A Newly Incompatibility F Replicon Allele (FIB81) in Extensively Drug-Resistant Escherichia coli Isolated from Diseased Broilers.

Multiple drug resistance (MDR) has gained pronounced attention among Enterobacterales. The transfer of multiple antimicrobial resistance genes, frequently carried on conjugative incompatibility F (IncF) plasmids and facilitating interspecies resistance transmission, has been linked to Salmonella spp. and E. coli in broilers. In Egypt, the growing resistance is exacerbated by the limited clinical efficacy of many antimicrobials. In this study, IncF groups were screened and characterized in drug-resistant Salmonella spp. and E. coli isolated from broilers. The antimicrobial resistance profile, PCR-based replicon typing of bacterial isolates pre- and post-plasmid curing, and IncF replicon allele sequence typing were investigated. Five isolates of E. coli (5/31; 16.13%) and Salmonella spp. (5/36; 13.89%) were pan-susceptible to the examined antimicrobial agents, and 85.07% of tested isolates were MDR and extensively drug-resistant (XDR). Twelve MDR and XDR E. coli and Salmonella spp. isolates were examined for the existence of IncF replicons (FII, FIA, and FIB). They shared resistance to ampicillin, ampicillin/sulbactam, amoxicillin/clavulanate, doxycycline, cefotaxime, and colistin. All isolates carried from one to two IncF replicons. The FII-FIA-FIB+ and FII-FIA+FIB- were the predominant replicon patterns. FIB was the most frequently detected replicon after plasmid curing. Three XDR E. coli isolates that were resistant to 12-14 antimicrobials carried a newly FIB replicon allele with four nucleotide substitutions: C99→A, G112→T, C113→T, and G114→A. These findings suggest that broilers are a significant reservoir of IncF replicons with highly divergent IncF-FIB plasmid incompatibility groups circulating among XDR Enterobacterales. Supporting these data with additional comprehensive epidemiological studies involving replicons other than the IncF can provide insights for implementing efficient policies to prevent the spreading of new replicons to humans.

Assessment of the implementation of risk minimization measures for bosentan: a retrospective study.

BACKGROUND: Bosentan is associated with adverse hepatic effects. To minimize such risk, regulators implemented risk minimization measures (RMMs), including testing for liver injury biomarkers (alanine and aspartate transaminase and bilirubin) prior to therapy initiation and monthly throughout therapy. This study aimed to examine the adherence to hepatic monitoring requirements. RESEARCH DESIGN AND METHODS: This retrospective cohort study collected data about bosentan new-users from the Real-world Evidence Research Network from 2016 to 2022. We ascertained hepatic tests from laboratory files. Adherence to RMM definition was performing the required tests within 90 days before initiation and categorized adherence to monthly testing requirement based on the expected number of tests throughout therapy as low (<50%), moderate (50-74%), and high (≥75%). RESULTS: One hundred patients entered the study cohort and 71% were females, with a median age of 25 years. Adherence to testing prior to bosentan initiation was 60%. Adherence to monthly testing was low in the majority of patients (58.2%). CONCLUSIONS: Adherence to bosentan RMMs relevant to minimizing risk of hepatotoxicity either before starting or throughout therapy was low. Our findings could be used as a baseline for monitoring trends in implementation of RMMs over time or to compare performance of various minimization strategies.

Microcystin levels in irrigation water and field-vegetable plants, and food safety risk assessment: A case study from Egypt.

