenced by dietary factors, including dietary fiber. Hyperactive WNT signaling occurs in colorectal cancer and may regulate inflammation. This study investigated (i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DII), and markers of WNT signaling, and (ii) whether DII status modulated the response to supplementation with two types of dietary fiber. Seventy-five healthy participants were supplemented with resistant starch and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected before and after intervention and used to assess WNT pathway gene expression and crypt cell proliferation. E-DII scores were calculated from food frequency questionnaire data. High-sensitivity C-reactive protein (hsCRP) and fecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores [least square means (LSM) 4.7 vs. 2.4 mg/L, = 0.03]. Baseline E-DII score correlated with ( = 0.503, = 0.003) and ( = 0.472, = 0.006) expression, after adjusting for age, gender, body mass index, endoscopy procedure, and smoking status. expression was more than 2-fold greater in individuals with higher E-DII scores (LSM 0.131 vs. 0.059, = 0.002). Baseline E-DII modulated the effects of PD supplementation on expression ( = 0.04). More proinflammatory diets were associated with altered WNT signaling and appeared to modulate the effects of PD supplementation on expression of . This is the first study to investigate relationships between the E-DII and molecular markers of WNT signaling in rectal tissue of healthy individuals. PREVENTION RELEVANCE: Our finding that more inflammatory dietary components may impact large bowel health through effects on a well-recognised pathway involved in cancer development will strengthen the evidence base for dietary advice to help prevent bowel cancer.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0335DOI Listing
October 2020

Diet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiber.

Cancer Prev Res (Phila) 2020 Oct 28. Epub 2020 Oct 28.

Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.

Inflammation drives colorectal cancer development, and colorectal cancer risk is influenced by dietary factors, including dietary fiber. Hyperactive WNT signaling occurs in colorectal cancer and may regulate inflammation. This study investigated (i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DII), and markers of WNT signaling, and (ii) whether DII status modulated the response to supplementation with two types of dietary fiber. Seventy-five healthy participants were supplemented with resistant starch and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected before and after intervention and used to assess WNT pathway gene expression and crypt cell proliferation. E-DII scores were calculated from food frequency questionnaire data. High-sensitivity C-reactive protein (hsCRP) and fecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores [least square means (LSM) 4.7 vs. 2.4 mg/L, = 0.03]. Baseline E-DII score correlated with ( = 0.503, = 0.003) and ( = 0.472, = 0.006) expression, after adjusting for age, gender, body mass index, endoscopy procedure, and smoking status. expression was more than 2-fold greater in individuals with higher E-DII scores (LSM 0.131 vs. 0.059, = 0.002). Baseline E-DII modulated the effects of PD supplementation on expression ( = 0.04). More proinflammatory diets were associated with altered WNT signaling and appeared to modulate the effects of PD supplementation on expression of . This is the first study to investigate relationships between the E-DII and molecular markers of WNT signaling in rectal tissue of healthy individuals. PREVENTION RELEVANCE: Our finding that more inflammatory dietary components may impact large bowel health through effects on a well-recognised pathway involved in cancer development will strengthen the evidence base for dietary advice to help prevent bowel cancer.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0335DOI Listing
October 2020

Probing Mg Intercalation in the Tetragonal Tungsten Bronze Framework VNbO.

Inorg Chem 2020 Jul 7;59(14):9783-9797. Epub 2020 Jul 7.

Department of Chemistry, University College London, 20 Gower Street, London WC1H 0AJ, U.K.

While commercial Li-ion batteries offer the highest energy densities of current rechargeable battery technologies, their energy storage limit has almost been achieved. Therefore, there is considerable interest in Mg batteries, which could offer increased energy densities in comparison to Li-ion batteries if a high-voltage electrode material, such as a transition-metal oxide, can be developed. However, there are currently very few oxide materials which have demonstrated reversible and efficient Mg insertion and extraction at high voltages; this is thought to be due to poor Mg diffusion kinetics within the oxide structural framework. Herein, the authors provide conclusive evidence of electrochemical insertion of Mg into the tetragonal tungsten bronze VNbO, with a maximum reversible electrochemical capacity of 75 mA h g, which corresponds to a magnesiated composition of MgVNbO. Experimental electrochemical magnesiation/demagnesiation revealed a large voltage hysteresis with charge/discharge (1.12 V vs Mg/Mg); when magnesiation is limited to a composition of MgVNbO, this hysteresis can be reduced to only 0.5 V. Hybrid-exchange density functional theory (DFT) calculations suggest that a limited number of Mg sites are accessible via low-energy diffusion pathways, but that larger kinetic barriers need to be overcome to access the entire structure. The reversible Mg intercalation involved concurrent V and Nb redox activity and changes in crystal structure, as confirmed by an array of complementary methods, including powder X-ray diffraction, X-ray absorption spectroscopy, and energy-dispersive X-ray spectroscopy. Consequently, it can be concluded that the tetragonal tungsten bronzes show promise as intercalation electrode materials for Mg batteries.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01013DOI Listing
July 2020

A Sensor Array for the Nanomolar Detection of Azo Dyes in Water.

