Wool-biting is a prevalent stereotypic behavior that negatively affects sheep welfare and productivity. This study aimed to dietary boron, and/or dicalcium phosphate (DCP) supplementation, as a potential dietary strategy to reduce wool-biting while improving metabolic and mineral status in lactating Akkaraman sheep. The study was conducted using 28 lactating Akkaraman sheep, which were randomly assigned to four groups (n = 7 per group): a control group (C), a DCP-supplemented group (D), a boron-supplemented group (B), and a group receiving both boron and DCP (BD). The study lasted for two weeks, and the feed supplements were administered to the animals on a daily schedule. The results showed that wool-biting behavior was significantly lower in the BD group than in the other groups (P < 0.001). It was also found that wool-biting behavior decreased over time in the experimental groups (P < 0.001). Non-esterified fatty acids and beta-hydroxybutyric acid (BHBA) were found to be higher in the BD group (P < 0.001). While an increase in BHBA levels was observed (P < 0.001), a decrease in total cholesterol levels was found (P = 0.023). Blood urea nitrogen concentrations in the experimental groups were higher than in the control group (P = 0.020). Only the effects of time (P = 0.049) and group x time (P = 0.047) on Ca value were found to be significant. These findings indicate that dietary supplementation with boron in combination with DCP may effectively mitigate wool-biting behavior in sheep, potentially by modulating metabolic and mineral parameters in the blood.
Interest in precision medicine has accelerated efforts to identify sex-dependent responses to treatments and interventions. Those efforts have, both historically and today, been concentrated in fields related to the brain and behavior. Here, we show that even though articles claiming sex-dependent effects are far more prevalent in the neurosciences than in other fields, those claims are infrequently supported by appropriate statistical evidence. Of 200 recent articles in the behavioral and brain sciences with a claim of a sex- or gender-dependent effect in the title, only 24% supported the claim with appropriate evidence-that is, they compared the effect statistically across sex and reported results consistent with the claim. In 9%, an appropriate test was described but the results were incomplete or missing; another 9% contained results that directly contradicted the claim. In most articles (58%), the effect was not compared statistically across sex. Across six brain-related research areas (behavioral sciences, clinical neurology, neurosciences, psychiatry, psychology, and substance abuse), neurosciences had the lowest rate of appropriate evidence (18%) and psychology the highest (39%). Studies on nonhuman animals supported the claim significantly less frequently (15%) than studies on human participants (34%; P = 0.002). The use of appropriate analytical approaches was unrelated to journal rank or the citation impact of the article. We conclude that claims of sex- or gender-dependent effects in the behavioral and brain sciences are often not supported by appropriate evidence, revealing a widespread inferential gap that may undermine translation of sex-dependent findings into evidence-based treatments.
Isolated REM sleep behavior disorder (iRBD) is recognized as a prodromal stage of α-synucleinopathies. Iron metabolism and inflammation have been implicated in the pathogenesis of neurodegeneration. This study investigated the peripheral iron metabolism and inflammation in relation to prodromal clinical features and disease progression in iRBD. This prospective observational cohort study recruited patients with iRBD at Sleep Medicine Center of West China Hospital. We measured peripheral iron metabolism markers and analyzed their associations with clinical characteristics; REM sleep without atonia (RSWA); and inflammatory markers including C-reactive protein (CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α. Patients with iRBD were further stratified based on sex-specific ferritin levels. Cox regression was used to assess the risk of neurodegenerative diseases. A total of 113 patients with iRBD (65.33 ± 6.80 years, 23.1% female) and 99 healthy controls (HCs) (64.92 ± 7.12 years, 22.1% female) were enrolled. Patients with iRBD showed dysregulated iron metabolism, with particularly elevated serum ferritin levels compared with HCs (338.48 ± 200.16 vs 238.73 ± 129.50, p < 0.001). Serum ferritin was positively associated with RBD symptom severity, autonomic dysfunction, olfactory impairment, motor symptoms, and RSWA. In the longitudinal analysis, 79 patients with iRBD were included, with a follow-up duration of 4.06 ± 2.1 years. During this period, 23 patients (29.1%) developed neurodegenerative diseases. In a Cox regression model adjusted for age and sex, elevated ferritin levels were significantly associated with an increased risk of phenoconversion (hazard ratio 2.91, 95% CI 1.06-7.99, p = 0.038). Patients with iRBD with high ferritin demonstrated increased IL-10 (3.21 ± 1.71 vs 2.53 ± 1.24, p = 0.029) and TNF-α (4.27 ± 3.41 vs 2.77 ± 2.38, p = 0.046) levels. Serum ferritin levels were positively correlated with CRP (r = 0.204, p = 0.003) and TNF-α (r = 0.160, p = 0.020). This study showed the dysregulation of peripheral iron metabolism in patients with iRBD. Elevated serum ferritin was associated with a more severe prodromal neurodegenerative phenotype in iRBD. Furthermore, our findings indicate that peripheral iron metabolism potentially correlates with inflammation in the neurodegeneration of iRBD.
