Search Results (247,253)

Rural communities face significant healthcare access barriers that contribute to persistent health disparities. Mobile health clinics (MHCs) have emerged as a promising strategy for expanding healthcare access, yet their effectiveness in rural settings remains understudied. The aim of this review was to examine the literature to determine what is known about access, health outcomes, and the cost-effectiveness of rural MHCs, specifically with regard to their impact on patient access and outcomes, return on investment (ROI)/financial, and program sustainability. We conducted a comprehensive search of peer-reviewed and grey literature sources. Systematic screening yielded 34 documents for full analysis. Thematic analysis was conducted across three domains: patient access, patient outcomes, and ROI/sustainability. All 34 documents provided data on patient access, with common themes including expanded service utilization, multi-service integration, overcoming geographic and transportation barriers, and improved healthcare affordability. Thirty-two documents addressed patient outcomes, reporting improvements in preventive care delivery, chronic disease management, and high patient satisfaction. Twenty-eight documents included ROI/sustainability information, with evidence suggesting cost-effectiveness particularly through emergency department visit avoidance and multi-service integration. Across the literature reviewed, the quality of evidence varied considerably, yet we concluded mobile health clinics demonstrate promise for expanding healthcare access and improving outcomes in rural populations. Key success factors include multi-service integration, diverse funding partnerships, technological integration, and strong community engagement. More rigorous research with longitudinal clinical outcome measures and robust economic analyses is needed. Full article

Background: Adaptive deep brain stimulation (aDBS) for Parkinson’s disease (PD) relies on accurate detection of beta oscillatory activity. However, electrocardiographic (ECG) artifacts frequently contaminate local field potentials (LFPs), compromising control algorithms. While offline cleaning methods exist, their feasibility for real-time operation within the strict timing constraints of current sensing-enabled devices remains unknown. Methods: We evaluated four ECG removal algorithms, template subtraction (TS), singular value decomposition (SVD), extended SVD (eSVD), and the Perceive toolbox (PR), on simulated datasets (contaminated at −30 to +20 dB) and clinical recordings from 20 PD patients. Algorithms were assessed for artifact removal quality (beta power preservation, signal-to-noise ratio) and real-time feasibility (99th percentile processing latency—P₉₉ < 50 ms). Results: Only TS and standard SVD met the real-time feasibility threshold, with TS achieving superior timing consistency (P₉₉ ≈ 10 ms). eSVD and PR proved incompatible with closed-loop requirements (P₉₉ > 90 ms). While eSVD yielded the highest artifact suppression at extreme contamination, it suffered from poor signal preservation at moderate levels. TS demonstrated the best balance, maintaining beta power accuracy within ±12% across clinically relevant contamination levels. Conclusions: TS is the recommended method for real-time aDBS applications, offering a safety-critical balance of computational efficiency and biomarker fidelity. Full article

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation, epithelial barrier disruption and immune dysfunction. Alleviating and curing these pathological manifestations is the goal of IBD treatment. Despite substantial advances in targeted immunotherapies and anti-inflammatory strategies, achieving sustained intestinal mucosal healing remains a major clinical challenge. Dynamin-related protein 1 (Drp1) is a GTPase that mediates mitochondrial fission and plays a crucial role in maintaining the dynamic balance of mitochondrial morphology and function. In IBD, Drp1 expression is frequently upregulated and continuously activated, resulting in excessive fission and fragmentation of mitochondria. This mitochondrial dysregulation contributes to ATP depletion and excessive reactive oxygen species (ROS) production, thereby exacerbating disease progression and amplifying inflammatory signaling. This review highlights the distinctive role of Drp1 as an integrative node in IBD. Specifically, we connect mitochondrial dynamics with epithelial barrier failure, immune dysregulation, inflammatory cell death, and intestinal microenvironment remodeling. We further emphasize the potential relevance of Drp1 for biomarker-based patient stratification and mechanism-informed therapeutic targeting, thereby distinguishing this review from more descriptive accounts of mitochondrial dysfunction in intestinal inflammation. Full article