ACS Sens 2020 06 9;5(6):1541-1547. Epub 2020 Jun 9.

Center for Optoelectronic Materials and Devices, School of Polymer Science and Engineering, The University of Southern Mississippi, 118 College Drive, Hattiesburg, Mississippi 39406, United States.

Azo dyes are ubiquitous pollutants that contaminate water supplies and threaten human, biota, and ecosystem health. Their detection and discrimination are a considerable challenge owing to the numerous structural, chemical, and optical similarities between dyes, complexity of the wastewater in which they are found, and low environmental concentrations. Here, we demonstrate that the inner filter effect (IFE), in combination with conjugated polymer array-based sensing, offers a rapid approach for the quantitative profiling of these pollutants. The array was constructed using three anionic conjugated polyelectrolytes whose varying spectroscopic properties led to distinct IFE patterns in the presence of various dyes. These unique fluorescence response patterns were identified and processed using linear discriminant analysis (LDA), enabling the individual identification of 12 closely related azo dyes. To demonstrate the potential for utility in the environment, the array was used to differentiate between these dyes at nanomolar concentrations in water.
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http://dx.doi.org/10.1021/acssensors.0c00342DOI Listing
June 2020

Forced Disruption of Anatomy Education in Australia and New Zealand: An Acute Response to the Covid-19 Pandemic.

Anat Sci Educ 2020 May 10;13(3):284-300. Epub 2020 May 10.

Centre for Human Anatomy Education, Department of Anatomy and Developmental Biology, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.

Australian and New Zealand universities commenced a new academic year in February/March 2020 largely with "business as usual." The subsequent Covid-19 pandemic imposed unexpected disruptions to anatomical educational practice. Rapid change occurred due to government-imposed physical distancing regulations from March 2020 that increasingly restricted anatomy laboratory teaching practices. Anatomy educators in both these countries were mobilized to adjust their teaching approaches. This study on anatomy education disruption at pandemic onset within Australia and New Zealand adopts a social constructivist lens. The research question was "What are the perceived disruptions and changes made to anatomy education in Australia and New Zealand during the initial period of the Covid-19 pandemic, as reflected on by anatomy educators?." Thematic analysis to elucidate "the what and why" of anatomy education was applied to these reflections. About 18 anatomy academics from ten institutions participated in this exercise. The analysis revealed loss of integrated "hands-on" experiences, and impacts on workload, traditional roles, students, pedagogy, and anatomists' personal educational philosophies. The key opportunities recognized for anatomy education included: enabling synchronous teaching across remote sites, expanding offerings into the remote learning space, and embracing new pedagogies. In managing anatomy education's transition in response to the pandemic, six critical elements were identified: community care, clear communications, clarified expectations, constructive alignment, community of practice, ability to compromise, and adapt and continuity planning. There is no doubt that anatomy education has stepped into a yet unknown future in the island countries of Australia and New Zealand.
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http://dx.doi.org/10.1002/ase.1968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264523PMC
May 2020

Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants.

Br J Nutr 2020 08 13;124(4):374-385. Epub 2020 Apr 13.

Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon TyneNE2 4HH, UK.

There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
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http://dx.doi.org/10.1017/S0007114520001312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369377PMC
August 2020

Increased Resistance of Nitrite-Admixed Concrete to Microbially Induced Corrosion in Real Sewers.

Environ Sci Technol 2020 02 7;54(4):2323-2333. Epub 2020 Feb 7.

Advanced Water Management Centre , The University of Queensland , Brisbane , QLD 4072 , Australia.

