Background: Complex bone defects are challenging to treat. Autografting is the gold standard for regenerating bone defects, however limitations include donor site morbidity and increased surgical complexity. Advancements in 3D bioprinting (3DBP) offer a promising alternative for viable bone grafts. Methods: Design of Experiments (DoE) was used to design 12 hydrogel bioinks of various Gelatin meth-acrylate/hydroxyapatite (GelMA/HA) concentrations. These bioinks were assessed for pipettability and equilibrium modulus. An optimal bioink was designed using the DoE data to produce the greatest stiffness while still being pipettable. Two bioinks, the DoE designed maximal stiff-ness and the experimentally defined maximal stiffness vs. a literature based control were then printed using a 3D bioprinter and assessed for print fidelity. The resulting hydrogels were combined with human bone-marrow-derived mesenchymal stromal cells (hMSCs) and evaluated for cell viability. Results: DoE ANOVA analysis indicated that the augmented 3 level factorial design model used was a good fit (p < 0.0001). Using the model, DoE correctly predicted that a composite hydrogel consisting of 12.3% GelMA, 15.7% HA, and 2% Gelatin would produce the maximum equilibrium modulus while still being pipettable. The hydrogel with the most optimal print fidelity was 10% GelMA, 2% HA, and 5% Gelatin. There were no significant differences in cell viability within hydrogels from day 2 to day 7 (p > 0.05). There was however a significantly lower cell viability in the gel composed of 12.3% GelMA, 15.7% HA, and 2% gelatin compared to the other gels with lower HA concentration (p < 0.05), showing that higher HA or print pressure may be cytotoxic within hydrogels. Conclusions: Extrusion-based 3DBP offers significant advantages for bone-tissue implants due to its high customizability. This study demonstrates it is possible to create printable bone-like grafts from GelMA and HA with increased HA levels, favorable mechanical properties (145kPa) and >80% cell viability.

An immune-inflammatory response is accompanied by increased nitro-oxidative stress. The aims of this mechanistic review are to review: a) the role of redox sensitive transcription factors and enzymes, ROS/RNS production and the activity of cellular antioxidants on the activation and performance of macrophages, dendritic cells, neutrophils, T cells, B cells and natural killer cells; b) the involvement of high-density lipoprotein (HDL), apolipoprotein (Apo)A1, paraoxonase (PON)-1, and oxidized phospholipids in the regulation of the immune response; and c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor (NF)-κB, HIF1alpha, the mechanistic target of rapamycin (mTor), the phosphatidylinositol 3‑kinase (PI3K) / protein kinase B (AKT) signalling pathway, mitogen-activated protein (MAP) kinases, 5' AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR). The performance and survival of individual immune cells is under redox control and sensitive to intracellular and extracellular levels of ROS/RNS and is heavily influenced by cellular anti-oxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2 (Nrf-2), and the HDL complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, those redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.

The vertebrate skeletal neuromuscular junction (NMJ) has long served as a model system for studying synapse structure, function and development. Over the last several decades a neuron-specific isoform of agrin, a heparan sulfate proteoglycan, has been identified as playing a central role in synapse formation at all vertebrate skeletal neuromuscular synapses. While agrin was initially postulated to be the inductive molecule that initiates synaptogenesis, this model has been modified in response to work showing that postsynaptic differentiation can develop in the absence of innervation, and that synapses can form in transgenic mice in which the agrin gene is ablated. In place of a unitary mechanism for neuromuscular synapse formation, studies in both mice and zebrafish have led to the proposal that two mechanisms mediate synaptogenesis, with some synapses being induced by nerve contact while others involve the incorporation of prepatterned postsynaptic structures. Moreover, the current model also proposes that agrin can serve two functions, to induce synaptogenesis and to stabilize new synapses, once these are formed. This review examines the evidence for these propositions, and concludes that it remains possible that a single molecular mechanism mediates synaptogenesis at all NMJs, and that agrin acts as a stabilizer, while its role as inducer is open to question. Moreover, if agrin does not act to initiate synaptogenesis, it follows that as yet uncharacterized molecular interactions are required to play this essential inductive role. Several alternatives to agrin for this function are suggested, including focal pericellular proteolysis and integrin signaling, but all require experimental validation.

This paper investigates calendar anomalies, volatility patterns, and the best forecasting model for predicting volatility in the cryptocurrency market, focusing on ten prominent cryptocurrencies: Binance USD, Bitcoin, Binance Coin, Cardano, Dogecoin, Ethereum, Solana, Tether, USD Coin, and Ripple. Spanning from January 2016 to December 2023, the study utilizes sophisticated statistical models such as GARCH (p,q), EGARCH (p,q), and GJR-GARCH (p,q) to analyze precise changes in market dynamics and the impact of day-of-week fluctuations on cryptocurrency returns. Empirical evidence reveals significant findings regarding the persistence of volatility, positive and negative news effects on volatility, and day-of-week effects on cryptocurrency returns. Post-COVID-19, Sunday emerges as the least volatile day for cryptocurrencies, while Thursdays and Tuesdays exhibit greater volatility. Binance, Ethereum, Dogecoin, and Tether show anomalies where returns on Tuesday and Thursday significantly differed from those on other days of the week. Many other currencies, like the USD coin, Cardano, and Ripple, show anomalies only in the pre-COVID-19 period. The findings highlight the best forecast model for volatility for each top cryptocurrency, offering practical implications for investors, traders, regulators, and policymakers. These insights emphasize the importance of understanding and addressing calendar anomalies in the cryptocurrency market for informed decision-making, trading strategies, regulatory frameworks, and market stability.

This paper investigates portfolio optimization methodologies and short-term investment strate-gies in the context of the cryptocurrency market, focusing on ten major cryptocurrencies from January 2020 to November 2023. We employ high frequency data and utilize the Kurtosis Mini-mization methodology, alongside other optimization strategies, to construct and evaluate port-folios under different rebalancing frequencies. The empirical analysis reveals that cryptocurren-cies exhibit significant volatility, skewness, and kurtosis, necessitating sophisticated portfolio management techniques. We find that the Kurtosis Minimization methodology consistently outperforms other optimization strategies, delivering optimal returns to investors, particularly in shorter-term investment horizons. We demonstrate the diversification benefits of integrating cryptocurrencies into multi-asset portfolios and emphasize the importance of regular portfolio rebalancing in the volatile cryptocurrency market. Our findings offer insights for portfolio man-agers and investors seeking to optimize their investment outcomes in the cryptocurrency market, highlighting the importance of risk management, diversification, and dynamic portfolio man-agement strategies.

Recently, the destructive impact of wildfires has proliferated; for instance, the August Complex wildfire in 2020 burned around 4% of California's landmass. This has caused increased economic damage and risk to human life. Additionally, climate change is anticipated to increase the severity of wildfires, making it imperative for accurate and efficient detection of wildfires. Machine Learning approaches allow for the automatic detection of wildfires, simultaneously prioritizing accuracy and efficiency, with minimal human intervention, thus decreasing the likelihood of increased economic damage and increasing firefighting responses. Convolutional Neural Networks (CNNs), while showing promise, are often limited by their inability to learn and capture deep spatial dependencies in satellite imagery tasks. In this paper, we propose FlameViT, a novel wildfire detection architecture based on Vision Transformers (ViT). Satellite images are more efficient to obtain and can cover wide areas prone to wildfires. We obtain a dataset of 40K+ satellite images from Canada's Open Government Portal, allowing FlameViT to be optimized to detect wildfires in satellite imagery. FlameViT uses Patch Extractor and Patch Embedding layers, followed by multiple Transformer Encoder layers with Multi-Head Self-Attention and feed-forward neural networks. FlameViT is hyperparameter-tuned and achieves a validation accuracy of 95%, outperforming various baselines in the wildfire detection task. FlameViT shows the power of Vision Transformers for wildfire detection tasks, and in conjunction with the use of satellite imagery, can provide an efficient and accurate way of detecting wildfires.

River estuaries are dynamic and complex ecosystems influenced by various natural processes, including climatic fluctuations and anthropogenic activities. The Pearl River estuary (PRE), one of the largest in China, receives significant land-based pollutants due to its proximity to densely populated areas and urban development. This study aimed to characterize the composition, diversity, and distribution patterns of sediment microbial communities (Bacteria, Archaea, and Eukaryotes) and investigated the connection with environmental parameters within the PRE and adjacent shelf. Physicochemical conditions, such as oxygen levels, nitrogen compounds, and carbon content, were analyzed. The study found that the microbial community structure was mainly influenced by site location and core depth, which together explained approximately 67% of the variation in each kingdom. Sites and core depths varied in sediment properties such as organic matter content and redox conditions, leading to distinct microbial groups associated with specific chemical properties of the sediment, notably C/N ratio and NH4+ concentration. Despite these differences, certain dominant taxonomic groups were consistently present across all sites: Gammaproteobacteria in Bacteria; Bathyarchaeia, Nitrososphaeria, and Thermoplasmata in Archaea; and SAR in Eukaryota. The community diversity index was the highest in the bacteria kingdom, while the lowest values were observed at site P03 across the three kingdoms and were significantly different from all other sites. Overall, this study underscores the critical role of microbial communities in shaping biogeochemical processes in estuarine environments and their sensitivity to environmental changes, providing valuable information for managing and preserving the health of estuaries and coastal ecosystems.

Complaint of transient impairment or loss of memory as an attendant feature in some migraine attacks has long been recognised. In some cases, migraine may be a trigger or precipitating factor for the syndrome of transient global amnesia (TGA). However, the exact frequency of this concurrence is unknown, perhaps related to the absence from the International Classification of Headache Disorders (ICHD3) of amnesia or memory loss symptoms in association with migraine, unlike the situation with epileptic seizure (migralepsy) or stroke (migrainous infarction). Similarly, headache has generally been regarded as an incidental feature of TGA, reported in about 10% of cases. We present further examples of TGA in the context of migraine headache; consider possible reasons why this concurrence might be under-recognised, such as the retrograde amnesia characteristic of TGA; review possible shared pathogenetic mechanisms; and suggest a new terminology, “migramnesia”, which may encourage clinicians to address the possible significance of migraine in the context of an episode of TGA.

Unlike electron microscopy, which can achieve very high resolutions, but to date can only be used to study static structures, time-resolved X-ray diffraction from contracting muscles can, in principle, be used to follow the molecular movements involved in force generation on a millisecond timescale albeit at moderate resolution. However, previous X-ray diffraction studies of resting muscles have come up with structures for the head arrangements in resting myosin filaments that are different from the apparently ubiquitous interacting heads motif (IHM) found by single particle analysis of electron micrographs of isolated myosin filaments from a variety of muscle types. This head organization is supposed to represent the super-relaxed state of the myosin filaments where ATP usage is minimized. Here we have tested whether the interacting heads motif structures will satisfactorily explain the observed low-angle X-ray diffraction patterns from resting vertebrate (bony fish) and invertebrate (insect flight) muscles. We find that the interacting heads motif does not, in fact, explain what is observed. Previous X-ray models fit the observations much better. We conclude that the X-ray diffraction evidence has been well interpreted in the past and that there is more than one ordered myosin head state in resting muscle. There is, therefore, no reason to question some of the previous X-ray diffraction results on myosin filaments; time-resolved X-ray diffraction should be a reliable way to follow crossbridge action in active muscle and may be one of the few ways to follow molecular changes in myosin heads on a millisecond timescale as force is actually produced.

Background. The characterization of new biomarkers of COVID-19 is extremely important. Few studies measured the soluble receptor for advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium and magnesium in COVID-19. Aims: To measure sRAGE, ACE2, interleukin (IL)-6, IL-10, CRP, calcium, magnesium, and albumin in COVID-19 patients in association with peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) including ground glass opacities. Methods. This study measured sRAGE, ACE2, IL-6, IL-10, CRP using ELISA techniques, and calcium, magnesium, and albumin using a spectrophotometric method in 60 COVID-19 patients and 30 healthy controls.Results. COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered levels of SpO2, albumin, magnesium and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients with calcium being the most important predictor followed by IL-6, and CRP. COVID-19 patients with CCTAs showed lower SpO₂ and albumin levels than those without CCTAs. SpO2 was significantly and inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium and calcium. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.Conclusion. The results show that immune-inflammatory and RAGE pathway biomarkers may be used as external validating criterion for the diagnosis COVID-19. Those pathways coupled with lowered SpO2, calcium and magnesium are drug targets that may help to reduce the consequences of COVID-19.

