This paper describes the optimal design of a miniature fiber-optic linear displacement sensor. It is characterized by its ability to measure displacements along a millimetric range with sub-micrometric resolution. The sensor consists of a triangular reflective grating and two fiber-optic probes. The measurement principle of the sensor is presented. The design of the sensor's triangular grating has been geometrically optimized by considering the step angle of the grating to enhance the sensor's resolution. The optimization method revealed a global optimum at which the highest resolution is obtained

Mycotoxins food contamination represents a serious risk for consumers health. They are secondary metabolites of fungi that can be present in a wide range of foodstuffs. Ochratoxin A (OTA) is one of the most toxic compound and it is classified as a possible carcinogenic molecule. The harmful effects of OTA on human and animal health lead to a big boost to develop and optimize highly sensitive and accurate methods for OTA detection. An innovative and rapid detection method based on microcantilever resonators for ochratoxin A identification in food matrix has been developed. This work demonstrates the possibility to apply microcantilever technology in food safety field, showing for the first time in literature the successful detection of one of the most dangerous mycotoxin in different food matrixes both solids and liquids, such as green coffee, grape juice and wine. Sensing performances are discussed in terms of calibration plot and limit of detection.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

COVID-19 is the most severe health crisis of the 21st century. COVID-19 presents a threat to almost all countries world-wide. The restriction of human mobility is one of the strategies used to control the transmission of COVID-19. However, it has yet to be determined how effective this restriction is in controlling the rise in COVID-19 cases, particularly in major capital cities such as Jakarta, Indonesia. Using Facebook's mobility data, our study explores the impact of restricting human mobility on COVID-19 case control in Jakarta. Our main contribution is showing how the restriction of human mobility data can give important information about how COVID-19 spreads in different places. We proposed modifying a global regression model into a local regression model by accounting for the spatial and temporal interdependence of COVID-19 transmission across space and time. We applied Bayesian hierarchical Poisson spatiotemporal models with spatially varying regression coefficients. We estimated the regression parameters using an Integrated Nested Laplace Approximation. We found that the local regression model with spatially varying regression coefficients outperforms the global regression model based on DIC, WAIC, MPL, and R2 criteria for model selection. In Jakarta's 44 districts, the impact of human mobility varies significantly. The impacts of human mobility on the log relative risk of COVID-19 range from –4.445 to 2.353. The prevention strategy involving the restriction of human mobility may be beneficial in some districts but ineffective in others. Therefore, a cost-effective strategy had to be adopted.

Concrete is the most utilized construction material worldwide. In the marine environment, it is subject to chemical degradation through reactions with chloride (the most important ion), sulfate and magnesium ions in seawater and to biodeterioration resulting from biological (initially microbiological) activities, principally acid production. These two types of corrosion are reviewed and the failure of attempts to predict the degree of deterioration resulting from each is noted. Chemical (abiotic) corrosion is greatest in the splash zone of coastal constructions, while phenomenological evidence suggests that biodeterioration is greatest in tidal zones. There have been no comparative experiments to determine the rates and types of microbial biofilm formation in these zones. Both chemical and microbiological concrete deterioration are complex and have not been successfully modeled. The interaction between abiotic corrosion and biofilm formation is considered. EPS can maintain surface hydration, potentially reducing abiotic corrosion. The early marine biofilm contains relatively specific bacterial colonizers, including cyanobacteria and proteobacteria; these change over time, producing a generic concrete biofilm, but adhesion of microorganisms to concrete in the oceans is little investigated. The colonization of artificial reefs is briefly discussed. Concrete appears to be a relatively prescriptive substrate, with modifications necessary to increase colonization for the required goal of increasing biological diversity.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Preparing high school students for engineering disciplines is crucial for sustainable scientific and technological developments in the USA. This paper discusses a pre-college program, which not only exposes students to various engineering disciplines but also enables them to consider engineering as the profession. The four-week long “Engineering Innovation (EI)” course is offered every year to high school students by the center of outreach, Johns Hopkins University. EI program is designed to develop problem-solving skills through extensive hands-on engineering experiments. A team consisting of an instructor, generally a PhD in Engineering, and a teaching fellow, generally a high school science teacher, closely work with students to pedagogically inculcate basics of core engineering disciplines such as civil, mechanical, electrical, materials, and chemical engineering. EI values independent problem-solving skills and simultaneously promote the team spirit among students. A number of crucial engineering aspects such as professional ethics, communications, technical writing, and understanding of common engineering principles are inculcated among high school students via well-designed individual and group activities. This paper discusses the model of EI program and its impact on students learning and their preparation for the engineering career.

Many insights into human disease have been built on experimental results in Drosophila, and research in fruit flies is often justified on the basis of its predictive value for questions related to human health. Additionally, there is now a growing recognition of the value of Drosophila for the study of rare human genetic diseases, either as a means of validating the causative nature of a candidate genetic variant found in patients, or as a means of obtaining functional information about a novel disease-linked gene when there is little known about it. For these reasons, funders in the US, Europe, and Canada have launched targeted programs to link human geneticists working on discovering new rare disease loci with researchers who work on the counterpart genes in Drosophila and other model organisms. Several of these initiatives are described here, as are a number of output publications that validate this new approach.

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.

As the global demand for water increases, so does the quantity of wastewater requiring treatment. Due to a relatively low carbon footprint, compared with conventional wastewater treatment technologies, anaerobic digestion (AD) was identified in the 1970s as a forerunner in the push for sustainability, when interest in sustainable technologies and renewable energy sources was first sparked. AD technology development ultimately resulted in the discovery of the ‘anaerobic granule’. It is a spontaneously-forming bio-aggregate of microbial cells capable of digesting pollutants and producing methane-rich biogas as a renewable source of bioenergy. The high settling velocity of such granules meant that AD systems could be operated as high-rate treatment processes, because the active, relatively-slow-growing, pollutant-removing biomass would be retained inside, and not washed out of, even bioreactors operated at extremely high volumetric loading rates. In the intervening years the emergence of the anaerobic ammonium oxidising (anammox) granule, aerobic granule, hydrogenic granule, oxygenic photogranule, and many other functionally-specialised granules, has opened new opportunities in wastewater treatment biotechnology. Whilst environmental engineering based around wastewater treatment is still a growing field of research and implementation, the granule (in all forms) is starting to catch the attention of microbial ecologists. It is a self-immobilised biofilm, with many of the properties of ‘conventional’ biofilms formed in Nature. However, as a single entity, a granule represents an entire community of microorganisms, competing or functioning cooperatively or in syntrophy. Together, inside a bioreactor, granules perform side-by-side arguably representing a meta-organism. Granules are gaining traction as the perfect samples for high-throughput studies on fundamental ecological concepts. Granular biofilms can be used to test hypotheses around drivers of diversity, community assembly, biofilm formation and maturation, community expansion and succession, community stress response, among others. This review outlines the history of three of the most influential types of granules: the anaerobic (methanogenic), aerobic and anammox granule. The main biochemical processes found in each type; their primary characteristics; and the typical makeup of the microbial community underpinning the processes are compared. Finally, the adoption of granules as the perfect ‘playground’ for experiments in microbial ecology is reviewed.

In the literature on occupational stress and recovery from work several facets of thinking about work in off-job time have been conceptualized. However, research on the focal concepts is currently rather disintegrated. In this study we take a closer look at the five most established concepts, namely (1) psychological detachment, (2) affective rumination, (3) problem-solving pondering, (4) positive work reflection, and (5) negative work reflection. More specifically, we scrutinized (1) whether the five facets of work-related rumination are empirically distinct, (2) whether they yield differential associations with different facets of employee well-being (burnout, work engagement, thriving, satisfaction with life, and flourishing), and (3) to what extent the five facets can be distinguished from and relate to conceptually similar constructs, such as irritation, worry, and neuroticism. We applied structural equation modeling techniques to cross-sectional survey data from 474 employees. Our results provide evidence that (1) the five facets of work-related rumination are highly related, yet empirically distinct, (2) that each facet contributes uniquely to explain variance in certain aspects of employee well-being, and (3) that they are distinct from related concepts, albeit there is a high overlap between (lower levels of) psychological detachment and cognitive irritation. Our study contributes to clarify the structure of work-related rumination and extends the nomological network around different types of thinking about work in off-job time and employee well-being.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

In addition to absorbing nitrogen from the soil, legumes have the ability to use atmospheric N2 through symbiotic nitrogen fixation. Therefore, legumes have developed mechanisms regulating nodulation in response to the amount of nitrate in the soil; in the presence of high nitrate concentrations, nodulation is inhibited while low nitrate concentrations stimulate nodulation and nitrogen fixation. This allows the legumes to switch from soil nitrogen acquisition to symbiotic nitrogen fixation. Recently, a particular interest has been given to the nitrate transporters, such as NPF or NRT2, having a role in the functioning of nodules. Nitrate transporters of the two model plants, Lotus japonicus and Medicago truncatula, shown to have a positive and/or a negative role in nodule functioning, depending on nitrate concentration, are presented in this review. Also, by exploiting available genomic and transcriptomic data in the literature we have identified the complete PsNPF family in Pisum sativum (69 sequences previously described and 21 new that we have annotated) and putative nitrate transporters candidate for playing a role in nodule functioning in P. sativum.

Dietary inclusion of trace minerals (TM), such as copper (Cu), manganese (Mn) and zinc (Zn) is of importance to cover the ever-evolving requirements for growth, production, and reproduction in ruminants. Various sources of TM are commercially available, such as inorganic (ITM), organic (OTM) or hydroxy (HTM) forms, however their bioavailability and efficiency to improve ruminant zootechnical parameters may be highly influenced by ruminal solubility and effects on the rumen environment. The objective of this review was to compile the most up-to-date information on the ruminal solubility of ITM, OTM and HTM, and their effects on fermentation parameters and rumen microbiota, aiming to support specialists from the animal feed industry when choosing TM products for ruminant supplementation. Some commonly used ITM sources, like sulfates, have a high ruminal solubility, while oxides are less soluble. The ruminal solubility of OTM is mostly found to be high, however data on these TM forms are still lacking. Regarding HTM, ruminal solubility is reported to be low, nevertheless results are inconsistent. Considering rumen fermentation, ITM show a negative effect, OTM might improve, while HTM do not affect parameters like dry matter degradability, volatile fatty acid production, pH, or microbial protein synthesis. As to rumen microbiota, ITM do not affect microbial populations; OTM could decrease abundance of some specific bacteria, like fibrolytic microorganisms, while studies with HTM are missing or inconclusive. Further research is necessary to better understand the ruminal solubility kinetics of TM sources and the different interactions with fermentation parameters and rumen microbiota to successfully apply precision TM supplementation of ruminants, tackling deficiency occurrences.

