Search Results (579)

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

Psychological stress and dietary behavior are interdependent forces that greatly influence mental and physical health. Thus, both what and how we eat impact our well-being. Maladaptive eating patterns, such as eating in response to emotional cues rather than physiological hunger, have become increasingly common amid modern stressors and an ultra-processed food environment. This narrative review synthesizes interdisciplinary findings from nutritional psychiatry, microbiome science, and behavioral nutrition to explore how stress physiology, gut–brain interactions, and dietary quality shape emotional regulation and eating behavior. It highlights mechanisms (e.g., HPA-axis dysregulation, blunted interoception, and inflammatory and epigenetic pathways) and examines the evidence for mindful and intuitive eating; phytochemical-rich, whole-food dietary patterns; and the emerging role of precision nutrition. Trauma-informed approaches, cultural foodways, structural barriers to healthy eating, and clinical implementation strategies (e.g., interprofessional collaboration) are considered in the context of public health equity to support sustainable mental wellness through dietary interventions. Ultimately, restoring a healthy relationship with food positions nutrition not only as sustenance but as a modifiable regulator of affect, cognition, and stress resilience, central to mental and physical well-being. Full article

An explorative study was conducted to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (SPP-004) in 10 pediatric patients with Leigh syndrome (LS) aged 3–24 months in 10 institutions between December 2014 and July 2019. The patients were randomized and allocated to the SPP-004 or placebo group for a 12-week double-blind period, followed by a 12-week open-label period with SPP-004 and then a long-term study of up to 180 weeks. The efficacy and safety were evaluated using the Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) and adverse events (AEs), respectively. No significant differences were found between groups in NPMDS scores, but prolonged SPP-004 treatment stabilized or improved scores. During the initial double-blind phase, the serum lactate levels increased in the placebo group but not in the SPP-004 group. Over the period of prolonged treatment with SPP-004, the average serum lactate level gradually decreased to a normal level. One patient died due to heart failure, presumably due to an underlying disease. Overall, 7 out of 10 patients received SPP-004 without developing severe AEs until the termination of the long-term study. Given the severe symptoms and poor prognosis of pediatric LS, NPMDS scores were indicative of stabilization in pediatric LS patients treated with SPP-004. Full article

Background: Psychological problems post-stroke can negatively impact stroke survivors. Although general psychological services exist (e.g., NHS Talking Therapies), access remains limited, particularly for individuals with post-stroke communication and cognitive impairments. Stroke service staff report low confidence in managing psychological distress. This study is the first to explore the barriers and facilitators to implementing a novel intervention package comprising a cross-service care pathway and staff training to enhance post-stroke psychological provision. Methods: Staff from stroke and mental health services in four UK regions, recruited through purposive sampling to ensure diversity of services and professional roles, participated in semi-structured interviews or focus groups, guided by the Theoretical Domains Framework (TDF), before and after implementation of the intervention package. Pre-implementation interviews/groups identified anticipated barriers and facilitators to implementation and training needs, informing the development of site-specific intervention packages; post-implementation interviews/groups explored experienced barriers, facilitators and perceptions of the intervention. Interviews underwent thematic analysis using the TDF. Results: Fifty-five staff participated pre-implementation and seventeen post-implementation, representing stroke (e.g., nurse, physiotherapist, consultant) and psychology (e.g., counsellor, psychological therapist) roles across acute, rehabilitation, community, and voluntary services. Challenges anticipated pre-implementation included: limited specialist post-stroke psychological support; low staff confidence; and fragmented service pathways. Post-implementation findings indicated increased staff knowledge and confidence, enhanced screening and referral processes, and stronger inter-service collaboration. Implementation success varied across sites (with some sites showing greater ownership and sustainability of the intervention) and across staff roles (with therapy staff more likely than nursing staff to have received training). Conclusions: Effective implementation of an intervention package to increase psychological provision post-stroke requires staff engagement at all levels across all services. Staff investment influenced ownership of the intervention package, beliefs about priorities and overall enhancement of service capability. Full article