Microbially induced concrete corrosion is a major deterioration process in sewers, causing a huge economic burden, and improved mitigating technologies are required. This study reports a novel and promising effective solution to attenuate the corrosion in sewers using calcium nitrite-admixed concrete. This strategy aims to suppress the development and activity of corrosion-inducing microorganisms with the antimicrobial free nitrous acid, which is generated in situ from calcium nitrite that is added to the concrete. Concrete coupons with calcium nitrite as an admixture were exposed in a sewer manhole, together with control coupons that had no nitrite admixture, for 18 months. The corrosion process was monitored by measuring the surface pH, corrosion product composition, concrete corrosion loss, and the microbial community on the corrosion layer. During the exposure, the corrosion loss of the admixed concrete coupons was 30% lower than that of the control coupons. The sulfide uptake rate of the admixed concrete was also 30% lower, leading to a higher surface pH (0.5-0.6 unit), in comparison to that of the control coupons. A negative correlation between the calcium nitrite admixture in concrete and the abundance of sulfide-oxidizing microorganisms was determined by DNA sequencing. The results obtained in this field study demonstrated that this novel use of calcium nitrite as an admixture in concrete is a promising strategy to mitigate the microbially induced corrosion in sewers.
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http://dx.doi.org/10.1021/acs.est.9b06680DOI Listing
February 2020

Slope selection in unstable multilayer growth in 1+1 dimensions: Step flow models with downward funneling.

Phys Rev E 2019 Nov;100(5-1):052802

Institute for Physical Science and Technology, Department of Mathematics, and Center for Scientific Computation and Mathematical Modeling, University of Maryland, College Park, Maryland 20742, USA.

We study analytically and numerically aspects of the dynamics of slope selection for one-dimensional models describing the motion of line defects, steps, in homoepitaxial crystal growth. The kinetic processes include diffusion of adsorbed atoms (adatoms) on terraces, attachment and detachment of atoms at steps with large yet finite, positive Ehrlich-Schwoebel step-edge barriers, material deposition on the surface from above, and the mechanism of downward funneling (DF) via a phenomenological parameter. In this context, we account for the influence of boundary conditions at extremal steps on the dynamics of slope selection. Furthermore, we consider the effect of repulsive, nearest-neighbor force-dipole step-step interactions. For geometries with straight steps, we carry out numerical simulations of step flow, which demonstrate that slope selection eventually occurs. We apply perturbation theory to characterize time-periodic solutions of step flow for slope-selected profiles. By this method, we show how a simplified step flow theory with constant probabilities for the motion of deposited atoms can serve as an effective model of slope selection in the presence of DF. Our analytical findings compare favorably to step simulations.
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http://dx.doi.org/10.1103/PhysRevE.100.052802DOI Listing
November 2019

A Paradigm in Immunochemistry, Revealed by Monoclonal Antibodies to Spatially Distinct Epitopes on Syntenin-1.

Int J Mol Sci 2019 Nov 29;20(23). Epub 2019 Nov 29.

Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, SA 5000, Australia.

Syntenin-1 is an essential multi-functional adaptor protein, which has multiple roles in membrane trafficking and exosome biogenesis, as well as scaffolding interactions with either the actin cytoskeleton or focal adhesions. However, how this functional multiplicity relates to syntenin-1 distribution in different endosome compartments or other intracellular locations and its underlying involvement in cancer pathogenesis have yet to be fully defined. To help facilitate the investigation of syntenin-1 biology, we developed two specific monoclonal antibodies (Synt-2C6 and Synt-3A11) to spatially distinct linear sequence epitopes on syntenin-1, which were each designed to be unique at the six-amino acid level. These antibodies produced very different intracellular staining patterns, with Synt-2C6 detecting endosomes and Synt-3A11 producing a fibrillar staining pattern suggesting a cytoskeletal localisation. Treatment of cells with Nocodazole altered the intracellular localisation of Synt-3A11, which was consistent with the syntenin-1 protein interacting with microtubules. In prostate tissue biopsies, Synt-3A11 defined atrophy and early-stage prostate cancer, whereas Synt-2C6 only showed minimal interaction with atrophic tissue. This highlights a critical need for site-specific antibodies and a knowledge of their reactivity to define differential protein distributions, interactions and functions, which may differ between normal and malignant cells.
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http://dx.doi.org/10.3390/ijms20236035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928784PMC
November 2019

Queensland Digital Health Clinical Charter: a clinical consensus statement on priorities for digital health in hospitals.

