Search Results (200)

Background: Neurodegenerative diseases are a major health problem, and the neuropsychiatric symptoms seen in these diseases adversely impact the lives of patients, families, and caregivers. Inappropriate aggressive behavior is a highly disruptive symptom and a leading cause of institutionalization. There are no approved drugs specifically for the treatment of problematic aggression, and the off-label use of antipsychotics has limited benefit with significant side effects and safety risks. This review discusses dysregulated arginine vasopressin (AVP) signaling in fear–threat circuitry as a key driver of inappropriate aggression. Because the AVP 1a receptor (V1aR) is the dominant subtype in the CNS, the selective antagonism of this receptor represents a well-rationalized target for the treatment of aggression across neurodegenerative, psychiatric, and neurodevelopmental disorders. Objectives: Our goal was to summarize the basis for using V1aR antagonists as a treatment for irritability and aggressive behavior. We describe its discovery, biosynthesis, receptor pharmacology, and CNS distribution, emphasizing V1aR localization in central fear–threat circuits. Translational evidence from animal studies, pharmacological neuroimaging, and lesion network mapping is presented. These data support the suggestion that heightened vasopressinergic tone biases socioemotional information processing toward negative valence, increasing threat sensitivity and the likelihood of inappropriate aggressive responses. Emerging clinical data support this framework. Highly selective, CNS-penetrant V1aR antagonists reduced aggressive behavior and had an excellent safety profile in phase 2 studies in Huntington’s disease and intermittent explosive disorder, with efficacy signals across caregiver-reported, clinician-rated, and incident-based measures. Furthermore, pharmacological neuroimaging showed that V1aR antagonism normalizes AVP-induced alterations in activity within fear–threat circuitry. Conclusions and Future Directions: Preclinical, translational, and clinical findings to date support V1aR antagonism as a promising strategy for treating pathological aggression across disorders. Additional experimental medicine studies and clinical trials are needed to conclusively establish efficacy in various disease populations, and we note the need for improved trial designs and analytical methods as part of the development process. Full article

With the growing adoption of electric vehicles (EVs) and increasing demand for efficient parking infrastructure, intelligent pallet-based parking systems with automated guided vehicles (AGVs) offer a promising solution for high-density EV storage and automated valet parking (AVP) operations. However, in such systems, orthogonal-motion AGVs often experience unstable transport conditions due to abrupt speed variations during operation, which can lead to vibrations and safety risks. Trigonometric acceleration and deceleration algorithms are known for their smooth transitions and low impact, but their high computational complexity makes them difficult to implement in embedded AGV systems that require real-time responsiveness. To address this challenge, this paper proposes an approach that approximates the sine function using a third-order Chebyshev polynomial, thereby constructing a complete acceleration and deceleration algorithm. The algorithm includes speed profile planning under conditions with and without constant-speed phases. Simulation analyses and scaled prototype experiments on an orthogonal-motion AGV were conducted. Compared with the traditional sine-based method, the scaled AGV prototype exhibited a maximum speed tracking error of 5 mm/s and a positioning error of 0.38 mm over an 800 mm travel distance. These results indicate that our approach not only preserves the smooth acceleration/deceleration profile of trigonometric curves but also enhances throughput, positional accuracy, and real-time responsiveness, making it suitable for practical EV parking and automated valet parking systems. Full article

