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Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Background: Precision oncology is gaining momentum in managing patients with gastrointestinal cancers. This study examines the implementation of personalized medicine technologies in upper gastrointestinal (UGI) oncology across European academic centers. Material and methods: Forty-five oncology specialists from 41 European institutions completed a survey designed by the Personalized Medicine Task Force of the European Organization of Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Working Group, providing insights into molecular testing, timing, availability of targeted therapies, funding sources, and utilization of molecular tumor boards (MTBs) for patients with UGI cancers. Frequencies and percentages were calculated. Results: Routine testing for human epidermal growth factor receptor 2 (HER2, 100%), programmed death-ligand 1 (PD-L1, 89%), and DNA mismatch repair (MMR, 91%) is implemented in most centers. Comprehensive gene panels on tumor tissue are frequently utilized, especially in biliary tract cancer, with almost all centers incorporating them into routine practice. Blood-based sequencing is increasingly employed, and half of centers carry out comprehensive gene panels for circulating tumor DNA analyses. MTBs are regularly held in 76% of centers, predominantly utilizing ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)-based recommendations for tissue molecular alterations. The translation of genomic information into prescribed treatments remains limited, however, with the majority of centers reporting ∼25% of molecularly stratified treatment decisions following comprehensive genetic testing. Conclusion: This survey provides important insights into current personalized medicine practice in European academic clinical centers for UGI oncology. Despite widespread adoption of molecular testing and implementation of MTBs, further efforts are needed to optimize the integration of personalized medicine into clinical practice.

The evaluation of programmed death-ligand 1 (PD-L1) expression and the methodology employed are central to identify suitable candidates for immunotherapy among patients with gastro-oesophageal cancer (GC). Yet, there are no comprehensive global studies comparing the various methods and antibodies utilized for assessing PD-L1 positivity in GC. The ASPIRE study, led by the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Group (EORTC GITCG) and the National University Health System, Singapore, seeks to standardize the assessment of PD-L1 expression in GC. By comparing various PD-L1 scoring systems and assays, the study aims to simplify and harmonize the quantification and qualification of PD-L1 expression. Ultimately, this effort aims to facilitate the translation of endpoints in companion diagnostic settings. Here, we report the protocol of the study.

The identification and reduction of methane sources is considered an important part of the fight to stem greenhouse gas (GHG) emissions to the atmosphere. One of the largest industrial contributors to national GHG emissions in Canada is the Alberta Oil Sands Region. To quantify and investigate the spatial distribution and temporal variability of methane emissions from this region, airborne measurements were conducted in 2017 and 2018 with three aircraft. 59 flights were conducted in total to assess emissions for both open-pit and in-situ facilities, in both cold and warm seasons. Derived emission rates were higher than those reported in national inventories by 30%–96% depending on the facility. In-situ facilities had emission rates an order of magnitude lower than surface mining operations and differed significantly from inventory estimates. No statistical differences in CH4 emissions between cold and warm seasons were observed, substantiating the use of simple upscaling to annual emissions within inventories. Rather than confirming a reported decrease in emissions between 2013 and 2018, the measurements suggest essentially no change from the 18 t h−1 for the region observed in 2013. Overall, the results suggest that current methods of CH4 emission determination within the oil sands region, for use in reporting, require improvement.

For decades, the stomach was considered a sterile organ, due to the acid environment. However, starting from the discovery of Helicobacter pylori, this concept has progressively refined. By damaging the hydrochloric acid-secreting glands, H. pylori infection primes the progression from acute to chronic inflammation in gastric mucosa resulting in atrophic gastritis, intestinal metaplasia, dysplasia and ultimately gastric cancer (GC). Due to the challenging identification of culturing bacteria, the carcinogenic role of gastric microbial community, other than H. pylori, remains underestimated. More recently, a growing body of evidence has pointed out the dynamism of gastric microbiota as a crucial step for GC development, besides elucidating some additional activity in modulating the efficacy of cancer treatments. In turn, anticancer therapies can shape gastric microbiota with consequent dysbiosis and a potential correlation with drug-related toxicity. In conclusion, the current review aims to deepen the role of gut microbiota as a key factor in gastric disease at multiple levels, from carcinogenesis to the metastatic phase. It also provides novel insights on gastric microbiota as potential target for tailoring multimodal strategies, either surgical or oncological, to finally provide our patients with more individualized treatment options.

This research designed and developed an ultrasonic reactor for a fast and on demand production of cold brew coffee, remarkably reducing the brewing time from 24 h to less than 3 min. The technology was engineered by utilizing resonance to induce ultrasonic waves around the walls of the brewing basket of an espresso machine. The sound transmission system comprised a transducer, a horn and a brewing basket. This arrangement transformed the coffee basket into an effective sonoreactor that injected sound waves at multiple points through its walls, thereby generating multiple regions for acoustic cavitation within the reactor. Furthermore, acoustic streaming induced greater mixing and enhanced mass transfer during brewing. The design was accomplished by modeling the transmission of sound, and acoustic cavitation. Brew characterization and chemical composition analysis was performed, considering factors such as pH, acidity, color, and the composition of caffeine, fatty acids, and volatiles. The efficiency of the extraction increased by decreasing the basket loading percentage (BLP). For instance, sonicating at 100 W doubled the extraction yield and caffeine concentration, from 15.05 % to 33.44 % at BLP = 33 %, and from 0.91 mg/mL to 1.84 mg/mL at BLP = 67 %, respectively. The total fatty acids increased from 1.16 mg/mL to 9.20 mg/mL, representing an eightfold increase, at BLP = 33 %. Finally, a sensory analysis was conducted to evaluate appearance, aroma, texture, flavor, and aftertaste, which demonstrated that coffee brewed for 1 and 3 min in the sonoreactor exhibited almost undistinguishable properties compared to a standard 24 h brewing without ultrasound.

