Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key polyphenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids was the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal and limited human studies for a dual preventative role of OO polyphenols in diabetes and cancer, especially that they share similar risk factors. Putative anti-oxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO phenolics, have produced paradoxical results making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anti-cancer and anti-diabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes.

Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in the developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literatures from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

The research is based on the inspection performed in June 2002 for carrying out a research program for the eradication of a termite infestation due a desertic species in the area of the Saint Catherine Holy Monastery at Mount Sinai - Egypt. The paper describes the application of the registered European bait system SentritechTM and the trend of eradication during the first year. The application of bait system blocked the termite infestation inside the Katholikon (Main church) and in the surrounding after 6 months. Nevertheless, the infestation restarted and even increased again in the surrounding of the main church. An explanation of this surprising event is attempted in this paper.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance, we are seeing an increased intersection of genomics, microbiology, and clinical epidemiology. Clear nomenclature for AMR gene families and pathogens is critical for communication. For CARD release version 3.0.3 (July 2019), we updated the entire CARD database to reflect the latest pathogen names. In total, we detected 48 name changes or updates, some of which reflect major changes in familiar names.

In this paper, we study the asymptotic behavior of the sequential empirical process and the sequential empirical copula process, both constructed from residuals of multivariate stochastic volatility models. Applications for the detection of structural changes and specification tests of the distribution of innovations are discussed. It is also shown that if the stochastic volatility matrices are diagonal, which is the case if the univariate time series are estimated separately instead of being jointly estimated, then the empirical copula process behaves as if the innovations were observed; a remarkable property. As a by-product, one also obtains the asymptotic behavior of rank-based measures of dependence applied to residuals of these time series models.

Among non-conventional yeasts of industrial interest, the dimorphic oleaginous yeast Yarrowia lipolytica appears as one of the most attractive for a large range of white biotechnology applications, from heterologous proteins secretion to cell factories process development. The past, present and potential applications of wild type, traditionally improved or genetically modified Yarrowia lipolytica strains will be resumed, together with the wide array of molecular tools now available to genetically engineer and metabolically remodel this yeast. The present review will also provide a detailed description of Yarrowia lipolytica strains and highlight the natural biodiversity of this yeast, a subject little touched upon in most previous reviews. This work intends to fill this gap by retracing the genealogy of the main Yarrowia lipolytica strains of industrial interest, by illustrating the search for new genetic backgrounds and by providing data about the main publicly available strains in yeast collections worldwide. At last, it will focus on exemplifying how advances in engineering tools can leverage a better biotechnological exploitation of the natural biodiversity of Yarrowia lipolytica and of other yeasts from the Yarrowia clade.

An ultra-low anti-reflection optical coating on both surfaces of a plastic cover slip was studied for use in confocal image measurement. The optical reflectance at a wavelength of 632.8 nm was less than 0.1% when the coated sample was placed in a liquid having a refractive index of 1.34 close to the aqueous solution of the biomaterial. The high- and low-index coating films, Substance-2 (PrTiO3) and silicon dioxide (SiO2), were measured by an ellipsometer to determine their optical refraction indices and extinction coefficients. Theoretically, when the two layer thicknesses are designed using the optical admittance diagram of the cover slip to approach the equivalent index of 1.34, a reflectance of 1.6×10-5% in the liquid could be obtained. Experimentally, the reflectance of the sample deposited on the two faces of the cover slip was 4.223±0.145% as measured in the air; and 0.050±0.002% as measured by a He-Ne laser in the liquid.

Management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wound care providers. Because of the chronic, non-healing nature of many DFUs, advances in the treatment and care of this disease process are particularly relevant. This case study aims to report the efficacy of the application of dehydrated amniotic membrane allograft (DAMA) to a diabetic foot ulcer. The patient in this study is a 44-year-old male who presented with an aggressive infection on his right foot, which resulted in an open wound of 18 months duration. This patient received weekly applications of dual-layer DAMA over seven weeks. Upon examination at the initial application, the wound was classified as a Wagner grade 3 with necrosis of the underlying muscle. Upon inspection at the final visit, the wound was closed entirely. The results that were shown include improvements in the size, depth, edges, necrotic tissue amount, and epithelization of the wound. This case study demonstrates that the ap-plication of DAMA has the potential to augment the body’s natural DFU healing response; however, future nonrandomized and randomized controlled trials are needed to establish its efficacy further.

Although the relations between sleep and academic performance have been extensively examined, how sleep predicts future academic performance (e.g., 2 -3 years) remains to be further investigated. Using wearable smartwatches and a self-report questionnaire, we tracked sleep activities of 45 college students over a period of approximate half a month to see whether their sleep activities predicted their academic performance, which was estimated by grade point average (GPA). Results showed that both nighttime sleep awakening frequency and its consistency in the tracking period were not significantly correlated with the GPA for the courses taken in the semester during sleep tracking (current GPA). However, both nighttime sleep awakening frequency and its consistency inversely predicted the GPA for the rest of the courses taken after that semester (future GPA). Moreover, students with more difficulty staying awake throughout the day obtained lower current and future GPAs, and students with lower inconsistency of sleep quality obtained lower future GPA. Together, these findings highlight the importance of nighttime sleep awakening frequency and consistency in predicting future academic performance and emphasize the necessity of assessing the consistency of sleep measures in future studies.

Little is known about how differences in water availability within the “super humid” tropics can influence the distribution of understory plant species and the composition of understory plant communities. We investigated variation in the physiological drought tolerances of understory plants and plant communities across a large elevation and precipitation gradient. We established 58 understory plots along a gradient of 400 – 3600 m asl elevation and 1000 – 6000 mm yr-1 rainfall in and around Manu National Park in southeastern Peru. Within the plots, we sampled all understory woody plants and measured three metrics of physiological leaf drought tolerance - turgor loss point (TLP), cuticular conductance (Gmin), and solute leakage (SL) - and assessed how the community-level means of these traits related to mean annual precipitation (MAP) and elevation (in the study gradient temperature decreases linearly and vapor pressure deficit increases monotonically with elevation). We did not find any correlations between the three metrics of leaf drought tolerance, suggesting that they represent independent strategies for coping with low water availability. Despite being widely used metrics of leaf drought tolerance, neither TLP nor Gmin showed any significant relationships with elevation or MAP. In contrast, SL, which has only recently been developed for use in ecological field studies, increased significantly at higher precipitations and at lower elevations (i.e., plants in colder and drier habitats have lower SL, indicating greater drought tolerances). Our results illustrate that differences in water availability may play a strong role in structuring plant communities even in in the wet tropics and highlight the potential for SL assays to be an efficient and effective tool for measuring drought tolerances in the field.

Purpose Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20-50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Methods Patients (N=36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). Results Median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and 9 (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and 15(42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax, and 9 (25%) to the abdomen or pelvis. Total dose ranged from 18 to 42.5 Gy in 6-17 fractions/ 2.67-5 Gy per fraction. Median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86), and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. Two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort, and 100, 87 (95%CI: 56.4-96.5%) and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI:59.9-90.5%), and 100, 66.1 (95% CI: 36.4-84.4%) and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. Conclusion HFRT in HM provides excellent local control without any increase in toxicity.

Mental wellness can be related to healthier living, the learning process and working environments for people in the university community. A wide range of mental wellness programmes have been explored to provide students with pleasant and satisfying experiences. The purpose of this study is to explore the effects of integrating Zen meditation(禪)and music listening on the mindfulness and happiness levels of university music therapy students. Qualitative methodology was used, and data were collected through surveys and semi-structured interviews. To investigate various aspects of data regarding the role of meditation and music (MM) programme for mindfulness and happiness, this study used thematic analysis within a qualitative research design. The results of this study indicate that the 8-week MM programme is effective in enhancing mindfulness and happiness and has positive responses to daily life stress (e.g., exam anxiety, financial difficulties, and emotional distress during the COVID-19 pandemic). The role of meditation and music in promoting mental health and well-being has long been discussed and the combination of the two has been recognised as a beneficial intervention. This paper could contribute to the support of mental health resources and coping strategies in higher education, as well as expand the potential range of integrating practices involving music and meditation.

Studies of discrete pride in the workplace are both few and on the rise. We examined what has, to date, been yet unstudied: the impact that a leader’s expressions of authentic and hubristic pride can have on the followers at that moment, and on their feelings about their task, leader, and group. Students working in groups building Lego structures rated their perceived leader regarding expressions of pride, both authentic and hubristic. Students who perceived the leader as expressing more authentic pride rated the task, group (satisfaction and cohesion), and leader more positively; while the reverse was generally true for perceptions of expressions of hubristic pride. We found these effects both at the individual level, and at the group level. We also predicted and found moderation for the type of task worked on, creative or detailed. Implications abound for leader emotional labor and emotion management.

Machines for direct digital inkjet printing on cylindrical containers are a new technology out on the market. Their commercialization in the industrial sector has been affected by their high precision. This leads to the use of mechanisms with narrow manufacturing tolerances and to the search for topologies that have the least accumulated error without affecting quality. Machines with topologies to work on flat substrates have printing and productivity problems working on cylindrical substrates. This research paper presents the qualitative design of a direct digital inkjet printer working over cylindrical substrates comparing five mechanical topologies; three topologies with radial distribution and two topologies with parallel distribution. The aim of these topologies is to find the precision, quality and efficiency of the printer taking into account the restrictions present in its construction. Each topology has separate constitutive mechanisms, it is analyzed the tolerance ranges between the print head and the substrate whose cumulative error maximizes the inkjet print resolution to determine precision. From five Topologies, number 1, 2 and 5 meet the requirements. the topology 2 meets the requirements but it is not able to be developed due to current technological limitations.

Knowledge about one’s innate health is central to a variety of positive mental health markers. However, men living in prison rarely receive education about how to access these internal resources. As such, this study seeks to replicate and extend emerging data on an innate health intervention. Volunteers from HMP Nottingham, England (n=126) participated in normal prison programming and the intervention group (n=65) received an additional 3-day intensive. The primary question: Does innate health function as a mediator in the same way self-control does within an incarcerated population? We conducted a mediation analysis, tested social desirability bias, and examined the impact of the intervention on crucial variables. This study found higher levels of innate health, self-control, wellbeing, and prosocial behavior and lower levels of aggression in the intervention group as compared to the control group. Importantly, innate health did play a mediating role equivalent to and/or partnering with self-control.

