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Abstract The abrupt cessation of ovarian hormone release is associated with declines in muscle contractile function, yet the impact of gradual ovarian failure on muscle contractility across peri‐, early‐ and late‐stage menopause remains unclear. In this study, a 4‐vinylcyclohexene diepoxide (VCD)‐induced ovarian failure mouse model was used to examine time course changes in muscle mechanical function. Plantar flexors of female mice (VCD: n = 10; CON: n = 8) were assessed at 40 (early perimenopause), 80 (late perimenopause), 120 (menopause onset) and 176 (late menopause) days post‐initial VCD injection. A torque–frequency relationship was established across a range of frequencies (10–200 Hz). Isotonic dynamic contractions were elicited against relative loads (10–80% maximal isometric torque) to determine the torque–velocity–power relationship. Mice then performed a fatigue task using intermittent 100 Hz isometric contractions until torque dropped by 60%. Recovery of twitch, 10 Hz and 100 Hz torque were tracked for 10 min post‐task failure. Additionally, intact muscle fibres from the flexor digitorum brevis underwent a fatigue task (50 repetitions at 70 Hz), and 10 and 100 Hz tetanic [Ca2+] were monitored for 10 min afterward. VCD mice exhibited 16% lower twitch torque than controls across all time points. Apart from twitch torque, 10 Hz torque and 10 Hz tetanic [Ca2+], where VCD showed greater values relative to pre‐fatigue during recovery, no significant differences were observed between control and VCD mice during recovery. These results indicate that gradual ovarian failure has minimal detriments to in vivo muscle mechanical function, with minor alterations observed primarily for low‐frequency stimulation during recovery from fatigue.

Abstract In the nucleus, biological processes are driven by proteins that diffuse through and bind to a meshwork of nucleic acid polymers. To better understand this interplay, we present an imaging platform to simultaneously visualize single protein dynamics together with the local chromatin environment in live cells. Together with super-resolution imaging, new fluorescent probes, and biophysical modeling, we demonstrate that nucleosomes display differential diffusion and packing arrangements as chromatin density increases whereas the viscoelastic properties and accessibility of the interchromatin space remain constant. Perturbing nuclear functions impacts nucleosome diffusive properties in a manner that is dependent both on local chromatin density and on relative location within the nucleus. Our results support a model wherein transcription locally stabilizes nucleosomes while simultaneously allowing for the free exchange of nuclear proteins. Additionally, they reveal that nuclear heterogeneity arises from both active and passive processes and highlight the need to account for different organizational principles when modeling different chromatin environments.

Background: Urban neighbourhood environments may impact older adults’ cognitive health. However, longitudinal studies examining key environmental correlates of cognitive health are lacking. We estimated cross-sectional and longitudinal associations of neighbourhood built and natural environments and ambient air pollution with multiple cognitive health outcomes in Australian urban dwellers aged 60+ years. Methods: The study included 1160 participants of the PATH Through Life study (60+ cohort) who were followed up for 12 years (four assessments; 2001/02 to 2013/15) and with data on socio-demographics, health, cognitive functions and diagnoses, and full residential address. Neighbourhood environmental features encompassed population and street-intersection densities, non-commercial land use mix, transit points, presence of blue space, percentages of commercial land, parkland and tree cover, and annual average PM2.5 and NO2 concentrations. All exposures except for tree cover were assessed at two time points. Generalised additive mixed models estimated associations of person-level average, and within-person changes in, exposures with cognitive functions. Multi-state hidden Markov models estimated the associations of neighbourhood attributes with transitions to/from mild cognitive impairment (MCI). Results: Dense, destination-rich neighbourhoods were associated with a lower likelihood of transition to MCI and reversal to no MCI. Positive cross-sectional and longitudinal associations of non-commercial land use mix, street intersection density and percentage of commercial land were observed especially with global cognition and processing speed. While access to parkland and blue spaces were associated with a lower risk of transition to MCI, the findings related to cognitive functions were mixed and supportive of an effect of parkland on verbal memory only. Higher levels of PM2.5 and NO2 were consistently associated with steeper declines and/or decreases in cognitive functions and worse cognitive states across time. Conclusion: To support cognitive health in ageing populations, neighbourhoods need to provide an optimal mix of environmental complexity, destinations and access to the natural environment and, at the same time, minimise ambient air pollution.

In India, scarcity of ground-based measurements of nitrogen dioxide (NO2) is a major challenge for estimating long-term exposure and associated health impacts. This study aimed to develop and validate a national-scale annual NO2 exposure model for India for 2019 and determine if model cross-validation predictive ability was improved by including non-continuous (manual) measurements along with reference-grade, continuous measurements.We used a supervised forward-addition linear regression method to fit land use regression (LUR) models developed with up to 804 Central Pollution Control Board ground monitoring stations (n = 157 continuous, n = 647 manual) and 209 spatial predictor variables, including satellite-based tropospheric NO2 columns. Two models were developed: one using continuous sites only and one using continuous and manual sites, with standard diagnostics and cross-validation (CV) methods. We also assessed if the kriging of final model residuals reduced spatial autocorrelation and improved model CV results. LUR coefficients for the best-performing model were applied to predictors for 2015–2021 and gridded at 100 m to estimate population-weighted exposure.The continuous sites-only model and combined continuous and manual sites models had CV-R2 values of 0.59 (root-mean-square error [RMSE]: 9.4 μg/m3) and 0.54 (RMSE: 8.3 μg/m3), respectively, and both included the satellite NO2 predictor. Kriging residuals increased the CV-R2 of the combined model to 0.70 (RMSE: 7.2 μg/m3) but offered no improvement for the continuous site model. National population-weighted average NO2 was 22.1 μg/m3 in 2019. We estimated over 92% of the Indian population was exposed to annual NO2 exceeding the WHO air quality guideline (10 μg/m3). In Delhi, Mumbai, and Kolkata, an estimated 45%, 100%, and 100% of the population, respectively, experienced annual NO2 levels that surpassed Indian standards (40 μg/m3). To our knowledge, this is the first such long-term NO2 LUR model specific to India, and predictions are available to interested researchers.

Summary: Greenspace is projected to decrease the burden of infectious illnesses. Here, we examine the association between greenspace (measured using normalized difference vegetation index and percentages of greenspaces) and the prevalence of three infectious illnesses: acute respiratory infection (ARI), fever, and diarrhea among children under 5 years old, obtained from Demographic and Health Surveys in 49 low- and middle-income countries. Among 699,904 children from 49 countries, greenspace is associated with decreased odds of having ARI, fever, and diarrhea among children under 5 years old. These associations are stronger among children from poorer families and those living in rural areas. The air temperature, drought levels, and particulate matter ≤ 2.5 μm mediate 0.20%–18.45% of the associations between greenspaces and infectious illnesses. Our findings indicate that children living in greener areas may have lower odds of having infectious illnesses, and the underlying pathways may include lowering air temperature, drought, and air pollutants levels. Science for society: Environment has a significant impact on children’s health. Our research demonstrates the pivotal role of greenspaces in children’s health. By analyzing data from 49 low- and middle-income countries, we find significant associations between access to greenspaces and reduced prevalence of infectious illnesses, including acute respiratory infections, fever, and diarrhea among children under 5 years old. These associations are stronger in economically disadvantaged families and those residing in rural areas. Furthermore, our study shows that greenspace influences children’s health through changing environmental factors, such as lowering air temperatures, reducing drought levels, and decreasing air pollution. This research advocates for an interdisciplinary approach, bringing together experts in urban planning, public health, and environmental science to further explore the potential of greenspaces as a powerful tool for improving childhood health in low- and middle-income countries.