Cardiac fibrosis is a central determinant of heart failure progression and arises from pathological remodeling characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. In contrast, physiological remodeling permits adaptive cardiac growth without net fibrosis. Pregnancy represents an underexplored physiological model of reversible cardiac remodeling. In response to hemodynamic load, the maternal heart undergoes hypertrophic growth that resolves postpartum, constituting a natural paradigm of fibrosis-resistant cardiac adaptation. Pregnancy and lactation are accompanied by profound endocrine and immune reprogramming of maternal tissues. We propose that this hormonal milieu orchestrates coordinated crosstalk among endothelial cells, fibroblasts, and immune cell populations to suppress profibrotic pathways and preserve extracellular matrix homeostasis. Candidate regulators include estrogen, progesterone, prolactin family peptides, relaxin, oxytocin, and components of the renin–angiotensin–aldosterone system. During the postpartum and lactational period, prolactin and oxytocin may further promote reverse remodeling. These hormones likely act by modulating local cytokine and growth factor networks that otherwise drive fibroblast activation. By focusing on non-myocyte cardiac cells and extracellular matrix dynamics, this review positions pregnancy as a translational model to uncover endogenous anti-fibrotic mechanisms and identify novel therapeutic strategies for cardiac fibrosis. Full article

Endothelial dysfunction (ED) arises in multiple pathologies, and its severity correlates with disease progression. Common ED biomarkers could provide prognostic value for associated complications. This study aims to identify shared ED biomarkers and assess their prognostic significance. Endothelial cells in culture (human microvascular endothelial cells, HMEC-1) were exposed to sera from patients in five disease groups (n = 20 patients/group)—liver cirrhosis with portal hypertension, idiopathic pulmonary arterial hypertension, placental disorders such as intrauterine growth restriction, coronary artery disease with acute myocardial infarction, and chronic kidney disease—or matched controls, in the absence/presence of anti-inflammatory (apixaban) and antioxidant (EUK134) compounds. We explored changes in: VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS). In serum samples, proteomics and metabolomics analyses (including lipids, amino acids, and polar metabolites) were performed through an extraction protocol to identify common ED biomarkers. Expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS increased in most groups versus controls (p < 0.05). Both drugs decreased all biomarker levels except eNOS (n = 6 for in vitro experiments). For serum ED biomarkers, 18 metabolites and 24 proteins showed AUC-ROC and hit rates >77.5%, and six metabolites were associated with event-free survival. These diseases share ED driven by systemic inflammatory, oxidative, and metabolic stress, are partially reversible in vitro, and are linked to biomarkers associated with clinical outcomes. Overall, ED emerges as a modifiable pathological axis with potential prognostic value. Full article

Today, microfluidics has become a revolutionary field of engineering due to its wide range of applications, including lab-on-a-chip devices, microscale biochemical reactors, drug delivery systems, and disease diagnostics. Efficient fluid mixing has been a significant challenge in these systems due to the dominance of laminar flow and low-Reynolds number conditions, where mixing relies primarily on slow molecular diffusion. It is very difficult to achieve rapid mixing and homogeneous mixing within a limited length. In this study, a bioinspired passive micromixer is developed based on the cristae architecture of mitochondria, which is known for maximizing surface area and transport efficiency in biological systems. The micromixer incorporates cristae-like microstructures within a straight microchannel to produce continuous flow deflection, stretching, and folding, thereby promoting chaotic advection without relying on external energy sources. It also includes mitochondrial granules, such as micropillars, within the channel to disrupt streamline flow. Thus, a numerical investigation was conducted to design four different micromixer geometries: conventional T-channel, and T-channels with a single, double and triple matrix of cristae. The analysis was performed in COMSOL Multiphysics, in which “Laminar flow” and “Transport of diluted species” physics were used, and a stationary study was executed. Simulations were conducted at different Reynolds numbers (Re = 0.1–100) to observe the feasibility of the proposed designs. For analysis, the mixing index and concentration profiles at the outlet and along the length were also examined. The results showed that the high cristae density channel performed well, achieving a mixing index of 95.85% at Re = 0.1 and 85.84% at Re = 100, proving that the proposed mitochondria-inspired cristae Mito-mixer delivers efficient mixing over a broad Reynolds-number range while maintaining a compact, length-efficient design. Full article

