Search Results (9,759)

Background/Objectives: Neuromedin U (NMU) is a highly conserved gene encoding a neuropeptide involved in the regulation of feeding behavior and energy homeostasis. We aimed to analyze the association between NMU genetic and epigenetic variations and cardio-metabolic parameters in an Italian population to identify the role of these variants in cardio-metabolic risk. Methods: A total of 4028 subjects were randomly selected from the Moli-sani study cohort. NMU haplotypes were estimated using seven SNPs located in the gene body and in the promoter region; DNA methylation levels in the promoter region, previously associated with lipid-related variables in the same population, were also used. Results: Among the haplotypes inferred, the haplotype carrying the highest number of minor variants (frequency 16.6%), when compared with the most frequent haplotype, was positively associated with insulin levels, HOMA-IR, and diastolic blood pressure, and negatively with HDL-cholesterol. The multivariable analysis that considered methylation levels along with their interactions with SNPs showed that increased methylation levels in two close CpG sites were associated with higher levels of lipid-related variables. Conclusions: This study supports a role for NMU as a regulator of human metabolism. This finding suggests that NMU could be a potential target for preventive interventions against coronary and cerebrovascular diseases, and that NMU genetic and epigenetic variability may serve as a biomarker for cardio-metabolic risk. Full article

Leishmaniasis, a vector-borne neglected tropical disease, affects over 6.2 million people globally. Case acquisition is increasingly recognized in the United States, and in Texas, most reported cases are locally acquired and speciated to Leishmania mexicana. We conducted a scoping literature review to systematically assess contemporary research on Leishmania in humans, animals, reservoir hosts, or vectors in Texas after 2000. Out of 22 eligible studies, the most prevalent themes were case reports, followed by studies on domestic animals, reservoirs, and vectors, with several studies bridging multiple disciplines. Climate change, urbanization, and habitat encroachment appear to be driving the northward expansion of L. mexicana, which is primarily attributed to shifts in the habitats of key vectors (Lutzomyia anthophora) and reservoirs (Neotoma spp.). Leishmania appears to be expanding into new areas, with potential for further spread. As ecological conditions evolve, strengthening surveillance and clinician awareness is crucial to understanding disease risk and improving early detection and treatment in affected communities. Full article

The ability to quantify equine kinematics is essential for clinical evaluation, research, and performance feedback. However, current methods are challenging to implement. This study presents a motion capture methodology for horses, where three-dimensional, full-body kinematics are calculated without instrumentation on the animal, offering a more scalable and labor-efficient approach when compared with traditional techniques. Kinematic trajectories are calculated from multi-camera video data. First, a neural network identifies skeletal landmarks (markers) in each camera view and the 3D location of each marker is triangulated. An equine biomechanics model is scaled to match the subject’s shape, using segment lengths defined by markers. Finally, inverse kinematics (IK) produces full kinematic trajectories. We test this methodology on a horse at three gaits. Multiple neural networks (NNs), trained on different equine datasets, were evaluated. All networks predicted over 78% of the markers within 25% of the length of the radius bone on test data. Root-mean-square-error (RMSE) between joint angles predicted via IK using ground truth marker-based motion capture data and network-predicted data was less than 10 degrees for 25 to 32 of 35 degrees of freedom, depending on the gait and data used for network training. NNs trained over a larger variety of data improved joint angle RMSE and curve similarity. Marker prediction error, the average distance between ground truth and predicted marker locations, and IK marker error, the distance between experimental and model markers, were used to assess network, scaling, and registration errors. The results demonstrate the potential of markerless motion capture for full-body equine kinematic analysis. Full article

