Caries is a prevalent oral disease that primarily affects children and teenagers. Advances in ma-chine learning have caught the attention of scientists working with decision support systems to predict early tooth decay. Current research has developed machine learning algorithm for caries classification and reached high accuracy especially in ML for image data. Unfortunately, most studies on dental caries only focus on classification and prediction tasks, meanwhile dental carries prevention is more important. Therefore, this study aims to design an efficient feature for decision support system machine learning based that can identify various risk factors that cause dental caries and its prevention. The data used in the research work was obtained from the 2018 Korean Children's Oral Health Survey, which totaled nine datasets. The experimental results show that combining the mRMR and GINI Feature Importance methods when training with the GBDT model achieved the optimum performance of 95%, 93%, 99%, and 88% for accuracy, F1 score, precision, and recall, respectively. So, the proposed method has provided effective predictive model for dental caries prediction.

Alzheimer's Disease (AD) presents a significant challenge in the wake of its multifaceted nature, characterized by cognitive decline, memory impairment, and neuroinflammation. Despite extensive research, effective pharmacological interventions remain elusive, prompting exploration into non-pharmacological approaches. Microcurrent therapy (MC), utilizing imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates its impact on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and preservation of neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. Our study discovered that MC therapy effectively reduces glial activation by inhibiting the TLR4-MyD88-NFκB pathway, consequently leading to decreased levels of inflammatory factors TNF-α, IL-1β, and IL-6, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.

23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2 % wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between both groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN- between 23-OH UA fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T-cell responses. In summary, our findings demonstrate that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.

Substantial studies have focused on early detection of Alzheimer's disease (AD). Cerebral amyloid beta (Aβ), is hallmark of AD, can be observed in vivo via positron emission tomography imaging using amyloid tracer or cerebrospinal fluid assessment, but costly expensive. The current study aims to identify and compared predictability in magnetic resonance imaging (MRI) markers and neuropsychological markers to predict cerebral Aβ status in AD cohort using machine learning (ML) approaches. The predictability in candidate markers for cerebral Aβ status was examined by analyzing 724 participants from the ADNI-2 cohort. Demographic variables, structural MRI markers, and neuropsychological test scores were used as input in several ML algorithms to predict cerebral Aβ positivity. Out of five combination of candidate markers, neuropsychological markers with demographics showed the most cost-efficient result. A feature selection model could distinguish abnormal levels of Aβ with the predictability of 0.85, indicating the same performance with MRI-based models. The result has first to identified the predictability in MRI markers using ML approaches, and secondary to demonstrate the neuropsychological model with demographics could predict Aβ positivity, suggesting a more cost-efficient method for detecting cerebral Aβ status compared to MRI markers.

The microtubule-associated protein TAU is sorted into the axon in healthy brain neurons. Somatodendritic missorting of TAU is a pathological hallmark of many neurodegenerative diseases called tauopathies, including Alzheimer’s Disease (AD). Cause, consequence, and (patho)physiological mechanisms of TAU sorting and missorting are understudied, in part also due to the lack of readily available human neuronal model systems. The human neuroblastoma cell line SH-SY5Y is widely used for studying TAU physiology and TAU-related pathology in AD and related tauopathies. SH-SY5Y cells can be differentiated into neuron-like cells (SH-SY5Y-derived neurons) using various substances. This review evaluates whether SH-SY5Y-derived neurons are a suitable model for i) investigating intracellular TAU sorting in general, and ii) with respect to neuron subtype-specific TAU vulnerability. I) SH-SY5Y-derived neurons show pronounced axodendritic polarity, high levels of axonally localized TAU protein, expression of all six major human brain isoforms, and TAU phosphorylation similar to the human brain. As proliferative cells, SH-SY5Y cells are readily accessible for genetic engineering, stable transgene integration and leading-edge genome editing are valuable and promising tools for TAU-related studies. II) Depending on the used differentiation procedure, SH-SY5Y-derived neurons resemble cells of distinct subcortical nuclei, i.e. the Locus coeruleus (LC), Nucleus basalis (NB) and Substantia nigra (SN), all of which early affected in many tauopathies. This allows to analyse neuron-specific TAU isoform expression and intracellular localization, also in the context of vulnerability to TAU pathology. Limitations are e.g. the lack of mimicking age-related tauopathy risk factors and the difficulty to define the exact neuronal subtype of SH-SY5Y-derived neurons. In brief, this review discusses the suitability of SH-SY5Y-derived neurons for investigating TAU (mis)sorting mechanisms and neuron-specific TAU vulnerability in disease paradigms.

Ecological footprint calculators are digital tools that help individuals calculate their environmental or climate impact, with the aim of stimulating pro-environmental behaviour change. These footprint calculators typically take an information-provision approach, but this strategy assumes that increased levels of knowledge result in increased levels of pro-environmental behaviour (i.e., a reduced footprint). This is not a given – existing literature on the relationship between environmental knowledge and pro-environmental behaviour is inconclusive, and this relationship may be different from that of environmental knowledge and ecological footprint. As such, we investigated the relationship between environmental knowledge and ecological footprint as estimated by a footprint calculator. 448 Dutch participants completed an online survey, including an ecological footprint calculator. We found no evidence for a relationship between environmental knowledge and ecological footprint calculator outcome. Rather, an exploratory analysis of our data showed that environmental values were more important predictors of ecological footprint. The finding that increased levels of knowledge are not related to a reduced ecological footprint suggests that calculators would do well to move beyond information provision, and employ additional behaviour change strategies. Based on our exploratory analysis, we provide several concrete examples of potential strategies.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

The aim of this study was to develop and validate a predictive early tooth loss multivariable model for periodontitis patients before periodontal treatment. A total of 544 patients seeking periodontal care at a university dental hospital were enrolled in the study. Teeth extracted after periodontal diagnosis and due to periodontal reasons were recorded. Clinical and sociodemographic variables were analyzed, considering the risk of short-term tooth loss. This study followed the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines for development and validation, with two cohorts considered as follows: 455 patients in the development phase and 99 in the validation phase. As a result, it was possible to compute a predictive model based on tooth type and clinical attachment loss. The model explained 25.3% of the total variability and correctly ranked 98.9% of the cases. The final reduced model area under the curve (AUC) was 0.809 (95% Confidence Interval (95% CI): 0.629 - 0.989) for the validation sample and 0.920 (95% CI: 0.891 - 0.950) for the development cohort. The established model presented adequate prediction potential of early tooth loss due to periodontitis. This model may have clinical and epidemiologic relevance towards the prediction of tooth loss burden.

GPR4, a member of proton activated GPCRs group. Previously we have reported that GPR4 is constitutively active at physiological pH and knockout of GPR4 has shown to protect dopaminergic neuronal cells from caspase-dependent mitochondrial apoptotic cell death. In this study we have investigated the role of GPR4 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treated mice model of Parkinson’s disease. Subchronic administration of MPTP in mice produces oxidative stress induced apoptotic cell death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor deficits. Treatment with NE52-QQ57, a selective antagonist of GPR4 reduced dopaminergic neuronal loss MPTP-intoxicated C57BL6/J mice and improved motor deficit and memory impairment. Co-treatment with NE52-QQ57 significantly decreases the protein level of proapoptotic marker (Bax), and increases the antiapoptotic marker (Bcl-2) in the SNpc and striatum tissue collected from the brain of MPTP inflicted mice. Further, MPTP induced activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP) was significantly decreased in the SNpc and striatum tissue of NE52-QQ57 cotreated mice. Further mice receiving both MPTP and NE52-QQ57 mice showed significantly higher TH positive cells in the SNpc and striatum than MPTP treated mice alone. Moreover, NE52-QQ57 cotreatment improved the motor activity in the rotarod test and pole test and also improved spatial memory in Y maze test. Our findings suggest GPR4 as a potential therapeutic target for PD whereas the activation GPR4 is involved in the caspase mediated apoptotic cell death in SNpc and striatum of MPTP-intoxicated mice.

Mutations of PKD1 coding for polycystin-1 (PC1) account for most of the autosomal dominant polycystic kidney disease (ADPKD). The extracellular region of PC1 contains many evolutionarily conserved domains for ligand interactions. Among these is the leucine-rich repeats (LRR) in the far N-terminus of PC1. Using zebrafish (Danio rerio) as an in vivo model system, we explored the role of LRR in the function of PC1. Zebrafish expresses two human PKD1 paralogs, pkd1a and pkd1b. Knockdown of both genes in zebrafish by morpholino antisense oligonucleotides produced phenotypes of dorsal axis curvature and pronephric cyst formation. We found that overexpression of LRR suppressed both phenotypes in pkd1-morphant zebrafish. Purified recombinant LRR domain inhibited proliferation of HEK cells in culture and interacted with the heterotrimeric basement membrane protein laminin-511 (α5β1γ1) in vitro. Mutations of amino acid residues in LRR structurally predicted to bind laminin-511 disrupted LRR-laminin interaction in vitro and neutralized the ability of LRR to inhibit cell proliferation and cystogenesis. Our data support the hypothesis that the extracellular region of PC1 plays a role in modulating PC1 interaction with the extracellular matrix and contributes to cystogenesis of PC1-deficiency.

This study explores the elements that influence consumer vegetarian diet choices in parts of South Korean provinces. The study examines these explanatory variables: ethical-animal-welfare, health, environment, social issues , mood-emotion, and religious-beliefs with vegetarianism serving as the dependent variable. The Likert scale data from 264 respondents were analyzed using logistic regression analysis. Results show that health, ethical-animal-welfare ideals as well as environmental concerns emerge as significant variables influencing the decision to embrace a vegetarian diet. This shows that consumers (international students) in Korea are becoming more aware of and concerned about health, ethical and sustainable dietary choices. Secondly, health plays a crucial role in the vegetarian diet selection, indicating that health-conscious people are more inclined to choose a vegetarian lifestyle. Religious belief and mood have various degrees of influence on the vegetarian diet decision. The findings of this study have consequences for consumer behavior, marketing managers, and decision-makers. Businesses in the food industry, in particular, can gain from catering to the needs and tastes of consumers that prioritize ethical-animal welfare ideals, as well as those that value health and environmental sustainability. Creating and advertising vegetarian and vegan choices in local restaurants can effectively attract and serve this specific target demographic.

(1) Background: Interparental conflict is a phenomenon that poses a serious threat not only to the quality of life for the couple but also to the father-child relationship, mother-child relationship, and well-being of adolescents. This study examined the influence of marital conflict on father-child and mother-child attachment and the psychosocial adjustment (2) Methods: 67 adolescents involved in Child Welfare Services (CWS) in disadvantaged neighbourhoods in southern Spain were examined. The sample was split into two groups according to the exposure to marital conflict. Subsequently, differences between groups were analysed on father attachment, mother attachment, aggression, antisocial behaviour, and emotional intelligence. (3) Results: Primarily, the data showed significantly worse attachment with the father among conflict-exposed versus non-conflict-exposed adolescents. These results were not found for the attachment with the mother. Additionally, greater anger and worse stress management were found in conflict-exposed adolescents. (4) Conclusions: The results partially confirmed the spillover and compensatory hypothesis. Practical implications point out that developing preventive interventions that protect the father-adolescent attachment in situations of family conflict is recommended.

