Search Results (43,261)

Background: Evaluating potassium intake can be a powerful tool in epidemiologic studies to reduce the burden of noncommunicable diseases (NCDs). In Saudi Arabia, NCDs are responsible for 35% of deaths in 2023. Monitoring people’s potassium intake can be a powerful tool to reduce the burden of NCDs. There is a significant lack of information on potassium intake. The aim is to assess potassium intake using 24 h urinary excretion; to investigate the urinary sodium-to-potassium (Na/K) excretion ratio among Saudi adults; and to explore other lifestyle factors that influence potassium intake. Methods: A cross-sectional survey was conducted among young adults (19–29 years old) residing in Jeddah, Saudi Arabia. Data collection included a self-reported questionnaire regarding participants’ general attitudes and practices related to potassium consumption (n = 600) of whom 173 participated in 24 h urine collection. Descriptive analyses and regression models were used to evaluate the associations between urinary potassium excretion (mmol/24 h), daily potassium intake (g/day), and the Na/K ratio (dependent variables), and descriptive variables such as age and gender (predictor variables). A p value < 0.05 indicated statistical significance for all tests. Results: The mean urinary potassium excretion was 48.6 ± 23 mmol/24 h, equivalent to a mean daily potassium intake of 1.9 ± 0.89 g/day, and only 4.1% of participants met the World Health Organization-recommended potassium intake of ≥90 mmol/day (≥3.90 g/day). The average potassium intake was significantly lower in females compared with males by 0.52 g (95% CI: −0.78 to −0.25; p < 0.001). Physical activity was also a significant factor, associated with both urinary potassium excretion (p = 0.039) and intake (p = 0.006). Besides the low potassium intake, the mean Na/K ratio was 3.2 ± 1.4, and the ratio differed significantly by physical activity habits (p = 0.050). Only 13% of participants consumed fruit 5–7 days per week (mean portion intake 1.4/day; 95% CI: 1.3–1.5), and 34.7% consumed vegetables 3–4 days per week (mean portion intake 1.5/day; 95% CI: 1.3–1.5). These findings reflect low adherence to recommended fruit and vegetable intake in the study population. Conclusions: The findings of this study can be used to create evidence-based nutritional strategies to help people achieve the recommended potassium intake. The study underscores the need for more research on potassium intake across Saudi Arabia. Full article

Stress is a predisposing factor for pulmonary diseases; however, its effects on the lungs of healthy individuals have not been fully elucidated. Since bovine lactoferrin (bLf) is a powerful immunomodulator, this study aimed to evaluate whether lactoferrin can modulate the effects of chronic stress on humoral and cellular immunity in the lungs. We performed chronic restraint stress (RS) and oral administration of bLf in a BALB/c model, assessing serum corticosterone, body weight, and various lung immunity parameters, including immunoglobulin concentrations in serum and tracheobronchial lavages (TBLs), secretory IgA (S-IgA) levels in TBLs, IgA-secreting plasma cells, relative expression of pIgR, CD4⁺ lymphocyte Th1 and Th2 populations, and antigen-presenting cell (APC) populations in the lungs. Our results demonstrate that stress increases corticosterone and production of total IgA and IgG, while decreasing levels of IgM and S-IgA, promotes a Th1/Th2 profile imbalance, and decreases APC populations. Interestingly, bLf modulates serum corticosterone levels and stress-induced weight loss, and it also modulates humoral and cellular effects produced by chronic stress. These results demonstrate that bLf should be considered a new therapeutic target for further studies, focusing on prophylactic and co-therapeutic administration to treat and prevent respiratory diseases. Full article