The global trend towards increased demand for organic food, greener environments, and the integration of biological control agents into pest management strategies has greatly enhanced the need for biological pesticides (biopesticides). Biopesticides are generally environmentally friendly and are made from micro-organisms or other natural substances. Despite their great potential, relatively few have been registered and commercialised in Nigeria compared to other African countries such as South Africa and Kenya. Biological active agents are so diverse such that ap-plying the same safety standards or environmental conditions to all of them is almost impossible. A review of risk assessment processes and comparative assessments of Nigeria's biopesticide regulations with other developing African countries and developed regions was conducted. Prolonged field testing, lack of bridged risk assessments and technical checklists have been identified as key factors hampering the timely development and commercialisation of biopesti-cides in Nigeria. Recommendations on necessary changes to the existing Nigeria biopesticide regulations have been made. Risk assessment matrices for microbial and biochemical biopesti-cides and a scientific/technical checklist have also been developed. Harmonisation and data ex-change among other countries in the region will also enhance the advancement of scientific and technical knowledge for sustainable regulation and cross-border trade.

Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. We analyzed recurrence and mortality dynamics in randomized clinical trials (RCTs) from Australia and Canada. The combined Australian RCTs evaluated, at median follow-up of 8.3 years, an 8-month pragmatic exercise intervention in 337 women with newly diagnosed breast cancer, while the Canadian RCT evaluated, at median follow-up of 7.4 years, supervised aerobic or resistance exercise during chemotherapy in 242 patients. For each RCT, the control arm consisted of patients undergoing usual care. We estimated the event dynamics by the discrete hazard function, through flexible regression of yearly conditional event probabilities with generalized additive models. In the considered RCTs, the recurrence and mortality risk of patients enrolled in the physical activity arm was stably reduced at medium/long term after five year of follow-up. In the Australian RCTs where patients were recruited by urban versus rural area, the latter group did not display benefit from physical activity. Estimated Odds Ratios (95% Confidence Intervals) for Disease Free Survival (DFS) in urban women were 0.63 (0.22-1.85); 0.27 (0.079-0.90); 0.11 (0.013-0.96) at the 3rd, 5th and 7th year of follow-up, respectively. For rural women, DFS patterns were overlapping with ORs approximating 1 at the different years of follow-up. Although not reaching statistical evidence, the estimates in the Canadian trial were in line with the results from the Australian urban women with ORs (95% CI) forDFS of 0.70 (0.33-1.50); 0.47 (0.19-1.18); 0.32 (0.077-1.29) at 3rd, 5th, 7th follow-up year, respectively. While we acknowledge that the analyzed RCTs were not designed for investigating disease recurrence over time, these results support the evidence that physical activity reduces the risk of developing medium/long-term metastases. Additional translational research is needed to clarify the mechanisms underlying these observations.

Scientific studies had shown that mixed forests of silver fir (Abies alba Mill.) and European beech (Fagus sylvatica L.) provide higher ecosystem services than monospecific forests. Mixed forests are known for their high resilience to climate change impacts and superior biodiversity compared to monospecific forests. In many countries, promotion of mixed forests in forest management is becoming a government policy since they can contribute to fulfill the Sustainable Development Goals set by the United Nation, respectively Goal 13 and 15. However, not much is known about public perceptions on mixed forests compared to monoculture forests. Our study on ecosystem services provided by mixed and monospecific forests in southwest Germany fill this gap. Based on a survey with 520 valid responses we analyzed people’s perception on 18 different supporting, cultural, regulating and provisioning ecosystem services measured by Likert scale. Stepwise regression analyses show relations between social profiles (gender, age, education, profession) and preferences on respondents’ perceptions. Our findings show that people perceive that mixed forests provide better cultural, regulating and supporting ecosystem services than monospecific forests of fir and beech whereas provisioning services were perceived as being equally or better provided by monospecific forests. Significant effects towards a positive perception on ecosystem services provided by mixed forests were mainly influenced by the perceived abundance of old trees, feeling of pleasantness in mixed forests, age, profession, and education. Our findings indicate that there is a high public support for the promotion of silver fir and beech mixed forests in Southwest Germany.

Numerous cities in our modern world are unfortunately encountering the negative effects of urban sprawl: this includes unrestricted settlement, degradation in the quality of their environment, traffic congestion, sub-standard buildings, and air pollution as well as flooding, swampy areas, landslides, and settlement zones with dilapidated utilities and infrastructures that are not safe for living. The Ulaanbaatar City land management master plan defined the settlement zone area suitable for living as 33,698 hectares. However, due to unrestricted urban sprawl caused by exponential growth of the city’s population, the settlement zone area reached 39,235 hectares, which exceeds the limit by 5,537 hectares. In order to tackle this issue, several urban planning concepts were developed to be implemented within the Ulaanbaatar City urban planning framework. It is, in any case, problematic to choose a single planning concept due to the fact that neither measurements nor analyses are being made of the respective spatial quantitative indicators in urban planning assumptions that are taking the current situation into consideration. One of the prerequisites for identifying an optimal concept in urban planning is an assessment of the current situation, and measuring the impacts against its quantitative data. In the current research, when defining Ulaanbaatar city sprawl, the base year was selected as 1990, the time when the city started to sprawl. Research analyses were made using geographic information systems based on the satellite data 1990, 1995, 2000, 2005 Landsat ТМ-5, 2010 Quickbird, 2015 World View and 2020 Sentinel2, respectively. Based on the results of determining the city sprawl using spatial indicators, the urban planning concepts applied thus far have been analyzed in relation to land use efficiency and land use structural changes. This research paper addresses the issue of reducing unrestricted urban sprawl by increasing the internal density of the city. The research results show that, by applying the concept of a compact city in urban redevelopment planning for 4,604 hectares, and by allocating the settlements in 12,479 hectares, it is possible to reduce the urban expansion threefold and increase land use efficiency accordingly.

Although work events can be regarded as pivotal elements of organizational life, only a few studies have examined how positive and negative events relate to and combine to affect work engagement over time. Theory suggests that to better understand how current events affect work engagement (WE), we have to account for recent events that have preceded these current events. We present competing theoretical views on how recent and current work events may affect employees (e.g., getting used to a high frequency of negative events or becoming more sensitive to negative events). Although the occurrence of events implies discrete changes in the experience of work, prior research has not considered whether work events actually accumulate to sustained mid-term changes in WE. To address these gaps in the literature, we conducted a week-level longitudinal study across a period of 15 consecutive weeks among 135 employees, which yielded 849 weekly observations. While positive events were associated with higher levels of WE within the same week, negative events were not. Our results support neither satiation nor sensitization processes. However, high frequencies of negative events in the preceding week amplified the beneficial effects of positive events on WE in the current week. Growth curve analyses show that the benefits of positive events accumulate to sustain high levels of WE. WE dissipates in the absence of continuous experience of positive events. Our study adds a temporal component and informs research that has taken a feature-oriented perspective on the dynamic interplay of job demands and resources.

Metabarcoding of prokaryotic and fungal ribosomal DNA was used to describe the microbial communities in soils of remnant equatorial rainforest, maize-bean intercrop, and sugarcane in western Kenya. Cropping systems influenced the microbial community composition and functional traits (energy source and nutrient cycling) of bulk soil in each crop. Microbial richness and diversity tended to increase with cultivation intensity. Soil of maize-bean intercrop had lower percentages and sugarcane had higher percentages of unique amplicon sequence variants of both bacteria and fungi compared to the remnant forest. Functional traits were altered by cultivation intensity. Compared to remnant forest soils, maize-bean intercrop soil had lower percentages of aerobic chemoheterotrophic bacteria and higher percentages of N-cycling bacteria, while sugarcane had higher percentages of aerobic chemoheterotrophic bacteria and lower percentages of N-cycling bacteria. In the face of increasing forest loss and pressures for agricultural productivity, this landscape provides a rich site for studying the impacts of cropping systems on soil health.

Agricultural productivity is expected to decrease under changing climate conditions that correspond to the stability of West African food systems. Although numerous studies evaluated food production gaps or impacts of climate variability on crop yields, many uncertainties are associated with climate extremes, but also rapid population growth and the corresponding dietary lifestyle determine farming activities. Here, we present a food supply and demand analysis based on the relationship between climate change, crop production, as well as population growth in three experimental sites from southwestern Burkina Faso to southwestern Ghana. The method consists of a tiered approach that encompassed a statistical analysis of historical climate as well as agricultural time series using boxplots and a trend test by Mann-Kendall. Food balance sheets were calculated by estimating the demand using a population growth model linked to food supply with local consumption patterns. Results of the boxplot analysis revealed for the majority of climate time series light to strong right-skewed distributions with either a few heavy rainfall or hot temperature events. We found almost insignificant rainfall and temperature trends for both sites in the Sudano-Guinean savannah. The rainfall regime of southwestern Ghana indicated an insignificant upward or downward trend while the temperature significantly increased over time. Crop yield boxplots demonstrated mainly right-skewed distributions for cereals, legumes and tubers as well as cash crops such as cotton. Backed by the Mann-Kendall test, maize and sorghum significantly enhanced in both study areas of the Sudano-Guinean savannah. Southwestern Ghana depicted a different crop pattern where cassava and plantain showed a strong upward trend at a confidence level of 1%. The grouped food balances sheets across the regions illustrated a surplus for the Sudano-Guinean savannah ranging from 221.2 megatons (Mt) to 4,846.77 Mt while southwestern Ghana exhibited a deficit between -193.33 Mt and -16,188.82 Mt. Despite a growing yield of various crops, food demand outpaces the regional production. Hence, it is recommended to focus on a larger array of commodities, imports and marketing of farm products.

Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS endowed with signalling properties are mainly produced by NADPH oxidases at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differs in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetics processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function as well as pharmacological strategies have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus, for which there is no vaccine or cure. This viral infection, once acquired, is life-long, residing latently in hematopoietic cells. However, latently infected individuals with weakened immune systems often undergo HCMV reactivation, which can cause serious complications in immunosuppressed and immunocompromised patients. Current anti-viral therapies target late stages of viral replication, and are often met with therapeutic resistance, necessitating the development of novel therapeutics. In this current study, we identified a naturally occurring flavonoid compound, deguelin, which inhibits HCMV lytic replication. Our findings reveal that nanomolar concentrations of deguelin significantly suppress the production of infectious virus. Further, we show that deguelin inhibits the lytic cycle during the phase of the replication cycle consistent with early (E) gene and protein expression. Importantly, our data reveal that deguelin inhibits replication of a ganciclovir-resistant strain of HCMV. Together, our findings identify a novel, naturally occurring compound that may prove useful in the treatment of HCMV replication.

Hidradenitis suppurativa and Langerhans cell histiocytosis are rare disorders that can reveal similar clinical manifestations, making differential diagnosis difficult. A definitive diagnosis requires biopsy and histological confirmation in suspicious cases. The complex pathophysiology of these diseases has still not been understood, therefore the treatment is still a challenge for physicians. It is seen with predilection in the intertriginous areas of the body, predominantly in the axillary region, rarely requiring a surgical procedure. However perineal, perianal, and gluteal HS usually necessitates some form of surgical treatment. Langerhans cell histiocytosis (histiocytosis X) is a very rare systemic disease manifested by clonal cell proliferation of histiocytic-dendritic nature, with pseudonodular manifestation that deeply infiltrates the hypodermis and ulcerates the epidermis on the surface. Langerhans cells are dendritic, antigen-presenting cells localized in the suprabasal regions of the squamous epithelium of the skin and mucous membranes, which help regulate the immune system. In this report, we present our experience with extensive gluteal, perineal, and perianal hidradenitis suppurativa and Langerhans cell histiocytosis cases, including our treatment methods and outcomes.