Obstructive sleep apnea (OSA) is a sleep-related respiratory disorder characterized by partial or complete obstruction of the upper airway, typically resulting in a decrease in arterial oxygen saturation and repeated awakenings from sleep. It is the most common sleep-related respiratory disorder, affecting 9% to 38% of adults. OSA is associated with loss of tone, improper contraction of the tongue, and pharyngeal dilator muscles of the upper airway during sleep. The gold-standard treatment for moderate-to-severe OSA is continuous positive airway pressure (CPAP). However, many patients have poor long-term compliance with CPAP. Stimulation of the upper airway with electrical activation of the hypoglossal nerve has emerged as a promising treatment for patients with moderate-to-severe OSA who have failed CPAP therapy. Objectives: The present paper aims to review the literature regarding neurostimulation for the treatment of OSA. Conclusions: Hypoglossal nerve stimulation (HNS) has shown favorable success and low morbidity in the management of moderate-to-severe OSA. Full article

Today, ‘social sustainability’ is a key feature of many organisations’ environmental, social, and governance strategies, as well as underpinning sustainable development goals. The term refers to the implementation of targets such as reduced societal inequalities, the promotion of social well-being, and the practice of positive community relations. Building a meaningful, accountable, and quantifiable evidence-base from which to translate these high-level concepts into tangible and achievable goals is, however, challenging. The complexities of measuring social capital—often described as a building block of social sustainability—have been documented. The challenge lies in measuring the person, group, or collective in interaction with the context under investigation, whether that be a climate goal, an institution, or a national policy. Social identity theory is a social psychological approach that articulates the processes through which an individual internalises the values, norms, and behaviours of their contexts. Levels of social identification—a concept capturing the state of internalisation—have been shown to be predictive of outcomes as diverse as communication and cognition, trust and citizenship, leadership and compliance, and health and well-being. Applying this perspective to the articulation and measurement of social sustainability provides an opportunity to build an empirical approach with which to reliably translate this high-level concept into achievable outcomes. Full article

Background: Family caregivers are a vital yet often under-recognized part of the healthcare system. They provide essential emotional, physical, and logistical support to individuals with illness, disability, or frailty, and their contributions improve continuity of care and reduce system strain. However, many healthcare and social service providers are not equipped to meaningfully engage caregivers as partners. In Alberta, stakeholders validated the Caregiver-Centered Care Competency Framework and identified the need for a three-tiered education model—Foundational, Advanced, and Champion—to help providers recognize, include, and support family caregivers across care settings. This paper focuses on the development and early evaluation of the Advanced Caregiver-Centered Care Education modules, designed to enhance the knowledge and skills of providers with more experience working with family caregivers. The modules emphasize how partnering with caregivers benefits not only the person receiving care but also improves provider effectiveness and supports better system outcomes. Methods: The modules were co-designed with a 154-member interdisciplinary team and grounded in the competency framework. Evaluation used the first three levels of the Kirkpatrick–Barr health workforce education model. We analyzed pre- and post-surveys from the first 50 learners in each module using paired t-tests and examined qualitative feedback and SMART goals through inductive content analysis. Results: Learners reported a high level of satisfaction with the education delivery and the knowledge and skill acquisition. Statistically significant improvements were observed in 53 of 54 pre-post items. SMART goals reflected intended practice changes across all six competency domains, indicating learners saw value in engaging caregivers as partners. Conclusions: The Advanced Caregiver-Centered Care education improved providers’ confidence, knowledge, and skills to work in partnership with family caregivers. Future research will explore whether these improvements translate into real-world practice changes and better caregiver experiences in care planning, communication, and navigation. Full article

Background/Objectives: Children with severe physical and communication disabilities face many challenges. They have very limited opportunities for upright, hands-free, self-initiated mobility. Current findings in neuroscience and theories on child development suggest that self-initiated mobility can have positive cascading effects on various developmental areas, including language and communication. This study was conducted to examine the current use of hands-free support walkers with children who have severe physical and communication disabilities and use augmentative and alternative communication and to identify the benefits and problems perceived by their parents and professionals from different disciplines. Methods: Online surveys were utilized to collect information from 127 participants, including 31 parents and 96 professionals or paraprofessionals. Results: The participants reported that these children could perform various motor activities in the hands-free support walkers to achieve different goals. Benefits identified by both parents and professionals included providing a way to exercise and stay active, improving motor control, enhancing independence, and bringing enjoyment. Professionals also observed positive impacts on communication, vocalization, use of eye contact, and problem solving. Conclusions: Results suggest that children with severe physical and communication disabilities can benefit from the upright, hands-free, self-initiated mobility provided by hands-free support walkers. Clinical implications and needs for future research are discussed. Full article