Artificial light at night (ALAN) disrupts biological processes across taxa and at all levels of organisation. Despite growing interest in this globally pervasive sensory pollutant, its impact on colour-guided processes remains largely unexplored. This is especially concerning given the rapid transition in recent years away from narrow-spectrum lighting and towards broad-spectrum options such as white LEDs, which are rich in the short wavelengths of light to which many taxa are particularly sensitive. Camouflage is particularly likely to be disrupted by broader spectra of ALAN due to changes in conspicuousness in background matching prey, which may alter prey recognition in visually guided predators. We simulated natural intensities of moonlight with and without ALAN, using both broad-spectrum (‘white’) ALAN and ALAN filtered to remove the characteristic short (blue) wavelength peak of broad-spectrum LEDs to test whether filtering might mitigate their effects. We tested how exposure to these light treatments impacted predator-prey interactions, using the intertidal crab Carcinus maenas and contrasting colour morphs of the colour-polymorphic snail Littorina obtusata as a model system. Exposure to broad-spectrum ALAN reduced overall predation and reversed the pattern of colour-based prey selection observed under control conditions. Snails were 55 % less likely to be attacked under broad-spectrum ALAN than in control conditions, with likelihood decreasing over 70 % for yellow snails. Yellow snails were over 26 % more likely to be attacked than brown ones under control conditions, but brown snails were over 40 % more likely to be attacked than yellow ones under broad-spectrum ALAN. Exposure to filtered ALAN removed any significant colour-based difference in prey recognition. Our results demonstrate that spectral composition is a crucial aspect of ALAN as a sensory pollutant, capable of instigating profound changes in predator-prey interactions that could drive changes in population demography and increase morphological homogeneity in species that depend on colour polymorphism for camouflage.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Background: Esophageal cancer [esophagogastric adenocarcinoma (OGA)] shows heterogeneity at the molecular level, leading to lower efficacy rates and highlighting the need for personalized treatment strategies. We have developed a computational model that uses both mechanistic and statistical approaches to integrate a patient’s genomic aberrations, revealing signaling pathway dysregulation and variable drug response. The model output, Therapy Response Index (TRI), has been used to predict therapeutic outcomes in this study. Design: TRI’s ability to predict patient outcomes was retrospectively evaluated in a prospectively collected cohort of patients with operable OGA from the UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium receiving neoadjuvant chemotherapy. Stratified random sampling was used to split the data into training and validation subsets. Multivariate Cox proportional hazard and proportional odds models were used to predict survival and pathological response as a function of TRI and clinical thresholds compared with clinical factors. Results: A total of 270 patients with OGA were selected who had 50× whole genome sequencing carried out on tissue derived from either biopsy or resection. Patients were treated with chemotherapy drugs or regimens according to UK clinical guidelines. The association of TRI with overall survival (OS) was significant above and beyond standard clinical factors (P = 0.0012). A significant association was also observed with disease-free survival (DFS; P = 0.0288). A TRI optimized for tumor regression grade also displayed a significant association (P = 0.0011). Conclusions: TRI was predictive of OS and DFS beyond clinical factors. These positive results suggest the potential utility of personalized biosimulation-informed therapy selection and that further assessment in prospective clinical studies is warranted.

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained. Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.

Advances in biomedical engineering continue to produce innovative wearable health sensors capable of real-time ambulatory assessments (e.g., of physiology, the environment), holding great potential for advancing precision monitoring and interventions through the integration of such devices and data into eHealth systems. As with any novel device, however, user views on acceptability and concerns about the technology must be evaluated to facilitate widespread implementation and user adoption of such devices. One factor that may strongly influence user views is the potential relevance to, and need for, self-care for chronic disease management. We examined if acceptability and concerns regarding innovative wearable devices differed between individuals living with or without chronic disease. A U.S. adult sample (N = 448; 20-70 yrs.; 34 % Female; 60 % White, 35 % Hispanic) completed a web-based survey regarding their thoughts/opinions related to innovative wearable sensors. Two-thirds (67 %, N = 298) reported at least one chronic disease; one-third (33 %, N = 150) reported no chronic health conditions. Participants viewed learning modules about two innovative devices: a watch to detect environmental gases for respiratory health, and a chest-patch monitoring real-time ECG. For each device, participants rated acceptability across multiple dimensions, and then rated potential concerns (including general concerns and specific worries about negative health impacts). Respondents with and without chronic disease differed in education, race, and ethnicity. Controlling for these differences, individuals with chronic disease reported significantly higher acceptability for the watch and for the chest-patch. Healthy participants reported significantly higher general concerns about technology. However, when concern questions were asked specifically about the potential negative impacts of the two study devices on physical health and well-being, participants with chronic disease reported significantly higher concerns. Overall, results show that living with chronic disease influences acceptability and concerns associated with adoption of innovative sensors. These findings suggest it is essential to take potential users' health status into account when studying the design and implementation of innovative wearable sensors. Dissemination strategies may benefit from emphasizing the beneficial features of these devices, addressing hesitations, and customizing implementation approaches by user group.

The building sector is responsible for the highest portion of energy consumption and carbon dioxide emissions. To partly address this issue, the scientific community is placing greater emphasis on the utilization of Building Integrated Solar Systems (BISS) as a means of improving building thermophysics and decreasing primary energy demand. Within this framework, Integrated Collector Storage Solar Water Heaters (ICSSWH) have the potential to significantly decrease the costs associated with the installation and maintenance of building-integrated solar systems (BISS), all while optimizing the utilization of solar power. Nevertheless, ICSSWHs exhibit certain limitations in their capacity to retain thermal energy, particularly during nocturnal periods. One potential approach for enhancing the efficiency of ICSSWH collectors involves the integration of Thermal Diodes (TD), which have the capability to optimize heat absorption while minimizing heat retention. In this context, to advance the state-of-the-art in the field, this paper presents a novel dynamic simulation tool conceived to assess the performance of an innovative Hybrid Photovoltaic Thermal ICSSWH (the HyPVT), incorporating a cutting-edge Planar Liquid Vapour Thermal Diode (PLVTD), and purposely designed to be integrated into buildings’ envelope. By using the developed simulation tool, the performance of the proposed HyPVT collector concept is investigated with the aim of assessing its collection and retention efficiencies under different boundary and operating conditions. Furthermore, to show the effect of the Planar Liquid Vapour Thermal Diode (PLVTD) adoption, a comparative analysis is conducted between the proposed ICSSWH and a conventional one (without a thermal diode). Finally, the developed tool will be utilized in forthcoming research to determine the optimal device configuration through the utilization of a model-based design methodology.

