Search Results (50,874)

Background: Mobile health has been increasingly integrated into tuberculosis care to support patient education, communication, and treatment engagement. However, evidence remains limited regarding whether positive engagement with mHealth is associated with knowledge, attitudes, and practices among patients with multidrug-resistant tuberculosis. This study aimed to examine the association between positive mHealth engagement and knowledge, attitude, practice, and total KAP among patients with multidrug-resistant tuberculosis, and to evaluate the psychometric properties of the engagement score used as the primary exposure variable. Methods: A cross-sectional study was conducted among patients with multidrug-resistant tuberculosis. A positive mHealth engagement score was constructed from 12 mHealth-related items after harmonizing item directionality so that higher scores indicated more favorable engagement. The 12 items reflected five behavioural domains: intensity of use, ease and acceptability of use, functional engagement (communication with providers, access to health information, and perceived benefit for disease self-management), continuity of use, and barriers to sustained engagement. The composite score was computed as the mean of the 12 standardised items, with higher values indicating more positive engagement. Internal consistency was assessed using Cronbach’s alpha and corrected item–total correlations, and structural validity was explored using principal component analysis. Adjusted linear regression models were used to examine associations between the engagement score and Knowledge, Attitude, Practice, and total KAP scores, controlling for age, sex, and occupation. Sensitivity analyses were performed after excluding a poorly performing item, and tertile analyses were used to assess dose–response patterns. Results: The positive mHealth engagement score showed good internal consistency, with a Cronbach’s alpha of 0.852. One item demonstrated poor psychometric performance, and Cronbach’s alpha increased to 0.864 after its exclusion. The data were suitable for dimensionality assessment, with a Kaiser–Meyer–Olkin value of 0.870 and a significant Bartlett’s test. Principal component analysis identified a dominant first component explaining 43.29% of the total variance. Using the refined score, higher positive mHealth engagement was significantly associated with higher Knowledge scores (β = 2.06; 95% CI: 1.28–2.85; p < 0.001), higher Attitude scores (β = 4.68; 95% CI: 3.30–6.06; p < 0.001), and higher total KAP scores (β = 6.68; 95% CI: 4.62–8.74; p < 0.001), whereas no significant association was observed for the Practice score (β = −0.07; 95% CI: −0.63 to 0.49; p = 0.804). In tertile analyses, Knowledge, Attitude, and total KAP scores increased significantly across engagement levels, while Practice scores did not. Conclusions: Positive mHealth engagement was associated with better knowledge, attitudes, and overall KAP among patients with multidrug-resistant tuberculosis, but not with practice. These findings are associative; the cross-sectional design does not permit causal conclusions. The engagement score demonstrated good reliability and acceptable structural validity and may be a useful summary measure for evaluating patient interaction with mHealth interventions in tuberculosis care. Integrated strategies combining mHealth with clinical follow-up, adherence counseling, and structural support may be needed to translate informational and attitudinal gains into practice change. Full article

The effects of pre-harvest application of Bacillus velezensis LYB73 on rhizosphere soil properties, microbial communities, fruit quality, and flavor-related traits in different peach cultivars are still not well understood. In this study, three peach cultivars, “Jinxia” (JX), “Wanhujing” (WHJ), and “Youpantao” (YPT), were subjected to B. velezensis LYB73 treatment or a sterile-water control under field conditions. Rhizosphere bacterial (16S rRNA) and fungal (ITS) communities were analyzed by high-throughput sequencing. Soil physicochemical properties, fruit nutritional and functional components, antioxidant capacity, and electronic sensory traits were also evaluated. The application of LYB73 was associated with lower rhizosphere soil pH (5.52–6.82) and changes in several soil nutrient-related parameters. Microbial community analyses indicated that LYB73 treatment was accompanied by shifts in the composition of rhizosphere bacterial and fungal communities. For example, the relative abundance of Pseudomonadota increased in the JX treatment group, while Ascomycota was enriched in the JX and YPT treatment groups. At the genus level, taxa such as Gemmatimonas, Saitozyma, and Cephalotrichum showed increased relative abundance in some treated groups. Compared with the control, LYB73-treated fruits generally showed higher levels of reducing sugars, titratable acids, amino acids, total phenols, total flavonoids, and antioxidant capacity. The magnitude of these responses varied among cultivars: JX showed larger increases in total phenols, total flavonoids, and DPPH scavenging activity, WHJ showed a greater increase in amino acids and ABTS scavenging activity, and YPT showed the largest increase in superoxide anion scavenging activity. Electronic sensory analysis further suggested that LYB73 treatment affected taste and aroma-related traits, although the responses differed among cultivars. Correlation analysis showed that several dominant microbial genera were significantly associated with soil properties, fruit quality indices, and sensory indicators. Overall, these results suggest that pre-harvest application of B. velezensis LYB73 may influence rhizosphere microecology and fruit quality in a cultivar-dependent manner, providing preliminary support for its potential use in peach production. Full article