Vasodilatory shock, primarily driven by sepsis, remains a leading cause of mortality in intensive care units (ICU), with mortality rates exceeding 90% in refractory cases. While norepinephrine is the first-line vasopressor, prolonged exposure to high doses of catecholamines is linked to severe adverse effects, including myocardial toxicity, arrhythmias, and immunodepression. Consequently, the concept of decatecholaminization, utilizing non-adrenergic vasopressors to reduce catecholamine burden, has emerged as a critical therapeutic strategy. This comprehensive review aims to define the current role of vasopressin and its analogues, terlipressin and selepressin, in managing patients with circulatory shock, evaluating their physiological rationale, clinical benefits, and adverse event profiles. The vasopressin system provides a multimodal approach to hemodynamic stability independent of α-adrenergic stimulation. Arginine vasopressin (AVP) acts on V1a receptors to induce vasoconstriction and improve glomerular filtration, and on V2 receptors for water reabsorption. Clinical trials indicate that while AVP may not reduce overall mortality, it significantly reduces the need for renal replacement therapy (RRT) and offers survival benefits in the less severe shock subgroup. Synthetic analogues like terlipressin offer a longer half-life but carry an increased risk of peripheral ischemia. Conversely, selepressin, a pure V1a agonist, was designed to mitigate fluid retention and edema, though recent trials have not yet demonstrated superior clinical outcomes over placebo. Modulation of the vasopressin system is a cornerstone of decatecholaminization in distributive and cardiogenic shock. Although a universal mortality benefit has not been established, these agents are crucial for protecting renal function, reducing catecholamine toxicity, and lowering the incidence of arrhythmias. Future strategies should focus on precision medicine, utilizing biomarkers like copeptin and artificial intelligence to optimize the timing and selection of multimodal vasopressor therapy. Full article

Background/Objectives: Lower urinary tract symptoms (LUTSs), particularly nocturia and urgency, often intensify during the menopause transition and may worsen with caffeine intake and cold exposure. This review aims to synthesize evidence relevant to a hypothesized caffeine–cold interaction in transitional menopause, focusing on water homeostasis and the estrogen–transient receptor potential melastatin 8 (TRPM8) cold-sensory axis, and to propose potentially actionable, nutrition-centered intervention candidates for future testing. Methods: Structured narrative review of PubMed, Embase, Web of Science, and citation tracking (inception–January 2026). Evidence was mapped into a mechanistic framework distinguishing established from hypothesis-generating links; no formal systematic-review study selection or meta-analysis was performed. Results: Caffeine can increase urine output via renal mechanisms (adenosine receptor antagonism and natriuresis) and may lower bladder sensory thresholds. Because half-life is long and variable, afternoon intake can extend into sleep, potentially increasing awakenings and nocturnal voids. Human studies link colder indoor environments to nocturia/overactive bladder, and passive pre-bedtime heating is associated with fewer nocturnal voids. We propose that repeated nighttime cold may amplify caffeine-related diuresis and may shift urine production toward the night, while estradiol decline may heighten TRPM8-mediated cold sensory gain, potentially contributing to urgency/frequency flares. A testable 2 × 2 cold × caffeine framework can operationalize dose, timing, and metabolism, pairing voiding diaries and bedroom temperature sensing with copeptin profiling. Conclusions: Transitional menopause may represent a susceptibility window in which endocrine instability and estradiol decline could plausibly increase sensitivity to indoor cold exposure and caffeine intake, potentially contributing to nocturia and urgency. The hypothesis label ‘dual hormone suppression’ (attenuated nocturnal AVP signal plus estradiol decline) may provide a mechanistic substrate for cold-exacerbated nocturnal polyuria, while an estrogen–TRPM8 axis may amplify cold-evoked urgency. Potentially actionable candidates include chronobiological caffeine timing/management and low-burden thermal strategies; nevertheless, menopause-stage-specific epidemiologic and clinical evidence for a caffeine × cold interaction remains limited and several mechanistic links are extrapolated, so prospective diary- and biomarker-enabled studies and controlled trials are needed to validate mechanisms and refine cold-sensitive endotypes. Full article

Background: Ultrasound (US)-guided axillary vein puncture (AVP) is an established technique for cardiac implantable electronic device (CIED) implantation. Yet real-world data concerning shifting from conventional venous access into US-guided AVP are not widely available. Methods: This is a single-center prospective registry reporting safety (complications) and efficacy (success rate: i.e., accomplishment of the vein access utilizing only the initially employed approach) of self-taught US-guided AVP integration into the standard workflow of CIED procedures. Results: A total of 539 patients (mean age 71.5 ± 12.4 years old, 78.7% males) were treated in our institution over a three-year period. Regarding CIED type and lead number, 58.3% used an implantable cardioverter defibrillator, 32% used permanent pacemakers, and two leads were involved in 65.8% of the cases and three leads in 8.9%. Before integration of US-guided AVP, the venous access success rate was 93.5%. The US-guided AVP success rate was 377/400 procedures (94.2%). After the first semester of US-guided AVP utilization, a pattern of increased success rate was observed (p = 0.002) and remained stable over the following semesters. No major complication (periprocedural or 30-day mortality, hemothorax, pneumothorax and tamponade) occurred after US AVP integration in our workflow. Conclusions: The integration of US-guided AVP in a self-taught manner is feasible among electrophysiologists with experience in US-guided vascular access. A high success rate can be reached quickly and safely. Full article