Microcystin (MC), a hepatotoxin that is harmful to human health, has frequently increased in freshwaters worldwide due to the increase in toxic cyanobacterial blooms. Despite many studies reported the human exposure to MC through drinking water, the potential transfer of this toxin to human via consumption of vegetables grown on farmlands that are naturally irrigated with contaminated water has not been largely investigated. Therefore, this study investigates the presence of MC in irrigation water and its potential accumulation in commonly consumed vegetables from Egyptian farmlands. The results of toxin analysis revealed that all irrigation water sites contained high MC concentrations (1.3-93.7 µg L-1) along the study period, in association with the abundance of dominant cyanobacteria in these sites. Meanwhile, MCs were detected in most vegetable plants surveyed, with highest levels in potato tubers (1100 µg kg-1 fresh weight, FW) followed by spinach (180 µg kg-1 FW), onion (170 µg g-1 FW), Swiss chard (160 µg kg-1 FW) and fava bean (46 µg kg-1 FW). These MC concentrations in vegetables led to estimated daily intake (EDI) values (0.08-1.13 µg kg bw-1 d-1 for adults and 0.11-1.5 µg kg bw-1 d-1 for children), through food consumption, exceeding the WHO recommended TDI (0.04 µg kg bw-1 d-1) for this toxin. As eutrophic water is widely used for irrigation in many parts of the world, our study suggests that cyanotoxins in irrigation waters and agricultural plants should be regularly monitored to safeguard the general public from inadvertent exposure to harmful toxins via food consumption.

Mammary fat globules as a source of mRNA to model alterations in the expression of some milk component genes during lactation in bovines.

BACKGROUND: The milk's nutritional value is determined by its constituents, including fat, protein, carbohydrates, and minerals. The mammary gland's ability to produce milk is controlled by a complex network of genes. Thereby, the fat, protein, and lactose synthesis must be boost in milk to increase milk production efficiency. This can be accomplished by fusing genetic advancements with proper management practices. Therefore, this study aimed to investigate the association between the Lipoprotein lipase (LPL), kappa casein CSN3, and Glucose transporter 1 (GLUT1) genes expression levels and such milk components as fat, protein, and lactose in different dairy breeds during different stages of lactation. METHODS: To achieve such a purpose, 94 milk samples were collected (72 samples from 36 multiparous black-white and red-white Holstein-Friesian (HF) cows and 22 milk samples from 11 Egyptian buffaloes) during the early and peak lactation stages. The milk samples were utilized for milk analysis and genes expressions analyses using non- invasive approach in obtaining milk fat globules (MFGs) as a source of Ribonucleic acid (RNA). RESULTS: LPL and CSN3 genes expressions levels were found to be significantly higher in Egyptian buffalo than Holstein-Friesian (HF) cows as well as fat and protein percentages. On the other hand, GLUT1 gene expression level was shown to be significantly higher during peak lactation than early lactation. Moreover, lactose % showed a significant difference in peak lactation phase compared to early lactation phase. Also, fat and protein percentages were significantly higher in early lactation period than peak lactation period but lactose% showed the opposite pattern of Egyptian buffalo. CONCLUSION: Total RNA can be successfully obtained from MFGs. The results suggest that these genes play a role in glucose absorption and lactose synthesis in bovine mammary epithelial cells during lactation. Also, these results provide light on the differential expression of these genes among distinct Holstein-Friesian cow breeds and Egyptian buffalo subspecies throughout various lactation phases.

Assessing the Acceptability of a Preschool-Based Multi-Component Physical Activity Intervention Entitled "I'm an Active Hero" (IAAH): Process Evaluation of a Feasibility Trial.

BACKGROUND: Interventions within preschool settings have gained prominence due to the need to increase physical activity (PA) in early childhood. We first developed a 10-week preschool-based behaviour change intervention, guided by the UK Medical Research Council's framework for complex interventions. We then conducted a cluster feasibility randomised controlled trial (RCT) among young children. AIM: This process evaluation was embedded within the cluster feasibility RCT and aimed to assess the acceptability of the 10-week IAAH intervention among both preschool staff and parents. METHODS: The study utilised a mixed method, involving post-intervention questionnaires completed by preschool staff (n = 4) and children's parents/caregivers (n = 9) and focus groups with preschool staff (n = 3) and parents/caregivers (n = 7). Quantitative data were analysed using SPSS to calculate acceptability scores, while qualitative data underwent thematic analysis using NVivo 12. RESULTS: The intervention was well-received, with preschool staff reporting a 94.5% acceptability rate (mean score of 10.4 out of 11) and parents/caregivers indicating an 86% acceptance rate (mean score of 5.2 out of 6). Thematic analysis of focus group discussions revealed facilitators to intervention delivery, such as user-friendly materials and alignment with preschool curricula, and identified barriers, including time constraints, spatial limitations, and policy conflicts. Parental engagement was hindered by time restrictions, although the intervention materials were praised for their clarity and visual appeal. CONCLUSIONS: The findings suggest that the IAAH programme was acceptable to both preschool staff and parents. However, the identified barriers to intervention delivery and engagement should be addressed in the planning of a future cluster RCT to evaluate the efficacy of the intervention.

