Usefulness of low-cost simulation models to learning surgical techniques for placenta accreta spectrum: An observational educational study.

OBJECTIVE: To evaluate the utility of low-cost simulation models to teach surgical techniques for placenta accreta spectrum (PAS), included in a multimodal education workshop for PAS. METHODS: This was an observational, survey-based study. Participants were surveyed before and after the use of low-fidelity mannequins to simulate two surgical techniques for PAS (one-step conservative surgery [OSCS] and modified subtotal hysterectomy [MSTH]), within a multimodal educational workshop. The workshops included pre-course preparation, didactics, simulated practice of the techniques using low-cost models, and viewing live surgery. RESULTS: Six OSCS/MSTH training workshops occurred across six countries and a total of 270 participants were surveyed. The responses of 127 certified obstetricians and gynecologists (OB-GYNs) were analyzed. Participants expressed favorable impressions of all components of the simulated session. Perceived anatomical simulator fidelity, scenario realism, educational component effectiveness, and self-assessed performance improvement received ratings of 4-5 (positive end of the Likert scale) from over 90% of respondents. When asked about simulation's role in technique comprehension, comfort level in technique performance, and likelihood of recommending this workshop to others, more than 75% of participants rated these aspects with a score of 4-5 (positively) on the five-point scale. CONCLUSION: Low-cost simulation, within a multimodal education strategy, is a well-accepted intervention for teaching surgical techniques for PAS.

Initial Experience and Surgical Setup of Robot-Assisted Nephroureterectomy Using the Hugo Robot-Assisted Surgery System.

Introduction and Hypothesis: Robot-assisted radical nephroureterectomy (RANU) has emerged as a valid alternative to open or laparoscopic nephroureterectomy in recent years. However, different types of robotic platforms can limit surgical maneuvers in various ways. This study aimed to describe the surgical procedure and demonstrate RANU's technical feasibility and safety using the Hugo robot-assisted surgery (RAS) system. Materials and Methods: Using the Hugo RAS system, we reported data from the first five consecutive patients who underwent RANU at Tottori University Hospital. We adjusted the docking angles of the four independent arm carts in each case and performed a complete RANU via a transperitoneal approach. We collected patients' sociodemographic and perioperative data, including complications, and compared them retrospectively with data obtained using the da Vinci surgical system. Results: Arms positions were modified after the first patient to be placed all at the back of the patient. Median overall operative time was 283 minutes (203-377) and the median time using the robotic system was 187 minutes (121-277). The median estimated blood loss was 20 mL (5-155). None of the patients required a blood transfusion and none suffered postoperative complications of Clavien-Dindo grade ≥3. These outcomes were similar to those obtained with the da Vinci Xi system. Conclusion: This series represents the first report of RANU executed using the novel Hugo RAS system. Our proposed arm-setup will assist other surgeons and help ensure safe implementation of RANU on the Hugo platform.

Comparative immune profiling of pancreatic ductal adenocarcinoma progression among South African patients.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. METHODS: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. RESULTS: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16- (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16- (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. CONCLUSION: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.

Does Ta Low-grade Urothelial Carcinoma of the Bladder With Focal High-grade Features Carry Worse Prognosis? The Roswell Park Comprehensive Cancer Center Experience.

OBJECTIVE: To describe the management and outcomes of patients with Ta predominantly low-grade urothelial carcinoma with focal high-grade features (FHG) (<5%), compared to those with Ta low grade (LG) and Ta high grade (HG). METHODS: Retrospective review of all patients who underwent transurethral resection of bladder tumor between 2005 and 2023. Patients with Ta disease were identified and categorized into LG, FHG, and HG. Kaplan Meier method was used to depict high-grade recurrence, T-stage progression, and radical cystectomy-free survival. RESULTS: Four hundred forty-nine patients with Ta disease were identified (LG 48%, FHG 12%, and HG 40%). Patients with FHG (32%) had a second-look transurethral resection of bladder tumor more frequently compared to LG (7%) and HG (29%) (P <.01). They received intravesical therapy more frequently compared to LG (36% vs 20%) but lower than HG (55%) (P <.01). They received radical cystectomy less frequently (7% compared to 20% for HG and 11% for LG, P = .01). HG recurrence-free survival at 1, 3, and 5years was HG (68%, 52%, and 43%), FHG (74%, 53%, and 49%), and LG (87%, 79%, and 73%) (log-rank P <.01). T progression-free survival at 1, 3, and 5years was HG (84%, 77%, and 70%), FHG (92%, 82%, and 82%), and LG (94%, 89%, and 85%) (log-rank P = .02). Cystectomy-free survival at 1, 3, and 5years was HG (92%, 84%, and 80%), FHG (96%, 94%, and 94%), and LG (99%, 95%, and 92%) (log-rank P <.01). CONCLUSION: Patients with Ta FHG seem to behave more like Ta HG disease in terms of high-grade recurrences, but they are less likely to experience T-stage progression and convert to cystectomy.