Abstract Background Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes. Methods We included 7000 participants in 2011–2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0–1; intermediate, 2–4; and favorable, 5–6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 μm [PM1], ≤ 2.5 μm [PM2.5], ≤ 10 μm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed. Results After adjusting for covariates, per 10 μg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05–1.14), PM2.5 (HR: 1.04, 95% CI: 1.00–1.08), PM10 (HR: 1.05, 95% CI: 1.03–1.08), and NO2 (HR: 1.11, 95% CI: 1.05–1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56–0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32–0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was − 0.98 (− 1.52 to − 0.44) for PM1, − 0.60 (− 1.05 to − 0.14) for PM2.5, − 1.84 (− 2.59 to − 1.09) for PM10, − 1.44 (− 2.10 to − 0.79) for NO2, and − 0.60 (− 1.08, − 0.12) for O3. Conclusions Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD.

Abstract The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual’s personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences.

This article reports on the development of key components required for a self-powered oscillator unit designed to wirelessly transmit its signal under full insertion in high-temperature (HT) harsh-environments (HE), such as those present in power plants and industrial settings (metallurgic, oil extraction, molding, and aerospace). The oscillator employed a silicon carbide power transistor and HT passive components on a screen-printed alumina circuit board capable of operation beyond 300 °C. The HT oscillator circuit was powered solely by in-situ energy-scavenging thermoelectric generator (TEG) modules using passive cooling, eliminating the need for an external power supply or active cooling. In addition, a silicon-based external booster circuit was used to achieve the required TEG voltage regulation to test the TEG-powered HT oscillator circuit. The TEG-powered oscillator circuit was tested inside a nonmetallic furnace from room temperature to over 300 °C for transmission of a wireless signal, which was detected outside the furnace at 11 ft (3.4 m). Such a wireless transmitting system powered only by in-situ TEGs, with no requirement for external power or active cooling, is very attractive for flexible, mobile standalone control and sensor units targeted for operation in HT HE conditions found in power plants and industrial settings.

Previous studies of resting electroencephalography (EEG) correlates of personality traits have conflated periodic and aperiodic sources of EEG signals. Because these are associated with different underlying neural dynamics, disentangling them can avoid measurement confounds and clarify findings. In a large sample (n = 300), we investigated how disentangling these activities impacts findings related to two research programs within personality neuroscience. In Study 1 we examined associations between Extraversion and two putative markers of reward sensitivity—Left Frontal Alpha asymmetry (LFA) and Frontal-Posterior Theta (FPT). In Study 2 we used machine learning to predict personality trait scores from resting EEG. In both studies, power within each EEG frequency bin was quantified as both total power and separate contributions of periodic and aperiodic activity. In Study 1, total power LFA and FPT correlated negatively with Extraversion (r ∼ -0.14), but there was no relation when LFA and FPT were derived only from periodic activity. In Study 2, all Big Five traits could be decoded from periodic power (r ∼ 0.20), and Agreeableness could also be decoded from total power and from aperiodic indices. Taken together, these results show how separation of periodic and aperiodic activity in resting EEG may clarify findings in personality neuroscience. Disentangling these signals allows for more reliable findings relating to periodic EEG markers of personality, and highlights novel aperiodic markers to be explored in future research.

Background:. Carpal tunnel syndrome (CTS) is a clinical diagnosis involving numerous confirmatory diagnostic tools, including patient questionnaires, ultrasound (US), and electrodiagnostic studies (EDX.) Patients may experience clinical symptoms of CTS with false negative diagnostic testing. The purpose of this study was to identify characteristics of patients with clinical symptoms of CTS with negative diagnostic testing. Methods:. An existing database of 295 hands containing the six-item CTS-6, US of the median nerve, and EDX was queried. Patients with symptoms of carpal tunnel scoring 12.5 or higher on CTS-6 were sorted into those with all positive testing or negative testing. Results:. In 60 patients, 103 hands had both positive US and EDX and a CTS-6 of 12.5 or higher. Twenty-nine hands in 25 patients had a CTS-6 of 12.5 or higher and both negative ultrasound and EDX. There was a significantly younger average age of 43 (P = 0.007) and lower average BMI of 28 (P < 0.0001) of patients in the negative diagnostic study group, compared with the average age of 53, and a body mass index (BMI) of 34 in the positive diagnostic study. Conclusions:. In this series, patients with symptoms of carpal tunnel syndrome and negative diagnostic studies were on average younger and had a lower BMI. These patients may warrant more careful consideration of CTS clinical diagnosis and counseling regarding a higher risk of false-negative confirmatory testing. Further studies are needed to determine possible effects of age and BMI on electrodiagnostic studies and ultrasound testing in CTS.

Introdution: During development, planes of cells give rise to complex tissues and organs. The proper functioning of these tissues is critically dependent on proper inter- and intra-cellular spatial orientation, a feature known as planar cell polarity (PCP). To study the genetic and environmental factors affecting planar cell polarity, investigators must often manually measure cell orientations, which is a time-consuming endeavor. To automate cell counting and planar cell polarity data collection we developed a Fiji/ImageJ plug-in called PCP Auto Count (PCPA).Methods: PCPA analyzes binary images and identifies “chunks” of white pixels that contain “caves” of infiltrated black pixels. For validation, inner ear sensory epithelia including cochleae and utricles from mice were immunostained for βII-spectrin and imaged with a confocal microscope. Images were preprocessed using existing Fiji functionality to enhance contrast, make binary, and reduce noise. An investigator rated PCPA cochlear hair cell angle measurements for accuracy using a one to five agreement scale. For utricle samples, PCPA derived measurements were directly compared against manually derived angle measurements and the concordance correlation coefficient (CCC) and Bland-Altman limits of agreement were calculated. PCPA was also tested against previously published images examining PCP in various tissues and across various species suggesting fairly broad utility.Results: PCPA was able to recognize and count 99.81% of cochlear hair cells, and was able to obtain ideally accurate planar cell polarity measurements for at least 96% of hair cells. When allowing for a

Background: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program’s office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively. Results: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive. Conclusion: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota.

Abstract Background Evidence on the relationship between air pollution and allergic sensitisation in childhood is inconsistent, and this relationship has not been investigated in the context of smoke events that are predicted to increase with climate change. Thus, we aimed to evaluate associations between exposure in two early life periods to severe levels of particulate matter with an aerodynamic diameter

Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads (i.e., immunogens) against gastric damage. In this study, hollowed nanocarriers (NCs: silica nanospheres and gold nanocages) with poly-l-lysine (PLL) coating and mammalian orthoreovirus cell attachment protein σ1 functionalization (NC-PLL-σ1) were explored as functional oral drug delivery vehicles (ODDVs). The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells (M-cells) mediated transcytosis (via σ1-α2–3-linked sialic acids adherence) across gastrointestinal epithelia. PLL coating provided protection and slow-release of rhodamine 6 G (R6G), a model payload. The transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in vitro. When compared with other experimental groups, the fully functionalized ODDV system (with PLL-σ1) demonstrated two significant advantages: a significantly higher transport efficiency (198% over blank control at 48 h); and protection of payloads which led to both better transport efficiency and extended-release of payloads (61% over uncoated carriers at 48 h). In addition, it was shown that the M cell presence in intestinal organoid monolayers (modulated by Rank L stimulation) was a determining factor on the transport efficiency of the ODDVs: more M-cells (induced by higher Rank L) in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload (R6G). The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines.