In vitro and in silico evaluation of bioactivities and chemical composition of the aerial parts of Anchusa officinalis L. methanol extract.

The main objective of the study is to evaluate the antioxidant, anticancer, and antimicrobial activities of Anchusa officinalis L. in vitro and in silico. The dried aerial parts of A. officinalis L. were extracted with methanol. Total phenolic and flavonoid content was analyzed. Antioxidant and antimicrobial effects were tested against both gram-positive and gram-negative bacteria. Gas chromatography-mass spectrometry analysis revealed the presence of 10 phytochemical compounds, and cyclobutane (26.07%) was identified as the major photochemical compound. The methanol extract exhibited the maximum amount of total phenolic content (118.24 ± 4.42 mg QE/g dry weight of the dry extract) (R2 = 0.994) and the total flavonoid content was 94 ± 2.34 mg QE/g dry weight of the dry extract (R2 = 0.999). The IC50 value for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid was 107.12 ± 3.42 µg/mL, and it was high for 1,1-diphenyl-2-picryl hydrazyl (123.94 ± 2.31 µg/mL). The IC50 value was 72.49 ± 3.14 against HepG2 cell lines, and a decreased value was obtained (102.54 ± 4.17 g/mL) against MCF-7 cell lines. The methanol extract increased the expression of caspase mRNA and Bax mRNA levels when compared to the control experiment (p < .05). The conclusions, A. officinalis L. aerial parts extract exhibited antibacterial, antifungal, and antioxidant activities.

The Use of Middle Meningeal Artery Embolization to Treat Chronic Subdural Hematoma in the Pediatric Population: A Review of the Literature.

Chronic subdural hematoma (cSDH) is rare in the pediatric population and typically arises from various causes. These include trauma (accidental, non-accidental, or birth-related injuries), coagulopathies (such as hemophilia or von Willebrand disease), vascular malformations (such as arteriovenous malformations), and complications from previous surgeries. These diverse etiologies contribute to the complexity of managing this condition. Although middle meningeal artery (MMA) embolization is proven effective in adults, limited studies have investigated its applicability in pediatrics. This study aims to assess the efficacy, safety, and outcomes of MMA embolization in the pediatric age group, guiding future research and treatment strategies. A systematic review of the literature was conducted using PubMed, Web of Science, and Embase. No restrictions were applied regarding publication status or follow-up duration. The inclusion criteria were studies that integrated MMA embolization as a treatment for cSDH in pediatric patients. Data extracted included patient sample and characteristics, cSDH etiology and characteristics, prior intervention, procedural technique and indication, and clinical and radiological outcomes. Twelve studies were included in the review, comprising a total of 14 patients. There were no randomized clinical trials or large-scale cohort studies. The included literature consisted of 11 case reports and one case series, and the results described a clinical and radiological outcome in a varied mix of patients with different characteristics and backgrounds for cSDH. No neurological complications attributed to MMA embolization were reported. Follow-up showed resolved or decreased size of cSDH in all patients except for one, who experienced hematoma expansion despite treatment. MMA embolization may be considered a primary or adjuvant treatment modality for cSDH in the pediatric population. However, further research is needed to investigate the impact of different etiologies on outcomes and to highlight long-term complications and results.

Real-World Evidence on Levetiracetam-Induced Hypokalemia: An Active Comparator Cohort Study.