Behavioural disorders in dogs are common and have severe welfare consequences for dogs. This study aimed to assess the factors that are significant and predictive of behaviour problems in dogs using the Animal Welfare Assessment Grid (AWAG) to further understand what factors influence their welfare. 177 AWAG assessments were undertaken across 129 dogs that clinicians deemed to have a behavioural disorder. Wilcoxon-rank sum tests were used to assess the difference in scores between dogs with behaviour disorders and a cohort of healthy dogs (n=117). This analysis showed that all physical factors besides body condition, all procedural factors besides procedure pain, and all psychological, and environmental factors were significantly different between healthy dogs and dogs with behaviour disorders. Spearman Rank Correlation Coefficient (RS) revealed several significant strong positive correlations including the procedural impact on the dog’s daily routine with aggression towards unfamiliar people and procedure pain, as well as other correlations between the dog’s behaviour during assessment with the frequency at which they encounter fears and anxieties, clinical assessment and procedure pain, and reaction to stressors and social interactions. These findings highlight the interdependent nature of the various influences of welfare. Logistic regression analysis identified that aggression towards the caregiver, fears and anxieties frequency, and choice, control, and predictability were all significant predictors of behaviour disorders. The findings have important implications for veterinary, behaviour, and animal welfare professionals as any changes across these factors may indicate poor welfare linked to emotional disorders in dogs.

This article explains how resistance alleles have become rare or have disappeared from honey bee populations in Europe (and probably also in North America). Honeybees have the highest recombination frequency of all animals, indicating that pathogenic bacteria, viruses, fungi and microsporidia are an important source of selection. To respond to new virulent strains of pathogens, honeybees need to have access to rare alleles that could foster immunity against a new pathogen. By mating in a large panmictic population, new rare alleles can be recruited, which can then be combined into new genotypes through recombination with useful alleles of other genes. Bee breeders, by selecting small samples from a large population tend to select common alleles and lose the rare ones. Rare alleles can become important when a new virulent pathogen arrives. The loss of rare alleles makes bees vulnerable to disease and parasites and explains, together with the problems caused by modern agriculture, why managed bees have high mortality rates.

Education for Sustainable Development (ESD) is crucial in higher education, providing students with the knowledge, skills, and values necessary for a sustainable future. ESD seeks a holistic understanding of sustainability and promotes critical thinking and innovative approaches. Specifically, ESD is very important to address in engineering careers, as engineers will need to establish sustainable solutions in the future. For this reason, the integration of sustainability into university curricula has been studied for some time. In this way, this research analyses the perceptions (attitudes towards teachers; knowledge about sustainable development; environmental, economic and social attitudes; sustainable behaviours) that engineering students in the Dominican Republic have towards sustainable development. 626 questionnaires completed by engineering students were obtained. Subsequently, the data was analysed in SPSS and PLS-SEM. The results showed that attitudes towards teachers have an impact on engineering students' knowledge of sustainable development. In turn, the results also showed that knowledge about sustainable development influences both attitudes (economic, social and environmental) and sustainable behaviours of engineering students. Contrary to other research, this study suggested that economic attitudes are not identified as an antecedent of sustainable behaviours among engineering students. From these results, implications and future lines of research are generated.

The aim of this work was to study age-related changes in the behaviour of adult Wistar rats using the open field (OF) and elevated plus maze (EPM) tests. Behavioural changes related to motor activity and anxiety were of particular interest. Results showed that as male and female rats progressed from 2 to 5 months of age there was a decrease in the level of motor and exploratory activities, and an increase in the level of anxiety. Age-related changes were dependent upon initial individual characteristics of behaviour. For example, animals that demonstrated high motor activity at 2 months become significantly less active by 5 months, and animals that showed a low level of anxiety at 2 months become more anxious by 5 months. Low-activity and high-anxiety rats did not show any significant age-related changes in OF and EPM tests from 2 to 5 months of age, except for a decrease in the number of rearings in EPM. Significant individual differences in the behaviour of rats in OF and EPM tests observed at 2 months were not apparent by 5 months.

Globally, football as a sport has recorded the highest rate of injury morbidity compared with other sports due to the high degree of contact between the players. Coaches play an important role in reducing injuries among the players. The objective of this study was to explore the pattern of football-related sports injuries among junior high school footballers in Dhaka, Bangladesh. A descriptive cross-sectional study was conducted between January 2019 to March 2019 in 20 junior high schools in Dhaka Metropolitan city. We observed 368 boys in the age range of 10 to 18 years old. A pre-structured questionnaire was provided to six trained junior physiotherapists to conduct the face-to-face interview with the boys in the school setting. Most students were from middle-income families. The injury prevalence of defenders was the most (157, 42.7%) followed by mid-fielders (132, 35.94%), forwards (63, 17.1%), and goalkeepers (16, 4.3%). Tackling was the main cause of injury in 21.1% of cases followed by foul play in 19.1% of the cases. In July, there were more injuries (69.0%) and associated muscle strain. Injured footballers did not visit sports physiotherapists as much as they did other health profession and the association was significant. When considering scientific knowledge, students were aware of fitness, flexibility & endurance (25.5%), sports massage (24.5%), the relation of body structure with sports Injury (21.2%), warm-up and/or cool down (19.6%). Based on the study, it was seen that students had no scientific knowledge of sports. As sports is a key activity for school-going children, comprehensive sports injury preventive knowledge is needed for students and sports teachers and coaches. Access to sports physiotherapists is also needed to prevent and manage sports injury at the field level and for rehabilitation.

Objective: To determine demographic predictors and comorbidities in hospitalized children with conduct disorder. Methods: A retrospective analysis was performed using Nationwide Inpatient Sample (2012–2014). All patients were ≤18 years and cases with primary diagnosis of conduct disorder (N = 32345) and a comparison group with another psychiatric diagnosis (N = 410,479) were identified using ICD-9-CM diagnosis codes. A logistic regression model was used to generate the Odds Ratio (OR) between both groups. Results: Children <11 years old have five times greater chances of admission for conduct disorder than adolescent (OR 5.339). African American males are more likely to be admitted for conduct disorder. Children with conduct disorder from low-income families have a 1.5 times higher likelihood for inpatient admission compared to high-income families. These children have about eleven times higher odds of comorbid psychosis (OR 11.810) and seven times for depression (OR 7.093) compared to the comparison group. Conclusion: Conduct disorders are more debilitating for children and families than many providers realize. African American male under 11 years is at the highest risk for inpatient management for conduct disorder. These patients have a higher risk of comorbid psychosis and depression which may further deteriorate the severity of illness and require acute inpatient care.

The current neural networks for tomato leaf disease recognition have problems such as large model parameters, long training time, and low model accuracy. To solve these problems, a lightweight convolutional neural network LBFNet is proposed in this paper.First, a lightweight convolutional neural network LBFNet is established as the base model. Secondly, a three-channel attention mechanism module is introduced to learn the disease features in tomato leaf disease images and reduce the interference of redundant features. Finally, a cascade module is introduced to increase the depth of the model, solve the gradient descent problem, and reduce the loss caused by increasing the depth of the model. The quantized pruning technique is also used to further compress the model parameters and optimize the model performance. The results show that the LBFNet model achieves 99.06% accuracy on the LBFtomato dataset, with a training time of 996s and a single classification accuracy of over 94%. Further training using the saved weight file after quantized pruning makes the model accuracy reach 97.66%. Compared with the base model, the model accuracy was improved by 28%, and the model parameters were reduced by 96.7% compared with the traditional Resnet50. It was found that LBFNet can quickly and accurately identify tomato leaf diseases in complex environments, providing effective assistance to agricultural producers.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and 3 (PON1 and PON3) protein expression have been described in tissues with no PON1 and PON3 gene expression. In the present study, we aimed to examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: We used peroxidase-based and fluorescence-based immunohistochemistry in 5 brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3 positive staining in star-shaped cells surrounding Aβ plaques in all Tg2576 mouse brain regions studied. Although we could not co-localize PON1 and PON3 with astrocytes, brain star-shaped cells, we found some co-localization of PON3 with microglia. Conclusions: These results suggest that 1) PON1 and PON3 cross the blood-brain barrier in discoidal HDLs and are transferred to specific brain cell types, and 2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular cell types, likely astrocytes and microglia, in AD pathology, and potentially in other neurodegenerative diseases

Alzheimer’s disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders have proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured by passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured by ELISA kits, Western blotting, and immunostaining techniques. Data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p &lt; 0.05 ~ p &lt; 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg. p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments, ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue Considering the data obtained, DTZ exhibited a potential neuroprotective anti-dementia role in ICV-STZ-induced SAD-type conditions in rats and might be repurposed as a potential therapeutic agent in the treatment and management of AD and related dementia pathologies.

Background: Phylogroup B2 Escherichia coli have been associated with Ulcerative Colitis (UC). In this study, we aimed to compare colonization with the UC-associated E. coli p19A in different mice strains, to investigate the role of alpha hemolysin in a UC mouse model. Methods: In this study, Sigirr -/- and C57BL/6 mice were chosen, and UC was induced by adding Dextran Sulfate Sodium (DSS) to the drinking water. The mice were pre-treated with ciprofloxacin. p19A expressing luminescence and GFP, alpha-hemolysin knock out p19A-∆hlyI II, and non-pathogenic lab E. coli DH10B were cultured in LB broth, and orally gavaged into the mice. Colonization with p19A WT was visualized using an in-vivo imaging system. Results: p19A WT colonized the colon, ileum, Peyer’s patches, liver, and spleen of infected C57BL/6 and Sigirr -/- mice. A total of 99% of the p19A WT infected C57BL/6 mice and 29% of the p19A WT infected Sigirr -/- mice survived to the 4th post infection day. Conclusion: UC-associated E. coli p19A WT colonized the intestines of DSS-treated mice and caused extra-intestinal infection. Hemolysin is an important factor in this pathogenesis, since isogenic hemolysin mutants did not cause the same inflammation.

Abstract: Sickle cell disease (SCD) is an autosomal recessive monogenic disorder caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, hemolysis, vaso-occlusion and sterile inflammation. Oral l-glutamine administration has been shown to reduce the frequency of pain crisis in SCD patients, however, the long-term effect of l-glutamine in SCD remains to be determined. To understand the long-term effect of l-glutamine administration in SCD liver we used quantitative liver intravital microscopy and biochemical analysis in humanized SCD mice. We here show that chronic l-glutamine administration reduces hepatic hemoglobin-heme-iron level, but fails to ameliorate ischemic liver injury. Remarkably, we find that this failure in resolution of hepatobiliary injury and persistent liver fibrosis is associated with reduced expression of hepatic Kupffer cells post l-glutamine treatment. These findings establish the importance to investigate the long-term effects of l-glutamine therapy on liver pathophysiology in SCD patients.