The aim of this study was to assess the effects of supplementation of inorganic sources of manganese (MnO, MnSO4), zinc (ZnO, ZnSO4) and copper (CuSO4) at different levels (0.06%DM for Mn, 0.05%DM for Zn; and 0.01 and 0.05%DM for Cu) on in vitro rumen fermentation, solubility and bioavailability. Fermentation activity was measured by total gas production (TGP) and dry matter degradability after 70hrs of fermentation (dDM%). Trace-mineral (TM) solubility was estimated by the TM concentration in the supernatant of the final fermentation medium (SOL) and TM bioavailability by the TM concentration in a bacterial enriched fraction (BACT). Mn (regardless of source) and ZnO tended (p<0.10) to decrease, while Cu showed no significant effect on TGP. The addition of inorganic Mn and of ZnO tended (p<0.10) to decrease, ZnSO4 tended to increase (p<0.10), whilst Cu showed no effect on dDM%. Concerning solubility, Mn (MnO and MnSO4), ZnSO4 and CuSO4 significantly (p<0.05, p<0.001 and p<0.01) increased, while ZnO did not affect TM content of the SOL. These results indicate that MnSO4, ZnSO4 and CuSO4 are highly soluble, MnO is quite soluble, while ZnO has a low solubility in the rumen. Based on the TM content of BACT, MnO, MnS4 and CuSO4 have a high bioavailability, while ZnO is poorly assimilated by rumen bacteria. However, the lack of clear inhibition or improvement of fermentations suggests that the rumen microbiota has low requirement for TM supplementation.

Phytoplasma diseases pose a substantial threat to diverse crops of agricultural importance. Management measures are usually implemented only after the disease has already occurred. Early detection of such phytopathogens, prior to disease outbreak, has rarely been attempted but would be highly beneficial for phytosanitary risk assessment, disease prevention and mitigation. In this study we present the implementation of a recently proposed proactive disease management protocol (DAMA: Document, Assess, Monitor, Act) for a group of vector-borne phytopathogens. We used insect samples collected during a recent biomonitoring program in southern Germany to screen for the presence of phytoplasmas. Insects were collected with Malaise traps in different agricultural settings. DNA was extracted from these mass trap samples and subjected to PCR-based phytoplasma detection and COI sequence metabarcoding. In about 1% of the analyzed samples, phytoplasma DNA was detected. Phytoplasma group identification was performed by 16S rRNA gene sequence analysis and the detected phytoplasmas could be assigned to the 16SrI subgroups B and L. Insect species in the sample were identified by DNA metabarcoding. By using established databases, checklists, and archives, we documented historical associations and records of phytoplasmas and its hosts in the study region. For the assessment in the DAMA protocol, phylogenetic triage was performed in order to determine the risk for tri-trophic interactions (plant-insect-phytoplasma) and associated disease outbreaks in the study region. A phylogenetic heat map constitutes the basis for risk assessment and was used here to identify a minimum number of seven leafhopper species suggested to be monitored by stakeholders in this region. A proactive stance in monitoring changing patterns of association between hosts and pathogens can be a cornerstone in capabilities to prevent future phytoplasma disease outbreaks. To our knowledge, this is the first time that the DAMA protocol has been applied in the field of phytopathology and vector-borne plant diseases.

Self-employed individuals comprise around 15% of Canada’s workforce. For those with cancer, frequent functional loss and diminished work ability due to side effects of the disease and its treatment significantly impact their well-being and business vitality. Compared to salaried can-cer survivors, the self-employed experience greater reductions in work hours and up to 48% greater income loss, yet most research addresses the former population. To describe self-employed Canadian cancer survivors’ experiences continuing and returning to work, our quali-tative study examines their strategic efforts to continue working throughout the disease trajecto-ry or return to work post-recovery. Employing an interpretive description approach and an in-terview guide based on a vocational rehabilitation model for cancer survivors, we analyze data from 23 participants—both French- and English-speaking—from six Canadian provinces, with eight different job types and nine different cancer diagnoses. Our constant comparative analysis of the transcribed interviews reveals four major themes and twelve sub-themes: Impact of can-cer on the self-employed function (physical, cognitive, and psychological), on their ability to maintain their business, and financial well-being, and facilitating factors for working with can-cer. Cancer disclosure and non-disclosure were both deemed viable strategies, but ceasing work was not. We thus recommend professional support for self-employed cancer survivors in plan-ning any necessary business modifications to accommodate their condition and cancer treatment to lessen the negative impact of cancer on self and on their business well-being.

Traceability is the ability to determine the path of a product from purchase to consumption to determine when and where it originated. This paper aimed to determine the factors that influence fishers’ decision-making to participate in tuna traceability program, it also explores the determinants of fish catch for small-scale fishers and the feasibility of implementing tuna traceability in the Davao Gulf, Philippines. The result of the interview showed that the significant factors that highly affected the decision-making of fishers in implementating tuna traceability program: boat capacity, fishing hours and communication of fishers (P≤0.05). Household size, years in community, fishing hours, volume of fish sold, and the fishers' communication in the fishing ground (P≤0.05) were other factors that determined the daily catch of the fishers. The results of this study showed that fishers from the Davao Gulf were willing to be part of traceability program that would sustain and increase the value of their fish catch. Moreover, communication was shown to be critically needed in such programs adjusting it for the fish catch to remain fresh or of good quality. Our study will help in deterring and mitigating illegal, unregulated and unreported fishing (IUU) through fish catch traceability.

Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome 27-31kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and 9 accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are 7 known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2 responsible for the Covid-19 pandemic. Antivirals that have been approved by the FDA for use against Covid-19 such as Paxlovid can potentially target and successfully inhibit the main protease (MPro) activity of multiple human CoVs, however alternative proteomes encoded by CoV genomes have a closer genetic similarity to each other, suggesting that antivirals could be developed now that target future CoVs. New zoonotic introductions of CoVs to humans are inevitable and unpredictable. Therefore, new antivirals are required to control not only the next human CoV outbreak, but also the 4 common human CoVs (229E, OC43, NL63, HKU1) that circulate frequently and to contain sporadic outbreaks of the severe human CoVs (SARS-CoV, MERS and SARS-CoV-2). The current study found that emerging antiviral drugs, such as Paxlovid, have only been proven to target SARS-CoV-2. Other drugs which have the potential to target other human CoVs, are still within clinical trial and are not yet available for public use. Monoclonal antibody (mAb) treatment and vaccines for SARS-CoV-2 can reduce mortality and hospitalisation rates, however they target the Spike protein whose sequence mutates frequently and drifts. Spike also is not applicable for targeting other HCoVs as these are not well conserved sequences among human CoVs. Thus, there is a need for readily available treatments globally that target all 7 human CoVs and improve the preparedness for inevitable future outbreaks. Here we discuss antiviral research contributing to the control of common and severe CoV replication and transmission, including the current SARS-CoV-2 outbreak. The aim was to identify common features of CoVs for antivirals, biologics and vaccines that could reduce the scientific, political, economic and public health strain caused by CoV outbreaks now and in the future.

Endo-reticular stress induces the unfolded protein response including a highly conserved set of genes crucial for cell survival against a variety of onslaughts. Among the activated stress response genes is Ire1, which undergoes auto-phosphorylation and acquires a regulated Ire1-dependent mRNA decay activity. Ire1P non-canonically splices the mRNA for Xbp1 in the cytoplasm. This spliced Xbp1 serves as mRNA encoding a transcription factor for unfolded protein response genes. Meanwhile the mRNA decay function of Ire1P degrades other cellular mRNAs and can cause changes to the translation machinery by altering regulators in a cell specific manner. Naïve splenic B cells differentiate into Antibody Secreting Cells and activate Ire1 phosphorylation early on after LPS stimulation, within 18 hrs. When Ire1 is activated in B cells, in addition to Xbp1 splicing, there are large-scale changes in mRNA; inhibition of the mRNA degradation function of Ire1 both reduces the number and changes the type of genes involved in altered splicing patterns, including factors for snRNA transcription. Some of the splicing changes seen at 18 hrs after LPS persist into the late stages of antibody secretion, up to 72 hrs, while others are supplanted by new splicing changes introduced by the induction of ELL2, a transcription elongation factor. ELL2 changes mRNA processing patterns and is necessary for Immunoglobulin secretion. RNA splicing patterns in antibody secreting cells are thus shaped by endo-reticular stress, ELL2 induction, and are associated with changes in the levels of snRNAs.

This study examines demographic factors which may influence opinions concerning medical students’ self-care and substance use behaviors as a means of providing insights into how future doctors view these issues compared to Australian doctors and members of the public. We conducted national, multicenter, prospective, on-line cross-sectional surveys using hypothetical scenarios to three cohorts- Australian medical students, medical doctors, and the public. Participants’ responses were compared for the different contextual variables within the scenarios and the participants’ demographic characteristics. In total 2,602 medical students, 809 doctors and 503 members of the public participated. Compared with doctors and the public, medical students were least tolerant of alcohol intoxication, and most tolerant of using stimulants to assist with study, and cannabis for anxiety. Doctor respondents more often aligned with the public’s opinions on the acceptability of the medical students’ behaviors. Although opinions are not equivalent to behaviour, Australian students’ views on the acceptability for cannabis to help manage anxiety, and inappropriate use of prescription-only drugs are concerning; these future doctors will be responsible for prescribing drugs and managing patients with substance abuse problems. However, if current Australian medical student’s opinions on alcohol misuse persist, one of the commonest substance addictions amongst doctors may decrease in future.

We aimed at analyzing Chlorophyll-a and CDOM dynamics from field measurements and at assessing the potential of multispectral satellite data for retrieving water-quality parameters in three small surface reservoirs in the Brazilian semiarid region. More specifically, this work comprises i) analysis of Chl-a and trophic dynamics; ii) characterization of CDOM; iii) estimation of Chl-a and CDOM from OLI/Landsat-8 and RapidEye imagery. The monitoring lasted 20 months within a multi-year drought, which contributed to water-quality deterioration. Chl-a and trophic state analysis showed a highly eutrophic status for the perennial reservoir during the entire study period, while the non-perennial reservoirs ranged from oligotrophic to eutrophic, with changes associated with the first events of the rainy season. CDOM characterization suggests that the perennial reservoir is mostly influenced by autochthonous sources, while allochthonous sources dominate the non-perennial ones. Spectral-group classification assigned the perennial as CDOM-moderate and highly eutrophic reservoir, whereas the non-perennial ones were assigned as CDOM-rich and oligotrophic-dystrophic reservoirs. The remote sensing initiative was partially successful: the Chl-a was best modelled using RapidEye for the perennial; whereas CDOM performed best with Landsat-8 for non-perennial reservoirs. This investigation showed high potential for retrieving water quality parameters in dry areas with small reservoirs.