Haematobia irritans (L.) (Diptera: Muscidae), commonly known as the horn fly, is one of the most economically significant ectoparasites of cattle worldwide, causing substantial losses in meat, milk, and hide production. Its management has historically relied on broad-spectrum insecticides, whose overuse has driven the emergence of resistant populations and raised environmental concerns, emphasizing the urgent need to alternative, ecofriendly control strategies. A key yet underexplored aspect of horn fly biology is behind one of its characteristic behaviors, oviposition behavior: gravid females deposit eggs almost exclusively in very fresh cattle dung, a preference that diminishes rapidly with time post-defecation. Although volatile organic compounds (VOCs) from dung are known to mediate this behavior, the biological origin of these chemical cues remains poorly characterized. This review proposes that microbial volatile organic compounds (mVOCs) produced by the cattle dung microbiota-particularly anaerobic bacteria derived from the bovine rumen-are major elicitors of horn fly oviposition behavior, constituting a transkingdom chemical signaling system. By systematically cross-referencing VOCs reported in fresh cattle dung with compounds known to elicit electrophysiological and behavioral responses in H. irritans, we identified four key semiochemicals of probable microbial origin: phenol, p-cresol, indole, and α-pinene, produced by bacterial families including Enterobacteriaceae, Clostridiaceae, Paenibacillaceae, and Lactobacillaceae. The temporal decline in dung attractiveness is proposed to reflect the succession of the microbial community from anaerobic to aerobic dominance, with a concomitant shift in the mVOC profile. This hypothesis is further supported by the observation that the early developmental stages of H. irritans harbor an anaerobe-dominated microbiota. This framework may provide opportunities for the development of environmentally friendly blends for horn fly management.
Schizophrenia is a neuropsychiatric illness characterized by progressive deterioration of thought processes and marked behavioral abnormalities arising from an unknown pathogenesis underlying the false perceptions, primarily hallucinations and delusions. The clinical symptoms of schizophrenia also include apathy, communication disorders and suicidal thoughts. Although the etiopathogenesis of schizophrenia remains not fully elucidated, the development of schizophrenia has been linked to adverse pregnancy, obstetric complications, neurodevelopmental disorders, neurotransmission imbalance and aberrant neurogenic events. Astrocytes are the most predominant glial cell type in the central nervous system (CNS), where they provide metabolic support, regulate neuroimmune mechanisms, facilitate neurotransmitter reuptake, and sustain synaptic homeostasis. Abnormal neural transmission is considered central to the pathogenesis of schizophrenia. Recent studies have highlighted that malformations in glial cells, particularly dysfunctional or reactive astrocytes, play a crucial role in the pathophysiology. Astrocytic dysregulation in schizophrenia is likely to result in synaptic dysfunction due to altered levels of key gliotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and D-serine leading to altered neurobehavioral outcomes. Thus, insight into the scientific concepts that interrelate the pathophysiology of schizophrenia with astroglia dysregulation at the level of gliotransmitter imbalance could provide innovative hints for developing therapeutic strategies for the treatment of schizophrenia. This chapter describes the key roles of astrocytes and emphasizes imbalances in gliotransmitters as main contributors to the pathophysiology of schizophrenia.