Chemotherapy-induced cognitive impairment (CICI), often referred to as “chemobrain,” is a common and sometimes persistent consequence of cancer treatment, characterized by deficits in memory, attention, executive function, and processing speed; it disproportionately affects older adults and women, suggesting a role for aging- and sex-related biological factors, including estrogen depletion. This work examines the potential of dietary phenolic compounds as multi-target modulators of mechanisms underlying CICI. A narrative synthesis of preclinical and clinical evidence was conducted, focusing on major phenolic subclasses (flavonoids, phenolic acids, stilbenes, lignans, and secoiridoids) and their effects on pathways implicated in chemotherapy-related neurotoxicity. The reviewed data indicate that phenolic compounds can influence redox balance, neuroinflammatory responses, mitochondrial function, synaptic plasticity, and estrogen-related signaling, with effects that appear to be structure-dependent; however, evidence remains heterogeneous and largely derived from experimental models rather than studies in humans. Overall, the current findings suggest that selected phenolic compounds could mitigate vulnerability to CICI, particularly in higher risk groups such as older individuals and women with low estrogen levels. These compounds represent promising and safe adjunctive strategies, although further well-designed clinical studies are needed to confirm their efficacy and clarify the underlying mechanisms. Full article

Drying in granular porous media is governed by coupled thermal and hydraulic processes that can be substantially modified by biological activity. This proof-of-concept study investigated how surface heating and fungal colonization influence the evolution of thermal conductivity (λ) and matric suction (ψ) as functions of volumetric water content ${\theta }_v$ in Ottawa 20/30 sand. Four treatments were examined: sterile sand at 22 °C (T1), sterile sand at 28 °C (T2), fungal-amended sand with 10% biomass and 9-day incubation (T3), and fungal-amended sand with 15% biomass and 30-day incubation (T4). Samples were instrumented to monitor ${\theta }_v$, λ, and ψ during controlled evaporation using synchronized HYPROP and VARIOS measurements on the same specimen. Across all treatments, λ increased with ${\theta }_v$ (that is, λ declined as drying progressed), and ψ reflected the transition from hydraulically connected to disconnected pore water. Heating shortened the drying time but did not materially change the form of the λ–${\theta }_v$ relationship or generate strong matric gradients in sterile sand. Low biomass (T3) produced thermal and hydraulic responses comparable to the heated sterile control (T2), indicating limited pore-scale modification at early colonization. In contrast, high biomass (T4) widened the effective saturation range, maintained low and nearly uniform ψ across depth, and exhibited the steepest mid-range λ–${\theta }_v$ slope with a higher peak λ (~4 Wm⁻¹K⁻¹), consistent with hyphae and extracellular polymers stabilizing thin water films. A soil water retention curve (SWRC) analysis using the van Genuchten model further indicated increased water retention and delayed air entry with an increasing fungal biomass, with approximate air-entry values increasing from ~1.8 kPa (T3) to ~3.0 kPa (T4). Tests were terminated upon tensiometer cavitation rather than complete gravimetric dryness, constraining observations at very low ${\theta }_v$. These results indicate that heating primarily affects the rate of drying, whereas fungal networks alter the pathway by preserving hydraulic and thermal continuity at relatively high ${\theta }_v$. This behavior suggests a potential role of bio-mediated structuring in influencing near-surface thermo-hydraulic processes relevant to energy foundations, soil covers, and desiccation management in biologically active or bio-engineered soils. Full article