Alzheimer’s disease (AD) is an age-related neurodegenerative disease and is clinically characterized by cognitive impairment, memory loss, and personality disorder. Oligomers of amyloid beta-peptides (Aβ) and enhanced oxidative stress in senile plaques are prevalent pathologic hallmarks of AD. In this study, we detected the behavioral performance of Lycium ruthenicum Murray anthocyanin (LRA) -treated rats using the Morris water maze test and then investigated the effect of LRA on oxidative damage, neuronal apoptosis, and inflammatory response induced by Aβ1–42. Our results showed that LRA treatment markedly ameliorated the behavioral performance of Aβ1–42-induced rats and reduced the level of malondialdehyde, formation of protein carbonyl, and 8-hydroxy-2’-deoxygua-nosine. Furthermore, LRA also inhibited activated astrocytes and neuroinflammation via suppression of glial fibrillary acidic protein and tumor necrosis factor-alpha in the hippocampus of Aβ1–42-treated rat brain. These data suggest that LRA could be a potential anti-oxidant and anti-neuroinflammatory agent for the treatment of AD.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamin-ergic neurons responsible for unintended or uncontrollable movements. Mutations in leu-cine-rich repeat kinase 2 locus, contributes to genetic forms of PD. The fruit fly Drosophila mela-nogaster carrying this mutation (LRRK2-Dm), is an in vivo model of PD that develops motor impairment and stands for an eligible non mammalian paradigm to test novel therapeutic ap-proaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger. Pre-sents anti-inflammatory, antioxidant and neuroprotective properties making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1mM, for 14 and 21 days, in the LRRK2-Dm, with the aim to assess changes for rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-Bars). The shorter treat-ment with both molecules revealed efficacy at the higher dose improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-Bars failure was observed with the DHZ-DIM. Our data indicates that the DHZ-DIM exerts a more potent neuroprotective effect respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

A balanced diet model, rich in fruits and vegetables and ensuring the intake of natural products, has been shown to reduce or prevent the occurrence of many chronic diseases. However, the choice to consume large quantities of fruits and vegetables leads to an increase in the amount of waste, which can cause the alteration in environmental sustainability. To date, the concept of "by-product" has evolved, understood as a waste product, from which it is still possible obtain useful compounds. Therefore, the by-products in the agricultural sector, are a rich source of bioactive compounds, capable to possess a second life, decreasing the amount of waste products, the disposal costs and the environmental pollution. A promising and well-known citrus of the Mediterranean diet is the bergamot (Citrus bergamia, Risso et Poiteau). The composition of bergamot is known and the rich presence of phenolic compounds and essential oils has justified countless beneficial properties found, including anti-inflammatory, antioxidant, anti-cholesterolemic and protective activity for the immune system, heart failure and coronary heart diseases. The industrial processing of bergamot fruits leads to the formation of bergamot juice and bergamot oil. The solid residues, referred as "pastazzo", are normally used as feed for livestock or pectin production. The fiber of bergamot (BF) can be obtained from pastazzo and could exert an interesting effect thanks to its content of polyphenols. The purpose of this work was to test the effects of BF on an in vitro model of neurotoxicity induced by treatment with amyloid beta protein. In particular, this experimental model included both neurons and oligodendrocytes in order to measure the involvement of the glia and compare it with the neurons one. The results obtained showed a protective activity of BF, although the oligodendrocytes were more sensitive and fragile than neurons. Further experiments are necessary and if the trend was confirmed, solid residues of bergamot could be used in AD, and, at the same time, could help to avoid the accumulation of waste products.

We present a new mathematical model of disease spread reflecting specialties of covid-19 epidemic by elevating the role social clustering of population. The model can be used to explain slower approaching herd immunity in Sweden, than it was predicted by a variety of other mathematical models; see graphs Fig. \ref{GROWTH2}. The hierarchic structure of social clusters is mathematically modeled with ultrametric spaces having treelike geometry. To simplify mathematics, we consider homogeneous trees with $p$-branches leaving each vertex. Such trees are endowed with algebraic structure, the $p$-adic number fields. We apply theory of the $p$-adic diffusion equation to describe coronavirus' spread in hierarchically clustered population. This equation has applications to statistical physics and microbiology for modeling {\it dynamics on energy landscapes.} To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider {\it linearly increasing barriers.} This structure matches with mild regulations in Sweden. The virus spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This behavior matches with the covid-19 epidemic, with its cluster spreading structure. Our model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. We present socio-medical specialties of the covid-19 epidemic supporting our purely diffusional model.

Abstract: This article aims to better understand the mechanisms that connect climate change perceptions and general willingness to engage in pro-environmental behavior using Spanish cross-sectional data (N = 403). To do this, we first developed and validated the General Willingness for Environmental Behavior Scale (GWEBS), which includes the classical approach of voluntarily doing new actions but also actions implying not doing things (degrowth) and actions forced by social constraints. The exploratory and confirmatory factor analysis showed a good fit for the one-factor structure, which had adequate validity based on their relationship with other variables. Additionally, the GWEBS distinguished between women and men, left- and right-oriented people, and people who belonged to pro-environmental groups and people who did not. In the second place, we tested the parallel mediator role of eco-anxiety and trust in science in the relationship between climate change perceptions and the GWEBS. The results showed that eco-anxiety, fully, and trust in science partially mediated such a relationship, making them crucial to mobilize the intention to act following the perception. This study contributes to our understanding of the psychological mechanisms that eventually drive pro-environmental behaviors and provides a clear direction for future research.

Flowering in cassava is crucial for generation of botanical seed for breeding. However, most farmer preferred genotypes are poor at flowering, exhibit great disparity in time and amount of flowering or never flower. To elucidate the genetic basis of such a flowering behaviour, 293 diverse cassava accessions were evaluated for flowering traits under two locations and seasons in Uganda. Genotyping by the Diversity Array Technology Pty Ltd. (DArTseq) platform identified 24,040 single-nucleotide polymorphisms (SNPs) distributed on the 18 cassava chromosomes. Population structure analysis using principal components (PC) and kinships showed clustering, the first five PCs accounted for 49.2% of the observed genetic variation. Linkage disequilibrium (LD) estimation was averagely 0.32 at a distance of ~2850kb (kilo base pairs). Polymorphism information content (PIC) and minor allele frequency (MAF) were 0.25 and 0.23, respectively. Genome-wide association study (GWAS) analysis uncovered 53 significant marker-trait associations (MTA) with flowering traits involving 27 loci. Two loci, SNPs S5_29309724 and S15_11747301 were associated with all the flowering traits. Using five of the 27 SNPs with Phenotype_Variance_Explained (PVE) ≥ 5%, 37 candidate genes were identified in the peak SNP sites located within 50kb upstream or downstream, most were associated with branching traits. Eight of the genes, orthologous to Arabidopsis and other plant species, had known functional annotations related to flowering, e.g. eukaryotic translation initiation factor and myb family transcription factor. This study identified genomic regions associated with flowering in cassava, the identified SNPs could be useful in marker-assisted selection to overcome hybridization challenges like unsynchronized flowering, and candidate gene validation.

This work focuses on an inland area of North Sardinia (Italy), which is currently subject to depopulation and economic crisis because it is not affected by the summer tourism typical of the region. Despite this, the area shows an interesting architectural and natural heritage, as of today insufficiently known and valued. Therefore, the purpose of this paper is to illustrate the application of the Conjoint Analysis methodology on this case study aimed at supporting processes of valorisation, diversification of the tourist offer and promotion of the through the detection of the preferences of a sample of residents and visitors on a set of 9 cards (itinerary profiles) which also promote the peculiarities of small rural centres. Thus, by valorising the material and immaterial heritage and their intrinsic characteristics, it is shown that inland areas can generate an economy by offering new types of tourism, not just the typically invasive summer and maritime tourism. The research, therefore, seeks to estimate the economic value of the area from a public point of view through the WTP measured by a questionnaire of 600 interviews between inhabitants (300) and tourists (299).

The main objective of this review is to determine the main risks that agricultural workers are exposed to during pesticide application, which may have a harmful effect on their health and on public health. This systematic review was based on the PRISMA guidelines. A search for articles was conducted in the Medline/PubMed, ScienceDirect, and Web of Science databases. Fifteen articles were selected considering their assessment of agricultural workers' knowledge, perceptions, attitudes, practices, and behaviours, identifying the main risks and risk factors for disease associated with the unsafe handling of pesticides. The main risk factors identified were age, education, pesticide safety training, farming experience, and contact with other farmers/intermediaries resulting in pesticide access. The most frequent risk behaviours were: application of pesticides without personal protective equipment (PPE), incorrect disposal of empty packaging and waste, and undervaluation of label information, as well as other unsafe practices. A multidisciplinary and more effective training must be delivered in order to enhance pesticide safe usage. This will empower workers to adopt more conscious and safer behaviours while using pesticides.

Wash’Em is a process that supports humanitarians in assessing and designing rapid but context-specific hygiene programmes in crises or outbreaks. The process consists of training implementers, using tools to learn from populations, and entering findings into a software which generates contextualised activities. A process evaluation of Wash’Em use was conducted in a drought-affected area in Midland province, Zimbabwe. Data was collected during the programme design and following implementation, using a mix of qualitative methods. Findings were classified against the intended stages of Wash’Em, and the evaluation domains were defined by the UKRI Medical Research Council. The Wash’Em process was not fully implemented as intended. An abridged training was utilised, some of the tools for learning from populations were omitted, many of the recommended activities were not implemented, the delivery modalities were different from intended, the budget available was minimal, and the number of people exposed to activities were fewer than hoped. Despite these ‘on the ground’ challenges and adaptations, the Wash’Em process was considered feasible by implementers and was seen to be less top-down than most programme design approaches. The populations exposed to the intervention found the activities engaging, understood the content, and reportedly took action to improve handwashing behaviour.

This research paper examines the evolution of car purchasing behaviour among consumers in India from 2010 to the present. Through extensive literature review and questionnaire survey, it explores the reasons behind the changing preferences and decision-making processes of consumers in the Indian automobile market. The study draws upon various sources, including market research reports, industry publications, academic studies, and consumer surveys, to provide a comprehensive analysis of the factors influencing car purchasing behaviour in India over the last decade. The findings of this research paper can help automakers and marketers better understand consumer preferences and develop effective strategies to cater to the evolving needs of the Indian car market.

The genetic systems of Paspalum species have not been extensively studied. We analysed the ploidy, reproductive mode, mating system, and fertility of four Paspalum species - P. durifolium, P. ionan-thum, P. regnellii, and P. urvillei. An analysis of 378 individuals from 20 populations of north-eastern Argentina was conducted. All populations of the four Paspalum species were pure tetraploid and had a sexual and stable reproductive mode. However, some populations of P. durifolium and P. ionanthum showed low levels of apospory. Populations of P. durifolium and P. ionanthum had low seed sets under self-pollination but were fertile under open pollination, showing that self-incompatibility likely caused self-sterility. In contrast, populations of P. regnellii or P. urvillei showed no evidence of apospory and seed set in both self- and open pollination conditions were high, suggesting that they are self-compatible, due to the absence of pollen-pistil molecular in-compatibility mechanisms. The evolutionary origin of the four Paspalum species could explain these differences. This study supplies valuable insights into the genetic systems of Paspalum species, which could have implications for their conservation and management.