Abstract The Aerosol Cloud meTeorology Interactions oVer the western ATlantic Experiment (ACTIVATE) field campaign provides accurate data for aerosol characterization and trace gas profiles, and establishes knowledge of the relationships between aerosols and water. The dropsonde dataset provides an in situ characterization of the vertical thermodynamic structure of the atmosphere during 165 research flights by NASA Langley’s King Air research aircraft between February 2020 and June 2022 and four test flights between December 2019 and November 2021. The research flights covered the western North Atlantic region, off the coast of the Eastern United States and around Bermuda and covered all seasons. The dropsonde profiles provide observations of temperature, pressure, relative humidity, and horizontal and vertical winds between the surface and about 9 km. 801 dropsondes were released, of which 796 were processed and 788 provide complete profiles of all parameters between the flight level and the surface with normal parachute performance. Here, we describe the dataset, the processing of the measurements, general statistics, and applications of this rich dataset.

Lithium–sulfur batteries (LSBs) are widely studied as an alternative to lithium-ion batteries, this emphasis being due to their high theoretical energy density and low cost, and to the high natural abundance of sulfur. Lithium polysulfide shuttling and lithium dendrite growth have limited their commercialization. Porous polyvinylidene fluoride (PVDF) separators have shown improved performance (relative to hydrocarbon separators) in lithium-ion batteries due to faster lithium-ion migration and higher Li+ transference number. A thin polar PVDF membrane has now been fabricated via phase inversion (an immersion-precipitation method) yielding a β (polar) phase concentration of 72%. Preparation from commercial PVDF used dimethylformamide (DMF) solvent at the optimized crystallizing temperature of 70 °C, and pores in the membrane were generated by exchange of DMF with deionized water as non-solvent. The polar PVDF film produced has the advantages of being ultrathin (15 µm), lightweight (1.15 mg cm−2), of high porosity (75%) and high wettability (84%), and it shows enhanced thermal stability relative to polypropylene (PP). The porous, polar PVDF membrane was combined with a commercially available PP membrane to give a hybrid, two-layer, separator combination for LSBs. A synergy was created in the two-layer separator, providing high sulfur utilization and curbing polysulfide shuttling. The electrochemical performance with the hybrid separator (PP–β-PVDF) was evaluated in LSB cells and showed good cyclability and rate capability: those LSB cells showed a stable capacity of 750 mA h g−1 after 100 cycles at 0.1 C, much higher than that for otherwise-identical cells using a commercial PP-only separator (480 mA h g−1).

Background and objective: The association between air pollution and poor respiratory health outcomes is well established. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. This study investigated maternal exposure to air pollution during pregnancy and oxidative stress (OS), inflammation, and infant lung function at 4 weeks of age. Methods: Data from the Barwon Infant Study were available for 314 infants. The exposure to NO2 and PM2.5 were estimated. Infant lung function (4 weeks) was measured by multiple-breath washout. Glycoprotein acetyls (GlycA) (36 weeks prenatal), cord blood, and OS biomarkers were measured in maternal urine (28 weeks). A genetic pathway score for OS (gPFSox) was calculated. Linear regression was used and potential modification by the OS genotype was tested. Results: There was no relationship between maternal exposure to air pollution and infant lung function, or with GlycA or OS during pregnancy. We found an association in children with a genetic propensity to OS between NO2 and a lower functional residual capacity (FRC) (β = −5.3 mls, 95% CI (−9.3, −1.3), p = 0.01) and lung clearance index (LCI) score (β = 0.46 turnovers, (95% CI 0.10, 0.82), p = 0.01). Conclusion: High prenatal exposure to ambient NO2 is associated with a lower FRC and a higher LCI score in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.

Eukaryotic gene expression is linked to chromatin structure and nucleosome positioning by ATP-dependent chromatin remodelers that establish and maintain nucleosome-depleted regions (NDRs) near transcription start sites. Conserved yeast RSC and ISW2 remodelers exert antagonistic effects on nucleosomes flanking NDRs, but the temporal dynamics of remodeler search, engagement, and directional nucleosome mobilization for promoter accessibility are unknown. Using optical tweezers and two-color single-particle imaging, we investigated the Brownian diffusion of RSC and ISW2 on free DNA and sparse nucleosome arrays. RSC and ISW2 rapidly scan DNA by one-dimensional hopping and sliding, respectively, with dynamic collisions between remodelers followed by recoil or apparent co-diffusion. Static nucleosomes block remodeler diffusion resulting in remodeler recoil or sequestration. Remarkably, both RSC and ISW2 use ATP hydrolysis to translocate mono-nucleosomes processively at ~30 bp/s on extended linear DNA under tension. Processivity and opposing push–pull directionalities of nucleosome translocation shown by RSC and ISW2 shape the distinctive landscape of promoter chromatin.

Background: Evidence suggests that maternal exposure to heat might increase the risk of preterm birth (PTB), but no study has investigated the effect from urban heat island (UHI) at individual level. Aims: Our study aimed to investigate the association between individual UHI exposure and PTB. Methods: We utilized data from the ongoing China Birth Cohort Study (CBCS), encompassing 103,040 birth records up to December 2020. UHI exposure was estimated for each participant using a novel individual assessment method based on temperature data and satellite-derived land cover data. We used generalized linear mixed-effects models to estimate the association between UHI exposure and PTB, adjusting for potential confounders including maternal characteristics and environmental factors. Results: Consistent and statistically significant associations between UHI exposure and PTB were observed up to 21 days before birth. A 5 °C increment in UHI exposure was associated with 27 % higher risk (OR = 1.27, 95 % confident interval: 1.20, 1.34) of preterm birth in lagged day 1. Stratified analysis indicated that the associations were more pronounced in participants who were older, had higher pre-pregnancy body mass index level, of higher socioeconomic status and living in greener areas. Conclusion: Maternal exposure to UHI was associated with increased risk of PTB. These findings have implications for developing targeted interventions for susceptible subgroups of pregnant women. More research is needed to validate our findings of increased risk of preterm birth due to UHI exposure among pregnant women.

IntroductionThere is a growing body of evidence suggesting a causal relationship between interstitial lung disease (ILD) and air pollution, both for the development of the disease, and driving disease progression. We aim to provide a comprehensive literature review of the association between air pollution, and ILD, including idiopathic pulmonary fibrosis (IPF).MethodsWe systematically searched from six online database. Two independent authors (DL and CF) selected studies and critically appraised the risk of bias using the Newcastle-Ottawa Scale (NOS). Findings are presented through a narrative synthesis and meta-analysis. Meta-analyses were performed exclusively when there was a minimum of three studies examining identical pollutant-health outcome pairs, all evaluating equivalent increments in pollutant concentration, using a random effects model.Results24 observational studies conducted in 13 countries or regions were identified. Pollutants under investigation encompassed ozone (O3), nitrogen dioxide (NO2), Particulate matter with diameters of 10 micrometers or less (PM10) and 2.5 micrometers or less (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO), nitric oxide (NO) and nitrogen oxides (NOx). We conducted meta-analyses to assess the estimated Risk Ratios (RRs) for acute exacerbations (AE)-IPF in relation to exposure to every 10 μg/m3 increment in air pollutant concentrations, including O3, NO2, PM10, and PM2.5. The meta-analysis revealed a significant association between the increased risk of AE-IPF in PM2.5, yielding RR 1.94 (95% CI 1.30–2.90; p = 0.001). Findings across all the included studies suggest that increased exposure to air pollutants may be linked to a range of health issues in individuals with ILDs.ConclusionA scarcity of available studies on the air pollutants and ILD relationship underscores the imperative for further comprehensive research in this domain. The available data suggest that reducing levels of PM2.5 in the atmosphere could potentially reduce AE frequency and severity in ILD patients.

