Search Results (33,060)

Antimicrobial resistance (AMR) constitutes a critical and escalating global public health challenge, severely limiting the potential of existing antimicrobial drugs and escalating infection-associated morbidity and mortality rates. This analysis focuses on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are prioritized by the World Health Organization (WHO) and represent a significant cause of nosocomial infections due to their extensive drug resistance. We provide an in-depth review of the global prevalence and specific antibiotic-resistant mechanisms of these pathogens. Due to the decline in the traditional antibiotic development pipeline, accelerated development of alternative therapeutic strategies is essential. The review comprehensively discusses innovative non-traditional therapies currently being explored to bypass traditional antibiotic limitations, such as phage therapy, antimicrobial peptides (AMPs), anti-virulence therapies, fecal microbiota transplantation (FMT), and targeted CRISPR-based approaches. Addressing the ESKAPE challenge requires a concerted, multi-sectoral strategy guided by the One Health principle, focusing on enhancing public awareness, improving surveillance and research, optimizing judicious antibiotic use, and cultivating sustainable investment in novel interventions. Full article

Background/Objectives: COVID-19 vaccine resistance was detrimental to herd immunity and worsened COVID-19 morbidity and mortality during outbreaks. Despite more evidence showing reactionary behavior among residents exposed to vaccine mandates, little research has been conducted on the effects of state proof-of-vaccine (POV) mandate bans in the United States (US). We sought to investigate the causal effects of POV mandate bans, overall and stratified by policy passage via executive order or state legislature, on first-dose COVID-19 vaccinations. Methods: In the contiguous US, 21 states enacted POV mandate bans from 8 February 2021–25 October 2021. Using a geographic regression discontinuity design, we selected treatment and control counties within 150 miles of the POV mandate ban state border. The resulting sample was 4612 county-observations and 2466 unique counties. We conducted two-way fixed-effects estimation to compare changes in weekly, first-dose COVID-19 vaccinations among individuals <65 years old before and after POV mandate ban enactment between treatment and control counties. Results: Among executive order POV mandate ban counties, we saw an additional increase in weekly, first-dose COVID-19 vaccinations following POV mandate ban enactment when compared to controls. There was an additional 38.2% increase in Weeks 1–2, 40.6% in Weeks 3–4, 41.3% in Weeks 5–6, and 43.9% in Weeks 7–8. Conclusions: While seemingly counterintuitive, these findings follow Psychological Reactance Theory. Once the perceived threat to freedom was removed, reactance to COVID-19 vaccinations declined and constituents received the COVID-19 vaccine of their own volition. Future public health efforts should consider potential reactance to mandatory policies and tailor efforts to community values. Full article

Background: Antimicrobial resistance (AMR) is a growing global health threat, disproportionately affecting low- and middle-income countries such as Sudan. Conflict-related health system disruption has further intensified inappropriate antibiotic use and weakened stewardship capacity. Objective: This narrative review synthesizes contemporary evidence on antibiotic prescribing practices in Sudan, with emphasis on ambulatory care, and examines their implications for AMR control in the context of ongoing conflict. Methods: A non-systematic, structured narrative review was conducted successfully. PubMed, Google Scholar, WHO/EMRO databases, and Sudan’s National Action Plan (NAP) materials were examined for literature published between January 2010 and December 2025. Peer-reviewed research, government guidelines, surveillance reports, and gray literature were among the eligible sources. A total of 78 studies were included after titles, abstracts, and full texts were screened. Two reviewers independently confirmed the data extraction, and the synthesis aligned with SANRA guidelines. Results: Antibiotic prescribing in Sudan is frequently inappropriate, particularly in ambulatory and community settings, where empirical treatment, polypharmacy, and extensive use of Watch antibiotics are common. Alignment with WHO AWaRe recommendations remains suboptimal. Recent clinical and molecular evidence demonstrates increasing multidrug resistance among Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus, including ESBL production and emerging carbapenemase genes (e.g., NDM 1, IMP 1). Conflict-related disruptions—such as reduced laboratory capacity, supply chain breakdown, and unregulated community dispensing—have further accelerated AMR. Pilot stewardship interventions show promise but remain limited in scale. Conclusions: Inappropriate antibiotic use in Sudan is driven largely by ambulatory and community practices and has been exacerbated by conflict. Strengthening stewardship beyond hospitals, enforcing prescription-only regulations, operationalizing the AWaRe framework, and aligning empirical therapy with local resistance patterns are critical for mitigating AMR in Sudan and similar conflict-affected settings. Full article