This study analysed through the perspective of networks the association between physical activity (PA), sedentary behaviour (SB), and cardiovascular risk factors in overweight low-income schoolchildren from the perspective of complex systems. Methods: The sample consisted of 41 overweight children between 6 and 10 years old (56% girls). PA and SB were analysed by accelerometer, and the measures of cardiovascular factor risk were: anthropometric and hemodynamic measurements, body fat, lipid profile and glucose, cardiorespiratory fitness (CRF), left ven-tricular mass (LVM), and Sokolov-Lyon. Network analysis with Boot-strap-1000 was performed to analyze the association between PA, SB and the cardiovascular risk factors. Results: Moderate to vigorous PA was positive related with Waist circumference (WC; 0.499), HDL-C (0.307), and CRF (0.276), and negatively associated with BMI (-0.251) and Fat (-0.341). For SB, positive associations were seen with WC (0.326), CRF (0.296), LVM (0.250) and Sokolov (0.215). Adicionalment, the centrality indicators highlighted WC as the most important variable in the network. Conclu-sion: Interventions that aim to mitigate the harmful effects of obesity on cardiovascular risk factors in overweight children should consider WC as an important variable in of system.

The marine red algae Asparagopsis armata is an invasive species which competitive advantage arises from the production and release of large amounts of toxic compounds to the surrounding invaded area, reducing the abundance of native species. The main objective of this study was to evaluate the effects of this invasive seaweed on marine invertebrates by exposing the common prawn Palaemon elegans and the marine snail Gibbula umbilicalis to the exudate of this macroalgae. The seaweed was collected and placed in tanks, for 12 hours, in the dark in a 1:10 ratio. Afterwards the media containing its secondary metabolites was collected for further testing. Lethal and sublethal effects of A. armata were investigated. Biochemical biomarkers responses associated with energy metabolism (lactate dehydrogenase, LDH; electron transport system activity, ETS; content in lipids, proteins and carbohydrates) were analysed. The biomarker responses showed invertebrates’ physiological status impairment after exposure to low concentrations of this algae exudate. Highest concentrations of exudate significantly increased lipid content in both organisms. In the shrimp, protein content, ETS, and LDH were also significantly increased. On the contrary, these parameters were significantly decreased in G. umbilicalis. A behavioural impairment was also observed in G. umbilicalis exposed to A. armata exudate, with reduction in feeding consumption. These results represent an important step in the research of natural toxic exudates released to the environment and prospective effects of this seaweed in invaded communities under increasing global change scenarios.

Obesity is one of the main causes of morbidity and mortality, and food addiction has been considered one of its phenotypes. The study aims to determine the effectiveness of physical activity (PA), exercise, and sedentary behaviour management in attenuating food addiction in obese and overweight healthy adults. A search strategy was undertaken using MEDLINE, CENTRAL, PsycINFO, and CINAHL until April 2019. A total of 295 studies were found from which seven studies, after duplicates were removed, were included. The acute effect of PA of moderate intensity had an effect on attentional bias, craving, and sweet taste perception, although no difference was observed between genders and body mass index groups. No effect was observed on the hedonic and reward value. The acute effects of PA of moderate intensity may be a useful tool to control the levels of food addiction. More research is needed to clarify if this effect also occurs during chronic application, at different doses and types of PA, and for all populations.

The reinforcement of concrete by using polyolefin fibres may be considered in structural design to meet the requirements of the applicable code rules. In order to achieve a reliable use of such a composite material, use of full-scale real structures is needed. The conversion of lab testing data into real practice properties is challenging and significantly influenced by various aspects, among which the size effect is a key one. Given that the available literature does not report coinciding conclusions about such an effect on quasi-brittle materials reinforced with fibres, further research is justified. Therefore, this work studies the behaviour of notched beams with three proportional sizes by using self-compacting polyolefin reinforced concrete with a fibre volume fraction of 1.1%. Flexural testing was carried out according to the standard EN-14651, with the results revealing the existence of the size effect. In addition, a reduction of the residual strength identified in the larger specimens was observed in fracture surfaces with equal fibre content.

Recent research has revealed surprisingly important connections between animals’ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hosts’ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research venues focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish model candidates and their key potential for advancing research fields linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish, sticklebacks, guppies and cleaner-client dyads, will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades.

OBJETIVE: This study analyses the views of four groups of healthcare professionals who may play a role in the management of suicidal behaviour. The goal was to identify key factors for suicide prevention in different areas of the healthcare system. METHODOLOGY: Qualitative research was conducted using focus groups made up of different healthcare professionals who participated in the identification, management and prevention of suicidal behaviour. Professionals included were primary care physicians, psychologists, psychiatrists and emergency physicians. RESULTS: ‘Suicide’ was amongst the most relevant terms that came up in discussions most of the times it appeared associated with words such as ‘risk’, ‘danger’ or ‘harm’. In the analysis by categories, the four groups of professionals agreed that interventions in at-risk behaviours are first in importance. Prevention was the second main concern with greater significance among psychiatrists. DISCUSSION: Primary care professionals claim for more time to address patients at risk for suicide and an easier access to and communication with the mental health network. Emergency care professionals have a lack of awareness of their role in the detection of risk for suicide in patients who seek attention at emergency care facilities for reasons of general somatic issues. Mental health care professionals are in high demand in case of self-harm but they would like to receive specific training in dealing with g suicidal behaviour.

Since autism was first recognised, prevalence has increased rapidly. The growing economic as well as social cost to society can only be mitigated by effective interventions and supports. It is therefore not surprising that most governments have developed public policy documents to address the management of autism. Over the past 40-50 years, meaningful evidence has accrued showing that interventions based on the scientific discipline of Applied Behaviour Analysis (ABA) can help people with autism reach their potential. In view of this, nearly all of North America has laws to mandate that ABA-based interventions are available through the health care systems. In contrast, across Europe there are no such laws. In fact, the National Institute for Health and Care Excellence (NICE), the body guiding health and social policy in the UK, concluded that it could not find any evidence to support ABA, and therefore could not recommend it. This paper addresses the reasons for these diametrically opposed perspectives. In particular, it examines what happens when health and social care policy is misinformed about effective autism intervention.

The effect of aqueous extracts of the biomass of the adult Ulomoides dermestoides beetle on the delayed effects of the defoliant paraquat causing parkinsonism in experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrains of experimental and control mice was studied by immunohistochemistry. In the model in vitro system with SH-SY5Y human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and presence of the neurotoxin MPP⁺. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used in this study.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

Exposure to particulate matter (PM) causes considerable breathing-related health risks. We assessed the inhibitory effect of Siraitia grosvenorii extract (SGE) on airway inflammation in mice exposed to a fine dust mixture of PM10 (PM diameter &lt; 10 mm) and diesel exhaust particles (DEPs) known as PM10D. SGE attenuated neutrophil infiltration and the number of immune B and T cells in lung tissue and bronchoalveolar lavage fluid (BALF) of PM10D-exposed mice. SGE reduced the secretion of cytokines and chemokines, including interleukin (IL)-1a, tumor necrosis factor (TNF)- a, IL-17, chemokine (C-X-C motif) ligand (CXCL)-1, and macrophage inflammatory protein (MIP)-2 in BALF. Airway inflammation, accumulation of inflammatory cells, and collagen fibrosis in the lung after PM10D exposure were investigated by histopathological analysis, and SGE treatment ameliorated these symptoms. SGE decreased the mRNA expression of mucin 5AC (MUC5AC), CXCL-1, TNF-a, MIP-2, and transient receptor potential vanilloid and ankyrin 1 ion channels in the lung tissues of mice. Furthermore, SGE ameliorated mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling activated by PM10D in mice. We conclude that SGE attenuated PM10D-induced neutrophilic airway inflammation via inhibiting MAPK/NF-κB activation. These results show that SGE may be a candidate for the treatment of inflammatory respiratory diseases.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

(1) The present study investigated the effect of orally administered Limosilactobacillus fermentum HY7302 (HY7302) on the relationship between ocular tissue and the microbiome in the corneal injured dry eye mice model. (2) 0.1% benzalkonium chloride (BAC) was applied to the ocular surface for 14 days to induce corneal injury in male Balb/c mice. During the BAC treatment period, HY7302 (1 × 108 CFU/kg/day or 1 × 109 CFU/kg/day) or omega-3 positive control (200 mg/kg/day) were administered orally (n = 8/group). To examine signaling pathways affected by HY7302 treatment, the in vitro effects of HY7302 on tight junctions and the inflammatory response were investigated in a mouse colon epithelial cell line, CMT-93. (3) BAC exposure decreased tear production, induced ocular inflammation and corneal epithelial detachment, and altered gut microbiota. However, oral administration of HY7302 restored tear secretion and decreased corneal epithelial detachment in BAC-treated corneal injury mice. Further, HY7302 alleviated corneal inflammation via modulation of matrix metalloproteinase-9 (MMP-9) expression and alterations in gut microbiota composition. (4) These findings suggest that the gut–eye axis interaction between gut microbiota and eye tissue affects disease severity in corneal injury, and that alteration of the microbiota by HY7302 could improve eye health by regulating the inflammatory response.

Cannabidiol is a well-known non-psychotropic phytocannabinoid from Cannabis sativa, which exerts a broad range of neuropharmacological activities in the central nervous systems. Over the past years, compelling evidence from preclinical and clinical studies support therapeutic potentials of cannabidiol in various neurological disorders, including neurodegenerative diseases. Neurodegenerative diseases are characterized by the accumulation of misfolded or aggregated protein due to the defective protein homeostasis or proteostasis network, termed as proteinopathies. Because of its role in the protein homeostasis network, cannabidiol could be a potent molecule to revert not only age-associated neurodegeneration but also other protein misfolding disorders. In this review, we discuss the potentiality of cannabidiol as a pharmacological modulator of the proteostasis network, highlighting its neuroprotective and aggregates clearing system inducing potentials in the neurodegenerative diseases.

This research investigates the fatigue behaviour and fracture mechanics of high-performance concrete (HPC), including various compositions such as HPC with basalt aggregates (HPC-B), HPC with gravel (HPC-G), and high-strength coarse mortar (CM) static and cyclic tensile loading within the special priority program SPP 2020. The study aims to integrate fracture mechanics into structural analysis to enhance design guidelines for slender cross-sections and safety-related high-performance structural components. The experimental investigations reveal HPC-B's re-markable superiority, displaying higher compressive strength, modulus of elasticity, and tensile strength compared to HPC-G and CM. A modified disk-shaped compact tension (MDCT) based on ASTM standards, aided by digital image correlation (DIC) unveils fracture behaviour, empha-sizing fracture energy as a crucial parameter. HPC-B exhibits improved crack resistance and notch sensitivity reduction attributed to crushed basalt aggregates and enhanced interfacial transition zone (ITZ). The research scrutinizes factors like material characterization, aggregate morphology, stress levels, and displacement rate on crack formation. High-cycle fatigue tests show HPC-B's superior performance, and post-fatigue analysis reveals enhanced residual fracture toughness attributed to nano-level structural changes, stress redistribution and aggregate-matrix interac-tion. 3D image analysis via Computed Tomography (CT) scans captures mesostructural crack propagation and provide quantitative insights. This study advances the understanding of HPC fatigue behaviour, emphasizing the interplay of aggregate types, morphologies, and their dy-namic response to cyclic loading, offering valuable insights for optimizing design guidelines and fostering innovation in structural engineering.

