Dr Mohammed Mahmoud Youssif

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.

INTRODUCTION: About 20-30% of cases of infertility are attributed to male factor and males are also contributing to infertility in a further 20%. Idiopathic male subfertility is the commonest cause in most cases. D-aspartic acid (D-Asp) is an endogenous amino acid occurring in several tissues and cells of both invertebrates and vertebrates. The current study is one of the first to evaluate the in vivo supplementation of D-aspartic acid in idiopathic male infertility. Thus, we aimed in the current study to evaluate the in vivo effect of D-aspartic acid, zinc and co-enzyme Q 10 supplementation on different semen parameters and serum testosterone level in idiopathic male infertility.

METHODS: A total of 75 infertile patients were recruited from the outpatient andrology clinic from March 2023 to June 2024. The current study was registered at the UMIN clinical registry trials prior to initiating the study (UMIN000050023). Group (A) included 24 infertile patients who received 2660 mg d-aspartic acid plus 200 mg of ubiquinol plus 10 mg zinc once daily for 3 months. Group (B) included 24 infertile patients who received placebo (starch granules) daily for 3 months.

RESULTS: Interestingly, patients in group (A) who received 2660 mg d-aspartic acid plus 200 mg of ubiquinol plus 10 mg zinc once daily for 3 months showed significant improvement in progressive sperm motility after 3 months (10.63 ± 8.64 vs 15.21 ± 12.11, p=0.047). Also, they showed highly significant increase in total testosterone level (5.06 ± 1.74 vs 5.89 ± 1.62, p=0.009).

CONCLUSIONS: D-aspartic acid plus ubiquinol plus zinc are promising ingredients that showed good results when administrated once daily to infertile males.

In vitro maturation (IVM) of oocytes retrieved from ovum pick-up (OPU) or ovarian tissue (OT) is a standard approach for patients with specific conditions where prior hormonal stimulation is contraindicated. However, the developmental competence of oocytes matured in vitro is still inferior to that of oocytes matured in vivo. Capacitation IVM (CAPA-IVM) includes an extra step of pre-maturation culture (PMC) with c-type natriuretic peptide (CNP) as a meiotic arrestor to better synchronize cytoplasmic and nuclear maturity in oocytes by allowing the cytoplasm additional time to acquire essential components critical for optimal competency. This study aims to evaluate the effect of CAPA-IVM on equine oocyte quality and developmental competence. Immature cumulus-oocyte complexes (COCs) were retrieved from slaughterhouse ovaries and matured in vitro either in CAPA-IVM (short 6 h, long 24 h pre-maturation) or standard IVM. Mature oocytes from each group were analyzed for calcium-releasing potential ( = 52) and single-oocyte proteomics ( = 44), and embryo development ( = 229) was assessed after fertilization with piezo-drilled intracytoplasmic sperm injection (ICSI). Genetic analysis of developed blastocysts ( = 41) was performed to detect chromosomal aberrations. Our findings demonstrate that CAPA-IVM of equine COCs yields significantly higher maturation rates than controls. Moreover, short CAPA-IVM with six hours pre-maturation culture showed substantially higher embryo development potential than the control group (20/69 vs. 9/63, respectively). Genetic analysis revealed a high euploidy rate in equine blastocysts regardless of the maturation conditions. Live calcium imaging of the fertilized oocytes demonstrated that the majority of oocytes displayed non-continuous calcium oscillation patterns, irrespective of maturation conditions. Single-oocyte proteomics reveals a comparable proteomic landscape between mature oocytes subjected to short CAPA-IVM and standard IVM. However, we identified four enriched gene sets with positive enrichment scores after short CAPA-IVM, related to cytoskeleton regulation, ribosomal function, and cytosolic components. Our findings indicate that CAPA-IVM holds the potential to improve oocyte quality and competence in horses. However, further fine-tuning of culture conditions would benefit the effective use of these IVM systems. Moreover, given that the mare serves as an excellent model for human reproduction, the molecular trends identified in this study could provide valuable insights for advancing human artificial reproductive technologies.