The cerebellum is increasingly recognized for its crucial role in high-level cognitive processes, particularly in the domain of social cognition and action prediction. Disruptions in cerebellar circuits can lead to significant impairments in anticipating others' intentions and behaviors, affecting daily social interactions. This randomized, double-blind, sham-controlled trial protocol investigates the combined effects of personalized cerebellar High-Definition transcranial Alternating Current Stimulation (HD-tACS) and Immersive Virtual Reality (IVR) training on social prediction abilities. The study involves two clinical populations: adolescents and young adults with congenital cerebellar malformations (CM) and adults with acquired neurodegenerative cerebellar atrophy (CA). Participants undergo eight daily sessions of IVR training designed to enhance internal models of social events through interactive scenarios. Simultaneously, they receive either active or sham HD-tACS delivered at their Individual Gamma Frequency (IGF), determined via baseline EEG. The primary outcomes include behavioral responses to context-based social prediction tasks (action intentions, emotions, and personality traits). Secondary outcomes encompass electrophysiological measures, neuropsychological functioning, and adaptive behavior. By integrating neuromodulation with embodied virtual experiences, the project aims to facilitate cerebello-cerebral plasticity and provide a novel transdiagnostic rehabilitative approach for socio-cognitive impairments. The present protocol has been registered on ClinicalTrials.gov (NCT07500103).
Opioid use disorder is characterized by compulsive drug seeking and heightened relapse vulnerability following abstinence, a phenomenon known as incubation of craving. Although preclinical data suggest similar behavioral expression of opioid use between sexes, conclusive evidence on sex differences in craving and relapse across abstinence periods remains lacking. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength, glutamate release probability, and intrinsic excitability of NAcSh medium spiny neurons (MSNs) following 1 (acute) or 14 (prolonged) days of forced abstinence. No sex differences were observed in oxycodone self-administration or somatic withdrawal. However, females exhibited greater cue-induced relapse after prolonged but not acute abstinence. Prolonged abstinence produced comparable increases in PVT-NAcSh synaptic strength and presynaptic glutamate release probability in both sexes, while inhibitory transmission and MSN excitability were largely unaltered. The dissociation between comparable circuit-level plasticity and sex-specific relapse vulnerability suggests that PVT-NAcSh strengthening represents a shared neuroadaptation to oxycodone abstinence, while mechanisms driving heightened relapse in females likely involve additional circuit elements that remain to be identified.
Nitric oxide (NO), synthesized from L-arginine by nitric oxide synthases (NOS), acts as a conserved signaling molecule involved in the regulation of food intake across animal taxa. Understanding its function has gained importance in veterinary medicine, animal production, and comparative physiology, especially given species-specific differences in arginine metabolism and immune-nutritional interactions. This review provides a comparative synthesis of the role of NO in appetite regulation in mammals, birds, and aquatic animals, highlighting conserved mechanisms, species-specific differences, and gaps requiring further investigation. In mammals, NO modulates hypothalamic circuits controlling satiety and hunger in a bidirectional, energy-dependent manner. Birds, lacking endogenous arginine synthesis, show reduced feed intake with elevated NO levels. In fish, NO-especially via agmatine-suppresses feeding by downregulating orexigenic signals and enhancing insulin-mediated pathways. NO functions as a conserved but flexible regulator of food intake across taxa. Future studies employing molecular, nutritional, and behavioral tools are needed to clarify species-specific mechanisms and optimize NO-targeted feeding strategies in production animals.
Metabolism underpins cellular physiology, whereby the preference for specific substrates and catabolic pathways shapes the production of energy, anabolic substrates, and metabolite signals to address bioenergetic demands. Substrate catabolism can be directly examined by measuring metabolic endpoints. For instance, substrate oxidation can be quantified by the incorporation of carbon from labelled glucose or fatty acids into carbon dioxide, providing a sensitive and specific readout of metabolic flux. However, current platforms require relatively large culture volumes, lacking adaptability for small-scale or complex cell culture formats. Herein, we develop and validate a modular platform that can quantify substrate oxidation in a range of cell culture systems, including two- and three-dimensional cultures grown in 12- and 96-well plate formats. This platform was engineered for precise gas equilibration, minimal gas leakage, and bioinert adapters suitable for smaller-scale cultures, using inexpensive and accessible components. We demonstrate the versatility of this system by showing that: (i) dendritic cells modulate glucose catabolism in response to a tolerance-inducing biologic (AIP-2), and (ii) human cardiac organoids maintain fatty acid oxidation during acute inflammatory stress. This platform can be performed in parallel with orthogonal metabolomics assays and live-cell imaging, enabling integrated analysis of metabolic and functional readouts. Together, this platform expands access to measuring substrate oxidation across a range of cellular systems.