Large-scale crowd phenomena are complex to model because the behaviour of pedestrians needs to be described at both strategic, tactical, and operational levels and is impacted by the density of the crowd. Microscopic models manage to mimic the dynamics at low densities, whereas mesoscopic models achieve better performances in dense situations. This paper proposes and evaluates a novel agent-based architecture to enable agents to dynamically change their operational model based on local density. The ability to combine microscopic and mesoscopic models for multi-scale simulation is studied through a use case of pedestrians at the Festival of Lights, Lyon, France. Pedestrian outflow data is extracted from video recordings of exiting crowds at the festival. The hybrid model is calibrated and validated using a genetic algorithm that optimizes the match between simulated and observed outflow data. Additionally, a local sensitivity analysis is then conducted to identify the most sensitive parameters in the model. Finally, the performance of the hybrid model is compared to different models in terms of density map and computation time. The results demonstrate that the hybrid model has the capacity to effectively simulate pedestrians across varied density scenarios while optimizing computational performance compared to other models.

Context and aim: Environmental awareness is the first step to climate change risk perceptions and environmental behaviour. However, this pathway is not always possible within different population segments and trust contexts. This study explores the conditional effect of trust on environmental behaviour in the Zed Generation in Albania. The consideration of the Zed generation due to two opposing traits, such as social courage and anti-social, make them an interesting topic to understand, especially for their importance in online communities. Method: The youth engagement environmental programme and the climate change risk perceptions framework are adopted in an input-output design. Environmental awareness (input) is the initiating factor, and climate change risk perception and community engagement as mediators of environmental behaviour(output). Individual and institutional trust is the moderating factor that inhibits/enhances engagement and environmental behaviour. Results: The moderation-mediation show that climate change risk perceptions did not mediate environmental behaviour. Environmental awareness directly affects it. However, low institutional trust inhibits the general trust that, in turn, lowers the impact of awareness in climate change perceptions and community engagement toward environmental protection. Practical recommendation: The application of the input-output model shows that the pathway that directly affects environmental behaviour among Zed Generation in Albania is not Climate change risk perception. In low-trust contexts, positive environmental behaviour can be generated through community engagement. Policymakers and educational programmes in low-middle-income countries might consider community engagement to mitigate trust issues and effectively deal with environmental problems with a global segment such as the Zed generation.

Animal welfare assessment protocols are important for identifying welfare problems in conservation programs. This study aimed to develop a baseline welfare protocol for the assessment of welfare in huemul (Hippocamelus bisulcus) in conservation centers. This protocol is based on the Welfare Quality® (WQ) framework for cattle, considering the available literature on the behaviours, ecology, conservation plans, captive management of this species, and welfare assessment protocols for other ungulate species. As a result, the protocol was specifically developed for huemuls and included four principles, 12 criteria, and 23 animal- and resource-based indicators. The 12 criteria of the WQ protocol were reduced to nine, and three new criteria were added because they were both feasible and essential for welfare assessment in captive huemuls. This protocol is mainly intended to identify welfare problems in endangered species in the context of conservation centers (reproduction, rescue, rehabilitation, or treatment centers). Thus, aggregation of different measures to obtain a global score has not been proposed. However, a scoring system that assigns a value on a 0-2 scale (0= No welfare concern; 1= welfare concern; 2= urgent welfare concern) is proposed for each category. Although further research is still needed to fully validate the protocol, this is the first development of a completed protocol for huemul welfare assessment.

The chondrichthyan lineage diverged from the osteichthyan line around 440 million years ago, resulting in a vast evolutionary gulf between modern elasmobranchs and other vertebrates. Though this has supported the assumption that sharks are ancient, dangerous, and binary-minded, intelligent actions including social interactions have been noted in the field, while laboratory studies have confirmed a variety of cognitive capacities. Yet, due to fear of sharks and the difficulties of observing them in their aquatic environments, few ethological studies have been done, so their natural behaviour remains little known. On noting that Carcharhinus melanopterus displayed complex actions during incidental meetings, a long-term ethological study of the species was carried out on the north shore of Mo’orea Island, French Polynesia. During the 6.5 years of the study, new behaviours continued to present. The 35 context-specific actions identified as comprising the behavioural repertoire of C. melanopterus are described.

High-resolution GPS/GSM dataloggers provide spatial information of the highest quality, which outperform previous tracking methods, such as Argos telemetry or conventional VHF ground-tracking. As a result, this has improved our knowledge of home-range behavior and spatial ecology of many species, including large raptors. In this paper, we use high-resolution GPS/GSM dataloggers to assess the home-range size and the role of sex, season (breeding or non-breeding season), and breeding status (reproductive or non-reproductive individuals) on the space use of Bonelli’s eagle (Aquila fasciata). To this end, 51 territorial individuals (25 females and 26 males) were equipped with GPS/GSM transmitters and were tracked over 7 years (2015–2021) in eastern Spain. Overall, we recorded 4,791,080 fixes that were analyzed through kernel density methods (50%, 75%, and 95% fixed kernels). The average individual home-range size according to the 95%, 75%, and 50% kernels was 54.84 ± 20.78 km², 24.30 ± 10.18 km², and 11.17 ± 4.90 km², respectively. Overall, the home-range size of individuals occupying the same territory was similar, mainly due to the cooperative hunting behavior exhibited by the species. We did not find interannual differences in the home-range size (95% fixed kernel) of the majority of individuals, showing a strong territorial fidelity of the breeding pairs. In general, females’ home-range size was slightly smaller than males’ size due to the decrease in activity in the breeding season as a result of laying, incubation, and chick attendance at nests. No seasonal variation in the 95% kernel was found, but it was found in the 75% and 50% kernels. In regard to the breeding status, higher home-range size was recorded in the non-reproductive individuals. Moreover, we found a low neighbor overlap among the territories (4.18% ± 3.06%), which evidences a high level of intraspecific competition in the Bonelli’s eagle. Finally, this study highlights the advantages of the use of accurate telemetry information to improve our understanding of the spatial ecology of the endangered Bonelli’s eagle, which ultimately will serve to better inform management actions for its conservation.

Previous studies implied the different behavioral intention formation of a specific object for individuals in different age groups, but few research to Chinese consumers’ sustainable fast fashion behaviour were found considering the enormous amount of consumption and waste of fast fashion products in China. Meanwhile, as a fast developing country, it might be insufficient to conduct research ignoring the consequences of different education level and growing environment among different generations. Thus, to generate in-depth and heuristic Chinese consumers information, this study developed proposed theoretical framework (TORA) based on research by Fishbein and Ajzen (1975), while the validity among Chinese consumers was tested as well. Following the TORA model, this study aims to investigate if consumers’ age will moderate the relationship between attitude and intention, and the relationship between subjective norms to behavioral intention. Through structural equation modelling in AMOS, it was found that the model has a well fit to large sample of Chinese consumers, while the moderation effect of age was not significant in the whole sample. Further hierarchical regression analysis conducted in SPSS and Process was able to locate the moderation effect of if divide the consumers into groups by age. Which is, age is significantly and positively moderating the path subjective norms to intention in younger generation (18-25), but significantly positive moderating attitude to intention in consumers aged 26-39. Implications in marketing and to policy makers are discussed at the end of this research.

Introduction: Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficit and anxiety-like behavior. In this study, minocycline was compared to memantine, the NMDA receptor antagonist, for its effects on LPS-induced locomotor deficit and anxiety-like behavior in rats. Methodology: Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to LPS (5 mg/kg, i.p.) injection. The locomotor activity and anxiety-like behavior were assessed using the open field test (OFT). The phosphorylated tau protein level was measured using ELISA while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and western blot, respectively. Results: In the mPFC, minocycline treatment reduced the locomotor deficit and anxiety-like behavior, reduced phosphorylated tau protein level, and upregulated BDNF/CREB protein expression comparable to memantine, with the higher dose of minocycline having better benefits. Conclusion: Minocycline treatment attenuated LPS-induced locomotor deficit and anxiety-like behavior in rats, possibly via a decrease in phosphorylated tau protein levels and an increase in the expression of the BDNF/CREB proteins.

Breaking up prolonged sitting by short bouts of light physical activities including standing and walking has been shown to be beneficial for people with type 2 diabetes (T2D). This paper presents the development of an android mobile app to deliver a just-in-time adaptive intervention (JITAI) to reduce sedentary time in people with T2D. A total of six design workshops were conducted with seven experts to identify design requirements, a behavioural framework, and required contextual adaptations for the development of a bespoke mobile app (iMOVE). Moreover, a focus group was conducted among people with T2D as potential end-users (N=10) to ascertain their perceptions of the app. Feedback from the focus group was used in subsequent iterations of the iMOVE app. Data were analysed using an inductive qualitative thematic analysis. Based on workshops, key features of iMOVE were developed, including simplicity (e.g., navigation, login), colours and font sizes, push notifications, messaging algorithms and a triggering system for breaking up sitting time and moving more. Based on the user testing results, a goal setting tab was added, font sizes were made larger, the brightness of colours was reduced, and a colour indicator was used to indicate device connectivity with an activity tracker. A user-centric app was developed to support people with T2D to transition from sedentary to active lifestyles.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

Children with Fetal Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD) experience significantly higher rates of sleep disturbances than their typically developing peers. Pre-sleep anxiety and waking emotional content is known to affect the content and frequency of nightmares, which can be distressing to children and caregivers. This is the first study to analyse nightmare frequency and content in FASD, and to assess its association with psychometric outcomes. We assessed reports from 277 caregivers of children with ASD (n=61), FASD (n=112), and TD children (n=104) using the Children’s Sleep Habits Questionnaire (CSHQ), the Child Behavior Checklist (CBCL), the Spence Children’s Anxiety Scale (SCAS) and the Behavior Rating Inventory for Executive Functioning (BRIEF). Within the ASD group, 40.3% of caregivers reported their children had nightmares. Within the FASD group, 73.62% of caregivers reported their children had nightmares and within the TD group, 21.36% of caregivers reported their children had nightmares. Correlation analysis revealed significant associations between anxiety and nightmares, maladaptive behaviour and nightmares, and executive functioning and nightmares in the TD and FASD groups, but not ASD group. This paper adds to the emerging body of work supporting the need for sleep interventions as part of clinical practice with regard to children with ASD and FASD. As a relatively niche but important area of study this warrants much needed further research.