BACKGROUND: Levetiracetam is an anti-seizure medication (ASM) with an established safety profile. However, a potential safety signal of hypokalemia following levetiracetam use was published in the World Health Organization newsletter. OBJECTIVE: To investigate the possible causal association between the use of levetiracetam and the development of hypokalemia. METHOD: This was a new-user, active-comparator retrospective cohort study using Real-world Evidence Research Network data at the Saudi Food and Drug Authority from 2016 to 2022. Adults (≥ 18 years old) with an incident prescription for either levetiracetam or carbamazepine were followed for up to 6 months from the prescription date. Hypokalemia was ascertained by using diagnostic code (i.e., E87.6) or by serum potassium level below 3.5 mmol/L. A Cox proportional hazards model, adjusted with stabilized inverse probability of treatment weight, was fitted to compare the hazard of hypokalemia between levetiracetam and carbamazepine exposed patients. RESULTS: A total of 8,982 patients entered the study cohort. The incidence rate of hypokalemia was 303 cases per 10,000 patient-years in the levetiracetam-exposed cohort compared to 57 cases per 10,000 patient-years among carbamazepine users. Compared to carbamazepine users, patients exposed to levetiracetam had an adjusted hazard ratio related to induced hypokalemia of 1.99 (95% confidence interval, 0.88-4.49). Results of sensitivity analyses were comparable to the main analysis. CONCLUSION: The hazard ratio for hypokalemia with the use of levetiracetam versus carbamazepine was statistically comparable. However, the potential association between levetiracetam use and hypokalemia cannot be ruled out given the elevated hazard ratios from the main and sensitivity analyses. Further studies may provide a more precise assessment of this association.

Molecular and agro-morphological characterization of new barley genotypes in arid environments.

BACKGROUND: Genetic diversity, population structure, agro-morphological traits, and molecular characteristics, are crucial for either preserving genetic resources or developing new cultivars. Due to climate change, water availability for agricultural use is progressively diminishing. This study used 100 molecular markers (25 TRAP, 22 SRAP, 23 ISTR, and 30 SSR). Additionally, 15 morphological characteristics were utilized to evaluate the optimal agronomic traits of 12 different barley genotypes under arid conditions. RESULTS: Substantial variations, ranging from significant to highly significant, were observed in the 15 agromorphological parameters evaluated among the 12 genotypes. The KSU-B101 barley genotype demonstrated superior performance in five specific traits: spike number per plant, 100-grain weight, spike number per square meter, harvest index, and grain yield. These results indicate its potential for achieving high yields in arid regions. The Sahrawy barley genotype exhibited the highest values across five parameters, namely leaf area, spike weight per plant, spike length, spike weight per square meter, and biological yield, making it a promising candidate for animal feed. The KSU-B105 genotype exhibited early maturity and a high grain count per spike, which reflects its early maturity and ability to produce a high number of grains per spike. This suggests its suitability for both animal feed and human food in arid areas. Based on marker data, the molecular study found that the similarity coefficients between the barley genotypes ranged from 0.48 to 0.80, with an average of 0.64. The dendrogram constructed from these data revealed three distinct clusters with a similarity coefficient of 0.80. Notably, the correlation between the dendrogram and its similarity matrix was high (0.903), indicating its accuracy in depicting the genetic relationships. The combined analysis revealed a moderate correlation between the morphological and molecular analysis, suggesting alignment between the two characterization methods. CONCLUSIONS: The morphological and molecular analyses of the 12 barley genotypes in this study effectively revealed the varied genetic characteristics of their agro-performance in arid conditions. KSU-B101, Sahrawy, and KSU-B105 have emerged as promising candidates for different agricultural applications in arid regions. Further research on these genotypes could reveal their full potential for breeding programs.

Advantages of CoS2 nano-particles on the corrosion resistance and adhesiveness of epoxy coatings.

Researchers face significant challenges because of the inadequate corrosion resistance and weak adherence of epoxy (EP) coatings. We deal with these issues here by means of a novel nano-composite coating (EP/nano-CoS2). In order to create a composite coating (EP/nano-CoS2), CoS2 nanoparticles (nano-CoS2) were prepared and incorporated to an epoxy (EP) resin. The synthesized CoS2 was characterized using XRD and FT-IR spectroscopic techniques. The mean particle size was determined using Scherer equation and found to be 19.38 nm. The zeta potential was also determined (- 9.78 mV). Electrochemical impedance spectroscopies (EIS) as well as pull-off assessments were used to quantify the EP/nano-CoS2 coating's anti-corrosion capabilities and adhesive power. The findings demonstrate that the EIS variables of the EP/nano-CoS2 composite coating are markedly improved when compared to raw EP coating. The corrosion resistance or even adhesion of EP protective layer can be markedly increased by using the synthesized nanoparticles as nano-fillers.