Chromatin remodeling plays a central role in regulating plant development and physiology by shaping the gene expression patterns that drive biological processes. Among epigenetic modifications, histone acetylation is particularly relevant as it alters chromatin structure and influences transcriptional activity. MYST-type histone acetyltransferases (HAT) are evolutionarily conserved components of the Nucleosome Acetyltransferase of histone H4 (NuA4) complex, a key regulator that acetylates histones H4, H2A, and the histone variant H2A.Z. Growing evidence supports the presence of a canonical NuA4-C in plants, similar to that described in yeast. In this review, we summarize recent studies that have begun to uncover its broad role in plant biology, highlighting its involvement in diverse processes such as the skoto- to photomorphogenesis switch, chloroplast development, shade avoidance responses, thermomorphogenesis, the vegetative-to-reproductive transition, plant growth, reproduction and hormonal signalling. In addition, we discuss recent advances in understanding the crosstalk of NuA4-C-mediated H4ac and H2A.Z deposition with other chromatin remodeling complexes in plants. Although significant progress has been made, a full understanding of the complex functions remains unavailable. Current evidence indicates that NuA4-C in yeast and TIP60 in humans are central regulators of transcription, acting not only through histone acetylation but also by influencing transcription elongation and RNA splicing, although direct evidence for similar functions in plant NuA4-C still remains limited. This regulatory role might be critical for integrating developmental programs with environmental signalling pathways. While initial insights into the recruitment of NuA4-C to target genes have emerged, further research is needed to clarify how its activity is controlled and modulated in different biological contexts.
Vision plays a pivotal role in development. Congenital and early acquired visual impairment (VI) may adversely impact several domains related to everyday functioning, such as social and academic inclusion, autonomies and quality of life. In recent years, the inclusion of these dimensions as key targets of the assessment and re-habilitation of paediatric VI has received increasing consensus. This cross-sectional study enrolled patients attending 5 centres specialized in paediatric VI care and aimed to draw an integrated profile of functioning, autonomies, quality of life and emotional-behavioural domains in a large cohort of children with VI. 91 caregivers of as many visually impaired children (age range 6-18, mean age 11.05 years, 47 females) - split into two age groups: 6-10 years; 11-18 years - were enrolled in an on-line survey including three validated questionnaires to assess children's: a) autonomies, via a Patient Reported Outcome Measure (PROM) tool; b) socio-emotional and behavioural problems; c) quality of life (QoL). Clinical and socio-demographic information were also collected. Both age groups showed medium-high average level of autonomy in every investigated area as well as appropriate socio-emotional, behavioral, and QoL scores. Interestingly, adolescents showed lower scores in autonomies compared to the younger age group overall. Autonomy score significantly associated with better QoL and less socio-emotional and behavioural problems, both internalizing and externalizing. Our results highlight the importance of assessing autonomy in the context of paediatric VI re-habilitation as they largely associate and potentially impact on young patients' psychological well-being.
Metacognitive monitoring, or the capacity to assess and regulate one's cognitive activities, is essential for maintaining optimal mental functioning. Metacognitive monitoring may be particularly important for individuals as they age, fostering self-awareness of cognitive strengths and limitations, guiding strategy selection to enhance performance, compensating for age-related changes to cognitive abilities, and identifying the earliest cognitive symptoms of disease. By evaluating one's own understanding, individuals can align their confidence with actual ability, promoting better decision making and behavioral control. This review synthesizes the current literature on age-related differences in the accuracy of metacognitive monitoring across different types of metacognitive judgments, including judgments of learning, feelings of knowing, and post-decision confidence. We begin by discussing two key components of metacognitive monitoring: metacognitive sensitivity and metacognitive calibration. Then, we examine existing studies to address two main questions: whether age-related differences in one component (e.g., metacognitive calibration) can be explained by variations in the other (e.g., metacognitive sensitivity), and whether these differences can be attributed to age-related changes in underlying cognitive or perceptual processes. We find that the current literature does not provide definitive evidence for or against the decline of metacognitive monitoring in older adults. Rather, findings suggest that aging may differentially affect metacognitive accuracy depending on the type of judgment and task demands, with some domains showing preserved or even enhanced performance. These mixed findings underscore the conceptual and methodological complexity of studying metacognition in aging. We conclude by outlining key theoretical and empirical directions to clarify mechanisms and advance the field.