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression as well as infections associated with compromised immune system, such as tuberculosis (TB). Our aim was to overcome the gap in the literature concerning the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. We used a novel algorithm to identify patients with newly diagnosed granulomatous polyangiitis (GPA) or microscopic polyangiitis (MPA) between January 1, 2000 and December 31, 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2,257 patients with AAV and a propensity-score matched cohort of 9,028 patients were studied. Overall, patients with AAV were at a 1.48x higher risk of contracting incidental TB than were patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02-2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01-3.60). Female AAV patients were 3.24x more likely than females without AAV to develop TB (adjusted HR 3.24; 95%CI, 1.85-5.67). Conclusion: Patients with AAV face an elevated risk of contracting incidental TB, particularly within the first two years after AAV diagnosis. The risk of contracting TB is higher among female AAV patients than among females without AAV.

Background: The frequency of visits to restaurants has been suggested to contribute to the pandemic of obesity. However, few studies have examined how individual use of these restaurants is related to BMI using new technology of reminding to avoid memory error. Aim: To investigate the association between the usage of different types of food outlets and BMI among adults in Scotland. Method: The study was cross-sectional. Participants (n = 681) completed an online survey for seven consecutive days where all food purchased at food outlets was reported each day. We explored the relationship between BMI and usage of these restaurants using auto-reminder text system. Results: Body Mass Index (BMI) of both males and females was not related to frequency of use of Full-Service Restaurants (FSRs), Fast Food Restaurants (FFRs), delivery or takeaways, when assessed individually, or combined (TFO= Total Food Outlet). Conclusion: These data do not support the widespread belief that consumption of food out of the home at fast-food and full-service restaurants, combined with that derived from deliveries and takeaways, is a major driver of obesity in UK.

We bring a strength-based and socially-oriented lens to behaviors observed in profound autism. Social deficits are a defining characteristic of autism. Yet humans’ biological drive for social connection is sufficiently strong that is should be observable, in some form at least, in individuals with autism. We describe a case that validates this view. Mahad is a 20-year-old Pakistani-American male, with intellectual disability, and minimal verbal abilities. Mahad has an intense interest in food and the steps involved in food preparation. He employs and capitalizes on his family’s meal routines to ensure continual social attention from his mother. When not immersed in food, Mahad uses his limited capacities to pursue the additional biological needs of exploring his environment, seeking information, and developing his cognitive abilities.

Appropriate diagnosis, treatment and care contributes to better service engagement, improvements to wellbeing, cost savings, reductions in morbidity and mortality for people with Alcohol Related Brain Damage. In the North-East of England large amounts of alcohol are consumed, reflected in the number of alcohol-related deaths in the region. However, the pathway for people with Alcohol Related Brain Damage to receipt of diagnosis, treatment and care is unknown and could be unwittingly influenced by stigma. Qualitative in-depth semi-structured interviews were completed with 25 health and social care professionals from organisations involved with people with Alcohol Related Brain Damage recruited via snowball-sampling. Interviews were recorded, transcribed verbatim, coded, and analysed. People with Alcohol Related Brain Damage were stigmatised both by society and professionals which inhibited entry into services therefore Alcohol Related Brain Damage remained underdiagnosed and misdiagnosed. There was no dedicated service but silos with revolving doors and underfunded generic care with long waiting lists typically excluding those with alcohol or neurological problems. Professionals need to be challenged on the assumption that Alcohol Related Brain Damage is self-inflicted via training aimed at challenging unconscious bias. Reducing stigmatising processes associated with Alcohol Related Brain Damage could counteract professionals’ reluctance to provide care.

The rapid urbanization that takes place in developing regions such as Sub-Saharan Africa is associated with a large range of environmental and social issues. In this context, remote sensing is essential to provide accurate and up-to-date spatial information to support risk assessment and decision making. However, mapping urban areas remains a challenge because of their heterogeneity, especially in developing regions where the highest rates of misclassification are observed. Nevertheless, urban areas located in arid climates --- which are among the most vulnerables to anthropogenic impacts, suffer from the spectral confusion occurring between built-up and bare soil areas when using optical imagery. Today, the increasing availability of satellite imagery from multiple sensors allow to tackle the aforementioned issues by combining optical data with Synthetic Aperture Radar (SAR). In this paper, we assess the complementarity of the Landsat 8 and Sentinel-1 sensors to map built-up areas in twelve Sub-Saharan African urban areas, using a pixel-level supervised classification based on the Random Forest classifier. We make use of textural information extracted from SAR backscattering data in order to reduce the speckle noise and to introduce contextual information at the pixel level. Results suggest that combining both optical and SAR features consistently improves classification performances, mainly by enhancing the differentiation between built-up and bare lands. However, the fusion was less beneficial in mountainous case studies, suggesting that including features derived from a Digital Elevation Model (DEM) could improve the reliability of the proposed approach. As suggested by previous studies, combining features computed from both VV and VH polarizations consistently led to better classification performances. On the contrary, introducing textures computed from different spatial scales did not improve the classification performances.

In recent years, Web APIs have become a de facto standard for exchanging machine-readable data on the Web. Despite this success though, they often fail in making resource descriptions interoperable due to the fact that they rely on proprietary vocabularies that lack formal semantics. The Linked Data principles similarly seek the massive publication of data on the Web, yet with the specific goal of ensuring semantic interoperability. Given their complementary goals, it is commonly admitted that cross-fertilization could stem from the automatic combination of Linked Data and Web APIs. Towards this goal, in this paper we leverage the micro-service architectural principles to define a SPARQL Micro-Service architecture, aimed at querying Web APIs using SPARQL. A SPARQL micro-service is a lightweight SPARQL endpoint that provides access to a small, resource-centric, virtual graph. In this context, we argue that full SPARQL Query expressiveness can be supported efficiently without jeopardizing servers availability. Furthermore, we demonstrate how this architecture can be used to dynamically assign dereferenceable URIs to Web API resources that do not have URIs beforehand, thus literally ``bringing'' Web APIs into the Web of Data. We believe that the emergence of an ecosystem of SPARQL micro-services published by independent providers would enable Linked Data-based applications to easily glean pieces of data from a wealth of distributed, scalable and reliable services. We describe a working prototype implementation and we finally illustrate the use of SPARQL micro-services in the context of two real-life use cases related to the biodiversity domain, developed in collaboration with the French National Museum of Natural History.

Single-particle cryo-electron microscopy (cryo-EM SPA) has recently emerged as an exceptionally well-suited technique for determining the structure of membrane proteins (MPs). Indeed, in the last years, it was observed a huge increase in the number of MPs solved by cryo-EM SPA at a resolution better than 3.0 Å in the Protein Data Bank (PDB). However, sample preparation remains a significant challenge in the field. Here, we evaluated in the MPs solved by cryo-EM SPA deposited in the PDB in the last two years at a resolution below 3.0 Å the most critical parameters for sample preparation: i) the surfactant used for protein extraction from the membrane, ii) the surfactant, amphiphiles, nanodiscs or other molecules present in the vitrification step, iii) the vitrification method employed, and iv) the type of grids used. The aim is not to provide a definitive answer on the optimal sample conditions for cryo-EM SPA of MPs, but rather assess the current trends in the MP structural biology community towards obtaining high-resolution cryo-EM structures.

In a safety-critical system typically not all provided services have the same criticality, which we call mixed-criticality systems. Criticality arithmetic, also called SIL arithmetic, is an approach to lower the development effort of a service by providing redundancy with tasks that are developed for a lower criticality level. In this paper we present ATMP-CA, which is a derivation of the multi-core scheduler ATMP. ATMP-CA is able to take into account the knowledge about the use of criticality arithmetic. ATMP-CA has a modified core allocation and procedure for utility optimisation, considering the context of the replicated tasks. We conducted experiments that show that ATMP-CA is able to provide the services using criticality arithmetic, while the reference schedulers were not.

Phosphorus (P) is a vital macronutrient crucial for crop productivity. Plants absorb P salts, mainly orthophosphate, from soil, yet the primary P source resides in organic materials. Soil phosphomonoesterases (APases) play a vital role in releasing P from organics via hydrolysis. Acid and alkaline phosphatases are crucial for alleviating P deficiency in plants. In this review focused on agricultural soils, we studied the relationship of biophysicochemical, agricultural management, and climate factors on APases also its connection with crop growth and yields. Our findings indicate a strong linkage between both APases and soil pH, positively influenced by clay content, organic matter, microbial biomass carbon, and nitrogen. Adopting healthy soil practices like balanced organic fertilizer usage, optimal soil water levels, reduced tillage, crop rotation, and using beneficial plant microbes help boost APase activity. However, the connection between APases and crop productivity remains uncertain due to insufficient research in this area. Our review emphasizes the vital need to evaluate the relationship between APases and meso-macrofauna, alongside essential plant nutrients such as potassium, nutrient ratios, and the synergistic effects of various factors. Understanding the rapid, efficient assimilation of P through APases in the plant-soil and/or plant-microbiota ecosystem it can be crucial for crop productivity and yields.

Companion animals play a central role in many families and are especially valued by those who are socially isolated. Crisis situations such as acute hospitalizations, homelessness and natural disasters can make it difficult to preserve the human-animal bond and can result in animals being surrendered or euthanized. Social support programs like the RSPCA NSW Emergency Boarding and Homelessness program support people experiencing crisis situations with emergency pet boarding, access veterinary treatment and individualized case management. This study aimed to estimate the social return on investment (SROI) for this program using standard SROI methodology. In-depth interviews were conducted with 13 program stakeholders and questionnaire responses were received from 29 program clients. Outcomes were quantified for four stakeholder groups: program clients, client’s animals, RSPCA Inspectors, animal pounds and shelters. Clients and their animals experienced the bulk of the benefit from the program, estimated to have a combined value of over $5 million AUD for the 2020-21 financial year. The estimated social return on investment was $8.21 for each $1 invested. The study demonstrates that keeping people together with their companion animals, or ensuring they are reunited as soon as possible, can reduce stressors, and improve outcomes for people and animals.

Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). B. miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and thus has been uniquely labeled a hard tick-borne relapsing fever Borrelia. Burgeoning research has uncovered new aspects of B. miyamotoi in human patients, nature, and the lab. Of particular interest are novel findings on disease pathology, prevalence, diagnostic methods, ecological maintenance, transmission, and genetic characteristics. Herein we review recent literature on B. miyamotoi, discuss how findings adapt to current Borrelia doctrines, and briefly consider what remains unknown about B. miyamotoi.

Calcium carbonate cements have been synthesized by mixing amorphous calcium carbonate and vaterite powders with water to form a cement paste and study how mechanical strength is created during the setting reaction. In-situ XRD was used to monitor the transformation of ACC and vaterite phases into calcite and a rotational rheometer was used to monitor the strength evolution. There are two characteristic time scales of the strengthening of the cement paste. The short timescale of the order 1 hour is controlled by smoothening of the vaterite grains, allowing closer and therefore adhesive contacts between the grains. The long timescale of the order 10-50 hours is controlled by the phase transformation of vaterite into calcite. This transformation is, unlike in previous studies using stirred reactors, found to be mainly controlled by diffusion in the liquid phase. The evolution of shear strength with solid volume fraction is best explained by a fractal model of the paste structure.

Temporomandibular disorders (TMD) affect a high percentage of children and adults worldwide. Surgery may be indicated in severe or recalcitrant case. Several recent advancements in the TMD and temporomanidbular joint (TMJ) surgery have elevated understanding and ability to treat affected patients. We discuss recent advances in TMD epidemiology, juvenile idiopathic arthritis (JIA) of the TMJ, and surgical techniques and technologies. Technical advancements have been identified in TMJ arthroscopy, treatment of TMJ subluxation and dislocation, and extended prosthetic total TMJ reconstruction (eTMJR). Overall, this review provides valuable insights into significant recent advancements of TMJ disorders and their surgical management.

Inteins, often referred to as protein introns, are highly mobile genetic elements that invade conserved genes throughout the tree of life. Inteins have been found to invade a wide variety of key genes within actinophages. While in the process of conducting a survey of these inteins in actinophages we discovered that one protein family of methylases contained a putative intein, and two other unique insertion elements. These methylases are known to occur commonly in phages as orphan methylases (possibly as a form of resistance to restriction-modification systems). We found that the methylase family is not conserved within phage clusters and has a disparate distribution across divergent phage groups. We determined that two of the three insertion elements have a patchy distribution within the methylase protein family. We also found that the third insertion element is likely a second homing endonuclease, and that all three elements (the intein, the homing endonuclease, and what we refer to as the ShiLan domain) all have different insertion sites that are conserved in the methylase gene family. Furthermore, we find strong evidence that both the intein and ShiLan domain are partaking in long distance horizontal gene transfer events between divergent methylases in disparate phage hosts within the already dispersed methylase distribution. The reticulate evolutionary history of methylases and their insertion elements reveals high rates of gene transfer and within-gene recombination in actinophages.

Pediatric obstructive sleep apnea (OSA) has significant negative effects on health and behavior in childhood including depression, failure to thrive, neurocognitive impairment, and behavioral issues. It is strongly associated with an increased risk for chronic adult disease such as obesity and diabetes, accelerated atherosclerosis, and endothelial dysfunction. Accumulating evidence suggests that adult-onset non-communicable diseases may originate from early life through a process by which an insult applied at a critical developmental window causes long-term effects on the structure or function of an organism. Recently, much attention has been paid to the role of epigenetic mechanisms in the pathogenesis of adult disease susceptibility. Epigenetic mechanisms that influence adaptive variability include histone modifications, non-coding RNAs, and DNA methylation. This review will highlight what is currently known about the phenotypic associations of epigenetic modifications in pediatric OSA and will emphasize the importance of epigenetic changes as both modulators of chronic disease and potential therapeutic targets.

Folk nomenclature is habitually established for species that have attained high utilitarian and cultural significance by custodians of such plants worldwide. Such folk names assigned to species often carry etymological values such as therapeutic effects, morphological features, mythical connotations, and their allegorical values. This research sought to unveil the etymology in folk nomenclatures of Sphenostysis stenocarpa (Hosch ex A. Rich) Harms (African Yam Bean). Three hundred and fifty respondents were randomly selected from 13 local communities in Ebonyi State in South-eastern, Nigeria. Data were collected through oral interviews with semi-structural questionnaires, along with focused group discussions. Analysis of data was carried out using simple statistical methods involving frequencies and percentages. The results recorded ten folk nomenclatures assigned to this species in seven dialects affiliated to cultural values within these communities. Etymologically, the results also revealed that out of the ten folk names of AYB cryptic connotations, five reflected their trust in the gods that answered their prayers, two were attributed to the healing potentials inherent in this crop for medicine, three names were associated with the seeds, while one referred to feminist attachment to the crop, another to its resilience/ adaptability to climatic stress and one as a sustainer of farmers. Considering that folk nomenclature is based mainly on qualitative data and the information outside the scientific domain, they are nonetheless highly valued because they are based on long-term interactions, utilization and observations of the custodians of these natural resources. However, these data are equally vulnerable to erosion if not properly documented and conserved for posterity.

Care coordination (CC) for children with special healthcare needs and medical complexity (CSHCN-CMC) is challenging, and medication management is especially difficult for providers, parents/caregivers, and patients alike. While numerous strategies for CC have been suggested and implemented, barriers to medication optimization remain. The report describes the creation of a pediatric clinical pharmacotherapy practice, related standard operating procedures to assure consistent application of screening tools and care provision through comprehensive medication management (CMM), and establishment of a collaborative practice agreement (CPA) to guide drug therapy delegation, monitoring, and modification. The methodology of a prospective case series is also presented to highlight drug therapy problems and their resolution in CSHCN-CMC. Future opportunities to expand the practice for engagement in population health management as well as prior authorization activities on behalf of physicians will be discussed.

Abstract: Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin. During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), SEC-HPLC and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX-heme interactions to approximate physiological conditions (from extremely low to more than 2-fold heme excess). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggests more than one binding site in both plasma and rhHPX. Further, our study provides a useful analytical platform for detailed characterization of HPX-heme interactions and potentially, novel HPX fusion constructs.

Androgen deprivation therapy (ADT) for prostate cancer treatment is associated with adverse physiological changes, however exercise can improve outcomes. This systematic review and meta-analysis aimed to determine exercise intervention adherence, and its effects on physiological outcomes in men diagnosed with prostate cancer undergoing ADT. Uniquely, this review incorporates a meta-aggregation of qualitative data, providing perspectives from the men’s experiences. A systematic review and meta-analysis were completed following PRISMA Guidelines. Databases (CINAHL, Cochrane, PubMed) were searched for studies using “prostate cancer”, “exercise intervention”, and “androgen deprivation therapy”. Quantitative randomised controlled trials describing adherence to exercise interventions were selected, with qualitative articles selected based on descriptions of experiences around participation. Subgroup meta-analyses of adherence, exercise mode, and intervention duration were completed for quality of life, aerobic fitness, fatigue, and strength. Articles (n=64) articles were identified, with 29 (n=23 quantitative; n=6 qualitative) articles from 25 studies included. Exercise had no effects (p<0.05) on quality of life and fatigue. Significant effects (all p<0.05) were observed for aerobic fitness, and upper- and lower-body strength. Adherence to exercise-based interventions was 80.38%, with improvements observed in aerobic fitness and strength. Subgroup analysis revealed exercise adherence impacted fatigue and strength, with greater improvements observed in programs >12-weeks.

contaminated sites located in each school district. Previous studies showed that various environmental factors, such as exposure to toxic substances negatively impacts human health depending on their concentration and occurrence. Therefore, the study aims to use Geographical Information System (GIS) technology and secondary data on IEP numbers of each school district, chemical occurrence in contaminated sites, and demographic data to conduct a correlational analysis. The secondary data obtained from school districts and contaminated sites from Iowa Department of Natural Resources Facility Explorer were populated in ArcMap 10.5 (a GIS software) for generating maps and data to conduct statistical analysis. The contaminants were categorized into metals, polyaromatic hydrocarbons (PAH), and solvents with weighing factors as 1, 0.5, and 0.25. A total of 1 Superfund site and 39 CERCLA sites were identified as contaminated sites for this study. The majority of contaminants were heavy metals such as lead, arsenic, mercury, and cadmium. The mean toxic score of all contaminated sites combined was 13.4 (sd 14.4). The correlational analysis between the IEP numbers from each school districts and toxic scores from the contaminated sites was positive indicting that increased toxic score increased the number of students enrolled in the IEP program (F=23.7, p<0.0001). The correlational analysis between toxic score and demographics indicated some interesting results. Children under the age of 10 were living in areas with high toxic score and the showed mild correlation (p<0.00052). Similarly, higher number of black population resided in areas with high toxic score (p=0.0032) than the white population (p<0.0001). The result also indicated that children enrolled in IEP were predominantly among the black population (p<0.0001). The correlational analysis between household income and poverty percentage of people residing near the contaminated area indicated that people had low average household income (p=0.0002) and high poverty percentage (p=0.0203) residing in areas with higher toxic score. Regarding the educational status, less number of people with post graduate degree (p<0.0001) resided in areas with high toxic score and more number of people with no degree (p<0.0001) resided in areas with high toxic score. Finally, the study showed the increasing trend of eligible children enrolling in free and reduced lunch programs with increasing toxic scores (p=0.0012) and IEP levels (p=0.0416). This study emphasize on developing multiple exposure to correlate environmental factors contributing to the negative health outcome on people.

