Dr Mohammed Mahmoud Youssif

In this case‒control study conducted at Cairo's National Cancer Institute, the associations between bisphenol A (BPA), an endocrine-disrupting chemical (EDC), and ovarian cancer were investigated. BPA levels in the urine, oxidative stress markers (reactive oxygen species (ROS) and superoxide dismutase (SOD) activity), and KRT4 gene expression were analyzed in 30 patients and 30 controls. Significant risk factors for BPA exposure included consuming microwave meals, consuming canned beverages, using PVC food storage, eating fast food, handling thermal paper, exposure to dust, and recurrent hospitalizations (all p < 0.001). Compared with normal controls, ovarian cancer patients presented increased BPA levels, ROS, and KRT4 expression, along with reduced SOD activity (p < 0.001). A strong positive correlation was found between BPA and KRT4, suggesting that KRT4 is a potential biomarker. The cutoff values for urinary BPA and KRT4 achieved 100% sensitivity and specificity in distinguishing patients from controls. These findings suggest that BPA plays a role in ovarian cancer pathogenesis, likely through oxidative stress and gene dysregulation. This study emphasizes the importance of minimizing BPA exposure (e.g., by reducing the use of canned or packaged foods) and calls for larger studies to further investigate the role of EDCs in hormone-dependent cancers.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide. Performance of non-invasive tests (NITs) in patients with MASLD recruited from different regions of the world was evaluated.

METHODS: MASLD patients with liver biopsies and NIT data [fibrosis-4 index (FIB-4), enhanced liver fibrosis (ELF), and liver stiffness measurement (LSM)] were enrolled through the Global NASH Council collaboration (G-MASLD). FibroScan-AST (FAST) and Agile-3+/Agile-4 were calculated. NITs' performance for predicting ≥F2 (significant fibrosis), ≥F3 (advanced fibrosis), or cirrhosis (F4) was determined in patients from different regions.

RESULTS: A total of 17,792 MASLD patients from 41 countries were included: 14% had F0, 32% F1, 18% F2, 22% F3, 13% F4 (cirrhosis); 48% NAS ≥5. Advanced fibrosis prediction by NITs was variable across regions for FIB-4 [pooled AUC (95% CI)=0.80 (0.79-0.81)], the lowest in Latin America [0.75 (0.71-0.79)], the highest in MENA [0.84 (0.82-0.87)], and ELF [pooled AUC=0.77 (0.76-0.79)], the lowest in Europe [0.72 (0.69-0.76)], the highest in North America [0.80 (0.78-0.82)]. Prediction of advanced fibrosis by LSM [pooled AUC=0.84 (0.83-0.85)] was similar across regions except North America [0.78 (0.76-0.81)]. In addition, FAST [AUC=0.75 (0.74-0.76)] and Agile-3+ [AUC=0.87 (0.86-0.88)] performed similarly across regions. Similar trends were observed for the NITs predicting significant fibrosis. Finally, the accuracy of Agile-4 for predicting cirrhosis [AUC=0.90 (0.89-0.91)] was the lowest in North America [0.85 (0.83-0.87)], the highest in MENA [0.96 (0.94-0.98)].

CONCLUSIONS: The diagnostic performance of common NITs for fibrosis in MASLD varies across the world. In the large multinational G-MASLD sample, the most accurate NITs were Agile-3+ and Agile-4 composite scores.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide. Performance of non-invasive tests (NITs) in patients with MASLD recruited from different regions of the world was evaluated.

METHODS: MASLD patients with liver biopsies and NIT data [fibrosis-4 index (FIB-4), enhanced liver fibrosis (ELF), and liver stiffness measurement (LSM)] were enrolled through the Global NASH Council collaboration (G-MASLD). FibroScan-AST (FAST) and Agile-3+/Agile-4 were calculated. NITs' performance for predicting ≥F2 (significant fibrosis), ≥F3 (advanced fibrosis), or cirrhosis (F4) was determined in patients from different regions.

RESULTS: A total of 17,792 MASLD patients from 41 countries were included: 14% had F0, 32% F1, 18% F2, 22% F3, 13% F4 (cirrhosis); 48% NAS ≥5. Advanced fibrosis prediction by NITs was variable across regions for FIB-4 [pooled AUC (95% CI)=0.80 (0.79-0.81)], the lowest in Latin America [0.75 (0.71-0.79)], the highest in MENA [0.84 (0.82-0.87)], and ELF [pooled AUC=0.77 (0.76-0.79)], the lowest in Europe [0.72 (0.69-0.76)], the highest in North America [0.80 (0.78-0.82)]. Prediction of advanced fibrosis by LSM [pooled AUC=0.84 (0.83-0.85)] was similar across regions except North America [0.78 (0.76-0.81)]. In addition, FAST [AUC=0.75 (0.74-0.76)] and Agile-3+ [AUC=0.87 (0.86-0.88)] performed similarly across regions. Similar trends were observed for the NITs predicting significant fibrosis. Finally, the accuracy of Agile-4 for predicting cirrhosis [AUC=0.90 (0.89-0.91)] was the lowest in North America [0.85 (0.83-0.87)], the highest in MENA [0.96 (0.94-0.98)].

CONCLUSIONS: The diagnostic performance of common NITs for fibrosis in MASLD varies across the world. In the large multinational G-MASLD sample, the most accurate NITs were Agile-3+ and Agile-4 composite scores.

IL-21/IL-21R signaling is crucial in various immune diseases and cellular development, however, its role in bacterial pneumonia remains unclear. Here, IL-21R knockout (IL-21R) mice were more susceptible to Actinobacillus pleuropneumoniae (APP) than wild-type (WT) mice. High-dimensional mass cytometry analysis revealed that IL-21R deficiency inhibited neutrophil activation, decreased the numbers of monocytes and proinflammatory macrophages, and augmented the defective CD3 T cells in the lungs. Intracellular cytokine staining showed decreased IFN-γ/TNF-α/IL-6 production in IL-21R mice, particularly in CD8⁺ T cells. Furthermore, a previously unrecognized Ly6CLy6GCD4 T cell subset emerged only in the lungs of WT mice post-APP infection, which was in an activated status with stronger secretion capacities of IL-10, IL-21, granzyme B, and perforin by flow cytometry. These cells polarized macrophages into M2- or M1- phenotype without/with infection, respectively, and enhanced proliferation, phagocytosis, and macrophage extracellular traps/ROS-mediated bactericidal activity of macrophages against-APP, Klebsiella pneumoniae, or Escherichia coli infection. Thus, our study demonstrated that IL-21 drives the differentiation of neutrophils, monocytes, and macrophages into pro-inflammatory subsets. IL-21-induced Ly6CLy6GCD4 T cells cooperate with macrophages to enhance bacterial clearance, providing a promising target for preventing bacterial pneumonia.

Bladder cancer (BLCA) is a malignant growth that originates from the urothelial lining of the urinary bladder. Diagnosing BLCA is complex due to the variety of tumor features and its heterogeneous nature, which leads to significant morbidity and mortality. Understanding tumor histopathology is crucial for developing tailored therapies and improving patient outcomes. Early diagnosis and treatment are essential to lower the mortality rate associated with bladder cancer. Manual classification of muscular tissues by pathologists is labor-intensive and relies heavily on experience, which can result in interobserver variability due to the similarities in cancerous cell morphology. Traditional methods for analyzing endoscopic images are often time-consuming and resource-intensive, making it difficult to efficiently identify tissue types. Therefore, there is a strong demand for a fully automated and reliable system for classifying smooth muscle images. This paper proposes a deep learning (DL) technique utilizing the EfficientNet-B3 model and a five-fold cross-validation method to assist in the early detection of BLCA. This model enables timely intervention and improved patient outcomes while streamlining the diagnostic process, ultimately reducing both time and costs for patients. We conducted experiments using the Endoscopic Bladder Tissue Classification (EBTC) dataset for multiclass classification tasks. The dataset was preprocessed using resizing and normalization methods to ensure consistent input. In-depth experiments were carried out utilizing the EBTC dataset, along with ablation studies to evaluate the best hyperparameters. A thorough statistical analysis and comparisons with five leading DL models-ConvNeXtBase, DenseNet-169, MobileNet, ResNet-101, and VGG-16-showed that the proposed model outperformed the others. The EfficientNet-B3 model achieved impressive results: accuracy of 99.03%, specificity of 99.30%, precision of 97.95%, recall of 96.85%, and an F1-score of 97.36%. These findings indicate that the EfficientNet-B3 model demonstrates significant potential in accurately and efficiently diagnosing BLCA. Its high performance and ability to reduce diagnostic time and cost make it a valuable tool for clinicians in the field of oncology and urology.