Background: Smoking is disproportionately prevalent among Aboriginal and Torres Strait Islander Australian peoples, with 39% of Indigenous Australians aged over 15 years smoking daily. Efforts to reduce this high prevalence include culturally focused media campaigns, designed using community consultation, highlighting the need to determine how such health messaging is received by smokers. This study aimed to examine Indigenous Australian smokers’ reactions to a culturally focused anti-smoking mass media campaign—'Give up Smokes’. Methods: Intercept surveying across health services and events used recorded demographics, smoking status, quit attempts, smoking health effects, anti-smoking campaign recall, social support, and campaign reactions. Participants rated campaign images in five domains: 1) whether it made them stop and think; 2) personal relevance; 3) believability of design and message; 4) prompting concern about smoking; and 5) motivation towards quitting. Cluster analysis was used to segment smoker types. Results: Smoking health effects knowledge was high, and did not differ by quit readiness, attempts, or social support. Cessation support access was higher among those with greater readiness to quit. Social smoking behaviour and confidence to support others quitting did not significantly differ between participants, however importance of others quitting did. Quit readiness, attempts, and social support were associated with reaction to campaign design, but not message recall. Four types of smokers were described, using smoking characteristics, who differed in campaign message reactions. Conclusions: Strategies using campaign-exposed smoker characteristics to inform culturally focused health promotion are discussed in relation to four identified types of smokers.

The Van der Pol oscillator is a chaotic non-linear system. Small perturbations in initial conditions may result in wildly different trajectories. Because of its chaotic nature, controlling, or forcing, the behavior of a Van der Pol oscillator is difficult to achieve through traditional adaptive control methods. Connecting two Van der Pol oscillators together where the output of one oscillator, the driver, drives the behavior of its partner, the responder, is a proven technique for controlling the Van der Pol oscillator. Deterministic AI (DAI) is an adaptive feedback control method that leverages the known physics of the Van der Pol system to learn optimal system parameters for the forcing function. We assessed the performance of DAI employing three different online parameter estimation algorithms. Our evaluation criteria include mean absolute error (MAE) between the target trajectory and the response oscillator trajectory over time. RLS with exponential forgetting (RLS-EF) had the lowest MAE overall, with a 2.46% reduction in error. However, another method was notable. Least Mean Squares with normalized gradient adaptation (LMS-NG) had worse initial error in the first 10% of the simulation, but after that point had consistently better performance. We found that over the last 90% of the simulation, DAI with LMS-NG had a 48.7% reduction in MAE compared to feedforward alone.

Consumer food environments have transformed dramatically in the last decade. The number of food outlets has increased, and a large proportion of the UK population now purchase food from a takeaway or restaurant at least once a week. Despite these developments, national spending on food control has reduced and many Local Authorities struggle to meet health inspection targets. This work presents a data driven approach to enhance current inspection processes with a view to reduce consumer risk of foodborne illness whilst eating outside the home. We explore the utility of three machine learning algorithms to predict non-compliant food outlets in England and Wales as defined by Food Hygiene Rating Scheme scores >= 2. Using socio-demographic, business type and urbanness features we experiment with under and over sampling strategies at five ratios to address problems of class imbalance in the dataset prior to analysis. We find that Synthetic Minority Over Sampling Technique alongside a Random Forest algorithm with a 1:1 sampling strategy provides the best predictive power. Our final model retrieves 84% of total non-compliant outlets in a test set of 92,595 (sensitivity=0.843, specificity=0.745, precision=0.274). We discuss the utility of machine learning algorithms to prioritise high risk establishments for inspection by Local Authority officials and make recommendations for weighting outcomes to improve their appropriateness in an applied setting.

COVID-19 has been extremely difficult to control. The lack of understanding of key aspects of pandemics has affected virus transmission. On the other hand, there is a demand to incorporate Computational Thinking (CT) in the curricula with applications in STEM. However, there are still no exemplars in the curriculum that apply CT to real-world problems such as controlling a pandemic or other similar global crises. In this paper, we fill this gap by proposing exemplars of CT for modeling the pandemic. We designed exemplars following the three pillars of the APEC InMside framework for CT: algorithmic thinking, computational modeling, and machine learning. For each pillar, we designed a progressive sequence of activities that covers from elementary to high school. In an experimental study with elementary and middle school students from 2 schools of high vulnerability, we found that the computational modeling exemplar can be implemented by teachers and correctly understood by students. We conclude that it is feasible to introduce the exemplars at all grade levels, and that this is a powerful example of STEM integration that helps reflect and tackle real-world and challenging public health problems of great impact for students and their families.

Google Trends data can be informative for infectious disease incidences, including Lyme disease. However, the use of Google Trends for predictive purposes is underutilized. In this study, we tested the ability of Google Trends search data to predict monthly state-level Lyme disease case counts in the United States. We requested Lyme disease data for the years 2010-2021. We downloaded Google Trends search data on terms for Lyme disease, symptoms of Lyme disease, and diseases with similar symptoms as Lyme disease. We built mixed negative binomial models based on a training dataset (2010-2016) and tested the models on a test dataset (2017-2021). A model was built for each search term and monthly lags of search terms were included as predictors. The highest performing models had high predictive ability, indicated by low Root Mean Squared Errors (RMSEs) and close association between observed and predicted case counts. The highest performing model was for the search term “Summer Flu”, which indicates low specificity of some of the terms. We outline challenges of using Google Trends data, including data availability and a mismatch between geographic units. We discuss opportunities for Google Trends data, including prediction of additional zoonotic diseases and incorporating environmental and companion animal data.

This study aims to assess using a smartphone app (DecibelX), as a noise measuring alternative to the more costly traditional use of measuring noise levels with a Sound Level Meter (SLM). The study compares the accuracy of the app to readings taken with a SLM and dosimeter, and also evaluates the app’s performance for pure tone and narrow band noise. And a usability study identifies strengths and weaknesses related to usability of the app.

Predator-prey interactions present heightened opportunities for pathogen spillover, as predators are exposed to novel parasites through consumption of prey harboring potentially infectious agents. Epizootics with high morbidity and mortality have been recorded following prey-to-predator spillover events with significant conservation implications, particularly for sensitive species. However, relatively few virulent infections following prey consumption are reported, given the very large number of exposures that presumably occur. Further, many transmitted agents are infectious but clinically silent and thus go unrecognized. Mechanisms that determine outcome of predator exposure to prey-based pathogens therefore represent an important, understudied component of disease dynamics that should be considered in modeling approaches and empirical research to better understand disease risk and emergence, particularly in vulnerable or threatened species.

This paper is a follow-up to a previous study that was conducted in a research forest and identified the optimal method for Diameter at Breast Height (DBH) estimation as a circular scanning and fitting ellipses to 4cm stem cross-sections at breast height. The aim of this study was to determine whether the identified method is applicable to natural boreal forests as well. The iPad Pro LiDAR scanner was used to acquire point clouds for 15 sites representing a range of natural boreal forest conditions in Ontario, Canada, and estimate DBH. The secondary objective was to determine if tested stand (Species composition, age, density, understory) or tree (Species, DBH) factors affected the accuracy of estimated DBH. Overall, estimated DBH values were within 1cm of actual DBH values for 78 of 133 measured trees (59%). An RMSE of 1.5cm (8.6%) was achieved. Stand age had a large effect (&gt;0.15) on the accuracy of estimated DBH values, while density, understory, and DBH had moderate effects (0.05-0.14). No trend was identified between accuracy and stand age. Accuracy improved as understory density decreased and as tree DBH increased. Inertial Measurement Unit (IMU) and positional accuracy errors with the iPad Pro scanner limit the feasibility of using this device for forest inventories.

A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water—at monthly intervals—delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s–1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (ug/L) compared to a one-time maximum measured value of 215 ug/L and exceeded the U.S. Environmental Protection Agency’s current maximum contaminant level (MCL) of 5 ug/L during the period November 1957–February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 ug/L compared to a one-time maximum measured value of 1,400 ug/L during the period August 1953–December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 ug/L) and intermittently during the period June 1972–February 1985 (maximum reconstructed TCE concentration of 66 ug/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach.

Escherichia coli phage Eco_BIFF was isolated from several laboratory stocks of E. coli K-12 MG1655 derivatives. The source of the contamination is unknown. Eco_BIFF is a lytic phage that shows effective growth inhibition of E. coli K-12. Here, we announce the complete genome sequence of Eco_BIFF, and major findings from its genome annotation.

Alignment of picornavirus proteinase/polymerase sequences reveals this family evolved into five ‘supergroups’. Interestingly, the nature of the 2A region of the picornavirus polyprotein is highly correlated with this phylogeny. Viruses within supergroup 4, the Paavivirinae, have complex 2A regions with many viruses encoding multiple 2A^NPGP sequences. In vitro transcription/translation analyses of a synthetic polyprotein comprising green fluorescent protein (GFP) linked to b-glucuronidase (GUS) via individual 2A^NPGPs showed two main phenotypes: highly active 2A^NPGP sequences - similar to Foot-and-Mouth Disease Virus 2A^NPGP and, surprisingly, a novel phenotype of some 2A^NPGP sequences which apparently terminate translation at the C-terminus of 2A^NPGP - without detectable re-initiation of downstream sequences (GUS). Probing databases with the short sequences between 2A^NPGPs did not reveal any potential ‘accessory’ functions. The novel, highly active, 2A-like sequences we identified substantially expands the toolbox for biomedical / biotechnological co-expression applications.

The United Nations Convention on the Rights of Persons with Disabilities (hereafter CRPD) has provided a radical imperative for the reform of mental health and capacity legislation around the world. The interpretation of the CRPD has been controversial, ranging from complete abolition of detention, forcible treatment and substitute decision making, to acceptance that elements of these measures need to be retained but based on non-discriminatory criteria, additional safe-guards and a comprehensive shift towards supported decision-making. While the potential ef-fects of the CRPD on mental health social work and social work generally are considerable given their shared commitment towards social justice, to date there has been no review of research evi-dence exploring their relationship. In addressing this knowledge gap, this study held a prelimi-nary discussion with practitioners and academics at the European Association of Social Work Mental Health Special Interest Group in Amsterdam 2022, followed by a scoping literature re-view on the question: What impact, if any, has the CRPD had on social work practice? The review produced four main findings: impact on legislation; positive impact on practice; limited impact on practice; and impact on social work education and research. In sum, while there were some positive indications of social work and mental health social work practice being influenced by the CRPD, these were scant. Barriers to change included tendencies among some social workers to practise substitute decision-making, in part related to resourcing and policy contexts, and under-standings of disability aligned to individualised/medical rather than social perspectives. The results indicate that legal reform on its own is insufficient to impact social work practice, and that realising the potential of the CRPD will necessitate good quality training, as well as improv-ing social workers’ knowledge of the human rights of people with mental impairment.

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to eradication failure in many cases, but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. Targeting the three EPSs secreted by P. aeruginosa (alginate, Psl and Pel) is currently under investigation as a way of disrupting the biofilm extracellular matrix to potentiate the action of antibiotics. In this review, we look at each EPS as a potential therapeutic target for combatting pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

Bone involvement occurs in 75% of patients with Gaucher disease (GD), and comprises structural changes, debilitating pain, and bone density abnormalities. Osteoporosis is a silent manifestation of GD until a pathologic fracture occurs. Thus early diagnosis is crucial for identifying high-risk patients to prevent irreversible complications. Thirty-one patients with GD were assessed prospectively to identify predictive markers associated with bone density abnormalities, osteopenia (OSN), and osteoporosis (OSR). Subjects were categorized into three cohorts based on T- or Z- scores of bone mineral density (BMD): In GD cohort with no bone complication (Z-score≥-0.9; T-scores≥-1), the OSN group (-1.8 ≥ Z-score ≥ -1; -2.5 ≥ T-score ≥ -1) and OSR group (Z-score ≤ -1.9; T-scores ≤ -2.5). Serum levels of TRAP5b, RANKL, OPG, and RANK were quantified by enzyme-linked immunosorbent assays. TRAP5b was increased in GD and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (Lyso-Gb1), macrophage activation markers CCL18 and chitotriosidase. The highest levels of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Elevation of TRAP5b, RANKL, and RANKL/OPG indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities.

