Superheated storms: climate drivers, health effects and responses.

Nil.

Can a Greenhouse Gas Emissions Tax on Food also Be Healthy and Equitable? A Systemised Review and Modelling Study from Aotearoa New Zealand.

Policies to mitigate climate change are essential. The objective of this paper was to estimate the impact of greenhouse gas (GHG) food taxes and assess whether such a tax could also have health benefits in Aotearoa NZ. We undertook a systemised review on GHG food taxes to inform four tax scenarios, including one combined with a subsidy. These scenarios were modelled to estimate lifetime impacts on quality-adjusted health years (QALY), health inequities by ethnicity, GHG emissions, health system costs and food costs to the individual. Twenty-eight modelling studies on food tax policies were identified. Taxes resulted in decreased consumption of the targeted foods (e.g., -15.4% in beef/ruminant consumption, N = 12 studies) and an average decrease of 8.3% in GHG emissions (N = 19 studies). The "GHG weighted tax on all foods" scenario had the largest health gains and costs savings (455,800 QALYs and NZD 8.8 billion), followed by the tax-fruit and vegetable subsidy scenario (410,400 QALYs and NZD 6.4 billion). All scenarios were associated with reduced GHG emissions and higher age standardised per capita QALYs for Maori. Applying taxes that target foods with high GHG emissions has the potential to be effective for reducing GHG emissions and to result in co-benefits for population health.

Lifetime based axial contrast enable simple 3D-STED imaging.

Stimulated Emission Depletion (STED) microscopy increase spatial image resolution by laterally sharpening the illumination profile of the confocal microscope. However, it remains compromised in axial resolution. To improve axial STED resolution, constructive interference of the STED depletion beam must be formed surrounding the focal plane to turn off the fluorophores beyond the focal plane. For isotropic 3D-STED resolution, this axial STED interference pattern must be overlayed with the doughnut STED beam at nanometer accuracy. Such optical configurations can be challenging in alignment. In this current work, we introduced a straightforward lifetime based axial contrast in STED microscope by imaging the samples on an ITO coated glass coverslip. The STED laser generates surface plasmon resonance on the ITO surface that enhanced the metal induced energy transfer MIET effect on the ITO surface. The enhanced MIET effect established a lifetime gradient with ∼20% dynamic range that extend for mor than 400 nm from the ITO surface. The axial contrast based on the lifetime gradient was directly used for 3D-STED imaging of tubulin fibers inside COS-7 cells, where the vertical displacement of single tubulin fiber was revealed. Lifetime gating could be applied to further improve lateral spatial resolution. Considering that most common implementation of STED microscopes uses pulsed lasers and timing electronics, there is no optical modification of the microscope is required in the current 3D-STED approach.

Rapid FLIM Measurement of Membrane Tension Probe Flipper-TR.

In the following protocol, we describe the application of rapid fluorescence lifetime imaging to the measurement of membrane tension. The recent developments in tension sensing probes have resulted in probes which allow for quantification of membrane tension through measurement of fluorescence lifetime change with increasing or decreasing tension. In this protocol, we describe the acquisition and analysis steps required for these types of experiments and demonstrate how the fluorescence lifetime reports on change in membrane tension as a result of osmotic shock in live HeLa cells.

Local-Indigenous Autonomy and Community Streetscape Enhancement: Learnings from Maori and Te Ara Mua-Future Streets Project.

In settler countries, attention is now extending to the wellbeing benefits of recognising and promoting the Indigenous cultural identity of neighbourhoods as a contributing factor to more equitable and healthier communities. Re-indigenisation efforts to (re)implement cultural factors into urban design can be challenging and ineffective without the leadership and collaboration of local-Indigenous peoples. Undertaken in Aotearoa New Zealand, Te Ara Mua - Future Street project, demonstrated that co-design has critical potential in the reclamation of Indigenous autonomy, increased local-Indigenous presence and revitalisation of cultural identity. Employing a Kaupapa Maori (Maori-centred) research approach, we focused on the workings and perspectives of mana whenua (local-Indigenous peoples) and community stakeholder engagement in Te Ara Mua. An Indigenous theoretical framework, Te Pae Mahutonga, was utilised in the data analysis to explore perspectives of Indigenous collective agency, empowerment, and wellbeing. Our research demonstrates that developing capacity amongst Indigenous communities is integral for effective engagement and that the realisation of autonomy in urban design projects has broader implications for Indigenous sovereignty, spatial justice and health equity. Significantly, we argue that future community enhancement strategies must include not only re-designing and re-imagining initiatives, but also re-indigenising.

Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma.