BACKGROUND: Feline parvovirus (FPV) causes feline panleukopenia (FPL) and cerebellar ataxia (CA) in cats. to date, only two complete Egyptian VP2 sequences have been available in GenBank. To investigate FPV diversity And evolution in Egypt, we generated 24 complete VP2 sequences from diseased cats during two FPV activity peaks in 2023 (January-February and November-December). Egyptian sequences were Analyzed with 967 global references to assess selection pressure and phylogenetic relationships. In silico predictions of VP2 Antigenic sites, 3D structure, and phosphorylation potential were performed to evaluate the impact of identified mutations.

RESULTS: Egyptian sequences showed 99.3-100% nt And 99.8-100% aa identity among themselves, And 98.6-100% nt And 98.4-100% aa identity with global references. The overall dN/dS ratio was 0.121, with codon 101 under positive selection. Compared to the prototype FPV-b strain (M38246), Egyptian strains had 32 mutations (3 nonsynonymous: Ala5Thr, Ile101Thr, and Thr390Ala; 29 synonymous), forming 19 nt And 3 aa sequence types. Notably, Thr390Ala was unique to Egyptian sequences and absent from all global references. Phylogenetically, Egyptian strains formed two subclades: one composed solely of sequences carrying Thr390Ala (n = 13), And Another including the remaining 11 sequences clustering with 19 global strains sharing the synonymous mutation C135T in addition to A927G and/or A1236G. The Thr390Ala variant predominated in the first peak (11/17, 64.7%) but declined in the second (2/7, 28.6%). Residue 390 lies within an epitope-rich region (aa 350-450) and was predicted to be a phosphorylation site. Thr390Ala caused a modest drop in epitope score, disrupted local hydrogen bonding, and abolished predicted phosphorylation.

CONCLUSIONS: Beyond expanding the global dataset with the largest number of Egyptian full-length VP2 sequences to date, this study highlights the Thr390Ala mutant as a classic example of evolutionary trade-off: it emerged and predominate during the first peak, potentially as an immune escape variant, but declined in the second peak, likely due to structural constraints and competition with fitter variants. Despite strong purifying selection, this case illustrates that FPV evolution is not entirely static. This underscores the need for continuous genetic monitoring to capture viral evolution in real time and inform effective control strategies.

BACKGROUND: Gastric ulcer is one of the most common gastrointestinal tract diseases with a higher extent in male patients. Selenium nanoparticles (SeNPs) possess therapeutic benefits, including antimicrobial, antioxidant, anti-inflammatory, and anti-ulcerative agents. The study aimed to investigate the modulatory effect of yeast-mediated SeNPs on gastric ulcers and microbiota dysbiosis in a rat model.

METHOD: Twenty-four rats were randomly divided into four groups. Both the control and SeNPs-only groups received distilled water orally, and after 1 h, they received 2 % carboxymethyl cellulose (CMC). The ulcer model and SeNPs-treated groups received 99 % ethanol (5 ml/kg orally) for ulcer induction, followed by 2 % CMC after one hour. The SeNPs-treated group got SeNPs (60 mg/kg) suspended in 2 % CMC. We measured ulcer markers (ulcer index and gastric juice pH and volume and stomach tissue oxidative stress markers (malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), and catalase (CAT)), in addition to histopathological examination of gastric tissues stained with three different satins: hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), and Masson's trichrome stains (many-color dye), and microbiological analysis of freshly collected fecal sample.

RESULTS: SeNPs treatment significantly decreased gastric volume, ulcer index, malondialdehyde, and increased glutathione levels. A macroscopic examination of the treated stomach revealed decreased ulcer lesion numbers. Furthermore, histopathological examination showed that SeNPs treatment repaired ulcerative gastric tissue through the regeneration of epithelial cells and reduction in damaged areas and collagen fibers. In the treated group, microbiological analysis of rat feces showed a significant increase in Leuconostoc pseudomesenteroides, Escherichia coli, and Enterococcus faecium counts.

CONCLUSION: This research suggests that SeNPs exhibit anti-ulcer activity and can accelerate ulcer healing via their antioxidant action. They also have a modulatory effect on gut microbiota dysbiosis associated with gastric ulcers. This is the first research studying the impact of safe yeast-mediated SeNPs on rat's gastric ulcer and gut microbiota.

The neuroprotective potential of tyrosine kinase inhibitors (TKIs), potent anticancer drugs, was verified against various neurodegenerative insults, but not Huntington's disease (HD). These promising outcomes were due to their ability to modulate various intracellular signalling pathways. Hence, the current study aimed to evaluate the neuroprotective effects of lapatinib and pazopanib in the 3-nitropropionic (3-NP)-induced HD model in rats. After 14 days of 3-NP administration, rats received saline, lapatinib, or pazopanib for 21 days. Treatment with lapatinib or pazopanib improved the striatal microscopic architecture, neuronal survival, and neuroinflammatory responses, with a pronounced effect observed for pazopanib. At the molecular level, lapatinib and pazopanib reduced the striatal gene expression of NF-κB and TNF-α receptors, curbed the glutamate/calpain-2 axis, and modified the striatal content of inflammatory molecules as well as neurotransmitters. In addition, they activated the neuroprotective trajectory viz., m-Tor/ULK-1/Beclin-1/LC3-II, an effect dependent on tyrosine kinase inhibition. Moreover, treated groups showed normalised tyrosine hydroxylase and glial fibrillary acidic protein in the striatum. In conclusion, this study provides strong evidence that lapatinib or pazopanib significantly improved motor function, alleviated cognitive decline, and attenuated neurodegeneration in HD rats via modulating key signalling pathways implicated in HD pathogenesis. These results underscore the promising therapeutic potential of TKIs in managing HD and warrant further investigation into their clinical application.

BACKGROUND: Epidermolysis bullosa dystrophica (EBD) is characterized by mucocutaneous fragility with blistering, scarring and severe growth retardation attributed to many factors.

METHODS: This cross-sectional study included 51 patients aged 1-12 years with recessive dystrophic EB (RDEB). Weight and height were measured, with the calculation of weight standard deviation (SD), height SD, and body mass index (BMI), followed by plotting them on Egyptian growth curves. Serum levels of basal growth hormone (GH), insulin-like growth factor 1 (IGF-1), hemoglobin (Hb) level, erythrocyte sedimentation rate (ESR), and thyroid functions (TSH and free T4) were measured. Growth hormone stimulation test was performed in 11 patients.

RESULTS: Weight SD and height SD were lower than normal measurements (p < 0.05*). Growth hormone, growth hormone stimulation, and IGF-1 were lower than the normal range (p < 0.05*). Hb levels were lower than normal, whereas ESR levels were elevated (p < 0.001*). A negative correlation was found between ESR and basal GH, and a positive correlation between ESR and IGF-1.

CONCLUSION: Children with generalized RDEB have poor growth and low circulating GH and IGF-1 levels, likely due not only to malnutrition and anemia, but possibly also as a consequence of inflammation that suppresses the GH/IGF-1 axis. Future treatments targeting the correction of GH and IGF-1 levels as well as the chronic inflammatory state should be considered.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05390073.

BACKGROUND: Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment.

METHODS: This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories. Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys. Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool. A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD.

FINDINGS: Globally, in 2023, 788 million (95% uncertainty interval 743-843) people aged 20 years and older were estimated to have CKD, up from 378 million (354-407) in 1990. The global age-standardised prevalence of CKD in adults was 14·2% (13·4-15·2), a relative rise of 3·5% (2·7-4·1) from 1990. The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9-19·4). Most people had stage 1-3 CKD, with a combined prevalence of 13·9% (13·1-15·0). In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30-1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8-857·4) per 100 000. Impaired kidney function as a risk factor accounted for 11·5% (8·4-14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs.