MicroRNA-141-regulated KLK10 and TNFSF-15 gene expression in hepatoblastoma cells as a novel mechanism in liver carcinogenesis.

Liver cancer is one of the most pivotal global health problems, leading hepatocellular carcinoma (HCC) with a significant increase in cases worldwide. The role of non-coding-RNA in cancer proliferation and carcinogenesis has attracted much attention in the last decade; however, microRNAs (miRNAs), as non-coding RNA, are considered master mediators in various cancer progressions. Yet the role of miR-141 as a modulator for specific cellular processes in liver cancer cell proliferation is still unclear. This study identified the role of miR-141 and its potential functions in liver carcinogenesis. The level of miR-141 in HepG2 and HuH7 cells was assessed using quantitative real-time PCR (qRT-PCR) and compared with its expression in normal hepatocytes. A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HepG2 cells. The protein profile of the kallikrein-related peptidase 10 (KLK10) and tumor necrosis factor TNFSF-15 was investigated in HepG2 cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced inflammatory cytokines from transfected HepG2 cells. Our findings showed that the expression of miR-141 significantly increased in HepG2 and HuH7 cells compared to the normal hepatocytes. Transfection of HepG2 cells with an inhibitor, antagonist miR-141, showed a significant reduction of HepG2 cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HepG2 cells overexpressed miR-141 provided a hundred downregulated genes, including KLK10 and TNFSF-15. Furthermore, the expression profile of KLK10 and TNFSF-15 markedly depleted in HepG2 cells transfected with miR-141 overexpression accompanied by a decreasing level of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α), indicating the role of miR-141 in HepG2 cell proliferation and programmed cell death. Interestingly, the experimental rats with liver cancer induced by Diethylnitrosamine injection further confirmed the upregulation of miR-141 level, IL-10, and TNF-α and the disturbance in KLK10 and TNFSF-15 gene expression compared with their expression in normal rats. The in-silico online tools, IntaRNA and miRWalk were used to confirm the direct interaction and potential binding sites between miR-141 and identified genes. Thus, the seeding regions of potential targeted sequences was cloned upstream of luciferase reporter gene in pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HepG2 cells pre-transfected with miR-141 overexpression vector, while increasing in cells pre-transfected with miR-141 specific inhibitor. In summary, these data suggest the crucial role of miR-141 in liver cancer development via targeting KLK10 and TNFSF-15 and provide miR-141 as an attractive candidate in liver cancer treatment and protection.

Selective and brain-penetrant ACSS2 inhibitors target breast cancer brain metastatic cells.

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to a significant reduction in colony formation, lipid storage, acetyl-CoA levels and cell survival in vitro. In an ex vivo brain-tumor slice model, treatment with AD-8007 and AD-5584 reduced pre-formed tumors and synergized with irradiation in blocking BCBM tumor growth. Treatment with AD-8007 reduced tumor burden and extended survival in vivo. This study identifies selective brain-penetrant ACSS2 inhibitors with efficacy towards breast cancer brain metastasis.

Novel risk index integrating practical operation limits enhances probabilistic contingency ranking for large-scale photovoltaic plant planning.

This research addresses the pressing need for heightened grid security amid increasing uncertainties in photovoltaic PV generation. The research problem lies in the limitations of conventional contingency analysis metrics, failing to adequately consider both contingency occurrences and uncertainties inherent in PV generation. In response, a comprehensive algorithm is proposed that introduces a novel severity function framework, enhancing traditional contingency ranking metrics. This approach incorporates grid remedial actions and refines line and bus voltage classification by considering available correction time, aiming to offer a more robust security assessment. Motivated by the imperative to address uncertainty in PV generation, the proposed work builds on established analysis tools. A probabilistic load flow algorithm manages PV generation uncertainties, utilizing historical data for contingency incidence uncertainty. Additionally, a probabilistic model for PV plants integrates historical solar data, deriving hourly probability density functions to meet grid code requirements, including reactive power considerations. The justification for this work lies in the algorithm's demonstrated efficacy, validated on the IEEE 14-bus network. Results highlight its ability to identify risks associated with line overloading and bus voltage breaches. Comparative evaluations underscore proper coupling buses for security, favoring distributed capacity to mitigate line overloading risks. The study's key results emphasize voltage risk amplification with reactive power omission, stressing the significance of compensation strategies. This research addresses a critical problem, presenting a comprehensive algorithmic solution to enhance grid security amidst uncertainties in PV integration. Findings offer valuable insights for strategically interaction between large scale PV plants and electrical grid, contributing to an improved grid security paradigm in a dynamic and uncertain energy model.