A high proportion of dogs and cats are fearful during veterinary visits, which in some cases may escalate into aggression. Here, we discuss factors that contribute to negative emotions in a veterinary setting and how these can be addressed. The set-up of the waiting area (e.g. spatial dividers; elevated places for cat carriers), tailoring the examination and the treatment to the individual, considerate handling (minimal restraint when possible, avoiding leaning over or cornering animals) and offering high-value food or toys throughout the visit can promote security and, ideally, positive associations. Desensitisation and counterconditioning are highly recommended both to prevent and address existing negative emotions. Some negative experiences such as short-term pain from injections can be minimised by using tactile and cognitive distractions. Preemptive analgesia is recommended for known painful procedures. Recommendations for handling fearful animals to minimise aggressive responses are discussed. However, anxiolytics or sedation should be used whenever there is a risk of traumatising an animal or for safety reasons. Stress-reducing measures can decrease stress and fear in patients and consequently their owners – thus strengthening the relationship with the clients as well as increasing the professional satisfaction of veterinary staff.

Inert gas asphyxiation is a rarely observed form of suffocation in which the decedent breathes in an inert chemical, such as helium or nitrogen, in the absence of oxygen. The ultimate cause of death is not a result of the chemical itself, but rather from the oxygen starvation as the inert gas displaces vital oxygen. In this case report, a 66-year-old Caucasian female with a history of gastroparesis, degenerative disc disease, and chronic pain was found deceased with a plastic bag secured around her head. Plastic tubing terminated inside the bag and connected to a nearby canister of nitrogen gas. This case study discusses the challenges in determining inert gas asphyxiation as the cause of death in a postmortem setting and emphasizes the importance of understanding the decedent’s history and context of the environment in which they were found.

It is important to be familiar with the presentation of Turner syndrome and to understand the common causes of death associated with the disease. Using the autopsy case as an example, this case report will outline the classic presentation of Turner syndrome, go over its physiology, epidemiology, pathogenesis and explain the cause of death in this particular case while also highlighting other common causes of death/risk factors within Turner syndrome. Differential diagnosis and mimicking disease processes will also be discussed. This report will also highlight the molecular tests used for the diagnosis of Turner syndrome, discuss developments using in situ hybridization, and discuss why this method is best for the determination of Turner syndrome over conventional karyotyping.

Objective: To explore the effect of rural-urban residence on self-reported health status with UK cancer survivors. Design: A cross-sectional postal questionnaire that collected data on demographics, post-code and self-reported health status. Methods: Independent Samples t test was used to detect differences in health status between rural and urban respondents. Pearson’s χ2 was used to control for confounding variables and multivariate analysis was conducted using Stepwise linear regression. Setting: East Midlands of England. Participants: Adult cancer survivors who had undergone primary treatment in the last five years. Participants were excluded if they had recurrence or metastatic spread, started active oncology treatment in the last twelve months and were in receipt of palliative or end of life care. Main Outcome: Residence was measured using the UK ONS RUC2011 Rural-Urban Classifications and Health Status via the UK ONS self-reported health status measure. Results: 227 respondents returned a questionnaire. Forty-five per cent (N=103) were resident in a rural area and fifty-three per cent (N=120) in an urban area. Rural (4.11±0.85) respondents had significantly (p<0.001) higher self-reported health status compared to urban (3.65±0.93) respondents (MD 0.47; 95% CI 0.23, 0.70). Conclusion: Rural respondents had significantly higher self-reported health status compared to their urban counterparts. It is hoped that the results will stimulate further work in this area and that researchers will be encouraged to collect data on rural-urban residency where appropriate.

The incorporation of unmanned aircraft terminal operations into the scope of Detect and Avoid systems necessitates analysis of the safety performance of those systems—principally, an assessment of how well those systems prevent loss of well clear from and collision with other aircraft. This type of analysis has typically been conducted by Monte Carlo simulation with synthetic, statistically representative encounters between aircraft drawn from an appropriate encounter model. While existing encounter models include terminal airspace classes, none explicitly represents the structure expected while engaged in terminal operations, e.g., aircraft in a traffic pattern. The work described herein is an initial model of such operations, scoped at this time specifically for assessment of unmanned aircraft landings and encounters with other aircraft either landing or taking off. The model shares the Bayesian network foundation of other MIT Lincoln Laboratory encounter models but tailors those networks to address structured terminal operations, i.e., correlations between trajectories and the airfield and each other. This initial model release is intended to elicit feedback from the standards-writing community.

Local air quality is a major concern for the population regularly exposed to high levels of air pollution. The airport, mainly due to its aircraft engines activities during taxiing and take off, is often submitted to heterogeneous but important concentrations of NOx and PM. The study suggests an innovative approach to determine the air traffic impact on air quality at the scale of the airport, its runways and terminals, in order to be able to locate the persistent high concentrations spots. The pollutants concentrations at 10 m resolution and 1 s time step are calculated in order to identify the most affected areas of an airport platform. A real day of air traffic on a regional airport is simulated, using real data as aircraft trajectories (from radar streams). In order to estimate the aircraft emissions, the Air Transport Systems Evaluation Infrastructure (IESTA) is used. Regarding local air quality, IESTA relies on the non-hydrostatic meso-scale atmospheric model Meso-NH using grid-nesting capabilities with 3 domains, for this study. The detailed cartography of the airport distinguishes between grassland, parking and terminals, allowing to compute exchanges of heat, water and momentum between the different types of surfaces and the atmosphere as well as the interactions with the building using a drag force. The dynamic parameters like wind, temperature, turbulent kinetic energy and pollutants concentration are computed at 10 m resolution over the 2 × 4 km airport domain. The pollutants are considered in this preliminary study as passive tracers, without chemical reactions. This preliminary study aims at proving the feasibility of high scale modelling over an airport with state of the art physical models.

TGF-β signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix remodeling. In this article, we will review how TAK1 activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we will discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development will be critical in designing therapeutics which inhibit tumor progression while bolstering the immune response.

This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium phosphate putty scaffold material (TCP-P) and of a particulate tricalcium phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor augmentation (SFA) in 7 patients applying a split-mouth design. Biopsies were processed for immunohistochemical analysis of resin embedded sections. Sections were stained for collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP). Furthermore, the bone area and particle area fraction were determined histomorphometrically. Cone-beam CT data recorded after SFA and 6 month later were used for calculating the graft volume at these two time points. TCP-P displayed more advantageous surgical handling properties and a significantly greater bone area fraction and smaller particle area fraction. This was accompanied by significantly greater expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced reduction in grafting volume with TCP-P. SFA using both types of materials resulted in formation of sufficient bone volume for facilitating stable dental implant placement with all dental implants having been in function without any complications for 6 years. Since TCP-P displayed superior surgical handling properties and greater bone formation than TCP-G, without the Hyac hydrogel matrix having any adverse effect on bone formation or graft volume stability, TCP-P can be regarded as excellent grafting material for SFA in a clinical setting.

Smartwatches provide technology-based assessments in Parkinson’s disease (PD). We present results for sensor validation and disease classification via Machine Learning (ML). A comparison setup was designed with two different series of Apple smartwatches, one Nanometrics seismometer and a high-precision shaker to measure tremor-like amplitudes and frequencies. Clinical smartwatch measurements were acquired from a prospective study including 450 participants with PD, differential diagnoses (DD) and healthy participants. All participants wore two smartwatches and within a 15-min examination. Symptoms and medical history were captured on the paired smartphone. A broad range of different ML classifiers were cross-validated. Amplitude and frequency differences between smartwatches and the seismometer were under the level of clinical significance. The most advanced task of distinguishing PD vs DD was evaluated with 74,1% balanced accuracy, 86,5% precision and 90,5% recall by Multilayer Perceptrons. Deep Learning architectures significantly underperformed in all classification tasks. Smartwatches are capable of capturing subtle-tremor signs with low noise. This study provided the largest PD sample size of two-hand smartwatch measurements and our preliminary ML-evaluation shows that such a system provides powerful means for diagnosis classification and new digital biomarkers but it remains challenging for distinguishing similar disorders.

The constant increase in current density in electrical wires leads to increasingly significant heat losses due to Joule effect. Therefore, reducing the electrical resistivity of copper wires becomes necessary. To achieve this goal, the development of a composite material incorporating a more conductive reinforcement, the graphene, is a promising way. The design of a copper/graphene composite using a powder metallurgy-based method is presented. This synthesis method allows for interface control through the growth of CuO(Cu) nanoparticles tightly bonded to the reinforcement. It also involves the dispersion of graphene through ultrasonic treatment and its alignment within the matrix using a uniaxial pressing densification method. The increase in the hardness (+12 HV) demonstrates the effective dispersion and separation of graphene layers. The impact on the electrical properties of dendritic copper (ρe = 2.30 µΩ.cm) remains limited, with a decrease in electrical resistance of approximately 1.4%. However, for copper with higher electrical resistivity, flake copper (at 2.71 µΩ.cm) and brass at (7.66 µΩ.cm), reductions of 2.7% and 10% have been achieved, respectively. With the improvement of graphene quality, there is more room to improve the electrical properties. This work paves the way for the development of composites with improved electrical resistivity.

The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades with current research unable to fully account for this dramatic increase in prevalence. One explanation proposes that both intrinsic (e.g., genetic) and extrinsic (e.g., environmental) risk factors may be involved in the etiology of ASD. The goal of this review paper is to explore modifiable pathways for intervention in children at risk for ASD, specifically examining how early social experience may be correlated with epigenetic change in genes associated with autism. We present an innovative model which proposes that polygenic risk and social experience (via epigenetic mechanisms) may both contribute to the observed ASD phenotype. Previous research on genetic, environmental, and epigenetic mechanisms implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which is epigenetically altered by early social experience, plays a crucial role in mammalian social and cognitive development, and is associated with both genetic and epigenetic risk for ASD. Identifying intrinsic (e.g., genetic) and extrinsic (e.g., social experience) risk markers for ASD, a combination of which has not previously been examined, would transform our understanding of this condition, facilitate earlier identification of ASD risk, and guide early intervention efforts. This may have a far-reaching impact on individuals with ASD, their families, and society.

The study purpose was to train and validate a deep-learning approach to detect micro-scale streetscape features related to pedestrian physical activity. This work innovates by combining computer vision techniques with Google Street View (GSV) images to overcome impediments to conducting audits (e.g., time, safety, and expert labor cost). The EfficientNETB5 architecture was used to build deep-learning models for eight micro-scale features guided by the Microscale Audit of Pedestrian Streetscapes-Mini tool: sidewalks, sidewalk buffers, curb cuts, zebra and line crosswalks, walk signals, bike symbols, and streetlights. We used a train--correct loop, whereby images were trained on a training dataset, evaluated using a separate validation dataset, and trained further until acceptable performance metrics were achieved. Further, we used trained models to audit participant (N=512) neighborhoods in the WalkIT Arizona trial. Correlations were explored between micro-scale features and GIS-measured- and participant reported-macro-scale walkability. Classifier precision, recall, and overall accuracy were all >84%. Total micro-scale was associated with overall macro-scale walkability (r=0.300,p<.001). Positive associations were found between model-detected and self-reported sidewalks (r=0.41,p<.001) and sidewalk buffers (r=0.26,p<.001). Computer vision model results suggest an alternative to trained human raters, allowing for audits of hundreds or thousands of neighborhoods for population surveillance or hypothesis testing.