Background: Regorafenib is a recognised treatment for refractory metastatic colorectal cancer (mCRC). The phase II ReDOS trial indicated that a stepwise dose escalation approach could enhance tolerability and persistence while maintaining efficacy. The ReTrITA study, a significant multicentre real-world cohort in Italy, served as the foundation for this sub-analysis concentrating solely on patients treated with regorafenib. Methods: This retrospective analysis encompassed 713 patients treated at 17 Italian centres from 2012 to 2023. Patients were categorised into two groups: ReDOS-like escalation (n = 313) and fixed dosing (no-ReDOS) (n = 400). The endpoints assessed were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and safety. Survival was assessed using Kaplan–Meier and Cox models, accompanied by exploratory subgroup analyses. Results: The median overall survival (OS) was comparable between the escalation and fixed dosing groups, recorded at 7.4 months and 6.7 months, respectively (HR 1.00, 95% CI 0.85–1.18, p = 0.93). Progression-free survival (PFS) demonstrated a significant improvement with escalation, recording 3.1 months compared to 3.9 months (HR 0.76, 95% CI 0.65–0.89, p = 0.0007). Subgroup analyses demonstrated a consistent progression-free survival (PFS) benefit in patients aged ≥70 years (HR 0.71, p = 0.015), with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1 (HR 0.76, p = 0.022), RAS wild-type tumours (HR 0.69, p = 0.026), and rectal primaries (HR 0.72, p = 0.043). The disease control rate (DCR) and objective response rate (ORR) were comparable, at 23.2% versus 25.3% and 2.0% compared 2.6%, respectively. Although not statistically significant, the fixed dose group’s duration of response (DoR) was numerically longer (15.4 months) than that of the variable dosing group (8.9 months). A lower percentage of patients experienced grade 3/4 adverse events with escalation (35.4% compared to 39.5%, p = 0.0042). Conclusions: This sub-analysis of the ReTrITA cohort demonstrates that regorafenib dose escalation is achievable in real-world settings, resulting in notable improvements in progression-free survival and enhanced tolerability, while not adversely affecting overall survival. These results support and improve the findings of the ReDOS study, showing that dosage escalation is possible and helpful in a diverse, unselected group of people, which is what is performed in routine oncology treatment. The findings are consistent with both randomised and observational studies, endorsing individualised dosing as a practical strategy in refractory mCRC. Full article

Ticks transmit diseases and harm animals worldwide, and their control primarily relies on pesticides. Resistance to these pesticides has developed consistently over centuries. Arginine Kinase (AK, EC 2.7.3.3) is a conserved, ancestral enzyme that provides reserve energy in emergency situations and a viable target for novel antiparasitic drugs. Our aim was to evaluate six carbamoyl carboxylic acid analogues (CCAs) as potential lead compounds by investigating their interaction with the active site of Rhipicephalus sanguineus AK (RsAK) using a structural modeling approach. The binding was characterized using fluorescence quenching (Stern–Volmer analysis) and molecular dynamics simulations. The simulations, performed with GROMACS using the CHARMM 26 force field over 100 ns, provided atomic-level insight into the ligand–protein interactions and stability. CCA4 exhibited the lowest dissociation constant (K_D~13·10⁻⁶ M) among the analogues, which we attribute to its end moieties (carboxylate and a pyridine on the ends). Purely aromatic ends (CCA1) or those with dual carboxylates (CCA6) showed lower affinity, suggesting that electrostatic complementarity and steric fit are processes involved in the binding. Despite requiring optimization, the CCA scaffold represents a novel strategy for tick control. These compounds provide a foundation for developing synergistic agents to enhance the efficacy of sustainable acaricides. Full article

Throughout the 2019 coronavirus disease pandemic, various vaccine regimens were implemented. Real-world data comparing their effectiveness during the BA.1/BA.2 Omicron wave remain limited. We prospectively enrolled healthcare workers who had completed two doses of mRNA or ChAdOx1 (A) vaccine and received an mRNA vaccine booster (BNT162b2 (P) or mRNA-1273 (M)). Neutralizing antibody levels were measured 6 months after the primary vaccinations and 1 month post-booster vaccination using a surrogate virus neutralization assay. Breakthrough infections were identified through institutional surveillance and the national reporting system. Among 318 participants (P-P-P: 71; A-A-P: 205; A-P-P: 19; M-M-M: 23), pre-booster neutralizing activity was lowest in the ChAdOx1-primed groups. One month post-booster vaccination, the neutralizing activity exceeded 97% across all regimens. The cumulative incidence of breakthrough infection varied significantly from 43.7% (P-P-P) to 84.2% (A-P-P). In adjusted Cox models, A-P-P showed the highest infection risk (HR 2.99, 95% CI 1.65–5.42). In summary, mRNA boosters restored neutralizing activity, but during the early BA.1/BA.2 Omicron wave they were less effective in preventing infections regardless of disease severity. Therefore, antibody titers alone are insufficient for evaluating protection, underscoring the need for continuous monitoring to support timely policy decisions during epidemic surges. Full article