Background and Objectives: This study explored the lived experiences of individuals with post-COVID condition (PCC) who participated in a 12-week exercise rehabilitation and recovery programme (PCCRRP) delivered by a professional football club community trust (FCCT). The aim was to understand the effects of the programme on physical function and quality of life (QoL). This study aims to address the gap in the literature of a lack of qualitative research exploring the experiences and perspectives of individuals engaging in exercise and physical activity as part of their recovery from PCC. Furthermore, it seeks to provide in-depth participant accounts to better understand outcome-level data. Methods: A qualitative approach was employed, involving semi-structured interviews with seven participants (mean age of 52 ± 8.54 years, with ages ranging from 45 to 60 years) following the 12-week PCCRRP to explore perceived changes in physical function and QoL. Thematic analysis was used to analyse the interview data, including participants’ narratives on their QoL experiences. Results: Participants reported improvements in exercise capacity, fatigue, and breathlessness, leading to enhanced physical function and QoL. They also experienced improvements in emotional well-being, including increased confidence and reduced anxiety. The programme’s focus on tailored exercise plans empowered participants to manage their symptoms and regain control over their lives. Conclusions: The PCCRRP delivered by an FCCT had positive effects on the physical function and QoL of individuals with PCC. This highlights the potential of FCCTs in providing effective rehabilitation and support for individuals with PCC. Full article

Background: Leigh’s Disease is a rare mitochondrial disorder primarily affecting the central nervous system, with frequent secondary cardiac manifestations such as hypertrophic and dilated cardiomyopathies. Early detection of cardiac complications is crucial for patient management, but manual interpretation of cardiac MRI is labour-intensive and subject to inter-observer variability. Methodology: We propose an integrated deep learning framework using cardiac MRI to automate the detection of cardiac abnormalities associated with Leigh’s Disease. Four CNN architectures—Inceptionv3, a custom 3-layer CNN, DenseNet169, and EfficientNetB2—were trained on preprocessed MRI data (224 × 224 pixels), including left ventricular segmentation, contrast enhancement, and gamma correction. Morphological features (area, aspect ratio, and extent) were also extracted to aid interpretability. Results: EfficientNetB2 achieved the highest test accuracy (99.2%) and generalization performance, followed by DenseNet169 (98.4%), 3-layer CNN (95.6%), and InceptionV3 (94.2%). Statistical morphological analysis revealed significant differences in cardiac structure between Leigh’s and non-Leigh’s cases, particularly in area (212,097 vs. 2247 pixels) and extent (0.995 vs. 0.183). The framework was validated using ROC (AUC = 1.00), Brier Score (0.000), and cross-validation (mean sensitivity = 1.000, std = 0.000). Feature embedding visualisation using PCA, t-SNE, and UMAP confirmed class separability. Grad-CAM heatmaps localised relevant myocardial regions, supporting model interpretability. Conclusions: Our deep learning-based framework demonstrated high diagnostic accuracy and interpretability in detecting Leigh’s disease-related cardiac complications. Integrating morphological analysis and explainable AI provides a robust and scalable tool for early-stage detection and clinical decision support in rare diseases. Full article

Cell membrane capacitance (C_m) is a potential biomarker that reflects the structural and functional integrity of cell membranes. It is essential for physiological processes such as signal transduction, ion transport, and cellular homeostasis. In clinical practice, C_m can be determined using bioimpedance spectroscopy (BIS), a non-invasive technique for analysing the intrinsic electrical properties of biological tissues across a range of frequencies. C_m may be relevant in various clinical fields, where high capacitance is associated with healthy and intact membranes, while low capacitance indicates cellular damage or disease. Despite its promise as a prognostic indicator, several knowledge gaps limit the broader clinical application of C_m. These include variability in measurement techniques (e.g., electrode placement, frequency selection), the lack of standardised measurement protocols, uncertainty on how C_m is related to pathology, and the relatively low amount of C_m research. By addressing these gaps, C_m may become a valuable tool for examining cellular health, early disease detection, and evaluating treatment efficacy in clinical practice. This review explores the fundamental principles of C_m measured with the BIS technique, its mathematical basis and relationship to the biophysical Cole model, and its potential clinical applications. It identifies current gaps in our knowledge and outlines future research directions to enhance the understanding and use of C_m. For example, C_m has shown promise in identifying membrane degradation in sepsis, predicting malnutrition in anorexia nervosa, and as a prognostic factor in cancer. Full article