Aust Health Rev 2020 Sep;44(5):661-665

Queensland Clinical Senate, Butterfield Street, Herston, Qld 4006, Australia. Email:

Digital transformation of Australian hospitals is occurring rapidly. Although the clinical community has had limited ability to influence high-level decision making and investments into digital health technologies, as these technologies increasingly transform the way patients are cared for, the clinical community must influence the digital health agenda and be an integral part of the decision-making process. This case study details the process and lessons learnt during the development of the state-wide consensus statement detailing the clinical requirements for digital health initiatives to form the Queensland Digital Health Clinical Charter. To the best of our knowledge, Queensland is the first Australian jurisdiction to create a Digital Clinical Charter to be specifically referenced in the investment in and governance of digital health in hospitals. By developing this clinical charter for digital health, and in articulating the needs of clinicians, a clinical framework will be added to both the decision-making process around the investments in digital health and the definition and realisation of the expected benefits from these sizable investments.
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http://dx.doi.org/10.1071/AH19067DOI Listing
September 2020

Full-scale investigation of in-situ iron and alkalinity generation for efficient sulfide control.

Water Res 2019 Dec 5;167:115032. Epub 2019 Sep 5.

The University of Queensland, Advanced Water Management Centre (AWMC), QLD, 4072, Australia.

Hydrogen sulfide induced corrosion of concrete sewer pipes is a major issue for wastewater utilities globally. One of the most commonly used methods to combat hydrogen sulfide is the addition of ferric chloride. While a reliable and effective method, ferric chloride is acidic causing OH&S concerns as well as alkalinity consumption in sewage. This study investigates, under full-scale field conditions, an alternative method for sulfide control by in-situ electrochemical generation of iron ions using sacrificial iron electrodes. This method concomitantly produces alkalinity through cathodic OH generation, rather than consumption. The gaseous hydrogen sulfide concentrations at the discharge wet well of a real-life rising main (length: ∼1 km in, diameter: 150 mm) decreased from 173 ppm to 43 ppm (90 percentile of peak values), when a current of 0.86 A/m of sewage was applied. The 90 percentile peak HS value was further reduced to 6.6 ppm when the applied current was increased to 1.14 A/m sewage. Moreover, methane generation was almost completely inhibited from 25.3 ± 1.46 mg COD/L to 0.06 ± 0.04 mg COD/L. The overall cell voltage remained constant throughout the experimental period clearly showing the stability of the process. Detailed characterization of the down-stream sewer pipe biofilm revealed the complexity of the iron chemistry as the in-situ produced iron ions undergo transformation into a variety of iron species. Overall, this study demonstrates that in-situ generation of iron and alkalinity is an effective alternative method for hydrogen sulfide control in sewers.
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http://dx.doi.org/10.1016/j.watres.2019.115032DOI Listing
December 2019

Retiring the Flip Phones: Exploring Social Media Use for Managing Public Health Incidents.

Disaster Med Public Health Prep 2019 12;13(5-6):859-867

Public Health Ontario, Toronto, ON, Canada.

Objective: Communication is essential during public health emergencies and incidents. This research aimed to understand current uses and challenges for public health agencies using social media during these incidents.

Methods: An exploratory, qualitative study was conducted using the structured interview matrix facilitation technique. Focus groups were held with professionals from local public health agencies across Ontario, Canada. Representation from different geographic regions was sought to capture differences in participant experience. An inductive approach to content analysis was used to identify emergent themes.

Results: A diverse group of public health professionals (n = 36) participated. Six themes were identified. Social media is identified as a communication tool used to expand reach of messages, to engage in dialogue with the public, and to inform the scope of potential incidents. Barriers to its use include hesitancy to adapt, lack of trust and credibility, and organizational structure and capacity constraints. Key strategies proposed to promote social media use and address barriers resulted from participant discussions and are presented.

Conclusion: Social media use is highly variable across public health agencies in Ontario. This study identifies and provides strategies to address barriers and practice gaps related to public health agencies' use of social media during emergencies.
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http://dx.doi.org/10.1017/dmp.2018.147DOI Listing
December 2019

An Interscholastic Network To Generate LexA Enhancer Trap Lines in .

G3 (Bethesda) 2019 07 9;9(7):2097-2106. Epub 2019 Jul 9.

Dept. of Developmental Biology, Stanford University School of Medicine, Stanford CA 94305

Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology, and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the index line. This includes 76 insertions into novel, distinct gene loci not previously associated with enhancer traps or targeted LexA constructs. Additionally, our studies revealed evidence for selective transposase-dependent replacement of a previously-undetected element on chromosome III within the StanEx genetic background during hybrid dysgenesis, suggesting a molecular basis for the over-representation of LexA insertions at the locus in our screen. Production and characterization of novel fly lines were performed by students and teachers in experiment-based genetics classes within a geographically diverse network of public and independent high schools. Thus, unique partnerships between secondary schools and university-based programs have produced and characterized novel genetic and molecular resources in for open-source distribution, and provide paradigms for development of science education through experience-based pedagogy.
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http://dx.doi.org/10.1534/g3.119.400105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643891PMC
July 2019

"Seeing is Believing." Enhancing student engagement with dynamic protein-model visualization.