Background: Sleep dysfunction is disabling in people with Parkinson’s disease and is linked to worse motor and non-motor outcomes. Sleep-specific adaptive Deep Brain Stimulation has the potential to target pathophysiologies of sleep. Objective: Develop an adaptive Deep Brain Stimulation algorithm that modulates stimulation parameters in response to intracranially classified sleep stages. Methods: We performed at-home, multi-night intracranial electrocorticography and polysomnogram recordings to train personalized linear classifiers for discriminating the N3 NREM sleep stage. Classifiers were embedded into investigational Deep Brain Stimulators for N3 specific adaptive DBS. Results: We report high specificity of embedded, autonomous, intracranial electrocorticography N3 sleep stage classification across two participants and provide proof-of-principle of successful sleep stage specific adaptive Deep Brain Stimulation. Conclusion: Multi-night cortico-basal recordings and sleep specific adaptive Deep Brain Stimulation provide an experimental framework to investigate sleep pathophysiology and mechanistic interactions with stimulation, towards the development of therapeutic neurostimulation paradigms directly targeting sleep dysfunction.

Summary: Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3–4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor β partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS.

Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD). Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS. The Flagship adopted a tiered approach to GS analysis. Tier 1 analysis assessed genes with established clinical validity for each cardiovascular condition. Tier 2 analysis assessed lesser-evidenced research-based genes. Tier 3 analysis assessed the functional impact of VUS that remained after tier 1 and tier 2 analysis. Results: Overall, a pathogenic or likely pathogenic variant was identified in 41% of participants with a cardiomyopathy, 40% with an arrhythmia syndrome, and 15% with a familial CHD/CHD+Extra Cardiac Anomalies. A VUS outcome ranged from 13% for arrhythmias to 34% for CHD/CHD+Extra Cardiac Anomalies participants. Tier 2 research analysis identified a likely pathogenic/pathogenic variant for a further 15 participants and a VUS for an additional 15 participants. Conclusion: The Flagship successfully facilitated a model of care that harnesses clinical GS and functional genomics for the resolution of VUS in the clinical setting. This valuable data set can be used to inform clinical practice and facilitate research into the future.

Background: With the spread of SARS-CoV-2 impacting upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread during the pandemic. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy. Methods: Sera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 antibodies. Samples were assessed using an Elecsys anti-SARS-CoV-2 or anti-SARS-CoV-2 S ECLIA (Roche) on an automated cobas e 801 analyser. Samples were also assessed via an anti-SARS-CoV-2 ELISA (Euroimmun). A subset of samples assessed via the Elecsys anti-SARS-CoV-2 ECLIA were subsequently analysed in an ACE2 pseudoneutralisation assay using a V-PLEX SARS-CoV-2 Panel 7 for IgG and ACE2 (Meso Scale Diagnostics). Results: Across three testing rounds (June–July 2020, November–December 2020 and June–July 2021 (rounds 1–3 respectively)), 4844 residual sera/plasma specimens were assayed for anti-SARS-CoV-2 antibodies. Seropositivity rates increased across the study, peaking at 11.6 % (95 % CI 10.4 %–13.0 %) during round 3. Varying trends in SARS-CoV-2 seropositivity were noted based on demographic factors. For instance, highest rates of seropositivity shifted from older to younger demographics across the study period. In round 3, Alpha (B.1.1.7) variant neutralising antibodies were most frequently detected across age groups, with median concentration of anti-spike protein antibodies elevated in 50–69 year olds and anti-S1 RBD antibodies elevated in 70+ year olds, relative to other age groups. Conclusions: With seropositivity rates of

Objective: The purpose of this study was to identify barriers and design interventions to promote adherence to 2017 Guideline for Syncope Evaluation and Management. Methods: Focus groups and interviews were conducted to understand preferences, needs and barriers from patients and providers. Educational materials for patients were developed following a co-design, iterative process with patients, providers and hospital staff. The academic medical center's (AMC) Patient Education Department and Patient & Family Advisory Council reviewed materials to ensure health literacy. We piloted usability and feasibility of delivering the materials to a small cohort of patients. Results: From Feb to March 2020, 24 patients were asked to watch the video. Twenty-two watched the intake video; of those 8 watched the discharge video. 95% of participants found the intake video informational and 86% would recommend it to others; 100% found the discharge video informational and would recommend it to others. Patients who watched both videos reported the videos improved their overall stay. Conclusion: Our study described a patient-clinician-researcher codesign process and demonstrated feasibility of tools developed to communicate risk and uncertainty with patients and facilitate shared decision making in syncope evaluation. Innovation: Engaging end users in developing interventions is critical for sustained practice change.

Emerging technologies are transforming agriculture from a labour-intensive to a technology-intensive sector that meets current and future societal needs without compromising environmental integrity. Using primary data collected through a survey, this study sheds light on the development and commercialization of advanced agricultural technologies in the Canadian Prairies by investigating the objectives, drivers, barriers, co-operation and funding for innovation activities. Results show that Prairie agtech enterprises have undertaken various innovation activities ranging from internal R&D, creative work, software development, to personal training. Those activities are financed mainly with internal funds but also trigger some public subsidies. Not only are customers, educational institutions and suppliers key valued cooperation partners, but also the greatest sources of information when it comes to innovation. Research facilities, including research parks, incubators and accelerators are identified as concurrent drivers for innovation. This exploratory analysis illustrates the opportunities and potential challenges agtech enterprises face during the technology commercialization process.