INTERPRETATION: CKD is a major global health issue, with rising prevalence and increasing importance as a cause of death and as a risk factor for cardiovascular death. A better understating of aetiology, appropriate screening, and implementation programmes are needed to translate advances in CKD treatment into improved patient outcomes.

FUNDING: Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

In the current medical era, Topoisomerase II is recognized as an essential enzyme that regulates DNA topology during critical biological processes such as DNA replication, transcription, and repair. This study aimed to design, synthesize, and biologically evaluate a new series of pyrazolo[3,4-]pyridines (-, -, and ) as potential anticancer agents and Topoisomerase II inhibitors. The synthesized compounds were subjected to in vitro anticancer screening at the National Cancer Institute (NCI, USA). Active derivatives were further evaluated through a five-dose screening to determine their antiproliferative potency. Selected compounds were examined for their effects on leukemia cell lines (K562 and MV4-11), and mechanistic studies were performed to assess DNA damage, cell cycle distribution, and apoptosis-related protein modulation. Additionally, enzyme inhibition assays were conducted to determine Topoisomerase IIα (TOPIIα) inhibition. Initial single-dose screening identified several active compounds, notably , , , , , , , and . Among these, compound exhibited potent and broad-spectrum antiproliferative activity across the NCI cancer cell line panel, with a GI MG-MID value of 1.33 µM (range: 0.54-2.08 µM). The synthesized molecules showed moderate to good anti-leukemic efficacy against K562 and MV4-11 cells. Mechanistic investigations revealed that compound induced DNA damage and S-phase cell cycle arrest, leading to apoptosis as evidenced by the modulation of PARP-1, Bax, XIAP, and Caspases. Furthermore, target-based assays confirmed that compound significantly inhibited the DNA relaxation activity of TOPIIα in a dose-dependent manner, comparable to etoposide. The study highlights compound as a promising pyrazolo[3,4-]pyridine derivative with potent antiproliferative activity and effective inhibition of Topoisomerase IIα. These findings suggest its potential as a lead scaffold for further optimization in anticancer drug development..

BACKGROUND: This study compared ultrasound-guided supraclavicular subclavian vein (SCV) cannulation and internal jugular vein (IJV) cannulation in neonates and infants weighing less than 5 kg.

METHODS: A total of 108 neonates and infants were randomly assigned to either the SCV group (n = 54) or the IJV group (n = 54). The primary outcome was the success rate on the first insertion attempt. Secondary outcomes included procedure times, adverse events, and other characteristics of venous cannulation.

RESULTS: In neonates and infants weighing less than 5 kg, the SCV group demonstrated a significantly higher first-attempt success rate compared to the control group [43 (79.6%) vs. 30 (55.6%), relative risk (95% CI): 0.7 (0.53-0.92), p =  0.007]. Additionally, the SCV group experienced fewer adverse events (5.6 % vs. 29.6%, p =  0.002).

CONCLUSION: Ultrasound-guided SCV cannulation resulted in a significantly higher first-attempt success rate and a lower incidence of adverse events compared to IJV cannulation in neonates and infants weighing under 5 kg. These findings indicate that SCV cannulation may offer a preferable approach for improving success rates.

REGISTRATION: ClinicalTrial.gov(NCT05956028).

Otitis media (OM) is a frequent infectious condition that affects the middle ear especially in children. The purpose of this project was to create fenchone-augmented novasomes to enhance the trans-tympanic penetration of levofloxacin (LFX) and improve its antibacterial efficacy. Novasomes were formulated using the ethanol injection technique and optimized using a 2 factorial design. The factors analyzed included the stearic acid to drug ratio (A), cholesterol to fenchone ratio (B), and surfactant concentration (%) (C). The optimization feature of Design-Expert® software was utilized to identify the optimal formulation by minimizing particle size (PS) and poly-dispersity index (PDI) while maximizing entrapment efficiency (EE%) and the absolute value of the zeta potential (ZP). The best formulation achieved a desirability of 0.964, with an EE% of 73.39%, a PS of 179.25 nm, and a ZP of - 31.95 mV. The formulation will be subjected to additional evaluations, including in vitro, ex vivo, microbiological, and in vivo testing. A thorough in vitro analysis revealed a biphasic release profile, significant stability, and a spherical morphology. Novasomes exhibited greater ex vivo permeation and superior flux values compared to the LFX solution. The optimum formula demonstrated high otic tolerance. The optimized formula demonstrated markedly enhanced antibacterial activity, with significantly lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against Staphylococcus aureus and Pseudomonas aeruginosa compared to the drug solution. Moreover, it exhibited superior biofilm inhibition, even at sub-MIC concentrations, underscoring its efficacy. These findings highlight the potential of LFX-loaded novasomes as an efficient non-invasive method for managing middle ear infections.

: Lower-grade gliomas (LGGs) are a biologically and clinically heterogeneous group of brain tumors, for which molecular stratification plays essential role in diagnosis, prognosis, and therapeutic decision-making. Conventional unimodal classifiers do not necessarily describe cross-layer regulatory dynamics which entail the heterogeneity of glioma. : This paper presents a protein-protein interaction (PPI)-informed hybrid model that combines multi-omics profiles, including RNA expression, DNA methylation, and microRNA expression, with a Graph Attention Network (GAT), Random Forest (RF), and logistic stacking ensemble learning. The proposed model utilizes ElasticNet-based feature selection to obtain the most informative biomarkers across omics layers, and the GAT module learns the biologically significant topological representations in the PPI network. The Synthetic Minority Over-Sampling Technique (SMOTE) was used to mitigate the class imbalance, and the model performance was assessed using a repeated five-fold stratified cross-validation approach using the following performance metrics: accuracy, precision, recall, F1-score, ROC-AUC, and AUPRC. : The findings illustrate that a combination of multi-omics data increases subtype classification rates (up to 0.984 ± 0.012) more than single-omics methods, and DNA methylation proves to be the most discriminative modality. In addition, analysis of interpretability using attention revealed the major subtype-specific biomarkers, including UBA2, LRRC41, ANKRD53, and WDR77, that show great biological relevance and could be used as diagnostic and therapeutic tools. : The proposed multi-omics based on a biological and explainable framework provides a solid computational approach to molecular stratification and biomarker identification in lower-grade glioma, bridging between predictive power, biological clarification, and clinical benefits.

BACKGROUND/OBJECTIVES: Diabetic nephropathy (DN) is a prevalent microvascular diabetic complication that is not totally unveiled. In this study, we considered GAS6, AXL, GAS6-AS1, and GAS6-DT as possible early diagnostic biomarkers of DN.

SUBJECTS/METHODS: The study included 70 patients with normoalbuminuria type 2 diabetes (DM), 70 patients with microalbuminuria type 2 diabetes (DN), and 60 apparently healthy controls. Fasting plasma glucose, glycosylated hemoglobin, and plasma creatinine were enzymatically assayed. Albuminuria, plasma GAS6, and AXL levels were determined using ELISA. Long non-coding RNAs GAS6-AS1 and GAS6-DT levels were determined in blood using qRT-PCR. Several bioinformatics databases were employed to suggest interactions with the studied biomolecules.

RESULTS: GAS6 and AXL were downregulated in DM + DN compared to controls, being the lowest in DN (p < 0.0001). GAS6-DT was upregulated in DM + DN compared to controls, being the highest in DN (p < 0.0001). GAS6-AS1 was higher in DN than in controls (p = 0.013). GAS6, AXL, and GAS6-DT showed fair-to-moderate significant correlations with HbA1c, fasting glucose, creatinine, and albuminuria. ROC curves showed remarkable diagnostic power of GAS6, AXL, and GAS6-DT (AUC = 0.72-1.0), but not GAS6-AS1, in DN and DM, with moderate-to-excellent agreement with conventional diagnostics.

CONCLUSIONS: The current findings emphasize the significance of the GAS6/AXL pathway in DM and DN progression, where GAS6, AXL, and GAS6-DT showed significantly altered values in DM, and further in DN, with notable diagnostic power for both diseases. To date, this is the first study confirming the diagnostic power of AXL and GAS6-DT in DN and DM. Future studies are warranted to evaluate therapeutically targeting this pathway to manage DN.