Pre-school-based behaviour change intervention to increase physical activity levels amongst young children: a feasibility cluster randomised controlled trial.

Background: A significant rise in childhood obesity worldwide over the past three decades highlights the urgent need for early interventions, especially in preschools as key settings for child development. This study aimed to assess the feasibility and fidelity of a randomised controlled trial of "I'm an Active Hero" (IAAH), a theory- and evidence-based multi-component behaviour change intervention targeting physical activity and sedentary behaviour amongst preschool-aged children. Methods: Two preschools in Taif city, Saudi Arabia were randomly assigned to either the intervention (n = 3 classrooms) or the usual curriculum control group (n = 3 classrooms). The intervention ran for 10 weeks from February to April 2023 and consisted of teacher-led physical activity and sedentary behaviour sessions in preschools, with an additional interactive home component. Primary outcome measures included intervention fidelity, recruitment rates, attrition rates, and compliance with trial procedures. Secondary outcomes included body mass index (BMI), objectively measured physical activity, and sedentary time via the ActiGraph GT3X accelerometer. Outcomes were measured at baseline and at 10 weeks in both study arms. Results: The preschool intervention component had high fidelity (93.3%), but the home component fidelity was lower (74%). A cluster-level recruitment rate of 12% (13/112 centres) was attained, whilst the individual-level recruitment rate stood at 36% (52/143 children, mean age of 4.16 years; 23 girls). Attrition was 10%. Compliance varied with 90% for BMI, 71% for accelerometery, and 45% for questionnaires. The intervention group showed small decreases in BMI, slight increases in physical activity, and decreases in sedentary time at follow-up compared to the control group. Parents, facilitators, and assistant teachers considered the intervention to be feasible and beneficial. Conclusion: The IAAH intervention was feasible to implement in Saudi Arabian preschools. Facilitators showed high fidelity in delivering it. However, preliminary data did not demonstrate effectiveness. A more comprehensive evaluation across a broader population is warranted. The intervention could be revised to optimise recruitment, compliance, and fidelity of the home-based component. Successful elements from this pilot should be retained whilst adaptations to implementation are made to strengthen key areas.Clinical trial registration: ClinicalTrials.gov, NCT05754359.

Serum interleukin-10 and alpha-fetoprotein: A combined diagnostic approach for hepatocellular carcinoma in Egyptians with HCV.

PURPOSE: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although alpha-fetoprotein (AFP) has been used for 60+ years as an HCC diagnostic serum marker, its accuracy is debated. Notably, the role of interleukin 10 (IL-10) in cancer development and metastasis is elevated in various tumor types, including HCC and chronic HCV infection. Our study aimed to investigate the diagnostic performance of IL-10 and AFP as biomarkers for HCV-induced HCC in an Egyptian population. METHODS: Eighty participants were recruited and categorized into three groups: HCV-related HCC (n=40), HCV-related cirrhosis (n=40), and control (n=20).The collected blood samples were analyzed to evaluate liver function, AFP levels, and IL-10 levels. RESULTS: Our analysis showed that AFP demonstrated low sensitivity (40% false-negative) and low specificity (33% false-positive).IL-10 levels were significantly higher (P < 0.001) in patients with HCC than in the cirrhosis and control groups. The serum AFP and IL-10 combination revealed significantly increased sensitivity (97.5%), diagnostic accuracy (71.1%), AUC (0.798), PPV (73.3%), and NPV ( 69.5%) when compared with either of them alone. CONCLUSION: the reliability of AFP as a major HCC marker was poor. However, IL-10 levels are a novel biomarker for the degree of HCC inflammation, considering IL-10's potential role in HCV-HCC development. We suggest combining AFP with IL-10 to improve the diagnostic and prognostic value of HCC considerably. Future research on these biomarkers should prioritize their clinical validity, prognostic usefulness, and compatibility with other therapeutic approaches as immunotherapy.