UNLABELLED: Porcine contagious pleuropneumonia caused by (APP) is a fatal respiratory disease that threatens the worldwide farming industry's health. The immune responses of extrapulmonary tissues play an important role in developing porcine contagious pleuropneumonia; however, the immune responses of extrapulmonary tissues induced by APP are rarely uncovered. Here, we used high-dimensional mass cytometry to investigate the immune cell response in the spleen and peripheral blood during APP infection in mice. We found that the immune response triggered by APP was highly tissue-specific. Numerous infection time- or tissue-specific immune cell clusters, including previously unrecognized ones, were also identified in the spleen and peripheral blood. Integrative analysis of splenic lymphoid and myeloid cell clusters maps the dynamic immune response cellular network during APP infection. Surprisingly, during the early stages of APP infection, the majority of the top 6 cell clusters contributing to the infection time-specificity in the spleen were adaptive immune cell clusters rather than innate immune cell clusters, among which CD24MHCIICD8T cells exhibited a stronger expression of IFN-γ, IL-17A, and IL-10 compared to the CD24 compartment. In peripheral blood, there was unprecedented heterogeneity in the immune cell composition. Also, peripheral immune cell clusters closely related to the severity of APP infection were identified. In summary, our data provide a systemic and comprehensive overview of the immune responses to APP infection in the spleen and peripheral blood. This provides a foundation for understanding the immune pathogenesis of APP and identifying potential diagnostic biomarkers and therapeutic targets.

IMPORTANCE: This study explored the cross-tissue immune dynamic landscape in the APP-induced pneumonia model by utilizing high-dimensional mass cytometry. We discovered that APP-induced immune responses are tissue-specific. Key infection-specific clusters in the spleen and peripheral blood were identified, some of which were previously unrecognized. Meanwhile, the specific functions of APP infection-related immune subsets were explored. The research systematically outlined an overview of immune responses in these tissues, deepening the understanding of APP pathogenesis and laying the foundation for the search for diagnostic and therapeutic targets.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease affecting the oral mucosa, with immune mediated pathogenesis. Both zinc and vitamin D are essential micronutrients implicated in OLP pathogenesis, with zinc influencing epithelial growth, wound healing, and oxidative stress mitigation, while vitamin D modulates immune cell function, cytokine activity, and keratinocyte behavior. The current trial was conducted to assess the effect of topical corticosteroid supplemented with zinc or vitamin D compared to topical corticosteroid in management of symptomatic oral lichen planus.

METHODS: Forty-two patients diagnosed with symptomatic oral lichen planus (atrophic, erosive, or bullous types) were included in the study, based on clinical examination and histopathological confirmation in accordance with the modified World Health Organization (WHO) criteria (2003). Participants were divided randomly into three parallel groups. Group I received topical corticosteroid; Group II received topical corticosteroid with systemic zinc; Group III received topical corticosteroid with systemic vitamin D. The outcome measures included pain intensity using Visual Analogue Scale and clinical improvement using Thongprasom et al. scoring system. Treatment lasted for 8 weeks; patients were clinically evaluated at baseline and on weekly basis.

RESULTS: Intergroup comparisons revealed that by Week 3, pain scores were significantly lower in Groups II and III compared to Group I. Intragroup analysis showed significant reductions in pain scores over time for all groups, with Group II showing the most pronounced decrease from baseline to Week 7. Thongprasom scores decreased significantly in all groups, with Group II showing the most significant reduction by Week 8.

CONCLUSIONS: Systemic zinc supplementation combined with topical corticosteroid can be used as an adjunct therapy for OLP management. Topical corticosteroid supplemented with vitamin D has comparable effect to topical corticosteroid alone on pain and clinical improvement in symptomatic OLP.

CLINICAL TRIAL REGISTRATION: NCT04765267 (full protocol can be accessed). Date of Initial Clinical Trial Registration: 4 February 2021.