Barley straw was used to reinforce PHB in a discontinuous semi-industrial process. Four different fibres were used as reinforcing material : sawdust (SW), defibred (DFBF), delignified (DBF) and bleached (BBF) fibres. Looking at the mechanical properties, onlythe elastic moduli (Et) revealed an improvement. Oppositely, the strengths at break, under both tensile and bending assays, tended to decrease, evidencing a poor affinity between both components. Thanks to the mechani-cal treatment applied on the fibre, DFBF appeared as the most promising filler with the mechani-cal properties of the composites closest to those of neat PHB. DFBF-based composites were then produced by means of a process intensification using a twin-screw extruder, and then moulded into flowerpots. Mechanical results showed almost the same properties between the discontinuous and intensification processes. The suitability of the material to be used on agriculture flowerpots was demonstrated by simulation. . PHB-DFBF composite material can be considered an alterna-tive to replace petrol-based products for applications in agriculture and horticulture.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

Molecularly imprinted polymers (MIPs) have been widely used in nanomedicine during the last few years. However, their potential is limited by their intrinsic properties resulting, for instance, in lack of control in drug release processes or complex detection for in vivo imaging. Recent attempts in creating hybrid nanomaterials combining MIPs with inorganic nanomaterials succeeded in providing a wide range of new interesting properties suitable for nanomedicine. Through this review, we aim to illustrate how hybrids molecularly imprinted polymers may improve patient care with enhanced imaging, treatments and combination of both.

The global increase of recreational escape rooms has inspired teachers around the world to implement escape rooms in educational settings. As escape rooms are increasingly popular in education, there is a need to evaluate their use, and a need for guidelines in order to develop and implement escape rooms in the classroom. This systematic review synthesizes current practices and experiences, focussing on important educational and game design aspects. Subsequently, relations between the game design aspects and the educational aspects are studied. Finally, student outcomes are related to the intended goals. In different disciplines, educators appear to have different motives to use aspects such as time constraints or teamwork. These educators make different choices for related game aspects such as the structuring of the puzzles. Other educators base their choices on common practices in recreational escape rooms. However, in educational escape rooms players need to reach the game goal by achieving the educational goals. More alignment in game mechanics and pedagogical approaches are recommended. These and more results lead to recommendations for developing and implementing escape rooms in education, and will help educators creating these new learning environments, and eventually help students’ foster knowledge and skills more effectively.

There is a general lack of research involving older lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) people. This systematic review aimed to synthesize Japanese and Swedish qualitative research on LGBTQ people aged 60 years or older. PRISMA guidelines were followed. Japanese and Swedish articles, published in English-language journals, were searched across PsychINFO, Medline, CINAHL, and Sociological Abstracts databases. Additional searches were carried out to include studies written in Japanese or Swedish. There were no papers from Japan, and five from Sweden were reviewed. Four articles were included, including 48 participants aged 60–94 years. We summarized the findings using a deductive thematic synthesis. Two major themes emerged: (a) quality of life, minority joy, and resilience (positive aspects), and (b) experiences of discrimination, stigmatization, and minority stress (negative aspects). The participants described a wish to be acknowledged for their own assets and unique life histories, and to be treated as everyone else. They emphasized the importance of knowledge of LGBTQ issues among nursing staff, so that older LGBTQ people are treated in a competent and affirmative way. The study revealed several important topics for understanding older LGBTQ people’s life circumstances and the severe lack of qualitative studies in Japan and Sweden.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo wheat allergen-specific skin prick test (SPT), blood test for serum immunoglobulin E (sIgE) levels or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its novel diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis and basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability and safety of related clinical trials will then be discussed.

Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat; one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating compositions independently to their relative intake. Additionally, it is unknown how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining individual fatty acid compositions we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was an increase in the circulating C17:0 compositions as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent to the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 composition is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).

Red beetroot, is a well-recognized and established source of bioactives (e.g., betalains and polyphenols) with anti-inflammatory and antimicrobial properties. It is proposed as a potential alternative to zinc oxide, with a focus on gut microbiota modulation and metabolite production. In this study, weaned pigs aged 28-days were fed either a control diet, diet supplemented with zinc oxide (3,000 mg/kg), or 2% and 4% pulverized whole red beetroot (CON, ZNO, RB2 and RB4; respectively) for 14 days. After the pigs were euthanized, blood and digesta samples were collected for microbial composition and metabolite analyses. Results showed, red beetroot supplemented diet at 2% improved the gut microbial richness relative to other diets, but marginally influenced the caecal microbial diversity compared to zinc oxide supplemented diet. Further increase in red beetroot levels (4% -RB4) lead to loss of caecal diversity, decreased short chain fatty acids and secondary bile acid concentrations. An increased Proteobacteria abundance, presumably due to increased lactate/lactic acid producing bacteria was also observed. Summarily, red beetroot contains several components conceived to improve the gut microbiota and metabolite output of weaned pigs. Future studies investigating individual components in red beetroot will better elucidate their contributions to gut microbiota modulation and pig health.

Monitoring glycosylation changes within cells upon response to stimuli remains challenging because of the complexity of this large family of post-translational modifications (PTMs). We have developed an original tool enabling labeling and visualization of the cell cycle key-regulator b-catenin in its O-GlcNAcylated form based on intramolecular Förster resonance energy transfer (FRET) technology in cells. We opted for a bioorthogonal chemical reporter strategy based on the dual-labeling of b-catenin with a green fluorescent protein (GFP) for protein sequence combined with a chemically-clicked imaging probe for PTM resulting in a fast and easy to monitor qualitative FRET assay. We validated this technology by imaging the O-GlcNAcylation status of b-catenin in HeLa cells. Moreover, the changes in O-GlcNAcylation of b-catenin were varied by perturbing global cellular O-GlcNAc levels with inhibitors of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Finally, we provided a flowchart demonstrating how this technology is transposable to any kind of glycosylation.

Autoimmune hemolytic anemias (AIHAs) are conditions whereby a person produces an antibody to their own red blood cells (RBCs). These conditions can be primary with unknown cause or secondary, associated with diseases or infections. There are seven different categories of AIHA, warm-antibody AIHA (wAIHA); cold-antibody AIHA that includes cold agglutinin syndrome (CAS) and cold agglutin disease (CAD); mixed AIHA, also called combined cold and warm AIHA; paroxysmal cold hemoglobinuria (PCH) also termed Donath-Lansteiner test-positive AIHA; direct antiglobulin test-negative AIHA (DAT-neg AIHA); drug-induced immune hemolytic anemia (DIIHA); and passenger lymphocyte syndrome. This review will discuss each of these AIHAs and provide information on diagnosis and treatment.

Background: There is a lack of knowledge about how nurses and general practitioners (GPs) collaborated during the COVID-19 pandemicin primary care settings. Our study examined the roles of primary care nurses during the pandemic’s first wave, between March and June 2020, in Switzerland. Methods: The study involved all eight general practices implementing of a nursing role to the practice’s team. Primary care practice staff members (nurses, GPs and medical assistants) have been involved on the development of a new organizational model. A mixed-methods design study collected quantitative data using daily activity monitoring and an electronic survey. Additionally, eight nurses and nine GPs participated in a focus group discussion and individual interviews. Results: GPs recognized the substantial contributions, versatility, and autonomy of the primary care nurses in their practices during the pandemic. Those nurses experienced their involvement positively, mainly thanks to their perceived autonomy. The distribution of activities between primary care practice professionals was heterogenous due to extrinsic and intrinsic factors. Conclusion: Both nurses and GPs agreed that there was added value in having primary care nurses ingeneral practices in time of crisis, and this agreement will bolster plans to integrate this workforce across the canton. The development of nurses’ roles in primary care during the pandemic was reliant on many factors, including practice organization and Switzerland’s healthcare reimbursement and payment system

Lactic acid bacteria are traditionally applied in a variety of fermented food products and have the capability to produce a wide range of bioactive ingredients during fermentation including vitamins, bacteriocins, bioactive peptides and bioactive compounds. The bioactivity and health benefits associated with these ingredients have gained interest in applications in the functional dairy market and have relevance both as components produced in situ and as functional additives. This review provides a brief description of the regulations regarding the functional food market in the European Union as well as an overview of some of the functional dairy products currently available in the Irish and European markets. A better understanding of the production of these ingredients excreted by lactic acid bacteria can further drive the development and innovation of the continuously growing functional food market.

Deficient wound healing is frequently observed in patients diagnosed with diabetes, a clinical complication that compromises mobility and leads to limb amputation, decreasing patient autonomy and family lifestyle. Fibroblasts are crucial for secreting the extracellular matrix to pave the wound site for endothelial and keratinocyte regeneration. The biosynthetic pathways for collagen production are one of the main components of the extracellular matrix, as the crosslinking of extracellular collagen fibers is intimately related to fibroblast redox homeostasis. In this study, human dermic fibroblasts were cultured with 1 mM sodium selenite (inorganic) and 1 mM of two selenium amino acids (organic), Se-cysteine and Se-methionine. This concentration was compatible with long-term exposure necessary for extracellular matrix production and allowed us to examine the impact of these three compounds on the state and response of the thiol-based HyPer biosensor expressed in the cytoplasm. In addition, the abundance of extracellular matrix and ultrastructural properties were evaluated by Picrus Sirius red staining and scanning electronic microscopy, respectively. We also evaluated whether these selenium compounds effectively ameliorated the perturbations induced by culturing fibroblasts at high glucose levels (25 mM) regarding cytoplasmic redox, extracellular matrix, and glycation on collagen fibers. Our results indicate that cytoplasm protein oxidation was sensitive to selenium compound supplementation. Selenium amino acids increased the sensitivity to protein oxidation, and only Se-cysteine increased the disulfide bond reduction in fibroblasts maintained in high glucose. Despite the lack of effect of selenium compounds on the glu-cose-induced increase in matrix fiber thickness, we found that endothelial migration improved in the matrix generated by high glucose-cultured fibroblasts.

The bivalve mollusk, Anadara tuberculosa (Black Shell, in Spanish Concha prieta, "CP"), is found on America's Pacific coast, where it is harvested for subsistence and commercial markets. This paper aims to diagnose the performance of the black shell's value chain. We also identify several challenges that must be addressed to improve the sustainability of the black shell fishery in Ecuador. The descriptive methodology was quantitative, with a non-experimental, field, cross-sectional, and ex post facto design. Similar questionnaires were designed, validated, and applied to each link in the production chain to collect information. The performance of the value chain was diagnosed in the dimensions of productivity, competitiveness, and quality of life, reaching a 75.1% index, a result that indicates that the value chain has a moderate to good performance level. However, the value chain can be improved if the following challenges are met: 1) Restoration of the mangrove ecosystem, 2) Promotion of low-intensity shellfish aquaculture, 3) Good sanitary management and purification, 4) Promotion of value-focused ventures, 5) Strengthening of organizations and agreements for the use and custody of mangroves, and 6) Strengthening of institutions that contribute to the advancement of these challenges.

This paper summarizes opinions on the economic impacts of horticulture research and extension at MSU Coastal Research and Extension Center. More than 8,400 horticulture producers, master gardeners, research and extension staff, and non-profit organizations participated in horticulture events during the last five years. Qualitative assessments of horticulture research and extension performed by the faculty and staff were solicited during voluntary surveys.