Background: Cancer remains a major global health challenge, with treatment efficacy often limited by drug resistance and adverse effects. Drug repurposing offers promising opportunities for developing novel anticancer strategies. This study evaluated the cytotoxic, antiproliferative, and pro-apoptotic effects of metformin and caffeine, administered individually and in combination, in human cancer cell lines, as well as their potential interaction mechanisms. Methods: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), and colorectal carcinoma (HT29) cell lines were treated with metformin (0.05–50 mM) and caffeine (0.5–5 mM), either alone or in combination, for 24 and 48 h. Cell viability and proliferation were assessed using Trypan Blue and sulforhodamine B (SRB) assays. Apoptosis was analyzed by Annexin V/propidium iodide flow cytometry, and p53 expression in HeLa cells was determined by ELISA. Statistical analysis was performed using a one-way ANOVA followed by Tukey’s post hoc test. Results: Metformin induced dose- and time-dependent cytotoxicity in all tested cell lines, with the lowest IC₅₀ values observed in HeLa and A549 cells after 48 h (2.28 and 3.30 mM, respectively; p < 0.05). Caffeine showed moderate antiproliferative activity, with the strongest effects observed at 2.03 mM in HeLa cells and 2.01 mM in HT29 cells (p < 0.05). The combined treatment produced effects that varied depending on both the cell line and exposure time. At earlier time points, transient synergistic effects were observed in certain cell lines, particularly HeLa cells; however, these effects were not sustained over time. With prolonged exposure, the interaction shifted predominantly toward antagonistic effects, indicating the reduced overall efficacy of the combination compared with the expected additive outcomes. Increased apoptosis and elevated p53 expression further supported the activation of tumor-suppressive pathways. Conclusions: Metformin exhibited significant anticancer activity in vitro, supporting its potential repurposing in oncology. However, the addition of caffeine did not uniformly enhance its efficacy and appeared to exert context-dependent effects. Further in vivo studies are required to confirm the clinical relevance of these findings. Full article

Anxiety disorders are disabling and treated with cognitive-behavioral or exposure-based psychotherapy. However, many patients remain symptomatic, fail to remit, relapse, or discontinue treatment. This narrative review examined whether psychotherapy non-response, defined here as persistent clinically significant anxiety symptoms, avoidance, or functional impairment after an apparently adequate psychotherapy trial, may reflect mismatch between therapeutic mechanisms and the dominant processes maintaining anxiety, and aimed to develop a usable taxonomy of mechanistic non-response. This structured narrative review followed SANRA principles. PubMed/MEDLINE, Scopus, PsycINFO, Web of Science, and the Cochrane Library were searched for peer-reviewed literature published from 1 January 2000 to 30 April 2026, including selected earlier landmark studies. Clinical, experimental, neurobiological, psychophysiological, process, and theoretical evidence were synthesized narratively. Psychotherapy mechanisms were organized around inhibitory learning, cognitive reappraisal, attentional modulation, emotion regulation, avoidance reversal, and interpersonal learning. Anxiety maintenance was multilevel, involving threat neurocircuitry, stress-related learning conditions, intolerance of uncertainty, attentional threat capture, safety behaviors, avoidance reinforcement, developmental adversity, and attachment insecurity. Non-response was framed as mismatch between the dominant maintaining process and the therapeutic mechanism expected to modify it. Six failure modes were identified: impaired inhibitory learning, cognitive rigidity/intolerance of uncertainty, stress-related learning impairment, attentional dysregulation, attachment-related barriers, and chronic avoidance dominance. Psychotherapy non-response in adult anxiety disorders should prompt mechanistic reformulation rather than repetition of the same intervention or labeling as treatment resistance. The taxonomy links recognizable failure signatures to mechanism-matched adaptations: redesigned exposure, uncertainty-focused work, attentional interventions, sequencing when arousal or sleep impairs learning, relational repair, and reduction in avoidance contingencies. The narrative review provides a concise clinical taxonomy and practical mechanism-matched adaptations to guide reformulation and treatment redesign after psychotherapy non-response in routine care. The taxonomy supports mechanism-matched reformulation after psychotherapy non-response and requires prospective validation. Full article