Aging is a major risk factor for Alzheimer's disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood-brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models.

Schizophrenia is widely seen as a disorder of dysconnectivity. Neuroimaging studies have examined both structural and functional connectivity in the disorder, but these modalities have rarely been integrated directly. We scanned 29 patients with schizophrenia and 25 healthy control subjects and acquired resting state fMRI and diffusion tensor imaging. The Functional and Tractographic Connectivity Analysis Toolbox (FATCAT) was used to estimate functional and structural connectivity of the default mode network. Correlations between modalities were investigated, and multimodal connectivity scores (MCS) were created using principal components analysis. Nine of 28 possible region pairs showed consistent (>80%) tracts across participants. Correlations between modalities were found among those with schizophrenia for the prefrontal cortex, posterior cingulate, and lateral temporal lobes with frontal and parietal regions, consistent with frontotemporoparietal network involvement in the disorder. In patients, MCS values correlated with several aspects of the Positive and Negative Syndrome Scale, positively with those involving inwardly directed psychopathology, and negatively with those involving external psychopathology. In this preliminary sample, we found FATCAT to be a useful toolbox to directly integrate and examine connectivity between imaging modalities. A consideration of conjoint structural and functional connectivity can provide important information about the network mechanisms of schizophrenia.

The harrowing second wave of COVID-19 in India has led to much discussion over the quality and timeliness of reporting of deaths attributed to the pandemic. In this brief report, we aim to present the existing evidence, as well as the broader complexities surrounding the mortality burden of COVID-19 in India. This article sheds light on the following epidemiological issues: (1) general and India-specific challenges to COVID-19 death reporting, (2) latest COVID-19 mortality estimates in India as of May 16, 2021, (3) the apparent scale of uncaptured COVID-19 deaths, and (4) the role of disaggregated historic mortality trends in quantification of excess deaths attributed to COVID-19. We conclude with a set of high-level policy recommendations for improving the vital surveillance system and tracking of causes of death in India. We encourage direct efforts to integrate health data and indirect strategies for cross-validation of registered deaths. Such system-wide advances would drastically aid epidemiological research efforts and strengthen India’s position to overcome future public health crises.

An 18 month-old male was evaluated after presenting with disproportionate transaminitis in the setting of acute gastroenteritis. He had marked hepatomegaly on physical exam that was later confirmed with an abdominal ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation disorder was raised. Further investigation revealed that his initial newborn screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency - a rare autosomal recessive disorder of long-chain fatty acid oxidation. Confirmatory biochemical testing in the newborn period showed carnitine levels to be unexpectedly low with a normal acylcarnitine profile. Thus, it was considered to be a false-positive newborn screen and metabolic follow up was not recommended. Repeat biochemical testing during this hospitalization revealed a normal acylcarnitine profile. The only abnormalities noted were a low proportion of acylcarnitine species from plasma, an elevated free-to-total carnitine ratio, and mild hypoketotic medium chain decarboxylic aciduria on urine organic acids. Gene sequencing of CPT1A revealed a novel homozygous splice site variant that confirmed his diagnosis. CPT1A deficiency has a population founder effect in the Inuit and other Arctic groups, but has not been previously reported in persons of Ashkenazi Jewish ancestry.

Marek’s Disease (MD) has a significant impact on both the global poultry economy and animal welfare. The disease pathology can include neurological damage and tumour formation. Sexual dimorphism in immunity and known higher susceptibility of females to MD makes the chicken Z chromosome (GGZ) a particularly attractive target to study the chicken MD response. Previously, we used a Hy-Line F6 population from a full-sib advanced intercross line to map MD QTL regions (QTLRs) on all chicken autosomes. Here we mapped MD QTLRs on GGZ in the previously utilized F6 population with individual genotypes and phenotypes, and in eight elite commercial egg production lines with daughter-tested sires and selective DNA pooling (SDP). Four MD QTLRs were found from each analysis. Some of these QTLRs overlap regions from previous reports. All QTLRs were tested by indiviuals from the same eight lines used in the SDP and genotyped with markers located within and around the QTLRs. All QTLRs were confirmed. The results exemplify the complexity of MD resistance in chickens and the complex distribution of P-values and LD pattern and their effect on localization of the causative elements. Considering the fragments and interdigitated LD blocks while using LD to aid localization of causative elements, one must look beyond the insignificant markers, for possible distant markers and blocks in high LD with the significant block. The QTLRs found here may explain at least part of the gender differences in MD tolerance, and provide targets for mitigating the effects of MD.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Background: A large majority of primary school pupils fail to achieve 30-minutes in-school moderate-to-vigorous physical activity (MVPA). The aim of this study was to investigate MVPA accumulation and subject frequency during academic lesson segments and the broader segmented school day. Methods: 122 children (42.6% boys; 9.9±0.3yrs) from six primary schools in North East England, wore uniaxial accelerometers for eight consecutive days. Subject frequency was assessed by teacher diaries. Multilevel models (children nested within schools) examined significant predictors of MVPA across each school-day segment (lesson one, break, lesson two, lunch, lesson three). Results: Pupils averaged 18.33±8.34 minutes of in-school MVPA and 90.2% failed to achieve the in-school 30-minute MVPA threshold. Across all school-day segments, MVPA accumulation was typically influenced at the individual level. Lesson one and two - dominated by Math and English - were less active than lesson three. Break and lunch were the most active segments. Conclusion: This study breaks new ground, revealing MVPA accumulation and subject frequency varies greatly during different academic lessons. Morning lessons were dominated by the inactive delivery of Math and English, whereas afternoon lessons involved a greater array of subject delivery that resulted in marginally higher levels of MVPA.

The rapid integration of Generative AI technologies in academic and research environments marks the beginning of a new digital era, characterized by enhanced efficiency and innovative capabilities. This technological advancement, however, brings forth significant challenges and ethical dilemmas. One of the primary concerns is the potential diminishment of authentic human intellect in scholarly works, fueled by the capabilities of AI to generate ambiguous, fabricated, or even biased and inappropriate content. These issues highlight the critical need for developing comprehensive frameworks and establishing a dedicated field of study to govern the use of AI-generated content in academic and professional contexts. This autoethnography explores the impact of generative AI on educational practices, detailing the development of the SPARRO framework in healthcare and nursing classes. Through personal reflections, interviews, and observations, it addresses specific challenges, offering insights into integrating GenAI ethically and effectively to enhance teaching and learning.

Oscillations in global modes of variability (MoV) form global teleconnections that affect regional climate variability and modify the potential for severe and damaging weather conditions. Understanding the link between certain MoVs and regional climate can improve the ability to more accurately predict environmental conditions that impact human life and health. In this study, we explore the connection between different MoVs, including the Arctic Oscillation (AO), Eurasian teleconnection, Indian Ocean Dipole (IOD), North Atlantic Oscillation (NAO), and El Niño Southern Oscillation (Nino34), with winter and summer climate in the High Mountain Asia (HMA) region, including geopotential height at 250 hPa (z250), 2-m air temperature (T2M), total precipitation (PRECTOT), and fractional snow cover area (fSCA). Relationships are explored for the same monthly period between the MoVs and the climate variables, but also using a lagged correlation analysis to investigate whether any relationship exists at different time lags. We find that T2M has a negative correlation with the Eurasian teleconnection in the Inner Tibetan Plateau and Central China in both winter and summer and a positive correlation in Western China in summer. PRECTOT has a positive correlation with all MoV in most regions in winter, especially with the IOD, and a negative correlation in summer, especially with the Eurasian teleconnection. Snow cover in winter is positively correlated with most indices throughout many regions in HMA, likely due to wintertime precipitation also being positively correlated with most indices. Generally, the AO and NAO show similar correlation patterns with all climate variables, especially in the winter, possibly due to their oscillations being so similar. Furthermore, the AO and NAO are shown to be less significant in explaining the variation in HMA climate compared to other MoVs such as the Eurasian teleconnection. Overall, our results pinpoint different time-windows and specific regions within HMA that exhibit high correlation between climate and MoVs, which might offer additional predictability of the MoVs as well as of climate and weather patterns in HMA and throughout the globe.

histology, the processing and staining of cells, tissues and organs to highlight contrast, visualize and analyze their microstructure under microscopy, encompasses a vast array of techniques used to confirm, refine, or refute the macroscopic findings in forensic investigations, for example in the case of autopsies. This review presents several applications of histological protocols, staining methods and techniques to case studies, with the aim of illustrating the established, current and potential applications of histological investigations to forensic sciences. The list of disciplines include anthropology, cytology, dendrochronology, diatomology, entomology, fiber analysis, palynology,human and veterinary pathology, taphonomy and thanatology.

Fire-tolerant eucalypt forests of south eastern Australia are assumed to fully recover from even the most intense fires but surprisingly very few studies have quantitatively assessed that recovery. Accurate assessment of horizontal and vertical attributes of tree crowns after fire is essential to understand the fire’s legacy effects on tree growth and on forest structure. In this study, we quantitatively assessed individual tree crowns 8.5 years after a 2009 wildfire that burnt extensive areas of eucalypt forest in temperate Australia. We used airborne lidar data validated with field measurements to estimate multiple metrics that quantified the cover, density, and vertical distribution of individual-tree crowns in 51 plots of 0.05 ha in fire-tolerant eucalypt forest across four wildfire severity types (unburnt, low, moderate, high). Significant differences in the field-assessed mean height of fire scarring as a proportion of tree height, and in the proportions of trees with epicormic (stem) resprouts were consistent with the gradation in fire severity. Linear mixed-effects models indicated persistent effects of both moderate- and high-severity wildfire on tree crown architecture. Trees at high-severity sites had significantly less crown projection area and live crown width as a proportion of total crown width than those at unburnt and low-severity sites. Significant differences in lidar-based metrics (crown cover, evenness, leaf area density profiles) indicated that tree crowns at moderate- and high-severity sites were comparatively narrow and more evenly distributed down the tree stem. These conical-shaped crowns contrasted sharply with the rounded crowns of trees at unburnt and low-severity sites, and likely influenced both tree productivity and the accuracy of biomass allometric equations for nearly a decade after the fire. Our data provide a clear example of the utility of airborne lidar data for quantifying the impacts of disturbances at the scale of individual trees. Quantified effects of contrasting fire severities on the structure of resprouter tree crowns provide a strong basis for interpreting post-fire patterns in forest canopies and vegetation profiles in lidar and other remotely-sensed data at larger scales.

Background: Epithelial-mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between epithelial and mesenchymal stage is essential for tissue homeo-stasis. Many of the genes promoting mesenchymal transformation has been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify genes responsible for maintaining the epithelial phenotype and in-hibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expres-sion was determined by qPCR and Western blot analysis. Knockout of CTGF was done using the CTGF sgRNA CRISPR/CAS9. Tumorigenic potential was determined using NCG mice. Results: Knocked-out of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as Anoikis resistance, cytoskel-eton remodeling, increased cell stiffness, and acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for conserva-tion of epithelial structure and function. These findings provide a new window to understand the early stages on mesenchymal transformation

Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.

Conductive hearing losses are typically present in disorders of the external/middle ear. However, there is a rare group of inner ear conditions called third windows that can also generate a conductive hearing loss. This is due to an abnormal connection between the middle and the inner ear or between the inner ear and the cranial cavity. X-linked gusher disorder is an extremely rare congenital inner ear dysplastic syndrome with such an abnormal connection due to a characteristic incomplete cochlear partition type 3 and an incomplete internal auditory meatus fundus. The disorder is inherited in an X-linked fashion due to the mutation of the POU3F4 gene. We present 2 siblings diagnosed with the condition and their long term follow ups. They both presented with audiovestibular symptoms and showed progressive mixed losses and bilateral vestibular weakness. They were treated with cochlear implant, digital amplification and with vestibular rehabilitation. Significant others around them were involved in their journey with the medical team and in both, a very favourable outcome was achieved. This is the first time that we are reporting evolving audiovestibular function with vestibular quantification in X-linked gusher disorder and emphasize on the multidisciplinary holistic approach to manage these children effectively.