This study sought to clarify the role of after-death communication in resilience in grief. The primary research question guiding this study was: In what way do experiences of after-death communication inform the cultivation of gratitude and compassion as part of the grieving process? For Study 1, measures of grief, continuing bonds, compassion, and gratitude were administered to a diverse demographic pool (N = 329). Bivariate correlational analysis revealed strong correlations among the total scores of the four surveys. Of the 329 participants, 67.2% (n = 221) identified as having experienced after-death communication in some form, while 32.8% (n = 108) claimed that they did not. A series of one-way ANOVAs revealed that those identifying as having after-death communication and a spiritual practice showed significantly higher scores on all measures. Study 2 was a grounded theory study that conducted interviews with people claiming a significant after-death communication experience (N = 44). Results supported the survey data, suggesting that after-death communication was a catalyst and facilitator of grief that enhanced spirituality, shifted or enhanced belief structures, and reduced death anxiety. Conclusions support the recognition of after-death communication as a possible vehicle for enhanced grief resilience and spirituality. Full article

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. As a critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high-throughput structure-based computational screening using ensemble docking for small-molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein. Prior knowledge of the contact sites from binary complex studies and experimental work was incorporated into the docking studies. The top 20 scoring ligands from the in silico studies after post analysis were subjected to in vitro functional assays. Among these compounds, the ligand with the second-highest calculated binding affinity experimentally showed an ~84% inhibitory effect on IL6-induced STAT3 reporter activity at 10 μM concentration. This finding may pave the way for designing small-molecule inhibitors of hIL-6 of therapeutic significance. Full article

Many macrofungi are impractical or impossible to culture. Consequently, DNA for long-read sequencing required for the assembly of high-quality genomes must be isolated from samples taken from the environment. Collection is often in remote locations, limiting the options for stabilising samples to methods that do not require refrigeration. Fungi contain species-specific arrays of metabolites that may complicate purification techniques and call for judgement to be made to apply appropriate modifications to the DNA extraction protocol in specific cases. The protocols and commentary we describe are informed by the preparation of DNA from a range of Australasian ectomycorrhizal and saprotrophic macrofungi. We collect samples into isopropanol at ambient temperature and employ a strategy of chromatin isolation followed by the sequential removal of unwanted molecular components to purify DNA. Full article

Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills. Full article

This study explores the potential of calcium carbide residue (CCR) as an alternative activator for ground granulated blast-furnace slag (GGBS) to reduce reliance on ordinary Portland cement (OPC) in mortar production. A series of OPC-GGBS-CCR ternary binders were prepared and evaluated for their fresh and mechanical properties over various curing periods. The findings showed that mortars’ fresh and mechanical characteristics were significantly improved with longer curing times, suggesting CCR’s potential to efficiently activate GGBS, thereby benefiting the environment and economy. Significant enhancements in compressive strengths were observed after 7 days of curing, with increases of 44%, and 69–144% for OPC and OPC-GGBS-CCR ternary binders, respectively, while the utilization of activated binders led to flexural strength growth compared to three days of curing, with improvements of 70–173% for OPC-GGBS-CCR ternary binders, respectively. Microstructural analyses confirmed accelerated hydration and increased product formation due to CCR’s calcium content. An optimal mix ratio of OPC:GGBS:CCR = 1:1:0.5 demonstrated mechanical properties comparable to OPC mortars after 28 days, highlighting CCR’s potential for sustainable cementitious materials. Full article