Identification of drug targets and biochemical investigations on mechanisms of action is a are major issues in modern drug development. The present article reviews the classical “one drug” – “one target” paradigm. Novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adapta-tion mechanisms are involved in responses of pathogens to xenobiotics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer. For this review we have searched Pubmed (pubmed.ncbi.nlm.nih.gov) and Web of Science (webofscience.com) using the key words listed below (status May 2024)

After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex anti-tumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these fields of research for more efficient development and effective treatments.

The Clinical Trials Transformation Initiative (CTTI) Investigator Qualification Project addresses the need for a more efficient and effective means of identifying qualified clinical investigators and delegates. Selection of investigators and delegates who are qualified by training and experience to conduct clinical trials is essential to safeguarding protections for study participants and ensuring data quality and integrity. Sponsors generally document investigator qualification through training on the principles of good clinical practice (GCP), as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), adopted by regulatory authorities in the US, Japan and the European Union. Although these GCP principles provide an important foundation for promoting the conduct of quality clinical trials, the industry standard “one-size-fits-all” GCP training may not fully prepare investigators and delegates for conducting quality clinical trials. Routine GCP training alone may not be sufficient to prepare an inexperienced member of a site team, while repeating such training is unlikely to enhance the qualifications of an experienced researcher. The CTTI project team used findings from qualitative research activities, as well as input from an expert meeting with multiple stakeholders, to identify gaps and redundancies in the current training of investigators and their delegates and recommend practical, action-based solutions. CTTI provides recommendations on how to implement a more efficient and effective means of qualification for investigators and delegates, determine whether a site team is a good fit for a particular protocol, and improve the quality of clinical trial conduct.

This study aimed to discuss the combined theoretical and experimental results of elastic properties of the tungsten trioxide films supported on Quartz (YX)/45°/10° resonator, as surface acoustic wave (SAW) device. The SAW system with different thicknesses of WO3 thin films were imaged and structurally characterized by X-Ray diffraction, atomic force and transmission electron microscopy. The deposited WO3 films (100 nm, 200 nm and 300 nm) were crystallized in a single monoclinic phase. The acoustoelectric properties of the SAW system were obtained by combining theoretical simulations with experimental measurements. The modeling of the SAW devices has been performed by the finite element and boundary element methods (FEM/BEM). The theoretical and experimental electrical admittances responses obtained at room temperature gave access to elastic constants. The gravimetric effect of the deposited layers is observed by a resonance frequencies shift to lower values with thicknesses film. Moreover, the acoustic losses are affected by the dielectric losses of the WO3 films, while the resonant frequency decreases almost linearly. SAW devices revealed strong displacement fields with low acoustic losses as a function of WO3 thicknesses. For all the deposited layers, the Young's modulus and the Poisson coefficient obtained are respectively of 8 GPa and 0.5.

This paper summarizes some works exploiting the ate-type addition of electron-withdrawing monomers to hydrogenosiloxane groups so as to generate new silicone materials. Two types of monomers were oligomerized onto silicone backbones, namely unsaturated phosphonate and sulfone monomers. Phosphonated silicones are thermally more resistant than conventional silicones and can be transformed into amphiphilic polymers after selective ester hydrolysis. Sulfoned silicones generate solid supramolecular elastomers thanks to the strong pseudo-ionic interactions in play between sulfone groups. Rheology and modulated DSC show a solid/viscoelastic transition around 175°C, which allows using these thermoplastic materials on a larger scale than conventional silicone urea copolymers. These results open new avenues in the generation of silicone block- and grafted-copolymers with unique functionality and properties.

The purpose of this study was to quantify characteristics of bimanual movement intensity during 30-hour Hand Arm Bimanual Intensive Therapy (HABIT) and bimanual performance (activities and participation) in real-world using accelerometers in children with unilateral cerebral palsy (UCP). Twenty-five children with UCP participated in a 30-hour HABIT program. Data was collected from bilateral wrist-worn accelerometers during 30-hours HABIT to quantify the movement intensity, and three days pre- and post-HABIT to assess real-world performance gains. Movement intensity and performance gains were measured using six standard accelerometer-derived variables. Bimanual capacity (body function and activities) was assessed using standardized hand function tests. We found that accelerometer variables increased significantly during HABIT, indicating increased bimanual symmetry and intensity. Post-HABIT, children demonstrated significant improvements in all accelerometer metrics, reflecting real-world performance gains. Children also achieved significant and clinically relevant changes in the hand capacity following HABIT. Therefore, our findings suggest that accelerometers can objectively quantify bimanual movement intensity during HABIT. Moreover, HABIT enhances hand function as well as activities and participation in real-world situation in children with UCP.

Foodborne illnesses can be infectious and dangerous and most of them are caused by bacteria. Some types of common food-related bacteria exist widely in nature and pose a serious threat to both humans and animals, and can cause poisoning, diseases, disabilities and even death. Rapid, reliable and cost-effective methods for bacteria detection are of paramount importance in food-safety and environmental monitoring. Polymerase chain reaction (PCR), lateral flow immunochromatographic assay (LFIA) and electrochemical method have been widely used in food-safety and environmental monitoring. In this paper, the recent developments (2013-2023) covering PCR, LFIA and electrochemical method for various bacteria detection (Salmonella, Listeria, Campylobacter, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)) considering different foods types, analytical performances and the reported limit of detection (LOD) are discussed. It is found that the bacteria type and food sample type contribute significantly to the analytical performance and LOD. Detection by LFIA has higher average LOD (24 CFU/ml) than detection by electrochemical method (12 CFU/ml) and PCR (6 CFU/ml). Salmonella and E. coli in the Pseudomonadota domain usually have low LODs. LODs are usually lower for detection in fish and eggs. LFIA with gold and iron nanoparticles are prominent in the majority of articles of 26 CFU/ml and 12 CFU/ml respectively. Electrochemical method reveals that the average LOD is highest for cyclic voltammetry (CV) of 18 CFU/ml), followed by electrochemical impedance spectroscopy (EIS) of 12 CFU/ml and differential pulse voltammetry (DPV) of 8 CFU/ml. LOD usually decreases when replicate number increases until it remain unchanged. Exponential relations with (R²>0.95) between LOD of Listeria in milk by LFIA and electrochemical method with replicate number have been obtained. Finally, the review discusses the challenges and future perspectives (including the role of nanomaterials/advanced materials) to improve the analytical performance for bacterial detection.

Cystic Fibrosis is a chronic disease affecting multiple systems including the GI tract. Clinical manifestation in patients can start as early as infancy and vary across different age groups. With the advent of new highly effective modulators, the life expectancy of PwCF has improved significantly. Various GI aspects of CF care such as nutrition are linked to the overall improvement in morbidity, lung function, and quality of life of PwCF. The variable clinical presentations and management of GI diseases in pediatrics and adults CF should be recognized. Therefore, it is necessary to ensure efficient transfer of information between pediatric and adult providers for proper continuity of management and coordination of care at the time of transition. The transition of care is a challenging process for both patients and providers and currently, there are no specific tools for GI providers to help ensure smooth transition. In this review, we aim to highlight the crucial features of GI care at the time of transition and provide a checklist that can assist in ensuring an effective transition and ease the challenges associated with it.

Beta-glucan-stimulated mammalian macrophages show an increased responsiveness to secondary stimulation in a nonspecific manner. This phenomenon is known as trained innate immunity. Our study aimed to explore training of primary chicken monocytes. We hypothesized that primary chicken monocytes, similar to their mammalian counterparts, can be trained with β-glucan resulting in increased responses of these cells to a secondary stimulus. Primary blood monocytes of white leghorn chickens were primary stimulated with β-glucan microparticulates (M-βG), LPS, recombinant chicken interleukin-4 (IL-4) or combinations of these components for 48 h. On day 6, the primary stimulated cells were secondary stimulated with LPS. Nitric oxide (NO) production levels were measured as an indicator of pro-inflammatory activity. In addition, the cells were analysed by flow cytometry to characterize the population of trained cells and to investigate the expression of surface markers associated with activation. After the secondary LPS stimulation, surface expression of CSF1R and the activation markers CD40 and MHC-II was higher on macrophages that were trained with a combination of M-βG and IL-4 compared to unstimulated cells. This increased expression was paralleled by enhanced NO production. In conclusion, this study showed that trained innate immunity can be induced in primary chicken monocytes with β-glucan, which is in line with previous experiments in mammalian species. Innate immune training may have potential to improve health and vaccination strategies within the poultry sector.

Pancakes are fast food snacks that are generally made with the basic ingredients of wheat flour, which is an imported commodity and detrimental for people who are allergic to gluten. To reduce the use of wheat, alternative raw materials derived from local commodities are used, such as modified cassava flour (mocaf), arrowroot flour, and suweg flour. The experiment was carried out by mixing mocaf flour, arrowroot flour, and suweg flour to produce composite flour with a ratio of 70:15:15 (CF1), 70:20:10 (CF2), and 70:20:5 (CF3). The result showed that the ratio of mocaf flour, arrowroot flour, and suweg flour had a significant effect on pasting temperature, peak viscosity, hold viscosity, breakdown viscosity, setback, L*, a*, hue, whiteness, ∆E, as well as swelling volume and solubility on the characteristics of the composite flour It also had a significant effect on the texture characteristics of hardness, adhesiveness, chewiness, color characteristics L*, a*, whiteness, ∆E, and preference for the flavor of gluten-free pancake products. It is known that the best formulation for the resulting pancake product is P1, with the addition of a 70% ratio of mocaf flour, 15% ratio of arrowroot tuber flour, and 15% ratio of suweg flour.

The determinants of metacognition are still poorly understood in bipolar disorders (BD). We aimed to examine the clinical determinants of metacognition, defined as the agreement between objective and subjective cognition in individuals with BD. The participants consisted of 281 patients with BD who underwent an extensive neuropsychological battery and clinical evaluation. To assess subjective cognition, participants provided a general rating of their estimated cognitive difficulties. Clinical characteristics of BD were also recorded, along with medication. We studied the potential moderation of the association between cognitive complaints and global objective cognitive performance by several clinical variables with ordinal logistic regressions. Depression and impulsivity were associated with greater cognitive complaints. The only variable that moderated the relationship between objective and subjective cognition in the global model was the prescription of antipsychotics. Patients taking antipsychotics had a poorer association between cognitive complaints and objective neuropsychological performance. This result suggests a role for dopamine in the modulation of metacognitive performance, and calls for the systematic control of antipsychotic medication in future studies documenting metacognitive deficits in severe and persistent mental disorders. Depression and impulsivity should be investigated as potential therapeutic targets for individuals with BD and cognitive complaints, before proposing an extensive neuropsychological evaluation.

This paper summarizes the estimates of the total changes in sales, expenses, and income of participants of the horticulture research and extension programs at the Mississippi State University - Coastal Research and Extension Center for the past five years. Major items outline the estimation procedures for the past five years. The average annual values were used in estimating the total economic impacts of added gross sales, expenses, and incomes of participants in horticulture events. The cumulative total impacts reach $8.7 million in sales, 76 jobs, $1.4 million in labor income, $2.4 million in value-added, and $0.4 million in local, state, and federal taxes. In addition, the total willingness to pay for the horticulture program by the adult participants reached $1.8 million. In comparison, the annual public spending on the horticulture program averaged $1.4 million, creating additional substantial economic impacts to the region.