Forest tree provenances have evolved diverse and complex mechanisms to acclimate to changes in environmental conditions. Pedunculate oak (Quercus robur L.), along with other European tree species, is increasingly exposed to the adverse effects of climate change, particularly prolonged drought periods and severe drought stress. Understanding the species’ capacity to acclimate to expected environmental changes requires knowledge of key functional traits linked to drought tolerance, such as leaf structure and gas exchange. To explore the acclimation mechanisms of pedunculate oak provenances to repeated drought events, a study was conducted under controlled conditions with plants from nine provenances spanning a north–south gradient across eastern Europe, from Estonia to Italy. The study consisted of two parts: first, leaf structural traits were analyzed after three years of experimentally induced drought by comparing drought and control treatments; second, both treatments were subjected to subsequent drought to analyze differences in gas exchange trait responses. Results demonstrated ecotypic differentiation among provenances in morphological, but not in gas exchange traits, suggesting that provenance adaptedness to drier habitats is more closely associated with structural than physiological traits. Provenances originating from drier habitats showed lower specific leaf area but also different acclimation to repeated drought events, including a stronger reduction in stomatal density and a smaller increase in leaf dry matter content, compared to provenances from more humid habitats. Gas exchange acclimation occurred through a shift in the strategy of photosynthesis down-regulation. These findings emphasize the importance of investigating multiple functional traits rather than focusing solely on individual key traits. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with limited therapeutic options, a high mortality rate, and poor overall survival, necessitating the development of new therapeutic and diagnostic strategies. This study investigated the potential of plasma-derived small extracellular vesicles (sEVs) as a source of molecular biomarkers associated with the treatment response. Methods: Plasma samples were obtained from patients with locally advanced and borderline resectable PDAC at baseline and following neoadjuvant chemotherapy, either FOLFIRINOX (5-FU [fluorouracil], leucovorin, oxaliplatin, and irinotecan) or GEM-ABRAX ( gemcitabine plus nab-paclitaxel), followed by stereotactic body radiation therapy (SBRT). sEVs were isolated from plasma at baseline, after neoadjuvant chemotherapy, and following SBRT, and were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), nano-flow cytometry, and real-time PCR (RT-PCR). Results: The isolated sEVs exhibited an average size of <200 nm, expressed canonical exosome markers (CD63 and CD9), and exhibited pancreatic cancer (PanC)-associated markers, including cholecystokinin A receptor (CCK-AR) and carbohydrate antigen 19-9 (CA19-9). The sEV cargo included several PanC-associated microRNAs (miRNAs). Notably, the expression profiles of these miRNAs demonstrated interpatient variability, though a subset of miRNAs showed statistically significant changes following treatment. Conclusions: These findings support the feasibility of sEV isolation and molecular profiling from patient plasma and warrant further investigation as a potential source of biomarkers in pancreatic cancer. Full article

Aesthetic medicine is shifting from symptomatic correction to biological structural restoration. Regenerative aesthetics represents a frontier in dermatology, focusing on the restoration of the skin microenvironment to enhance cellular vitality and tissue resilience. Central to this approach is the concept of “skin bed preparation”, a strategic priming phase designed to optimize the physiological terrain before the delivery of advanced aesthetic interventions. This review explores the molecular and cellular mechanisms by which skin bed preparation modulates the extracellular matrix (ECM) and the dermal niche to maximize the efficacy of subsequent treatments and promote long-term skin longevity. Evidence suggests that biostimulatory priming utilizing senolytics, senomorphics, mitochondrial, and/or epigenetic rejuvenators rehabilitates the fibroblast–collagen interactome. By reducing oxidative stress and chronic low-grade inflammation, these preparatory steps transition the skin from a catabolic to an anabolic state. This metabolic reset ensures that subsequent procedures, such as laser therapy, injectable fillers, encounter a responsive cellular environment, resulting in superior collagen induction and prolonged clinical outcomes. Optimizing the skin microenvironment via regenerative aesthetics is not merely an adjunctive step but a fundamental requirement for therapeutic success. Integrating skin bed preparation into clinical protocols provides a synergistic framework that enhances immediate procedural results while addressing the underlying hallmarks of skin aging, ultimately redefining the trajectory of skin health and longevity. Full article