MicroRNA-21 (miRNA-21) expression is increased in patients with kidney disease, and polysaccharides provide the structural scaffolding of the glomerular and tubular basement membranes.We investigated whether the induction of renal injury by the industrial toxic chemical thioacetamide (TAA) can dysregulate the kidney miRNA-21/SIRT1/NF-κB axis as well as the structural polysaccharide content of the kidney tissue, and whether treatment with the polyphenolic compound resveratrol can inhibit these adverse effects.Kidney injury was induced in rats by TAA (200 mg/kg) injections. The protective group of rats was pre-treated with resveratrol (20 mg/kg) prior to kidney injury and subsequently kept on resveratrol until culled.TAA intoxication caused a significant ( < 0.0001) modulation in kidney and blood levels of miRNA-21, the tissue renoprotective molecule SIRT1, NF-κB p65, kidney structural polysaccharides, the macrophage biomarker cluster of differentiation 68 (CD68), tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, hypernatremia, urea, and creatinine, as well as albuminuria that were significantly ( ≤ 0.0187) protected by resveratrol. Furthermore, a significant correlation between the miRNA-21/SIRT1/NF-κB axis, structural polysaccharides, renal fibrosis, and renal injury biomarkers was observed.These findings demonstrate an association between renal injury induced by TAA intoxication and the dysregulation of the kidney miRNA-21/SIRT1/NF-κB axis and polysaccharide levels while being protected by resveratrol.

BACKGROUND: Doxorubicin (DOX), a potent antineoplastic drug, can induce cardiotoxicity through its cardiotoxic metabolites catalyzed by CBR 3 and its accumulation in cardiac tissue via the ABCC1 transporter. Here, we investigated CBR3 and ABCC1 genetic polymorphisms affecting doxorubicin cardiotoxicity in breast cancer patients and explored the potential role of brain natriuretic peptide (BNP) as an early cardiac biomarker.

METHODS: One hundred Breast cancer patients are receiving DOX treatment. Blood samples were analyzed for CBR3 and ABCC1 gene polymorphisms and echocardiography and BNP biomarkers were used to assess cardiotoxicity at baseline and three months post-DOX treatment.

RESULTS: Following the DOX treatment, CBR3 genotypes showed significant differences in BNP levels and delta BNP ( = 0.001 and 0.014, respectively). There was a significant association between different CBR3 genotypes and BNP levels after DOX ( = 0.001) and delta BNP ( = 0.01), with AA genotypes associated with cardiotoxicity. ABCC1 was not associated significantly with cardiotoxicity ( = 0.67). There was a statistically significant difference between CBR3 genotypes and the occurrence of anemia ( = 0.023).

CONCLUSION: Detecting CBR3 genetic polymorphisms is crucial for assessing cardiotoxicity before administering DOX, and monitoring BNP levels helps early detection. CBR3 is also associated with DOX anemia.

PURPOSE: To evaluate the effectiveness and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in managing early-onset glaucoma secondary to Sturge-Weber syndrome (SWS).

DESIGN: A retrospective interventional case series.

PARTICIPANTS: Medical records of 16 patients (22 eyes) diagnosed with early-onset glaucoma secondary to SWS who underwent GATT surgery were reviewed.

METHODS: All patients underwent GATT surgery using a 5-0 or 6-0 prolene suture under general anesthesia.

MAIN OUTCOME MEASURES: The primary outcomes were intraocular pressure (IOP) reduction, complete surgical success (IOP ≤ 18 mmHg without medications), qualified surgical success (IOP ≤ 18 mmHg with medications), and postoperative complications.

RESULTS: The mean IOP decreased significantly from 25.4 ± 4.8 mmHg at baseline to 15.7 ± 4.2 mmHg at the final follow-up (P < 0.001), representing a 38.19% reduction. The mean age at the time of GATT surgery was 33.6 ± 33.9 months. The mean follow-up duration was 16.3 ± 6.4 months. Complete surgical success was achieved in 45.4% of eyes (10 out of 22), while qualified success was reached in 81.8% of eyes (18 out of 22). Despite the overall success, 18.1% of eyes (4 eyes) required additional surgical interventions during the follow-up period. These included Ahmed glaucoma valve implantation in 1 eye, trabeculectomy in 2 eyes, and transscleral diode laser cyclophotocoagulation in 1 eye. Transient hyphema was the only reported complication, resolving spontaneously within 1 week without further intervention.