(1) Background: Premature infants require mothers’ milk fortification to meet nutrition needs, but breast milk composition may be variable leading to a risk of inadequate nutrition. We aimed at determining factors influencing mothers’ milk macronutrients. (2) Methods: Milk samples were analyzed for the first 5 weeks after premature delivery, by infrared spectroscopy. Mothers’ nutritional intake data were obtained during standardized interviews with dieticians then analyzed with reference software. (3) Results: Composition of 367 milk samples from 81 mothers was (Median [range]g/100mL): Carbohydrates 6.8[4.4-7.3], lipids 3.4[1.3-6.4], proteins 1.3[0.1-3.1]. There was a relationship of milk composition with mothers’ carbohydrates intake only (r=0.164; p<.01). Postnatal age was correlated with milk proteins (r=-0.505 p<.001) & carbohydrates (r=+0.202, p<.001). Multiple linear regression analyses showed (coefficient) a relationship between milk proteins r=0.547 and postnatal age (-0.028), carbohydrates intake (+0.449) and the absence of maturation (-0.066); and between milk lipids r=0.295 and carbohydrates intake (+1.279) and smoking (-0.557). Finally, between milk carbohydrates concentration r=0.266 and postnatal age (+0.012) and smoking (-0.167). (4) Conclusions: Variability of mothers’ milk composition is differentially associated for each macronutrient with maternal carbohydrates intake, antenatal steroids, smoking, and postnatal age. Improvement in milk composition could be achieved by modification of these related factors.

Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.

Previous studies have shown that agricultural works bear a disproportionately higher burden of HIV, which is the highest HIV prevalence ever reported in any working population in South Africa. This study aimed to assess HIV knowledge, attitudes and practices of agricultural workers, as a precarious and vulnerable workforce. A cross-sectional study design was employed. A pre-piloted paper-based questionnaire was administered to a consenting sample of agricultural workers. Descriptive and inferential statistics were performed using stata version 16.1 software, 0.05 level was used as a measure of significance. The majority of agricultural workers had adequate knowledge level (72.1%) regarding HIV/AIDS. Knowledge was significantly associated with having some level of education,) secondary education (AOR: 1.46, 95% CI:1.01-2.12), and post-matric qualification (AOR: 3.07, 95% CI: 1.61-5.83). The attitudes level of workers towards HIV was good (88.1%). Attitude was negatively associated with residing in informal settlements (AOR: 0.64, 95% CI 0.43-0.97). Majority of participants exhibited poor prevention practices regarding HIV (60.9%). Half of participants reported low condom usage (50.9%) and multiple sexual partners (50.6%). The portrayed risky sexual behavior establishes agricultural workers as an HIV high-risk population. Strategizing non-conventional approaches to HIV prevention and behavior change communication targeting agricultural workers is recommended.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

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 report the case of a four-year-old male patient with a complex medical history born prematurely as the result of intrauterine growth restriction due to placental insufficiency. His clinical manifestations include severe neurodevelopmental deficits, global developmental delay, Pierre-Robin sequence, and intractable epilepsy with both generalized and focal features. The proband’s low levels of citrulline and lactic acidosis provoked by administration of depakoke are evocative of a mitochondrial etiology. However, the genotype-phenotype correlation remains undefined in the absence of nuclear and mitochondrial pathogenic variants detected by deep sequencing of both genomes. However, live-cell mitochondrial metabolic investigations provide evidence of a deficient oxidative phosphorylation pathway responsible for ATP synthesis, leading to chronic energy crisis in the proband. In addition, our metabolic analysis reveals metabolic plasticity in favor of glycolysis for ATP synthesis. Our mitochondrial morphometric analysis by transmission electron microscopy confirms the suspected mitochondrial etiology, as the proband’s mitochondria exhibit an immature morphology with poorly developed and rare cristae. Thus, our results support the concept that sub-optimal levels of intrauterine oxygen and nutrients alter fetal mitochondrial metabolic reprogramming toward OXPHOS leading to a deficient postnatal mitochondrial energy metabolism. In conclusion, our collective studies shed light on the long-term postnatal mitochondrial pathophysiology caused by intrauterine growth restriction due to idiopathic placental insufficiency and its negative impact on the energy-demanding development of fetal and postnatal brain.

The plague caused by the Yersinia pestis bacterium is primarily a flea-transmitted zoonosis of rodents that can also be conveyed to humans and other mammals. In this work, we analyzed the spatial and temporal distribution of rodents’ populations during active and quiescent periods of the plague in the municipality of Exu, northeastern Brazil. The geospatial analyses had shown that all rodent species occurred through the whole territory of the municipality with different hotspots for the risk of occurrence of the different species. Important fluctuation in the rodent populations was observed with a reduction in the wild rodent fauna following the end of a plague epidemic period, mostly represented by Necromys lasiurus and increase of the commensally species Rattus rattus. A higher abundance of rats might lead to an increased exposure of humans populations, favoring spillovers of plague and other rodent-borne diseases. Our analysis contributed to further highlight the role of the wild rodent species as the amplifier hosts and of the commensally rats (Rattus rattus) as the preserver hosts on the quiescent period on that transmission infection area.

Purpose: Early glottic cancer is a highly curable malignancy. Disease control is achieved by resec-tion or external beam radiation with similar long-term results according survival. Surgery is predominantly performed by transoral endoscopic approach, due to reduced complication rates when compared to open cordectomy. Open cordectomy might still be warranted in cases of inad-equate surgical accessibility. Aim of the present study was to compare endoscopic versus open approach in relation to complications and outcome in an up-to-date patient group. Methods: 219 patients underwent primary tumor resection in early glottic cancer (UICC stages I-II). 168 opera-tions were performed endoscopically, 51 operations were open transcervical cordectomies. We compared survival data with non-parametric methods and functional outcome according to need of tracheostomy, feeding tube and voice functional outcome following ELS protocol. Results: There were no significant differences in overall survival (OS). 2 years OS after endoscopic surgery was 90.5% vs 95.3% after transcervical resection. As expected, OS in T1b and T2 tumors was worse than in T1a tumors. We found a statistically significant difference in disease free survival (DFS) within the T1a and T1b/T2 group (Log rank test: p=0.006) but no relevant difference be-tween the two surgical modalities, even when the data was stratified by T-categories performing a Cox regression (hazard ratio 1.21, p=0.712). Patients who underwent open surgery had a sig-nificantly worse peri- and postoperative course with longer hospital stay, higher frequency of tracheotomies and longer need for nasogastric tubes. Functional results were comparable within the two patient groups while higher tumor size / stage was an unfavorable predictor for voice re-habilitation. Conclusion: Open cordectomy leads to more complications but offers comparable oncological and functional outcome when compared to transoral endoscopic approach in early glottic cancer. Open surgery therefore continues to be a valid treatment option when endoscopic resection is not possible.

Environmental pollution management combined with food safety represent two of the main important challenges of the last decades. Soil and water contamination. have historically threatened food safety. As ubiquitous pollutants, microplastics (MPs) have attracted increasing attention over the last few years, due to their impact on the socio-ecological system. These particles can affect the balance of terrestrial, aquatic and aerial ecosystems. Their negative impacts are intensified when they adsorb and carry toxic chemicals. They can circulate through organisms and accumulate in the human food chain. Physiological dysfunctions in living beings continue to be reported, both in terrestrial and aquatic ecosystems. The question that remains is on what scale this might be affecting the global production of food. The present article addresses issues related to the food industry, including agriculture, livestock, and fish farming. In doing so it seeks to provide subsidies for the evaluation of the real impact of MP dispersion through the different world environments and the resulting effects on global food production.

In the Valpolicella area (Verona - Italy) Vitis vinifera cv. Corvina is the main grape variety used to produce Amarone wine. Before starting the winemaking process, the Corvina grapes are stored in a withering (i.e., dehydrating) warehouse until about 30% of the berry weight is lost (WL). This practice is followed to have the chemical metabolites concentrate in the berry and enrich the Amarone wine in aroma and antioxidant compounds. In compliance with the guidelines and strict Amarone protocol set by the Consorzio of Amarone-Valpolicella, withering must be carried out by setting the grapes in a suitable environment, either under controlled relative air humidity (RH) conditions and wind speed (WS) – no temperature modification is to be applied – or, following the traditional methods, in open-air natural environmental conditions. In general, the two processes have different dehydration kinetics due to the different conditions in terms of temperature, RH, and WS, which affect the accumulation of sugars and organic acids and the biosynthesis of sec-ondary metabolites such as stilbenes and glycoside aroma precursors. For this study, the two grape-withering processes were carried out under controlled (C) and not-controlled (NC) condi-tions and the final compositions of the Corvina dried grapes were compared also to evaluate the effects on the organoleptic characteristics of Amarone wine. The findings highlighted differences between the two processes mainly in terms of the secondary metabolites of the dried grapes, which affect the organoleptic characteristics of Amarone wine.

Synthesis and characterization of anhydrous LiZn(IO₃)₃ powders prepared from an aqueous solution are reported. Morphological and compositional analyses were carried out by scanning electron microscopy and energy dispersive X-ray measurements. The synthesized powders exhibit a needle-like morphology after annealing at 400°C. A crystal structure for the synthesized compound has been proposed from powder X-ray diffraction and density-functional theory calculations. Rietveld refinements led to a monoclinic structure, which can be described with space group P21, number 4, and unit-cell parameters a = 21.874(9) Å, b = 5.171(2) Å, c = 5.433(2) Å, and beta = 120.93(4)º. Density-functional theory calculations supported the same crystal structure. Infrared spectra were also collected and the vibrations associated to the different modes discussed. The non-centrosymmetric space group determined for this new polymorph of LiZn(IO₃)₃, the characteristics of its infrared absorption spectrum, and the observed second harmonic generation suggest a promising infrared non-linear optical material.

In T. gondii, as well as in other model organisms, gene knock-out using CRISPR-Cas9 is a suitable tool to identify the role of specific genes. The general consensus implies that only the gene of interest is affected by the knock-out. Is this really the case? In a previous study, we have generated knock-out (KO) clones of TgRH88_077450 (SRS29B; SAG1) which differed in the numbers of integrated dihydrofolate-reductase-thymidylate-synthase (MDHFR-TS) drug-selectable marker. Clones 18 and 33 had a single insertion of MDHFR-TS within SRS29B. Clone 6 was disrupted by the insertion of a short unrelated DNA-sequence, but the marker was integrated elsewhere. In clone 30, the marker was inserted into SRS29B and several other MDHFR-TS copies were found in the genome. KO and wild-type (WT) tachyzoites had similar shape, dimensions and vitality. This prompted us to investigate the impact of the genetic engineering as such on the overall proteome patterns of the four clones as compared to the respective WT. Comparative shotgun proteomics of the five strains was performed. Overall, 3236 proteins were identified. Principal component analysis of the proteomes revealed five distinct clusters corresponding to the five strains by both iTop3 and iLFQ algorithms. Detailed analysis of the differentially expressed proteins revealed that the target of the KO, srs29B, was lacking in all KO clones. Besides this protein, twenty other proteins were differentially expressed between KO clones and WT or between different KO clones. The protein exhibiting the highest variation between the five strains was srs36D encoded by TgRH_016110. The deregulated expression of SRS36D was further validated by quantitative PCR. Moreover, the transcript levels of three other selected SRS genes, namely SRS36B, SRS46, and SRS57 exhibited significant differences between individual strains. These results indicate that knocking out a given gene may affect the expression of other genes. Therefore, care must be taken when specific phenotypes are regarded as a direct consequence of the KO of a given gene.