Oyster mushroom (Pleurotus ostreatus), nopal (Opuntia ficus-indica) and amaranth (Amaranthus spp.) are pre-hispanic foods widely consumed in Mexico. However, there are no standard products developed with these ingredients as functional cookies. This study evaluated the impact of partial replacement (50%) of whole-wheat flour (WWF) with three formulations of P. ostreatus, nopal and amaranth flours (POF, NF and AF, respectively) in the nutritional/antioxidant properties of fortified cookies. The proportion of flours´ ingredients (WWF:AF:NF:POF) were 100% WWF (traditional cookies), 50:35:10:5 (formulation 1), 50:30:15:5 (formulation 2) and 50:40:5:5 (formulation 3). Proximal composition, phenolic/flavonoid contents, and ABTS+ scavenging activity were determined in flours and cookies. POF, NF and AF possess a high nutritional value comprising polyphenols/flavonoids and a significant antioxidant potential. Total protein, ashes and flavonoids were higher in fortified cookies than controls. Cookies prepared with Formulation 2 -highest nopal level- contained 5.29% of dietary fiber and 5-times higher polyphenol content than control cookies. The ABTS+ scavenging ability was similar in the three enriched cookies (87.73-89.58%) but higher than traditional cookies (75.60%). Applicability of POF/NF/AF for replacing up to 50% of WWF in production of functional cookies was demonstrated. The research promotes renewable local bioresouces for a sustainable agri-food chain, especially edible mushrooms.

Factors affecting the host-virus interaction must be understood for the effective application of bacteriophages to combat bacterial pathogens. Two novel E. coli phages, the T1-like siphophage LL5 and the rV5-like myophage LL12, were subjected to forward genetic screens against the Keio collection, a library of single non-essential gene deletions in E.coli str. BW25113. These genome-wide screens and subsequent experiments identified eight genes required for efficient propagation of phage LL5 and six genes required for propagation of LL12. The majority of the genes identified were involved in production of the phage receptors. E. coli mutants deficient in heptose II and the phosphoryl substituent of heptose I of the inner core lipopolysaccharide (LPS) were unable to propagate phage LL5, as were mutants deficient in the outer membrane protein TolC. Mutants lacking glucose I of the LPS outer core failed to propagate LL12. Two cytoplasmic chaperones, PpiB and SecB, were found to be required for efficient propagation of phage LL5 but not LL12. This approach may be useful for identifying phage receptors and required host factors in other phages, which would provide valuable information for their potential use as therapeutics and for phage engineering.

For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies into shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extra ordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer.

This paper presents the theory, design, and application of a dual-branch series-diode analog pre-distortion (APD) linearizer to improve the linearity and efficiency of a K-band high power amplifier (HPA). A first-of-its-kind, frequency-dependent large-signal APD model is presented. This model is used to evaluate different phase relationships between the linear and nonlinear branches, suggesting independent gain, and phase expansion characteristics with this topology. This model is used to assess the impact of diode resistance, capacitance, and ideality factor on the APD characteristics. This feature is showcased with two similar GaAs diodes to find the best fit for the considered HPA. The selected diode is characterized and modeled between 1-26.5 GHz. A comprehensive APD design and simulation workflow is reported. Before fabrication, the simulated APD is evaluated with the measured HPA to verify linearity improvements. The APD prototype achieves a large signal bandwidth of 6 GHz with 3 dB gain expansion and 8∘ phase rotation. This linearizer is demonstrated with a 17-21 GHz GaN HPA with 41 dBm output power and 35 % efficiency. Using a wideband 750 MHz signal, this APD improves the noise power ratio (NPR) by 6.5-8.2 dB over the whole HPA bandwidth. Next, the HPA output power is swept to compare APD vs. power back off for the same NPR. APD improves the HPA output power by 1-2 W and efficiency by approximately 5-9 % at 19 GHz. This efficiency improvement decreases by only 1-2 % when including the APD post-amplifier consumption, thus suggesting overall efficiency and output power improvements with APD at K-band frequencies.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p&lt;0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p&lt;0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p&lt;0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

Zika virus (ZIKV) co-circulates with several closely related flaviviruses which exhibit similar clinical manifestations thus, clinicians rely on molecular and serological techniques for diagnosis. Cross-reactivity of patient specimens to flaviviruses is a significant impediment to serological diagnosis in areas where multiple flaviviruses co-circulate. Furthermore, patient exposure history to any of these viruses could complicate serological response patterns which could result in over and/or underdiagnosis of ZIKV infection. Three strains of ZIKV, dengue serotypes 1-4, West Nile virus, Japanese Encephalitis virus, and Yellow Fever virus were evaluated for neutralizing properties against 3 monoclonal antibodies, 4 ZIKV-naïve patients with flavivirus exposure history, 5 patients with verified ZIKV exposure and unknown flavivirus exposure history, and 5 flavivirus-naive patients with ZIKV-only exposure. Patients naïve for ZIKV exposure effectively neutralized multiple strains of ZIKV. Overall, the prototype ZIKV isolate MR-766 did not behave like the other ZIKV isolated used in this study. MR-766 was neutralized more completely by polyclonal patient serum than recent ZIKV isolates. MR-766 was neutralized better than dengue virus in ZIKV-naïve patients with prior dengue exposure. MR-766 was neutralized significantly less than recent ZIKV isolates when treated with monoclonal antibodies. The data herein show that without RT-PCR, serological diagnosis may not be possible in areas where multiple flaviviruses are endemic.

Background: Although widely believed to be safe for use in infants and children when used as directed, increasing evidence indicates that early life exposure to paracetamol (acetaminophen) may cause long-term neurodevelopmental problems. Further, recent studies in animal models demonstrate that cognitive development is exquisitely sensitive to paracetamol exposure during early development. In this study, evidence for the claim that paracetamol is safe was evaluated using a systematic literature search. Methods: Publications on PubMed between 1974 and 2017 that contained the keywords “infant” and either “paracetamol” or “acetaminophen” were considered. Of those initial 3096 papers, 218 were identified that made claims that paracetamol was safe for use with infants or children. From these 218, a total of 103 papers were identified as sources of authority for the safety claim. Results and Conclusions: A total of 52 papers contained actual experiments designed to test safety, and had a median follow-up time of 48 hours. None monitored neurodevelopment. Further, no trial considered total exposure to drug since birth, eliminating the possibility that the effects of drug exposure on long-term neurodevelopment could be accurately assessed. On the other hand, abundant and sufficient evidence was found to conclude that paracetamol does not induce acute liver damage in babies or children when used as directed.

To date, recanalization interventions are the only available treatments for ischemic stroke patients, however, there are no effective therapies for reducing stroke-induced neuroinflammation. We recently reported that H+ extrusion protein Na+/H+ exchanger-1 (NHE1) plays an important role in stroke-induced inflammation and white matter injury. In this study, we tested the efficacy of two potent NHE1 inhibitors, HOE642 and Rimeporide, with a delayed administration regimen starting at 24 h post-stroke in adult C57BL/6J mice. Post-stroke HOE642 and Rimeporide treatments accelerated motor and cognitive function recovery without affecting the initial ischemic infarct, neuronal damage or reactive astrogliosis. However, delayed administration of NHE1 blockers after ischemic stroke significantly reduced microglial inflammatory activation while enhanced oligodendrogenesis and white matter myelination, with increased proliferation and decreased apoptosis of the oligodendrocytes. Our findings suggest that NHE1 protein plays an important role in microglia-mediated inflammation and white matter damage. Pharmacological blockade of NHE1 protein activity reduced microglia inflammatory responses and enhanced oligodendrogenesis and white matter repair, leading to motor and cognitive function recovery after stroke. Our study reveals the potential of targeting NHE1 protein as therapeutic strategy for ischemic stroke therapy.

Evidence that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible children has mounted for more than a decade. Evidence is diverse, including extensive work with laboratory animals, otherwise unexplained associations, factors associated with the metabolism of acetaminophen, and some limited studies in humans. Although evidence has reached an overwhelming level and has been reviewed in detail recently, some controversy remains. In this narrative review, some of those controversies are evaluated. First, the associations through time between acetaminophen use and the prevalence of neurodevelopmental disorders are considered. A systematic review reveals that the use of acetaminophen in the pediatric population was never tracked carefully, but historical events that affected use of the drug were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Second, problems with exclusive reliance on results from meta-analyses of large datasets and from studies involving small time frames of drug exposure are reviewed. Third, the potential bias in a study designed to separate the role of vaccines and acetaminophen in the induction of autism spectrum disorder (Autism 2008;12:293-307) is carefully evaluated. Finally, evidence demonstrating why some children are susceptible to acetaminophen-induced neurodevelopmental injury is examined. It is concluded that, at least among the factors considered, there is no valid rationale for controversy regarding the conclusion that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible babies and small children.

This investigation pioneers an examination of the scarcely explored terrain of social diversity in medical education, assessing the complex impacts of socioeconomic status (SES), prior working experiences, and completed apprenticeships on a spectrum of psychological and academic facets among first-year medical students (n = 336) in an urban university setting. By utilizing a systematic and detailed approach, the study illuminates prior anatomical knowledge and various psycholog-ical constructs, marking a significant stride into a domain where knowledge remains profoundly limited. Analyses indicated that SES significantly affects financial anxiety (F(4, 331) = 17.391, p < .001) and academic behavioral confidence (F(4, 331) = 4.323, p = 0.002). Students with prior working experience reported higher self-perceived clinical experience but lower A-level grades (t(279.459) = -6.690, p < .001), competence in natural sciences (t(321.045) = -3.178, p = 0.002), and online competence (t(319.429) = -2.026, p = 0.044). Those who completed an apprenticeship showed higher resilience, academic confidence, self-efficacy, and greater concerns about balancing studies and work (t values ranging from 2.020 to 3.158, p < 0.05). Correlation analysis revealed a positive relationship between resilience (RQS) and coping with academic stress (CAS) (r = 0.632, p < .001), as well as between resilience and academic behavioral confidence (ABC) (r = 0.608, p < .001). Negative correlations were observed between resilience, coping with academic stress, academic confidence, and cognitive test anxiety (CTA) (r values from -0.235 to -0.404, p < .001). The findings emphasize the need for tailored support for students from diverse SES backgrounds and with varying expe-riences. The study highlights the value of a comprehensive approach in medical education, con-sidering the diverse backgrounds and experiences of students. Future research should explore the long-term impact of these factors on professional competencies and patient care, leveraging the diversity of the student body for a holistic educational experience.

Topoisomerases, common targets for anti-tumor therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effect of thiosemicarbazones (TSC) and metal-TSC complexes has been demonstrated by targeting several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases.

(1) Background: Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. (2) Methods: To elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. (3) Results: We found PKD1 renal cysts displayed the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. (4) Conclusions: These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.

There is significant lack of information on the presence of plant pathogens in aquifer, increasingly used for irrigation during last decades and considered mostly free of them. In this work, we report the presence of bacteria from the Pseudomonas syringae complex (referred as PsyC) including phytopathogenic bacteria, in groundwater of Avignon, France. Their concentration was variable and inversely correlated with water electrical conductivity. Their mean abundance were hundred times lower than in the river Durance, connected with the aquifer but surprisingly, their genetic structure were more homogeneous. Moreover, most strains (97 %) from groundwater were tested as potentially pathogenic on plants, when in the river they were only 71 %. Determinants of this low diversity and high aggressiveness remain to be identified. We conclude that aquifers must be considered potential plant pathogenic reservoirs even if more surveys are needed to understand the real impact on crops during irrigation. These results could be included in prediction models and new approaches to disease forecasting and surveillance and could lead to adaptation of agricultural practices.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs known as SINE-VNTR-Alu (SVA) demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), however the exact mechanism has yet to be identified. In this study we used whole genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Center ALS Consortium, to elucidate the influence of reference SVA elements on gene expression genome-wide within central nervous system (CNS) tissues. To investigate this, we applied matrix expression quantitative trait loci analysis and demonstrated that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position, and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative disease. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

Surfing is a growing, high participation recreational and competitive activity. It is relatively unique being performed on, in, and through water with a range of temperatures. In other sports, warm-up and heat retention have proved useful at augmenting performance and ameliorating injury risk. Little work has been done examining this in surfing. The purpose of this work was to measure thermal profiles in surfers with and without warm-up and passive heat retention, and secondarily to assess any potential influence on free surfing. A repeated measures pre- and post- design was adopted whereby participants surfed in an artificial wave pool following an active warm-up combined with passive heat retention (experimental condition), and after no warm-up (control). Core body temperature was measured both occasions. Our results showed a clear advantage to body temperature for the experimental condition versus control. Both groups showed a warm-up effect in the water itself, presumably due to further activity (e.g. paddling) and wetsuit properties. Finally, performance trended to being superior following warm-up. We conclude, body warmth in surfers may be facilitated by an active warm-up and passive heat retention. In free surfing this is associated with a trend towards better performance; it may also reduce injury risk.