Cell transplantation using olfactory ensheathing cells (OECs) is a promising approach for nerve repair but there are numerous limitations with their delivery method. Three-dimensional (3D) cell culture systems potentially offer a powerful approach for cell production and delivery options. To further optimise the use of OECs, strategies to promote cell viability and maintain cell behaviours in 3D cultures become important. We previously demonstrated an anti-diabetic drug, liraglutide, could modulate OEC migration and re-model extracellular matrix in two-dimensional (2D) cultures. In the present study, we further investigated its beneficial effects in our 3D culture system using primary OECs. OECs treated with liraglutide at 100 nM showed improved cell viability and had modulated expression of N-cadherin and β1-integrin (two important cell adhesion molecules). When formed into 3D spheroids, the pre-treated OECs generated spheroids with an increased volume and a decreased cell density compared to control spheroids. OECs that subsequently migrated out of the liraglutide pre-treated spheroids had higher capacity for migration with increased duration and length, which was attributed to a reduction in the pauses during the migration. Moreover, OECs that migrated out from liraglutide spheroids had a more bipolar morphology consistent with higher migratory capacity. In summary, liraglutide improved the viability of OECs, modulated cell adhesion molecules, and resulted in stable 3D cell constructs which conferred enhanced migratory capacity on the OECs. Overall, liraglutide may potentially improve the therapeutic use of OECs for neural repair by enhancing the generation of stable 3D constructs and increasing the migratory behaviour of OECs.

Costa Rica's rice production, a large determinant of the country's food security, is being negatively impacted by frequently increasing periods of intense drought. Costa Rican scientists have applied CRISPR/Cas9 to develop drought resistant rice varieties they believe the country's rice producers could benefit from. However, would Costa Ricans consume gene edited rice or products derived from this crop? A three-part, 26-question survey administered in-person to 1096 Costa Ricans uncovers their attitudes, knowledge, and perceptions of gene editing technology and crops. Multiple regressions were built where the independent variables were age, gender, education level, and subjective economic situation. No statistically significant relationships were found in the regression coefficients. Moreover, the k-means procedure (cluster analysis) was used to categorize respondents according to their attitudes on the consumption of gene-edited foods: negative, neutral, and positive. Results show that overall, Costa Rican consumers are open to the application of gene editing in agriculture and would consider consuming products derived from the application of the technology. They are also open to gene editing technology being used to address human and animal health issues. However, Costa Rican consumers are not open to gene editing being used to “design” human traits. This study adds evidence to the emerging literature on the acceptance of gene-edited food. It also highlights the importance of informing societies of just how vulnerable agriculture, and therefore food security, is to the increasingly adverse effects of climate change.

Adamantinoma is a rare primary low-grade malignant tumour of the appendicular skeleton most commonly found in the tibia. It has an indolent course, with local recurrences and lung metastases occurring over a protracted duration. There have been several suggestions pertaining to a vascular origin in the literature, however, histogenesis remains unclear. Currently, guidelines are not available pertaining to clinical management.This paper presents an overview of the current literature regarding this unusual malignancy. It also explores disease etiology and acknowledges the benefits and challenges of investigations pertaining to diagnosis. It recognizes a paucity of recommendations regarding appropriate surveillance and follow up. This review aims to assist clinicians in the building of a consensus opinion for optimal adamantinoma case management under current circumstances where formal guidelines do not exist.

Summary: Background: While low sodium intake (40 years with stable blood pressure (BP), without heart failure or postural hypotension were randomised to intensive dietary counselling (target sodium intake

The Sustainable Forestry Initiative (SFI) Fiber Sourcing Standard (FSS) aims to extend the reach of sustainable forest management onto uncertified forestlands through the use of Best Management Practices (BMPs) for water quality and other requirements intended to promote multiple conservation outcomes. Conservation of biological diversity is one of the pillars of the SFI FSS, yet no study has examined its effect on biodiversity conservation at the landscape level. We analyzed BMP implementation rates (inside, outside, and within overlapped wood baskets of certified wood-consuming mills) across five levels (very high, high, medium, low, and very low) biodiversity habitats to measure the impact of the SFI FSS in four states (Alabama, Florida, Georgia, and South Carolina) in the SE United States. BMP implementation rates were not significantly different inside, outside, or within multiple wood baskets of mills certified to the SFI FSS. We also find that the SFI FSS facilitates the same level of adherence to sustainable forest practices across various levels of biodiversity habitats, regardless of the presence or absence of imperiled species. High compliance rates across the region indicate that all tracts of land, irrespective of biodiversity categories, typically receive the same level of conservation attention. In this context, the SFI FSS is broadening the reach of sustainable forest management beyond certified forests in the SE United States.

Cutibacterium acnes, previously known as Proprionobacterium, is a commensal Grampositive bacterium of the skin commonly implicated in prosthetic joint infections. However, it has been documented to play a role in other conditions, including SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), a rare autoinflammatory disorder. Diagnosing SAPHO syndrome is cumbersome, as the clinical manifestations are variable and overlap with many inflammatory joint disorders. Herein, we describe a 56-year-old female patient with a presumed diagnosis of longstanding seronegative rheumatoid arthritis and history of C. acnes prosthetic joint infection following revision arthroplasty of the right shoulder. She presented to our clinic with a rash over the upper extremities and trunk and joint symptoms involving the right shoulder. Treatment was initiated with ceftriaxone followed by doxycycline suppressive therapy, with clinical improvement of joint and skin involvement. Symptoms recurred upon brief cessation of antibiotic therapy due to adverse gastrointestinal effects; however, symptoms abated once again upon re-initiation of treatment. Given the patient’s cutaneous lesions and longstanding history of arthritis that improved with antimicrobial therapy against C. acnes, the diagnosis of SAPHO syndrome was entertained. The present case demonstrates the clinical challenges of diagnosing SAPHO syndrome and the importance of its consideration on the differential for a patient with osteoarticular and cutaneous features. Additional literature is needed to improve diagnostic criteria and treatment guidelines.