Supplying rats with halfa-bar and liquorice extracts ameliorate doxorubicin-induced nephrotic syndrome.

In the current work, we aimed to evaluate the protective effects of liquorice and halfa-bar extract against doxorubicin (DOX)-induced nephritic syndrome (NS) in rats. Twenty albino male rats were intraperitoneally injected with 50 mg/kg of DOX. The injected rats were supplied daily with 400 mg/kg of liquorice, halfa-bar extract, or their combination for 2 weeks. Our findings confirmed the induction of NS in rats indicated by alteration in Bowman's space, damaged in glomerular capsules, and tubules. Moreover, the levels of produced tumour necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were increased, accompanied by decreasing levels of IL-4 and IL-10. Supplement NS-rats with liquorice and halfa-bar extracts restored the glomerular and tubules damage and adjusted the level of produced TNF-α and IL-8. Interestingly, both extracts can stimulate the expression profile of small proline-rich protein 2 F (sprr2f) and metalloproteinase-10 (MMP-10), which are responsible for repairing and regeneration mechanisms of renal syndromes.

Omics technology draws a comprehensive heavy metal resistance strategy in bacteria.

The rapid industrial revolution significantly increased heavy metal pollution, becoming a major global environmental concern. This pollution is considered as one of the most harmful and toxic threats to all environmental components (air, soil, water, animals, and plants until reaching to human). Therefore, scientists try to find a promising and eco-friendly technique to solve this problem i.e., bacterial bioremediation. Various heavy metal resistance mechanisms were reported. Omics technologies can significantly improve our understanding of heavy metal resistant bacteria and their communities. They are a potent tool for investigating the adaptation processes of microbes in severe conditions. These omics methods provide unique benefits for investigating metabolic alterations, microbial diversity, and mechanisms of resistance of individual strains or communities to harsh conditions. Starting with genome sequencing which provides us with complete and comprehensive insight into the resistance mechanism of heavy metal resistant bacteria. Moreover, genome sequencing facilitates the opportunities to identify specific metal resistance genes, operons, and regulatory elements in the genomes of individual bacteria, understand the genetic mechanisms and variations responsible for heavy metal resistance within and between bacterial species in addition to the transcriptome, proteome that obtain the real expressed genes. Moreover, at the community level, metagenome, meta transcriptome and meta proteome participate in understanding the microbial interactive network potentially novel metabolic pathways, enzymes and gene species can all be found using these methods. This review presents the state of the art and anticipated developments in the use of omics technologies in the investigation of microbes used for heavy metal bioremediation.

Expression profile of viability and stress response genes as a result of resveratrol supplementation in vitrified and in vitro produced cattle embryos.

BACKGROUND: Resveratrol, a potent antioxidant, is known to induce the up-regulation of the internal antioxidant system. Therefore, it holds promise as a method to mitigate cryopreservation-induced injuries in bovine oocytes and embryos. This study aimed to (i) assess the enhancement in the quality of in vitro produced bovine embryos following resveratrol supplementation and (ii) monitor changes in the expression of genes associated with oxidative stress (GPX4, SOD, CPT2, NFE2L2), mitochondrial function (ATP5ME), endoplasmic reticulum function (ATF6), and embryo quality (OCT4, DNMT1, CASP3, ELOVL5). METHODS AND RESULTS: Three groups of in vitro bovine embryos were cultured with varying concentrations of resveratrol (0.01, 0.001, and 0.0001 µM), with a fourth group serving as a control. Following the vitrification process, embryos were categorized as either good or poor quality. Blastocysts were then preserved at - 80 °C for RNA isolation, followed by qRT-PCR analysis of selected genes. The low concentrations of resveratrol (0.001 µM, P < 0.05 and 0.0001 µM, P < 0.01) significantly improved the blastocyst rate compared to the control group. Moreover, the proportion of good quality vitrified embryos increased significantly (P < 0.05) in the groups treated with 0.001 and 0.0001 µM resveratrol compared to the control group. Analysis of gene expression showed a significant increase in OCT4 and DNMT1 transcripts in both good and poor-quality embryos treated with resveratrol compared to untreated embryos. Additionally, CASP3 expression was decreased in treated good embryos compared to control embryos. Furthermore, ELOVL5 and ATF6 transcripts were down-regulated in treated good embryos compared to the control group. Regarding antioxidant-related genes, GPX4, SOD, and CPT2 transcripts increased in the treated embryos, while NFE2L2 mRNA decreased in treated good embryos compared to the control group. CONCLUSIONS: Resveratrol supplementation at low concentrations effectively mitigated oxidative stress and enhanced the cryotolerance of embryos by modulating the expression of genes involved in oxidative stress response.