The level of ambiguity in describing glycan structure has significantly increased with the upsurge of large scale glycomics and glycoproteomics experiments. Consequently, an ontology-based model appears as an appropriate solution for navigating this data. However, navigation is not sufficient and the model should also enable advanced search and comparison. A new ontology with a tree logical structure is introduced to represent glycan structures irrespective of the precision of molecular details. The model heavily relies on the GlycoCT encoding of glycan structures. Its implementation in the GlySTreeM knowledge base was validated with GlyConnect data and benchmarked with the Glycowork library. GlySTreeM is shown to be fast, consistent, reliable and more flexible than existing solutions for matching parts of or whole glycan structures. The model is also well suited to painless future expansion. Availability:https://glyconnect.expasy.org/glystreem/wiki

Rural landscapes all over the world are subject to great transformations, first of all the continuous and slow depopulation of land and villages. It is a dramatic phenomenon that causes devastating consequences for environmental systems and for the tangible and intangible heritage of entire territories. The situation becomes more ambiguous when it comes to cultural landscapes, especially those internationally recognized as exceptional (i.e. inscribed on the UNESCO World Heritage List). In this case, the risk is to abandon agricultural production in favor of consumerist tourist economies, which can damage the territorial authenticity. In this paper we question the role of the landscape project in strengthening territorial resilience. In particular, a composite and interdependent action is proposed between landscape design and implementation of a multifunctional agriculture model, oriented towards teaching and tourism. To undertake this investigation, a master's thesis work on Landscape Architecture is examined, as an opportunity for a research-by-design method. The application case is the Italian UNESCO site of Vignale Monferrato, a depopulated rural village, characterized by abandoned land and buildings. The paper concludes by outlining replicability application scenarios for the proposed model.

The rich emission and absorption line spectra of Fe I may be used to extract crucial information on astrophysical plasmas, such as stellar metallicities. There is currently a lack, in quality and quantity, of accurate level-resolved effective electron-impact collision strengths and oscillator strengths for radiative transitions. Here, we discuss the challenges in obtaining a sufficiently good structure for neutral iron and compare our theoretical fine-structure energy levels with observation for several increasingly large models. Radiative data is presented for several transitions for which the atomic data is accurately known.

A low-resource emotional speech synthesis system for empathetic speech synthesis based on modelling prosody features is presented here. Secondary emotions, identified to be needed for empathetic speech, are modelled and synthesised in this paper. As secondary emotions are subtle in nature, they are difficult to model compared to primary emotions. They are also less explored, and this is one of the few studies that model secondary emotions in speech. Current speech synthesis research uses large databases and deep learning techniques to develop emotion models. There are many secondary emotions, and hence, developing large databases for each of the secondary emotions is expensive. This research presents a proof-of-concept using hand-crafted feature extraction and modelling of these features using a low resource-intensive machine learning approach, thus creating synthetic speech with secondary emotions. Here, a quantitative model-based transformation is used to shape the emotional speech fundamental frequency contour. Speech rate and mean intensity are modelled via rule-based approaches. Using these models, an emotional text-to-speech synthesis system to synthesise five secondary emotions - anxious, apologetic, confident, enthusiastic and worried is developed. A perception test to evaluate the synthesised emotional speech is also conducted.

SMARCA4-deficient non-small cell lung cancer (NSCLC) is a more recently recognized subset of NSCLC. We describe the 18F-fluorodeoxyglucose (FDG) PET/CT findings in a rare case of SMARCA4-deficient NSCLC and response to therapy. A 45-year-old male patient with a history of heavy smoking (10 years) underwent an 18F-fluorodeoxyglucose (FDG) PET/CT dynamic (chest) + static (whole-body) scan for diagnosis and pre-treatment staging. 18F-FDG PET/CT showed an FDG-avid mass in the upper lobe of the left lung (SUVmax of 22.4) and FDG-avid lymph nodes (LN) in the left pulmonary hilar region (SUVmax of 5.7). In addition, there are multiple metastases throughout the body, including distant LNs, adrenal glands, bone, and brain. Pathological findings confirmed SMARCA-4 deficient NSCLC. After 4 cycles of chemotherapy and immune checkpoint inhibitors（ICI）, the patient underwent again an 18F-FDG PET/CT scan (including dynamic scan) for efficacy evaluation. We report cases that deepen the understanding of the 18F-FDG PET/CT presentation of SMARCA4-deficient NSCLC as well as dynamic imaging features and parametric characteristics.

We investigated 328 SARS-CoV-2 cases in Barwon South West Victoria, Australia, in the 2020 pre-vaccination period, comparing infections with symptoms to those that remained asymptomatic. De-identified self-reported data from three sequential questionnaires on case characteristics and symptom progression were examined. Multivariable logistic regression were used to model associations between demographic profile and symptoms. Asymptomatic cases were more than three times as likely to be from ethnic minority groups [OR 3.2, 95% CI 1.5 – 6.7, p&lt;0.01], and approximately seven times more likely to be seniors (≥ 65 years) [OR 7.3, 95% CI 1.0 – 50.1] after adjusting for sex and occupation. The overrepresentation of ethnic minority groups among asymptomatic infections is suggestive of genetic haplotype variability by ethnic group, conferring greater cross protection from other coronaviruses in the early stages of the COVID-19 pandemic. This research should be repeated post-vaccination to reassess symptom expression according to ethnicity, and better comprehend case ascertainment impacts of cultural biases in testing and infection reporting, and the reliance on symptoms to trigger testing. These findings may in part reflect differences in testing patterns by ethnicity and true differences in disease expression, both important for appropriate transmission prevention strategies, and tailoring testing messaging towards ethnic minority communities.

Saccharomyces cerevisiae are a phenotypically diverse species that adapt to a wide variety of environments by exploiting standing genetic diversity and selecting for advantageous mutations. Glyphosate and copper-based herbicides/ fungicides affect non-target organisms, these incidental exposures can impact microbial populations. In this study, glyphosate resistance was found in the historical collection of yeast which was collected over the last century, but only in yeast isolated after the introduction of glyphosate. The highest glyphosate-resistant yeasts were isolated from agricultural sites. However, herbicide application at these sites was not recorded. In an effort to assess glyphosate resistance and impact on non-target microorganisms, yeast were harvested from 15 areas with known herbicidal histories, including an organic farm, conventional farm, remediated coal mine, suburban locations, state park, and a national forest. Yeast representing 23 genera were isolated from 237 samples of plant, soil, spontaneous fermentation, nut, flower, fruit, feces, and tree material samples. Saccharomyces, Candida, Metschnikowia, Klyveromyces, Hanseniaspora, and Pichia were other genera commonly found across our sampled environments. Managed areas had less species diversity and at the brewery, only Saccharomyces and Pichia were isolated. A conventional farm growing RoundUp Ready™ corn had the lowest phylogenetic diversity and the highest glyphosate resistance. The mine was sprayed with multiple herbicides including a commercial formulation of glyphosate; however, the yeast did not have elevated glyphosate resistance. In contrast to the conventional farm, the mine was exposed to glyphosate only one year prior to sample isolation. Glyphosate resistance is an example of the anthropogenic selection of nontarget organisms.

The marine environment is the largest ecological habitat on Earth, albeit one of the least explored, particularly in terms of its microbial inhabitants. The marine fish gut is host to a diverse microbial community from which diverse bioactive molecules can be sourced. Due to the unique environmental pressures these microbial communities experience, the bioactive molecules they produce often evolve unique adaptations that give them diverse structures and activities, differentiating them from terrestrial homologues. Of particular interest, due to their structural and functional diversity, are the ribosomally-synthesized antimicrobial peptides (bacteriocins). With increasing pressure from emerging antibiotic-resistant disease and industrial demand for novel therapeutics, the marine fish gut microbiome represents a relatively untapped resource of novel bacteriocins that could prove beneficial to human health and aquaculture. This review presents an overview of the marine fish gut microbiome and explores its potential as a source of bacteriocins for human health with considerations for applications and future research in this area.

The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.

In recent years, technical processes for the sequestration of CO2 through industrial waste mineral carbonation have been explored and developed. There is a large portfolio of Carbon Capture, Uti-lisation and Storage (CCUS) techniques that have been employed on a laboratory and at pilot scale. These include geological storage, ocean storage and mineralisation by carbonate ores. In view of this, the main purpose of this research was to investigate and explore chemical variables, particularly ammonium salts as lixiviants for calcium mineral extraction from iron making slag. The slag in use was acquired from a Steel Mill in the Vaal Triangle Region in Gauteng, South Af-rica. The experimental test work was conducted using different ammonium lixiviants, namely, NH4NO3, NH4Cl and CH3COONH4 to understand the influence of anion type as well as possible differences in mechanisms of interactions. Lixiviant concentration as well as the reaction time were varied in this research study. The three selected ammonium based lixiviants showed different extents of calcium extraction owing to differences in the anion groups. NH4NO3, NH4Cl and CH3COONH4 were found capable of dissolving 50% to 80% of calcium from the selected slag for different molar concentrations. Anion type and leaching time also had significant influences on the leaching of calcium from the slag. Rapid pH degradation resulted in better calcium extraction ca-pabilities. This work has shown that the selected ammonium salts have a potential as lixiviants for calcium dissolution from iron making blast furnace slags. These lixiviants would therefore be important to consider during calcium mineral carbonation for CO2 sequestration.

The present investigation focuses on the impact of jet nozzle orientation on mixing time in a cylindrical tank. The aim is to identify nozzle positions that improve mixing performance and to elucidate the governing parameters that influence it. A water tank was employed for the experiment. The vertical inclination angle (α) and the horizontal inclination angle (β) of the jet nozzle determined the nozzle positions. Mixing time was determined using an inert tracer and spectrophotometry measurements. The findings show that the mixing time is significantly influenced by the position of the jet nozzle position. The accuracy of existing jet turbulence and the circulation models for the prediction of mixing time was evaluated for the different nozzle positions. Our results indicate that both models provide accurate predictions for the conventional centrally aligned (β = 0°), upward-pointing jet nozzle positions only (α > 0). For the other nozzle positions where β > 0° and at varying α, the data follow the same trends as the jet turbulence and circulation models, however, the proportionality constants vary. Shorter mixing times can be attributed principally to longer jet path lengths and therefore higher fluid entrainment and circulation, as well as higher dissipation rates per jet length squared. However, it is suspected that the 3-dimensional nature of the flow pattern generated in the tank also plays a non-negligible role since mixing is hindered when the nozzle points more towards the tank wall.