Biochem Mol Biol Educ 2019 05 28;47(3):247-248. Epub 2019 Mar 28.

Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, Adelaide, South Australia, 5000, Australia.

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http://dx.doi.org/10.1002/bmb.21238DOI Listing
May 2019

QT Assessment in Early Drug Development: The Long and the Short of It.

Int J Mol Sci 2019 Mar 15;20(6). Epub 2019 Mar 15.

Cardiac Safety Services, Celerion, 2420 W Baseline Rd, Tempe, AZ 85283, USA.

The QT interval occupies a pivotal role in drug development as a surface biomarker of ventricular repolarization. The electrophysiologic substrate for QT prolongation coupled with reports of non-cardiac drugs producing lethal arrhythmias captured worldwide attention from government regulators eventuating in a series of guidance documents that require virtually all new chemical compounds to undergo rigorous preclinical and clinical testing to profile their QT liability. While prolongation or shortening of the QT interval may herald the appearance of serious cardiac arrhythmias, the positive predictive value of an abnormal QT measurement for these arrhythmias is modest, especially in the absence of confounding clinical features or a congenital predisposition that increases the risk of syncope and sudden death. Consequently, there has been a paradigm shift to assess a compound's cardiac risk of arrhythmias centered on a mechanistic approach to arrhythmogenesis rather than focusing solely on the QT interval. This entails both robust preclinical and clinical assays along with the emergence of concentration QT modeling as a primary analysis tool to determine whether delayed ventricular repolarization is present. The purpose of this review is to provide a comprehensive understanding of the QT interval and highlight its central role in early drug development.
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http://dx.doi.org/10.3390/ijms20061324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471571PMC
March 2019

Degradation behaviors and cytocompatibility of Mg/β-tricalcium phosphate composites produced by spark plasma sintering.

J Biomed Mater Res B Appl Biomater 2019 10 1;107(7):2238-2253. Epub 2019 Feb 1.

Department of Bioengineering, University of California at Riverside, Riverside, California 92521.

Magnesium (Mg)-based materials have shown great potentials for bioresorbable implant applications. Previous studies showed that Mg with 10 and 20 vol % β-tricalcium phosphate (β-TCP) composites produced by spark plasma sintering, improved mechanical properties when compared with pure Mg. The objectives of this study were to evaluate the degradation behaviors of Mg/10% β-TCP and Mg/20% β-TCP composites in revised stimulated body fluid (rSBF), and to determine their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs) using the direct culture method. During the 11 days of immersion in rSBF, Mg/β-TCP composites showed different degradation behaviors at different immersion periods, that is, the initial stage (0-1 hr), the mid-term stage (1 hr to 2 days), and the long-term stage (2-11 days). The counter effects of mass loss due to microgalvanic corrosion and mass gain due to deposition of Ca-P containing layers resulted in slower Mg ion release for Mg/20% β-TCP than Mg/10% β-TCP in the mid-term, but eventually 16% mass loss for Mg/20% β-TCP and 10% mass loss for Mg/10% β-TCP after 11 days of immersion. The in vitro studies with BMSCs showed the highest cell adhesion density (i.e., 68% of seeding density) on the plate surrounding the Mg/10% β-TCP sample, that is, under the indirect contact condition of direct culture. The β-TCP showed a positive effect on direct adhesion of BMSCs on the surface of Mg/β-TCP composites. This study elucidated the degradation behaviors and the cytocompatibility of Mg/β-TCP composites in vitro; and, further studies on Mg/ceramic composites are needed to determine their potential for clinical applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2238-2253, 2019.
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http://dx.doi.org/10.1002/jbm.b.34316DOI Listing
October 2019

Tailoring the electrochemical activity of magnesium chromium oxide towards Mg batteries through control of size and crystal structure.

Nanoscale 2019 Jan;11(2):639-646

Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.