Alzheimer's disease (AD) is a progressive, irreversible, and multifaceted neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral impairment, posing a major global health challenge. Its multifactorial pathology includes cholinergic dysfunction, amyloid-β deposition, tau hyperphosphorylation, oxidative stress, and neuroinflammation. Among these, impairment of the cholinergic system, characterized by reduced acetylcholine levels, plays a crucial role in cognitive deficits. The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which hydrolyze acetylcholine, are closely involved in disease progression and serve as important therapeutic and diagnostic targets in AD. This book chapter provides a comprehensive overview of therapeutic and diagnostic agents targeting AChE and BChE in AD, and discusses small-molecule inhibitors, multifunctional ligands, and emerging strategies to modulate cholinesterase activity and restore cholinergic neurotransmission, alleviating disease symptoms. In addition, the chapter highlights advances in diagnostic approaches using fluorescent probes, particularly near-infrared (NIR) probes, for selective detection and imaging of AChE and BChE, including their molecular design, photophysical properties, enzyme selectivity, and mechanisms of action, all of which are critically examined. Targeting AChE and BChE offers a dual advantage in AD by enabling both symptomatic treatment and early-stage diagnosis. This chapter aims to present a clear and comprehensive overview of recent advances in therapeutic and diagnostic approaches, offering meaningful insights for researchers in developing effective strategies for the treatment and monitoring of AD.
Adrenal crisis is a life-threatening condition which is caused by an insufficient level of glucocorticoids in the body. Most patients have preexisting adrenal insufficiency, and physical or emotional stress triggers the adrenal crisis. This includes acute illness and surgery. It is important that patients receive a life-saving emergency injection of 100 mg hydrocortisone immediately and a continuous supplementation afterwards. This article focuses on the pathophysiology, trigger factors, prevention and emergency treatment of adrenal crisis in adult patients. By adjusting the regular dosage of glucocorticoids in stressful situations, adrenal crisis can be prevented. Patients at risk for adrenal crisis should keep an emergency injection kit and a standardised European emergency card and receive life-saving doses of glucocorticoids in emergency situations as quickly as possible.
Pregnancy is accompanied by profound neuroendocrine adaptations that prepare the maternal brain for caregiving and social responsiveness. Although empathy represents a key component of maternal behavior, it remains unclear whether pregnancy is associated with distinct patterns of emotional and cognitive empathy and how these patterns relate to neuroendocrine factors. This cross-sectional study included 111 women (68 pregnant and 43 nulligravid controls). Empathy was assessed using the Interpersonal Reactivity Index, with separate evaluation of emotional and cognitive components. Salivary oxytocin and serum testosterone levels were measured using ELISA. The second-to-fourth digit ratio (2D:4D) was assessed as an indirect marker of prenatal androgen exposure. Pregnant participants exhibited higher emotional empathy and lower cognitive empathy than controls, whereas total empathy scores did not differ between groups. Emotional empathy differed across pregnancy trimesters and was highest in the second trimester. Pregnant women also showed higher salivary oxytocin and lower serum testosterone levels (p < 0.05). Oxytocin levels were positively correlated with empathy measures in the control group but not in pregnant women. No significant correlations were observed between the 2D:4D ratio and empathy measures. Pregnancy was characterized by a distinct pattern of affective and cognitive empathy within a complex neuroendocrine milieu. These findings support the view that empathic processing during pregnancy should be considered a multidimensional phenomenon shaped by coordinated neuroendocrine influences rather than the action of a single hormone. A better understanding of these neuroendocrine mechanisms may contribute to future research on maternal socio-emotional functioning and maternal mental health.