Summary: In the conventional model of transcriptional activation, transcription factors bind to response elements and recruit co-factors, including histone acetyltransferases. Contrary to this model, we show that the histone acetyltransferase KAT7 (HBO1/MYST2) is required genome wide for histone H3 lysine 14 acetylation (H3K14ac). Examining neural stem cells, we find that KAT7 and H3K14ac are present not only at transcribed genes but also at inactive genes, intergenic regions, and in heterochromatin. KAT7 and H3K14ac were not required for the continued transcription of genes that were actively transcribed at the time of loss of KAT7 but indispensable for the activation of repressed genes. The absence of KAT7 abrogates neural stem cell plasticity, diverse differentiation pathways, and cerebral cortex development. Re-expression of KAT7 restored stem cell developmental potential. Overexpression of KAT7 enhanced neuron and oligodendrocyte differentiation. Our data suggest that KAT7 prepares chromatin for transcriptional activation and is a prerequisite for gene activation.

Having recently experienced the three worst wildfire seasons in British Columbia's history in 2017, 2018 and 2021, and anticipating more severe impacts in the future, a key Carbon (C) research priority is to develop reliable models to explore options and identify a portfolio of regionally differentiated solutions for wildfire and forest management. We contribute to this effort by developing a prototype integrated C modeling framework which includes future wildfires that respond to forest stand characteristics and wildfire history. Model validation evaluated net GHG emissions relative to a ‘do-nothing’ baseline for several management scenarios and included emissions from forest ecosystems, harvested wood products and substitution benefits from avoided fossil fuel burning and avoided emissions-intensive materials. Data improvements are needed to accurately quantify the baseline and scenario GHG emissions, and to identify trade-offs and uncertainties.• A Fire Tolerant scenario included post-fire restoration with planting of climatically suitable fire-resistant species and salvage harvest in place of clearcut harvest.

Uncertainty surrounding the total cost of ownership, system costs, and life cycle environmental impacts means that stakeholders may lack the required information to evaluate the risks of transitioning to low-carbon fuels and powertrains. This paper assesses the life cycle costs and well-to-wheel environmental impacts of using electricity and electrofuels in Heavy Good Vehicles (HGVs) whilst considering input parameter uncertainty. The complex relationship between electricity cost, electrolyser capacity factor, CO2 capture cost and electricity emissions intensity is assessed within a Monte Carlo based framework to identify scenarios where use of electricity or electrofuels in heavy goods vehicles makes economic and environmental sense. For vehicles with a range of less than 450 km, battery electric vehicles achieve the lowest total cost of ownership for an electricity cost less than 100 €/MWh. For vehicles that require a range of up to 900 km, hydrogen fuel cell vehicles represent the lowest long-term cost of abatement. Power-to-methane and power-to-liquid scenarios become economically competitive when low-cost electricity is available at high-capacity factors and CO2 capture costs for fuel synthesis are below 100 €/tCO2; these fuels may be more applicable to decarbonise shipping and aviation. Battery electric HGVs reduce greenhouse gas emissions by 50% compared to the diesel baseline with electricity emissions of 350 gCO2e/kWh. Electricity emissions less than 35 gCO2e/kWh are required for the power-to-methane and power-to-liquid scenarios to meet EU emissions savings criteria. High vehicle capital costs and a lack of widespread refuelling infrastructure may hinder initial uptake of low-carbon fuels and powertrains for HGVs.

Objective: Surveillance of health problems at the 2019 17/U & 19/U Australian Netball National Championships (ANNC) and compare this data with the 2018 17/U & 19/U ANNC. Determine the rate for risk of low energy availability and poor sleep quality in athletes competing at the 2019 ANNC. Design: Prospective observational cohort study. Method: One hundred and ninety-two netball athletes were observed during a six-day tournament. Injuries were defined in three ways: 1) self-reported, 2) medical attention, and 3) sports incapacity. Medical attention health problems were recorded prospectively by the 16 team physiotherapists during the tournament and athlete self-reported health problem data was collected on four occasions (pre-tournament, post-tournament, 1-week post tournament and 4-weeks post tournament) using their smartphones. The same method was also used for health problem surveillance at the 2018 17/U & 19/U ANNC. Athletes also completed the Low Energy Availability in Females Questionnaire (LEAF-Q) and Pittsburgh Sleep Quality Index (PSQI). Results: Ninety-five medical attention injuries were sustained by 73 athletes, at an incidence rate of 82.5 injuries/1000 player competition hours. Ankle sprains (n ​= ​16) and lumbar pain (n ​= ​12) had the highest incidence of medical attention injuries. Thirty per cent of athletes started the tournament with a self-reported health problem. Twelve sports incapacity injuries were recorded, with concussion (n ​= ​5) and ACL rupture (n ​= ​4) the most frequent. Fifty percent of athletes who completed the LEAF-Q were identified as being at risk of having low energy availability and 57% of PSQI respondents demonstrated poor sleep quality. There was no association between injury and athletes who were identified as being at risk of low energy availability or having poor sleep quality. Conclusions: Ankle sprains, lumbar pain, and foot blisters are the most frequent medical attention injury and concussion, and ACL rupture were the most frequent sports incapacity injuries in pre-elite netball athletes. Also, a high number of athletes were identified as being at risk of low energy availability (n ​= ​76, 50%) and poor sleep quality (n ​= ​74, 57%). These athletes were not at higher risk of injury compared to those that were not identified as being at risk of low energy availability and poor sleep quality.