Chromium oxides with the spinel structure have been predicted to be promising high voltage cathode materials in magnesium batteries. Perennial challenges involving the mobility of Mg2+ and reaction kinetics can be circumvented by nano-sizing the materials in order to reduce diffusion distances, and by using elevated temperatures to overcome activation energy barriers. Herein, ordered 7 nm crystals of spinel-type MgCr2O4 were synthesized by a conventional batch hydrothermal method. In comparison, the relatively underexplored Continuous Hydrothermal Flow Synthesis (CHFS) method was used to make highly defective sub-5 nm MgCr2O4 crystals. When these materials were made into electrodes, they were shown to possess markedly different electrochemical behavior in a Mg2+ ionic liquid electrolyte, at moderate temperature (110 °C). The anodic activity of the ordered nanocrystals was attributed to surface reactions, most likely involving the electrolyte. In contrast, evidence was gathered regarding the reversible bulk deintercalation of Mg2+ from the nanocrystals made by CHFS. This work highlights the impact on electrochemical behavior of a precise control of size and crystal structure of MgCr2O4. It advances the understanding and design of new cathode materials for Mg-based batteries.
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http://dx.doi.org/10.1039/c8nr08347aDOI Listing
January 2019

Lipid profiles of prostate cancer cells.

Oncotarget 2018 Oct 30;9(85):35541-35552. Epub 2018 Oct 30.

Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia.

Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three approaches identified significant difference in the lipid profiles of the three prostate cancer cell lines (DU145, LNCaP and 22RV1) and one non-malignant cell line (PNT1a). Specific lipid classes and species, such as phospholipids (e.g., phosphatidylethanolamine 18:1/16:0 and 18:1/18:1) and cholesteryl esters, detected by LC-ESI-MS/MS, allowed statistical separation of all four prostate cell lines. Lipid mapping by FTIR revealed that variations in these lipid classes could also be detected at a single cell level, however further investigation into this approach would be needed to generate large enough data sets for quantitation. Visualisation by fluorescence microscopy showed striking variations that could be observed in lipid staining patterns between cell lines allowing visual separation of cell lines. In particular, polar lipid staining by a fluorescent marker was observed to increase significantly in prostate cancer lines cells, when compared to PNT1a cells, which was consistent with lipid quantitation by LC-ESI-MS/MS and FTIR spectroscopy. Thus, multiple technologies can be employed to either quantify or visualise changes in lipid composition, and moreover specific lipid profiles could be used to detect and phenotype prostate cancer cells.
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http://dx.doi.org/10.18632/oncotarget.26222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238979PMC
October 2018

NOX2 oxidase expressed in endosomes promotes cell proliferation and prostate tumour development.

Oncotarget 2018 Oct 23;9(83):35378-35393. Epub 2018 Oct 23.

Infection and Immunity Program, Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Melbourne, Victoria 3800, Australia.

Reactive oxygen species (ROS) promote growth factor signalling including for VEGF-A and have potent angiogenic and tumourigenic properties. However, the precise enzymatic source of ROS generation, the subcellular localization of ROS production and cellular targets that influence tumour-promoting processes, are largely undefined. Here, using mRNA microarrays, we show increased gene expression for NOX2, the catalytic subunit of the ROS-generating NADPH oxidase enzyme, in human primary prostate cancer compared to non-malignant tissue. In addition, NOX4 gene expression was markedly elevated in human metastatic prostate cancers, but not in primary prostate tumours. Using a syngeneic, orthotopic mouse model of prostate cancer the genetic deletion of NOX2 (i.e. NOX2 mouse) resulted in reduced angiogenesis and an almost complete failure in tumour development. Furthermore, pharmacological inhibition of NOX2 oxidase suppressed established prostate tumours in mice. In isolated endothelial cells, and in human normal and prostate cancer cells, NOX2 co-located to varying degrees with early endosome markers including EEA1, Appl1 and Rab5A and the late endosome marker Rab7A, and this correlated with significant VEGF-A-dependent ROS production within acidified endosomal compartments and endothelial cell proliferation that was NOX2 oxidase- and hydrogen peroxide dependent. We concluded that NOX2 oxidase expression and endosomal ROS production were important for prostate cancer growth and that this was required to positively regulate the VEGF pathway. The research provides a paradigm for limiting tumour growth through a better understanding of NOX2 oxidase's effect on VEGF signalling and how controlling the development of tumour vasculature can limit prostate tumour development and metastasis.
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http://dx.doi.org/10.18632/oncotarget.26237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226044PMC
October 2018

The use of bone conduction hearing implants in paediatric chronic otitis media: An audit of outcomes of 32 devices in 22 patients.

Clin Otolaryngol 2019 01 23;44(1):83-86. Epub 2018 Oct 23.

Department of ENT, Newcastle upon Tyne, UK.

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http://dx.doi.org/10.1111/coa.13235DOI Listing
January 2019

Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and WNT-pathway-related markers of bowel cancer risk.