In medico-administrative database, certain prognostic factors cannot be taken into account. The main objective was to estimate the performance of two models based on two databases: Epi-thor clinical and medico-administrative databases. For each of the two databases, we randomly sampled a development dataset with 70% of the data and a validation dataset with 30%. Performance of models was assessed by Brier score, the area under the receiver operating characteristic (AUC ROC) curve and the calibration of the model. For Epithor and medico-administrative databases, the development dataset included 10,516 patients (with resp. 227 (2.16%) and 283(2.7%) deaths) and the validation dataset included 4,507 patients (with resp. 93 (2%) and 119 (2.64%) deaths). 15 predictors were selected in the models (including FEV, Body Mass Index, ASA score and TNM stage for Epithor). The Brier score values were similar in the models of the two databases. For validation data, the AUC ROC curve was 0.73 [0.68-0.78] for Epithor and 0.8 [0.76-0.84] for medico-administrative databases. The slope of the calibration plot was less than 1 for the two databases. This work shows the good performances of a model developed from a medico-administrative database, despite the absence of clinical variables used in practice by surgeons, such as FEV1, ASA score or TNM stage.

Rotavirus (RV) replicates within viroplasms, membrane-less electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single and double-stranded virus RNAs, and host components such as microtubules, perilipin-1 and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

Obesity in children is associated with vitamin D (VD) deficiency and cardiometabolic abnormalities. To analyze the effects of VD supplementation in adolescents with obesity enrolled in a weight-loss program. Adolescents with obesity (n=26) and with normal weight (n=23; controls) were matched for age, sex, and puberty stage. The obesity group followed a 3-month weight-loss program that combined a reduced caloric intake with interval training physical activity and during which they received or not VD supplementation (4000 IU/d) (n=13/group; random assignation). The anthropometric parameters (BMI z-score, fat mass); serum levels of 25(OH)D, calcium and parathyroid hormone (PTH), cardiometabolic factors (triglycerides, HDL, and LDL cholesterol), fasting glucose and insulin, and homeostasis model assessment of insulin resistance index; diastolic, systolic and mean blood pressure, and inflammatory status (C-reactive protein, CRP) were measured at baseline and at the end of the 3-month program. At baseline, 25(OH)D concentration was lower and VD insufficiency (25(OH)D levels <50 nmol/L) rate was higher (73% vs 22%) in the obesity than in the normal-weight group. All cardiometabolic factors were altered in the obesity compared with the normal-weight group. After the 3-month weight-loss program, 25(OH)D levels was >50 nmol in all adolescents with obesity, but only in 46% of normal-weight adolescents. Moreover, the weight-loss program improved the cardiometabolic factors, inflammatory status (CRP) and physical performance, but VD supplementation did not have any additional effect. Analysis only of the adolescents with obesity and VD deficiency (25(OH)D <50 nmol/L) at baseline showed a significant correlation between the change in PTH and CRP (p=0.02) in the supplemented obesity group, while the increase in 25(OH)D only tended to be correlated with CRP decrease. Vitamin D supplementation could reduce VD insufficiency in adolescent with obesity, but does not have any additional effect on cardiometabolic factors when combined with a weight-loss program.

The progressive impairment analysis in gait from neurological diseases patients such as Hereditary Ataxias (HA) has been carried out using gait data collected with movement sensors. This research is focused on finding the minimum amount required of gait features to recognize efficiently and less intrusive way, HA patients based on data collected with iPhone movement sensors placed on the ankles from 14 HA patients and 14 healthy people. A twofold proposal is made , first a local minimum prominent peak criterion to find out the starting point of each stride, to get 10-stride window about which 56 spatial-temporal features are derived; second a search strategy based on Hill Climbing algorithm to reduce the number of gait features and sensors. The main results were the findings that with two gait patterns a 96% of classification accuracy was achieved by using K-Nearest Neighbors (KNN) and Multi-Layer Perceptron (MLP) algorithms, but in addition, MLP only right ankle sensor patterns were required which also allows to reduce the intrusion.

The spectra currently emerging from modern ground- and space-based astronomical instruments are of exceptionally high quality and resolution. To meaningfully analyse these spectra researchers utilise complex modelling codes to replicate the observations. The main inputs to these codes are atomic data such as excitation and photoionisation cross sections as well as radiative transition probabilities, energy levels and line strengths. In this publication the current capabilities of the numerical methods and computer packages used in the generation of these data are discussed. Particular emphasis is given to Fe-peak species and the heavy systems of tungsten and molybdenum. Some of the results presented to highlight certain issues and/or advances have already been published in the literature, while other sections present, for the first time, new recently evaluated atomic data.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Antibiotic resistant Pseudomonas aeruginosa infections are the primary cause of mortality in people with cystic fibrosis (CF). Yet it has only recently become appreciated that resistance mutations can also increase P. aeruginosa virulence, even in the absence of antibiotics. Moreover, the mechanisms by which resistance mutations increase virulence are poorly understood. In this study we tested the hypothesis that mutations affecting efflux pumps can directly increase P. aeruginosa virulence. Using genetics, physiological assays, and model infections, we show that efflux pump mutations can increase virulence. Mutations of the mexEF efflux pump system increased swarming, rhamnolipid production, and lethality in a mouse infection model, while mutations in mexR that increased expression of the mexAB-oprM efflux system increased virulence during an acute murine lung infection without affecting swarming or rhamnolipid gene expression. Finally, we show that an efflux pump inhibitor, which represents a proposed novel treatment approach for P. aeruginosa, increased rhamnolipid gene expression in a dose-dependent manner. This finding is important because rhamnolipids are key virulence factors involved in dissemination through epithelial barriers and cause neutrophil necrosis. Together, these data show how current and proposed future anti-Pseudomonal treatments may unintentionally make infections worse by increasing virulence. Therefore, treatments that target efflux should be pursued with caution.

Greek yogurt (GY), a high-protein-low-fat dairy product, particularly prized for its sensory and nutritional benefits, revolutionized the North American yogurt market in less than a decade, bringing with it new sustainability challenges. The standard production of GY generates large volumes of acid whey, a co-product that is a potential source of environmental pollution if not recovered. This study aims to assess the environmental performance of different technologies and identify the main factors for improving GY production. A complete life cycle assessment (LCA) was performed to compare the standard technology (centrifugation) with two new technologies (fortification and ultrafiltration) to reduce acid whey volumes. Three milk protein concentrate alternatives were also assessed. Results show that the technology choice is not a clear discriminant factor. However, minimizing losses and wastage (accounting for 23 to 25% of the environmental impacts for all indicators) beyond the processing plant and selecting milk ingredients (accounting for 63 to 67% of the impacts) with low environmental impacts are key factors in improving the environmental performance of GY systems. From a methodological perspective, the results also highlight a shortcoming in the current International Dairy Federation LCA guidelines (2015) for treating the multifunctionality of GY systems.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

Background and aim: To explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of Non-Alcoholic Fatty Liver Disease (NAFLD), and cardiovascular disease (CVD) risk in the general population. Methods: Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. Receiver Operating Characteristic (ROC) curve, linear/logistic regression models and Spearman's correlations were used. Results: Intricate associations were found between CK18, FLI and CVD risk scores. While M30 was the only independent predictor of FLI≥60, M65 discriminated best NAFLD individuals at very-high 10-years CVD risk according to SCORE2 (AUC:0.71; p=0.001). Values above the predefined manufacturer cut-off (400 U/l), were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p=0.01), with negative predictive value of 93%. Conclusions: Confirming that NAFLD is associated with an increased CVD risk, our results point to CK18 M65 as a candidate biomarker to identify NAFLD individuals at low CVD risk in European general population.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Quality of life (QoL) assessments are integral to cancer care, yet their effectiveness in providing essential information for supporting survivors varies. This study aimed to elucidate key indicators of QoL among colorectal cancer survivors from the perspective of healthcare professionals, and to evaluate existing QoL questionnaires in relation to these indicators. Two studies were conducted: a Delphi study to identify key QoL indicators and a scoping review of questionnaires suitable for colorectal cancer survivors. Fifty-four healthcare professionals participated in the Delphi study's first round, with 25 in the second. The study identified two primary QoL domains (Physical and Psychological) and 17 subdomains deemed most critical. Additionally, a review of 12 questionnaires revealed two instruments assessing the most important general domains. Findings underscored a misalignment between existing assessment tools and healthcare professionals' clinical priorities in working with colorectal cancer survivors. To enhance support for survivors' QoL, efforts are needed to develop instruments that better align with the demands of routine QoL assessment in clinical practice.

Natural killer (NK) cells are part of the innate immune system, protects against pathogens and tumor cells and are the main cell effectors of monoclonal antibodies (mAbs) generating antibody-dependent cell cytotoxicity (ADCC). Hence it is relevant to understand NK physiology and status to investigate the biological effect of mAbs in the clinic. The presence of viral-sculpted NK cell populations has already been described, but the presence of cancer-sculpted NK remains unknown. Cancer induces a broad NK cell dysfunction. We investigated the NK cell population by Uniform Manifold Approximation and Projection (UMAP) embed maps in Hodgkin lymphoma (HL) and acute myeloid leukemia (AML) patients at diagnosis and at least 30 days after treatment, which correlates with tumor cell clearance. The NK lineage largely responded to the tumor by generating antitumor NK cells and renewing the population with a subset of immature NK cells. However, we failed to identify specific “memory-like” subsets. Moreover, in patients in relapse we found essentially the same NK populations that at diagnostic, suggesting that NK cells equally respond to the first or second tumor rise. Finally, previous CMV infection largely affects tumor-associated changes in NK population, but the CMV-associated CD57+NKG2C+ NKs do not appear to play any role in tumor immunity.

The assimilation of Soil Moisture and Ocean Salinity (SMOS) data into the ECMWF (European Centre for Medium Range Weather Forecasts) H-TESSEL (Hydrology revised - Tiled ECMWF Scheme for Surface Exchanges over Land) model is presented. SMOS soil moisture (SM) estimates have been produced specifically by training a neural network with SMOS brightness temperatures as input and H-TESSEL model SM simulations as reference. This can help the assimilation of SMOS information in several ways: (1) the neural network soil moisture (NNSM) data have a similar climatology to the model, (2) no global bias is present with respect to the model even if regional differences can exist. Experiments performing joint data assimilation (DA) of NNSM, 2 metre air temperature and relative humidity or NNSM-only DA are discussed. The resulting SM was evaluated against a large number of in situ measurements of SM obtaining similar results to those of the model with no assimilation, even if significant differences were found from site to site. In addition, atmospheric forecasts initialized with H-TESSEL runs (without DA) or with the analysed SM were compared to measure of the impact of the satellite information. Although, NNSM DA has an overall neutral impact in the forecast in the Tropics, a significant positive impact was found in other areas and periods, especially in regions with limited in situ information. The joint NNSM, T2m and RH2m DA improves the forecast for all the seasons in the Southern Hemisphere. The impact is mostly due to T2m and RH2m, but SMOS NN DA alone also improves the forecast in July- September. In the Northern Hemisphere, the joint NNSM, T2m and RH2m DA improves the forecast in April-September, while NNSM alone has a significant positive effect in July-September. Furthermore, forecasting skill maps show that SMOS NNSM improves the forecast in North America and in Northern Asia for up to 72 hours lead time.