Abstract Background COVID-19 outbreaks have disproportionately affected Residential Aged Care Facilities (RACFs) around the world, with devastating impacts for residents and their families. Many factors such as community prevalence, facility layout, and infection control practices have been linked to resident outcomes. At present, there are no scoring systems designed to quantify these factors and assess their level of association with resident attack rates and mortality rates. Methods We constructed a novel Infection Prevention and Control (IPC) scoring system to quantify facility layout, ability to cohort residents, and IPC practices in RACFs. We conducted a retrospective observational cohort study of COVID-19 outbreaks, applying our IPC scoring system to all COVID-19 outbreaks occurring in RACFs in Sydney Local Health District during the Delta and Omicron waves of the COVID-19 pandemic in New South Wales, Australia. Results Twenty-six COVID-19 outbreaks in 23 facilities in the Delta wave, and 84 outbreaks in 53 facilities in the Omicron wave were included in the study. A linear Generalised Estimating Equation model was fitted to the Omicron data. Higher IPC scores were associated with higher attack rates and mortality rates. Facilities with IPC scores greater than 75.0% had attack rates 19.6% higher [95% CI: 6.4%-32.8%] and mortality rates 1.7% higher [95% CI: 0.6%-2.7%] than facilities with an IPC score of less than 60.0%. Conclusions The results of this study suggest the utility of the IPC scoring system for identifying facilities at greater risk of adverse outcomes from COVID-19 outbreaks. While further validation and replication of accuracy is required, the IPC scoring system could be used and adapted to improve planning, policy, and resource allocation for future outbreaks.

Abstract Background Lung infections caused by Streptococcus pneumonia are a global leading cause of death. The reactive oxygen species H2O2 is one of the virulence factors of Streptococcus pneumoniae. The Golgi apparatus is essential for the inflammatory response of a eukaryotic cell. Golgi fragmentation was previously shown to be induced by bacterial pathogens and in response to H2O2 treatment. This led us to investigate whether the Golgi apparatus is actively involved and targeted in host–pathogen interactions during pneumococcal infections. Methods Following in vitro infection of BEAS-2B bronchial epithelial cells with Streptococcus pneumoniae for 16 h, the structure of the Golgi apparatus was assessed by fluorescence staining of the Golgi-associated protein, Golgin-97. To investigate the effect of H2O2 production on Golgi structure, BEAS-2B cells were treated with H2O2 or the H2O2 degrading enzyme Catalase, prior to Golgi staining. Artificial disruption of the Golgi apparatus was induced by treatment of cells with the GBF1 inhibitor, Golgicide A. A proinflammatory cellular response was induced by treatment of cells with the bacterial cell wall component and TLR4 ligand lipoteichoic acid. Results In vitro infection of bronchial epithelial cells with wild type Streptococcus pneumoniae led to a disruption of normal Golgi structure. Golgi fragmentation was not observed after deletion of the pneumococcal H2O2-producing gene, spxB, or neutralization of H2O2 by catalase treatment, but could be induced by H2O2 treatment. Streptococcus pneumoniae infection significantly reduced host cell protein glycosylation and artificial disruption of Golgi structure significantly reduced bacterial adherence, but increased bacterial counts in the supernatant. To understand if this effect depended on cell-contact or soluble factors, pneumococci were treated with cell-supernatant of cells treated with Golgicide A and/or lipoteichoic acid. This approach revealed that lipoteichoic acid conditioned medium inhibits bacterial replication in presence of host cells. In contrast, artificial Golgi fragmentation by Golgicide A treatment prior to lipoteichoic acid treatment rescued bacterial replication. This effect was associated with an increase of IL-6 and IL-8 in the supernatant of lipoteichoic acid treated cells. The increased cytokine release was abolished if cells were treated with Golgicide A prior to lipoteichoic acid treatment. Conclusion Streptococcus pneumoniae disrupts the Golgi apparatus in an H2O2-dependent manner, thereby inhibiting paracrine anti-infective mechanisms. Video Abstract

Abstract In-situ marine cloud droplet number concentrations (CDNCs), cloud condensation nuclei (CCN), and CCN proxies, based on particle sizes and optical properties, are accumulated from seven field campaigns: ACTIVATE; NAAMES; CAMP2EX; ORACLES; SOCRATES; MARCUS; and CAPRICORN2. Each campaign involves aircraft measurements, ship-based measurements, or both. Measurements collected over the North and Central Atlantic, Indo-Pacific, and Southern Oceans, represent a range of clean to polluted conditions in various climate regimes. With the extensive range of environmental conditions sampled, this data collection is ideal for testing satellite remote detection methods of CDNC and CCN in marine environments. Remote measurement methods are vital to expanding the available data in these difficult-to-reach regions of the Earth and improving our understanding of aerosol-cloud interactions. The data collection includes particle composition and continental tracers to identify potential contributing CCN sources. Several of these campaigns include High Spectral Resolution Lidar (HSRL) and polarimetric imaging measurements and retrievals that will be the basis for the next generation of space-based remote sensors and, thus, can be utilized as satellite surrogates.

Long-term exposure to ambient air pollution even at relatively low concentrations is associated with adverse health effects especially for children, the elderly and people with pre-existing chronic disease. Due to a variety of urban planning decisions, essential building premises attended by these vulnerable groups may be sited in locations exposed to higher levels of air pollution. Using high spatial resolution air pollution concentrations estimated by satellite-based Land Use Regression (LUR) models in Australia, we mapped and approximated the annual average concentrations of particulate matter (PM2.5) and nitrogen dioxide (NO2) at schools, child care centres, aged care facilities and hospitals across Sydney. We found that 137 (3.1 %) and 287 (6.4 %) of the total number of essential buildings assessed were exposed to annual average PM2.5 and NO2 concentrations, respectively, where: the air pollutant concentrations were greater than the median concentration of other locations in the surrounding Local Government Area (LGA), and; air pollutant levels were greater than the 90th percentile concentrations for Sydney, and; air pollution at the essential building location was at least 1 µg/m3 for PM2.5 or 2 ppb for NO2 greater than the 25th percentile concentration of other locations in the LGA. Based on these criteria, we found that many essential building premises in Sydney were in high air pollution locations and there were other meaningfully lower air pollution locations within the surrounding area. Air quality is becoming an increasingly important issue for local jurisdictions to consider as more essential amenities are required to serve denser populations in busier places exposed to more air pollution. Our study showed that high resolution maps can be used as a health-based planning tool to encourage the siting of buildings at locations better protective of health.

Abstract Insular epilepsy (IE) is an increasingly recognized cause of drug‐resistant epilepsy amenable to surgery. However, concerns of suboptimal seizure control and permanent neurological morbidity hamper widespread adoption of surgery for IE. We performed a systematic review and individual participant data meta‐analysis to determine the efficacy and safety profile of surgery for IE and identify predictors of outcomes. Of 2483 unique citations, 24 retrospective studies reporting on 312 participants were eligible for inclusion. The median follow‐up duration was 2.58 years (range, 0‐17 years), and 206 (66.7%) patients were seizure‐free at last follow‐up. Younger age at surgery (≤18 years; HR = 1.70, 95% CI = 1.09‐2.66, P = .022) and invasive EEG monitoring (HR = 1.97, 95% CI = 1.04‐3.74, P = .039) were significantly associated with shorter time to seizure recurrence. Performing MR‐guided laser ablation or radiofrequency ablation instead of open resection (OR = 2.05, 95% CI = 1.08‐3.89, P = .028) was independently associated with suboptimal or poor seizure outcome (Engel II‐IV) at last follow‐up. Postoperative neurological complications occurred in 42.5% of patients, most commonly motor deficits (29.9%). Permanent neurological complications occurred in 7.8% of surgeries, including 5% and 1.4% rate of permanent motor deficits and dysphasia, respectively. Resection of the frontal operculum was independently associated with greater odds of motor deficits (OR = 2.75, 95% CI = 1.46‐5.15, P = .002). Dominant‐hemisphere resections were independently associated with dysphasia (OR = 13.09, 95% CI = 2.22‐77.14, P = .005) albeit none of the observed language deficits were permanent. Surgery for IE is associated with a good efficacy/safety profile. Most patients experience seizure freedom, and neurological deficits are predominantly transient. Pediatric patients and those requiring invasive monitoring or undergoing stereotactic ablation procedures experience lower rates of seizure freedom. Transgression of the frontal operculum should be avoided if it is not deemed part of the epileptogenic zone. Well‐selected candidates undergoing dominant‐hemisphere resection are more likely to exhibit transient language deficits; however, the risk of permanent deficit is very low.