BackgroundAnti-Müllerian hormone (AMH) is a key biomarker of ovarian reserve, yet population-specific reference values remain limited for Middle Eastern women.ObjectivesEstablishing preliminary age-specific population estimates of AMH and gonadotropin is essential for improving clinical interpretation in this demographic.DesignCross-sectional, population-based exploratory study conducted between March 2025 and February 2026.Methods90 healthy women aged 19-47 years were recruited. Serum AMH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured on cycle day 3. Age-specific distributions were summarized as preliminary population-based estimates, given the modest sample size within each age stratum. Linear regression models were used to assess whether AMH independently predicted FSH, LH, or the LH/FSH ratio after adjusting for age.ResultsAMH showed a strong inverse correlation with age (r=-0.54). ROC analysis demonstrated that lower AMH levels were strongly associated with being older than 35 years, with an AMH value of 1.8 ng/mL (AUC≈0.80; sensitivity 0.94; specificity 0.61), indicating high sensitivity but limited specificity. FSH increased progressively with age (r=0.29), while LH remained relatively stable, resulting in a declining LH/FSH ratio. Regression analysis showed that AMH was independently associated with the LH/FSH ratio (β = 0.100, p < 0.001), but not FSH or LH after adjusting for age.ConclusionThis study provides the first preliminary age-specific population estimates of AMH and gonadotropins in Syrian women, demonstrating patterns consistent with global ovarian-aging trajectories. However, the absence of data on BMI, smoking, and lifestyle factors, along with the modest sample size, may limit the precision and generalizability of these estimates. This study looked at how ovarian reserve changes with age in healthy Syrian women. We measured three hormones that help show ovarian reserve: anti Müllerian hormone (AMH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). All tests were done on day 3 of the menstrual cycle, when these hormones are most stable. AMH is the most reliable marker of ovarian reserve. In this study, AMH levels were high in younger women and dropped steadily with age. Women aged 19–25 had much higher AMH levels than women aged 41–47. An AMH level of 1.8 ng/mL was strongly linked to being 35 years or older, meaning this value may help identify women whose ovarian reserve has begun to decline. FSH increased with age. Younger women usually had FSH levels below 10 mIU/mL, while women over 40 often had levels above 15 mIU/mL. Higher FSH levels indicate that the ovaries are working harder to produce eggs, which happens as ovarian reserve decreases. LH changed only slightly with age. Because FSH rises more than LH, the LH/FSH ratio became lower in older women. Younger women typically had ratios close to or above 1.0, while women over 35 often had ratios below 0.40. Overall, the study shows that AMH, FSH, and the LH/FSH ratio change in predictable ways as women age. These results provide the first population specific hormone estimates for Syrian women and can help doctors better interpret ovarian reserve in this region. However, the study did not include information on body weight, smoking, or lifestyle, and the sample size was modest, so larger studies are still needed.
Neuropsychiatric disorders are of great health concerns, and despite the availability of drugs, effective therapies are poor, emphasizing the need for novel therapeutics. Among the natural substances screened for neuromodulation properties, Spirulina platensis, a cyanobacterium, and its main bioactive compound (phycocyanin) have attracted great attention. Substantial evidence demonstrates that spirulina and phycocyanin possess neuroprotective properties by targeting multiple interconnected cellular and molecular pathways, including apoptosis, oxidative stress, neuroinflammation, and regulators of synaptic plasticity. Consequently, these compounds have shown therapeutic potential in experimental models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral ischemia, epilepsy, schizophrenia, depression, and autism spectrum disorder. Herein, we summarize various cellular and molecular pathways which are affected by spirulina and phycocyanin in neuropsychiatric disorders.
Enterococci are opportunistic uropathogens increasingly associated with recurrent urinary tract infections (UTIs) in companion animals, raising concerns about their virulence potential and high antimicrobial resistance. To characterize the species distribution, virulence-associated genes, and antimicrobial resistance profiles of urinary Enterococcus isolates from dogs and cats with recurrent UTIs, including vancomycin resistance determinants. This study analyzed 106 monomicrobial urinary Enterococcus isolates from 61 dogs and 45 cats with recurrent UTIs. Species identification was followed by multiplex polymerase chain reaction for vanA, vanB, vanC1, and vanC2 and for virulence-associated genes (fsr, efm, esp, cylA, cad1, ace, gelE, and asa1). The antimicrobial susceptibility was assessed by disc diffusion. The associations were evaluated using univariate comparisons and multivariable analyses. Among the 106 isolates, 68 (64.2%) were Enterococcus faecalis and 38 (35.8%) Enterococcus faecium. E. faecalis was more frequently isolated from cats than dogs (77.8% vs. 54.1%; odds ratio, 2.97). The virulence profiles differed according to species; E. faecalis was more likely to carry ace, gelE, asa1, cylA, fsr, and esp, and showed a higher overall virulence profile. The prevalence of resistance was high for erythromycin (82.1%), rifampicin (78.3%), tetracyclines (70.8%), and fluoroquinolones (~59%), with multidrug resistance detected in 84.9% of isolates. Nitrofurantoin resistance was more common in E. faecium than E. faecalis (47.4% vs. 5.9%) and was independently associated with E. faecium in multivariable analyses. The vancomycin-resistance gene vanB was detected in 2.83% of isolates. Recurrent UTIs in dogs and cats were associated with high rates of multidrug-resistant Enterococcus isolates and species-specific virulence and resistance patterns. These findings support the use of species-level identification and susceptibility testing-guided therapy to improve antibiotic stewardship and the clinical outcomes in recurrent UTIs in companion animals.