Contamination of water bodies by emulsified gasoline hydrocarbons, particularly BTEX compounds (benzene, toluene, ethylbenzene, and xylenes), represents a critical environmental challenge due to their toxicity and resistance to conventional treatment methods. In this study, carbonized biosorbents derived from rice husk (CRH) and walnut shell (CWS) were developed for efficient removal of emulsified gasoline from water. The materials were prepared via carbonization under CO₂ atmosphere (300–800 °C), enabling simultaneous carbonization and activation. Structural and surface properties were characterized using Brunauer–Emmett–Teller (BET) analysis, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and X-ray fluorescence spectroscopy (XRF). The results demonstrated a strong dependence of adsorption performance on carbonization temperature, with maximum removal efficiencies of 90.2% (CRH-600) and 96.5% (CWS-700). The superior performance of CWS-700 was associated with its highly developed hierarchical pore structure (up to 670 m² g⁻¹), increased carbon content, and enhanced hydrophobicity. Kinetic studies revealed pseudo-second-order behavior, with equilibrium achieved within 25–30 min at near-neutral pH. Gas chromatographic analysis confirmed the complete removal of BTEX and light hydrocarbons (C1–C9) using CWS-700, highlighting its high selectivity toward aromatic compounds. The adsorption mechanism was attributed to the synergistic effect of micropore filling, hydrophobic interactions, and π-π interactions with aromatic hydrocarbons. The obtained results demonstrate that biomass-derived carbon materials, particularly walnut shell-based sorbents, are promising low-cost candidates for the treatment of complex water systems contaminated with emulsified petroleum hydrocarbons. Full article

Gastrointestinal parasitism remains a major constraint in sheep production, and increasing anthelmintic resistance has stimulated interest in plant-based alternatives. This exploratory study evaluated the antiparasitic effect and preliminary biochemical safety of Chenopodium chilense Schrad., a plant species, in sheep from southern Chile. Thirty adult female Criollo Araucana sheep were allocated to five groups (n = 6): two groups received commercial anthelmintics, and three groups received oral C. chilense at 0.5, 1.0, or 2.0 g of “Paico powder” per kg of body weight. Fecal egg counts were monitored over a three-week follow-up period using the McMaster technique. Serum AST, GGT, ALP, total protein, albumin, total cholesterol, and triglycerides were evaluated before and after treatment in the C. chilense groups. Lower doses of C. chilense were associated with modest numerical reductions in fecal egg counts, whereas the highest dose showed greater variability and lower apparent efficacy. However, no statistically significant overall treatment effect was detected. In an exploratory analysis, parasite type was associated with variation in post-treatment egg counts. Biochemical analyses did not show a consistent dose-dependent pattern compatible with overt hepatotoxicity. These results suggest that C. chilense may have preliminary potential as a complementary phytotherapeutic candidate, but larger studies with improved sampling design, standardized phytochemical characterization, and greater statistical power are needed. Full article