Introduction: Caregivers are essential for the health, safety, and independence of many patients and incur financial and personal cost in this role, including increased burden and lower quality of life (QOL) compared to the general population. Extended-hours hemodialysis may be the preference of some patients, but little is known about its effects on caregivers. Methods: Forty caregivers of participants of the ACTIVE Dialysis trial, who were randomized to 12 months extended (median 24 hours/wk) or standard (12 hours/wk) hemodialysis, were included. Utility-based QOL was measured by EuroQOL–5 Dimension–3 Level (EQ-5D-3L) and Short Form–6 Dimensions (SF-6D) and health-related QOL (HRQOL) was measured by the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) and the Personal Wellbeing Index (PWI) at enrolment and then every 3 months until the end of the study. Results: At baseline, utility-based QOL and HRQOL were similar in both groups. At follow-up, caregivers of people randomized to extended-hours dialysis experienced a greater decrease in utility-based QOL measured by EQ-5D-3L compared with caregivers of people randomized to standard hours (–0.18±0.30 vs. –0.02±0.16, P = 0.04). There were no differences between extended- and standard-hours groups in mean change in SF-6D (0.03±0.12 vs. –0.04±0.1, P = 0.8), PCS (–1.2±9.8 vs. –5.6±9.8, P = 0.2), MCS (–4.1±11.2 vs. –0.5±7.1, P = 0.4), and PWI (2.3±17.6 vs. 0.00±20.4, P = 0.9). Conclusion: Poorer utility-based QOL, as measured by the EQ-5D-3L, was observed in caregivers of patients receiving extended-hours hemodialysis in this small study. Though the findings are exploratory, the possibility that mode of dialysis delivery negatively impacts on caregivers supports the prioritization of research on burden and impact of service delivery in this population.

Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans.

Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions.The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model.Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR.Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

The purpose of this study was to investigate the feasibility, acceptability, and short-term adherence to an adult outdoor group sport play program designed to maximize enjoyment that was modified to incorporate COVID-19 risk mitigation strategies. We enrolled 17 healthy, but sedentary, central Pennsylvania adults (meanage = 31.6 ± 7.3) without obesity via mail advertisements to participate in four, 60-minute sessions of instructor-led modified sport games (e.g., handball, Ultimate Frisbee, soccer) over a two-week period in October 2020. Durign recrutiment and the study period, there were approximately 1000–2000 new cases of COVID-19 daily in central Pennsylvania . The overall adherence rate to the sessions was 91%, and no participants reported new or existing COVID-19 symptoms or diagnoses during the two-week study period or 10-days following the final session. Despite enforcing mandatory COVID-19 safety measures (e.g., universal masking, social distancing), the participants reported enjoying the program and feeling socially connected with one another, while perceiving the program to be safe. Additionally, all participants expressed a desire to participate again, if the program were offered in the future. These results suggest that an outdoor group sport play program for adults can be feasible, acceptable, and well-adhered to despite enforcing mandatory COVID-19 safety precautions. Physical activity programs similar to the one presented here may provide an easily-adaptable approach to outdoor physical activity during the current and potential future pandemics that have viral transmission characteristics similar to COVID-19.

Transplantation of olfactory ensheathing cells (OECs) is a promising approach for repairing the injured nervous system that has been extensively trialed for nervous system repair. However, the method still needs improvement and optimization. One avenue of improving outcomes is to stimulate OEC migration into the injury site. Liraglutide is a glucagon-like peptide-1 receptor agonist used for management of diabetes and obesity. It has been shown to be neuroprotective and to promote cell migration, but whether it can stimulate glial cells remains unknown. In the current study, we investigated the effects of liraglutide on OEC migration and explored the involved mechanisms. We showed that liraglutide at low concentration (100 nM) overall promoted OEC migration over time. Liraglutide modulated the migratory behavior of OECs by reducing time in arrest, and promoted random rather than straight migration. Liraglutide also induced a morphological change of primary OECs towards a bipolar shape consistent with improved migration. We found that liraglutide activated extracellular signal-regulated kinase (ERK), which has key roles in cell migration; the timing of ERK activation correlated with stimulation of migration. Furthermore, liraglutide also modulated the extracellular matrix by upregulating laminin-1 and down-regulating collagen IV. In summary, we found that liraglutide can stimulate OEC migration and re-model the extracellular matrix to better promote cell migration, and possibly also to become more conducive for axonal regeneration. Thus, liraglutide may improve OEC transplantation outcomes.

Cutaneous non-tuberculous mycobacterial (NTM) infections are an emerging infectious disease and require a protracted course of combination antibiotics. Antimicrobial choice is limited by resistance and toxicity. Tedizolid is a new oxazolidinone antibiotic with in vitro activity against some NTM, but its use in the management of extrapulmonary NTM has not been described. We report on the utility of prolonged tedizolid use (8 months), after linezolid intolerance, in combination therapy in a case of difficult Mycobacterium chelonae cutaneous infection. Although tedizolid contributed to clinical remission, it may have also contributed to a multifocal peripheral neuropathy. Its efficacy may also have been limited by continued immunosuppression, with evidence to suggest disease relapse or treatment failure after completion of combination therapy. Tedizolid can be considered, with caution, in combination therapy for difficult cases of cutaneous NTM infection.

Anaerobic digestion provides renewable energy through waste valorisation, but the digestate by-product is underutilised and presents a risk to water quality. Mechanical separation partitions phosphorous into the solid fraction and further processing into a fuel pellet can provide an additional source of energy and revenue. Previous economic analyses looked only at aspects of the system (e.g. operational costs solely) and the system requires further investigation to determine viability. In this paper, an economic assessment of digestate fuel pellet production at farm-scale anaerobic digestion plants was carried out. The significance of this work is to provide a comprehensive assessment of the energy, phosphorous, and economic balances involved in digestate fuel pellet production at existing anaerobic digestion plants. The aim of this paper is to determine the financial viability of digestate fuel pellet production with objectives to compare two mechanical separation technologies: screw press, and decanting centrifuge. Economies of scale hold true for digestate pellet production and the available digestate in typical UK farm-based anaerobic digestion plants (≤500 kWe) is insufficient for profitability, with pellet production costing from £176/t (decanting centrifuge) to £215/t (screw press), compared to a typical wood pellet sale price of £185/t. Increasing digestate quantity by collaboration of plant operators can reduce the cost of pellet production to between £95/t and £121/t, improving financial viability and increasing the profit per head of cattle by 9–20% on a typical dairy farm utilising anaerobic digestion. The system has potential to aid rural development while also protecting the environment and contributing to the diversification of energy supply.