CONCLUSIONS: Gonioscopy-assisted transluminal trabeculotomy appears to be a promising surgical option for managing early-onset glaucoma in patients with SWS, offering significant IOP reduction and a favorable safety profile within the limitations of our study. However, further studies with longer follow-up periods and comparative groups are necessary to confirm these findings.

FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

BACKGROUND: Data on the epidemiology and molecular characterization of feline immunodeficiency virus (FIV) in Egypt are limited. This study aimed to estimate FIV prevalence in 240 Egyptian cats during 2022–2024 using three diagnostic techniques: two point-of-care antibody detection kits (Anigen and SNAP) and one end-point PCR targeting the gene. FIV infection is defined as positivity in at least two of the three diagnostic methods or PCR alone confirmed by sequencing, Additionally, FIV-associated clinicopathological abnormalities were assessed, and, for the first time in Egypt, circulating FIV subtypes were identified through partial sequencing and phylogenetic analysis of all gene-positive samples ( = 10), along with 4 additional gene-positive samples.

RESULTS: Using our diagnostic criteria, 76 of 240 cats (31.7%) were identified as FIV-infected. Of these 76 cases, 75 were positive on both rapid kits, yielding a sensitivity of 98.7% for sequential testing with Anigen and SNAP, whereas only 10 were positive on PCR and sequencing (13.2% sensitivity). FIV-infected cats exhibited lymphopenia, thrombocytosis, hyperglobulinemia, and reduced albumin/globulin ratios. On and gene-based phylogenetic analyses, Egyptian strains did not cluster with any known FIV subtype (A-F and U-NZ) but formed a distinct, previously uncharacterized clade. The Egyptian sequences displayed low intra-group diversity (2.8–3.7%) but high divergence from all known subtypes (21–25%), with no evidence of recombination observed. Moreover, these sequences were derived from both shelter-housed and client-owned cats across three Egyptian governorates within a one-year period.

CONCLUSION: Given their genetic distinctiveness and widespread detection, we propose a novel FIV subtype, tentatively designated “X-EGY.” Its dominance and limited variability among its strains suggest it represents an ancient lineage uniquely adapted to Egyptian cats, rather than a recently emerged variant. This subtype may partly contribute to Egypt’s notably high FIV prevalence. Serological testing, utilizing two point-of-care kits in screening and confirmation steps, is the most accurate FIV diagnostic approach, outperforming molecular testing, particularly in regions where genetic data on circulating strains are scarce. Overall, the findings enhance our understanding of FIV epidemiology and diagnostic strategies and offer new insights into viral diversity and evolution.

BACKGROUND: Breast cancer remains a leading cause of morbidity worldwide, necessitating innovative and accessible interventions that address both clinical and psychosocial needs. AI-powered chatbots are increasingly used in health education due to their 24/7 availability, personalization, and interactivity. However, empirical evidence on their effectiveness in enhancing knowledge, empowerment, and attitudes in oncology settings remains limited.

AIM: This randomized controlled trial (RCT) evaluated the impact of an AI chatbot intervention on knowledge, empowerment, and attitudes toward AI among breast cancer patients.

METHODS: A two-arm, pre-post RCT was conducted with 122 women diagnosed with breast cancer at Kafr El-Sheikh University Hospital. Participants were randomly assigned to an intervention group (n = 61) receiving structured AI chatbot-based education plus standard care, or a control group (n = 61) receiving standard care alone. Data were collected using validated questionnaires assessing breast cancer and AI knowledge, attitudes toward AI, and perceived empowerment. G*Power analysis determined sample adequacy for between-group comparisons.

RESULTS: Post-intervention, the intervention group showed significantly higher knowledge (20.3 ± 2.1 vs. 17.9 ± 3.4, p <.001) and more positive attitudes (82.4 ± 7.2 vs. 72.6 ± 8.9, p <.001) compared to controls. Logistic regression indicated that knowledge gain and higher education predicted a positive AI attitude. Path analysis revealed both direct and mediated effects of knowledge on attitude via empowerment. Usage data and chatbot session logs supported high engagement.