In vitro glucose uptake in yeast cell facilitated by Abelmoschus esculentus L. (okra seed) for management of type 2 diabetes was studied. Plant material was collected, identified, processed, and stored for further use. 80% methanol was employed for extraction and sonicated to release antidiabetic-bioactive component in solution and was filtered, concentrated, freeze-dried, and fractionated using standard techniques. Glucose uptake at an initial concentration of 5mM/L and 10mM/L by the crude extract was consistent to that of the known standard drug while at 25mM/L glucose concentration was equivalent with the crude extract. Also, at 0.625 mg/mL the linear equations, and R2 demonstrations that the crude extract was higher in dose predictability than the standard drug as presented by the equation; y = 35.754x - 57.822, and R² = 0.9502 (95%). The extract-fractions were employed to evaluate the ability of yeast cell line culture to take up glucose from the system through DPPH, FRAP, lipid peroxidation and anti-diabetes effect of extract-fraction assays. Extract-fractions were found to poses antioxidant activity high enough to inhibit stress-related diseases. The extract fractions were active as drug candidates both at low and high concentrations and were better compared with the standard drug and standard antioxidant was comparable. The high bioactive extract fractions require encapsulation with a nanoparticle as a drug candidate for type 2 diabetes patients. And an animal trial of the drug candidate may be necessary to monitor the in vivo performances of the extract fractions and subsequent human volunteered trial.

Plant breeding is central to agriculture, and shifts in plant breeding practices (e.g., hybrid development) and selection goals (e.g., response to synthetic fertilizer) have catalyzed monumental and persistent changes in agricultural production systems of all scales with social, political, economic, and environmental repercussions. While plant breeders are largely trained in the sciences of biology, genetics, and statistics, we posit an ethical imperative to examine the degree of equity with which the benefits of new research and plant varieties are distributed. In the United States, the history of plant breeding parallels the colonial history of agriculture, which compels reflection by current plant breeders about their role in shaping our agricultural system. In this perspective essay, we examine longstanding ideas about equitable food systems through the lens of public plant breeding in the United States. We propose a framework for equitable public plant breeding with respect to both its process and outcomes, and we intend for the ideas presented herein to catalyze reflection, discussions, and actions as the plant breeding community seeks greater equity in the food and seed systems our work supports.

The requirement for developing tools capable of detecting and monitoring heavy metals (HMs) has recently taken on more significance due to worries about their toxic effect on human health and aquatic habitats. In this study, a simple electrochemical sensing carbon paste electrode (CPE) based on composite of Zinc/Iron layered double hydroxide (LDH) and polyaniline (PANI) was developed for the determination of lead ions in aquatic solutions. For this purpose, Zn-Fe LDH/PANI was prepared and characterized by Fourier transform infrared (FTIR), X ray diffraction (XRD), and scanning electron microscopy (SEM). Modified carbon electrode based Zn-Fe LDH/PANI was electrochemically characterized compared with unmodified electrode in FCN as a redox probe using cyclic voltammetry (CV). Thus, Zn-Fe LDH/PANI was utilized as sensing material for the electrochemical determination of lead ions using differential pulse voltammetry (DPV). Zn-Fe LDH/PANI/CPE show limits of detection (LOD) and quantification (LOQ) of 167.8 nM and 559.4 nM, respectively. Zn/Mg/Fe LDH was prepared using co-precipitation method and characterized by XRD, FTIR, SEM and BET, used for removal of Pb+2 ions. Removal process was investigated at different conditions as pH, metal ion concentrations, starting adsorbent dose at first and contact time. Zn/Mg/Fe LDH was evaluated as an effective adsorbent material for lead ions elimination in aquatic solutions, with capacity of adsorption 700 mg/g. The elimination of lead ions on Zn/Mg/Fe LDH fitted the pseudo first-order kinetics model and the isotherm was matched with Langmuir model. Studies revealed that the ideal removal conditions were pH = 5.0, an adsorbent mass of 0.05 g, and 20 ml of 50 ppm metal ion concentration at 60 min. The Zn-Fe LDH/PANI composite also showed potential anti-cancer properties against lung cancer cells (A549) while maintaining safety for normal lung fibroblast cells (WI-38). Collectively, advancements in electrochemical sensors offer promising solutions for lead ion detection, with wide-reaching applications in wastewater treatment and cytotoxicity assessment. These innovations have the potential to enhance environmental monitoring and public health safety.

Increasing evidence points to the role of endogenous retroviruses (ERVs) in driving cancer cell proliferation. The purpose of this study was to explore the possibility of repurposing antiretroviral agents to inhibit ERVs as a new approach in cancer treatment. We found that an integrase strand-transfer inhibitor, dolutegravir (DTG), effectively inhibited the proliferation of multiple cancer cell lines and its antiproliferative potency was positively correlated with the expression levels of the human endogenous retrovirus type K (HERV-K). DTG inhibited the expression of HERV-K in multiple human cancer cell lines and the mouse mammary tumor virus (MMTV) in the murine 4T1 mammary cancer cell line. We chose the fast-growing BT-20 cell line as a model to study the in vitro antiproliferative mechanisms of DTG. BT-20 cells overexpressing both HERV-K env and pol genes became more resistant to DTG than cells transduced with vector alone. Knockdown of HERV-K also increased DTG resistance of BT-20 cells. The antiproliferative effect of DTG correlated with enhanced expression of E-cadherin and reduction in cell motility and invasiveness. Surprisingly, DTG stimulated expression of the env gene of MMTV in vivo and promoted metastasis of 4T1 tumor cells to the lungs. Taken together, our data support a role of ERVs in tumor development and encourage further search for antiretroviral agents to treat malignancies in which endogenous retroviruses are active.

Understanding whether the long-term follow-up (LTFU) system is working for families is critical to measuring the success of newborn screening (NBS) and understanding why some families are lost to follow-up. Caregivers were recruited from six pediatric specialty care clinics. Data was gathered from caregivers via six focus groups (n=24) and open-ended responses on a survey (n=33). Caregiver participants represented a wide range of NBS-related conditions and children’s ages. While this is not the first study to gather caregivers’ input, it is unique in its breadth of perspectives (e.g., metabolic, endocrine, hemoglobinopathy, etc.) and its focus on LTFU. When asked about goals for their children, caregivers identified health-related goals (i.e., ability for children to care for themselves, not being hindered by diagnosis) and non-health related goals (i.e., defining themselves outside of disease, participating in sports, making friends). In qualifying the LTFU care they want and need for their child and the key factors that influence access and engagement, caregivers identified three themes: communication and relationships with providers; care team roles and factors; and care access and utilization factors. The themes identified are not disjoint; they are intertwined and collectively illustrate the lived experiences of families at the epicenter of LTFU care.

More than 20 lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations previously indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in-silico methods to create an ideal (virtual) population of 120000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal data set shows little to no risk of acetaminophen use if cofactors which create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors which impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD.

Individuals with Parkinson’s Disease (PD) are at an increased risk of falls due to associated motor symptoms and impaired postural control. Gait dysfunction, observed soon after diagnosis, leads to disability with disease progression. The purpose of this study was to determine if there were differences in dynamic postural control during self-paced walking and obstacle-crossing between persons with mild to moderate PD and healthy controls. Participants included nine individuals with mild to moderate PD (PD cohort) and nine age- and gender-matched controls (CON cohort). Anatomical marker trajectories and ground reaction forces were collected as participants walked along the pathway. Three successful representative right and left gait cycles were analyzed using Visual3D biomechanical software. Analyses, involving a mixed model ANOVA using R Statistical Software, examined spatiotemporal (ST) gait parameters for strides involving the leading and trailing limbs and dynamic balance variables, including COM - COP inclination angle, and the COP - COM M/L, COP - XCOM M/L, UMAX - XCOM M/L distances, at distinct points from the stance limb related to the leading and trailing legs. There were no differences between CON and PD for all ST gait parameters during obstacle crossing, except for a significantly reduced step length (p = 0.00489) for the PD group related to the trailing limb. However, there were significant main effects of Step and Condition interacting with Step for swing time, stance time, and step length. For both CON and PD groups the COP - COM , COP - XCOM , UMAX - XCOM metrics demonstrated that the COM was medial to the BOS from first double support, generally moving more medially through second double support for the stance limb during motion of the leading and trailing limbs. Event and Event interacting with Condition were significant for the COP - COM and COP - XCOM variables, while UMAX – XCOM was significant only for Event (p < 0.001). The PD group demonstrated significantly larger mean values for COP – COM M/L at first double support (p = 0.00435) and COP - XCOM M/L at second double support (p = 0.0158) for the second step. Our results suggest that the margin of stability may be useful in discerning dynamic postural control adaptations during walking and obstacle negotiation in persons with mild PD.

Biobanks linked to electronic health records provide a rich data resource for health-related research. With the establishment of large-scale infrastructure, the availability and utility of data from biobanks has dramatically increased over time. As more researchers become interested in using biobank data to explore a diverse spectrum of scientific questions, resources guiding the data access, design, and analysis of biobank-based studies will be crucial. The first aim of this review is to characterize the types of biobanks that are discussed in the recent literature and provide detailed descriptions of specific biobanks including their location, size, data access, data linkages and more. The development and accessibility of large-scale biorepositories provide the opportunity to accelerate agnostic searches, new discoveries, and hypothesis-generating studies of disease-treatment, disease-exposure and disease-gene associations. Rather than spending time and money designing and implementing a single study with pre-defined objectives, researchers can use biobanks’ existing data-rich resources to answer scientific questions as quickly as they can analyze them. While the data are becoming increasingly available, additional thought is needed to address issues related to the design of such studies and analysis of these data. In the second aim of this review, we discuss statistical issues related to biobank research in general including study design, sampling strategy, phenotype identification, and missing data. These issues are illustrated using data from the Michigan Genomics Initiative, UK Biobank, and Genes for Good. We summarize the current body of statistical literature aimed at addressing some of these challenges and discuss some of the standing open problems in this area. This work serves to complement and extend recent reviews about biobank-based research and aims to provide a resource catalog with statistical and practical guidance to researchers pursuing biobank-based research.

Understanding surfactant self-assembly in deep eutectic solvents (DES) is important to their potential use in industrial formulations. We have recently reported the formation of a fracto-eutectogel comprising SDS fractal aggregates at a concentration as low as 1.6 wt% in glyceline (a DES comprising glycerol and choline chloride) at room temperature. The building units of the fractals consisted of multilayers of self-assembled SDS lamellae arranged in a dendritic pattern. Here we report that this fractal phase transitions into a fluid phase above a critical gelation temperature, TCG ~ 45 oC, evident from polarized light microscopy (PLM) observations. Small-angle neutron scattering (SANS) reveals that this phase transition is underpinned by the nanoscopic morphological transformation of the SDS lamellae into cylindrical micelles at T &gt; TGC. Fitting SANS profiles confirms that the morphology of the micelles is SDS-concentration (cSDS) dependent at T &gt; TGC: cylindrical at cSDS &gt; 0.6 wt% and spherical at cSDS = 0.6 wt%. At cSDS &lt; 0.6 wt%, only isotropic scattering was observed in the SANS profiles. Such SDS self-assembly behaviors contrast with those we have previously observed in glycerol, which we attribute to the presence of ions (i.e. choline chloride) in glyceline. Our findings have general implications to surfactant self-assembly in DES, solvents that are rich in hydrogen bonding and ions.