Schizophrenia is a severe psychiatric disorder marked by significant cognitive, perceptual, and social deficits, the neurobiological basis of which remains incompletely elucidated. Increasing evidence implicates disruptions in protein homeostasis, including misfolding and aggregation of key neuronal proteins, as contributing factors to its pathogenesis. While proteinopathies have been extensively studied in neurodegenerative diseases, their role in schizophrenia has only recently gained attention. Central to these processes is endoplasmic reticulum (ER) stress and the activation of the unfolded protein response, which regulate protein folding and cellular quality control. Dysregulation of ER stress pathways, alongside impaired chaperone protein function and mitochondrial dysfunction, can lead to accumulation of misfolded proteins and neuronal dysfunction. Proteins such as DISC1, CRMP1, NOS1AP, and others have been identified with altered expression and aggregation patterns in schizophrenia, linking protein abnormalities to disease pathology. Additionally, mounting evidence suggests that chronic ER stress can activate microglia, the brain's immune cells, triggering the release of proinflammatory cytokines and promoting neuroinflammation. Sigma-1 receptor, a unique ER chaperone protein involved in modulating ER stress and calcium signaling, has emerged as a critical regulator of neuronal proteostasis and survival. Agonists of the sigma-1 receptor show promising therapeutic potential by alleviating ER stress, enhancing neuroprotection, halting inflammation, and restoring cellular homeostasis in preclinical models of schizophrenia and other brain disorders. In this review, we will discuss these interconnected molecular mechanisms, highlighting novel therapeutic pathways focused on proteostasis restoration and sigma-1 receptor modulation, which offer a promising avenue for future interventions in schizophrenia.

Streptozotocin (STZ) is an alkylating agent that has neurotoxic effects when injected into the cerebral ventricles (ICV) and also models many other features of Alzheimer's disease. However, the mechanisms of STZ neurotoxicity are not well understood. In this study, we hypothesized that some of the neurotoxic effects of STZ could be due to direct activities on brain endothelial cells and astrocytes, which are key in forming and supporting the functions of the blood-brain barrier (BBB), respectively. To test this hypothesis, we characterized the changes induced by STZ either in cultures of human-induced pluripotent stem cell (iPSC)-derived brain endothelial-like cells (iBECs), which form an in vitro BBB model, or in primary human astrocytes. We found that STZ at a dosage of 5 mM caused a delayed reduction in the transendothelial electrical resistance (TEER) of iBECs at 7-11 days post-treatment, indicating induction of BBB leakage. Additionally, we observed significant increases in albumin leakage across the monolayer, altered iBEC morphology, and reductions in tight junction proteins, suggesting that STZ causes BBB disruption. We further found that the BBB glucose transporter GLUT-1 was reduced in iBECs, as was the total number of iBECs. In astrocytes, the 5 mM dose of STZ reduced the GFAP signal and total number of cells, suggesting that STZ has anti-proliferative and/or toxic effects on astrocytes. Together, these data support that STZ's neurotoxic effects could be due, in part, to its direct toxic activities on brain endothelial cells and astrocytes.

IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.

OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches.

DESIGN, SETTING, AND PARTICIPANTS: This case series used data from the international, multicenter Global Alagille Alliance (GALA) study accrued between May 14, 2018, and March 20, 2023. Children born at full term between January 1, 1997, and August 31, 2019, with a clinically and/or genetically confirmed ALGS diagnosis and their native liver were included. Data from children with a known history of prematurity were excluded for the development of the growth charts. Data were analyzed from March 25, 2023, to December 30, 2024.

EXPOSURE: Growth of children with Alagille syndrome.

MAIN OUTCOMES AND MEASURES: Generalized additive models for location scale and shape were fitted to generate percentile plots for weight and height relative to age and superimposed on US Centers for Disease Control and Prevention (CDC) growth charts to illustrate differences in growth patterns compared with children with typical development.

RESULTS: Data from 1204 children with ALGS in overlapping cohorts (median [IQR] gestational age, 38 [37-39] weeks) were analyzed (1204 in the weight cohort; 695 boys [57.7%]; 9855 weight observations; 995 with neonatal cholestasis [82.6%]; 306 receiving a liver transplant [25.4%]; 98 deaths [8.1%] and 1106 in the height cohort, 635 boys [57.4%]; 8464 height observations; 906 with neonatal cholestasis [81.9%]; 287 receiving a liver transplant [25.9%]; 86 deaths [7.8%]) were included for the modeling of the weight-for-age and height-for-age charts, respectively. The median birth weight was 2.8 kg (IQR, 2.5-3.0 kg) for boys and 2.6 kg (IQR, 2.4-2.9 kg) for girls. The median birth length was 48.0 cm (IQR, 46.0-50.0 cm) for boys and 47.0 cm (IQR, 45.0-49.0 cm) for girls. The weight-for-age and height-for-age growth charts for boys and girls with AGLS differed significantly from CDC growth charts. The estimated height at age 18 years corresponded to the 50th percentile was 171.5 cm for boys and 156.5 cm for girls on the condition-specific charts vs 176 cm and 163 cm, respectively, on the CDC growth charts.

CONCLUSIONS AND RELEVANCE: These findings suggest that condition-specific growth charts for ALGS may provide a crucial tool for clinicians to evaluate growth and aid in decision-making around listing children for liver transplant.

Diabetes mellitus is a metabolic disorder with escalating prevalence. It's a chief cause of microvascular complications, notably diabetic retinopathy (DR), which can predispose to permanent vision loss. Inflammation and oxidative stress are pivotal contributors to the progression of DR. Luteolin (LUT), a naturally occurring flavonoid, possesses strong anti-inflammatory and antioxidant properties, offering therapeutic potential against DR. However, its clinical use is impeded by its restricted intestinal permeability and poor water solubility. In this study, twelve lipid-polymer hybrid nanoparticles (LPNPs) were developed using a 12 complete factorial design to explore the impact of three formulation variables: poly(ε-caprolactone) (PCL): d-alpha-Tocopheryl polyethylene glycol 1,000 succinate (TPGS) ratio (A), preparation technique (B) and phospholipid (PL) content (C). The optimized formulation (LP8), composed of 50 mg of phospholipid, PC: TPGS (2:1) and prepared via the emulsion solvent evaporation method, demonstrated a high zeta potential (-34.9 ± 5.2  mV), a small particle size (215.3 ± 10.3  nm), and a high entrapment efficiency (93.1 ± 2.4 %). Compared to LUT suspension, LP8 demonstrated prolonged in vitro drug release and markedly enhanced ex vivo intestinal permeability. In streptozotocin (STZ)-induced diabetes, LP8 resulted in significant reduction in hyperglycemia, retinal inflammation, oxidative stress and angiogenesis while preserving retinal structure. Moreover, LP8 significantly downregulated the expression of MDA, IL-1β, NLRP3, ASC, and VEGF while upregulated GSH and Nrf2 levels in the retina. Additionally, pharmacokinetic study confirmed a substantial improvement in oral bioavailability of LUT-loaded LP8 compared to LUT-suspension. These findings proposed that the optimized LUT-loaded LPNPs represent a potential oral nanoplatform for the effective management of DR.

Primary ciliary dyskinesia is a rare autosomal recessive disorder that impairs mucociliary clearance and predisposes children to chronic respiratory infections. Invasive fungal infections caused by are typically confined to profoundly immunocompromised hosts and are exceptionally uncommon in patients without systemic immunosuppression. We report the case of a 6-year-old boy with genetically confirmed primary ciliary dyskinesia (C3orf67 mutation) and right-middle-lobe bronchiectasis who developed persistent cough and increased sputum production. High-resolution chest computed tomography demonstrated right-lower-lobe consolidation and segmental atelectasis. Bronchoalveolar lavage microscopy revealed broad, aseptate/pauci-septate hyphae, and the culture yielded , establishing the diagnosis of pulmonary mucormycosis. The child received intravenous liposomal amphotericin B for 18 days, followed by oral azole step-down therapy, resulting in complete clinical and radiological recovery. This case expands the spectrum of invasive mucormycosis to include pediatric patients with primary ciliary dyskinesia in the absence of classical immunosuppressive risk factors. Early bronchoscopy, mold-directed culture, and prompt antifungal therapy, supported by multidisciplinary care, are critical for favorable outcomes.