CONCLUSION: Integrating AI chatbots into oncology nursing care significantly enhances knowledge, empowerment, and AI acceptance. These findings support chatbot integration in patient-centered digital health strategies, particularly in oncology.

CLINICAL TRIAL NUMBER: Not applicable.

TRIAL REGISTRATION: NCT06943911 (retrospectively registered on 24/4/2025).

Erectile dysfunction (ED) poses a significant challenge to male sexual health globally, prompting the exploration of alternative treatments beyond conventional pharmaceutical interventions targeting the phosphodiesterase-5 (PDE5) enzyme. This study comparatively investigates the efficacy of essential oils hydrodistilled from expanded and unexpanded flowers (EF and UF) of Citrus reticulata L. in addressing ED by targeting two key enzymes: Rho-kinase II (ROCK-II) and PDE5A1. Gas chromatography-mass spectrometry (GC/MS) was utilized to analyze the chemical composition of these oils and revealed the presence of 35 and 40 compounds in EF and UF, respectively, across various classes. Monoterpene hydrocarbons are deemed to be the dominant class, constituting 64.33% and 71.93% of the total oil composition in EF and UF, respectively. The results highlight the significant efficacy of UF, represented by their ability to modulate ROCK-II and PDE5A1 activities with IC values of 2.64 ± 0.09 and 0.42 ± 0.015 µg/mL, respectively, compared to sildenafil citrate (IC = 0.97 ± 0.03 and 0.042 ± 0.001 µg/mL). Besides, two molecular docking processes were applied to evaluate the activity of major identified volatile constituents toward PDE5A1 and ROCK-II target receptors. These findings offer valuable insights into future therapeutic strategies in ED management.

In continuous search for RANKL induced osteoclastogenesis inhibitors, twenty-six fungal isolates were obtained from ten Red Sea marine sponges collected from Egypt and the ethyl acetate fractions of their cultures' methanol extracts were assessed in RAW264 macrophages. Active fractions were profiled via LC-MS/MS, followed by untargeted molecular networking, leading to the tentative identification of eight unreported compounds (1, A2, C1, C2, C4-C7), and thirteen known compounds. The two active fungi were identified and deposited in GenBank with accession numbers PQ423742 and PQ423748 for Aspergillus flavus and Cladosporium colombiae, respectively. Bioassay-guided isolation afforded two bisphenol diglycidic ethers, 1 and 2, and two diketopiperazines, 3 and 4 from A. flavus, while C. colombiae yielded cinnamic acid (5), two diketopiperazines (6 and 7), and altenuene (8). Structures were elucidated by NMR and mass spectroscopic analyses, which revealed 1 to be isolated for the first time from natural sources. Isolated compounds were biologically evaluated. Only 1 and 8 inhibited RANKL-induced formation of mature multinucleated osteoclasts with IC 57.14 and 38.35 µM, respectively, without cytotoxicity against RAW264 macrophages. The ADMET properties for 1 and 8 were predicated using SwissADME and pkCMS platforms. 8 showed superior solubility and lower toxicity than compound 1.

