Potentiation of Synaptic GluN2B NMDAR Currents by Fyn Kinase Is Gated through BDNF-Mediated Disinhibition in Spinal Pain Processing

In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropa

Modeling infection risk and energy use of upper-room Ultraviolet Germicidal Irradiation systems in multi-room environments

The effectiveness of ultraviolet irradiation at inactivating airborne pathogens is well proven, and the technology is also commonly promoted as an energy-efficient way of reducing infection risk in comparison to increasing ventilation. However, determining how and where to apply upper-room Ultraviolet Germicidal Irradiation devices for the greatest benefit is still poorly understood. This article links multi-zone infection risk models with energy calculations to assess the potential impact of a Ultraviolet Germicidal Irradiation installation across a series of inter-connected spaces, such as a hospital ward. A first-order decay model of ultraviolet inactivation is coupled with a room air model to simulate patient room and whole-ward level disinfection under different mixing and ultraviolet field conditions. Steady-state computation of quanta-concentrations is applied to the Wells–Riley equation to predict likely infection rates. Simulation of a hypothetical ward demonstrates the relative influence of different design factors for susceptible patients co-located with an infectious source or in nearby rooms. In each case, energy requirements are calculated and compared to achieving the same level of infection risk through improved ventilation. Ultraviolet devices are seen to be most effective where they are located close to the infectious source; however, when the location of the infectious source is not known, locating devices in patient rooms is likely to be more effective than installing them in connecting corridor or communal zones. Results show an ultraviolet system may be an energy-efficient solution to controlling airborne infection, particularly in semi-open hospital environments, and considering the whole ward rather than just a single room at the design stage is likely to lead to a more robust solution

The 2022 report of the MJA-Lancet Countdown on health and climate change: Australia unprepared and paying the price

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017 and produced its first national assessment in 2018 and annual updates in 2019, 2020 and 2021. It examines five broad domains: climate change impacts, exposures and vulnerability; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In this, the fifth year of the MJA-Lancet Countdown, we track progress on an extensive suite of indicators across these five domains, accessing and presenting the latest data and further refining and developing our analyses. Within just two years, Australia has experienced two unprecedented national catastrophes - the 2019-2020 summer heatwaves and bushfires and the 2021-2022 torrential rains and flooding. Such events are costing lives and displacing tens of thousands of people. Further, our analysis shows that there are clear signs that Australia's health emergency management capacity substantially decreased in 2021. We find some signs of progress with respect to health and climate change. The states continue to lead the way in health and climate change adaptation planning, with the Victorian plan being published in early 2022. At the national level, we note progress in health and climate change research funding by the National Health and Medical Research Council. We now also see an acceleration in the uptake of electric vehicles and continued uptake of and employment in renewable energy. However, we also find Australia's transition to renewables and zero carbon remains unacceptably slow, and the Australian Government's continuing failure to produce a national climate change and health adaptation plan places the health and lives of Australians at unnecessary risk today, which does not bode well for the future.Paul J Beggs, Ying Zhang, Alice McGushin, Stefan Trueck, Martina K Linnenluecke, Hilary Bambrick, Anthony G Capon, Sotiris Vardoulakis, Donna Green, Arunima Malik, Ollie Jay, Maddie Heenan, Ivan C Hanigan, Sharon Friel, Mark Stevenson, Fay H Johnston, Celia McMichael, Fiona Charlson, Alistair J Woodward, Marina B Romanell

Temperature-related changes in airborne allergenic pollen abundance and seasonality across the northern hemisphere: a retrospective data analysis

Background: Ongoing climate change might, through rising temperatures, alter allergenic pollen biology across the northern hemisphere. We aimed to analyse trends in pollen seasonality and pollen load and to establish whether there are specific climate-related links to any observed changes.Methods: For this retrospective data analysis, we did an extensive search for global datasets with 20 years or more of airborne pollen data that consistently recorded pollen season indices (eg, duration and intensity). 17 locations across three continents with long-term (approximately 26 years on average) quantitative records of seasonal concentrations of multiple pollen (aeroallergen) taxa met the selection criteria. These datasets were analysed in the context of recent annual changes in maximum temperature (Tmax) and minimum temperature (Tmin) associated with anthropogenic climate change. Seasonal regressions (slopes) of variation in pollen load and pollen season duration over time were compared to Tmax, cumulative degree day Tmax, Tmin, cumulative degree day Tmin, and frost-free days among all 17 locations to ascertain significant correlations.Findings: 12 (71%) of the 17 locations showed significant increases in seasonal cumulative pollen or annual pollen load. Similarly, 11 (65%) of the 17 locations showed a significant increase in pollen season duration over time, increasing, on average, 0·9 days per year. Across the northern hemisphere locations analysed, annual cumulative increases in Tmax over time were significantly associated with percentage increases in seasonal pollen load (r=0·52, p=0·034) as were annual cumulative increases in Tmin (r=0·61, p=0·010). Similar results were observed for pollen season duration, but only for cumulative degree days (higher than the freezing point [0°C or 32°F]) for Tmax (r=0·53, p=0·030) and Tmin (r=0·48, p=0·05). Additionally, temporal increases in frost-free days per year were significantly correlated with increases in both pollen load (r=0·62, p=0·008) and pollen season duration (r=0·68, p=0·003) when averaged for all 17 locations.Interpretation: Our findings reveal that the ongoing increase in temperature extremes (Tmin and Tmax) might already be contributing to extended seasonal duration and increased pollen load for multiple aeroallergenic pollen taxa in diverse locations across the northern hemisphere. This study, done across multiple continents, highlights an important link between ongoing global warming and public health—one that could be exacerbated as temperatures continue to increase.</p

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes

The MJA-lancet countdown on health and climate change: Australian policy inaction threatens lives

Summaryl J Beggs, Ying Zhan

The 2020 special report of the MJA–Lancet Countdown on health and climate change: lessons learnt from Australia’s “Black Summer”

The MJA–Lancet Countdown on health and climate change was established in 2017, and produced its first Australian national assessment in 2018 and its first annual update in 2019. It examines indicators across five broad domains: climate change impacts, exposures and vulnerability; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In the wake of the unprecedented and catastrophic 2019–20 Australian bushfire season, in this special report we present the 2020 update, with a focus on the relationship between health, climate change and bushfires, highlighting indicators that explore these linkages. In an environment of continuing increases in summer maximum temperatures and heatwave intensity, substantial increases in both fire risk and population exposure to bushfires are having an impact on Australia’s health and economy. As a result of the “Black Summer” bushfires, the monthly airborne particulate matter less than 2.5 ?m in diameter (PM2.5) concentrations in New South Wales and the Australian Capital Territory in December 2019 were the highest of any month in any state or territory over the period 2000–2019 at 26.0 ?g/m3 and 71.6 ?g/m3 respectively, and insured economic losses were $2.2 billion. We also found growing awareness of and engagement with the links between health and climate change, with a 50% increase in scientific publications and a doubling of newspaper articles on the topic in Australia in 2019 compared with 2018. However, despite clear and present need, Australia still lacks a nationwide adaptation plan for health. As Australia recovers from the compounded effects of the bushfires and the coronavirus disease 2019 (COVID-19) pandemic, the health profession has a pivotal role to play. It is uniquely suited to integrate the response to these short term threats with the longer term public health implications of climate change, and to argue for the economic recovery from COVID-19 to align with and strengthen Australia’s commitments under the Paris Agreement