Little research has been done on occupational health ramifications of informal electronic waste (e-waste) recycling work, which is increasingly common in low- and middle-income countries, and very little is known about this in high-income countries. Our study evaluated informal and formal e-waste recycling workers in Chile, which was recently recognized as a high-income country. In 2017 we recruited 78 informal recycling workers from two cities, and 15 formal e-waste recycling workers from one recycling facility. Participants completed a questionnaire and health assessment regarding their involvement in, and potential impacts of, e-waste recycling, among other measures. Participants were primarily male, middle-aged, married with children, and had worked in e-waste recycling for an average of 12 years. Participants generally reported good health status, and chronic disease prevalence was similar to the national prevalence. Workers commonly reported exposures to several occupational stressors, including mental health stressors and noise, as well as insufficient income. Occupational injuries were common and use of safety equipment was low. No significant differences were found between informal and formal workers. Informal e-waste workers in Chile face occupational health challenges. The extent to which these issues impact the health of informal Chilean e-waste workers is unclear and warrants further research.

A growing body of literature suggests a causative relationship between severe adverse neurological outcomes and early life exposure to paracetamol (acetaminophen) in the presence of oxidative stress. Review of the literature revealed that, although its use is not regularly monitored, paracetamol has achieved near universal acceptance, with exposure in some pediatric populations exceeding 90%. In addition, use of the drug as well as associated adverse outcomes may have risen as a result of pharmaceutical advertising rather than need, and inappropriate use of the drug, both in terms of dose and indication, is widespread. These findings indicate that many clinicians and patients do not, at the present time, evenly weigh the potential risks with the potential benefits of paracetamol exposure early in life. Although retrospective studies might be envisioned to further address the neurodevelopmental risks of paracetamol use during early development, in silico simulations demonstrated that such studies can be thwarted by very high rates of use of the drug combined with associations between paracetamol use and oxidative stressors that act as cofactors in the induction of neurodevelopmental injury. These findings suggest that, despite persistent uncertainty, clinicians and patients should be more aware of available information pointing toward the potential dangers for neurodevelopment of early life exposure to paracetamol. Most importantly, health care workers need to provide a more balanced view, weighing both risks and benefits, when providing advice for patients regarding paracetamol use during periods of brain development.

Studies have shown that vehicle trajectory data are effective for calibrating microsimulation mod-els. Light Detection and Ranging (LiDAR) technology offers high-resolution 3-D data, allowing for detailed mapping of the surrounding environment, including road geometry, roadside infrastruc-tures, and moving objects such as vehicles, cyclists, and pedestrians. This research presents a comprehensive framework for integrating LiDAR sensor data into simulation models and accu-rately calibrating for proactive safety analysis. Vehicle trajectory data were extracted from LiDAR point cloud collected at six urban signalized intersections in Lubbock, Texas in USA. Each study intersection was modelled with PTV VISSIM and calibrated to replicate the observed field scenarios. The Directed Brute Force method was used to calibrate two car-following and two lane-change parameters of Wiedemann 1999 model in VISSIM, resulting in an average accuracy of 92.7%. Rear-end conflicts extracted from the calibrated models combined with a ten-year historical crash dataset were fitted into a Negative Binomial (NB) model to estimate the model's parameters. In all the six intersections, rear-end conflict count is a statistically significant predictor (p-value < 0.05) of observed rear-end crash frequency. The outcome of this study provides a framework for the com-bined use of LiDAR-based vehicle trajectory data, microsimulation and surrogate safety assessment tools to transportation professionals for proactive safety evaluation.

Background and Objectives: The IPED study showed that a smartphone-based event recorder increased the number of patients in whom an ECG was captured during symptoms over five-fold to more than 55% at 90 days compared to standard care [1] and concluded that this safe, non-invasive and easy to use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. This study reports the process of establishing a smartphone palpitation and pre-syncope service. Materials and Methods: A clinical Standard Operating Procedure (SOP) was devised, and funding was secured through a business case for the purchase of 40 AliveCor devices in the first instance. The clinic was launched on 22nd July 2019. Results: Between 22nd July 2019 and 31st October 2019, 68 patients seen in the ED with palpitations or pre-syncope were referred to SPACC. 30 were male and 38 female and mean age was 45.8 (SD 15.1) with a range from 18 to 80 years. 50 (74%) patients underwent full investigation. 7 (11%) patients were deemed on first assessment to have non-cardiac palpitations and were not fitted with the device. All patients who underwent full investigation achieved symptomatic rhythm correlation most with sinus rhythm, ventricular ectopics or bigeminy. A symptomatic cardiac dysrhythmia was detected in 6 (8.8%) patients. 3 patients had supraventricular tachycardia; SVT (4%), 2 had atrial fibrillation (3%) and 1 atrial flutter (2%). Qualitative feedback from the SPACC team suggested several areas where improvement to the clinic could be made. Conclusion: We believe a smartphone palpitation service based in ambulatory care is simple to implement and is effective at detecting cardiac dysrhythmia in ED palpitation patients.

Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ERBB4 is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples. Using immunohistochemistry, we characterized the localization of total and phosphorylated ERBB4 (p-ERBB4) and EGFR protein in archived GBM samples and assessed their association with patient survival. Furthermore, we evaluated the effect of ERBB4 phosphorylation on angiogenesis and tumorigenicity in GBM xenograft models. Total ERBB4 mRNA was significantly lower in GBM than NNB samples, with the JM-a and CYT-2 variants predominating. ERBB4 protein was ubiquitously expressed in GBM but was not associated with patient survival. However, high p-ERBB4 in 11% of archived GBM samples, independent of p-EGFR, was associated with shorter patient survival (12.0±3.2 months) than was no p-ERBB4 (22.5±9.5 months). Increased ERBB4 activation was also associated with increased proliferation, angiogenesis, tumorigenicity and reduced sensitivity to anti-EGFR treatment in xenograft models. Despite low ERBB4 mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.

Background: Handheld cameras may increase access to teleretinal diabetic retinopathy screenings (TDRS), as they are more economical and nimbler than traditional desktop cameras. However, their use in safety-net clinical settings is less understood. Methods: The Los Angeles County Department of Public Health collaborated with the Los Angeles County Department of Health Services (DHS) to pilot the use of handheld cameras in DHS’s TDRS program. This study assessed screening metrics and interviewed TDRS coordinators and photographers about their experiences using these cameras. Results: Handheld cameras are harder to operate and performed less optimally on key screening metrics (e.g., image quality) compared to desktop cameras. However, this challenge appeared to be linked to the selected model, rather than to all handheld cameras. The adoption of handheld cameras in DHS was aided by their integration into an existing agency infrastructure that already supports the use of desktop cameras; these operational supports include an established workflow, a data platform, and experienced photographers. Conclusions: The use of handheld cameras for TDRS is a promising practice for assuring equitable access to screenings. Handheld cameras are portable, smaller in size, and lower in cost than desktop cameras. Future projects should invest in and assess the performance of higher-quality models of these cameras, especially their use in safety-net clinical settings.

HIV-associated neurocognitive disorders (HAND) persist despite the advent of antiretroviral therapy (ART), suggesting underlying systemic and central nervous system (CNS) inflammatory mechanisms. The endogenous cannabinoid receptors 1 and 2 (CB1 and CB2) modulate inflammatory gene expression and play an important role in maintaining neuronal homeostasis. Cannabis use is disproportionately high among people with HIV (PWH) and may provide a neuroprotective effect for those on ART due to its anti-inflammatory properties. However, expression profiles of CB1 and CB2 in the brains of PWH on ART with HAND have not been reported. In this study, biochemical and immunohistochemical analyses were performed to determine CB1 and CB2 expression in brain specimens of HAND donors. Immunoblot revealed CB1 and CB2 were differentially expressed in frontal cortices from HAND brains compared to neurocognitively unimpaired (NUI) brains from PWH. CB1 expression levels negatively correlated with memory and information processing speed. CB1 was primarily localized to neuronal soma in HAND brains versus a more punctate distribution on neuronal processes of NUI brains. CB1 expression was increased in cells with glial morphology and showed increased colocalization with an astroglial marker. These results suggest that targeting the endocannabinoid system may be a potential therapeutic strategy for HAND.

Gut protozoan parasites are neglected and not targeted by specific control initiatives and this have led to a knowledge gap concerning their regional diversity and epidemiology. The present study aims to explore Giardia duodenalis genetic diversity and assess the epidemiologic scenario of subclinical infections in different Brazilian biogeographic regions. Cross-sectional surveys (n=1,334 subjects) were conducted in the Amazon, Cerrado, Semiarid and Atlantic Forest. Microscopy of non-diarrheal feces and nucleotide sequencing of a β-giardin gene fragment were performed. Twenty-seven (52.9%) β-giardin sequences were characterized as assemblage A and 24 (47.1%) as assemblage B. In Amazon, assemblage B was the most frequently detected with 2 novel sub-assemblages. Assemblage A predominated in the extra-Amazon region, with 5 novel sub-assemblages. Prevalence rates reached 17.8% in Amazon, 8.8% in Atlantic Forest, 7.4% in Cerrado and 2.3% in the Semiarid. People living in poverty and extreme poverty presented significantly higher positivity rates, reaching 11.9% and 14.5%, respectively. Giardiasis tended to be more frequent in stunted (21.6%) than in eutrophic children (12.9%). In conclusion, subclinical giardiasis in endemic in Brazilian communities in different biogeographic regions, presenting high genetic diversity and a heterogeneous genotypic distribution.

During 2021 and 2022 summers, we measured the total and dissolved (&lt; 0.45 mm) concentration of 25 elements in Utah Lake using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Utah regulates twelve of these elements. ICP-OES sensitivity is at the ppb-level but is not the approved regulatory method. All regulations are for dissolved concentrations; except aluminum (Al) and phosphorus (P) which are for total recovery. We found total Al concentrations above allowable, but dissolved concentrations were well below allowable concentrations. We attribute high total concentrations to suspended clays. Dissolved copper (Cu) concentrations were below regulatory levels in 2021, but some samples were above regulatory levels in 2022. This could be related to the use of Cu-based algaecide treatments, or from other sources. Lead (Pb) data were inconclusive; dissolved Pb concentrations were well below the acute (1-hour average) limit, but the chronic concentration limit (4-hour average) is below the ICP-OES minimal detection limit. Arsenic (As) concentrations exhibit a seasonal trend that we attribute to groundwater inflows. This ppb-level study provides insight into regulated elements in Utah Lake previously not available due to the high sensitivity of the method and measurements of both total and dissolved concentrations.

Management of sarcomas in specialist centers delivers significant benefits. In much of the world specialists are not available and development of expertise is identified as a major need. However the terms ‘specialist’ or ‘expert’ center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term ‘Sarcoma Intelligent Specialist Network’ to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement.

myfood24 is a comprehensive self-completed online 24-hour dietary recall tool currently used for nutritional assessments in epidemiological research. However, its clinical application has been unexplored. This mixed methods prospective observational study explores the acceptability and usability of myfood24 in a clinical population, women with gestational diabetes (GDM). Women were recruited at their first diabetes antenatal clinic appointment. To assess acceptability and usability, they were asked to complete five 24-hour dietary recalls using myfood24 over two weeks and a user experience questionnaire; with a subset invited to participate in a one-to-one semi-structured interview. Of the 199 participants, mean maternal age was 33 years, mean booking BMI 29.7kg/m2, 36% primiparous, 57% White, 33% Asian. Of these 121 (61%) completed myfood24 at least once and 73 (37%) completed the user questionnaire; 15 were interviewed. Usability of myfood24 was measured using the System Usability Scale (SUS) and found to be good (mean 70.9, 95%CI 67.1, 74.6). Interviews identified several areas for improvement, including optimising its use for mobile devices. myfood24 appears to be acceptable and have potential to support self-management and behaviour change for women with GDM but requires adaptation to record blood glucose results alongside real-time tracking of diet.