The ability of the neuropeptide oxytocin to affect glial cell function is receiving increasing attention. We previously reported that oxytocin at a low nanomolar concentration could inhibit both astrocytic Ca²⁺ signals and glutamate release. Here, we investigate the ability of oxytocin receptors to couple both inhibitory and stimulatory pathways in astrocytes, as already reported in neurons. We assessed the effects of oxytocin at concentrations ranging from low to high in the nanomolar range on intracellular Ca²⁺ signals and on the glutamate release in astrocyte processes freshly prepared from the striatum of adult rats. Our main findings are as follows: oxytocin could induce dual responses in astrocyte processes, namely the inhibition and facilitation of both Ca²⁺ signals and glutamate release; the inhibitory and the facilitatory response appeared dependent on activation of the G_i and the G_q pathway, respectively; both inhibitory and facilitatory responses were evoked at the same nanomolar oxytocin concentrations; and the biased agonists atosiban and carbetocin could duplicate oxytocin’s inhibitory and facilitatory response, respectively. In conclusion, due to the coupling of striatal astrocytic oxytocin receptors to different transduction pathways and the dual effects on Ca²⁺ signals and glutamate release, oxytocin could also play a crucial role in neuron–astrocyte bi-directional communication through a subtle regulation of striatal glutamatergic synapses. Therefore, astrocytic oxytocin receptors may offer pharmacological targets to regulate glutamatergic striatal transmission, which is potentially useful in neuropsychiatric disorders and in neurodegenerative diseases. Full article

Climate change is generally having a negative impact on forest health by inducing drought stress and favouring the spread of pest species, such as bark beetles. The terrestrial monitoring of bark beetle infestation is very time-consuming, especially in the early stages, and therefore not feasible for extensive areas, emphasising the need for a comprehensive approach based on remote sensing. Although numerous studies have researched the use of optical data for this task, radar data remains comparatively underexplored. Therefore, this study uses the weekly and cloud-free acquisitions of Sentinel-1 in the Bavarian Forest National Park. Time series analysis within a Multi-SAR framework using Random Forest enables the monitoring of moisture content loss and, consequently, the assessment of tree vitality, which is crucial for the detection of stress conditions conducive to bark beetle outbreaks. High accuracies are achieved in predicting future bark beetle infestation (R² of 0.83–0.89). These results demonstrate that forest vitality trends ranging from healthy to bark beetle-affected states can be mapped, supporting early intervention strategies. The standard deviation of 0.44 to 0.76 years indicates that the model deviates on average by half a year, mainly due to the uncertainty in the reference data. This temporal uncertainty is acceptable, as half a year provides a sufficient window to identify stressed forest areas and implement targeted management actions before bark beetle damage occurs. The successful application of this technique to extensive test sites in the state of North Rhine-Westphalia proves its transferability. For the first time, the results clearly demonstrate the expected relationship between radar backscatter expressed in the Kennaugh elements K₀ and K₁ and bark beetle infestation, thereby providing an opportunity for the continuous and cost-effective monitoring of forest health from space. Full article

The Surface Water and Ocean Topography (SWOT) mission provides unprecedented high-resolution observations of sea-surface height. However, their direct use in ocean circulation studies is complicated by the presence of small-scale unbalanced motion signals and instrumental noise, which hinder accurate estimation of geostrophic velocities. To address these limitations, we developed an adaptive convolutional neural network (CNN)-based filtering technique that refines SWOT-derived sea-level observations. The network includes multi-head attention layers to exploit information on concurrent wind fields and standard altimetry interpolation errors. We train the model with a custom loss function that accounts for the differences between geostrophic velocities computed from SWOT sea-surface topography and simultaneous in-situ drifter velocities. We compare our method to existing filtering techniques, including a U-Net-based model and a variational noise-reduction filter. Our adaptive-filtering CNN produces accurate velocity estimates while preserving small-scale features and achieving a substantial noise reduction in the spectral domain. By combining satellite and in-situ data with machine learning, this work demonstrates the potential of an adaptive CNN-based filtering approach to enhance the accuracy and reliability of SWOT-derived sea-level and velocity estimates, providing a valuable tool for global oceanographic applications. Full article