EML4-ALK-positive lung cancer represents an important molecular subtype of non-small-cell lung cancer (NSCLC) that initially responds to ALK inhibitors but invariably develops resistance, highlighting the need for novel targeted therapeutic strategies. Death receptors DR4 and DR5 are frequently upregulated in malignancies and can selectively induce tumor cell apoptosis upon binding TRAIL. ISZ-sTRAIL, a trimer-stabilized soluble TRAIL fusion protein, exhibits potent antitumor effects via DR4/DR5 signaling activation. However, the expression status of DR4/DR5 in EML4-ALK-positive NSCLC cells and the therapeutic potential of targeting this pathway remain poorly defined. In this study, we evaluated DR4/DR5 protein expression in EML4-ALK-positive NSCLC cells and investigated the antitumor effect of ISZ-sTRAIL produced in an Escherichia coli expression system. Our results showed that DR4 and DR5 were abundantly expressed in EML4-ALK-positive NCI-H2228 and NCI-H3122 cells compared with normal human bronchial epithelial 16HBE cells. Furthermore, ISZ-sTRAIL significantly suppressed the proliferation of NCI-H2228 and NCI-H3122 cells, with IC₅₀ values of 4.51 ± 0.22 nM and 14.98 ± 3.34 nM, respectively, while showing low cytotoxicity toward normal 16HBE cells (IC₅₀ > 1 μM). Moreover, ISZ-sTRAIL induced caspase-dependent apoptosis in both cell lines via activation of extrinsic and intrinsic pathway, and these effects were markedly abrogated by the pan-caspase inhibitor Z-VAD. These findings identify DR4/DR5 as a potential therapeutic target and provide preclinical evidence for the development of TRAIL-based strategies in the treatment of EML4-ALK-positive NSCLC. Full article

Background/Objectives: Tuberculosis (TB) treatment adherence remains suboptimal globally, contributing to relapse, transmission, and drug-resistant TB. Adherence is a culturally embedded behavioral process shaped by psychological readiness, social relationships, and structural conditions. This study aimed to validate a culturally grounded counseling model integrating the Sunrise Model of transcultural nursing and the Information–Motivation–Behavioral Skills (IMB) framework for TB treatment adherence in Kupang City, Indonesia. Methods: A cross-sectional study enrolled 172 pulmonary TB patients across all 11 primary healthcare centers in Kupang City (June–September 2025). A validated questionnaire measuring eight transcultural determinants, culturally grounded counseling (mediator), and adherence (outcome) was developed through expert validation, cognitive interviewing, and pilot testing. Structural Equation Modeling–Partial Least Squares (SEM-PLS) tested structural and mediation relationships via bootstrapped indirect effects (p < 0.05). Results: Reliability (CR: 0.842–0.959; ρA: 0.791–0.957), convergent validity (AVE: 0.577–0.921), and discriminant validity (all HTMT < 0.85) were confirmed. The model showed strong explanatory power (R² = 0.649 for adherence; SRMR = 0.074). Culturally grounded counseling was positively associated with adherence (β = 0.245, p = 0.003) and statistically mediated five antecedent–adherence relationships, including full mediation for economic conditions. Cultural values and lifestyle showed the strongest counseling association (β = 0.345, p < 0.001). Conclusions: Cross-sectional evidence supports a culturally grounded counseling model for TB adherence in diverse settings. Causal conclusions require longitudinal and interventional validation. The model offers a foundation for nurse-led intervention development and multi-site validation. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed obesity treatment, producing substantial weight loss during active therapy. However, real-world effectiveness may be limited by gastrointestinal adverse events, reduced dietary intake, fat-free mass loss as part of total weight reduction, and weight regain after discontinuation. Methods: This narrative review synthesizes current pharmacological, nutritional, gastrointestinal, body-composition, and implementation evidence to propose an evidence-informed nutrition-first framework for patients receiving incretin-based therapy for obesity. Results: We translate pharmacologic mechanisms into practical dietary strategies, including protein prioritization, structured meal patterns, hydration and fiber management, symptom-targeted interventions, resistance-training support, and maintenance planning. Because direct trials of structured nutrition interventions in GLP-1RA- or dual incretin-treated populations remain limited, several recommendations are extrapolated from the broader obesity, caloric restriction, body-composition, gastrointestinal, and expert-consensus literature. Conclusions: Integrating structured nutrition care into pharmacotherapy pathways may help address meal-related symptom burden, support protein and fluid adequacy, identify patients at higher nutritional or body-composition risk, and prepare patients for long-term weight-management behaviors. Embedding practical nutrition management within multidisciplinary obesity care may help translate pharmacologic efficacy into durable, patient-centered outcomes. Full article