Importance: The rapidly expanding 2019 novel coronavirus pandemic (COVID-19, caused by the SARS-CoV-2 virus) has challenged the medical community to an unprecedented degree. Physicians and healthcare workers are at added risk of exposure and infection during the course of the patient care. Due to the rapid spread of this disease through respiratory droplets, healthcare providers such as otolaryngologists-head & neck surgeons who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures are particularly at risk. Here we present a set of safety recommendations based on our review of literature and communications with physicians with first-hand knowledge of safety procedures during the 2019 COVID-19 pandemic.Observations: A high number of healthcare providers were infected during the first phase of the pandemic in Wuhan province. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for healthcare providers without jeopardizing the care of patients. We reviewed the most common procedures related to the examination and treatment of upper aerodigestive tract diseases. Each category was reviewed based on the potential risk imposed to healthcare workers. Specific recommendations were made, based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in COVID-19 patients. Conclusions and Relevance: Preserving highly skilled healthcare work force is a top priority for any community and healthcare system. Based on the experience of healthcare systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of healthcare providers could be significantly reduced, while providing high levels of care. The provided recommendations could be used as broad guidance for all healthcare workers who are involved with the care of COVID-19 patients.

Background: The role played by the non-dominant parietal lobe in motor cognition, attention and spatial awareness networks has potentiated the use of awake surgery. When this is not feasible, asleep monitoring and mapping techniques should be used to achieve an onco-functional balance. Objective: This study aims to assess the feasibility of a dual-strip method to obtain direct cortical stimulation for continuous real-time cortical monitoring and subcortical mapping of motor and visual pathways simultaneously in parietal lobe tumour surgery. Methods: Single-centre prospective study between May’19-November’20 of patients with intrinsic non-dominant parietal-lobe tumours. Two subdural strips were used to simultaneously map and monitor motor and visual pathways. Results: Fifteen patients were included. With regards to motor function, a large proportion of patients had abnormal interhemispheric resting motor threshold ratio (iRMTr) (71.4%), abnormal Cortical Excitability Score (CES) (85.7%), close distance to the corticospinal tract – Lesion-To-Tract Distance (LTD) – 4.2mm, Cavity-To-Tract Distance (CTD) – 7mm and intraoperative subcortical distance - 6.4mm. Concerning visual function, the LTD and CTD for optic radiations (OR) were 0.5mm and 3.4mm, respectively; the mean intensity for positive subcortical stimulation of OR was 12mA±2.3mA and 5/6 patients with deterioration of VEPs>50% had persistent hemianopia and transgression of ORs. 12 patients remained stable, one patient had a de-novo transitory hemiparesis, and two showed improvements in motor symptoms. A higher iRMTr for lower limbs was related with a worse motor outcome (p=0.013) and a longer CTD to OR was directly related with a better visual outcome (p=0.041). At 2 weeks after hospital discharge, all patients were ambulatory at home and all proceeded to have oncological treatment. Conclusion: We propose motor and visual function boundaries for asleep surgery of intrinsic non-dominant parietal tumours. Pre-operative abnormal cortical excitability of the motor cortex, deterioration of the VEP recordings and CTD<2mm from the OR were related to poorer outcomes.

Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium, Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative real-time PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly protective scrub typhus vaccine.

Abstract: The genus Acaryochloris is unique among phototrophic organisms due to the dominance of chlorophyll d in its photosynthetic reaction centres and light-harvesting proteins. This allows Acaryochloris to capture light energy for photosynthesis over an extended spectrum of up to ~760 nm in the near infra-red (NIR) spectrum. Acaryochloris sp. has been reported in a variety of ecological niches, ranging from polar to tropical shallow aquatic sites. Here, we report a new Acarychloris strain isolated from an NIR-enriched stratified microbial layer 4-6 mm under the surface of stromatolite mats located in the Hamelin Pool of Shark Bay, Western Australia. Pigment analysis, by traditional spectrometry/fluorometry, flow cytometry and spectral confocal microscopy identify unique patterns in pigment distribution that likely reflect niche adaption. For example, unlike the original A. marina species (type strain MBIC11017), this new strain, Acarychloris LARK001, shows little change in the chlorophyll d/a ratio in response to changes in light wavelength, displays a different Fv/Fm response and lacks detectable levels of phycocyanin. Indeed, 16S rRNA analysis supports the identity of the A. marina LARK001 strain as distinct from the A. marina HICR111A strain first isolated from Heron Island, previously found on the Great Barrier Reef, under coral rubble on the reef flat. Taken together, A. marina LARK001 is a new cyanobacterial strain adapted to the stromatolite matts in Shark Bay.

Background: The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assesses circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. Aim: Evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes. Identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities related to social determinants of health (SDoH). Design: IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon. Survival analyses utilized Kaplan–Meier curves. Setting/Participants: Single-institution study involving patients receiving whole-brain radiotherapy. Collected demographic, disease, and socioeconomic parameters from electronic medical records. Results: Morning treatment (n=158) showed a trend towards improved overall survival vs. afternoon (n=79), median survival 158 vs. 79 days (p=0.20, HR=0.84, CI95% 0.84–0.91). Subgroup benefits for morning treatment in females (p=0.04) and trends in controlled primary disease (p=0.11) and breast cancer metastases (p=0.08). SDoH-based disparities observed, with Black and lower-income patients exhibiting diminished circadian influence. Conclusions: Emphasizes chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlates with improved survival, particularly in specific subgroups. Identifies potential circadian influence disparities based on SDoH, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

The cassava whitefly, Bemisia tabaci, causes direct damage to cassava in the tropics by feeding on the phloem of leaves, inducing leaf chlorosis and abscission which can result in considerable yield loss of up to about 50% on susceptible varieties. The pest is also known to impart its indirect damage through sooty mold formation. Most of the improved cassava varieties in Uganda were developed for CMD resistance and CBSD tolerance and little is known about their reaction to whitefly infestation. A study was conducted to evaluate the reaction of 24 improved cassava varieties which were sourced from 5 different countries in the region (Uganda, Kenya, Tanzania, Malawi, and Mozambique) to whitefly infestation. These varieties were evaluated in three agro-ecological zones of Uganda, namely; North-Western Savannah Grassland, Lake Victoria Crescent and the Kyoga Plains in the second rains of 2016. Monthly data were taken on adult and nymph counts, whitefly and sooty mold damage, CMD and CBSD severities from 2 up-to 9 Months after planting (MAP). Results show that the whitefly population was highly significantly (P

Background: Medical comorbidities increase the risk of severe COVID-19 infection. In some studies, obstructive sleep apnea (OSA) has been identified as a comorbid condition that is associated with an increased prevalence of COVID-19 infection and hospitalization, but few have investigated this association in a general population. Research Question: In a general population, is OSA associated with increased odds of COVID-19 infection and hospitalization and are these altered with COVID-19 vaccination? Study Design: Cross-sectional survey of a diverse sample of 15,057 U.S. adults Results: COVID-19 infection and hospitalization rates were 38.9% and 2.9% respectively. OSA or OSA symptoms were reported in 19.4%. In logistic regression models adjusted for demographic, socio-economic and comorbid medical conditions, OSA was positively associated with COVID-19 infection (aOR: 1.58, 95%CI: 1.39-1.79) and COVID-19 hospitalization (aOR: 1.55, 95% CI: 1.17-2.05). In fully adjusted models, boosted vaccination status was protective against both infection and hospitalization. Boosted vaccination status attenuated the association between OSA and COVID-19 related hospitalization, but not infection. Participants with untreated or symptomatic OSA were at greater risk for COVID-19 infection; those with untreated, but not symptomatic OSA were more likely to be hospitalized. Interpretation: In a general population sample, OSA is associated with a greater likelihood of having had a COVID-19 infection and a COVID-19 hospitalization with the greatest impact observed among persons experiencing OSA symptoms or who were untreated for their OSA. Boosted vaccination status attenuated the association between OSA and COVID-19 related hospitalization.

Background: Research suggests that cognitive and behavioural factors, including lifestyle behaviours, contribute to the mitigation of perceived stress and stress-related health outcomes in later life. Given that stress management and lifestyle behaviour interventions for older adults are an important target for healthcare efforts, there is a need to comprehensively measure stress and coping resources in later adulthood. Additionally, researchers need a relatively short, standardized assessment tool that can robustly measure stress and coping for longitudinal and intervention-based studies to reduce burden on participants and for cross-comparison across research. Methods: The Stress Assessment Inventory (SAI), a valid and reliable 123-item measure designed to assess occupational stress and coping resources in younger adults was examined in 294 independent older adults. Results: A shortened and revised SAI is proposed for older adults, with good internal consistency and strong criterion validity. The revised SAI for older adults was found to have a 4-factor model that captures Adaptive Cognitive Resources, Maladaptive Behavioural and Cognitive Habits, Social Support and Adaptive Health Habits. Conclusion: The current study supports the use of the inventory in community-dwelling older adult populations as a comprehensive tool to assess stress and coping for use by researchers and healthcare professionals.

The European Union of Aquarium Curators (EUAC) includes 150 members and is an important association for the European public aquarium community. Since 2004, over one quarter of a million euros were awarded by the EUAC Conservation Fund to approximately 50 projects, which spanned across the globe. While projects varied greatly in content and scope, several achieved a significant impact in local populations and/or their focus species. This paper reports on results achieved by these conservation efforts and what improvements can be made, to ensure that the funding is indeed invested in conservation efforts per se. Perhaps the most valid conclusion to be drawn from the list of projects covered in this work is the fact that, regardless of the outcome, as far as preservation of the species are concerned, local communities were actively engaged in a subject that would, otherwise, remain unknown to them. Additionally, these EUAC funded projects highlight how public aquarium activities reach far beyond the acrylic panels surrounding the tanks and indeed the walls of the institution, as they spread around the world and raise awareness within local communities to preserve biodiversity. These results further suggest that a future direction for EUAC, as well as the public aquaria it consists of, could – indeed should - include more strenuous lobbying with legislating bodies, to ensure more adequate – and stronger – in situ conservation measures. In conclusion, with so many doubts being raised by different movements about the existence of aquaria and zoos, it is important that the public is aware that it is their visit to see the ambassadors of different species of animals that supports the funding of many of these pilot projects that aim to preserve species in their natural environment.

We aimed to explore university students’ perceptions and experiences of SARS-CoV-2 mass asymptomatic testing, social distancing and self-isolation during the COVID-19 pandemic. This qualitative study comprised of four rapid online focus groups conducted at a higher education institution in England during high alert (tier 2) national COVID-19 restrictions. Data were analysed thematically. Participants were purposively sampled university students (n = 25) representing a range of gender, age, living circumstances (on/off campus) and SARS-CoV-2 testing/self-isolation experiences. Six themes with 16 sub-themes emerged from the analysis of the qualitative data: ‘Term-time Experiences’, ‘Risk Perception and Worry’, ‘Engagement in Protective Behaviours’, ‘Openness to Testing’, ‘Barriers to Testing’ and ‘General Wellbeing’. Students described feeling safe on campus, believed most of their peers are adherent to protective behaviours and were positive towards asymptomatic testing in university settings. University communications about COVID-19 testing and social behaviours need to be timely and presented in a more inclusive way to reach groups of students who currently feel marginalised. Barriers to engagement with SARS-CoV-2 testing, social distancing and self-isolation were primarily associated with fear of the mental health impacts of self-isolation, including worry about how they will cope, high anxiety, low mood, guilt relating to impact on others and loneliness. Loneliness in students could be mitigated through increased intra-university communications and a focus on establishment of low COVID-risk social activities to help students build and enhance their social support networks. These findings are particularly pertinent in the context of mass asymptomatic testing programmes being implemented in educational settings and high numbers of students being required to self-isolate. Universities need to determine the support needs of students during self-isolation and prepare for the long-term impacts of the pandemic on student mental health and welfare support services.