This exploratory study examined whether brief high-intensity cycling exercise, performed either before or after a single online Portuguese language lesson, improved language acquisition or retention in older adolescents with ADHD, compared to a resting control condition. Participants (n = 29; mean age 19.2; no prior Portuguese knowledge) were randomly assigned to one of the three conditions: control, exercise before, and exercise after. The 29-minute Portuguese lesson introduced vocabulary, grammar, and syntax. Immediate learning (Day 1) and retention (Day 7) were assessed through sentence production, free recall, and recognition memory. The exercise groups completed three 30-second leg cycling sprints with active recovery. The language lesson and assessments were identical across conditions. Although no statistically significant differences were found, effect size analyses revealed that exercising before the lesson was associated with moderately better recognition memory on both Day 1 (d = 0.51) and Day 7 (d = 0.77), along with small improvements in free recall (d = 0.21 to 0.44). In contrast, exercising after the lesson was linked to worse recognition memory (d = -0.51) and fewer sentences created (d = -0.69 to -0.99) compared to control. The findings from this exploratory study show that in a sample of older adolescents with ADHD the brief, intense cycling exercise prior to an initial Portuguese lesson was associated with a pattern suggesting higher free-recall and recognition memory for Portuguese words, while the similar exercise performed after the language lesson was associated with a pattern suggesting worse memory performance on sentence production, a more complex cognitive task. Further research with larger and more diverse samples is needed to confirm the present findings and clarify optimal exercise timing during the initial and subsequent days of second language learning.
Skeletal muscle plasticity progressively declines from middle age onward, and exercise may partially mitigate this deterioration through microRNA (miRNA)-mediated regulatory networks. However, whether the timing of aerobic exercise initiation during middle age (early vs. late) differentially influences muscle function and miRNA expression profiles remains incompletely understood. Male C57BL/6 mice were assigned to four groups: middle-aged control (MC, 12 months), old-aged control (MC18, 18 months), early exercise (PRE18, 12-15 months), and late exercise (POS18, 15-18 months). Gastrocnemius muscles were collected for miRNA sequencing and subsequent functional analyses. The MC18 group exhibited sarcopenic-like phenotypes, with 176 differentially expressed miRNAs (DEmiRNAs) identified relative to the MC group. Aerobic exercise was associated with attenuation of age-related muscle atrophy, with PRE18 showing comparatively more pronounced effects than POS18. miRNA sequencing identified 21 DEmiRNAs with reversed expression patterns in the PRE18 group, whereas only 2 such miRNAs were identified in the POS18 group. Bioinformatic analysis of predicted targets suggested that early-exercise-induced miRNAs may be involved in suppressing FOXO/ubiquitin-mediated proteolysis and restoring Wnt/cAMP signaling, whereas late-exercise-induced miRNAs appeared to have a limited capacity to restore Wnt signaling. miR-195a-5p_R+1, miR-298-5p_R-2, miR-671-5p_R+1 and miR-150-5p were identified as candidate hub miRNAs based on target enrichments within these pathways. Western blot analyses indicated that PRE18 was associated with elevated expression of Wnt‑related (β‑catenin) and cAMP‑related (CREB1, PGC‑1α) proteins, alongside reduced levels of atrophic markers (FOXO3A, FBXO32, and MuRF1). In contrast, POS18 primarily affected atrophic protein expression, with relatively modest influence on Wnt signaling components. These preliminary findings collectively suggest that the sustained benefits of exercise initiated in early middle age might be partially attributable to exercise‑induced miRNAs dually targeting both regenerative and atrophic pathways. Conversely, late initiation appears to be predominantly linked to anti‑atrophic effects, with less impact on regenerative signaling. Together, these observations provide initial evidence for temporal epigenetic plasticity and suggest broader molecular advantages of earlier intervention, although further mechanistic studies are warranted.