Br J Nutr 2019 09 26;122(5):509-517. Epub 2018 Sep 26.

Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon TyneNE2 4HH, UK.

Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman's rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3β), catenin β1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.
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http://dx.doi.org/10.1017/S0007114518002520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330067PMC
September 2019

User-Driven Comments on a Facebook Advertisement Recruiting Canadian Parents in a Study on Immunization: Content Analysis.

JMIR Public Health Surveill 2018 Sep 20;4(3):e10090. Epub 2018 Sep 20.

Toronto Public Health, Toronto, ON, Canada.

Background: More people are searching for immunization information online and potentially being exposed to misinformation and antivaccination sentiment in content and discussions on social media platforms. As vaccination coverage rates remain suboptimal in several developed countries, and outbreaks of vaccine-preventable diseases become more prevalent, it is important that we build on previous research by analyzing themes in online vaccination discussions, including those that individuals may see without actively searching for information on immunization.

Objective: The study aimed to explore the sentiments and themes behind an unsolicited debate on immunization in order to better inform public health interventions countering antivaccination sentiment.

Methods: We analyzed and quantified 117 user-driven open-ended comments on immunization posted in the Comments section of a Facebook advertisement that targeted Canadian parents for recruitment into a larger study on immunization. Then, 2 raters coded all comments using content analysis.

Results: Of 117 comments, 85 were posted by unique commentators, with most being female (65/85, 77%). The largest proportion of the immunization comments were positive (51/117, 43.6%), followed by negative (41/117, 35.0%), ambiguous (20/117, 17.1%), and hesitant (5/117, 4.3%). Inaccurate knowledge (27/130, 20.8%) and misperceptions of risk (23/130, 17.7%) were most prevalent in the 130 nonpositive comments. Other claims included distrust of pharmaceutical companies or government agencies (18/130, 13.8%), distrust of the health care system or providers (15/130, 11.5%), past negative experiences with vaccination or beliefs (10/130, 7.7%), and attitudes about health and prevention (10/130, 7.7%). Almost 40% (29/74, 39%) of the positive comments communicated the risks of not vaccinating, followed by judgments on the knowledge level of nonvaccinators (13/74, 18%). A total of 10 positive comments (10/74, 14%) specifically refuted the link between autism and vaccination.

Conclusions: The presence of more than 100 unsolicited user-driven comments on a platform not intended for discussion, nor providing any information on immunization, illustrates the strong sentiments associated with immunization and the arbitrariness of the online platforms used for immunization debates. Health authorities should be more proactive in finding mechanisms to refute misinformation and misperceptions that are propagating uncontested online. Online debates and communications on immunization need to be identified by continuous monitoring in order for health authorities to understand the current themes and trends, and to engage in the discussion.
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http://dx.doi.org/10.2196/10090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231725PMC
September 2018

Technology's Cutting Edge: Futurism and Research in the Red Army, 1917-1937.

Authors:
Ian Johnson

Technol Cult 2018 ;59(3):689-718

Seeking to defend the new Soviet Union with a devastated economic base and a vast technical gap with the West, Soviet military planners sought in new technology and the language of science the possibility of self-defense. Within that context, a group of young officers emerged as military futurists. Specifically, they theorized that technology was the decisive factor in war, and that technology had changed so fundamentally after 1918 that the operational lessons of the First World War were limited in usefulness. As a result of their leadership, the Red Army invested tremendous sums in new and exotic military technologies. This paper explores the military futurists' unique understanding of technology through an examination of two of the technological systems that they patronized: robotic tanks and a particle beam designed by Nikola Tesla.
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http://dx.doi.org/10.1353/tech.2018.0063DOI Listing
October 2018

Comparing Twitter data to routine data sources in public health surveillance for the 2015 Pan/Parapan American Games: an ecological study.

Can J Public Health 2018 06 20;109(3):419-426. Epub 2018 Apr 20.

Public Health Ontario, 480 University Avenue, Suite 300, Toronto, Ontario, M5G 1V2, Canada.

Objectives: This study examined Twitter for public health surveillance during a mass gathering in Canada with two objectives: to explore the feasibility of acquiring, categorizing and using geolocated Twitter data and to compare Twitter data against other data sources used for Pan Parapan American Games (P/PAG) surveillance.