Background/Objectives: Developing next-generation mRNA-based seasonal influenza vaccines remains challenging, primarily because of the relatively low immunogenicity of influenza B hemagglutinin (HA) antigens. We describe a systematic vaccine development strategy that combined vector and antigen design optimization. Methods: Novel untranslated region (UTR) sequences and a hybrid poly(A) tail were used to increase plasmid stability and mRNA expression. Fusion proteins containing HA antigens linked by T4 foldon domains were engineered to enhance the immune responses against influenza B HA antigens and to permit the expression of multiple HA ectodomains from a single mRNA species. The vaccine performance was verified in a traditional encapsulated lipid nanoparticle (LNP) formulation that requires long-term storage at temperatures below −15 °C as well as in a proprietary thermo-stable LNP formulation developed for the long-term storage of the mRNA vaccine at 2–8 °C. Results: In preclinical studies, our next-generation seasonal influenza vaccine tested alone or as a combination influenza/COVID-19 mRNA vaccine elicited hemagglutination inhibition (HAI) titers significantly higher than Fluzone HD, a commercial inactivated influenza vaccine, across all 2024/2025 seasonal influenza strains, including the B/Victoria lineage strain. At the same time, the combination mRNA vaccine demonstrated superior neutralizing antibody titers to 2023/2024 Spikevax, a commercial COVID-19 comparator mRNA vaccine. Conclusions: Our data demonstrate that the multimerization of antigens expressed as complex fusion proteins is a powerful antigen design approach that may be broadly applied toward mRNA vaccine development. Full article

Background: Recreational nasal cocaine use (RNCU) presents a significant challenge for rhinologists due to cocaine-induced midline destructive lesions (CIMDLs). This clinical consensus statement (CCS) offers guidelines for diagnosing, assessing, and managing both proven and suspected cases of CIMDL (including those without a prior RNCU history). It aims to support clinicians in addressing these complex cases effectively. Methods: An international, multidisciplinary panel of 18 specialists employed a three-round modified Delphi-method survey to evaluate statements covering CIMDL management issues such as definition, clinical evaluation and diagnosis, initial management approaches, and surgical management of complications and reconstructions. This study primarily targets otorhinolaryngologists. Results: Out of 44 evaluated statements, 20 achieved strong consensus, 20 reached consensus, 3 approached near-consensus, and 1 failed to achieve consensus. Consensus-covered areas included the definition of CIMDL, clinical evaluations, first-line management, and management of complications. However, reconstructive techniques remained a contentious topic. Conclusions: In the absence of extensive data, this CCS establishes a management framework for CIMDL, significantly bridging a knowledge gap. It highlights the need for standardized assessments, multidisciplinary cooperation, and customized follow-up care for patients with CIMDL. Considering the widespread use of cocaine, physicians should consistently consider the possibility of RNCU when encountering chronic inflammatory lesions in the sinonasal tract. Full article

Weed management is a persistent challenge in Southeast Asian rice production, particularly in direct-seeded rice (DSR), due to the diversity of weed species and variable field and environmental conditions that can compromise weed control, necessitating innovative solutions. An integrated weed seed impact mill (iWSIM) reduces weed seed banks by destroying weed seeds during the harvest process. This mixed study is the first to fully explore the applicability of iWSIM technology in Southeast Asian rice systems, focusing on both combine harvester and iWSIM specifications and operation, determinants of efficacy, and field and harvest conditions. Weed seed bank reduction with an iWSIM depends on several factors, including weed seed retention and subsequent capture by the combine at harvest, weed seed separation into the chaff fraction, and the iWSIM’s efficacy against weed seeds captured in the chaff fraction. Observations from Southeast Asia indicate variable seed retention among key weed species, presenting challenges for harvesting strategies and iWSIM effectiveness. To optimize the iWSIM efficacy, recommendations include larger fields to reduce the weed seed produced on bunds, achieving complete early-season weed control, lowering the harvest header height to about 15 cm to capture more weed seeds, cleaning mechanism adjustments to ensure weed seeds are retained in the chaff fraction, and greater combine harvester engine power to allow a lower header height and power the iWSIM. The estimated weed control benefits of the iWSIM should also be weighed against additional equipment operating costs. iWSIM technology holds promise as part of a sustainable solution for weed control in Southeast Asian rice, contingent upon further region-specific research and adaptation. Full article