Fungi of the genus Trichoderma have attracted attention because of their potential activity against phytophagous mites; however, information regarding their non-target effects on predatory mites remains limited. This study evaluated the effects of spore suspensions and secondary metabolites of Trichoderma afroharzianum Tr132 and Trichoderma virens Tvr2 on three predatory mite species widely used in biological control programs: Phytoseiulus persimilis, Neoseiulus californicus, and Amblyseius swirskii. Predator egg hatchability and adult mortality were assessed under laboratory conditions. Spore suspension treatments did not significantly affect egg hatchability, which remained high (97–99%) across all predator species. In contrast, secondary metabolites slightly reduced egg hatchability to 94–96%, compared with 99.5% in the control. Exposure to spore suspensions caused moderate mortality in adult predatory mites, increasing from 10 to 13% at 3 days post-application (dpa) to 15–19% at 6 dpa. Secondary metabolites produced higher mortality that increased over time, reaching 9–11% at 1 dpa, 17–18% at 3 dpa, and up to 22–25% at 6 dpa. Mortality responses were similar among predator species. Overall, Trichoderma applications had minimal effects on predator egg hatchability but caused moderate mortality in adult predatory mites, particularly following exposure to secondary metabolites. These findings highlight the importance of evaluating the compatibility of Trichoderma-based products with beneficial predatory mites before their integration into IPM programs. Full article

A circulating tumor DNA (ctDNA) assay is an emerging non-invasive diagnostic approach providing real-time insights into the heterogeneous tumor molecular landscape of advanced prostate cancer, overcoming the limitations of traditional tissue biopsies and PSA. Detection methods include droplet digital PCR, next-generation sequencing, and new epigenomic and fragmentomic strategies (investigational) designed to improve sensitivity in cases of low ctDNA shedding. While ctDNA’s role in localized prostate cancer is limited, it offers significant prognostic value in metastatic cases, where high ctDNA levels correlate with shorter survival. Additionally, longitudinal ctDNA monitoring can predict treatment response and identify emerging resistance mechanisms, including androgen receptor alterations associated with androgen receptor pathway inhibitor therapy and BRCA reversion mutations linked to PARP inhibitors. Importantly, liquid biopsy enables genomic characterization to inform treatment decision-making, particularly in clinical scenarios where tissue biopsy is challenging, such as bone-only disease. However, the widespread clinical implementation of ctDNA analysis is hindered by several analytical challenges, including low sensitivity in localized disease and low disease burden, and the risk of false positives due to clonal hematopoiesis. Furthermore, greater efforts are required to standardize pre-analytical workflows and post-analytical data interpretation and reporting across institutions. This review aims to summarize the evolving role of cfDNA technologies in localized and advanced prostate cancer, highlighting their prognostic and predictive value and their role in uncovering mechanisms of treatment resistance. Full article

Reparative dentin formation is a defensive response that restores a mineralized barrier to protect the dental pulp following various stimuli, such as bacterial invasion, tooth preparation, or restorative materials. However, reparative dentin is limited, and to avoid pathological calcification or pulp canal obliteration, mineral deposition must be restricted to the injured area and temporally restrained once the barrier is reestablished. This suggests the existence of negative regulators that can halt odontoblastic differentiation; however, such inhibitory regulators remain incompletely defined. Spondin-1 (SPON1) is an extracellular matrix protein known to regulate bone homeostasis and act as a negative regulator of bone mass; however, the effects of SPON1 on odontoblastic differentiation of dental pulp stem cells (DPSCs) remain unclear. This study aimed to analyze the effects of SPON1 on odontoblastic differentiation of human DPSCs (HDPSCs). SPON1 was expressed in the odontoblastic layer and dental pulp tissue, and its expression was significantly decreased at the beginning of reparative dentin formation in rats. Treatment with SPON1 inhibited odontoblastic differentiation of HDPSCs by blocking the expression of non-phosphorylated β-catenin, while neutralizing SPON1 significantly enhanced odontoblastic differentiation of HDPSCs. These findings suggest that SPON1 functions as a negative regulator of odontoblastic differentiation during reparative dentin formation. Full article