In the field of antiviral peptide (AVP) design, one of the most prominent limiting factors is the time and material cost required to perform the initial screening of novel AVPs. In particular, traditional target identification as well as traditional preclinical screening of novel drug candidates can be a very lengthy and expensive process. In recent decades, target identification and initial screening of AVPs has been increasingly carried out using machine learning (ML). The use of ML to initially screen potential interactions reduces the financial cost and lengthy time scale of preclinical AVP development, allowing for candidate peptides to be identified and screened faster, at a lower cost to both manufacturer and consumer. Additionally, the use of ML in generating and screening AVP candidates allows a more diverse chemical space to be explored than high-throughput screening methodologies allow. In silico generation and validation of AVP candidates also limits researcher contact with high BSL-rated viruses, thereby increasing the safety and accessibility of AVP design. This review seeks to provide a broad overview of the current uses of ML in early-stage AVP design, and to shed some light on the future direction of the field. Full article

Introduction: HPV vaccination rates for adolescents in the United States are below recommended levels. The Adolescent Vaccination Program (AVP) guides pediatric clinics on how to implement evidence-based strategies to increase HPV vaccination rates. These strategies comprise the adoption of (1) immunization champions, (2) provider assessment and feedback, (3) continuing education, and (4) prompts, (5) parent reminders, and (6) parent education. The AVP systems-based intervention has demonstrated increased HPV vaccination rates in large urban pediatric clinic networks. The purpose of this study was to assess the feasibility of using an online decision support tool, the AVP Implementation Tool (AVP-IT), to implement AVP strategies in safety-net clinics to improve healthcare for the medically underserved in Texas. Methods: AVP immunization clinic staff champions in four urban safety-net clinics completed tailored Action Plans within the AVP-IT to guide strategy implementation, received webinar training from the research team commensurate to each AVP strategy, and participated in monthly monitoring calls with AVP-IT project staff over a 33-month period from 2022 to 2024. Results: All clinics made progress toward full implementation of AVP strategies. Interrupted time series (ITS) trend analysis demonstrated that AVP-IT implementation was associated with an immediate boost in HPV vaccine initiation rates (p < 0.001) and that long-term trends (ITS slopes) were significant for HPV, MCV4, and Tdap vaccines despite low post-COVID-19 pandemic rates (p < 0.001). Vaccination rates using raw data (mean differences) were not longitudinally significant except for older youth aged 13–17 years. Conclusions: The AVP-IT promises accessible and practical decision support to implement strategies to increase HPV vaccination rates in safety-net clinics. Scale-up in these clinics will require leadership support, technical assistance, and EHR optimization. Full article

Depression represents a leading cause of global disability, yet its pathogenesis remains incompletely understood. This review synthesizes emerging evidence highlighting the multifaceted role of Aquaporin-4 (AQP4), the central nervous system’s predominant water channel, in the pathophysiology of depression. Preclinical studies frequently report AQP4 dysregulation in depression models, characterized by reduced perivascular expression and impaired polarization in mood-relevant brain circuits. We delineate how AQP4 impairment is implicated in depression through several interconnected mechanistic pathways: (1) exacerbating glutamate excitotoxicity by disrupting astrocytic glutamate clearance; (2) impairing monoaminergic neurotransmission and synaptic plasticity; (3) potentiating neuroinflammatory cascades; (4) inducing mitochondrial functional impairment and oxidative stress; and (5) participating in hypothalamic–pituitary–adrenal (HPA) axis dysregulation by disrupting perineuronal osmotic and ionic homeostasis in response to arginine vasopressin (AVP) signaling. Furthermore, we explore the therapeutic relevance of AQP4, noting that diverse antidepressant treatments appear to partly exert their effects by modulating AQP4 expression and function. Collectively, the evidence positions AQP4 not as a solitary causative factor, but as a critical contributing component within the broader astrocyte–neuron–immune network. We therefore propose AQP4 as a promising node for therapeutic intervention, whose modulation may help counteract core pathophysiological processes in depression, offering a potential avenue for novel treatment development. Full article