In recent years, diseases caused by species of the genus Campylobacter have increased, due to improvements in identification methods, but also because, as part of global travel and trade, these species have spread to countries where no cases had previously been reported. The methodologies for their identification, whether classic through culture media and morphological characteristics, or using molecular biology or even proteomics techniques, play a fundamental role in establishing their diagnosis and providing timely treatment. Likewise, epidemiology will help guide this diagnosis when dealing with poorly defined diarrhoea, as well as the control and prevention of these infections. Similarly, expanding information on the relationship between these species and Guillain-Barré syndrome will lead to a better understanding and timely identification. We must not forget that both intrinsic and acquired antimicrobial resistance are key factors to consider for the successful treatment of infections caused by Campylobacter species. Full article

Enzyme-Induced Carbonate Precipitation (EICP) represents a sustainable advancement in geotechnical engineering for stabilizing fine-grained soils (e.g., silt). Utilizing plant-derived urease (~12 nm) to catalyze urea hydrolysis, this technique generates calcium carbonate (CaCO₃) for soil reinforcement. Unlike Microbially Induced Carbonate Precipitation (MICP), EICP overcomes microbial size constraints (0.5–3 µm) by penetrating soil micropores, enabling uniform cementation. Its innovative single-phase low-pH method achieves >98% calcium conversion efficiency, yielding 6.41 MPa unconfined compressive strength (UCS) in sand—a 92.97% improvement over MICP. EICP demonstrates versatility: enhancing soil strength (up to 650% for silt), erosion resistance (wind erosion modulus increased ~20-fold), anti-seepage performance (permeability reduced from 10⁻⁶ to <10⁻⁹ cm/s), and heavy metal immobilization (>99%). However, challenges include unstable crystal morphologies (e.g., excessive vaterite), urease stability/cost constraints, and environmental concerns related to NH₃ emissions from urea hydrolysis. The manuscript acknowledges these emissions’ impacts and introduces mitigation strategies: ammonia capture technologies, optimized dosing protocols, and exploration of alternative N-sources. Long-term durability data under complex field conditions remain insufficient. Ongoing research addresses these gaps through nucleating agents (dried skim milk, biochar), enzyme immobilization, process optimization, and byproduct treatment. As a low-carbon technology with targeted mitigation measures, EICP advances environmentally conscious soil stabilization practices. This study presents a comparative narrative analysis of EICP’s performance and challenges, integrating laboratory findings and field applications. Full article

Background: Vasculogenic mimicry (VM) is a tumor-driven vascularization strategy in which aggressive cancer cells form perfusable, endothelium-independent channels that support tumor growth, metastasis, and therapy resistance. VM is prevalent in triple-negative breast cancer (TNBC), but within this group of tumors, VM heterogeneity is underexplored. Likewise, VM competence and its relationship to classical endothelial angiogenesis (EA) remain incompletely understood. Methods: Here, as a proof of concept, we combine functional analysis of three molecularly distinct TNBC cell lines with a panel-wide DepMap transcriptomic survey to characterize VM heterogeneity. Results: Using an in vitro tube formation assay, we show that the VM-competent TNBC cell lines MDA-MB-231 and MDA-MB-231-4175 form robust 3D vessel-like networks in a matrigel matrix, whereas the VM-incompetent line MDA-MB-468 does not. As a control, we use an immortalized endothelial cell line, 3B-11, that forms classical EA vessel-like networks. Moreover, we visualize VM (Laminin-5⁺) and EA (CD31⁺) markers in vessel-like networks of VM-competent TNBC xenografts using immunohistochemical staining and show that while they are distinctly labeled, they can also coexist to form mosaic-like vessels. Then, we use DepMap-based transcription profiles and reveal that VM competence is associated with a distinct signature. Interestingly, VM and EA transcription profiles partially overlap, yet they also remain transcriptionally distinct, with inferred mechanistic divergence, with VM being more associated with cancer cell stemness (CSC), epithelial-to-mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling programs and EA being more associated with vessel strength. In addition, VM-competent TNBC cells display migration patterns and transcriptomic features consistent with endothelial-like mechanosensitivity. Conclusions: Together, these findings indicate that VM is a distinct, heterogeneous, and therapy-relevant state in TNBC that complements classical angiogenesis. Finally, the mechanistic distinction between VM and EA programs made here will motivate future studies on dual-targeting strategies that inhibit both vascularization processes while also motivating future studies on VM for precision treatment in TNBC. Full article