Abstract The Antarctic ice sheet (AIS) is the largest freshwater body on Earth and a major component of the sea level budget. Over the satellite era, the AIS has experienced ∼130 Gt/year of mass loss. Net losses are partially mitigated by snow accumulation that varies ∼100–130 Gt/yr, underscoring a need to understand the drivers of snowfall variability. Here, we evaluate impacts of decreased sea ice in the Amundsen Sea region of West Antarctica on the overlying atmosphere and surface mass balance of the adjacent AIS using composites, spatial correlations, and a causal effect network method. Importantly, our findings show sea ice declines in the Amundsen Sea lead to enhanced integrated water vapor that is subsequently transported to the AIS resulting in positive anomalies in West Antarctic ice sheet snowfall. Our results suggest future decreases in sea ice may likely enhance ice sheet snowfall, thus partially offsetting Antarctic sea level contributions.

The forelimbs of hominoid primates (apes) are decidedly more flexible than those of monkeys, especially at the shoulder, elbow and wrist joints. It is tempting to link the greater mobility of these joints to the functional demands of vertical climbing and below-branch suspension, but field-based kinematic studies have found few differences between chimpanzees and monkeys when comparing forelimb excursion angles during vertical ascent (upclimbing). There is, however, a strong theoretical argument for focusing instead on vertical descent (downclimbing), which motivated us to quantify the effects of climbing directionality on the forelimb kinematics of wild chimpanzees (Pan troglodytes) and sooty mangabeys (Cercocebus atys). We found that the shoulders and elbows of chimpanzees and sooty mangabeys subtended larger joint angles during bouts of downclimbing, and that the magnitude of this difference was greatest among chimpanzees. Our results cast new light on the functional importance of downclimbing, while also burnishing functional hypotheses that emphasize the role of vertical climbing during the evolution of apes, including the human lineage.

Despite an increasing number of studies demonstrating the potential mental health benefits of greenspace, few longitudinal studies have been reported. We aimed to assess associations between two metrics of residential greenspace exposure and anxiety symptoms in a cohort of Australian women living in major cities.Our study comprised 3,938 women, born between 1973 and 78. Anxiety symptoms in the previous month were assessed at follow-up every three years during 2003–2018, using the anxiety subscale of the Goldberg Anxiety and Depression Scale. The three-month seasonal average normalized difference vegetation index (NDVI) was estimated from 30 m Landsat satellite images in a 500 m buffer (NDVI500m) around participants’ address at each survey (higher NDVI indicates more green vegetation). The annual fractional cover of non-photosynthesising vegetation was estimated (fNPV500m, with higher values indicating greater levels of dead leaf litter or dry grass).A generalised estimating equation assessed associations between greenspace measures and anxiety symptoms (as odds ratios [ORs]), adjusting for repeated outcomes and individual-level covariates. Additional analyses focused on women experiencing substantial changes in between-survey exposure due to moving, and adjusting for nitrogen dioxide (NO2) and fine particulate matter (PM2.5) exposure, among others.A standard deviation (SD) (0.12 units) increase in NDVI500m was significantly associated with lower odds of anxiety symptoms (OR: 0.96, 95% CI: 0.93–0.99) in the adjusted model. An SD (5.2%) increase in annual fNPV500m was consistent with the direction expected for that exposure, but not significant in the adjusted model (OR: 1.03, 95% CI: 0.99–1.07). NDVI500m was modestly attenuated when air pollutants were adjusted for, while fNPV500m only became significant when PM2.5 was adjusted for. Between-survey contrasts had no clear effect for NDVI500m. Moving to a higher fNPV500m area, compared with a similar fNPV500m area, was consistently associated with anxiety symptoms (OR: 1.15, 95% CI: 1.02–1.31). NDVI500m was generally associated with lower odds of anxiety symptoms, while fNPV500m was generally associated with higher odds of anxiety, depending on the covariates considered.

Birth weight is an indicator linking intrauterine environmental exposures to later-life diseases, and intrauterine metal exposure may affect birth weight in a sex-specific manner. We investigated sex-specific associations between prenatal exposure to metal mixtures and birth weight in a Chinese birth cohort. The birth weight of 1296 boys and 1098 girls were recorded, and 10 metals in maternal urine samples collected during pregnancy were measured using inductively coupled plasma mass spectrometry. Bayesian Kernel Machine Regression was used to estimate the association of individual metals or metal mixtures and birth weight for gestational age (BW for GA). The model showed a sex-specific relationship between prenatal exposure to metal mixtures and BW for GA with a significant negative association in girls and a non-significant positive association in boys. Cadmium (Cd) and nickel (Ni) were positively and negatively associated with BW for GA in girls, respectively. Moreover, increasing thallium (Tl) concentration lowered the positive association between Cd and BW for GA and enhanced the negative association between Ni and BW for GA in girls. When exposure to other metals increased, the positive association with Cd diminished, whereas the negative association with Ni or Tl increased. Our findings provide evidence supporting the complex effects of intrauterine exposure to metal mixtures on the birth weight of girls and further highlight the sex heterogeneity in fetal development influenced by intrauterine environmental factors.

In the Canadian prairies, pulse crops such as field pea (Pisum sativum L.) and lentil (Lens culinaris L.) are economically important and widely grown. However, in recent years, root rot, caused by a variety of fungal and oomycete pathogens, including Aphanomyces euteiches, has become a limiting factor on yield. In this study, we examined the impacts of nitrogen (N) fertilization and a commercial arbuscular mycorrhizal fungal (AMF) inoculant on pea and lentil plant health and agronomic production at three locations in Saskatchewan: Swift Current, Indian Head and Melfort. The AMF inoculation had no impact on root rot severity, and therefore is not considered a reliable method to manage root rot in pea and lentil. In contrast, N fertilization led to reductions in root rot in Swift Current, but not the other two sites. However, N fertilization did reduce nodulation. When both pea and lentil are considered, the abundance of A. euteiches in soil increased from pre-seeding to mid-bloom. A negative correlation between soil pH and disease severity was also observed. The high between-site variability highlights the importance of testing root rot mitigation strategies under multiple soil conditions to develop site-specific recommendations. Use of N fertilizer as a root rot management strategy merits further exploration, including investigation into its interactions with other management strategies, soil properties, and costs and benefits.