To address the urgent need for high-fidelity motion data for validating navigation algorithms for Unmanned Underwater Vehicles (UUVs), this paper proposes a data generation method based on a parametric motion model. First, based on the principles of rigid body dynamics and fluid mechanics, a decoupled six-degrees-of-freedom (6-DOF) Linear and Angular Acceleration Vector (LAAV) model is constructed, establishing a dynamic mapping relationship between the rudder angle and speed setting commands and motion acceleration. Second, a segmentation–identification framework is proposed for three-dimensional trajectory segmentation, integrating Gaussian Process Regression and Ordering Points To Identify the Clustering Structure (GPR-OPTICS), along with a Dynamic Immune Genetic Algorithm (DIGA). This framework utilizes real vessel data to achieve motion segment clustering and parameter identification, completing the construction of the LAAV model. On this basis, by introducing sensor error models, highly credible Inertial Measurement Unit (IMU) data are generated, and a complete attitude, velocity, and position (AVP) motion sequence is obtained through an inertial navigation solution. Experiments demonstrate that the AVP data generated by our method achieve over 88% reliability compared with the real vessel dataset. Furthermore, the proposed method outperforms the PSINS toolbox in both the reliability and accuracy of all motion parameters. These results validate the effectiveness and superiority of our proposed method, which provides a high-fidelity data benchmark for research on underwater navigation algorithms. Full article

Wireless Sensor Networks (WSNs) are pivotal for data acquisition, yet reliability is severely constrained by routing voids induced by sparsity, uneven energy, and high dynamicity. To address these challenges, the Hybrid Acoustic-Optical Adaptive Void-handling Protocol (HAO-AVP) is proposed to satisfy the requirements for highly reliable communication in complex underwater environments. First, targeting uneven energy, a reinforcement learning mechanism utilizing Gini coefficient and entropy is adopted. By optimizing energy distribution, voids are proactively avoided. Second, to address routing interruptions caused by the high dynamicity of topology, a collaborative mechanism for active prediction and real-time identification is constructed. Specifically, this mechanism integrates a Markov chain energy prediction model with on-demand hop discovery technology. Through this integration, precise anticipation and rapid localization of potential void risks are achieved. Finally, to recover damaged links at the minimum cost, a four-level progressive recovery strategy, comprising intra-medium adjustment, cross-medium hopping, path backtracking, and Autonomous Underwater Vehicle (AUV)-assisted recovery, is designed. This strategy is capable of adaptively selecting recovery measures based on the severity of the void. Simulation results demonstrate that, compared with existing mainstream protocols, the void identification rate of the proposed protocol is improved by approximately 7.6%, 8.4%, 13.8%, 19.5%, and 25.3%, respectively, and the void recovery rate is increased by approximately 4.3%, 9.6%, 12.0%, 18.4%, and 24.2%, respectively. In particular, enhanced robustness and a prolonged network life cycle are exhibited in sparse and dynamic networks. Full article