Chronic kidney disease (CKD) affects over 10% of the global population, with end-stage renal disease (ESRD) necessitating renal replacement therapy. Kidney transplantation remains the optimal treatment for ESRD. However, the global donor kidney shortage crisis has led to increased reliance on deceased donor kidneys. Donors are classified as either donation after brain death (DBD) or donation after circulatory death (DCD), each associated with distinct ischemic injuries that impact graft function. Ischemia–reperfusion injury (IRI) plays a pivotal role in transplant outcomes, triggering oxidative stress, inflammation, and endothelial dysfunction. While static cold storage (SCS) remains the gold standard for organ preservation, alternative strategies such as hypothermic or normothermic machine perfusion (HMP and NMP), use of oxygen carriers during storage, and supplemental compounds to storage solutions have emerged, offering potential benefits in preserving graft viability. This review explores the cellular and molecular mechanisms of ischemic injury in deceased donor kidneys, preservation strategies tested in preclinical models, and emerging therapeutic interventions aimed at improving adverse post-transplant outcomes. Full article

The rapid emergence and evolution of avian viral pathogens present a major challenge to global poultry health and food security. Traditional vaccine development is often slow, costly, and limited by antigenic diversity. In this study, we present a comprehensive artificial intelligence (AI)-driven pipeline for the rational design, modeling, and optimization of multi-epitope vaccines targeting economically important RNA and DNA viruses affecting poultry, including H5N1, NDV, IBV, IBDV, CAV, and FPV. We utilized advanced machine learning and deep learning tools for epitope prediction, antigenicity assessment, and structural modeling (via AlphaFold2), and codon optimization. B-cell and T-cell epitopes were selected based on binding affinity, conservation, and immunogenicity, while adjuvants and linker sequences enhanced construct stability and immune response. In silico immune simulations forecasted robust humoral and cellular responses, including cytokine production and memory cell activation. The study also highlights challenges such as data quality, model interpretability, and ethical considerations. Our work demonstrates the transformative potential of AI in veterinary vaccinology and offers a scalable model for rapid, data-driven vaccine development against avian diseases. Full article

Nuts are nutrient-rich foods that help reduce the risk of coronary heart disease (CHD), but their potential contamination with aflatoxins (AFs) may increase the risk of liver cancer. In this study, the European Benefit–Risk Analysis for Foods (BRAFO) framework was used to evaluate both the health risks and benefits of nut consumption among Chinese adults. Based on the actual consumption patterns of nuts among the Chinese population, the current consumption level was set as the reference scenario (4.66 g/day), and three alternative scenarios were simulated with a daily nut consumption of 10, 20, and 30 g, respectively. Dose–response relationships were established using a two-stage dose–response analysis for nut consumption and CHD risk, and a one-stage dose–response analysis for aflatoxin B1 (AFB1) exposure and liver cancer risk. A Monte Carlo probabilistic model quantified the CHD prevention benefits and liver cancer risks associated with AF exposure. Disability-Adjusted Life Year (DALY) analysis indicated net health benefits in all scenarios, with nut consumptions of 10, 20, and 30 g/day reducing DALYs per 100,000 population by 104.39, 143.63, and 181.47 in men, and by 58.79, 81.29, and 102.94 in women, respectively. A nut consumption of 10 g/day was recommended for Chinese adults, considering both health benefits and the risk of AF exposure. This study presents the first application of the BRAFO framework to evaluate the net health effect of nut consumption in a Chinese population, filling a critical gap in the risk–benefit assessment of nut consumption. Full article

Highly selective inhibitors of the members of the cAMP-selective cyclic nucleotide phosphodiesterases, or PDE4 family, have shown clinically meaningful activity in two different classes of lung disease: roflumilast in obstructive lung disease, specifically chronic obstructive pulmonary disease (COPD), and nerandomilast in restrictive lung diseases characterized by inflammation/fibrosis of the alveolar interstitium, including idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). The beneficial therapeutic benefit of these agents in both of these disorders suggests that they share a common mechanism that underlies their effects on different pulmonary cells and tissues. This review outlines the biochemical, pharmacologic and cellular effects of PDE4-selective inhibitors, emphasizing their role in signal transduction pathways common to many pulmonary cell types. It then compares and contrasts the myriad cellular effects of these agents and their effects in pre-clinical animal models of these disorders. The emerging data are compatible with PDE4-selective inhibitors having targets of action in a large number of pulmonary cell types, only a subset of which is dysregulated in either COPD or IPF. This suggests that differences between the benefits observed with these individual agents in their various clinical indications reflect differences in disease pathogenesis, rather than proven differences in the enzyme-inhibitory effects of the various PDE4 inhibitors that have been studied to date. Full article