Hyperglycemia is a key risk factor for death and disability worldwide. To better inform prevention strategies, we aimed to delineate and predict the temporal, spatial, and demographic patterns in mean fasting plasma glucose (FPG) levels and their related disease burden globally. Based on the Global Burden of Disease Study 2019, we estimated the distributions of mean FPG levels and high FPG-related disease burden by age, sex, year, socioeconomic status (SES), and geographical region from 1990 to 2050. We also investigated the possible associations of demographic, behavioral, dietary, metabolic, and environmental factors with FPG levels and high FPG-related disease burden. In 2019, the global mean FPG level was 5.40 mmol/L (95% uncertainty interval [UI]: 4.86–6.00), and high FPG contributed to 83.0 deaths (95% UI, 64.5–107.1) and 2,104.3 DALYs (95% UI: 1,740.7–2,520.7) per 100,000 people. For both historical (1990–2019) and future (2020–2050) periods, the mean FPG levels and the high FPG-related disease burden increased globally, with greater increases among the middle-aged and elderly, and people in low-to-middle SES countries, relative to their counterparts. Aging, unhealthy lifestyles, elevated body mass index, and lower air temperatures were potential risk factors for high FPG levels and the high FPG-related disease burden. This study demonstrates that high FPG continues to contribute to the global disease burden and is expected to do so for at least the next 30 years. Older people and those living in low-to-middle SES countries should receive more attention in glycemic management health interventions. In addition, effective interventions that target identified risk factors should be adopted to handle the increasingly large disease burden of high FPG.

Abstract Reproductive propagation by asexual fragmentation in the reef-building coral Acropora millepora depends on (1) successful attachment to the reef substrate through modification of soft tissues and (2) a permanent bond with skeletal encrustation. Despite decades of research examining asexual propagation in corals, the initial response, cellular reorganisation, and development leading to fragment substrate attachment via a newly formed skeleton has not been documented in its entirety. Here, we establish the first "coral attachment model" for this species ("Am-CAM") by developing novel methods that allow correlation of fluorescence and electron microscopy image data with in vivo microscopic time-lapse imagery. This multi-scale imaging approach identified three distinct phases involved in asexual propagation: (1) the contact response of the coral fragment when contact with the substrate, followed by (2) fragment stabilisation through anchoring by the soft tissue, and (3) formation of a "lappet-like appendage" structure leading to substrate bonding of the tissue for encrustation through the onset of skeletal calcification. In developing Am-CAM, we provide new biological insights that can enable reef researchers, managers and coral restoration practitioners to begin evaluating attachment effectiveness, which is needed to optimise species-substrate compatibility and achieve effective outplanting.

Abstract Background Alternative treatment strategies in melanoma beyond immunotherapy and mutation-targeted therapy are urgently needed. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme protects cancer cells under metabolic stress, including nutrient limited conditions in the tumor microenvironment. Specifically, IDH1 generates NADPH to maintain redox homeostasis and produces α-ketoglutarate to support mitochondrial function through anaplerosis. Herein, the role of wtIDH1 in melanoma is further explored. Methods The expression of wtIDH1 was determined by qRT-PCR, and Western blot in melanoma cell lines and the effect of wtIDH1 on metabolic reprogramming in melanoma was interrogated by LC-MS. The impact of wtIDH1 inhibition alone and in combination with chemotherapy was determined in cell culture and mouse melanoma models. Results Melanoma patients express higher levels of the wtIDH1 enzyme compared to normal skin tissue, and elevated wtIDH1 expression portends poor patient survival. Knockdown of IDH1 by RNA interference inhibited cell proliferation and migration under low nutrient levels. Suppression of IDH1 expression in melanoma also decreased NADPH and glutathione levels, resulting in increased reactive oxygen species. An FDA-approved inhibitor of mutant IDH1, ivosidenib (AG-120), exhibited potent anti-wtIDH1 properties under low magnesium and nutrient levels, reflective of the tumor microenvironment in natura. Thus, similar findings were replicated in murine models of melanoma. In light of the impact of wtIDH1 inhibition on oxidative stress, enzyme blockade was synergistic with conventional anti-melanoma chemotherapy in pre-clinical models. Conclusions These results demonstrate the clinical potential of wtIDH1 inhibition as a novel and readily available combination treatment strategy for patients with advanced and refractory melanoma. Graphical Abstract Schematic shows increased wild-type IDH1 expression and activity as an adaptive response to metabolic stress induced by chemotherapy.

Abstract Background There is a dearth of studies on how neighbourhood environmental attributes relate to the metabolic syndrome (MetS) and profiles of MetS components. We examined the associations of interrelated aspects of the neighbourhood environment, including air pollution, with MetS status and profiles of MetS components. Methods We used socio-demographic and MetS-related data from 3681 urban adults who participated in the 3rd wave of the Australian Diabetes, Obesity and Lifestyle Study. Neighbourhood environmental attributes included area socio-economic status (SES), population density, street intersection density, non-commercial land use mix, percentages of commercial land, parkland and blue space. Annual average concentrations of NO2 and PM2.5 were estimated using satellite-based land-use regression models. Latent class analysis (LCA) identified homogenous groups (latent classes) of participants based on MetS components data. Participants were then classified into five metabolic profiles according to their MetS-components latent class and MetS status. Generalised additive mixed models were used to estimate relationships of environmental attributes with MetS status and metabolic profiles. Results LCA yielded three latent classes, one including only participants without MetS (“Lower probability of MetS components” profile). The other two classes/profiles, consisting of participants with and without MetS, were “Medium-to-high probability of high fasting blood glucose, waist circumference and blood pressure” and “Higher probability of MetS components”. Area SES was the only significant predictor of MetS status: participants from high SES areas were less likely to have MetS. Area SES, percentage of commercial land and NO2 were associated with the odds of membership to healthier metabolic profiles without MetS, while annual average concentration of PM2.5 was associated with unhealthier metabolic profiles with MetS. Conclusions This study supports the utility of operationalising MetS as a combination of latent classes of MetS components and MetS status in studies of environmental correlates. Higher socio-economic advantage, good access to commercial services and low air pollution levels appear to independently contribute to different facets of metabolic health. Future research needs to consider conducting longitudinal studies using fine-grained environmental measures that more accurately characterise the neighbourhood environment in relation to behaviours or other mechanisms related to MetS and its components.

Abstract Alzheimer’s disease (AD) is progressive and ultimately fatal, with current drugs failing to reverse and cure it. This study aimed to find plant species which may provide therapeutic bioactivities targeted to causal agents proposed to be driving AD. A novel toolkit methodology was employed, whereby clinical symptoms were translated into categories recognized in ethnomedicine. These categories were applied to find plant species with therapeutic effects, mined from ethnomedical surveys. Survey locations were mapped to assess how this data is at risk. Bioactivities were found of therapeutic relevance to 15 hypothesised causal bases for AD. 107 species with an ethnological report of memory improvement demonstrated therapeutic activity for all these 15 causal bases. The majority of the surveys were found to reside within biodiversity hotspots (centres of high biodiversity under threat), with loss of traditional knowledge the most common threat. Our findings suggest that the documented plants provide a large resource of AD therapeutic potential. In demonstrating bioactivities targeted to these causal bases, such plants may have the capacity to reduce or reverse AD, with promise as drug leads to target multiple AD hallmarks. However, there is a need to preserve ethnomedical knowledge, and the habitats on which this knowledge depends. Graphical Abstract

Abstract In a field experiment, we evaluated the impact of 37 years of contrasting water stress history on the microbial response in various plant compartments at two distinct developmental stages when four wheat genotypes were exposed to contemporary water stress. Seeds were collected and sampled at the end of the experiment to characterize endophytic and epiphytic microbial communities. Amplicon sequencing data revealed that plant development stage and water stress history were the main factors shaping the microbiome of the major plant parts in response to contemporary water limitation. Our results indicate that seeds can become colonized by divergent microbial communities within a single generation based on the initial pool of microbes as determined by historical contingencies, which was modulated by the contemporary environmental conditions and the plant genotype. Such information is essential to incorporate microbial-based strategies into conventional plant breeding to enhance plant resistance to stress.