The global citrus industry is under severe threat from devastating diseases, including Huanglongbing (HLB), caused by Candidatus Liberibacter asiaticus (CLas), and Citrus tristeza disease, caused by Citrus tristeza virus (CTV). Establishing efficient pathogen elimination techniques is crucial for developing virus-free citrus nursery systems and helps facilitate the prevention and control of devastating diseases. This study systematically evaluated the multiple effects of hot water treatment and plant growth regulator application on bud germination, pathogen elimination, antioxidant enzyme activities, and CsWUS expression in citrus scion. The results showed that moderate hot-water treatment at 40 °C for 5 min promoted bud germination, while higher temperatures or extended durations were inhibitory. Both 6-benzylaminopurine (6-BA) and melatonin (MT) significantly enhanced germination, with 50 mg/L 6-BA and 100 μM MT being most effective. All treatments significantly enhanced pathogen elimination and increased the activities of antioxidant enzymes SOD, POD, and CAT, with melatonin concentrations of 100 μM and above reducing CLas and CTV titers by over 93.64% and 96.07%. Furthermore, hot-water treatment and MT, but not 6-BA, upregulated the expression of the virus-resistance-related gene CsWUS. A combined treatment of hot water and MT did not yield synergistic benefits. In conclusion, melatonin treatment, particularly at 100 μM, optimally balances high bud germination with effective pathogen elimination, likely through activating antioxidant defenses and CsWUS-mediated immunity. This study provides a practical and efficient strategy for citrus pathogen-free seedling production. Full article

Colorectal cancer (CRC) progression stems from dynamic metabolic crosstalk between malignant cells and the tumor microenvironment (TME). Among stromal components, cancer-associated fibroblasts (CAFs) have emerged as pivotal metabolic drivers rather than mere structural elements. Specifically, evidence indicates that mitochondrial reprogramming in CAFs significantly orchestrates tumor growth, therapeutic resistance, and immune evasion in CRC. This review synthesizes recent insights into how CAF mitochondrial dynamics and metabolic reprogramming dictate CRC biology. We first examine the functional diversity of CAF subpopulations and their distinct mitochondrial requirements. We then contrast mitochondrial dynamics—including fission–fusion balance and mitophagy—between CRC cells and CAFs, highlighting how tumor-derived signals modulate stromal mitochondrial function. We systematically evaluate key regulatory pathways of CAF mitochondrial reprogramming, including TGF-β/HIF-1α, ROS-NF-κB, PI3K–AKT–mTOR, AMPK–PGC-1α, YAP/TAZ mechanotransduction, and mtDNA-mediated cGAS–STING signaling. Furthermore, we discuss how remodeled CAF mitochondria foster metabolic symbiosis via lactate, ketone, and glutamine shuttling; maintain redox homeostasis through the NADPH–glutathione axis and UCP2; and establish immunosuppressive niches via mitochondrial stress signaling. Collectively, these mechanisms drive resistance to chemotherapy, targeted agents, radiotherapy, and immunotherapy. By integrating mitochondrial metabolism, stromal signaling, and clinical responses, this review identifies CAF mitochondria as an actionable target within the CRC TME. Targeting these CAF-specific pathways offers a novel strategy to disrupt tumor–stroma metabolic cooperation and overcome treatment resistance in colorectal cancer. Full article