Elephant grass (Pennisetum purpureum Schumach, EG) is a promising biomass energy crop due to its high productivity and adaptability to harsh environments. In the transition to renewable energy, varietal evaluation is essential to identify cultivars that maximize biomass and energy yield. This study assessed three varieties (VS-19, VA-06, and VDP as control) across three harvest cycles (new planting, first regrowth, and second regrowth) between 2022 and 2024 at the Cotton and Agricultural Development Research Institute, Ninh Thuan Province, Vietnam. The site was characterized by mean temperatures of 25–36 °C, relative humidity of 65–82%, and average precipitation of 75.7 mm per month. Agronomic traits, energy potential (heating oil equivalent per hectare, HOE/ha), forage quality, and soil amendment value of the EG were examined to address the research question whether EG can be integrated into a three-cycle utilization model (energy, forage, soil amendment) to support a circular bioeconomy in Vietnam. All cultivars showed good growth, strong drought tolerance, and resistance to pests and diseases. VS-19 showed superior tillering, strong lodging resistance, and the highest biomass yield (63.8 t/ha) with an energy output of 32,636 HOE/ha, while VA-06 (56.1 t/ha; 28,699 HOE/ha) and VDP (54.7 t/ha; 27,952 HOE/ha) produced slightly lower but comparable outputs. Forage evaluation indicated moderate nutritional quality, while residues from the third cycle showed favorable carbon and nutrients content, making EG suitable as a soil amendment. EG thus demonstrates high biomass and energy yields, forage potential, and soil improvement capacity, reinforcing its role in integrated bioenergy and agricultural systems. Full article

Background/Objectives: In-hospital cardiac arrest (IHCA) remains a critical event with high mortality, requiring coordinated multidisciplinary response. Return of spontaneous circulation (ROSC) and hospital discharge rates are key quality indicators in resuscitation efforts. In Costa Rica, there is limited published data on team performance, protocol adherence, and the pharmacist’s role in code blue events, despite similar evidence gaps across Latin America. This study aimed to evaluate clinical outcomes and operational performance of in-hospital cardiac arrest events at a Costa Rica hospital. Methods: This retrospective cohort study included 77 adult patients who experienced IHCA at Clínica Bíblica between 2020 and 2024. Data collection was conducted between February and May 2025 from electronic medical records and code blue activation logs. Clinical variables, comorbidities, pharmacologic interventions, and outcomes were analyzed. Predictive models (Charlson Comorbidity Index [CCI], IHCA-ROSC, RISQ-PATH) and Kaplan–Meier survival analysis were applied. Results: ROSC was achieved in 55.8% of patients, and 21% were discharged alive. Asystole was the predominant initial rhythm (76.6%), and comorbidities such as renal disease and myocardial infarction were most frequent. A higher comorbidity burden was significantly associated with lower discharge rates (p = 0.032). Despite 98.7% of patients being classified as low probability for ROSC by the IHCA-ROSC model, observed outcomes exceeded expectations (predicted: 5.53% vs. actual: 55.84%; p < 0.000001). The code team adhered to institutional protocols in 100% of cases, with clinical pharmacists playing a key role in documentation and medication tracking. Conclusions: Structured multidisciplinary response was associated with ROSC rates notably higher than predicted by validated models. Opportunities for improvement include post-event laboratory testing, pharmacist-led documentation, and therapeutic hypothermia in shockable rhythms. Full article