Fenestrated and blood-brain barrier (BBB)-forming endothelial cells constitute major brain capillaries, and this vascular heterogeneity is crucial for region-specific neural function and brain homeostasis. How these capillary types emerge in a brain region-specific manner and subsequently establish intra-brain vascular heterogeneity remains unclear. Here, we performed a comparative analysis of vascularization across the zebrafish choroid plexuses (CPs), circumventricular organs (CVOs), and retinal choroid, and show common angiogenic mechanisms critical for fenestrated brain capillary formation. We found that zebrafish deficient for Gpr124, Reck, or Wnt7aa exhibit severely impaired BBB angiogenesis without any apparent defect in fenestrated capillary formation in the CPs, CVOs, and retinal choroid. Conversely, genetic loss of various Vegf combinations caused significant disruptions in Wnt7/Gpr124/Reck signaling-independent vascularization of these organs. The phenotypic variation and specificity revealed heterogeneous endothelial requirements for Vegfs-dependent angiogenesis during CP and CVO vascularization, identifying unexpected interplay of Vegfc/d and Vegfa in this process. Mechanistically, expression analysis and paracrine activity-deficient vegfc mutant characterization suggest that endothelial cells and non-neuronal specialized cell types present in the CPs and CVOs are major sources of Vegfs responsible for regionally restricted angiogenic interplay. Thus, brain region-specific presentations and interplay of Vegfc/d and Vegfa control emergence of fenestrated capillaries, providing insight into the mechanisms driving intra-brain vascular heterogeneity and fenestrated vessel formation in other organs.

Metastatic spinal melanoma is a rare and aggressive disease process with poor prognosis. We review the literature on metastatic spinal melanoma, focusing on its epidemiology, management, and treatment outcomes. Demographics of metastatic spinal melanoma are similar to those for cutaneous melanoma, and cutaneous primary tumors tend to be most common. Decompressive surgical intervention and radiotherapy have traditionally been considered mainstays of treatment, and stereotactic radiosurgery has emerged as a promising approach in the operative management of metastatic spinal melanoma. While survival outcomes for metastatic spinal melanoma remain poor, they have improved in recent years with the advent of immune checkpoint inhibition, used in conjunction with surgery and radiotherapy. New treatment options remain under investigation, especially for patients with disease refractory to immunotherapy. We additionally explore several of these promising future directions. Nevertheless, further investigation of treatment outcomes, ideally incorporating high-quality prospective data from randomized controlled trials, is needed to identify optimal management of metastatic spinal melanoma.

Abstract It is hypothesised that the avian compass relies on spin dynamics in a recombining radical pair. Quantum coherence has been suggested as a resource to this process that nature may utilise to achieve increased compass sensitivity. To date, the true functional role of coherence in these natural systems has remained speculative, lacking insights from sufficiently complex models. Here, we investigate realistically large radical pair models with up to 21 nuclear spins, inspired by the putative magnetosensory protein cryptochrome. By varying relative radical orientations, we reveal correlations of several coherence measures with compass fidelity. Whilst electronic coherence is found to be an ineffective predictor of compass sensitivity, a robust correlation of compass sensitivity and a global coherence measure is established. The results demonstrate the importance of realistic models, and appropriate choice of coherence measure, in elucidating the quantum nature of the avian compass.

Abstract To investigate aldo–keto reductase 1C3 (AKR1C3) expression in T and B acute lymphoblastic leukemia/lymphoma (ALL) patients. Three commercial antibodies were evaluated for AKR1C3 immunohistochemistry (IHC) staining performance: Polyclonal Thermofisher scientific (Clone#PA523667), rabbit monoclonal Abcam [EPR16726] (ab209899) and Sigma/Millipore anti-AKR1C3 antibody, mouse monoclonal, clone NP6.G6.A6, purified from hybridoma cell culture. Initial optimization was performed on cell line controls: HCT116 (negative control); genetically modified cell line HCT116 with AKR1C3 overexpression; Nalm and TF1 cell lines. Twenty normal bone marrows from archival B and T-ALL patient samples were subsequently examined. AKR1C3 expression levels in these samples were evaluated by immunohistochemistry, Protein Wes and quantitative RT-PCR. Sigma/Millipore Anti-AKR1C3 antibody (mouse monoclonal, clone NP6.G6.A6) showed higher specificity compared to rabbit polyclonal antibody by immunohistochemistry. H-score was used to quantify percent of nuclear immunoreactivity for AKR1C3 with varying disease involvement. T-ALL samples had a higher H-score (172–190) compared to B-ALL cases (H-score, 30–160). The AKR1C3 expression in peripheral blood by Protein Wes and RT-qPCR showed concordance in relapsed/refractory and/or minimal residual T-ALL cases. Sigma/Millipore Anti-AKR1C3 antibody and mouse monoclonal, clone NP6.G6.A6 can be used to aid in AKR1C expression of T-ALL and in cases of relapsed/refractory and/or minimal residual disease.

Circumscribed interests (CI) encompass a range of different interests and related behaviors that can be characterized by either a high intensity but otherwise usual topic [referred to as restricted interests (RI)] or by a focus on topics that are not salient outside of autism [referred to as unusual interests (UI)]. Previous research has suggested that there is pronounced variability across individuals in terms of the endorsement of different interests, however, this variability has not been quantified using formal subtyping approaches. Therefore, using Latent Profile Analysis in a sample of 1,892 autistic youth (Mage = 10.82, SDage = 4.14; 420 females), this study aimed to identify subgroups based on the RU and UI profiles. Three profiles of autistic individuals were identified. They were characterized as Low CI, Predominantly RI, and Predominantly UI. Importantly, profiles differed on several key demographic and clinical variables, including age, sex composition, IQ, language level, social and communication abilities, anxiety, and obsessive-compulsive behaviors. Although replication across other samples is needed, the profiles identified in this study are potentially promising for future research given their distinct profiles of RI and UI and unique patterns of associations with key cognitive and clinical variables. Therefore, this study represents an important initial step towards more individualized assessment and support for diverse presentations of CI in autistic youth.

Abstract Background There is a dearth of studies on the effects of the neighbourhood environment on adults’ cognitive function. We examined how interrelated aspects of the built and natural neighbourhood environment, including air pollution, correlate with adults’ cognitive function, and the roles of physical activity and sedentary behaviours in these associations. Methods We used data from 4,141 adult urban dwellers who participated in the Australian Diabetes, Obesity and Lifestyle 3 study on socio-demographic characteristics, neighbourhood self-selection, physical activity and sedentary behaviours, and cognitive function. Neighbourhood environmental characteristics included population density, intersection density, non-commercial land use mix, and percentages of commercial land, parkland and blue space, all within 1 km residential buffers. We also calculated annual mean concentrations of NO2 and PM2.5. Generalised additive mixed models informed by directed acyclic graphs were used to estimate the total, direct and indirect effects of environmental attributes on cognitive functions and the joint-significance test was used to examine indirect effects via behaviours. Results In the total effects models, population density and percentage of parkland were positively associated with cognitive function. A positive association of PM2.5 with memory was also observed. All neighbourhood environmental attributes were directly and/or indirectly related to cognitive functions via other environmental attributes and/or physical activity but not sedentary behaviours. Engagement in transportation walking and gardening frequency partially mediated the positive effects of the neighbourhood environment on cognitive function, while frequency of transportation walking mediated the negative effects. Conclusions In the context of a low-density country like Australia, denser urban environments with access to parkland may benefit residents’ cognitive health by providing opportunities for participation in a diversity of activities. A more fine-grained characterisation of the neighbourhood environment may be necessary to tease out the negative and positive impacts of inter-related characteristics of urban neighbourhood environments on cognitive function.