Climate change is one of the biggest challenges of our times. Its impact on human populations is not yet completely understood. Many studies have focused on single aspects with contradictory observations. However, climate change is a complex phoenomenon that cannot be adequately addressed from a single discipline's perspective. Hence, we propose a comprehensive conceptual framework on the relationships between climate change and human responses. This framework includes biological, psychological and behavioural aspects, and provides a multidisciplinary overview and critical information for focused interventions. The role of tipping points and regime shifts is explored, and a historical perspective is presented to describe the relationship between climate evolution and socio-cultural crisis. Vulnerability, resilience and adaptation are analyzed from an individual and a community point of view. Finally, emergent behaviours and mass effect phenomena are examined that account for mental maladjustment and conflicts.

.Most of the accident cases at work are caused by unsafe behaviour. Scholars have thus extensively researched factors of safe behavior.Safety leadership is stated as the most effective factor in safety behaviour. Besides, safety knowledge and safety attitudes are also found to influence safety behaviour. The purpose of this paper is to investigate the nature of the relationship between safety leadership, safety knowledge, safety attitude, and safety behavior, which has been found to be limited or rare in previous research.A self-administered questionnaire was applied and was distributed randomly to 140 SME manufacturing workers and they were analysed using the structural equation modelling partial least squares (PLS-SEM). The results prove that safety leadership has a significant effect on safety knowledge, safety attitude, and safety behaviour, with safety knowledge and safety attitude mediating the safety leadership-safety behaviour relationship. Consequently, the results provide a more in-depth view of the relationship between safety leadership and safety knowledge-attitude-behaviour via adapting social-cognitive theory and social learning theory in solving safety issues in SME. This study also provides a starting point for researchers to better understand how effective safety leadership is provided by supervisors in terms of improving worker safety and safety knowledge-attitude-behaviour.

The functioning of the parents’ emotional sphere is very important to a child’s mental and physical health. This study focused on investigating the association between mothers’ emotional intelligence (EI) and paediatric type I diabetes (T1DM) disease management in their children. We hypothesized that mothers’ EI is associated with T1DM outcomes. Mothers of children with T1DM aged 6-12 years were surveyed. One hundred and thirty-four mothers, the main caregivers of their diabetic children, provided measures of EI and completed a demographic questionnaire. The primary indicator of diabetes management was haemoglobin A1c (HbA1c; the main form of glycosylated haemoglobin). EI scales and subscales were associated with glycaemic management indices. Logistic regression analysis was applied for the assessment of the association between parents’ EI and their paediatric with T1DM disease management. The analysis demonstrated a statistically significant correlation between T1DM management and mothers’ ability to understand and control own emotions, to transform their own negative emotions into positive and to control own negative emotions. Mothers’ EI scales and subscales of understanding and regulating their own emotions, subscales of transforming their own negative emotions into positive ones and controlling their own negative emotions were statistically reliable predictors of glycaemic control in children with T1DM.

A characteristic feature of lightweight constructions is their low thermal mass which causes high internal temperature fluctuations that require high heating and cooling demand throughout the year. Phase Change Materials (PCMs) is effective in providing thermal inertia to low thermal mass buildings. The aim of this paper is to analyse the thermal behaviour of two proposed lightweight buildings designed for homeless people and to investigate the potential benefit achievable through the use of different types of PCM in the temperate climatic conditions of Christchurch, New Zealand. For this purpose, over 300 numerical simulations have been conducted using the simulation software DesignBuilder®. The bulk of the simulations were carried out under the assumption that the whole opaque building envelope is equipped with PCM. The results showed significant energy saving and comfort enhancement through the application of PCMs. Thereby, annual energy saving of over 50 % was reached for some of the PCMs considered. Additionally, the effectiveness of single, PCM-equipped structure components was investigated and substantial benefits between 19 and 27 % annual energy saving were achieved. However, occupant behaviour in terms of ventilation habits, occupancy of zones etc. remains one of the biggest challenges in any simulation work due to insufficient data.

Analgesic products for piglet castration are critically needed. This requires extensive animal experimentation such as to meet regulatory-required proof of efficacy. At present, there are no validated methods of assessing pain in neonatal piglets. This poses challenges for investigators to optimize trial design and to meet ethical obligations to minimize the number of animals needed. Pain in neonatal piglets may be subtle, transient and / or variably expressed and, in the absence of validated methods, investigators must rely on using a range of biochemical, physiological and behavioural variables, many of which appear to have very low (or unknown) sensitivity or specificity for documenting pain, or pain-relieving effects. A previous systematic review of this subject was hampered by the high degree of variability in the literature base both in terms of methods used to assess pain and pain mitigation, as well as in outcomes reported. In this setting we provide a narrative review, to assist in determining the optimal methods currently available to detect piglet pain during castration and methods to mitigate castration-induced pain. In overview, the optimal outcome variables identified are nociceptive motor and vocal response scores during castration, and quantitative sensory-threshold response testing and pain-associated behaviour scores following castration.

Purpose: To explore the influence of education and other factors on an athlete’s decision to return to sport post-concussion injury, and whether general risk-taking tendencies are related to return to sport post-concussion decisions in these athletes. Participants and Methods: A self-administered electronic survey was designed to examine their decision-making process when faced with scenario-based questions regarding returning to sport post-concussion injury. Students from the Health Sciences and Medicine Faculty at Bond University were invited to participate. Participants were allocated to a concussion education or non-education group prior to commencement of questionnaire via the random generator on Qualtrics software function. The risk propensity scale was used to assess the risk aversion of each participant. Results: Sixteen respondents were randomized evenly to education and non-education groups. Seven (43.8%) had previously received concussion education training prior to completing the questionnaire, with one (14%) choosing to return to sport in the scenario-based questions. The education group reported two (25%) respondents return to sport, while three (75%) respondents out of four returned to sport with no education or previous concussion training. Influential factors that impacted the decision whether to return to sport or not included: game importance, concussion severity and symptoms, and various internal and external factors. Finally, there was a divergence in results from the risk propensity scale when deciding to return to sport and general risk-taking propensities. Conclusion: This study identified several influential factors including game importance, concussion severity and symptoms which play a significant role in the return to sport decisions post-concussion injury.

Integrated information theory (IIT) was initially proposed to describe human consciousness in terms of intrinsic-causal brain network structures. This theory could potentially be used for conceptualising complex living systems. In a previous study, we analysed collective behaviour in {\it Plecoglossus altivelis}. We found that IIT 3.0 exhibits qualitative discontinuity between three and four schools of fish in terms of $\Phi$ values (i.e., group integrity). Other measures, such as mutual information, did not show such characteristics. In this study, we follow up on our previous findings and introduce two new factors. First, we define the global parameter settings to determine a different kind of group integrity. Second, we set several timescales (from $\Delta t =5/120$ s to $\Delta t =120/120$ s). The results showed that we succeeded in classifying fish school according to their group size in terms of the degree of group integrity, despite the small group size. The concrete classification includes the followership for a two-fish school, fission--fusion for a three-fish school, emergence of leadership for a four-fish school, and emergence of Boid-like behaviour for a five-fish school. These minute classifications have never been revealed before. Finally, we discuss one of the longstanding paradoxes in collective behaviour, known as the heap paradox, for which two tentative answers could be provided through our IIT analysis.

Dispersal represents a key life-history trait with several implications for the fitness of organisms, population dynamics and resilience, local adaptation, meta-population dynamics, range shifting and biological invasions. Plastic and evolutionary changes of dispersal traits have been intensively studied over the past decades in entomology, in particular in wing-dimorphic insects for which literature reviews are available. Importantly, dispersal polymorphism also exists in wing-monomorphic and wingless insects, and except for butterflies, fewer syntheses are available. In this perspective, by integrating the very last research in the fast moving field of insect dispersal ecology, this review article provides an overview of our current knowledge of dispersal polymorphism in insects. After having provided a definition of the main terms characterising insects’ movements, some of the most often used experimental methodologies for the separation of dispersers and residents in wing-monomorphic and wingless insects are presented. The existing knowledge on the morphological and life-history trait differences between resident and disperser phenotypes is then synthetized. The fourth part examines the effects of range expansion on dispersal traits and performance, in particular for insects from range edges and invasion fronts. Finally, some research perspectives are proposed in the last part of the review.

The aim of this study was to identify gender differences in technical-tactical behaviour in football. To this end 68 matches of the first division of the Spanish men’s and women´s league, corresponding to 2016/17 season were analyzed. A comparison of medians was carried out using the Mann-Whitney U-test were conducted as post hoc test and a grouping of the variables through the clustering bootstrapping technique in both groups. We have detected statistically significant differences regarding all accurate passes, in favour of men, as well as a greater number of yellow cards. In female football, a greater number of picking up free balls, interceptions, lost balls, recoveries, challenges and attacks, both positional and counterattacks, are produced. The clustering analysis also allowed that in male football, the circumstance of receiving a red card is closely related to the number of goals conceded and most of the shots on goal are achieved by positional attacks. In women's football, ball possession on own half is closely related to the number of losses. These results could be useful for gender-specific training information for optimal preparation. However, more research is warranted to establish the main gender differences and characterize women's football.

Integrated information theory (IIT) was initially proposed to describe human consciousness in terms of intrinsic, causal brain-network structures. This theory has the potential to be useful for conceptualising complex living systems. In a previous study, we analysed collective behaviour in Plecoglossus altivelis and found that IIT 3.0 exhibits qualitative discontinuity between three and four fish. Other measures like mutual information did not have such characteristics. In this study, we followed up on our previous findings and examined timescale effects on integrated information of collective behaviour. We found that a long timescale (1 s) causes Boid-like local interactions to dominate over interactions with the whole, but only when the group size is five at a given time scale (i.e. around 0.2 s). Interestingly, the most suitable time scale is roughly equal to fish reaction time. We used these data to propose a new classification for fish schools, with each size group being a unique and autonomous system, despite small group sizes.

This article addresses the role the Word-Acaid Philosophy plays in directing or guiding human behaviour in all situations and circumstances. It discusses the origin of the philosophy when I asked myself the following question: “Why do I do what I do when I do what I do?” This question led me to carefully self-examine to discover the reason for my behaviours. Once the philosophy was crafted, I observed that all other human beings seem to go through the same process. The philosophy did not originate as a formal study. However, in this article I did a systematic study on the concepts to verify the initial propositions. In order to achieve my goal a formal study was done using a descriptive approach to explicate the modus operandi of the philosophy with a view of understanding its nature and the role each of the essential elements plays. A conceptual analysis method was used focusing on the definition of key concepts. It was conclusively found that each concept played a significant role in driving human behaviour in every situation. The findings’ implications are very significant to trainers, coaches, educators and all whose goal is to affect human beings towards particular exit outcomes. The findings made it very simple also for me to deductively conclude that the philosophy is a system and is valid.