Advanced stage neuroblastoma is an aggressive disease with limited treatment options for patients with drug-resistant tumors. Targeted delivery of chemotherapy for pediatric cancers offers promise to improve treatment efficacy and reduce toxicity associated with systemic chemotherapy. The EnGeneIC Dream Vector (EDVTM) is a nanocell, which can package chemotherapeutic drugs and target tumors via attachment of bispecific proteins to the surface of the nanocell. Phase I trials in adults with refractory tumors have shown an acceptable safety profile. Herein we investigated the activity of EGFR-targeted and doxorubicin-loaded EDVTM (EGFREDVTMDox) for the treatment of neuroblastoma. Two independent neuroblastoma cell lines with variable expression of EGFR protein [SK-N-BE(2), high; SH-SY-5Y, low] were used. EGFREDVTMDox induced apoptosis in these cells compared to control, doxorubicin, or non-doxorubicin loaded EGFREDVTM In three-dimensional tumor spheroids, imaging and fluorescence life-time microscopy revealed that EGFREDVTMDox had a marked enhancement of doxorubicin penetration compared to doxorubicin alone, and improved penetration compared to non-EGFR-targeted EDVTMDox, with enhanced spheroid penetration leading to increased apoptosis. In two independent orthotopic human neuroblastoma xenograft models, short-term studies (28 days) of tumor-bearing mice led to a significant decrease in tumor size in EGFREDVTMDox-treated animals compared to control, doxorubicin, or non-EGFR EDVTMDox There was increased TUNEL staining of tumors at day 28 compared to control, doxorubicin, or non-EGFR EDVTMDox Moreover, overall survival was increased in neuroblastoma mice treated with EGFREDVTMDox (P < 0007) compared to control. Drug-loaded bispecific-antibody targeted EDVsTM offer a highly promising approach for the treatment of aggressive pediatric malignancies such as neuroblastoma. Mol Cancer Ther; 17(5); 1012-23. ©2018 AACR.

Evidence on the longitudinal construct validity of major generic and utility measures of health-related quality of life in teens with depression.

PURPOSE: To examine the longitudinal construct validity in the assessment of changes in depressive symptoms of widely used utility and generic HRQL instruments in teens. METHODS: 392 teens enrolled in the study and completed HRQL and diagnostic measures as part of the baseline interview. HRQL measures included EuroQol (EQ-5D-3L), Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3), Quality of Well-Being Scale (QWB), Pediatric Quality of Life Inventory (PEDS-QL), RAND-36 (SF-6D), and Quality of Life in Depression Scale (QLDS). Youth completed follow-up interviews 12 weeks after baseline. Sixteen youth (4.1%) were lost to follow-up. We examined correlations between changes in HRQL instruments and the Children's Depression Rating Scale-Revised (CDRS-R) and assessed clinically meaningful change in multi-attribute utility HRQL measures using mean change (MC) and standardized response mean (SRM) among youth showing at least moderate (20%) improvement in depression symptomology. RESULTS: Spearman's correlation coefficients demonstrated moderate correlation between changes in CDRS-R and the HUI2 (r = 0.38), HUI3 (r = 0.42), EQ-5D-3L (r = 0.36), SF-6D (r = 0.39), and PEDS-QL (r = 0.39) and strong correlation between changes in CDRS-R and QWB (r = 0.52) and QLDS (r = - 0.71). Effect size results are also reported. Among multi-attribute utility measures, all showed clinically meaningful improvements in the sample of youth with depression improvement (HUI2, MC = 0.20, SRM = 0.97; HUI3, MC = 0.32, SRM = 1.17; EQ-5D-3L, MC = 0.08, SRM = 0.51; QWB, MC = 0.11, SRM = 0.86; and SF-6D, MC = 0.12, SRM = 1.02). CONCLUSIONS: Findings support the longitudinal construct validity of included HRQL instruments for the assessment of change in depression outcomes in teens. Results of this study can help inform researchers about viable instruments to include in economic evaluations for this population.

The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons.

In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.

Measuring Health-related Quality of Life in Teens With and Without Depression.

PURPOSE: To provide empirical evidence on the performance of common measures in assessing health-related quality of life (HRQL) in depressed and nondepressed youth. These measures can be used in research trials, cost-effectiveness studies, and to help develop policy for treating youth depression. BACKGROUND: Depression is one of the most common mental disorders among adolescents, with a chronic, episodic course marked by considerable impairment. Data on HRQL for teens with depression could more fully demonstrate the burden of depression and help to evaluate the comparative effectiveness of teen depression services, which in turn can be used to inform public and clinical policies. METHODS: We collected data on depression and HRQL from 392 depressed and nondepressed teens aged 13-17. RESULTS: Generic mental health, disease-specific, and generic preference-based measures of HRQL all do a reasonable job of distinguishing teens with and without depression and between teens with differing levels of depression. Generic mental health and disease-specific measures provide valuable information on burden of disease and perform well. For the purpose of economic evaluation, the HUI-3 and EQ-5D perform somewhat better than other preference-based measures. These results can aid future research on teens with depression by helping to guide which HRQL instruments are most useful in this population and can help to quantify the burden of depression in teens for policy and clinical planning.

PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells.

Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to a receptive growth factor might result in the expansion of a plastic and proliferative population of cells. To this end, we treated lineage-committed cells with AZA and screened a number of different growth factors with known activity in mesenchyme-derived tissues. Here, we report that transient treatment with AZA in combination with platelet-derived growth factor-AB converts primary somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells possess a distinct transcriptome, are immunosuppressive, and demonstrate long-term self-renewal, serial clonogenicity, and multigerm layer differentiation potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner and, unlike embryonic or pluripotent stem cells, do not form teratomas. Taken together, this vector-free method of generating iMS cells from primary terminally differentiated cells has significant scope for application in tissue regeneration.

Heterologously-expressed and Liposome-reconstituted Human Transient Receptor Potential Melastatin 4 Channel (TRPM4) is a Functional Tetramer.

Mutation, irregular expression and sustained activation of the Transient Receptor Potential Channel, type Melastatin 4 (TRPM4), have been linked to various cardiovascular diseases. However, much remains unknown about the structure of this important ion channel. Here, we have purified a heterologously expressed TRPM4-eGFP fusion protein and investigated the oligomeric state of TRPM4-eGFP in detergent micelles using crosslinking, native gel electrophoresis, multi-angle laser light scattering and electron microscopy. Our data indicate that TRPM4 is tetrameric, like other TRP channels studied to date. Furthermore, the functionality of liposome reconstituted TRPM4-eGFP was examined using electrophysiology. Single-channel recordings from TRPM4-eGFP proteoliposomes showed inhibition of the channel using Flufenamic acid, a well-established inhibitor of TRPM4, suggesting that the channels are functional upon reconstitution. Our characterisation of the oligomeric structure of TRPM4 and the ability to reconstitute functional channels in liposomes should facilitate future studies into the structure, function and pharmacology of this therapeutically relevant channel.

Trends in local newspaper reporting of London cyclist fatalities 1992-2012: the role of the media in shaping the systems dynamics of cycling.

BACKGROUND: Successfully increasing cycling across a broad range of the population would confer important health benefits, but many potential cyclists are deterred by fears about traffic danger. Media coverage of road traffic crashes may reinforce this perception. As part of a wider effort to model the system dynamics of urban cycling, in this paper we examined how media coverage of cyclist fatalities in London changed across a period when the prevalence of cycling doubled. We compared this with changes in the coverage of motorcyclist fatalities as a control group. METHODS: Police records of traffic crashes (STATS19) were used to identify all cyclist and motorcyclist fatalities in London between 1992 and 2012. We searched electronic archives of London's largest local newspaper to identify relevant articles (January 1992-April 2014), and sought to identify which police-reported fatalities received any media coverage. We repeated this in three smaller English cities. RESULTS: Across the period when cycling trips doubled in London, the proportion of fatalities covered in the local media increased from 6% in 1992-1994 to 75% in 2010-2012. By contrast, the coverage of motorcyclist fatalities remained low (4% in 1992-1994 versus 5% in 2010-2012; p=0.007 for interaction between mode and time period). Comparisons with other English cities suggested that the changes observed in London might not occur in smaller cities with lower absolute numbers of crashes, as in these settings fatalities are almost always covered regardless of mode share (79-100% coverage for both cyclist and motorcyclist fatalities). CONCLUSION: In large cities, an increase in the popularity (and therefore 'newsworthiness') of cycling may increase the propensity of the media to cover cyclist fatalities. This has the potential to give the public the impression that cycling has become more dangerous, and thereby initiate a negative feedback loop that dampens down further increases in cycling. Understanding these complex roles of the media in shaping cycling trends may help identify effective policy levers to achieve sustained growth in cycling.

Health, fairness and New Zealand's contribution to global post-2020 climate change action.

Health and wellbeing have been largely ignored in discussions around climate change targets and action to date. The current public consultation around New Zealand's post-2020 climate target is an opportunity for health professionals to highlight the health implications of climate change. Without urgent global efforts to bring down global GHG (greenhouse gas) emissions, the world is heading towards high levels of global warming, which will have devastating impacts on human health and wellbeing. New Zealand's action to bring down GHG emissions (as part of the global effort) has potential to improve health and reduce costs on the health sector, if health and fairness are put at the centre of policies to address climate change. New Zealand should commit to at least 40 % reductions in GHG emissions by 2030, and zero carbon emissions before 2050, with healthy and fair policies across sectors to enable reaching these targets.

Fluorescence recovery after photobleaching (FRAP): acquisition, analysis, and applications.

A significant number of biological processes occur at, or involve cellular membranes, including; cell adhesion, migration, endocytosis, signal transduction, and many biochemical reactions involving membrane anchored scaffolds. Each process involves a complex arrangement of interacting molecules whose location in space and time influence the outcome of the event. In this protocol we discuss the application of fluorescence recovery after photobleaching (FRAP) to study the dynamics of membrane associated molecules. We discuss the principles, acquisition and the analysis of FRAP data and address issues surrounding its interpretation.