Abstract Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that homozygous deletion of the CFHR1 gene, which encodes the plasma complement protein factor H-related protein 1 (FHR-1), was protective in two cohorts of patients with ACVD, suggesting that FHR-1 accelerates inflammation and exacerbates the disease. To test this hypothesis, FHR-1 was isolated from human plasma and was found to circulate on extracellular vesicles and to be deposited in atherosclerotic plaques. Surface-bound FHR-1 induced the expression of pro-inflammatory cytokines and tissue factor in both monocytes and neutrophils. Notably, plasma concentrations of FHR-1, but not of factor H, were significantly (p

Using the first high-resolution geophysical data set collected from the uThukela Banks Marine Protected Area (MPA), we reveal a plethora of hitherto unknown or poorly resolved seabed features. In tandem with several remotely operated vehicle dives, we improve on the previous National Biodiversity Assessment map for the area and reveal a more complex picture of the seabed geology and geomorphology on which the MPA is predicated. The upper slope (-120 m and deeper) is dominated by small canyons, gullies and rills that occasionally extend to the shelf edge and form a series of slumps. Suspected cold-water corals were imaged on the interfluves of the Thukela Canyon. The mid to outer shelf (-60 to -100 m) is mostly rocky, and is composed of Pliocene-age siltstones for the most part. Aeolianite shorelines are found at depths of 60 m and 100 m, in which palaeo-lagoons and parabolic aeolian dune systems are also preserved. These features provide habitat for mesophotic corals and demersal fishes. Overlying and abutting hard rock substrates are unconsolidated sandy sediments that are mobilised by the inshore movement of the Agulhas Current. An inshore mud belt characterised by pockmarks associated with free gas expulsion is mapped for the first time. A well-developed palaeo-drainage pattern is also revealed, posing exciting new opportunities for the study of benthic communities associated with palaeo-estuaries and lagoons now exposed at the seabed. Several new habitats, both inside and out of the MPA boundaries, should form the basis for future research within the MPA, in addition to informing expansions of the MPA. Significance: • Using a newly collected geophysical data set, we provide an unprecedented glimpse into the newly proclaimed uThukela Banks Marine Protected Area. • We reveal a complexity of marine habitats hitherto unknown from previous biodiversity surveys. These habitats include areas of possible expansion given the recognition of keystone species that occur just outside the MPA limits.

Category: Midfoot/Forefoot; Lesser Toes; Other Introduction/Purpose: Bio-integrative implants, uniquely designed with high mineral fiber content, were developed to encourage paced, gradual degradation while enhancing bio-integrative response. Previous publications demonstrated the safe use of these fiber-reinforced implants in both in vivo preclinical models and in clinical use. The main focus of this study was to assess the longer-term clinical outcomes and to evaluate implant bio-integration, using a newly developed Magnetic Resonance Imaging (MRI) scoring system. The device used in this study was a Proximal Interphalangeal Joint (PIPJ) fixation implant. The scoring system implemented in this study was developed based on the review of existing literature describing MRI evaluation of degradable orthopedic implants, concentrating on various local tissue reactions and the implant-to-bone interphase characteristics. Methods: Twenty-four patients were enrolled in this multicentre study, all previously treated for a single hammertoe deformity using the fiber-reinforced, bio-integrative fixation implant. Implant material is composed of continuous reinforcing mineral fibers (SiO2, Na2O, CaO, MgO, B2O3, and P2O5), bound together by a degradable polymer [poly (L-lactide-co-D,L-lactide), PLDLA]) in a 50% w/w ratio. Final study visit took place two years post-operatively. X-ray was used to assess radiographic PIPJ fusion, defined as at least 50% bridging across the osteotomy site. MRI scans were reviewed by an independent radiologist, using a newly developed bio-integration score on a scale of 0-10. The score focused on material bio-integration defined by the evaluation of implant and bone border visibility, and parameters for local tissue response; fluid accumulation, cyst formation and local bone edema. Patient Reported Outcomes of Visual Analogue Scale (VAS) for pain, were also collected. Results were analysed and compared to previously published data. Results: Radiographic PIPJ fusion rate was 96% (n=23) at the 2-year follow-up. MRI was performed and analyzed for all patients. The border between implant and surrounding bone was scored as not visible in 88% of subjects (n=21) and partially visible in remaining 12% (n=3) (100% partially visible at the 1 -year). Mild bone edema was detected in 4% (n=1) (29% at 1-year). The edema findings were not evaluated as adverse implant-related. There were no cyst formation or fluid accumulation findings. The mean bio-integration score was 9.70+-0.69 at the 2-year timepoint (7.71+-0.46 at 1-year). Patient reported outcomes showed improvement from baseline with pain score reduced to 0.04+-0.20 compared to the initial score of 5.3+-2.5 at screening. No implant-related adverse effects were reported. Conclusion: Study results provide evidence of safe bio-integration of the fiber-reinforced implants, with favourable clinical outcome at 2-years follow-up. MRI scans did not detect fluid accumulation, cyst formation or adverse implant-related edema findings. Primarily, these study results represent a first longer-term follow-up for these implants in a clinical setting. The advanced bio-integration results at 2-years corelate well with substantial degradation previously demonstrated in animal models at a similar timepoint. Proven to provide the mechanical strength and safe elimination of the material without adverse local inflammation, this technology shows promising potential to be implemented on broader applications in orthopaedic surgery.

The Cycle Nation Project (CNP) aimed to develop, test the feasibility of and optimize a multi-component individual-/social-level workplace-based intervention to increase cycling among office staff at a multinational bank (HSBC UK). To do this, we first explored barriers to cycling in a nationally-representative survey of UK adults, then undertook focus groups with bank employees to understand any context-specific barriers and ways in which these might be overcome. These activities led to identification of 10 individual-level, two social-level, and five organizational-level modifiable factors, which were mapped to candidate intervention components previously identified in a scoping review of cycling initiatives. Interviews with HSBC UK managers then explored the practicality of implementing the candidate intervention components in bank offices. The resultant pilot CNP intervention included 32 core components across six intervention functions (education, persuasion, incentivisation, training, environmental restructuring, enablement). Participants received a loan bike for 12-weeks (or their own bike serviced), and a 9-week cycle training course (condensed to 6 weeks for those already confident in basic cycling skills), including interactive information sharing activities, behavior change techniques (e.g., weekly goal setting), bike maintenance training, practical off-road cycling skill games and on-road group rides. Sessions were delivered by trained bank staff members who were experienced cyclists. The CNP pilot intervention was delivered across three sites with 68 participants. It was completed in two sites (the third site was stopped due to COVID-19) and was feasible and acceptable to both women and men and across different ethnicities. In addition, the CNP intervention was successful (at least in the short term) in increasing cycling by 3 rides/week on average, and improving perceptions of safety, vitality, confidence, and motivation to cycle. Following minor modifications, the long-term effectiveness and cost-effectiveness of the CNP intervention should be tested in a full-scale randomized controlled trial.

Summary: Background: More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods: We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings: Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation: Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Funding: Bill & Melinda Gates Foundation.

Paleocene deep-sea limestones from New Zealand contain densely packed micro-scale dissolution seams which potentially released carbon into the ocean that was previously thought to be stored, according to high-resolution multimodal X-ray microscopy.