Primary ciliary dyskinesia is a rare autosomal recessive disorder that impairs mucociliary clearance and predisposes children to chronic respiratory infections. Invasive fungal infections caused by are typically confined to profoundly immunocompromised hosts and are exceptionally uncommon in patients without systemic immunosuppression. We report the case of a 6-year-old boy with genetically confirmed primary ciliary dyskinesia (C3orf67 mutation) and right-middle-lobe bronchiectasis who developed persistent cough and increased sputum production. High-resolution chest computed tomography demonstrated right-lower-lobe consolidation and segmental atelectasis. Bronchoalveolar lavage microscopy revealed broad, aseptate/pauci-septate hyphae, and the culture yielded , establishing the diagnosis of pulmonary mucormycosis. The child received intravenous liposomal amphotericin B for 18 days, followed by oral azole step-down therapy, resulting in complete clinical and radiological recovery. This case expands the spectrum of invasive mucormycosis to include pediatric patients with primary ciliary dyskinesia in the absence of classical immunosuppressive risk factors. Early bronchoscopy, mold-directed culture, and prompt antifungal therapy, supported by multidisciplinary care, are critical for favorable outcomes.

Parkinson's disease (PD) is the fastest growing neurodegenerative disorder worldwide. Available treatments are only symptomatic, urging the demand for new therapies. Ferroptosis is increasingly reported as a critical player in neurodegeneration. Meanwhile, ferroptosis is activated by impaired mitophagy under rigorous milieu of oxidative stress that disrupts mitochondrial homeostasis. However, the interplay between ferroptosis and mitophagy is not fully elucidated in PD. Carvedilol is a cardiovascular antioxidant, antiferroptotic drug with lipophilic nature that allows its passage via blood brain barrier. Moreover, its effect on modulating mitochondrial balance is emerging in multiple disorders. Therefore, This study aimed to explore the possible neuroprotective mechanistic effects of carvedilol on rotenone-induced PD rat model in context of ferroptosis-mitophagy interaction. Rotenone-induced toxicities were detected by Immunohistochemistry, ELISA, qPCR and western blot analysis techniques. Rotenone disrupted key players of ferroptosis-mitophagy axes. Nrf2, Glutathione peroxidase (GPX4), Catalase, PINK 1/PARKIN levels were drastically decreased. Acyl coA synthetase long chain (ACSL4), MDA and NF-κB levels were significantly increased. Contrarily, carvedilol preserved adequate Nrf2, GPX4, PINK1 and PARKIN levels and increased catalase. Furthermore, it downregulated ACSL4, reduced NF-κB and MDA levels to maintain normal mitophagy and inhibit ferroptosis. Carvedilol's protective effects extended to alleviate α-synuclein and upregulate tyrosine hydroxylase in the striata and substantia nigra leading to distinguished improvements of motor functions. To the best of our knowledge, this is the first study to highlight carvedilol's neuroprotective capacity against PD pathologies in terms of ferroptosis - mitophagy interaction as a novel therapeutic approach to tackle PD at earlier stages.

Brucellosis is a zoonotic disease with significant global health implications, particularly in endemic regions such as Saudi Arabia. It is characterized by clinical manifestations that mimic both infectious and noninfectious diseases, making diagnosis challenging. Congenital brucellosis, a rare entity, can be transmitted transplacentally from a bacteremic mother or through exposure to maternal secretions during delivery. This report describes the case of a neonate with extremely low birth weight and severe respiratory distress syndrome, who was ultimately diagnosed with congenital brucellosis caused by . Despite treatment with trimethoprim-sulfamethoxazole (TMP/SMX) and rifampin, the infant developed abdominal distension and hypotension, showed a clinical picture consistent with sepsis, and succumbed on day 28 of life. This report underscores the importance of early recognition and management of congenital brucellosis to improve outcomes and highlights gaps in antenatal screening and preventive strategies. Diagnosis was confirmed by isolating from blood culture using standard microbiological methods. The patient was treated with trimethoprim-sulfamethoxazole (8 mg/kg/day) and rifampin (10 mg/kg/day). Clinical signs such as persistent hypoxemia and abdominal distension developed before death on day 28. Antenatal screening gaps in endemic regions such as Saudi Arabia contributed to delayed diagnosis.

Brucellosis is a zoonotic disease with significant global health implications, particularly in endemic regions such as Saudi Arabia. It is characterized by clinical manifestations that mimic both infectious and noninfectious diseases, making diagnosis challenging. Congenital brucellosis, a rare entity, can be transmitted transplacentally from a bacteremic mother or through exposure to maternal secretions during delivery. This report describes the case of a neonate with extremely low birth weight and severe respiratory distress syndrome, who was ultimately diagnosed with congenital brucellosis caused by . Despite treatment with trimethoprim-sulfamethoxazole (TMP/SMX) and rifampin, the infant developed abdominal distension and hypotension, showed a clinical picture consistent with sepsis, and succumbed on day 28 of life. This report underscores the importance of early recognition and management of congenital brucellosis to improve outcomes and highlights gaps in antenatal screening and preventive strategies. Diagnosis was confirmed by isolating from blood culture using standard microbiological methods. The patient was treated with trimethoprim-sulfamethoxazole (8 mg/kg/day) and rifampin (10 mg/kg/day). Clinical signs such as persistent hypoxemia and abdominal distension developed before death on day 28. Antenatal screening gaps in endemic regions such as Saudi Arabia contributed to delayed diagnosis.

Photoaging is a widespread skin health concern caused by UV radiation. It significantly contributes to premature wrinkles and exacerbates further skin damage. This study evaluates the enhanced anti-aging efficacy of a nano phytosome incorporating grape seed extract (GSE) as an innovative, naturally driven antiaging formula, demonstrating putative skin permeability. LC-HRMS analysis and molecular docking revealed the potential of GSE components against photoaging targets. A GSE-nano phytosome formula with phosphatidyl choline (PC)/GSE ratio of 50:1 and 10 mg Vitamin E TPGS displayed optimal physicochemical properties, including particle size (195.1 ± 0.4 nm), polydispersity index (0.312 ± 0.015), zeta potential (25.6 ± 0.4 mV), and complexation efficiency (76.2 ± 4.5 %). FTIR analysis confirmed the formation of hybrid phytosomes through complexation with PC and TPGS. ex vivo confocal microscopy displayed enhanced skin permeability. Biochemical studies confirmed the superior antiaging effect of GSE-phytosome(GSE-nanogel) compared to crude GSE in UV-irradiated rats. GSE nanogel promoted anti-aging by suppressing c-Jun N-terminal kinase (JNK) and NF-κB, caspase-3, enhancing GSH-Px level and reducing malondialdehyde level. These effects suppressed elastase and collagenase activity, significantly improving wrinkles and skin redness. Our findings underscore the efficiency of formulating high molecular weight GSE phytoconstituents as phytosomes that mimic the lipophilic nature of cell membranes, improve skin permeability, and therapeutic efficacy.

Non-small cell lung cancer (NSCLC) is considered a major contributor to cancer-related death rates worldwide, chiefly owing to late diagnosis, occurrence of metastasis, and treatment resistance. Growing evidence underscores the impact of long non-coding RNAs (lncRNAs) on NSCLC progression. These lncRNAs have been demonstrated to influence cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and drug resistance, contributing to cancer development and therapeutic failure. Concurrently, natural products and nutraceuticals are gaining attention for their anticancer properties, particularly in modulating signaling pathways involved in tumorigenesis and drug resistance. Compounds like curcumin, resveratrol, and epigallocatechin gallate have been shown to regulate oncogenic lncRNAs, inhibiting metastasis and reversing chemoresistance. Additionally, natural products upregulate tumor-suppressive lncRNAs, restoring cell cycle control and apoptosis. This review provides an in-depth analysis of the etiological significance of lncRNAs in NSCLC, with a particular emphasis on their contribution to tumorigenesis, metastasis, and therapeutic resistance. In addition, it explores the potential of natural products to modulate lncRNA expression, highlighting their efficacy in overcoming drug resistance and enhancing the therapeutic response. By elucidating the dynamic molecular cross-talk between lncRNAs and natural products, this review also aims to identify novel therapeutic strategies and potential biomarkers for the diagnosis and treatment of NSCLC.

