SAID SHEHATA

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.

Despite growing evidence for the renin-angiotensin system (RAS) involvement in Parkinson's disease (PD), its role in microglial polarization during disease progression remains unclear. This study explored the ability of modulating RAS using eprosartan, an AT1R antagonist, and xanthenone, an ACE2 activator, to support microglial M2 polarization in rats with PD highlighting the roles of miR-155, protein phosphatase 2 A (PP2A), and mitogen-activated protein kinase phosphatase 1 (MKP-1). Rotenone (1.5 mg/kg) was administered to Wistar rats to induce PD, with concurrent treatments of eprosartan (60 mg/kg/day) or xanthenone (2 mg/kg/day) for 28 days. Both agents improved motor function and neuronal damage, as evidenced by behavioral, histopathological, and immunohistochemical analyses. Eprosartan and xanthenone enhanced tyrosine hydroxylase activity and reduced α-synuclein accumulation in the substantia nigra. Eprosartan and xanthenone modulated the RAS axis by reducing angiotensin II level and increasing ACE2 activity and Ang 1-7 concentration in the striatum. Importantly, these agents induced a shift in microglial polarization from the M1 proinflammatory phenotype (marked by reduced IL-1β, iNOS, and CD86) to the M2 anti-inflammatory phenotype (marked by enhanced arginase1, Ym1, Fizz1 and CD163). This shift was associated with altered STAT signaling pathways, including decreased p-STAT1 and increased p-STAT6. Additionally, levels of miR-155 were decreased, and levels of SOCS1, MKP-1, and PP2A were increased. These findings address a critical gap in understanding how RAS modulation can influence neuroinflammation through microglial polarization via regulating the interplay between MKP-1/ miR-155 /SOCS1 and PP2A, offering a promising therapeutic strategy to mitigate neurodegeneration and inflammation in PD.

Despite growing evidence for the renin-angiotensin system (RAS) involvement in Parkinson's disease (PD), its role in microglial polarization during disease progression remains unclear. This study explored the ability of modulating RAS using eprosartan, an AT1R antagonist, and xanthenone, an ACE2 activator, to support microglial M2 polarization in rats with PD highlighting the roles of miR-155, protein phosphatase 2 A (PP2A), and mitogen-activated protein kinase phosphatase 1 (MKP-1). Rotenone (1.5 mg/kg) was administered to Wistar rats to induce PD, with concurrent treatments of eprosartan (60 mg/kg/day) or xanthenone (2 mg/kg/day) for 28 days. Both agents improved motor function and neuronal damage, as evidenced by behavioral, histopathological, and immunohistochemical analyses. Eprosartan and xanthenone enhanced tyrosine hydroxylase activity and reduced α-synuclein accumulation in the substantia nigra. Eprosartan and xanthenone modulated the RAS axis by reducing angiotensin II level and increasing ACE2 activity and Ang 1-7 concentration in the striatum. Importantly, these agents induced a shift in microglial polarization from the M1 proinflammatory phenotype (marked by reduced IL-1β, iNOS, and CD86) to the M2 anti-inflammatory phenotype (marked by enhanced arginase1, Ym1, Fizz1 and CD163). This shift was associated with altered STAT signaling pathways, including decreased p-STAT1 and increased p-STAT6. Additionally, levels of miR-155 were decreased, and levels of SOCS1, MKP-1, and PP2A were increased. These findings address a critical gap in understanding how RAS modulation can influence neuroinflammation through microglial polarization via regulating the interplay between MKP-1/ miR-155 /SOCS1 and PP2A, offering a promising therapeutic strategy to mitigate neurodegeneration and inflammation in PD.

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.