Methods: Syndrome definitions were created using keyword categorization to extract posts from Twitter. Categories were developed iteratively for four relevant syndromes: respiratory, gastrointestinal, heat-related illness, and influenza-like illness (ILI). All data sources corresponded to the location of Toronto, Canada. Twitter data were acquired from a publicly available stream representing a 1% random sample of tweets from June 26 to September 10, 2015. Cross-correlation analyses of time series data were conducted between Twitter and comparator surveillance data sources: emergency department visits, telephone helpline calls, laboratory testing positivity rate, reportable disease data, and temperature.

Results: The frequency of daily tweets that were classified into syndromes was low, with the highest mean number of daily tweets being for ILI and respiratory syndromes (22.0 and 21.6, respectively) and the lowest, for the heat syndrome (4.1). Cross-correlation analyses of Twitter data demonstrated significant correlations for heat syndrome with two data sources: telephone helpline calls (r = 0.4) and temperature data (r = 0.5).

Conclusion: Using simple syndromes based on keyword classification of geolocated tweets, we found a correlation between tweets and two routine data sources for heat alerts, the only public health event detected during P/PAG. Further research is needed to understand the role for Twitter in surveillance.
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http://dx.doi.org/10.17269/s41997-018-0059-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964588PMC
June 2018

Mitochondrial imaging in live or fixed tissues using a luminescent iridium complex.

Sci Rep 2018 05 29;8(1):8191. Epub 2018 May 29.

Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, 5001, Australia.

Mitochondrial morphology is important for the function of this critical organelle and, accordingly, altered mitochondrial structure is exhibited in many pathologies. Imaging of mitochondria can therefore provide important information about disease presence and progression. However, mitochondrial imaging is currently limited by the availability of agents that have the capacity to image mitochondrial morphology in both live and fixed samples. This can be particularly problematic in clinical studies or large, multi-centre cohort studies, where tissue archiving by fixation is often more practical. We previously reported the synthesis of an iridium coordination complex [Ir(ppy)(MeTzPyPhCN)]; where ppy is a cyclometalated 2-phenylpyridine and TzPyPhCN is the 5-(5-(4-cyanophen-1-yl)pyrid-2-yl)tetrazolate ligand; and showed that this complex (herein referred to as IraZolve-Mito) has a high specificity for mitochondria in live cells. Here we demonstrate that IraZolve-Mito can also effectively stain mitochondria in both live and fixed tissue samples. The staining protocol proposed is versatile, providing a universal procedure for cell biologists and pathologists to visualise mitochondria.
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http://dx.doi.org/10.1038/s41598-018-24672-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974328PMC
May 2018

Neuroprotective effect of acute prior inflammation with lipopolysaccharide for adult male rat facial motoneurones.

Brain Res 2018 10 26;1696:56-62. Epub 2018 May 26.

Department of Biomedical Sciences, Macquarie University, NSW 2113, Australia.

Increases in inflammatory cytokines are reported to have both neuroprotective and neurotoxic effects depending on the type and age of neurones studied. This study aimed to determine the effect of experimental inflammation induced by Lipopolysaccharide (LPS) on the survival of injured male adult rat facial motoneurones. Time- and dose-response studies were done to optimise the LPS administration time and dose, to best correlate with inflammatory levels previously reported for aged rats. 12 cytokines were assayed through multiplex analysis. 24 h after intraperitoneal injection of 0.5 mg/kg Lipopolysaccharide in rats, IL-1β, IL-5 and IL-12p70 levels were elevated, with no observed LPS-associated sickness behaviour. In other groups of 5-6 adult rats, the facial nerve was either crushed (as mild injury) or avulsed (as severe injury) after the LPS priming injection. Stereology revealed that most motoneurones survived 28 days after nerve crush only and LPS- or saline-priming preceding nerve crush. Most motoneurones died following nerve avulsion only, whereas over half survived when LPS-priming preceded nerve avulsion. We suggest that elevated levels of experimental inflammation are neuroprotective for severely injured adult male rat facial motoneurones.
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http://dx.doi.org/10.1016/j.brainres.2018.05.039DOI Listing
October 2018

Thermodynamics and defect chemistry of substitutional and interstitial cation doping in layered α-VO.

Phys Chem Chem Phys 2018 Jun;20(22):15002-15006

Department of Chemistry, Christopher Ingold Building, University College London, 20 Gordon Street, London WC1H 0AJ, UK.

A systematic study of the location and energetics of cation dopants in α-V2O5 has been conducted using pair-potential methods, supplemented by first-principles calculations. The consequences of doping on intrinsic defect equilibria have been discussed and the effects of selected dopants on Li+ and Mg2+ diffusion energy barriers have been investigated.
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http://dx.doi.org/10.1039/c8cp02187bDOI Listing
June 2018