Heart inflammation and oxidative stress are pivotal pathological drivers in the pathophysiology of various cardiovascular diseases. The present study aims to investigate the beneficial effects induced by extracts derived from edible plants, such as Olea europaea, and sugar cane on heart health. In particular, we investigated the effects of a novel combination constituting Olea europaea, Scutellaria baicalensis, and policosanol extracts on heart, in in vitro and ex vivo models. Olea europaea, S. baicalensis, policosanol extracts and their combination prevented H₂O₂-induced reduction in H9c2 cell (immortalized myoblasts, isolated from rat heart tissue) viability. Moreover, pre-incubation with the combination significantly reduced H₂O₂-induced ROS levels in the same cells. Our present findings also showed that Olea europaea, S. baicalensis and policosanol extracts, as well as their combination, increased lipopolysaccharide (LPS)-induced catalase gene expression at all concentrations tested, in mouse heart specimens. In addition, we also observed that Olea europaea, S. baicalensis and policosanol extracts, as well as their combination, significantly inhibited LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-kB, and tumor necrosis factor-α gene expression, in the same experimental model. Interestingly, the combination was more effective at decreasing the mRNA levels of all pro-inflammatory markers investigated. Finally, the combination was also able to suppress LPS-induced B-type natriuretic peptide and cardiac troponin I gene expression ex vivo. In conclusion, these findings suggest that this plant-based combination could offer potential benefits for cardiovascular health and support overall heart function in humans. Full article

Grape (Vitis vinifera L.) is an important fruit crop, but its production is severely threatened by ripe rot, a fungal disease caused by Colletotrichum gloeosporioides. However, V. pseudoreticulata ‘Dongan-1’ has been reported to have significant resistance to ripe rot. To investigate the molecular basis of this resistance, we employed RNA-Seq to profile transcriptome changes in the leaves and berry skins of ‘Dongan-1’ following infection. Gene Ontology (GO) enrichment analysis suggested that differentially expressed genes (DEGs) were mainly linked to stress response, cellular processes, and metabolic processes. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs in both tissues were predominantly enriched in the plant MAPK signaling pathway, peroxisome pathway, plant–pathogen interaction pathway, and plant hormone signal transduction pathway. Notably, VpCML41 was identified as a highly induced gene. Functional characterization through heterologous overexpression in Arabidopsis thaliana and transient expression in ‘Thompson Seedless’ grape leaves demonstrated that VpCML41 enhances resistance to C. gloeosporioides. This enhanced resistance involves the coordinated regulation of salicylic acid and jasmonic acid signaling cascades. Our findings provide valuable genetic resources for understanding ripe rot resistance and offer a foundation for developing resistant grape varieties. Full article

Background/Objectives: Lymphovascular space invasion (LVSI) is an established prognostic factor in endometrial cancer, yet current risk stratification relies on a binary focal/substantial classification. Whether further substratification into a “prominent” LVSI category (≥10 involved vessels) provides independent prognostic value beyond the FIGO 2023 staging framework remains unclear. We aimed to investigate the prognostic significance and clinical outcomes regarding the extent of lymphovascular space invasion (LVSI) in patients with LVSI-positive endometrioid endometrial cancer (EEC). Methods: We retrospectively identified 94 patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I–IV EEC who underwent surgical staging. LVSI-positive cases were classified as focal (1–4 involved vessels), substantial (5–9 involved vessels), or prominent (≥10 involved vessels). Results: Of the 94 LVSI-positive patients, 58 (61.7%) had focal, 11 (11.7%) had substantial, and 25 (26.6%) had prominent LVSI. Five-year overall survival (OS) rates were 95.3%, 72.7%, and 53.0% for focal, substantial, and prominent LVSI, respectively (p < 0.001), with corresponding progression-free survival rates of 87.6%, 71.6%, and 34.3% (p < 0.001). On multivariable analysis, prominent LVSI emerged as an independent predictor of both mortality (HR 14.31, p < 0.001) and disease progression (HR 4.02, p = 0.009), retaining significance after re-assessment for FIGO 2023 stage. Tumor size > 4 cm and p53-abnormal status were also independently associated with OS. Conclusions: Prominent LVSI was independently associated with aggressive disease and poor survival in EEC; recognizing its extent as a prognostic parameter may improve both clinical management and future risk classification frameworks. As these findings are derived from a single-institution, LVSI-positive cohort with an empirically defined threshold, external validation is warranted before clinical adoption. Full article