Polyolefin fibre reinforced concrete (PFRC) has become an attractive alternative to steel for the reinforcement of concrete elements mainly due to its chemical stability and the residual strengths that can be reached with lower weights. The use of polyolefin fibres can meet the requirements in the standards, although the main constitutive relations are based on the experience with steel fibres. Therefore, the structural contributions of the fibres should be assessed by inverse analysis. In this study, the fibre dosage has been fixed at 6kg/m³ and both self-compacting concrete and conventional concrete have been used to compare the influence of the positioning of the fibres. An idealized homogeneous distribution of the fibres with such fibres crossing from side to side of the specimen has been added to self-compacting concrete. The experimental results of three-point bending tests on notched specimens have been reproduced by using the cohesive crack approach. Hence, the constitutive relations were found. The significance of this research relies on the verification of the formulations found to build the constitutive relations. Moreover, with these results it is possible to establish the higher threshold of the performance of PFRC and the difficulties of limiting the first unloading branch typical of fracture tests of PFRC.

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.

AI is often looked at as a logical rational way to develop a games agent that methodically looks at options and delivers rational solutions. This paper is based on developing an AI agent that plays a game with a similar emotive content like a human. The purpose of the study was to see if the incorporation of this emotive content would influence the outcomes within the game Love Letter. In order to do this an AI agent with an emotive layer was developed to paly the game over a million times. A lower win/loss ratio demonstrates that to some extent this methodology was vindicated and a 100 per cent win for the AI agent did not happen. Machine learning techniques were modelled purposely so as to match extreme models of behavioural change. The results demonstrated a win/loss ration of 0.67 for the AI agent and in many ways reflectd the frustration that a normal player would exhibit during game play. As was hypothesised the final agent investment value was, on average, lower after matchplay than its initial value.

Non-alcoholic steatohepatitis (NASH) is a complex disease resulting from chronic liver injury associated with obesity, type 2 diabetes, and inflammation. Recently, multi-target drugs have been proposed to treat complex diseases including NASH; however, their manufacturing pro-cesses remain time- and cost-intensive and inefficient. Therefore, to overcome these limitations, we developed UniStac, a novel enzyme-mediated conjugation platform for multi-specific drug development. UniStac demonstrated high conjugation yields, optimal thermal stabilities, and robust biological activities. Through such platform, we designed a tetra-specific compound, C-192, targeting Glucagon-like peptide 1 (GLP-1), Glucagon (GCG), Fibroblast growth factor 21 (FGF21), and Interleukin-1 receptor antagonist (IL-1RA) simultaneously for the treatment of NASH. The biological activity and treatment efficacy of C-192 were confirmed both in vitro and in vivo using a methionine–choline-deficient (MCD) diet-induced mouse model. C-192 exhibited profound therapeutic efficacies compared to conventional drugs, including liraglutide and dulaglutide. C-192 significantly improved alanine transaminase levels, triglyceride accumula-tion, and the non-alcoholic fatty liver disease activity score. Our results collectively provide clin-ical feasibility of UniStac for developing multi-specific drugs, and C-192 as an innovative thera-peutic opportunity for severe NASH, as it exerts synergistic effects across multiple targets.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

We previously proposed a public intervention framework concept that would allow people to resume personal and economic activities. We showed that intervention measures are used in a quantitative scale to reduce transmission probabilities and disease severity. In this article, we systematically examine the origin, assumptions, performance and limitations of epidemiological models from different views used in past review. We found that nearly all model assumptions fail to hold or are remote from reality; R0 does not exit or has no utility in guiding treatment options; personalized intervention measures are vitally important to COVID-19 due to its transmission characteristic; and current epidemiological models are unable to accurately assess the true benefits of personalized intervention measures. We suggest that poor performance of the models are attributed to flawed assumption that health/disease properties can be treated as transferable properties. The flaw creates a fiction that disease properties such as infection probabilities and death risks can be transferred from any vulnerable persons to anyone in the population and thus severely limit societal ability to fight the pandemic. We finally show that the benefits of personalized mitigation measures could be determined directly by using variable Ri values for infected persons (or nodes) together assessment of death rate and disability rate; the attempt of avoiding the disease by defeating all potential transmission probabilities is unrealistic; but mitigating disease severity for specific persons is more feasible and reliable. A most reliable strategy for reviving economy is using personalized protective measures and improving person health before effective vaccine is available.

Alfalfa (Medicago sativa L.) is one of the most important forage crops in the world. In Bolivia it is cultivated in different parts of the High Andes and in the Interandean Valleys. The species is affected by several fungal diseases which reduce production, but before 2016 hardly any mention had been made of virus disease in the region. The aims of the present work were: 1) to describe the symptomology of this apparent viral disease, and ii) determine its effects on the yield of different alfalfa cultivars available from the CIF-UMSS. In 2016, a plot was established at Tiquipaya (Dept. of Cochabamba) (altitude 2480 m) was planted with 12 alfalfa cultivars. Disease incidence values were estimated and the area under the disease progress curves (AUDPC) calculated. The disease progress curves themselves were analyzed using logit functions for polycyclic diseases, and yields were determined. Disease symptoms included deformation of the folioles, thickened veins, the presence of vein enations and papillae on the abaxial leaves, reduced plant size - all symptoms of infection apparently caused by Alfalfa Dwarf Virus. The different cultivars returned different incidence values. They also returned different apparent infection rates ranging from 0.072/day for Cóndor, to 0.113/day for Tamborada. The different cultivars returned different dry weight yields, with yields inversely related to the AUDPC. In conclusion, based on the foliar symptoms registered, the viral disease is associated with the Alfalfa Dwarf Virus. The twelve cultivars evaluated presented different incidence levels of the viral disease.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

Crohn's disease (CD) results from an aberrant immune response against the commensal microbiota in genetically susceptible hosts. However, the nature of the immune defects, the microflora involved and the genetic susceptibility remain incompletely defined and controversial. Extraintestinal manifestations occur in up to 25-35% of patients and generally precede the onset of gastrointestinal symptoms, which are often of a colonic nature and are influenced by disease activity. Renal manifestations can be considered dependent on the same immune mechanism that determines inflammatory bowel disease in CD. This review seeks to describe the current state of association between CD and kidney disease.

Crohn's disease (CD) results from an aberrant immune response against commensal microbiota in genetically susceptible hosts. However, the nature of immune defects, the microflora involved, and genetic susceptibility remain incompletely defined and controversial. This review seeks to describe the present state of association between CD and renal disease; moreover, we highlight the convergence of CD with amyloidosis that can trigger sustained inflammation, producing the pathological alteration observed in both diseases. The following MESH terms were searched in PubMed, PubMed Central (PMC), and Web of Science: “Crohn´s disease” and “renal disease.” The R RISmed package was used for PubMed and PMC. The abnormal humoral immune response is described along with alterations in immune cell migration mechanisms in CD during inflammation.

Introduction: Crohn's disease (CD) is a chronic inflammatory granulomatous disease that can affect the entire gastrointestinal tract. It is characterized by various extraintestinal manifestations (EIM), of which oral manifestations (OM) are often possible. One of the possible OM is periodontal disease (PD) a chronic inflammatory condition of the supporting tissues of the teeth. This study aimed to show the existence of a mutual relationship between the clinical activity of PD and the clinical and endoscopic activity of CD. Materials and methods: Using one clinical and two endoscopic indexes for the assessment of CD activity and clinical attachment loss (CAL), bleeding on probing (BOP), pocket probing depth (PPD) and radiographic bone loss (RDL) on dental panoramic tomogram to assess PD in CD patients. Results: A total of 38 patients underwent the entire study process, of which 20 patients with CD and 18 patients with CD and PD. Considering all CD activity scores, there were 26 patients with active disease, and half of them had PD, and 85.7% of operated patients had active CD. Values of CAL, PPD, BOP and RBL were higher in active CD than remission, except BOP when compared to CDAI score which was higher in remission of CD. Discussion and conclusion: The results of this study indicate that there is a connection between the activity of CD and the worse condition of the supporting tissues of the gums in the oral cavity which is important to keep in mind the necessity of referring patients with CD to a dentist for timely and adequate therapeutic measures.

Weeds that infest crops are a primary factor limiting agricultural productivity world-wide. Weedy rice, also called red rice, has experienced independent evolutionary events through gene flow from wild rice relatives and de-domestication from cultivated rice. Each evolutionary event supplied/equipped weedy rice with competitive abilities that allowed it to thrive with cultivated rice and severely reduce yields in rice fields. Under-standing how competitiveness evolves is important not only for noxious agricultural weed management but also for the transfer of weedy rice traits to cultivated rice. Molec-ular studies of weedy rice using simple sequence repeat (SSR), restriction fragment length polymorphism (RFLP) and whole genome sequence have shown great genetic variations in weedy rice population globally. These variations are evident both at whole genome and at single allele level, including Sh4 (shattering), Hd1 (heading and flower-ing), and Rc (pericarp pigmentation). The goal of this review is to describe the genetic diversity of current weedy rice germplasm and the significance of weedy rice germplasm as a novel source of disease resistance. Understanding these variations, es-pecially at an allelic level, is also crucial as individual locus that control important traits can be of great target to rice breeders.

The concept of collecting data of people using a domestic space is not novel. However, the methods and processes used to decipher this raw data and transform it into useful and appropriate information (i.e., sequence, duration, and timing derived from domestic activities) have been challenging and the focus of many research groups. But how are the results of the decoded transposition received, interpreted and used by the various professionals (e.g., occupational therapists and architects) who consume the information? This paper describes the inclusive evaluation process undertaken, which involved architects, engineers and end-users (not the occupant, but the care team managing the occupant). Finally, our study evidence the importance of making accessible to a multidisciplinary audience spatial, temporal and sequential aspects derived from people's domestic routines. Shedding light on how a systematic approach to collecting, processing and mapping low-level sensor data into higher forms and representations can be a valuable source of knowledge for improving the domestic living experience.

Lifestyle physical activity (PA) and nutrition are known to be effective interventions in preventing and managing obesity related comorbidities is adult populations, but less so in children and adolescents. We examined the effectiveness of lifestyle interventions in children from minority ethnic populations in western high-income countries. Our systematic review included 53 studies involving 26045 children from minority ethnic populations within western countries, who followed lifestyle intervention programs lasting between 8 weeks and 5 years with an aim to prevent and/or manage childhood obesity and associated comorbidities, including adiposity and cardiometabolic risks. Studies were heterogenous in terms of lifestyle intervention components (nutrition, PA, behavioural counselling) and settings (community vs. schools and after schools). Our meta-analysis included 31 eligible studies and showed no significant effects of lifestyle interventions when they focused on body weight and body mass index (BMI) outcomes [pooled BMI mean change = -0.09 (95% CI -0.19, 0.01), p=0.09]. This was irrespective of the intervention program duration (< 6 months vs. ≥ 6 months), type (PA vs nutrition/combined intervention) and weight status (overweight or obese vs no normal weight), all showed no significant effects in the sensitivity analysis. Nonetheless, 19 of the 53 studies reported reduction in BMI, BMI z scores and body fat percentage. However, majority of lifestyle interventions adopting a quasi-design with a combined primary and secondary obesity measures (11 out of 15 studies), were effective in reducing obesity comorbidities of cardiometabolic risks including metabolic syndrome, insulin sensitivity, and blood pressure in children with overweight and obesity. Preventing childhood obesity and associated comorbidities in children from high-risk ethnic minority groups is best achieved using a combined PA and nutrition intervention approach, which jointly target preventing obesity and cardiometabolic disease primary and secondary outcomes, especially measures of diabetes, hypertension, and cardiovascular disease.