Enterovirus A71 (EV-A71) infection is a major cause of hand, foot and mouth disease (HFMD) which may be occasionally associated with severe neurological complications. There are currently a lack of treatment options for EV-A71 infection. The Raf-MEK-ERK signaling pathway, in addition to its critical importance in the regulation of cell growth, differentiation and survival, has been shown to be essential for virus replication. In this study, we investigated the anti-EV-A71 activity of vemurafenib, a clinically approved B-Raf inhibitor used in the treatment of late stage melanoma. Vemurafenib exhibits potent anti-EV-A71 effect in cytopathic effect inhibition and viral load reduction assays, with half maximal effective concentration (EC50) at nanomolar concentration. Mechanistically, vemurafenib interrupts both EV-A71 genome replication and assembly. These findings expand the list of potential antiviral candidates of anti-EV-A71 therapeutics.

Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

Fagonia indica is a perennial plant grown in arid climates and utilised in traditional medicine as a treatment for cancer. Previous research has highlighted potential antineoplastic effects of Fagonia indica against breast cancer cell lines. Despite this, there has been little research demonstrating the potential of an aqueous extract of Fagonia indica against colon cancer. Colon cancer is a leading cause of cancer-related mortality, with drug resistance remaining a barrier to treatment. The aim of the present study was to investigate the cytotoxic mechanisms of Fagonia indica in colon cancer cells, including pathways related to proliferation, angiogenesis and inflammation, and ABC membrane transporters. Treatment with Fagonia indica caused a reduction in cell viability in wild-type and chemotherapy resistant colon cancer. Results indicated a role for Akt/ MAPK signalling as a mechanism of Fagonia indica induced cell death, alongside a reduction in the expression of VEG-F, NK-κB and ICAM-1. RT-PCR demonstrated a reduction in expression of ABCG2/ABCC4 in resistant colon cancers, after treatment with Fagonia indica extract. Further research is required to isolate bioactive compounds of Fagonia indica for use against colon cancer.

We explored the impacts of the remote and return to in-person work periods on sleep and well-being as reported by faculty (n = 22) and non-teaching staff (n=21) with and without disabilities. Our results show that contrary to expectations, the Covid-19 remote teaching/working period resulted in better sleep, as well as greater well-being, than the return to in-person. With respect to sleep, faculty members had slightly more negative outcomes than staff, most evident in heightened anxiety and work aspects. Faculty with disabilities had somewhat worse sleep and well-being during the remote period than faculty without disabilities. During the return to in-person work, both faculty and non-teaching staff reported more negative than positive sleep and well-being outcomes. In particular, during the in-person period faculty members experienced slightly more negative sleep outcomes related to anxiety and work, while staff members experienced slightly more negative sleep outcomes related to the need to commute and lifestyle. Our findings show that there were benefits and disadvantages to both remote and in-person work periods, suggesting a hybrid work schedule should be considered in more detail, particularly as an optional reasonable accommodation for faculty and staff with disabilities. Our study highlights that training to keep faculty abreast of the latest technological innovations, ways to promote work-life balance and steps to remedy classroom size and building ventilation to prevent the spread of disease all need urgent attention.

To compare concentrations of endogenous N-acylethanolamines (NAEs) lipid mediators pal-mitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA) in fresh, decon-taminated, cryopreserved and freeze-dried amniotic membrane (AM) allografts. Thereby deter-mining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chro-matography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPARα receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher val-ues for all NAEs were detected in cryopreserved samples compared to fresh tissue before decon-tamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of PPARα receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue was found in cryopreserved, but not frieze-dried AM. Results in-dicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects of AM allografts.

This study examines the behavior of stearic acid (SA) and 12-hydroxystearic acid (12-HSA) aqueous mixtures as a function of temperature and 12-HSA/SA molar ratio (R). Whatever R, the system exhibits a morphological transition at a given threshold temperature, from multilamellar self-assemblies at low temperature towards small micelles at high temperature, as shown by a combination of transmittance measurements, Wide Angle X-ray diffraction (WAXS), small angle neutron scattering (SANS) and differential scanning calorimetry (DSC) experiments. Such transition originates from the melting of the crystallized fatty acids within the lamellar phase. The precise determination of the threshold temperature, which ranges between 20°C and 50°C depending on R, allows for the construction of the whole phase diagram of the system as a function of R. At high temperature the micelles that are formed are oblate for pure SA solutions (R = 0) and prolate for pure 12-HSA solution (R = 1). In the case of mixtures, there is a progressive continuous transition from oblate to prolate shape when increasing R, with micelles that are almost purely spherical for R = 0.33.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

Coral reefs are critical ecosystems globally for marine fauna, biodiversity and through the services they provide to humanity. However, they are significantly threatened by anthropogenic stressors, such as climate change. By combining 9 environmental variables and ecological and health-based thresholds obtained from the available literature, we develop, using fuzzy logic (discontinuous functions), a Coral Reef Stress Exposure Index (CRSEI) for remotely monitoring coral reef exposure to environmental stressors. Our approach capitalises on the abundance of readily available satellite Earth Observation (EO) data available in the Google Earth Engine (GEE) cloud-based geospatial processing platform. CRSEI values from 3157 distinct reefs were generated and mapped across 12 important coral reef ecosystem regions. Quantitative analyses indicated that the index detected significant temporal differences in stress and was, therefore, able to capture historic change at a global scale. We also applied the CRSEI to three case-study reef ecosystems, previously well-monitored for stress and disturbance using other methods. PCA analysis indicated that depth, current, sea surface temperature (SST) and SST anomaly accounted for the greatest contribution to the variance in stress in these three regions. The CRSEI corroborated temporal and spatial differences in stress exposure from known disturbances within these reference regions, in addition to identifying the potential drivers of inter- and intra-region differences in stress, namely depth, degree heating weeks and SST anomaly. We discuss how the index can be further improved in future with site-specific thresholds for each stress variable, and the incorporation of additional variables not currently available in GEE. This index provides an open access tool, built around a free and powerful processing platform, that has broad potential to assist in the regular monitoring of our increasingly imperilled coral reef ecosystems, and, in particular, those that are remote or inaccessible.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

The study aimed to compare the cardiovascular benefits of Omega-3 Polyunsaturated Fatty Acids from fish oil versus krill oil in different forms and dosages. Following PRISMA 2015, data analysis with R software, and databases were searched from 1993 to 2023, (ID PROSPERO: CRD42024502338). Sixty high-quality studies were analyzed, covering various forms of fish oil and krill oil at different dosages (fish oil (ethyl ester-EE, triglyceride-TG, re-esterified triglycerides-rTG, capsules, emulsion-EM); krill oil (phospholipid/free fatty acid-PL/FFA, high concentration phospholipid-HPL, low concentration phospholipid-LPL)). Meta-analysis revealed that krill oil with phospholipid/free fatty acid at doses 2000-2900 mg effectively lowered triglycerides, while fish oil in ethyl ester form at doses above 3000 mg significantly reduced total cholesterol. Fish oil in triglyceride form at doses 2000-2900 mg and other variations positively impacted HDL-C levels. Fish oil in EE form above 3000 mg and triglyceride form below 2000 mg notably reduced LDL-C. However, there was limited effectiveness observed for other interventions. Analysis for LDL-C exhibited publication bias, while other parameters demonstrated reliability (Egger's test). In conclusion, krill oil - PL/FFA, Fish oil - EE above 3000 mg, Fish oil - TG 2000-3000 mg, and fish oil - rTAG 300-1900 mg effectively in reducing heart risk patients.

We propose that a dietary reduction of Lipopolysaccharide (LPS) could reduce risk and slow the progression of cognitive decline and Alzheimer’s disease. LPS is a component of the highly inflammatory cell membrane of Gram-negative bacteria. The highest dietary sources of LPS are processed meat and dairy products, which can sharply raise plasma LPS within one to two hours. The LPS in these foods is packaged into chylomicrons, which enter the bloodstream. Smaller amounts of LPS from colonic microbiota do not account for the sharp postprandial increase of plasma LPS. Once in the bloodstream, LPS can trigger the release of inflammatory cytokines within three hours. LPS can increase cytokines via LPS binding protein and cluster of differentiation-14, triggering toll-like receptor-4, and activating nuclear factor kappa-B. Nuclear factor kappa-B can increase cytokine levels, including interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha. LPS and inflammatory cytokines are higher in Alzheimer’s disease, both in plasma and in the central nervous system. These cytokines can enter the brain via active transport and induce microglial activation and inflammatory damage in the brain, including loss of synapses and neurons. Elevated brain inflammation from dietary LPS can contribute to cognitive impairment and increased risk of dementia.

Mindfulness-based interventions (MBIs) have been shown to improve health and well-being in adolescents with chronic illnesses. Because they are most often delivered in person in a group setting, there are several barriers that limit access to MBIs for youth with limited mobility or who cannot access in-person MBIs in their communities. The objective of this study was to determine if eHealth is a viable platform to increase accessibility to MBIs for teens with chronic illnesses. This study reports the qualitative results of a mixed method randomized trial describing the experience of the Mindful Awareness and Resilience Skills for Adolescents (MARS-A) program, an 8-week MBI, delivered either in person or via eHealth. Participants were adolescents between the ages of 13 and 18 with a chronic illness recruited at a tertiary pediatric hospital in Toronto, Canada. Individual semi-structured post-participation audio-video interviews were conducted by a research assistant. A multiple-pass inductive process was used to review interview transcripts and interpret emergent themes from the participants’ lived experiences. Fifteen participants completed post-participation interviews. Four distinct themes emerged from participants in both the in-person and eHealth groups: creation of a safe space, fostering peer support and connection, integration of mindfulness skills into daily life and improved well-being through the application of mindfulness. Results from this study suggest that eHealth may be an acceptable and feasible mode of delivery for MBIs in adolescents with chronic illnesses. EHealth should be considered in future studies as a promising avenue to increase access to MBIs in this population.

We describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature, as function of the 12-HSA/(fatty acid) mole ratio R. The morphologies of the self-assembled aggregates are obtained by a multi-structural approach that combines confocal and cryo-TEM microscopies with Small-Angle Neutron Scattering (SANS) and Wide-Angle X-Rays Scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. The behavior is driven by the competition between mixing entropy and enthalpic effects. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multi-lamellar tubes are formed, similarly as for pure aqueous solutions of 12-HSA. The doping by a low amount of SA molecules only slightly modify the dimensions of the tubes (radius and length), and slightly decreases the bilayers rigidity. The solutions have a gel-like behavior originating from entanglements between tubes and show a yield stress. At intermediate R, a partial local partitioning occurs between the two types of fatty acids. The tubes coexist in solution with helical ribbons. The two structures possibly merge to form very long snaky objects with straight and curved parts. The rigidity of the bilayers and the rheological behavior of the solutions are very similar to those of the high R case. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems, respectively 2-D planar bilayers for SA and the tubes describe above for the 12-HSA molecules: they are facetted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus, compared to systems with larger R. The solutions remain however viscous fluids in this regime of low R.

Recently, the world has experienced severe food insecurity problems with most countries having inadequate access to affordable, nutritious and safe foods. Consequently, many food innovations and technologies have been approved to secure sustainable access to food for millions of people. This study investigated the implementation of two technologies to address food insecurity, namely genetically modified foods (GMOs) and the use of antibiotics in crops and animal production. In particular, the study explored how their implementation can be governed responsibly through approved legislation. Therefore, the knowledge, attitudes and practices as well as the governance of antibiotic resistance risks and GMO foods were assessed. In-depth key interviews were conducted for the qualitative survey with triangulation with quantitative data sources. The findings showed that 46% of the population have little knowledge about GMOs with about 79% indicating that food with GM ingredients were being consumed in the country. The main concerns reported on GM foods by most respondents were impact on environment, human health and adverse effects on traditional farming practices with 36% indicating that it intensifies contamination and 32% indicating that it contributes to loss of biodiversity. Notably, 64%) reported that GMOs are a solution to food security and that they are safe. On the use of antimicrobials mainly meant to prevent diseases and access better markets, respondents perceived their use to be associated with antimicrobial resistance a “large level of risk” (score 2 in a scale of 1-3) (M = 1.85, SD = 1.06). Overall, the study found that efforts towards promoting awareness on antibiotic resistance risks and response in human health is relatively limited as reported by 56% of the respondents. Findings show that most of the respondents have only seen minimal or small-scale awareness campaigns. On governance of the two technologies, 71% and 50% of the respondents reported that scientists and elected officials respectively have the greatest role in governance of GMOs with small scale farmers playing a negligible role. Further, it was noted that all the respondents were knowledgeable in AMR and GMO technologies and these findings are crucial to the advancement of food innovations that are geared towards achieving food security in Kenya. This study highlights the risks associated with the poor governance and implementation of technologies and the need for a framework for technological risk governance that is sensitive to local values and socio-economic circumstances that will benefit the achievement.

γδT have functions of innate and adaptive immunity, with the potential to induce durable responses while being well-tolerated, with limited adverse effects, making it attractive as a tool for immunotherapy. γδT faces challenges as a frontline tool in clinical oncology, with limited response rates due to difficulties in reaching tumor sites with consistent cytotoxic activity and strength. Modulated Electro-hyperthermia (mEHT) is a loco-regional treatment, whereby energy-transmission from an electromagnetic field selectively targets the plasma membrane of tumor cells, inducing apoptosis and activating immune cells. We hypothesized that mEHT could enhance therapeutic effects by drawing γδT to tumor cells, while also rendering tumor cells to be more susceptible to cytotoxic effects. In this study, NOD/SCID mice harboring subcutaneous human HepG2 tumors were treated with intravenous injections of γδT after mEHT treatment. This method increased infiltration of γδT into the tumor site, significantly inhibiting tumor growth as compared to monotherapy with either modality. These data suggest that γδT could mediate a potent anti-tumor effect when combined with mEHT, and provide a strong rationale for combining these modalities in clinical application for cancer treatment.

Soybean a pulse of considerable nutritional value due to its high protein, fibers and polyunsaturated fatty acid (PUFA) contents, also contains phytoestrogenic compounds that definitely hinder its recommendation for general consumption. Contrarily to ancient times when soybeans were boiled, modern commercial soy-foods can contain up to 150 mg/100g of estrogenic isoflavones. Interestingly, current estimations of isoflavone intake in the literature do not distinguish between the origins of soy-food i.e. home-made or commercial. As a result, the isoflavone exposure in Asian countries may well be over-estimated. This study aims to demonstrate, based on step-by-step monitoring of isoflavones, that traditional and domestic treatments, leveraging isoflavones water-solubility, can indeed significantly reduce their content in soy-foods. Indeed, when compared to commercial foods, the isoflavone contents was found to be 20, 2.6, 4.5 and 9.8 times lower in “home-made” soy-juice, tofu, tempeh and miso, respectively. Additionally, water soaking was found to reduce the isoflavones levels in soy-textured-proteins by more than 70%. Hence, this simple process has the potential to help drastically reduce overall xenoestrogens exposure. This study could serve as a basis for establishing the isoflavones Reference Dose and issuing food safety guidelines.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

Abstract: Background: Dental fear and uncooperative behavior can hinder dental treatment quality. Pediatric Procedural Sedation and Analgesia (PPSA) is used to facilitate treatment when coping capacity is exceeded. Out-of-hospital PPSA has been associated with more adverse outcomes compared to hospital-based settings. Updated Dutch PPSA guidelines recommending two anesthesiologists and a ventilator during out-of-hospital PPSA have increased costs and raised concerns about the accessibility to specialized high quality dental care for children in the Netherlands. Aim: This study aims to investigate the impact of the updated 2017 guideline on the occurrence rate of adverse events during PPSA, as recorded in the anesthesia complication database of twelve participating Dutch dental clinics, with adjustments made for age, weight, and duration of treatment. Method: Data of 25,872 children treated at 12 dental clinics performing out-of-hospital PPSA between 1997 and 2019 were analyzed. Eligible children were aged 2-18 with ASA classification I and II. A logistic two-level mixed-effects model is used to estimate the updated guideline’s impact on adverse events. Results: In the final model we analyzed the data of 21,759 children in nine dental clinics. The OR of the occurrence rate of an adverse event adjusted for age, weight, and duration of treatment was 0.75 (95% CI 0.64 – 0.89) after the implementation of the updated guideline, compared to before the updated guideline. This outcome was significant with a P=0.001, indicating a protective effect. The average odds per clinic of having an adverse event was 0.04 with a 3.81% chance. Conclusion: Our findings demonstrate a significant reduction in adverse events after the implementation of the updated guideline and highlight the importance of adherence to evidence-based guidelines in improving patient safety and the quality of care provided during pediatric procedural sedation and analgesia in out-of-hospital dental clinics. Our study underlines the necessity of considering the complex underlying mechanisms that play a role in the development and implementation of evidence-based practice and safety initiatives on the occurrence of adverse events.

This study aimed to estimate scattered radiation and its spatial distribution around three Cone Beam Computed Tomography (CBCT) devices, in order to determine relatively safe positions for an operator to stand if needed to be inside the CBCT room. The following devices were tested: Morita Accuitomo (CBCT1), Newtom Giano HR (CBCT2), Newtom VGi (CBCT3). Scattered radiation measurements were performed using different kVp, mA and Field of View (FOV) options. An anthropomorphic phantom (NATHANIA) was placed inside the x-ray gantry to simulate clinical conditions. Scattered measurements were taken with the ionization chamber Inovision model 451P Victoreen once placed at fixed distances from each irradiation isocenter, away from the primary beam. A statistically significant (p<0.001) difference was found in the mean value of the scattered radiation estimations between the CBCT devices. Scattered radiation was reduced with a different rate for each CBCT device as distance was increased. For CBCT1 the reduction was 0.047μGy, for the CBCT2 0.036 μGy and 0.079 μGy for CBCT3, for every one meter away from the x-ray gantry. Therefore, at certain distances from the central x-ray, the scattered radiation was below the critical 1mGy. Consequently, an operator could stay inside the room accompanying the patient being scanned, if necessary.

Background: In the span of just two years, tracking the COVID-19 pandemic through wastewater surveillance has advanced from early reports of successful SARS-CoV-2 RNA detection in untreated wastewater to implementation of programs in at least 60 countries. Early wastewater monitoring efforts primarily originated in research laboratories and are now transitioning into more formal surveillance programs run in commercial and public health laboratories. A major challenge in this progression has been to simultaneously optimize methods and build scientific consensus while implementing surveillance programs, particularly during the rapidly changing landscape of the pandemic. Translating wastewater surveillance results for effective use by public health agencies also remains a key objective for the field. Objectives: We examine the evolution of wastewater surveillance to identify model collaborations and effective partnerships that have created rapid and sustained success. We propose needed areas of research and key roles academic researchers can play in the framework of wastewater surveillance to aid in the transition of early monitoring efforts to more formalized programs within the public health system. Discussion: Wastewater surveillance has rapidly developed as a public health tool Clinical testing programs are ramping down and home testing is on the rise, making wastewater monitoring important for future surveillance of COVID-19. Our experience in initiating and implementing wastewater surveillance programs in the United States has allowed us to reflect on key barriers and organizational challenges and draw useful lessons. As wastewater surveillance programs are formalized, the working relationships developed between academic researchers, commercial and public health laboratories, and data users should continue and should promote knowledge co-development. While wastewater surveillance has demonstrated utility for tracking COVID-19, there remain technical challenges and open scientific questions that researchers are equipped to address, which will contribute to building robust surveillance programs that provide public health practitioners with new insights into population health.