Endoplasmic reticulum (ER) stress and misfolded proteins accumulation are recognized as central factors in the development of psychiatric disorders. This study evaluated the potential therapeutic effect of fluvoxamine, a potent sigma-1 receptor agonist in alleviating protein misfolding and the subsequent ER stress in ketamine-induced model of schizophrenia. NE100 hydrochloride, a sigma-1 receptor blocker, was used to investigate the role of this receptor in fluvoxamine-mediated effects. Rat model of schizophrenia was induced by intraperitoneal administration of ketamine (30 mg/kg/day) for 5 consecutive days. Then, rats were treated with fluvoxamine (30 mg/kg/day, p.o), with or without NE100 (1 mg/kg/day, i.p), for 14 days. Fluvoxamine improved the learning abilities, cognitive flexibility, and sociability functions of ketamine-subjected rats as evidenced in Morris water maze and three-chamber social interaction tests. It mitigated ketamine-induced inhibition of nNOS/PSD-95/NMDAR signaling pathway, thus augmented the function of parvalbumin-GABAergic neurons as indicated by increasing the prefrontal cortical levels of parvalbumin and GAD67. Fluvoxamine also attenuated the prefrontal cortical production of unfolded protein response markers, namely, IRE-1, PERK, and ATF-6, highlighting its ability to alleviate ER stress. Further, it exerted anti-apoptotic and anti-inflammatory effects as shown by lowering Iba-1, tumor necrosis factor-α (TNF-α), Bax, and caspase-12 levels contrary to elevating Bcl-2. Additionally, it attenuated the histopathological alterations in prefrontal cortical neurons. Noteworthy, the co-administration of NE100 reduced the advantageous effects of fluvoxamine, indicating the involvement of sigma-1 receptor in mediating the observed antipsychotic effects. Thus, sigma-1-mediated signaling pathways could be therapeutic targets for preventing or slowing schizophrenia progression.

The rising incidence of breast cancer (BC) among Egyptian females with a mortality rate of 11% and younger age at diagnosis implied the study of the interplay of BRCA gene variants with other BC risk factors. The study enrolled 500 BC Egyptian females with a mean age of 47.29 ± 13.26 years for whom BRCA1/2 testing was offered. A history of BC and/or other related cancer was recorded for all patients. Peripheral blood samples were obtained for genomic DNA extraction in view of germline BRCA gene testing on the MiSeq platform. A positive family history was reported in 352 patients (70.4%). Patients with hormone receptor-positive (HR+) BC constituted 195 cases (39%) cases, while 305 patients (61%) had hormone receptor-negative (HR-) BC. Among the HR- group, 268 patients (53%) had triple-negative BC (TNBC), and 37 patients had low estrogen receptor (ER) (1-10%) and/ or low progesterone receptor (PR) expression with HER2 negative status. Patients with HER2-positive BC were excluded from the enrollment and directed to specific targeted therapy. Variants were classified according to the American College of Medical Genetics (ACMG) and the Association for Molecular Pathology (AMP) criteria. Carriers of gBRCA1/2 PVs/LPVs were 58 patients (11.6%) of whom 34 (6.8%) had BRCA1 PVs/LPVs and 24 (4.8%) had BRCA2 PVs/LPVs. Patients with TNBC demonstrated a higher rate of gBRCA1/2 PVs/LPVs (17.5%). We recorded 55 PVs/LPVs in both genes, 44 single nucleotide variants (SNVs), and 11 copy number variations (CNVs). Three novel gBRCA1 LPVs; c.2791del, c.361G>T and c.4431dup and two novel gBRCA2 LPVs; gBRCA2 c.3139del and c.5690 dup were identified. Variants of uncertain significance (VUS) were found in 22 patients, of whom 13 (59%) had a positive family history of breast/ovarian cancer. Genomic testing for BRCA1/2 status as part of a routine BC diagnostic workup contributes to comprehensive BC risk assessment.Trial registration: Egyptian National Cancer Institute IRB approval number: 2301-305-051. Date of registration: 24th Jan 2023.