This study uses the social impact theory to analyse consumer behaviour amidst Covid-19. Fear of scarcity has changed consumer buying behaviour in crisis times such as the now abating global health crisis – i.e., Covid-19. The study asserts that the existing five-stage model of consumer purchasing decisions does not fit neatly in turbulent times. It proposes a shortened four-stage process of need recognition, purchase, ownership and satisfaction as a better and more adaptable fit. Cutting out information search and evaluation of alternatives in the old model, and replacing these with ownership, is where the main contribution of the study lies. The study has implications for managing the marketing mix as we know it. It asserts that not all the 4Ps of the marketing mix are important in crisis times.

Deep learning dominates automated animal activity recognition (AAR) tasks due to the high performance on large-scale datasets. However, constructing centralised data across diverse farms raises data privacy issues. Federated learning (FL) provides a distributed learning solution to train a shared model by coordinating multiple farms (clients) without sharing their private data. Whereas directly applying FL to AAR tasks often faces two challenges: client-drift during local training and gradient conflicts during global aggregation. In this study, we develop a novel FL framework called FedAAR to achieve AAR with sensor data. Specifically, we devise a prototype-guided local update module to alleviate the client-drift issue, which introduces global prototypes as shared knowledge to force clients to learn consistent features. To reduce gradient conflicts between clients, we design a gradient refinement-based aggregation module to eliminate conflicting components between client gradients during global aggregation, thereby improving the agreement between clients. Experiments are conducted on a public dataset to verify FedAAR’s effectiveness, which consists of 87,621 2-s motion data. The results demonstrate that FedAAR outperforms state-of-the-arts, with precision (75.23%), recall (75.17%), F1-score (74.70%), and accuracy (88.88%), respectively. The ablation experiments also show FedAAR’s robustness against various factors (i.e., different data sizes, communication frequency, and client numbers).

The world's growing population is highly dependent on animal agriculture. Animal products provide nutrient-packed meals that help to sustain individuals of all ages in communities across the globe. As the human demand for animal proteins grows, the agricultural industry must continue to advance its efficiency and quality of production. One of the most commonly farmed livestock is poultry and their significance is felt on a global scale. Current poultry farming practices result in the premature death and rejection of billions of chickens on an annual basis before they are processed for meat. This loss of life is concerning regarding animal welfare, agricultural efficiency, and economic impacts. The best way to prevent these losses is through the individualistic and/or group level assessment of animal on a continuous basis. On large-scale farms, such attention to detail was generally considered to be inaccurate and inefficient, but with the integration of Artificial Intelligence (AI) assisted technology individualized and per-herd assessments of livestock are possible and accurate. Various studies have shown cameras linked with specialized systems of AI can properly analyze flocks for health concerns, thus improving the survival rate and product quality of farmed poultry. Building on the recent advancements, this review explores the aspects of AI in the detection, counting and tracking of the poultry in commercial and research-based applications.

The outbreak of SARS-COV-2 disease 2019 (COVID-19) abruptly changed the patterns in electricity consumption, challenging the system operations of forecasting and balancing supply and demand. This is due to the mitigation measures that include lockdown and Work from Home (WFH), which decreased the aggregated demand and remarkably altered its profile. Here, we characterise these changes with various quantitative markers and compare it with pre-COVID-19 business-as-usual data using Great Britain (GB) as a case study. The ripple effects on the generation portfolio, system frequency, forecasting accuracy and imbalance pricing are also analysed. An energy data extraction and pre-processing pipeline that can be used in a variety of similar studies is also presented. Analysis of the GB demand data during the March 2020 lockdown indicates that a shift to WFH will result to a net benefit for flexible stakeholders, such as consumer on variable tariffs. Furthermore, the analysis illustrates a need for faster and more frequent balancing actions, as a result of the increased share of renewable energy in the generation mix. This new equilibrium of energy demand and supply will require a redesign of the existing balancing mechanisms as well as the longer-term power system planning strategies.

Social, cultural, environmental and economic factors closely regulate the selection, allocation and consumption of maternal diets. We developed a nutrition behaviour change intervention to promote a balanced diet in pregnancy through practical demonstration in rural Bangladesh and tested the impact with a cluster randomised controlled trial. This paper presents the findings of the process evaluation and describes the strategies that worked for intervention compliance. We conducted in-depth interviews with pregnant women, women who birthed recently, and their husbands; focus groups with mothers and mothers-in-law; key-informant interviews with community health workers, and observation of home visits. We identified six key areas within the intervention strategy that played a crucial role in achieving the desired adherence. These included practical demonstration of portion sizes; addressing local food perceptions; demystifying animal-source foods; engaging husbands and mothers-in-law; leveraging women’s social networks; and harnessing community health workers’ social role. Practical demonstration, opportunity to participate and convenience of making of the plate with the food available in their kitchen or neighbours’ kitchen were the most commonly mentioned reasons for acceptance of the intervention by the women and their families. The balanced plate intervention helped women through practical demonstration to learn about a balanced meal by highlighting appropriate portion sizes and food diversity. The women needed active involvement of community health workers in mobilising social support to create an enabling environment essential to bring changes in dietary behaviours. Programs to promote a nutritious maternal diet should focus on encouraging the use of healthy foods through practical demonstration of portion sizes and engagement of the women and family instead of replicating the traditional information-based counselling.

This paper attempts to alter a prevailing assumption that buildings use energy to an understanding that in fact, people use energy. Therefore, to successfully accelerate the transition to a low-carbon society and economy more emphasis should be on motivating people and increasing their awareness by making them energy conscious building users and therefore active players in the energy transition process. In this context, this paper provides insights from the Horizon 2020 MOBISTYLE project. It demonstrates research and development approaches, highlights the main project objectives, and presents findings of an ethnographic (qualitative) study of users’ habits, practices, and needs. The aim of the project is to motivate behavioural change by raising consumer awareness through the provision of attractive personalized information on user’s energy use, indoor environment and health, all enabled by an integrated information and communication technology (ICT) service. In this context, the anthropological people-centred approach is integrated into the MOBISTYLE approach putting users at the centre of the ICT tools development process. The main quantitative objective of the project is a reduction of energy use for at least 16 % prompted by the provision of combined information and feedback systems on energy, indoor environmental quality (IEQ) and health. The most relevant motivational factors and key performance indicators (KPIs) for encouraging a more energy conscious and healthy lifestyle were defined by means of a people-centred approach, adopting anthropological inquiries in different settings. Information about users’ lifestyles and their needs was collected in focus groups with potential users in five case studies, located in different European Union (EU) countries. Behaviour change is achieved through awareness campaigns, which encourage users to be pro-active about their energy consumption and to simultaneously improve health and well-being.

Using insights from cybernetics and an information-based understanding of biological systems, a precise, scientifically inspired, definition of free-will is offered and the essential requirements for an agent to possess it in principle are set out. These are: a) there must be a self to self-determine; b) there must be a non-zero probability of more than one option being enacted; c) there must be an internal means of choosing among options (which is not merely random, since randomness is not a choice). For (a) to be fulfilled, the agent of self-determination must be organisationally closed (a `Kantian whole'). For (c) to be fulfilled: d) options must be generated from an internal model of the self which can calculate future states contingent on possible responses; e) choosing among these options requires their evaluation using an internally generated goal defined on an objective function representing the overall `master function' of the agent and f) for `deep free-will', at least two nested levels of choice and goal (d-e) must be enacted by the agent. The agent must also be able to enact its choice in physical reality. The only systems known to meet all these criteria are living organisms, not just humans, but a wide range of organisms. The main impediment to free-will in present-day artificial robots, is their lack of being a Kantian whole. Consciousness does not seem to be a requirement and the minimum complexity for a free-will system may be quite low and include relatively simple life-forms that are at least able to learn.

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicat-ed in several neurological disorders, including Parkinson’s disease (PD). Here, we report results of an RNAi screen of genes differentially regulated in adr-2 mutants, normally encoding the only catalytically active ADAR in Caenorhabditis elegans, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegenera-tion, two PD pathologies, reveal that reduced expression of xdh-1, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegenera-tion. Further RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. Proteomic analysis indicates that the editing of one nucleotide in wht-2 RNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing its structure. Thus, we propose a model where wht-2, is edited by ADR-2 which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited provoking a reduction in xdh-1 transcription to limit uric acid production and maintain cellular homeostasis. In turn, ele-vation of uric acid is protective against dopaminergic neuronal cell death. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.

Background: This study analyzes sex-based differences in renal structure and response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Methods: ApoE-/- mice (8 weeks old) received enalapril (5 mg/kg/day, subcutaneous) or PBS as a control for an additional 14 weeks. Each group consisted of six males and six females. Results: Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in females), and the hypertrophy of PECs in males. Conclusion: This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Background: Little is known about the decisional background of choosing an appropriate disease model. Therefore, this paper aims, (1) to identify a spectrum of reasons for choosing between animal and non-animal disease models and (2) provides an ethical analysis of these reasons. Methods: 13 researchers from basic and preclinical research were interviewed, the interviews were analyzed qualitatively and the results were categorized. The ethical analysis was based on the principlism approach and a value judgement model. Results: This paper presents 66 reasons why researchers use animal (41 %) or alternative, non-animal disease models (59 %). Most of the reasons were be assigned to the work environment (29 reasons) and scientific standards (22 reasons). Other reasons were assigned to personal attitudes (11 reasons) and animal welfare (4 reasons). Qualitative relevant normative differences are presented in the ethical analysis. Even if few reasons can be rejected outright from an ethical point of view, there are good reasons to give some more weight than others. Conclusions: The spectrum of reasons and its ethical assessment provide a framework for reflection for researchers who may have to choose between animal models and (investing in) alternatives. This can help to reflect on and justify decisions.

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.

Wingless-type MMTV integration site (Wnt) signaling is one of the most critical pathways in developing and adult tissues. In the brain, Wnt signaling contributes to different neurodevelopmental aspects ranging from differentiation, axonal extension, synapse formation, neurogenesis and neuroprotection. Canonical Wnt signaling is mediated mainly by the multifunctional β-catenin protein which is a potent co-activator of transcription factors such as Lymphoid Enhancer Factor (LEF) and T Cell Factor (TCF). Accumulating evidence points to dysregulation of Wnt/β-catenin signaling in major neurodegenerative disorders. Here I focus on a “Wnt/β-catenin-glial connection” in Parkinson’s disease (PD), the most common movement disorder characterized by the selective death of midbrain dopaminergic (mDAergic) neuronal cell bodies in the subtantia nigra pars compacta (SNpc) and gliosis. I will summarize the work of the last decade documenting that Wnt/β-catenin signaling in partnership with glial cells is critically involved in each step and at every levels in the regulation of nigrostriatal DAergic neuronal health, protection and regeneration in the MPTP mouse model of PD, focusing on Wnt/β-catenin signaling to boost a full neurorestorative program in PD.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.