Edible green ants (Oecophylla smaragdina) are distributed in Asia, Australia, and the Pacific Islands, and are known for their pharmacological and nutritional applications, yet various properties are to be explored. Nutritional value, volatile compounds, antimicrobial and antioxidant potential were determined in four body regions [ant nest, whole ant, anterior part of the body, and gaster]. Proximate analysis revealed the anterior part have higher protein and fibre content, whilst fat content was higher in the gaster. GC–MS analysis revealed the complexity of ant nest with most compounds being organic acids, alcohols and alkanes. Antimicrobial activity was observed for whole ants (ZOI: 13.3 ± 0.8 mm) and anterior part (ZOI: 11.9 ± 0.5 mm) methanol extracted against Staphylococcus aureus (~104 CFU/ml). Whole ants methanol (813 ± 22.6 µg TROLOX eq/g of DW) and water (617.6 ± 59.2 µg TROLOX eq/g of DW) extracted exhibited higher free radical scavenging capacity amongst the four ant body regions. Whole ants water extracted (7 ± 0.4 mg GAE/g of DW) had the highest total phenolic content. In the methanol extracts, the gaster (6.2 ± 0.2 mg GAE/g of DW) exhibited the highest phenolic content. Whole ants exhibit good antioxidant and antimicrobial activity and considerable folate content.

Purpose: To describe two patients with bilateral ptosis, ophthalmoplegia, cataracts and corneal endothelial disease requiring corneal transplantation. Observations: Histopathological analysis of muscle biopsy samples from both patients identified features consistent with a mitochondrial cytopathy. A single multigenic mitochondrial deoxyribonucleic acid (DNA) deletion was detected in the first patient. Pathogenic mutations in the POLG gene which codes for mitochondrial DNA polymerase, tasked with replicating the mitochondrial genome were identified in the second patient. Conclusion: The collection of clinical features present in both cases described can be explained by a diagnosis of mitochondrial disease. Importance: Corneal endothelial disease, in addition to ptosis, ophthalmoplegia, cataract, pigmentary retinopathy and optic atrophy should be recognised as a feature of mitochondrial disease.

Introduction: Restart a Heart (RSAH) is an annual CPR mass training initiative delivered predominantly by ambulance services in the UK. The aim of this study was to identify to what extent voluntary participation in the 2019 initiative delivered training to the population with the highest need. Methods: A cross-sectional observational study of location characteristics for RSAH training events conducted by UK ambulance services. Descriptive statistics were used to analyse event and area characteristics. National cardiac arrest registry data were used to establish proportions of training coverage in “hot spot” areas with above national median incidence of cardiac arrest and below median bystander CPR rates. The significance of observed differences were tested using chi-square for proportions and t-test for means. Results: Twelve of 14 UK ambulance services participated, training 236,318 people. Most of the events (82%) were held in schools, and schoolchildren comprised most participants (81%). RSAH events were held in areas that were less densely populated (p

It should come as no surprise that innovation is linked to uncertainty, especially when its effects are wide-ranging and can be difficult to quantify, as is the case for plant genome editing. Thus, scientific innovation should be conducted responsibly. Both regulators and companies seek ways to minimize inherent uncertainties regarding technological development. Risk assessment offers a basis to evaluate human, environmental and societal risks of fledging technologies and their application. This paper describes a range of potential issues related to the safety of genome editing as identified through a survey of a consortium of international experts in plant biotechnology. A key finding is that genome edited crops pose marginal risk to the economy, human health and the environment. Yet, regulations governing biotechnology and some advocacy groups tend to discourage the use of new gene technologies in agriculture. In effect, discussions concerning the risks associated with genome editing, and targeted breeding techniques generally, are driven more by socio-political factors than by scientific principles.

Lysophosphatidic acids (LPAs) are bioactive radyl hydrocarbon-substituted derivatives of glycerol 3-phosphate. LPA metabolism and signaling are implicated in heritable risk of coronary artery disease. Genetic and pharmacological inhibition of these processes attenuate experimental atherosclerosis. LPA accumulates in atheromas, which may be a consequence of association with LDLs. The source, regulation, and biological activity of LDL-associated LPA are unknown. We examined the effects of experimental hyperlipidemia on the levels and distribution of circulating LPA in mice. The majority of plasma LPA was associated with albumin in plasma from wild-type mice fed normal chow. LDL-associated LPA was increased in plasma from high-fat Western diet-fed mice that are genetically prone to hyperlipidemia (LDL receptor knockout or activated proprotein convertase subtilisin/kexin type 9-overexpressing C57Bl6). Adipose-specific deficiency of the ENPP2 gene encoding the LPA-generating secreted lysophospholipase D, autotaxin (ATX), attenuated these Western diet-dependent increases in LPA. ATX-dependent increases in LDL-associated LPA were observed in isolated incubated plasma. ATX acted directly on LDL-associated lysophospholipid substrates in vitro. LDL from all human subjects examined contained LPA and was decreased by lipid-lowering drug therapies. Human and mouse plasma therefore contains a diet-sensitive LDL-associated LPA pool that might contribute to the cardiovascular disease-promoting effects of LPA.