Salinity represents a major constraint on plant development and crop productivity in wheat, which represents one of the most critical sources of dietary calories worldwide. Its detrimental effects are particularly pronounced during the early stages of growth, including seed germination and seedling establishment. Salinity tolerance is a multifaceted trait governed by several interrelated mechanisms, notably ion homeostasis, osmotic adjustment, activation of enzymatic antioxidant systems, and transcriptional regulation of ion transporter genes. In the present study, contrasting wheat genotypes exhibiting differential salinity tolerance were selected from a panel of 172 accessions evaluated under salinity stress (175 mM NaCl) and control conditions (0 mM NaCl). The objectives of the current study are to confirm the underlying physiological and molecular mechanisms conferring salinity tolerance. Key physiological and molecular parameters including Na⁺, K⁺, and P homeostasis; activities of major antioxidant enzymes; and expression profiles of the salinity-responsive ion transporter genes TaAVP1 and NHX1 were quantified in six tolerant genotypes and one susceptible genotype. The tolerant genotypes exhibited higher concentrations of Na⁺ and K⁺ and elevated activities of all antioxidant enzymes, compared with the susceptible genotype. Furthermore, the tolerant genotypes showed differential expression of TaAVP1 and NHX1: both genes were upregulated in Javelin 48 and Kandahar, whereas they were downregulated in genotype 1018d. Notably, genotype Kule demonstrated the highest Na⁺ accumulation, accompanied by markedly elevated activities of all major antioxidant enzymes, with ascorbate peroxidase and glutathione reductase increasing by 9.20-fold and 2.32-fold, respectively, under salinity stress. Based on these findings, the tolerant genotypes can be categorized into two functional groups: Javelin 48, Ghati, and 1018d (characterized by high K⁺ and salinity tolerance) are better suited to soils affected by low Na⁺ salinity, whereas Kandahar, Kule, and 1049 (characterized by high Na⁺ and sodicity tolerance) are more adapted to soils with elevated Na⁺ levels. In conclusion, the tolerant genotypes exhibited distinct, coordinated mechanisms to mitigate salinity stress, underscoring the complexity and plasticity of adaptive responses in wheat. Full article

Background: Maintaining an adequate mean arterial pressure (MAP) and cerebral perfusion pressure to ensure proper perfusion and oxygen delivery to all major organs is crucial—especially for neurosurgical patients after subarachnoid hemorrhage or traumatic brain injury—for preventing secondary brain damage or delayed cerebral ischemia. Currently, most neurosurgical intensive care units rely on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) values to guide therapy. Fluid resuscitation and norepinephrine are standard treatments for achieving a CPP between 60 and 70 mmHg; however, patients sometimes experience norepinephrine-refractory hypotension. In such cases, vasopressin is often the preferred medication; it is widely utilized and has gained interest in treating septic shock or refractory hypotension following cardiac surgery or hypovolemic shock. Recent studies have also shown the significant impact of vasopressin on resuscitation after traumatic brain injury (TBI) and its effect on CPP during ICU care. Nevertheless, little is known about how vasopressin affects cerebral perfusion and oxygenation, especially in patients with subarachnoid hemorrhage. Methods: This preliminary retrospective single-arm study examined how vasopressin affects P_btO₂ and cerebral blood flow using the non-invasive QuantixND^® device. After administering vasopressin for treating catecholamine-refractory hypotension, MAP, CPP, ICP, P_btO₂, and cerebral blood flow were measured over a 20-min period. Results: In this small cohort, vasopressin sufficiently improved MAP and CPP over a 20 min period following AVP bolus administration with a slight decline at later time points. The ICP decreased throughout this period, indicating some level of autoregulation. In contrast, cerebral blood flow did not improve despite the rise in CPP, and P_btO₂ levels remained below 20 mmHg. Conclusions: We conclude that vasopressin could be a viable option for maintaining MAP and CPP, but caution should be exercised in patients with already impaired cerebral perfusion. Furthermore, relying solely on CPP as the therapeutic guide in subarachnoid hemorrhage patients appears to be at least questionable. Full article