Lumpy Skin Disease (LSD) presents significant risks and economic challenges to global cattle farming. Effective and accurate classification of LSD is essential for managing the disease and reducing its impacts. Manual diagnosis is time-consuming, labor-intensive, and requires experienced personnel. Automated classification methods provide advantages by reducing labor and improving accuracy. This study proposes an automated algorithm for LSD classification using machine learning. The method uses a carefully curated dataset of images from both LSD-infected cattle and healthy cattle. Inception V3 was employed to extract features from complex lesion patterns in infected cattle images, comparing them to healthy cattle images. Support Vector Machines (SVM) were used to classify the extracted features. The results show the model achieved an 84% accuracy rate, with precision at 80%, recall at 83%, and an F1 score of 82%. These results were compared with other machine learning models, including Logistic Regression, Random Forest, Decision Tree, and AdaBoost. SVM outperformed other models, demonstrating consistent evaluation precision at 0.84. For further enhancement, expanding the dataset with high-quality images and applying advanced machine learning algorithms like Vision Transformers (ViTs), MobileNetV2, and Visual Geometry Group (VGG) could refine automated LSD classification. The aim is to improve disease management practices in the livestock industry through better classification systems.

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic care, while 27% were due to acute care. Chronic care needs increased with age, representing 86% of YLDs and 71% of YLLs, and accounting for 93% of YLDs from sequelae. These findings highlight that chronic care needs far exceed acute care needs globally, necessitating health systems to adapt accordingly.

BACKGROUND: Psoriasis is a common chronic systemic disease affecting the skin, nails, and joints. Nails are commonly associated with a greater severity of the disease. Radiofrequency (RF) is a nonionizing radiation that provides energy originating from electric current to generate heat inside the dermis with anti-inflammatory effects.

OBJECTIVE: To assess the efficacy of nonablative bipolar radiofrequency in treating fingernail psoriasis.

METHODS: Forty-three affected fingernails were treated with nonablative bipolar RF. Sessions were performed every 2 weeks for 2 months, with a maximum of 5 sessions. The 32-point target nail psoriasis severity index (tNAPSI), ultrasonography, and the physicians' global assessment were used for assessment at baseline, 1 month, and 3 months from the last treatment session.

RESULTS: One month after the last RF session, a significant reduction in median tNAPSI score from baseline was recorded ( p = .002), with a 58.33% reduction in pit count. The median thickness of subungual hyperkeratosis decreased significantly from baseline ( p = .024), and the median score of onycholysis was also significantly reduced ( p = .005). Ultrasonography revealed a significant reduction in the median nail matrix, bed thickness, and nail vascularity ( p = .020, p < .001, and p = .013, respectively).

CONCLUSION: Radiofrequency may offer a safe and effective treatment modality for fingernail psoriasis.

The present work aimed to load propranolol hydrochloride (PN), a beta-blocking agent with low oral bioavailability, into PLGA-lipid hybrid nanoparticles (PLHNPs) for augmenting its efficacy. PLHNPs contain phospholipid (PC) in addition to PLGA to augment the potential of PLGA nanoparticles in the intranasal delivery and PN avoidance of the blood-brain barrier for the management of migraine. PLHNPs were prepared by single emulsion/ solvent evaporation method and then optimized by applying 2 full factorial design using PC amount (mg) (X), PLGA amount (mg) (X), and surface active agent type (X) as independent variables, whilst their effect was inspected for entrapment efficiency percent (EE%) (Y) and particle size (PS) (Y). Design-Expert® was utilized to choose the optimum PLHNPs for more explorations. The optimum PLHNPs formulation (F2) had EE% of 78.00 ± 0.71 %, PS of 104.50 ± 2.04 nm, polydispersity index of 0.429 ± 0.033, and zeta potential of 23.70 ± 0.10 mV. The optimum PLHNPs formulation was stable for up to 90 days. Moreover, it showed a sustained release profile compared to PN solution. It also showed a spherical shape under a transmission electron microscope. The optimized PN-loaded PLHNPs formulation was radio formulated with radiolabeled isotope ([Tc]Tc) in maximum radiolabeling yield (91.40 ± 1.85 %) of [Tc]Tc-PLHNPs to be used in radiological evaluation for in-vivo biodistribution and brain targeting after oral and intranasal administration. [Tc]Tc-PLHNPs showed higher brain targeting (5.80 ± 0.12 % ID/g) with a high brain-to-blood ratio of (2.42 ± 0.14) at 0.5 h after intranasal administration in addition to controlled blood levels and sustained release up to 8 h that confirm the efficacy of PLHNPs for brain targeting.

ObjectivesTo investigate the clinical and serological features of autoimmunity with chronic hepatitis C virus infection before and after direct-acting antiviral therapy and assess their relation to treatment response.MethodsA prospective cohort study was performed in adult patients aged ≥18 years who had chronic hepatitis C virus infection, as confirmed by polymerase chain reaction, and were eligible for direct-acting antiviral therapy. Patients with rheumatological disease prior to the onset of hepatitis C virus infection, decompensated cirrhosis, or hepatocellular carcinoma were excluded. All patients were treated with sofosbuvir (400 mg once daily) plus daclatasvir (60 mg once daily) for 3 months. Patients were assessed before and 12 weeks after treatment.ResultsNinety patients completed the follow-up (66.7% females, 33.3% males, mean age: 49.2 ± 12.3 years); 85.55% of them had immune-mediated manifestations prior to direct-acting antiviral therapy. In patients with sustained virologic response, autoimmune manifestations persisted in 66 of the 71 (92.9%) patients with an observable rise in posttreatment erythrocyte sedimentation rate and C-reactive protein level (p > 0.01). The predictors of persistence of autoimmune manifestation were age ≥49 years (p = 0.009), female sex (p = 0.026), and tobacco use (p = 0.043).ConclusionDirect-acting antiviral drugs were not associated with a significant short-term change in the prevalence of autoimmune manifestations in patients who had hepatitis C virus infection with sustained virologic response.

OBJECTIVES: To assess the clinical value of ultrasound criteria for the "Morbidly Adherent Placenta" (MAP) and the diagnostic accuracy of a customized "pro forma" in predicting MAP, its extent, and its relationship to intra-operative results.

METHODS: Twenty-one pregnant women with a high possibility of placenta accreta were included in the study. Gray scale transabdominal and transvaginal ultrasound with color Doppler were done to confirm the MAP diagnosis and evaluate the signs of placental invasion. The ultrasound findings were compared with the operative details to predict placental invasion (focal or diffuse) and vascularity of the lower uterine segment to assess the clinical significance of the customized "pro forma."

RESULTS: There was a good accuracy of ultrasound signs to detect the vascularity of the lower uterine segment with a sensitivity of 94.12%, specificity of 25%, positive predictive value (PPV) of 84.21%, negative predictive value (NPV) of 50%, and accuracy of 80.95%; however, it was insignificant (p = 0.352). Additionally, we found a good accuracy of ultrasound signs to detect the degree of placental invasion (focal or diffuse), with a sensitivity of 71.43%, specificity of 100%, PPV of 100%, NPV of 63.64%, and accuracy of 80.95%, which was significant (p = 0.004).

CONCLUSION: This customized "pro forma" has satisfactory accuracy in predicting MAP cases with anterior placenta previa or anterior low-lying placenta.

BACKGROUND AND AIMS: Children undergoing median sternotomy often face moderate to severe postoperative discomfort, along with various other complications. Under ultrasound guidance, a pectointercostal fascial block (PIFB) might relieve this pain. This research aimed to assess the effectiveness of a single-level PIFB for poststernotomy analgesia in children.

METHODS: Sixty children scheduled for elective open-heart surgery through a midline sternotomy were randomly assigned to a pectointercostal group (PI) that was administered bilateral PIFB or a control group (C) that did not receive any intervention. The primary outcome was the postoperative Face, Legs, Activity, Cry, and Consolability (FLACC) pain scale score at 6 h. The analysis employed Student's -test for variables with a normal distribution and Chi-squared test/Fisher's exact test for categorical data, with a significance threshold established at a value < 0.05.