Purinergic receptors (P2X) are ATP-gated ion channels with an elusive role in the CNS. While the P2X2 and P2X4 subtypes are widely expressed in most neurons (i.e. at the edge of the postsynaptic densities of excitatory synapses), the direct contribution of P2X to synaptic transmission is uncertain. Several P2X have been shown to participate in receptor cross-talk: an interaction where one receptor (e.g. P2X2) influences the activity of another (e.g. GABA or AMPA receptors.) In this study, we tested for interactions between P2X2 or P2X4 and N-methyl-D-aspartate receptors (NMDARs). Using two-electrode voltage-clamp electrophysiology experiments in X. laevis oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an inhibitory manner. When investigating the molecular domains responsible for this phenomenon, we found that the P2X2 c-terminus (CT) could interfere with P2X2 and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 or P2X4. Collectively, these results provide new evidence for the modulatory nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the CNS.

The probiotic bacterial strain Lactobacillus plantarum ZS2058 has been proved to manifest comprehensive functions, which were due to ability to synthesise conjugated fatty acids (CFAs). To investigate the specific functions of CFAs produced by this probiotic bacterium, α-linolenic acid was isomerized by Lactobacillus plantarum strain ZS2058, and two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated lipid peroxidation was related to the antiproliferation activity of CLNAs. Examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. And no sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first report showing the ability of CLNAs to activate antioxidant defenses resulting in pyroptosis.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d &gt;0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d &lt;0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Background: COVID-19 is a disease of the elderly as 95% of deaths related to COVID-19 occur in people over 60 years of age. Despite the urgent need for a preventive treatment there are currently no serious leads, other than the vaccination. Objective: To find a preventive treatment of COVID-19 in elderly patients. Design: Retrospective case-control study. Setting: Robertsau Geriatric Hospital of the University Hospitals of Strasbourg, France. Patients: 179 elderly patients who had been in contact with the SARS-CoV-2, of whom 89 had tested RT-PCR-positive (COVID-pos) for the virus and 90 had tested RT-PCR-negative (COVID-neg). Measurements: Treatments within 15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), paracetamol, anticoagulant, oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected using the electronic patient record. Results: COVID-pos patients more frequently had a history of diabetes (P=.016) and alcoholism (P=.023), a lower leukocyte count (P=.014) and a higher mortality rate– 29.2% versus 14.4% – (P=.014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P=.0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-19 patients on antipsychotics (P=.0013) and OADs (P=.0166) were less likely to die. Limitations: retrospective study. Conclusion: PPIs treatment lowered the risk of development of COVID-19 infection, and antipsychotics and OADs decreased the risk of mortality in geriatric patients. If further studies confirm this finding, PPIs could be used preventatively in the elderly in this pandemic context. Moreover, OADS and antipsychotics should be tested in clinical trials.

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

Strategies implemented worldwide to contain COVID-19 outbreaks varied in severity across different countries, and established a new normal for work and school life (i.e. from home) for many people, reducing opportunities for physical activity. Positive relationships of physical activity with both mental and physical health are well recognised, therefore the aim was to ascertain how New Zealand’s lockdown restrictions impacted physical activity and mental health and wellbeing. Participants (n=4007; mean±SD: age 46.5±14.7y, 72% female, 80.7% New Zealand European) completed (10–26 April 2020) an online amalgamated survey (Qualtrics): International Physical Activity Questionnaire: Short Form; Depression, Anxiety and Stress Scale-9; World Health Organization-Five Well-being Index; Stages of Change Scale. Positive dose response relationships between physical activity levels and wellbeing scores were demonstrated for estimates that were unadjusted (moderate activity OR 3.79, CI 2.88-4.92; high activity OR 8.04, CI 6.07-10.7) and adjusted (confounding variables: age, gender, socioeconomic status, time sitting, co-morbidities) (moderate activity 1.57, CI 1.11-2.52; high activity 2.85, CI 1.97-4.14). The study results support previous research demonstrating beneficial effects of regular physical activity on mental health and wellbeing. Governments may use such results to promote meeting physical activity guidelines in order to protect mental health and wellbeing during the ongoing COVID-19 and future pandemics.

Treatment regimens are regularly evolving, together with novel therapies and drugs. Such evolution is necessary to circumvent resistance mechanisms and to give patients the best possible health care. When dealing with cancer, most regimens involve multiple treatments (surgery, radiation therapy, chemotherapy, immunotherapy, etc.). The purpose of this study was to associate in a single compound metal-based drugs and photosensitizers to combine chemotherapy and photodynamic therapy. Two arene-ruthenium tetrapyridylporphyrin compounds (2H-TPyP-arene-Ru and Zn-TPyP-arene-Ru) have been synthesized and evaluated on two colorectal cancer cell lines (HCT116 and HT-29). The cytotoxicity and phototoxicity have been evaluated. In addition, the anticancer mechanism and the cell death process mediated by the two compounds were studied. The results showed that the two arene-ruthenium photosensitizer-containing complexes have a strong phototoxic effect after photoactivation. The 2H-TPyP-arene-Ru induced outstanding cytotoxicity when compared to the Zn-TPyP-arene-Ru analogue. Moreover, under light, these two arene-ruthenium photosensitizers induce an apoptotic process in human colorectal cancer cell lines.

Cross-species investigations on cancer invasiveness are a new approach that identified new biomarkers potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated to mitochondrial proteome rewiring. The comparison of significant abundance changes between invasive and non-invasive rat tumors rat tumors gave a list of 433 proteins, including twenty-six proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines, and the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in the migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.

Purpose: To simplify the application of optical coherence tomography (OCT) for examination of subsurface morphology in the oral cavity and reduce barriers towards adoption of OCT as a biopsy guidance device. The aim of this work was to develop automated software tools for simplified analysis of the large volume of data collected during OCT. Methods: Imaging and corresponding histopathology were acquired in-clinic using a wide-field endoscopic OCT system. An annotated dataset (n = 294 images) from 60 patients (34 male, 26 female) was assembled to train four unique neural networks. A deep learning pipeline was built using convolutional and modified u-net models to detect the imaging field of view (network 1), detect artifacts (network 2), identify the tissue surface (network 3), and identify the presence and location of the basement membrane (network 4). Results: The area under the curve of the image and artifact detection networks was 1.00 and 0.94 respectively. The Dice similarity score for the surface and basement membrane segmentation networks was 0.98 and 0.83 respectively. Conclusion: Deep Learning (DL) techniques can identify the location and variations in the epithelial surface and basement membrane in OCT images of the oral mucosa. Segmentation results can be synthesized into accessible en face maps to allow easier visualization of changes.

Africa’s water needs are often supported by eutrophic waterbodies dominated by cyanobacteria posing health threats to riparian populations from cyanotoxins, and Lake Victoria is no exception. In two embayments of the lake (Murchison Bay and Napoleon Gulf), cyanobacterial surveys were conducted to characterize the dynamics of cyanotoxins in lake water and water treatment plants. Forty-six cyanobacterial taxa were recorded and out of these 14 were considered potentially toxigenic (i.e., from the genera Dolichospermum, Microcystis, Oscillatoria, Pseudanabaena and Raphidiopsis). A higher concentration (ranging from 5-10 µg MC-LR equiv. L-1) of microcystins (MCs) was detected in Murchison Bay compared to Napoleon Gulf, with a declining gradient from the inshore (max. 15 µg MC-LR equiv. L-1) to the open lake. In Murchison Bay, an increase either in Microcystis sp. biovolume and MC was observed over the last two decades. Despite high cell densities of toxigenic Microcystis and high MC concentrations, the water treatment plant in Murchison Bay efficiently removed the cyanobacterial biomass, intracellular and dissolved MC to below the lifetime guideline value for exposure via drinking water (&lt; 1.0 µg MC-LR equiv. L-1). Thus, the potential health threats stem from the consumption of untreated water and recreational activities, along the shores of the lake embayments. MC concentrations were predicted from Microcystis cell numbers regulated by environmental factors such as solar radiation, wind speed in the N-S direction and turbidity. Thus, an early warning through microscopical counting of Microcystis cell numbers is proposed to better manage health risks from toxigenic cyanobacteria in Lake Victoria.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m⁶A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m⁶A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

In this work, Gd-filled skutterudite GdxCo4Sb12 has been prepared in one-step method under high-pressure conditions in a piston-cylinder press at 3.5 GPa and moderate temperature of 800 °C. A detailed structural characterization was performed using synchrotron X-ray diffraction (SXRD), revealing a filling fraction of x = 0.066(4) and an average &lt;Gd–Sb&gt; bond length of 3.3499(3) Å. The lattice thermal expansion accessed via temperature-dependent SXRD led to a precise determination of a Debye temperature of 322(3) K, from the fitting of the unit-cell volume expansion using the second order Grüneisen approximation. Such parameter, when evaluated from the mean square displacements of Co and Sb, displayed a value of 265(2) K, meaning that the application of the harmonic Debye theory underestimates the Debye temperature in skutterudites. Regarding the Gd atom, its intrinsic disorder value is ~5× and ~25× higher than those of Co and Sb, respectively, denoting that Gd has a strong rattling behavior with an Einstein temperature of θE = 67(2) K. As a result, an ultra-low thermal conductivity of ~0.89 W/m·K at 773 K was obtained, leading to a thermoelectric efficiency zT of ~0.5 at 673 K.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Diffuse midline gliomas are among the deadliest human cancers and have had little progress in treatment in the last 50 years. Cell cultures of these tumors have been developed recently, but it is unknown the degree to which such cultures retain the characteristics of the source tumors. DNA methylation profiling offers a powerful tool to look at genome-wide epigenetic changes that are biologically meaningful and can help assess the similarity of cultured tumor cells to their in vivo progenitors. Paraffinized diagnostic tissue from three diffuse intrinsic pontine gliomas with H3 K27M mutations was compared with subsequent passages of neurosphere cell cultures from those tumors. Each cell line was passaged 3-4 times and analyzed with DNA methylation arrays and standard algorithms that provided comparison of diagnostic classification and cluster analysis. All samples tested maintained high classifier scores and clustered within the reference group of H3 K27M-mutant diffuse midline gliomas. There was a gain of 1q in all cell lines, with two cell lines initially manifesting the gain of 1q only during culture. In vitro cell cultures of H3 K27M-mutant gliomas maintain high degrees of similarity in DNA methylation profiles to their source tumor, confirming their fidelity even with some chromosomal changes.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.