Regulated proteolysis via autophagy is essential for cellular homeostasis, yet the specific role of autophagy-related gene 7 (ATG7) in corneal epithelial maintenance remains unclear. Using a conditional knockout mouse model (Atg7^f/f K14Cre^+/−), we investigated the impact of ATG7 deficiency on corneal epithelial autophagy, morphology, and vascular dynamics. Loss of ATG7 disrupted autophagosome formation, evidenced by increased LC3B expression but reduced LC3B-positive puncta and absence of autophagosomes ultrastructurally. Although gross corneal morphology was preserved, ATG7 deficiency led to thickened epithelium and increased peripheral lymphatic vessel sprouting, indicating a pro-inflammatory and pro-lymphangiogenic microenvironment. Proteomic analysis revealed upregulation of RAB8, TM9S3, and RETR3, suggesting activation of compensatory pathways such as exophagy, reticulophagy, and Golgiphagy. Inflammatory and angiogenic components were downregulated, suggesting a moderate loss of inhibitory capacity based on the lymphatic phenotypes observed. At the same time, while these two compensatory changes occur, other proteins that positively regulate lysosome formation are reduced, resulting in a phenotype linked to deficient autophagy. These findings demonstrate that ATG7-mediated autophagy maintains corneal epithelial homeostasis and immune privilege, with implications for understanding corneal inflammation and lymphangiogenesis in ocular surface diseases. Full article

Impaired bone regeneration and wound healing represent a major clinical and socioeconomic challenge for our aging and multimorbid population. Fracture and wound healing share many common features, with transforming growth factor beta (TGF-β) being a key regulator of inflammation, angiogenesis, fibroblast activation, and matrix remodeling. The dysregulation of TGF-β signaling is a hallmark of chronic wounds, excessive scar formation, and fracture non-union. Extracellular matrix protein 1 (ECM1) plays a crucial role in the activation of latent TGF-β. As a protein of the extracellular matrix, ECM1 offers ideal conditions for the biofunctionalization of bone implants or wound patches. Its mode of action has been studied mainly in fibrosis models of the liver or heart, where TGF-β acts as a driver of the disease. The controlled knock-out or overexpression of ECM1 either promoted or improved fibrosis development. In this review, we discuss how these findings can be applied to the biofunctionalization of implants to support bone and wound healing, considering the impact of TGF-β on the different healing phases. Full article

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. This review explains the connections between the genesis and progression of GBM and particular cellular tumorigenic mechanisms, such as angiogenesis, invasion, migration, growth factor overexpression, genetic instability, and apoptotic disorders, as well as possible therapeutic targets that help predict the course of the disease. Glioblastoma multiforme (GBM) diagnosis relies heavily on histopathological features, molecular markers, extracellular vesicles, neuroimaging, and biofluid-based glial tumor identification. In order to improve miRNA stability and stop the proliferation of cancer cells, nanoparticles, magnetic nanoparticles, contrast agents, gold nanoparticles, and nanoprobes are being created for use in cancer treatments, neuroimaging, and biopsy. Targeted nanoparticles can boost the strength of an MRI signal by about 28–50% when compared to healthy tissue or controls in a preclinical model like mouse lymph node metastasis. Combining the investigation of CNAs and noncoding RNAs with deep learning-driven global profiling of genes, proteins, RNAs, miRNAs, and metabolites presents exciting opportunities for creating new diagnostic markers for malignancies of the central nervous system. Artificial intelligence (AI) advances precision medicine and cancer treatment by enabling the real-time analysis of complex biological and clinical data through wearable sensors and nanosensors; optimizing drug dosages, nanomaterial design, and treatment plans; and accelerating the development of nanomedicine through high-throughput testing and predictive modeling. Full article

Background/Objectives: Local delivery of gene therapy products through the airways shows great promise for the treatment of a number of serious lung diseases, but its effectiveness is hampered by the mucus layer protecting the lung epithelium in the trachea and bronchi. Methods: To overcome this barrier, we engineered carbon dots (CDs) with mucus penetrating properties. Results: The CDs were synthesized by solvothermal treatment of citric acid and branched polyethyleneimine, and functionalized with maleamic acid groups to create cationic mucoinert nanoparticles with tunable charge. We characterized their interactions with a mucus model through turbidity and transport measurements, and assessed their impact on the viscoelastic properties of the biopolymer. We then demonstrated that the carriers are effective at delivering pDNA to a variety of cell models in vitro. In particular, mucus-producing Calu-3 cells cultured at the air–liquid interface (ALI) were used as a discriminating model to evaluate intracellular delivery of the genetic cargo through a thick layer of mucus at the cell surface. Conclusions: The functionalization of CDs with maleamic acid groups resulted in a 1000- to 10,000-fold increase in transfection efficiency in the mucus-producing model, offering new opportunities for lung gene therapy. Full article