The objective of this study was to evaluate the potential of age Opuntia-derivated digestate (OpDcm) as a nutrient source for photosynthetic microbial consortia (PMC), aiming to reduce dependence on mineral media and promote the valorization of locally available biomass in arid and semi-arid regions. Batch cultures were performed in bubble column photobioreactors (BCPBR) and open raceway (ORPBR) photobioreactors using different proportions of OpDcm and BG11₀ to assess biomass production, chlorophyll a dynamics, and physicochemical responses of a PMC dominated by Nostoc sp. Chemical characterization showed that OpDcm contained higher levels of K, Ca, Mg, and Mn than BG11₀, providing a robust ionic matrix for initial growth; however, potential limitations in P, Mg, and Fe were identified. In both BCPBR and ORPBR systems, OpDcm demonstrated nutrient compositions that stimulated biomass production in the PMC at levels comparable to those achieved with BG11₀ medium. Statistical analyses showed that specific treatments, particularly T1 (10% OpDcm in BCPBR) and T3 (10% OpDcm + 2.5% BG11₀ in ORPBR), produced biomass yields similar to or higher than those obtained with the conventional BG11₀ medium. However, chlorophyll a concentration was lower in OpDcm treatments due to limited light transmission and micronutrient constraints. The N–NH₄⁺ dynamics in BCPBR and ORPBR exhibited pronounced variability among the evaluated culture media, spanning from negligible changes (<1 mg L⁻¹) over the entire cultivation period to sustained ammonium production rates of 2–3 mg L⁻¹ day⁻¹. Morphological analysis confirmed a consortium dominated by Nostoc sp., supported by pH values within the optimal range (8–9). Overall, the use of age-Opuntia-derived digestates demonstrated it can serve as a partial or total substitute for a low-cost nutrient source for cyanobacterial cultivation, underscoring their relevance to circular bioeconomy strategies for producing photosynthetic biomass. Full article

Background/Objectives: Bipolar disorder affects about 40 million people worldwide, and the greatest burden of the disease is associated with depressive episodes. About 25% of patients experience drug-resistant depression, in which standard treatment turns out to be insufficient, and monotherapy often does not bring full remission. Despite the use of second-generation antipsychotics, the effectiveness of therapy in TRBD remains limited, which necessitates rational polypharmacotherapy and augmentation strategies. The paper discusses the receptor mechanisms of drug combination, current therapeutic regimens and new interventions such as ketamine acting on the glutamate anergic system. The aim was to synthetically compare the efficacy and safety of available augmentation strategies and polypharmacotherapy. Methods: The material consists of published clinical, observational and randomized trials on pharmacotherapy of drug-resistant bipolar depression, including atypical neuroleptics, ketamine, pramipexole, modafinil, lamotrigine, celecoxib and memantine. The authors analyze receptor mechanisms, neurobiological data and clinical trial results, comparing them with current definitions of TRBD according to ISBD and CINP. Biomarker data, such as the Systemic Immune-Inflammation Index, and the results of neuroimaging and metabolomic studies were also used in the work. Results: The analysis showed that atypical neuroleptics showed limited efficacy and high rates of side effects, while ketamine has the fastest and most pronounced antidepressant effect with a low risk of phase change. Pramipexole has shown promise in terms of long-term efficacy, but its use reduces the high risk of induction of mania and impulse control disorders. Celecoxib as an anti-inflammatory therapy significantly increased response and remission rates compared to escitalopram alone, and memantine showed only an early, short-term antidepressant effect. The results highlight that TRBD requires targeted polypharmacotherapy, with the most promising directions being glutamatergic modulation and anti-inflammatory therapies. Conclusions: Drug-resistant bipolar depression requires a departure from classical monotherapy in favor of rational, mechanistically justified polypharmacotherapy, targeting complex monoaminergic, glutamatergic and neuroinflammatory disorders. Available data indicate that ketamine has the greatest clinical potential among the current strategies, characterized by a rapid onset of action and a favorable safety profile compared to atypical neuroleptics or dopamine agonists. Modulation of inflammatory processes with the use of celecoxib also has promising results, which highlights the importance of biomarkers and personalization of therapy. However, further, large, and well-designed studies are needed to unambiguously determine optimal treatment strategies for TRBD and to verify the effectiveness of new pharmacological interventions. Full article