Steatosis, characterized by excessive fat accumulation in the liver, is a significant precursor to chronic liver disease and hepatocarcinoma. This condition is influenced by multiple contributing factors such as obesity, alcohol consumption, and exposure to chemicals or drugs. Systems biology approaches including transcriptomics and metabolomics can aid in grouping chemicals according to their mode of action. In this study, we analyze transcriptomic and metabolomic data from primary human and transformed hepatocytes, respectively, to differentiate between steatotic and non-steatotic chemicals. Rather than assessing each steatotic compound individually, we pooled several steatotic chemicals in order to minimize compound-specific noise and better identify features associated with the underlying process of steatosis. Differential gene expression analysis revealed established mechanisms involved in steatosis, consistent with the recently updated adverse outcome pathway. Likewise, metabolomic data enabled clear discrimination between steatotic and non-steatotic chemicals. These findings highlight the potential of omics technologies to support chemical grouping based on insights into the molecular mechanisms that drive steatosis development. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent mucosal inflammation and dysregulated immune–metabolic responses. Koumiss, a traditional fermented mare’s milk, has long been used in ethnomedicine for gastrointestinal disorders; however, its molecular mechanisms in UC remain unclear. In this study, an integrated multi-omics approach combining network pharmacology, quantitative proteomics, and molecular docking was employed to elucidate the therapeutic mechanism of koumiss powder (KP) in a dextran sulfate sodium (DSS)-induced murine colitis model. Network pharmacology identified twelve bioactive compounds targeting fourteen UC-associated proteins, predominantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In vivo experiments demonstrated that high-dose KP significantly alleviated disease activity, improved colon shortening and histopathological injury, reduced serum TNF-α and IL-6 levels, and restored anti-inflammatory cytokines IL-4 and IL-10. Proteomic analysis further revealed activation of the PPAR signaling pathway, with significant upregulation of Plin4 and Sorbs1. Immunofluorescence staining further confirmed that KP restored the expression of PPARA and increased the levels of Plin4 and Sorbs1 in colonic tissues. Molecular docking confirmed strong binding affinities between key koumiss-derived lipid metabolites, including 13(S)-HOTrE and stearoyl ethanolamide, and PPAR-related target proteins. Collectively, these findings demonstrate that koumiss exerts protective effects against experimental UC primarily through activation of PPAR-mediated lipid metabolic and anti-inflammatory pathways. This study provides mechanistic insight into the biological activity of koumiss and highlights the value of multi-omics integration in natural product research. Full article

Background/Objectives: Dental caries is one of the most prevalent chronic diseases in childhood, disproportionately affecting socially vulnerable populations. This scoping review aimed to analyze the clinical effects of selected minimally invasive materials and approaches, specifically mouthrinses, fluoride varnishes, silver diamine fluoride, and glass ionomer-based interventions, for the prevention and management of dental caries in pediatric patients, with emphasis on public health and community-based settings. Methods: This scoping review followed the Population, Concept, and Context (PCC) framework. Electronic searches were conducted up to 23 January 2026, using tailored strategies for mouthrinses, fluoride varnishes, silver diamine fluoride (SDF), and glass ionomer cements (GICs). Randomized clinical trials (RCTs) were included. Data extraction and qualitative synthesis focused on clinical outcomes and applicability in public health contexts. Results: Fifty-five RCTs were included. Fluoride- or chlorhexidine-based mouthrinses showed potential in controlling cariogenic biofilm, with evidence primarily based on microbiological outcomes. Fluoride varnishes were associated with enamel remineralization and control of early white spot lesions, particularly in supervised programs. SDF was reported to achieve high caries’ arrest rates in cavitated dentin lesions of primary teeth, while its preventive effect on sound surfaces appeared comparable to other fluoride-based interventions. GICs were associated with acceptable clinical performance as pit-and-fissure sealants and in atraumatic restorative treatment. Conclusions: Minimally invasive dentistry (MID) approaches show promise for the prevention and management of childhood dental caries in public health and community-based settings. However, these findings should be interpreted with caution due to the heterogeneity of interventions and outcome measures, the predominance of short-term and surrogate (microbiological) outcomes, and the absence of a formal risk-of-bias assessment. As a scoping review, the synthesis is narrative in nature, which limits the ability to draw definitive conclusions. Further studies with standardized clinical outcomes and longer follow-up are needed to strengthen the evidence. Full article

Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic presented significant psychosocial challenges to intensive care unit health care workers (ICU HCW). Prior studies typically used single cross-sectional samples to focus on elements of burnout and psychological stress. We sought to serially assess quality of life and willingness to work before, during, and after the first peak of COVID-19. Methods: Two survey instruments were prospectively administered at regular intervals to multidisciplinary ICU HCWs, initiating at the local onset of COVID-19 and ending 6 months after the first peak ICU census of COVID-19 patients. Results: ICU HCWs reported high levels of compassion satisfaction, burnout, and secondary traumatic stress before, during and after the first peak of COVID-19. Motivation to work declined, and hesitation to work increased from study initiation to the peak ICU census of COVID-19 patients. Hesitation to work was greater in female HCWs and cardiothoracic ICU HCWs. Motivation to work was higher in those working in operating rooms compared to those in the ICU. Concerns about becoming infected, feelings of isolation, and exhaustion were associated with high hesitation to work. Feeling protected by the government and hospital was associated with decreased hesitation and increased motivation to work. Conclusions: ICU HCWs experienced high levels of stress throughout the first year of COVID-19, while satisfaction with work remained high. Willingness to work was associated with gender, work location, ICU subtype, concerns about infection risk, feelings of exhaustion, and feelings of institutional protection. Because the study methodology precludes causal inference and low survey response rates indicate that findings should be interpreted with caution, these results are best viewed as hypothesis-generating for future work aimed at improving stress mitigation in ICU HCWs. Full article

Background: COVID-19 is primarily a respiratory disease, but increasing evidence suggests possible oral and maxillofacial complications. This study presents a case series of post-COVID maxillary osteonecrosis (PC-RONJ) cases from western Romania and explores the possible association between SARS-CoV-2 infection, its treatment, and this complication. Methods: We conducted a multicenter retrospective case series of two patients with recent PCR-confirmed SARS-CoV-2 infection who subsequently developed maxillary osteonecrosis (ONC) between 2021 and 2023. Clinical examination, CT imaging (including 3D reconstructions), and ENT assessment were used to assess the severity of the disease. All medical records were reviewed to identify comorbidities, details of COVID-19 treatment, and the appearance of maxillofacial symptoms. Results: Both patients had been hospitalized for severe COVID-19 and treated according to the national protocol with systemic corticosteroids, oxygen therapy, anticoagulation, and antivirals. CT scans revealed marked osteolytic destruction of the maxilla and maxillary sinus walls, with extension toward adjacent facial bones. Microbiological analysis revealed a complex polymicrobial profile, including Gram-positive and Gram-negative bacteria as well as opportunistic fungal species, consistent with a chronic biofilm-associated infectious process. Patients received surgical treatment, followed by local care and, in both cases, prosthetic rehabilitation with maxillary obturators, which improved speech, chewing, and oral function. Conclusions: This case series suggests a possible association between severe COVID-19, its treatment, and subsequent maxillary osteonecrosis in susceptible patients; however, the small number of cases precludes causal inference. To our knowledge, this is the first Romanian report describing such cases in patients without prior antiresorptive therapy. These findings highlight the need for careful use of systemic corticosteroids and vigilant post-recovery monitoring of maxillofacial complications. Further studies are required to clarify the underlying mechanisms and risk factors. Full article

Neuronal activity and cerebral blood flow are tightly coupled to support the high metabolic demands of the brain. Disruption of neurovascular coupling is a defining feature of many neurodegenerative disorders such as Alzheimer’s disease, stroke, small vessel disease, Parkinson’s disease, and aging. Progress in understanding the mechanisms underlying neurovascular coupling requires experimental approaches that can simultaneously measure neuronal activity and vascular dynamics with high spatial and temporal resolution, while also enabling targeted perturbations of the system. Here, we present a methodological framework that combines chronic electrophysiological recordings with two-photon imaging of cerebral blood flow and optogenetic manipulation of the vasculature in vivo. Using a chronically implanted flexible electrode array, we obtain measurements of the single- and multi-unit spiking activity, as well as local field potentials. Concurrently, two-photon microscopy enables high-resolution measurements of vessel diameter and blood flow within individual vascular segments. In addition, optogenetic control of vascular smooth muscle cells allows for rapid and reversible manipulation of the vessel diameter through the same cranial window while simultaneously recording the neural and vascular activity. We provide detailed protocols for surgical implantation, data acquisition, and analysis, and discuss experimental considerations and limitations. This combined platform offers a powerful tool for mechanistic studies of neurovascular coupling and its dysfunction in disease models. Full article