HMG-CoA reductase inhibitors, statins, are extensively used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic disorders. However, one of the common side effects of statin therapy is a mild elevation in liver aminotransferases, observed in less than 3% of patients. Atorvastatin and simvastatin, in particular, are most frequently associated with statin-induced liver injury, leading to treatment discontinuation. Recent research has highlighted the antioxidant and anti-inflammatory properties of glucagon-like peptide-1 receptor (GLP-1R) activation in protecting against liver injury. Nonetheless, the potential protective effects of liraglutide (LIRA), a GLP-1R agonist, against atorvastatin (ATO)-induced liver dysfunction have not been fully elucidated. In this context, the present study aimed to investigate the protective role of LIRA in mitigating ATO-induced liver injury in rats, offering new insights into managing statin-associated hepatotoxicity. Indeed, LIRA treatment improved liver function enzymes and attenuated histopathological alterations. LIRA treatment enhanced antioxidant defenses by increasing Nrf2 content and superoxide dismutase (SOD) activity, while reducing NADPH oxidase. Additionally, LIRA suppressed inflammation by downregulating the HMGB1/TLR-4/RAGE axis and inhibiting the protein expression of pY323-MAPK p38 and pS635-NFκB p65 content resulting in decreased proinflammatory cytokines (TNF-α and IL-1β). Furthermore, LIRA upregulated GLP-1R gene expression and promoted autophagic influx via the activation of the pS473-Akt/pS486-AMPK/pS758-ULK1/Beclin-1 signaling cascade, along with inhibiting apoptosis by reducing caspase-3 content. In conclusion, LIRA attenuated ATO-induced oxidative stress and inflammation via activation of the Nrf-2/SOD cascade and inhibition of the HMGB1/TLR-4/RAGE /MAPK p38/NFκB p65 axis. In parallel, LIRA stimulated autophagy via the AMPK/ULK1/Beclin-1 axis and suppressed apoptosis, thus restoring the balance between autophagy and apoptosis.

Multiple sclerosis (MS) is devastating motor disorders accompanied by cognitive impairments. Dalfampridine (Dal), was approved for treating MS via blocking voltage-gated potassium channel (Kv). Kv1.3 is one of Dals' targets that showed insults to cognitive function in preclinical and clinical cases. Yet, there is no study that has assessed the potentiality of Dal on Kv1.3-induced cognitive impairment in MS. Thus, the aim of the present study is to reveal the procognitive influence of Dal in the MS animal model. Mice were randomly assigned into four groups. Saline was administered to group 1, conversely groups 2, 3, and 4 received 2 shots of rat spinal cord emulsified with complete Freund's adjuvant. Group 3 received Dal (10 μg/mouse; p. o), while group 4 received Wortmannin (0.1 μg/mouse; i. c.v), a selective phosphoinositide 3-kinases (PI3K) inhibitor, before Dal administration. After 14 days, Dal alleviated motor deficits in the open field arena and rotarod with cognitive restoration in the novel object recognition task. These were accompanied by the reversal of hippocampal neuronal loss and demyelination in corpus callosum. Additionally, Dal inhibited Kv1.3 that enhanced survival signaling, viz; PI3K/Akt. Such activation abates neuroinflammatory markers, glycogen synthase kinase-3 beta (GSK-3β) and nuclear factor-κB levels with subsequent enhancement of BDNF. All these amendments were reversed by Wortmannin pre-administration. In conclusion, this study declares that blockade of Kv1.3 and modulation of PI3K/Akt/GSK-3β/BDNF axis with Dal could be proposed as a promising neuroprotective and memory-enhancing treatment in MS.

Oral cancer, particularly oral squamous cell carcinoma (OSCC), ranks as the sixth most prevalent cancer globally, with rates of occurrence on the rise. The diagnosis of OSCC primarily depends on histopathological images (HIs), but this method can be time-intensive, expensive, and reliant on specialized expertise. Manual diagnosis often leads to inaccuracies and inconsistencies, highlighting the urgent need for automated and dependable diagnostic solutions to enhance early detection and treatment success. This research introduces a deep learning (DL) approach utilizing EfficientNet-B3, complemented by learning rate tuning (LRT), to identify OSCC from histopathological images. The model is designed to automatically modify the learning rate based on the accuracy and loss during training, which improves its overall performance. When evaluated using the oral tumor dataset from the multi-cancer dataset, the model demonstrated impressive results, achieving an accuracy of 99.84% and a specificity of 99.92%, along with other strong performance metrics. These findings indicate its potential to simplify the diagnostic process, lower costs, and enhance patient outcomes in clinical settings.