RESULTS: Intraoperative PIFB decreased the total dose of fentanyl ( < 0.001) while maintaining a favourable haemodynamic profile. Postoperative PIFB reduced pain scores ( < 0.001), as evidenced by a delayed initial request for rescue analgesia ( < 0.001), reduced morphine consumption ( < 0.001) and improved predictive indicators such as extubation time ( < 0.001) and intensive care unit stay ( = 0.008) without complications.

CONCLUSION: Single-level, ultrasound-guided PIFB provides good analgesia and hastens recovery in children's open-heart surgery through a midline sternotomy.

Traditionally, taste receptors (TRs) have been understood to reside within the taste buds on the tongue, serving as initiators for different taste perceptions. However, recent research has expanded our understanding, revealing that TRs are found throughout the body and perform a wide range of functions beyond taste perception as non-tasting functions. These receptors, along with their genetic variations, have been linked to various human health conditions. They are activated by an array of substances, including hormones, nutrients, and toxins, indicating their involvement in numerous biological processes. Specifically, in males, TRs are notably present in the testes and epididymis, where they contribute to the hormonal production, spermatogenesis, and sperm maturation. In females, these receptors are found in the ovaries, uterus, and myometrium, playing crucial roles in ovulation, menstrual cycle regulation, and embryo implantation. There are a lot of missed areas regarding TRs research that imposes to fulfill the gaps in the current understanding of their role in reproduction. This review aims to provide a comprehensive overview of the emerging roles of extraoral TRs in reproductive health, highlighting their physiological and pathophysiological significance in various reproductive processes. As well, grabbing the attention towards the release of new pharmacological interventions to manage conception and contraception in male and female was considered.

Tau hyper-phosphorylation has been recognized as an essential contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies. In the last decade, tau hyper-phosphorylation has gained considerable concern in AD therapeutic development. Tauopathies are manifested with a broad spectrum of symptoms, from dementia to cognitive decline and motor impairments. Tau undergoes conformational changes and abnormal phosphorylation that mediate its detaching from microtubules, forming neurofibrillary tangles (NFTs). In the current study, a widely used P301S transgenic mice model of tauopathy was employed to evaluate the possible neuroprotective effects of semaglutide as an autophagy regulator through modifications of the brain renin-angiotensin system (RAS). Mice were divided into two groups according to their genotypes (wild type (Wt) and P301S), which were further subdivided to receive either vehicle (saline) or semaglutide (25 nmol/kg, i. p.), once every 2 days for 28 days. Current data suggest that semaglutide ameliorated the hyperactive pattern and alleviated the cognitive decline of P301S mice. It also hastened the autophagic flux through augmenting angiotensin-converting enzyme 2/sirtuin 1/forkhead box protein O1 signaling. Semaglutide also hindered the expression of phosphorylated adenosine monophosphate-activated protein kinase and phosphorylated glycogen synthase kinase-3 beta at serine 9, reducing the propagation of neuroinflammatory cytokines and oxidative reactions. Finally, semaglutide protected against hippocampal degeneration and reduced the immunoreactivity for total tau and ionized calcium-binding adapter molecule. Semaglutide showed promising neuroprotective implications in alleviating tauopathy-related AD's molecular and behavioral deficits through controlling autophagy and brain RAS.

BACKGROUND: Overweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050.

METHODS: Leveraging established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study, we estimated the prevalence of overweight and obesity among individuals aged 25 years and older by age and sex for 204 countries and territories from 1990 to 2050. Retrospective and current prevalence trends were derived based on both self-reported and measured anthropometric data extracted from 1350 unique sources, which include survey microdata and reports, as well as published literature. Specific adjustment was applied to correct for self-report bias. Spatiotemporal Gaussian process regression models were used to synthesise data, leveraging both spatial and temporal correlation in epidemiological trends, to optimise the comparability of results across time and geographies. To generate forecast estimates, we used forecasts of the Socio-demographic Index and temporal correlation patterns presented as annualised rate of change to inform future trajectories. We considered a reference scenario assuming the continuation of historical trends.

FINDINGS: Rates of overweight and obesity increased at the global and regional levels, and in all nations, between 1990 and 2021. In 2021, an estimated 1·00 billion (95% uncertainty interval [UI] 0·989-1·01) adult males and 1·11 billion (1·10-1·12) adult females had overweight and obesity. China had the largest population of adults with overweight and obesity (402 million [397-407] individuals), followed by India (180 million [167-194]) and the USA (172 million [169-174]). The highest age-standardised prevalence of overweight and obesity was observed in countries in Oceania and north Africa and the Middle East, with many of these countries reporting prevalence of more than 80% in adults. Compared with 1990, the global prevalence of obesity had increased by 155·1% (149·8-160·3) in males and 104·9% (95% UI 100·9-108·8) in females. The most rapid rise in obesity prevalence was observed in the north Africa and the Middle East super-region, where age-standardised prevalence rates in males more than tripled and in females more than doubled. Assuming the continuation of historical trends, by 2050, we forecast that the total number of adults living with overweight and obesity will reach 3·80 billion (95% UI 3·39-4·04), over half of the likely global adult population at that time. While China, India, and the USA will continue to constitute a large proportion of the global population with overweight and obesity, the number in the sub-Saharan Africa super-region is forecasted to increase by 254·8% (234·4-269·5). In Nigeria specifically, the number of adults with overweight and obesity is forecasted to rise to 141 million (121-162) by 2050, making it the country with the fourth-largest population with overweight and obesity.

INTERPRETATION: No country to date has successfully curbed the rising rates of adult overweight and obesity. Without immediate and effective intervention, overweight and obesity will continue to increase globally. Particularly in Asia and Africa, driven by growing populations, the number of individuals with overweight and obesity is forecast to rise substantially. These regions will face a considerable increase in obesity-related disease burden. Merely acknowledging obesity as a global health issue would be negligent on the part of global health and public health practitioners; more aggressive and targeted measures are required to address this crisis, as obesity is one of the foremost avertible risks to health now and in the future and poses an unparalleled threat of premature disease and death at local, national, and global levels.

FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Despite the well documented consequences of obesity during childhood and adolescence and future risks of excess body mass on non-communicable diseases in adulthood, coordinated global action on excess body mass in early life is still insufficient. Inconsistent measurement and reporting are a barrier to specific targets, resource allocation, and interventions. In this Article we report current estimates of overweight and obesity across childhood and adolescence, progress over time, and forecasts to inform specific actions.

METHODS: Using established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021, we modelled overweight and obesity across childhood and adolescence from 1990 to 2021, and then forecasted to 2050. Primary data for our models included 1321 unique measured and self-reported anthropometric data sources from 180 countries and territories from survey microdata, reports, and published literature. These data were used to estimate age-standardised global, regional, and national overweight prevalence and obesity prevalence (separately) for children and young adolescents (aged 5-14 years, typically in school and cared for by child health services) and older adolescents (aged 15-24 years, increasingly out of school and cared for by adult services) by sex for 204 countries and territories from 1990 to 2021. Prevalence estimates from 1990 to 2021 were generated using spatiotemporal Gaussian process regression models, which leveraged temporal and spatial correlation in epidemiological trends to ensure comparability of results across time and geography. Prevalence forecasts from 2022 to 2050 were generated using a generalised ensemble modelling approach assuming continuation of current trends. For every age-sex-location population across time (1990-2050), we estimated obesity (vs overweight) predominance using the log ratio of obesity percentage to overweight percentage.