The widely expressed lysophosphatidic acid (LPA) selective receptor 4 (LPAR4) contributes to vascular development in mice and zebrafish. LPAR4 regulates endothelial permeability, lymphocyte migration, and hematopoiesis, which could contribute to atherosclerosis. We investigated the role of LPAR4 in experimental atherosclerosis elicited by adeno-associated virus expressing PCSK9 to lower LDL receptor levels. After 20 weeks on a Western diet, cholesterol levels and lipoprotein distribution were similar in WT male and Lpar4Y/− mice (P = 0.94). The atherosclerotic lesion area in the proximal aorta and arch was ∼25% smaller in Lpar4Y/− mice (P = 0.009), and less atherosclerosis was detected in Lpar4Y/− mice at any given plasma cholesterol. Neutral lipid accumulation in aortic root sections occupied ∼40% less area in Lpar4Y/− mice (P = 0.001), and CD68 expression was ∼25% lower (P = 0.045). No difference in α-smooth muscle actin staining was observed. Bone marrow-derived macrophages isolated from Lpar4Y/− mice displayed significantly increased upregulation of the M2 marker Arg1 in response to LPA compared with WT cells. In aortic root sections from Lpar4Y/− mice, heightened M2 “repair” macrophage marker expression was detected by CD206 staining (P = 0.03). These results suggest that LPAR4 may regulate the recruitment of specific sets of macrophages or their phenotypic switching in a manner that could influence the development of atherosclerosis.

Background: Macrophage migration inhibitory factor (MIF) is an important immuno-regulatory cytokine and is elevated in inflammatory conditions. Neutrophils are the first immune cells to migrate to sites of infection and inflammation, where they generate, among other mediators, the potent oxidant hypochlorous acid (HOCl). Here, we investigated the impact of MIF on HOCl production in neutrophils in response to phagocytic stimuli. Methods: Production of HOCl during phagocytosis of zymosan was determined using the specific fluorescent probe R19-S in combination with flow cytometry and live cell microscopy. The rate of phagocytosis was monitored using fluorescently-labeled zymosan. Alternatively, HOCl production was assessed during phagocytosis of Pseudomonas aeruginosa by measuring the oxidation of bacterial glutathione to the HOCl-specific product glutathione sulfonamide. Formation of neutrophil extracellular traps (NETs), an oxidant-dependent process, was quantified using a SYTOX Green plate assay. Results: Exposure of human neutrophils to MIF doubled the proportion of neutrophils producing HOCl during early stages of zymosan phagocytosis, and the concentration of HOCl produced was greater. During phagocytosis of P. aeruginosa, a greater fraction of bacterial glutathione was oxidized to glutathione sulfonamide in MIF-treated compared to control neutrophils. The ability of MIF to increase neutrophil HOCl production was independent of the rate of phagocytosis and could be blocked by the MIF inhibitor 4-IPP. Neutrophils pre-treated with MIF produced more NETs than control cells in response to PMA. Conclusion: Our results suggest a role for MIF in potentiating HOCl production in neutrophils in response to phagocytic stimuli. We propose that this newly discovered activity of MIF contributes to its role in mediating the inflammatory response and enhances host defence.

Background: Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. Methods: This study (‘ENGAGE’) was a pre-planned element of the randomized controlled trial, ‘RAINBOW’ (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy (‘PST’)). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach. Findings: PST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability. Interpretation: The negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity. Funding: US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368

Agricultural biotechnology produced genetically modified (GM) crops, not only provide economic benefits to farmers, but are beneficial to the environmental, human health, and consumers. At a time when no tool in agriculture can be overlooked when dealing with increasing environmental, food security, and economic pressures, what do Canadian consumers think of GM food, following over 20 years of consumption? This article presents the results of a 2018 survey of 506 English-speaking Canadian consumers, about GM food, food labels and purchasing decisions. Results show the two most important factors that impact Canadian consumer food purchase decisions are: price and place of origin (Canadian made). Canadian consumers are responding to surveys about their willingness to consume GM food products in diametric opposition to their actual purchasing behavior. That is, consumers say they mistrust GM foods, but when consumers are making food purchase decisions in grocery stores, price is the key purchase determining factor.

Despite the myriad benefits associated with regular physical activity (PA), few American adults accrue sufficient weekly PA. Although “lack of time” is often cited as a correlate of physical inactivity, a growing body of evidence suggests that, perhaps more importantly, people allocate their leisure-time to activities they find more enjoyable than PA. These findings underscore the need to devise physical activities that will be chosen over other enjoyable, but less healthy, behavioral alternatives. As a first step in this direction, we designed a group social PA play program for adults, known as PlayFit. The overarching philosophy of PlayFit is that fun and enjoyment are among the most important influences on PA adherence. In PlayFit, traditional sport games are modified to fulfill basic psychological needs, in a non-competitive, and non-contact environment. We will randomize 280 sedentary adults 18–50 years of age to 12-months of PlayFit or traditional group exercise, matching the groups on intensity, frequency, and duration. The primary outcomes include cardiorespiratory fitness (VO2peak), group adherence, and group enjoyment. We hypothesize that, at 6 months, cardiorespiratory fitness will have increased to the same extent in both groups, but at 12 months, only those randomized to PlayFit will have maintained their fitness through better adherence than Group Exercise – and this outcome will be mediated by enjoyment of the assigned group. Findings from this study could provide evidence that a focus on providing fun and enjoyable PA experiences for adults may be a viable route toward improving PA adherence. A simple, inexpensive PA intervention, such as PlayFit, may represent one such approach to do so.

Summary: The proximity pattern and radial distribution of chromosome territories within spherical nuclei are random and non-random, respectively. Whether this distribution pattern is conserved in the partitioned or lobed nuclei of polymorphonuclear cells is unclear. Here we use chromosome paint technology to examine the chromosome territories of all 46 chromosomes in hundreds of single human neutrophils – an abundant and famously polymorphonuclear immune cell. By comparing the distribution of chromosomes to randomly shuffled controls and validating with orthogonal chromosome conformation capture technology, we show for the first time that human chromosomes randomly distribute to neutrophil nuclear lobes, while maintaining a non-random radial distribution within these lobes. Furthermore, we demonstrate that chromosome length correlates with three-dimensional volume not only in neutrophils but other human immune cells. This work demonstrates that chromosomes are largely passive passengers during the neutrophil lobing process but are able to subsequently maintain their macro-level organization within lobes.