Background/Objectives: Nonoperative management (NOM) of patients with locally advanced rectal cancer (LARC) who achieve a complete clinical response (cCR) to total neoadjuvant therapy (TNT) has been shown to be oncologically safe and is an attractive treatment option for patients. However, identifying responders to TNT that may benefit from nonoperative management is clinically challenging. Circulating tumor DNA (ctDNA) testing has shown promise in detecting minimal residual disease but has not yet been studied extensively within this clinical context. Methods: This is a single-institution retrospective case series study of LARC patients treated with TNT from 2019 to 2023 who underwent ctDNA testing as an adjunct to standard clinical response assessments. Results: A total of 28 patients had ctDNA testing as part of their response assessments after TNT. In total, 9 patients had positive ctDNA, and 19 patients had negative ctDNA during surveillance. Baseline characteristics of these two groups were not different. In this study, 6/9 (67%) patients who had positive ctDNA required surgery for residual rectal cancer, whereas only 4/19 (21%) patients who had negative ctDNA required surgery (p = 0.035). Conclusions: ctDNA testing has the potential to detect MRD in LARC patients treated with TNT. Full article

Background: Pulmonary involvement is the most common prognosis-related organ involvement in idiopathic inflammatory myopathy (IIM). Owing to the large number of antibodies, the evidence for lung involvement and rare antibodies is limited. In everyday clinical practice, the interpretation of positive myositis antibodies represents a challenge. Methods: This study is a retrospective monocentric analysis. The data collection regarding positive myositis antibodies and possible pulmonary involvement was carried out from July 2019 to May 2022. Data analysis revealed positive results for one of the following antibodies: EJ, PL7, OJ, PL12, Mi-2α, TIF1γ, MDA5, SAE, NXP2, SRP, Ku, PM-Scl100 and PM-Scl75. In our analysis, patients with IIM, patients with inflammatory rheumatic disease other than IIM and patients without inflammatory rheumatic disease are described. The results of high-resolution computed tomography (HRCT), pulmonary function tests, echocardiographic examinations and their associated clinical findings are examined. Results: In the entire cohort, 209 patients with positive myositis antibodies were detected. In total, 22 (10.5%) patients had interstitial lung disease (ILD) patterns on HRCT. In the subgroup of patients with IIM, a significantly higher proportion of patients with lung involvement (n = 13, 35.1%) was found than in the group with other inflammatory rheumatic diseases (IRDs) (n = 6, 6.7%) or in the group without IRDs (n = 3, 3.7%). When the antibody groups were considered, the PL12-positive patients had the largest proportion of ILD (42%), followed by the MDA5-positive patients (40%). Conclusions: In patients with IIM, myositis antibodies are highly relevant for assessing the risk of lung involvement. In groups with other IRD or without IRD, antibody detection does not represent this high relevance for lung involvement. A differentiated assessment of the various MSAs or MAAs detected, as well as clinical parameters, allows for further important risk assessment for prognosis-relevant lung involvement. Full article