This study aimed to unravel the genomic uniqueness of Streptomyces chrestomyceticus ADP4 using whole-genome sequence analysis, with a focus on identifying strain-specific genes/proteins associated with a novel therapeutic source. The genome of the strain ADP4 was sequenced and assembled to a total size of 9.64 MB. A total of 8378 coding regions were identified. Strain ADP4 was found to be clustered into a clade of the species S. chrestomyceticus. Fifty-one biosynthetic gene clusters were predicted in the genome of the strain ADP4, and three of them were common to all the strains of S. chrestomyceticus. A comparative metabolic profile of S. chrestomyceticus revealed a unique metabolic protein, supporting strain-level variations. Comparative genome analysis led to the identification of the genomic sequences that were specific to the strain ADP4. These strain-specific unique sequences of ADP4 were identified across the available data, underscoring their distinct genetic identity. Among these eight functionally uncharacterized hypothetical proteins (HPs), only two could be assigned with functional attributes, wherein one of them, HP2, was ascertained to be a peptide with possible antiviral activity, underscoring its potential as a novel drug candidate for aantiviraltherapy. The structural validation and peptide–protein molecular docking have evidently demonstrated anantiviralctivity of HP2 against significant human viral pathogens, for example, HIV, SARS-CoV2, HCV, ZIKV, JEV, and DENV. Full article

Binge drinking is defined as consuming a large amount of alcohol in a short period of time, whereas hangover is a cluster of unpleasant mental symptoms and physical signs that typically manifest the next day after binge drinking. Binge drinking is a prevalent pattern of alcohol consumption, especially in adolescents, with dualistic effects on social behavior. While some studies demonstrate that a single episode of binge drinking enhances sociability and preference for social novelty, other studies indicate that repeating cycles of binge drinking and hangover can lead to persistent negative affect and consequently social withdawal. This is an integrative narrative review synthesizing human studies and animal models of binge drinking (also known as alcohol intoxication) and hangover (also known as alcohol withdrawal). The major databases consulted were PubMed, Scopus, and Web of Science. The search terms used were “binge drinking” or “hangover”and “social behavior” or “social brain” in combination with “rats”, “mice” or “humans”. Finding the missing link between structural and functional changes in the social brain in the context of binge drinking and hangover is crucial for developing novel therapeutic strategies for alcohol intoxication and withdrawal. This review focuses on changes in hypothalamic neurohormones and extrahypothalamic neurotransmitters in these states, and concludes with the statement that targeting neuropeptides such as corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) and their receptors, which are involved in both binge drinking and social behavior, may prevent repeated cycles of binge drinking and hangover from spiraling into alcohol addiction and, ultimately, social isolation. Full article

Background: Vasopressin (AVP) and its V1a receptor (V1aR) are involved in the regulation of the cardiovascular system. Limited evidence suggests that AVP may also contribute to respiratory regulation. Arterial chemoreflex is the main reflex involved in cardiorespiratory regulation and is triggered from the carotid bodies (CBs), specialized organs that detect changes in arterial blood content. Both increased activity of the vasopressinergic system and enhanced arterial chemoreflex have been found in hypertension. Here, we aimed at determining cardiorespiratory responses to AVP in normo- and hypertensive rats and the involvement of CBs and V1aRs. Methods: Experiments were performed in urethane-anesthetized adult male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Arterial blood pressure (MABP), heart rate (HR), femoral artery blood flow (FABF), minute ventilation (MV), respiratory rate (RR), and end-tidal carbon dioxide (ETCO2) were recorded. We evaluated cardiorespiratory responses to arterial chemoreflex activation with potassium cyanide, intravenous AVP, V1aR antagonist, and CB denervation. Results: In comparison to normotensive animals, SHR rats had significantly greater resting MABP, HR, MV, and enhanced pressor and ventilatory components of arterial chemoreflex. CB denervation caused insignificant changes in cardiorespiratory parameters. Intravenous administration of AVP resulted in a significant increase in MABP in both groups, which was greater in SHR rats, and in ventilatory inhibition, which was present only in SHR rats. CB denervation reduced the pressor response to AVP in normotensive rats and abolished the inhibitory effect of AVP on ventilation in SHR rats. Intravenous administration of the V1aR antagonist caused a significantly greater decrease in MABP in the hypertensive group. Only SHR rats responded with an increase in ventilation after the V1aR antagonist. Effects of AVP were abolished after blockade of V1aRs in both groups. Conclusions: Our study indicates that (i) SHR rats show augmented cardiorespiratory response to AVP, (ii) cardiorespiratory effects of AVP depend on V1aRs; and (iii) respiratory effects of AVP in the hypertensive rats appear to be primarily mediated by CBs. Full article