Outcomes of Minimally Invasive Adrenalectomy for Large Adrenal Masses: A Multi-Centre Experience in Saudi Arabia.

Introduction Advancements in radiological imaging technology have increased the discovery of adrenal incidentalomas. Large adrenal tumors (LATs) are not common, and the likelihood of malignancy increases with tumor size. LATs were defined as tumors larger than four centimeters (cm) with various pathologic diagnoses. Traditionally, open adrenalectomy was considered the gold standard for LATs, but with recent advancements in minimally invasive surgery (MIS), optimum perioperative and long-term outcomes are achievable by the MIS approach. The findings presented in this paper show that even large adrenal masses measuring up to 21 centimeters can be safely removed using a minimally invasive approach. Methodology After Institutional Review Board (IRB) approval, we reviewed medical records of adult patients who had adrenalectomies at two Saudi Arabian centers from January 2013 to February 2023. Inclusion criteria were laparoscopic or robotic adrenalectomy and adrenal lesions ≥5cm. Pediatric patients and those with open adrenalectomies were excluded. Pre-surgery, patients had imaging studies to assess mass characteristics. Pheochromocytoma patients received a 2-week adrenergic blocker treatment. Perioperative data including demographics, comorbidities, mass characteristics, surgery details, and follow-up were analyzed using SPSS-23. Patients provided informed consent and had follow-up appointments and imaging. Results Our experience involved 35 patients, 29 of whom received laparoscopic treatment and six of whom underwent robotic surgery. Of the 35 patients, more than half were females (57.1%), with a mean age of 41.7±14.9 years, the youngest and oldest participants being 16 and 73 years of age, respectively. The mean body mass index (BMI) of the participants was in the overweight range (26±6.0 kg/m2). The most common mode of presentation was incidental (42.9%), followed by hypertension (17.1%). Most patients had right-sided adrenal gland involvement (48.6%), with only four patients showing bilateral involvement. Most of the patients were classified as American Society of Anesthesiology score (ASA) 2 (40.0%) or ASA 3 (40.0%). Most of the patients were diagnosed with myelolipoma or adenoma (22.9% each) followed by pheochromocytoma (17.1%). The average estimated blood loss (EBL) was 189.3±354.6 ml for patients who underwent laparoscopic surgery and 80.0 ±34.6 ml for patients who underwent robotic surgery. The average operative room time (ORT) was 220.1±98.7 minutes (min) for laparoscopic surgery and 188.3±10.3 min for robotic surgery. One patient had to be converted from laparoscopic to open surgery due to aortic injury. The average length of stay (LOS) was 9.5±6.7 days for laparoscopic treatment and 5.5±1.9 days for robotic surgery. The mean tumor size in the greatest dimension was 8.0±4.4 cm. Only one patient who underwent unilateral laparoscopy experienced perioperative complications and converted to open surgery; nine patients who underwent unilateral laparoscopy required blood transfusion, and none of the patients who underwent robotic surgery required transfusion. None of the 35 patients experienced a recurrence of their adrenal disease during the mean follow-up period which lasted around 58 months. Conclusion MIS in Saudi Arabia is growing and is a safe method for LATs, with satisfactory surgical results compared to the traditional open surgery approach. It offers advantages in terms of EBL, complications, and disease recurrence.