Background/Objectives: Benign paroxysmal positional vertigo (BPPV) is the most prevalent vestibular disorder encountered in clinical settings and is highly responsive to evidence-based diagnostic and therapeutic interventions. However, variations in practice patterns among physician specialties can compromise timely diagnosis and effective treatment. Understanding these variations is essential for improving clinical outcomes and standardizing care. This study aimed to assess the diagnostic and treatment practices for BPPV among Ear, Nose, and Throat (ENT) specialists, neurologists, general practitioners, and family physicians in Saudi Arabia and to examine how these practices are influenced by clinical experience and patient case exposure. Methods: A cross-sectional, questionnaire-based study was conducted between April 2023 and March 2024 at King Khalid University, Abha, Saudi Arabia. A total of 413 physicians were recruited using purposive sampling. Data were analyzed using IBM SPSS version 24.0. Parametric tests, including one-way ANOVA and chi-square tests, were used to assess differences across groups. A p-value of <0.05 was considered statistically significant. Results: Overall, all physician groups exhibited limited adherence to guideline-recommended positional diagnostic and therapeutic maneuvers. However, ENT specialists and neurologists demonstrated relatively higher compliance, particularly in performing the Dix–Hallpike test, with 46.97% and 26.79% reporting “always” using the maneuver, respectively (p < 0.001, Cramér’s V = 0.22). Neurologists were the most consistent in conducting oculomotor examinations, with 73.68% reporting routine performance (p < 0.001, Cramér’s V = 0.35). Epley maneuver usage was highest among neurologists (86.36%) and ENT specialists (77.14%) compared to family physicians (50.60%) and GPs (67.50%) (p = 0.044). Physicians with 11–15 years of experience and >50 BPPV case exposures consistently showed a greater use of diagnostic maneuvers, repositioning techniques, and guideline-concordant medication use (betahistine 76.67%; p < 0.001). Continuing medical education (CME) participation and the avoidance of unnecessary imaging were also highest in this group (46.67% and 3.33%, respectively; p < 0.001). Conclusions: Significant inter-specialty differences exist in the management of BPPV in Saudi Arabia. Greater clinical experience and higher case exposure are associated with improved adherence to evidence-based practices. Targeted educational interventions are needed, particularly in primary care, to enhance guideline implementation. Full article

Bone is the most frequent site of distant metastasis in advanced prostate cancer (PCa), contributing substantially to patient morbidity and mortality. Hypoxia, a defining feature of the solid tumour microenvironment, plays a pivotal role in driving bone-tropic progression by promoting epithelial-to-mesenchymal transition (EMT), cancer stemness, extracellular matrix (ECM) remodelling, and activation of key signalling pathways such as Wingless/Integrated (Wnt) Wnt/β-catenin and PI3K/Akt. Hypoxia also enhances the secretion of extracellular vesicles (EVs), enriched with pro-metastatic cargos, and upregulates bone-homing molecules including CXCR4, integrins, and PIM kinases, fostering pre-metastatic niche formation and skeletal colonisation. In this review, we analysed current evidence on how hypoxia orchestrates PCa dissemination to bone, focusing on the molecular crosstalk between HIF signalling, Wnt activation, EV-mediated communication, and cellular plasticity. We further explore therapeutic strategies targeting hypoxia-related pathways, such as HIF inhibitors, hypoxia-activated prodrugs, and Wnt antagonists, with an emphasis on overcoming therapy resistance in castration-resistant PCa (CRPC). By examining the mechanistic underpinnings of hypoxia-driven bone metastasis, we highlight promising translational avenues for improving patient outcomes in advanced PCa. Full article

In the trauma resuscitation literature, there are inconsistent definitions of what constitutes massive transfusion and a unit of blood, complicating the use of transfusion cut-points to declare futility. This is problematic as it can lead to the inefficient use of blood products, further exacerbating current blood product shortages. Previous studies have used various transfusion cut-points per hour to define futility in retrospective analyses but have not accurately defined futility at the bedside due to patient survival even at large rates and volumes of blood transfused. In an attempt to use transfusion cut-points as a marker to help define futility, guidelines have been proposed to limit blood product waste in transfusions for severely bleeding trauma patients, such as Suspension of Transfusion and Other Procedures (STOP) for patients older than 15 and the Futility of Resuscitation Measure (FoRM), used to determine futility in patients older than 60. In an effort to construct effective bedside futile resuscitation criteria with 100% positive predictive value and specificity, this review proposes the use of specific blood component transfusion cut-points combined with parameters from both STOP and FoRM to allow for a comprehensive and accurate method of declaring futility in severely bleeding trauma patients. Full article