The aim of this study was to analyze the effect of concomitant use of cannabigerol (CBG) and 3-O-ethylascorbic acid (EAA) on changes in the proteome of UVA-irradiated skin melanocytes, with particular emphasis on adduct formation between lipid peroxidation products and metabolically important proteins. Proteomic analysis allowed the identification of 1248 proteins with statistically significantly changed expression following melanocytes irradiation and/or incubation with CBG/EAA. The top 25 proteins with the most strongly differentially abundant expression included proteins involved in cell protection/antioxidant response, as well as pro-inflammatory and proapoptotic signalization. Moreover, in melanocytes irradiated with UVA, the levels of lipid peroxidation product, 4-hydroxynonenal (4-HNE) and its protein adducts were increased, as well as significant changes in the profile of proteins modified by 4-HNE were observed. CBG and EAA, especially when used together, largely reverse these effects. This study for the first time demonstrated the combined effect of CBG and EAA on the proteome of melanocytes after their exposure to UVA radiation, which applies to both changes in protein expression and intracellular signaling based on proteins modified by 4-HNE. It can be suggested that CBG and EAA may provide melanocytes with effective protection against the effects of oxidative stress and perhaps even protect the skin from carcinogenesis. Full article

Parkinson’s disease (PD) is characterized by progressive nigrostriatal degeneration and striatal dysfunction, yet its metabolic remodeling remains incompletely defined. Here, untargeted GC–MS metabolomics was used to investigate the effects of standardized Brazilian green propolis on the striatal metabolic profile in the 6-hydroxydopamine (6-OHDA) rat model. Discriminant metabolites, including suberic acid, gluconic acid, heptadecane, and tartaric acid, distinguished experimental groups, capturing key features of the metabolic response to dopaminergic injury and treatment. Suberic acid emerged as a prominently modulated metabolite, potentially linked to alterations in lipid catabolism associated with mitochondrial–peroxisomal pathways. Propolis treatment attenuated the elevation of suberic acid, accompanied by a reduction in gluconic acid levels, suggesting a metabolic profile linked to pathways involved in redox balance and glucose handling. Given previous reports identifying heptadecane as a hydrocarbon constituent of volatile propolis fractions, complementary GC-Q-TOF analyses demonstrated that heptadecane was absent from the administered extract, despite its consistent association with propolis-treated groups. Metabolic changes were accompanied by attenuation of nigrostriatal dopaminergic neurodegeneration and improved motor performance. Together, these findings delineate a striatal metabolic signature associated with Brazilian green propolis and identify suberic acid as a key metabolite linked to neuroprotection in experimental Parkinsonism. Full article

Ofloxacin (OFL) and sulfamethoxazole (SMX) are common co-occurring antibiotic contaminants in aquatic environments, yet their long-term combined toxicity to freshwater fish remains poorly elucidated. In this study, adult mosquitofish (Gambusia affinis) were used as a model to investigate histopathological alterations, oxidative stress responses, gene expression, and gut microbiota changes after 30 days of exposure to environmentally relevant concentrations of OFL and SMX (0 ng/L, 50 ng/L, 1 μg/L, and 20 μg/L), either individually or in combination. The results showed that both single and combined exposures induced liver and intestinal damage. Oxidative stress responses exhibited clear tissue specificity, with activation of antioxidant defenses in the liver, whereas the intestine was mainly characterized by decreased SOD and GST activities, as well as reduced MDA content. Changes in gene expression were relatively limited, with significant alterations observed only in hepatic sod2 and hsp90 and intestinal hsp70 in certain treatment groups. Gut microbiota analysis showed that OFL exerted a stronger disruptive effect than SMX, as reflected by increased alpha diversity, reduced abundance of core genera, and functional remodeling, whereas combined exposure triggered weaker microbial community restructuring relative to single exposures. Overall, OFL and SMX induced tissue-specific toxicity in mosquitofish by causing tissue injury, oxidative stress imbalance, and gut microbiota dysbiosis, with OFL showing the stronger overall effect. Full article