FINDINGS: Between 1990 and 2021, the combined prevalence of overweight and obesity in children and adolescents doubled, and that of obesity alone tripled. By 2021, 93·1 million (95% uncertainty interval 89·6-96·6) individuals aged 5-14 years and 80·6 million (78·2-83·3) aged 15-24 years had obesity. At the super-region level in 2021, the prevalence of overweight and of obesity was highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and the greatest increase from 1990 to 2021 was seen in southeast Asia, east Asia, and Oceania (eg, Taiwan [province of China], Maldives, and China). By 2021, for females in both age groups, many countries in Australasia (eg, Australia) and in high-income North America (eg, Canada) had already transitioned to obesity predominance, as had males and females in a number of countries in north Africa and the Middle East (eg, United Arab Emirates and Qatar) and Oceania (eg, Cook Islands and American Samoa). From 2022 to 2050, global increases in overweight (not obesity) prevalence are forecasted to stabilise, yet the increase in the absolute proportion of the global population with obesity is forecasted to be greater than between 1990 and 2021, with substantial increases forecast between 2022 and 2030, which continue between 2031 and 2050. By 2050, super-region obesity prevalence is forecasted to remain highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and forecasted increases in obesity are still expected to be largest across southeast Asia, east Asia, and Oceania (eg, Timor-Leste and North Korea), but also in south Asia (eg, Nepal and Bangladesh). Compared with those aged 15-24 years, in most super-regions (except Latin America and the Caribbean and the high-income super-region) a greater proportion of those aged 5-14 years are forecasted to have obesity than overweight by 2050. Globally, 15·6% (12·7-17·2) of those aged 5-14 years are forecasted to have obesity by 2050 (186 million [141-221]), compared with 14·2% (11·4-15·7) of those aged 15-24 years (175 million [136-203]). We forecasted that by 2050, there will be more young males (aged 5-14 years) living with obesity (16·5% [13·3-18·3]) than overweight (12·9% [12·2-13·6]); while for females (aged 5-24 years) and older males (aged 15-24 years), overweight will remain more prevalent than obesity. At a regional level, the following populations are forecast to have transitioned to obesity (vs overweight) predominance before 2041-50: children and adolescents (males and females aged 5-24 years) in north Africa and the Middle East and Tropical Latin America; males aged 5-14 years in east Asia, central and southern sub-Saharan Africa, and central Latin America; females aged 5-14 years in Australasia; females aged 15-24 years in Australasia, high-income North America, and southern sub-Saharan Africa; and males aged 15-24 years in high-income North America.

INTERPRETATION: Both overweight and obesity increased substantially in every world region between 1990 and 2021, suggesting that current approaches to curbing increases in overweight and obesity have failed a generation of children and adolescents. Beyond 2021, overweight during childhood and adolescence is forecast to stabilise due to further increases in the population who have obesity. Increases in obesity are expected to continue for all populations in all world regions. Because substantial change is forecasted to occur between 2022 and 2030, immediate actions are needed to address this public health crisis.

FUNDING: Bill & Melinda Gates Foundation and Australian National Health and Medical Research Council.

OBJECTIVE: The escalating incidence of de novo spinal infections poses a substantial neurological impact on patients. This has prompted a growing interest in discerning which patients would derive greater benefit from medical as opposed to surgical management of these occurrences. The authors assessed the predictive applicability of the Spinal Infection Treatment Evaluation (SITE) score in discerning between surgical intervention and medical management. This assessment represents the first external validation of the SITE score conducted in a cohort of patients with de novo spinal infections.

METHODS: A comprehensive retrospective chart review was conducted to identify patients diagnosed with de novo spinal infections (osteomyelitis, discitis, or epidural abscess) at a tertiary center between July 1, 2004, and March 31, 2023. All necessary data for calculating the SITE score were collected for each patient. Surgical intervention was advised for patients scoring 0-8 or exhibiting acute plegia or bladder or bowel dysfunction and optional for those scoring 9-12; medical treatment was recommended for patients scoring 13-15. Predictability of the score was scrutinized using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.

RESULTS: Among 194 identified patients, the mean ± SD age was 65.96 ± 13.66 years and 58% were men. Stratification of patients based on medical and surgical management revealed that 27% underwent medical treatment alone and 73% required surgical intervention. In the medical group, 72.2% of patients were neurologically intact compared to 50% in the surgical group (p = 0.006). Surgically managed patients exhibited a higher incidence of spinal stenosis with impingement of the spinal cord, with or without deformity, when compared to nonsurgical patients (38.6% vs 22.2%, p = 0.04). Additionally, surgically managed patients had a lower mean ± SD SITE score (7.16 ± 2.39 vs 8.2 ± 2.33, p < 0.005) and were more likely to have multilevel infection than patients who underwent medical management (59.3% vs 33.3%, p < 0.001). When patients were categorized on the basis of SITE score, the sensitivity of the score (using a threshold of 8) to predict surgical management was 68.6% and specificity was 59.3%. According to ROC curve, the SITE score exhibited an AUC of 0.66.

CONCLUSIONS: Validation of the SITE score could not accurately predict medical versus surgical management in a tertiary center cohort of patients with de novo spinal infections. Further multicenter studies incorporating additional variables and larger cohorts are imperative to develop an optimal predictive tool.

Chemotherapy is the most common cancer treatment, and metallic anticancer compounds have generated increasing amounts of interest since the discovery of cisplatin. More recently, scientists have focused on ruthenium-based compounds as alternatives for platinum compounds, which seem like ideal therapeutic anticancer alternatives to platinum derivatives. The present study aims to assess whether one or more of three Ruthenium-based nanocomposites, namely Ru+Lysine+CTAB (RCTL), Ru+CTAB (RCT), and Ru+Lysine (RL) exhibit pronounced anti-proliferative properties against different cancer cells. Three Ruthenium nanocomposites have been synthesized by standard chemical methods and characterized by Dynamic light scattering (DLS) and Transmission electron microscopy (TEM). The cytotoxic effect of the three composites has been evaluated by MTT in-vitro assay for different human cancer cell lines, namely MCF7, HepG2, A549, and PC3 versus normal human skin cell line (BJ1). The molecular underlying mechanisms of cytotoxicity have been assessed via qRT-PCR for pro-apoptotic makers P53 and Casp-3, and anti-apoptotic marker Bcl-2 as well as flow cytometric analysis of the cell cycle. Among the 3 nanocomposites, RCTL gave the best sensitivity and cytotoxicity especially on HepG2 with IC 0.55 µg/ml but was still toxic on normal cell line with dose <12.5 µg/ml. RCTL and RCT nanocomposites have demonstrated a significant increase in the expression of P53 and Casp-3 markers versus untreated controls, but a significant reduction in the expression of Bcl-2. There was a direct correlation between the cytotoxic effect and the degree of apoptosis in the different cancer cell lines. The present study has also proved cell cycle arrest at G2-M and pre-G1 phases under the effect of IC of RCTL and RCT nanocomposites in different cancer lines with the best effect being achieved in HepG2 cells. Ruthenium nanocomposites seem to open a new avenue in cancer therapy.

BACKGROUND: Among the serious quail diseases is coccidiosis, caused by several species, particularly cecal coccidiosis, with considerable economic losses.

AIM: First, 11 quail flocks showing brownish diarrhea tinged with blood and bloody cecal core were submitted for spp. detection. A selected was used to evaluate the comparative anticoccidial efficacy of a commercial herbal product containing oregano and garlic essential oils (EOs) as a prophylactic supplement via drinking water taking into consideration that it had never been applied in quails' coccidiosis before.

METHODS: A total of 300 Japanese quails were equally assigned to four groups. One of the groups was given basal drinking water and served as the control (G-4). The remaining groups (G-1, 2, and 3) received drinking water containing herbal (Coxan), chemical (Clazo-Fort), and herbal interchangeably with chemical products, respectively. At 14 days of age, each group was subdivided into two subgroups. The subgroups, 1B-4B were infected with sporulated oocysts of (4.1 × 10).

RESULTS: The infected group showed a typical cecal lesion of which was confirmed histopathologically by the presence of different developmental stages in both intracellular lining and cecal content. The alternative herbal product had the highest anticoccidial index with a value of 154.88. Anticoccidial sensitivity test and reduction of lesion score were 77.3, which indicated both herbal and chemical products were sensitive against . Additionally, quails supplemented with Coxan had the highest BWG ( < 0.05). Additionally, a high HI antibody titer against NDV was obtained in the Coxan group with a significant increase (7.66 ± 0.67 log; 0.039) at 21 days of age and a high CD4 antigen value (1762 ± 87.5 pg/ml) in sera at 14 days of age. In the jejunum of the Coxan group, a significant increase in villi length was associated with a reduction in the crypt depth, and the highest villi length and crypt depth ratio were represented, accompanied by a higher count of intestinal lactobacillus ( 0.0236) compared to the infected group.

CONCLUSION: The prophylactic supply of alternative herbal products containing oregano and garlic EOs could be a safe, potent anticoccidial in quails that is consistent with the world's transition to a green economy besides its immune-stimulant properties.