To evaluate the diagnostic yield of prenatal exome sequencing (pES) in fetuses with structural anomalies detected by prenatal ultrasound in a consanguineous population. This was a prospective study of 244 anomalous fetuses from unrelated consanguineous Egyptian families. Detailed phenotyping was performed throughout pregnancy and postnatally, and pES data analysis was conducted. Genetic variants were prioritized based on the correlation of their corresponding human phenotype ontology terms with the ultrasound findings. Analyses were carried out to determine the diagnostic efficiency of pES and its correlation to the organ systems involved. The largest clinical category of fetuses referred for pES was those manifesting multisystem anomalies (104/244, 42.6%). pES provided a definitive diagnosis explaining the fetal anomalies in 47.1% (115/244) of the cases, with the identification of 122 pathogenic or likely pathogenic variants completely fitting with the phenotype. Variants of uncertain significance associated with the fetal phenotypes were detected in 84 fetuses (34%), while 18.44% (45/244) had negative results. Positive consanguinity is associated with a high diagnostic yield of ES. The novel variants and new fetal manifestations, described in our cohort, further expand the mutational and phenotypic spectrum of a wide variety of genetic disorders presenting with congenital malformations.

Optimal nutrition during infancy and early childhood is crucial for promoting lifelong health and well-being. Complementary feeding is a crucial phase in the nutritional journey of growing babies, as their nutritional requirements begin to surpass those provided by breast milk at approximately 4-6 months of age. While a nutritional gap, notably iron deficiency, is prevalent in the Middle East and North Africa (MENA) region, optimal complementary feeding practices and fortified food items such as iron-fortified infant cereals can help bridge this gap and achieve nutritional targets. Healthcare professionals play a pivotal role in providing expert guidance and support to parents during this crucial stage of development. However, the MENA region, with its diverse populations and varied weaning practices in different cultures, lacks unified guidelines specific to the region. This consensus is intended to serve as a foundation for pediatricians and primary care physicians in the MENA region to advise parents and caregivers about optimal complementary feeding practices.

Optimal nutrition during infancy and early childhood is crucial for promoting lifelong health and well-being. Complementary feeding is a crucial phase in the nutritional journey of growing babies, as their nutritional requirements begin to surpass those provided by breast milk at approximately 4-6 months of age. While a nutritional gap, notably iron deficiency, is prevalent in the Middle East and North Africa (MENA) region, optimal complementary feeding practices and fortified food items such as iron-fortified infant cereals can help bridge this gap and achieve nutritional targets. Healthcare professionals play a pivotal role in providing expert guidance and support to parents during this crucial stage of development. However, the MENA region, with its diverse populations and varied weaning practices in different cultures, lacks unified guidelines specific to the region. This consensus is intended to serve as a foundation for pediatricians and primary care physicians in the MENA region to advise parents and caregivers about optimal complementary feeding practices.

Genetic causes of steroid-resistant-nephrotic-syndrome (SRNS) represent a rapidly growing number of monogenic diseases. The reported diagnostic yield of various studies applying genetic panels and exome-sequencing to diagnose SRNS is usually < 30%. We performed genome-sequencing in a cohort of Egyptian SRNS patients. We recruited 47 SRNS patients belonging to 41 unrelated families [28 males/19 females; median (range): 6 (0.5-22 years)]. We established a pipeline for genome sequencing, bioinformatics analysis, variant curation and protein modeling at the Egypt Center for Research and Regenerative Medicine (ECRRM). Disease-causing variants were detected in 27/47 patients (57.4%) belonging to 23/41 families (56.1%), including nine novel variants in NPHS1, NPHS2, COL4A3, MYO1E, NUP93, PLCE1, PODXL, SMARCAL1 and WT1. Novel variants were confirmed by Sanger sequencing and were segregated in families of affected patients. NPHS2 was the most common causative gene in 8/23 (34.8%) of confirmed families, followed by NPHS1, WT1, and SMARCAL1 in 2/23 families (8.7%) each. All detected missense variants were evaluated through protein modeling and were predicted deleterious. Our study expanded the spectrum of SRNS disease-causing variants and revealed a monogenic cause in 56.1% of investigated families. In our cohort, no deep intronic or regulatory variants were detected by genome-sequencing. Pursuing genetic diagnosis in SRNS patients is crucial to inform clinical decision making, genetic counseling, transplantation strategy and prenatal diagnosis thus improving clinical outcome of affected patients.