It was the aim of this study to provide a more precise timeframe of development of the gonads and genital ducts in the equine fetus around the time of sexual differentiation. This included the identification and localisation of the primordial germ cell population. Equine fetuses between 45 and 60 days of gestation were evaluated using a combination of micro-computed tomography scanning, immunohistochemistry, and multiplex immunofluorescence. Fetal gonads increased in size by 23-fold from 45 to 60 days of gestation, paralleled by a greater increase in metanephros volume. Signs of mesonephros atrophy were detected during this time. Tubular structures of the fetal testes were present from day 50 onwards, whereas cell clusters dominated in the fetal ovary. The genital ducts were well-differentiated and presented a lumen in all samples. No sign of mesonephric or paramesonephric duct degeneration was detected. Expression of AMH was strong in the fetal testes but absent in ovaries. Irrespective of sex, primordial germ cells selectively expressed LIN28. Migration of primordial germ cells from the mesonephros to the gonad was detected at 45 days, but not at 60 days of development. Their number and distribution within the gonad were influenced (p&lt;0.05) by fetal sex. Most primordial germ cells (86.8 ± 3.2% in females and 84.6 ± 4.7% in males) were characterized as pluripotent according to co-localization with CD117. However, only a very small percentage of primordial germ cells was proliferating (7.5 ± 1.7% in females and 3.2 ± 1.2% in males) based on co-localization with Ki67. It can be concluded that gonadal sexual differentiation in the horse occurs asynchronously with regard to sex but already before 45 days of gestation.

Background/Objectives: We defined the value of a machine learning algorithm to distinguish between the EEG response to no light or any light stimulation, and between red or green light stimulation in awake volunteers with closed eyelids. This new method of EEG analysis is visionary in the understanding of visual signal processing and will facilitate anaesthetic depth research. Methods: X-gradient boosting models were used to classify the cortical response to VEP stimulation (no light vs. any light stimulation; red vs. green light stimulation). For each of the two classifications, three scenarios were tested: training and prediction in all participants (all), training and prediction in one participant (individual), training across all but one participant with prediction in the participant left out (one out). Results: Ninety-four Caucasian adults were included. The machine learning algorithm had a very high predictive value and accuracy in differentiating between no light and any light stimulation (AUCROCall: 0.96; accuracyall: 0.94; AUCROCindividual: 0.96±0.05, accuracyindividual: 0.94±0.05; AUCROConeout: 0.98±0.04; accuracyo-neout:0.96±0.04). The machine learning algorithm was highly predictive and accurate in distinguishing between green and red colour stimulation (AUCROCall: 0.97; accuracyall: 0.91; AUCROCin-dividual: 0.98±0.04, accuracyindividual: 0.96±0.04; AUCROConeout: 0.96±0.05; accuracyoneout: 0.93±0.06). The predictive value and accuracy of both classification tasks was comparable between males and females. Conclusions: Machine learning algorithms could almost continuously and reliably differentiate between the cortical EEG responses to no light or any light stimulation and between green or red colour stimulation using VEPs in awake female and male volunteers with eyes closed. Our findings may open new possibilities for using VEPs in the intraoperative setting.

The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms toward the foreign material silicone. The aim of this work was to enlighten the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome, and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intra-individual absolute quantitation TMT-liquid chromatography-tandem mass spectrometry approach was applied to profile wound proteome formed around SMI the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation and adsorbed to SMI surfaces after 6-8 months. Characterization of the expander-adhesive proteome by label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse group of natural products. They feature a wide range of intriguing posttranslational modifications as exemplified by the biarylitides. These are a family of cyclic tripeptides found in Planomonospora, carrying a biaryl-linkage between two aromatic amino acids. Recent genomic analyses revealed the minimal biosynthetic prerequisite of biarylitide biosynthesis consisting of only one ribosomally synthesized pentapeptide precursor as substrate and a modifying cytochrome P450 dependent enzyme. In silico analyses revealed that the minimal biarylitide RiPP clusters are widespread among natural product producers across phylogenetic borders including myxobacteria. We report here the genome-guided discovery of the first myxobacterial biarylitide MeYLH termed Myxarylin from Pyxidicoccus fallax An d48. Myxarylin was found to be an N-methylated tripeptide surprisingly exhibiting a C–N biaryl crosslink. In contrast to Myxarylin, previously isolated biarylitides are N-acetylated tripeptides featuring a C–C biaryl crosslink. Furthermore, the formation of Myxarylin was confirmed by heterologous expression of the identified biosynthetic genes in Myxococcus xanthus DK1622. These findings expand the structural and biosynthetic scope of biarylitide type RiPPs and emphasize the distinct biochemistry found in the myxobacterial realm.

Hexane is a solvent used extensively in the food industry for the extraction of various products such as vegetable oils, fats, flavours, fragrances, colour additives or other bioactive ingredients. As it is classified as a "processing aid", it does not have to be declared on the label under current legislation. Therefore, although traces of hexane may be found in final products, especially in processed products, its presence is not known to consumers. However, hexane, and in particular the n-hexane isomer, has been shown to be neurotoxic to humans and has even been listed as a cause of occupational diseases in several European countries since the 1970s. In order to support the European strategy for a toxic-free environment (and toxic-free food), it seemed important to collect scientific information on this substance by reviewing the available literature. This review contains valuable information on the nature and origin of the solvent hexane, its applications in the food industry, its toxicological evaluation and possible alternatives for the extraction of natural products. Numerous publications have investigated the toxicity of hexane, and several studies have demonstrated the presence of its toxic metabolite 2,5-hexanedione (2,5-HD) in the urine of the general, non-occupationally exposed population. Surprisingly, a tolerable daily intake (TDI) has apparently never been established by any food safety authority. Since hexane residues are undoubtedly found in various foods, it seems more than necessary to clearly assess the risks associated with this hidden exposure. A clear indication on food packaging and better information on the toxicity of hexane could encourage industry to switch towards one of the numerous other alternative extraction methods already developed.

Mastectomy and hysterectomy with bilateral salpingo-oophorectomy are the first steps in surgical female-to-male (FtM) gender affirmation. We aimed to critically review our experience with the combined approach of hysterectomy/salpingo-oophorectomy and bilateral mastectomy and to focus on intra- and postoperative complications. In a retrospective cohort study, 108 consecutive patients were included who underwent combined hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy in a single operating session, between November 1998 and December 2017. Main outcome measures were operating times and intra- and postoperative courses, including major and minor adverse events. Patients were 28.9 ± 6.7 years of age and revealed a mean BMI of 24.4 ± 4.1 kg/m2. The median total operating time for patients without additional procedures was 237.6 ± 110.3 minutes. Taking all intra- and postoperative complications together, there were eight (7.4%) and 21 (19.4%) patients with major and minor complications, respectively. The most frequent complication was breast hematoma (18/108, 16.7%). There was a completely uneventful intra- and postoperative course in 82 cases (75.9%). In conclusion, for FtM reassignment surgery, the combined hysterectomy / salpingo-oophorectomy and bilateral mastectomy in a single operating session seems to be feasible and safe.

Background. The molecular mechanisms underlying de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials & Methods. Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/-, HER2-), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical-pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n=32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 x 10µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR, deconvolution was performed using CIBERSORTx to assess immune cell fractions. Paired Wilcoxon test was used to compare dnMBC and eBC groups, and corrected for false discovery rate (FDR). Results. Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusion. Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.

Minigastrin (MG) analogs for therapy of CCK2R-expressing malignancies are limited by low stability in vivo or excessive accumulation in non-target organs. By modifying the C-terminal receptor-binding sequence, metabolization could be prevented and tumor targeting significantly improved. In this work, N-terminal changes of the peptide length were evaluated. Based on the amino acid sequence of DOTA-MGS5 (DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1Nal-NH₂), two new MG analogs were synthesized, by either introduction of a penta-DGlu moiety or depletion of the four N-terminal amino acids and introduction of a non-charged hydrophilic linker. Two CCK2R-expressing cell lines were used to demonstrate receptor interaction. Stability of the ¹⁷⁷Lu-labeled peptide analogs was evaluated in human serum up to 24 h after incubation and in BALB/c mice up to 30 min after injection. The biodistribution profile and tumor targeting potential was evaluated in xenografted BALB/c nude mice. For both new MG analogs, the combination of strong receptor-specific cell interaction, high stability and enhanced tumor targeting could be demonstrated. Shortening of the peptide sequence lowered the absorption in the dose-limiting organs, whereas elongation increased uptake in renal tissue.

Human papillomavirus (HPV) can potentially compromise both unassisted conception and success rates with assisted reproductive technology (ART). We aimed to evaluate the rates of HPV vaccination among women presenting for fertility care. This was a prospective study analyzing a self-reported intake form completed by all new patients presenting to a fertility clinic. The primary outcome was HPV vaccination status. Among the 523 new patients included in this study 172 (32.9%) were fully vaccinated, 237 (45.3%) were unvaccinated, and 95 (18.2%) patients didn’t respond. There was a significant age difference between fully vaccinated patients (33.1 years) compared to unvaccinated patients (37.4 years) p&lt;0.001 and a significant difference in gravidity between fully vaccinated patients (average 0.65) and unvaccinated patients (average 1.11) p=0.0005. No significant association was found between HPV vaccination status and history of abnormal Pap smears or relationship status (single vs. married). Less than half of patients presenting to our fertility center were vaccinated against HPV, despite being eligible to receive the vaccine. Younger patients with lower gravidity were more likely to be vaccinated against HPV than older patients with higher gravidity. Reproductive Endocrinologists have the opportunity to recommend HPV vaccination for eligible patients presenting for fertility care.

The blackening of cut carrots decreases their shelf life and causes severe economic losses but the molecular and metabolic mechanisms that underpin this phenomenon remain poorly characterized. Studies were therefore undertaken to determine the molecular and metabolic causes of the blackening. The susceptibility of blackening was dependent on the period of time that the crop was stored underground prior to harvest. The structure of the cell walls in the black regions was substantially changed compared to the orange regions. The black regions of carrot batons had decreased immunodetection of xyloglucan, HG-pectin, RG-I pectin, galactan and arabinan but had higher levels of lignin and phenolic compounds compared to the orange regions. Transcript profiling analysis revealed that phytohormone signalling processes were activated in the black regions. Transcripts associated with auxin signalling and ethylene-responsive transcription factors were increased in the black regions. In contrast, the levels of transcripts encoding proteins associated with secondary metabolism were decreased in the black regions. These findings implicate ethylene and auxin-related processes in the control of the primary to secondary metabolism shift that results in lignification and cell wall disruption that underpin the blackening process.

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.

Kawasaki disease is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as disease progresses with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated to KD, but also evaluates the possibility of using circulating endothelial injury biomarkers such as, circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tool of KD: a “liquid biopsy” approach. The challenges of translating liquid biopsies to use in KD, and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostics is promising and we hope this will be translated to clinical applications in the near future.

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.

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.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.