Adolescents most often experience mild acute COVID-19 but may still face fatigue and persistent symptoms such as post-COVID-19 condition (PCC) and post-infective fatigue syndrome (PIFS). We explored the fecal microbiota in a prospective controlled cohort of 136 non-hospitalized SARS-CoV-2-positive and 32 SARS-CoV-2-negative controls aged 12–25 years. With a targeted qPCR approach, the quantities of 100 fecal bacterial taxa were measured at baseline (early convalescent stage) and after six months. Results: Faecalibacterium prausnitzii M21.2 and Gemmiger formicilis (both p&lt;0.001) were enriched in the SARS-CoV-2-positive participants compared to controls at baseline. Lower baseline abundance of Faecalibacterium prausnitzii M21/2 (p=0.013) and higher abundance of Clostridium spiroforme (p=0.006), Sutterella wadsworthensis (p&lt;0.001) and Streptococcus thermophilus (p=0.039) were associated with six-month fatigue. Sutterella wadsworthensis and Streptococcus thermophilus enrichment was additionally associated with PCC in the SARS-CoV-2-positive group (p&lt;0.001 and 0.042 respectively). Conclusions: In mild SARS-CoV-2 infection in adolescents and young adults, beneficial Faecalibacterium prausnitzii M21/2 and Gemmiger formicilis were enriched compared to SARS-CoV-2 negative controls. Additionally, both known (Faecalibacterium prausnitzii, Streptococcus thermophilus) and new (Clostridium spiroforme, Sutterella wadsworthensis) bacteria were associated with persistent symptoms in the COVID-19 infected group, warranting further exploration of the role of these bacteria in COVID-19 disease and PCC pathophysiology.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult neuromuscular clinics, with multi-gene panel testing currently being the most common approach; follow-up testing using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples to illustrate the unique ability of broad-based testing to improve diagnostic yield, resulting in identification of SORD-neuropathy, HADHB-related disease, ATXN2-ALS, MECP2 related progressive gait decline and spasticity, and DNMT1-related cerebellar ataxia, deafness, narcolepsy, and hereditary sensory neuropathy type 1E. We describe in each case the technological advantages that enabled identification of the causal gene, and the resultant clinical and personal implications for the patient, demonstrating the importance of offering exome or genome sequencing to adults with NMDs.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

We propose an experimental method for the unidirectional excitation of spin waves. By structuring Au nanowires arrays within a coplanar waveguide onto a thin yttrium iron garnet (YIG) film, we observe a chiral coupling between the excitation field geometry of the nanowires grating and several well-resolved propagating magnon modes. We report a propagating spin wave spectroscopy study with unprecedented spectral definition, wavelengths down to 130 nm and attenuation lengths well above the 100 μm over the 20 GHz frequency band. The proposed experiment paves the way for future non-reciprocal magnonic devices.

This paper focuses on the application of principal component analysis (PCA) to conduct a source apportionment of atmospheric aerosols from 8 sampling locations along the Marilao-Meycauayan-Obando River System (MMORS). Aerosols were collected on May 2016 during the same time that water samples were collected. Elemental analysis was conducted using a scanning electron microscope coupled with energy dispersive x-ray (SEM-EDX). Carbon (C), nitrogen (N), oxygen (O), sodium (Na), magnesium (Mg), aluminum (Al), silicon (Si), sulfur (S), chlorine (Cl), potassium (K), calcium (Ca), titanium (Ti), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), bromine (Br), niobium (Nb), barium (Ba), mercury (Hg), and lead (Pb) concentrations were measured and used as inputs in Principal Component Analysis (PCA). The aerosol samples showed the presence of heavy metals Pb and Hg, elements that were also detected in trace amounts in the water measurements. Concentrations of heavy metals Fe, Pb, Hg in the aerosols were attributed to industrial sources. However, it was determined that the primary source of aerosols in the area were traffic and crustal emissions (C, N, O, Si, Al, Ca). Thus, control of traffic emissions would be more beneficial in reducing aerosol emissions in Meycauayan.

Artificial intelligence (AI) is transforming many healthcare fields including pediatric urology. This in-depth review explores recent advances in AI tools for pediatric urology, emphasizing how state-of-the-art technologies can be used to enhance patient treatment. An initial overview of pediatric urology is given to provide context for this interdisciplinary field and the wide spectrum of problems this entails, before discussing potential uses of AI to improve diagnostic accuracy, treatment planning, and surgical results. AI-powered predictive models are already changing pediatric clinical practice by guiding interpretation of medical images and supporting decision making. In addition to outlining the aims, methods, and conclusions of previous studies on AI applications in pediatric urology, this review also highlights knowledge gaps and priority areas for future study. Particular focus is given to specialized surgeries such pyeloplasty, where AI-guided treatment may help overcome specific technical challenges of this complex procedure. Also highlighted are practical, ethical, and legal aspects of integrating AI into pediatric urology, which will be crucial for responsible innovation in patient-centered treatment. Overall, this article aims to enlighten and inspire clinicians, researchers, and other healthcare stakeholders by offering insight into the future of AI in pediatric urology.

Synechococcus sp. PCC 11901 reportedly demonstrates the highest, sustained growth of any known cyanobacterium under optimized conditions. Due to its recent discovery our knowledge of its biology, including the factors underlying sustained, fast growth, is limited. Furthermore, tools specific for genetic manipulation of PCC 11901 are not established. Here, we demonstrate that PCC 11901 shows faster growth than other model cyanobacteria, including the fast-growing species Synechococcus elongatus UTEX 2973, under optimal growth conditions for UTEX 2973. Comparative genomics between PCC 11901 and Synechocystis sp. PCC 6803 reveal conservation of most metabolic pathways but PCC 11901 has a simplified electron transport chain and reduced light-harvesting complex. This may underlie its superior light utilization, reduced photoinhibition and higher photosynthetic and respiratory rates. To aid biotechnology applications we developed a vitamin B12 auxotrophic mutant but were unable to generate unmarked knockouts using two negative selectable markers, suggesting that recombinase- or CRISPR-based approaches may be required for repeated genetic manipulation. Overall, this study establishes PCC 11901 as one of the most promising species currently available for cyanobacterial biotechnology and provides a useful set of bioinformatics tools and strains for advancing this field, in addition to insights into the factors underlying its fast growth phenotype.

Low-cost particulate matter (PM) sensors offer an excellent opportunity to improve our knowledge about this type of pollution. Their size and their cost, which support multi-node network deployment, along with their temporal resolution, enable them to report fine spatio-temporal resolution for a given area. These sensors have known issues across performance metrics. Generally, the literature focuses on the PM mass concentration reported by these sensors but some models of sensors also report particle number concentrations (PNC) segregated into different PM size bins. In this study, 8 units of each Alphasense OPC-R1, Plantower PMS5003 and Sensirion SPS30 have been exposed, under controlled conditions, to short-lived peaks of PM generated using two different combustion sources of PM, exposing the sensors to different particle size distributions to quantify and better understand the low cost sensors performance across a range of relevant environmental ranges. The PNC reported by the sensors were analysed. This study showed that there is added value in directly using the PNC reported by the sensors instead of the mass concentrations, which could aid the efforts to calibrate these sensors to a known accuracy. It demonstrated that all sensors tested here could track the fine temporal variation of PNC, that the Alphasense OPC-R1 could closely follow the variations of size distribution between the two sources of PM, and it showed that particle size distribution and composition are more impactful on the sensors measurement than relative humidity.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p&lt;0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the key focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection in pre-clinical models and human trials. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses delivered by replication-deficient vector ChAdOx1. It focuses T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the beta-coronavirus family.

Leishmania infantum is an hemopathogen of importance for the health of domestic dogs (Canis lupus familiaris), causing canine leishmaniasis (CanL), as well as it is the etiological agent of human visceral leishmaniasis (HVL). This parasite was not reported in southern Brazil until the early 2000s, but CanL and HVL were increasingly reported in the last 15 years, mainly in cities bordering Argentina. The present study aimed to detect L. infantum in urban dogs and to determine the main clinical manifestations in the infected animals from Uruguaiana, a city with a high incidence of CanL. Fifty-one dogs suspected of having CanL in the urban perimeter of the city were clinically examined by veterinarians and investigated for the occurrence of L. infantum with two immunoassays (rapid chromatography test and ELISA) and real-time PCR. Clinical signs were compared in positive and negative L. infantum animals. A total of 31 dogs (60.8%) were infected with L. infantum. The main clinical manifestations associated to CanL dogs were onychogryphosis and peeling (p&lt;0.05). L. infantum was frequently detected in urban dogs from Uruguaiana, highlighting the health concerning situation in this city. The occurrence of some clinical signs (onychogryphosis/peeling) could help to detect more frequently CanL in the canine population.

Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.

Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended recollections for babies with birth weight &lt;1500g (managed by the maternity service provider) and 3 weeks post-transfusion (managed by the laboratory). We aimed to determine adherence to current guidelines and review the guidelines to improve NBS performance. To do this we audited data from 348,584 babies between January 2018 and June 2022. Babies with a recorded birth weight of &lt;1500g were filtered for inclusion. For the overall review and visualization of the protocol, we sourced information from the literature, our professional society and tertiary hospital services. A total of 2647 babies had a birth weight recorded between 200 and 1499g. Of these 2036 (77%) had a second sample collected, indicating that &gt;1 in 5 babies were not receiving a follow-up collection. Our timing of recollections for transfused babies, requiring a 3-week follow-up collection, was longer than in other Australasian jurisdictions. A new combined “sick-prem-protocol” was launched to support recollections and after a one-year review achieve 95% compliance. We recommend NBS laboratories audit preterm and sick neonate recollections to ensure appropriate follow-up. This should be supported with a visual process map to aid education and compliance.

Despite the many advantages of lung ultrasound (LUS) in the diagnosis and management of patients with dyspnea, adoption among hospitalists has been slow. We performed semi-structured interviews of hospitalists from 4 diverse health systems in the US to understand determinants of adoption within a range of clinical settings. We used the Diffusion of Innovation Theory to guide a framework analysis of the data. Of 27 hospitalists invited, we performed in-terviews of 22 from 4 hospitals of diverse types. Median years post-residency of interviewees was 10.5 [IQR:5-15]. Four main themes emerged: 1) There are important clinical advantages to LUS despite operator dependence, 2) LUS enhances patient and clinician experience, 3) Investment of clinician time to learn and perform LUS is a barrier to adoption but yields improved efficiency for the health system and 4) Mandated training and use may be necessary to achieve broad adoption as monetary incentives are less effective. Despite perceived benefits of LUS for patients, clinicians and health systems, an important barrier to broad LUS adoption is the experience of time scarcity by hospitalists. Future implementation strategies should focus on changes to the clinical environment that address clinician barriers to learning and adoption of new skills.

Research on the coral-eating crown-of-thorns starfish (CoTS) has waxed and waned over the last few decades, mostly in accordance with the occurrence of population outbreaks at key locations, such as Australia’s Great Barrier Reef. This review considers advances in our understanding of the biology and ecology of CoTS based on the latest resurgence of research interest, which culminated in this current special issue on the Biology, Ecology and Management of Crown-of-Thorns Starfish. More specifically, this review considers progress against 41 specific research questions posed in the seminal review by P. Moran 30 years ago, as well as exploring new directions for CoTS research. Despite the plethora of research on CoTS (>1,200 research articles), there are persistent knowledge gaps that constrain effective management of outbreaks. Although directly addressing some of these questions will be extremely difficult, there have been considerable advances in understanding the biology of CoTS, if not the proximal and ultimate cause(s) of outbreaks. Moving forward, researchers need to embrace new technologies and opportunities to advance understanding of CoTS biology and behaviour, with focus given to key questions that will improve effectiveness of management to reduce the frequency and likelihood of future outbreaks, if not preventing them altogether.

This review explores the potential implementation of lithium tetraborate (Li2B4O7) as a scintillator medium for neutron detection applications. Several characteristics required for the neutron detection process suggest that Li2B4O7 could be a suitable material for scintillation-based neutron detection systems. The inherently large neutron capture cross-section due to 10B and 6Li isotopes, and the ease with which Li2B4O7 can be enriched with these isotopes, combined with the facile inclusion of rare-earth dopants are all expected to improve luminescent properties as well as neutron detection efficiency of Li2B4O7. The electronic structure of doped and undoped Li2B4O7 are explored using photoemission and inverse photoemission spectroscopies, optical measurements, and theoretical computational studies such as density functional theory. The scintillation properties are further enhanced because of the wide bandgap, and transparency towards the photons that are emitted following neutron capture.