Is Stent-Free Ureteroenteric Anastomosis Associated With Lower Ureteroenteric Strictures After Robot-Assisted Radical Cystectomy and Ileal Conduit?

INTRODUCTION: We aimed to investigate the differences in perioperative outcomes, especially ureteroenteric strictures, between patients who underwent a stented ureteroenteric anastomosis at the time of robot-assisted radical cystectomy (RARC) and ileal conduit vs those who did not. METHODS: A retrospective review of our RARC database was performed (2009-2023). Patients were divided into those who received stented ureteroenteric anastomosis vs those who did not. Propensity score matching was performed in the ratio of 3 (stented ureteroenteric anastomosis) to 1 (stent-free) in terms of age, gender, BMI, race, American Society of Anesthesiologists score, neoadjuvant chemotherapy, Charlson Comorbidity Index, prior radiation therapy, previous abdominal surgery history, clinical T3/clinical T4 stage, preoperative metastasis, and preoperative hydronephrosis. A cumulative incidence curve was used to depict ureteroenteric strictures and a Cox regression model was used to identify variables associated with ureteroenteric strictures. RESULTS: Four hundred eighty-eight patients underwent RARC, 366 individuals underwent a stented ureteroenteric anastomosis, and 122 patients underwent a stent-free approach. There was no significant difference in 90-day overall complications, high-grade complications, readmissions, UTIs, leakage, and ileus (P > .05). Ureteroenteric strictures occurred at a rate of 13% and 18% at 1 and 2 years, respectively in the stented group, vs 7% and 10% in the stent-free group (P = .05). Stent placement was significantly associated with ureteroenteric strictures. CONCLUSIONS: Stent-free ureteroenteric anastomosis was associated with fewer strictures following RARC and ileal conduit.

Multicenter validation of an artificial intelligence (AI)-based platform for the diagnosis of acute appendicitis.

BACKGROUND: The current scores used to help diagnose acute appendicitis have a "gray" zone in which the diagnosis is usually inconclusive. Furthermore, the universal use of CT scanning is limited because of the radiation hazards and/or limited resources. Hence, it is imperative to have an accurate diagnostic tool to avoid unnecessary, negative appendectomies. METHODS: This was an international, multicenter, retrospective cohort study. The diagnostic accuracy of the artificial intelligence platform was assessed by sensitivity, specificity, negative predictive value, the area under the receiver curve, precision curve, F1 score, and Matthews correlation coefficient. Moreover, calibration curve, decision curve analysis, and clinical impact curve analysis were used to assess the clinical utility of the artificial intelligence platform. The accuracy of the artificial intelligence platform was also compared to that of CT scanning. RESULTS: Two data sets were used to assess the artificial intelligence platform: a multicenter real data set (n = 2,579) and a well-qualified synthetic data set (n = 9736). The platform showed a sensitivity of 92.2%, specificity of 97.2%, and negative predictive value of 98.7%. The artificial intelligence had good area under the receiver curve, precision, F1 score, and Matthews correlation coefficient (0.97, 86.7, 0.89, 0.88, respectively). Compared to CT scanning, the artificial intelligence platform had a better area under the receiver curve (0.92 vs 0.76), specificity (90.9 vs 53.3), precision (99.8 vs 98.9), and Matthews correlation coefficient (0.77 vs 0.72), comparable sensitivity (99.2 vs 100), and lower negative predictive value (67.6 vs 99.5). Decision curve analysis and clinical impact curve analysis intuitively revealed that the platform had a substantial net benefit within a realistic probability range from 6% to 96%. CONCLUSION: The current artificial intelligence platform had excellent sensitivity, specificity, and accuracy exceeding 90% and may help clinicians in decision making on patients with suspected acute appendicitis, particularly when access to CT scanning is limited.

In vitro antibacterial and antioxidant activity of flavonoids from the roots of Tephrosia vogelii: a combined experimental and computational study.

Tephrosia vogelii is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CH2Cl2/MeOH (1:1) roots extract of T. vogelii afforded seven compounds namely; ß-sitosterol (1a), stigmasterol (1b), 6a, 12a-dehydro-deguelin (2), tephrosin (3), maackiain (4), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6). GC-MS analysis of essential oils from the root of T. vogelii displayed a total of 17 compounds of which cis-nerolidol (41.7 %) and cadinol (19.7 %) were the major constituents. CH2Cl2/MeOH (1:1) extract, MeOH extract, maackiain (4) and obovatin (5) showed moderate inhibitory activity against Pseudomonas aeruginosa with MIC value of 0.5, 0.66, 0.83 and 0.83 mg/mL, respectively, compared to ciprofloxacin (MIC of 0.078 µg/mL). 6a, 12a-dihydro-deguelin (2), and 6-oxo, 6a, 12a-dehydro-deguelin (6) displayed significant activity against S. epidermis with MIC values of 0.66 mg/mL. Tephrosin (3) and maackiain (4) also showed moderate antibacterial activity against Staphylococcus aureus and Proteus mirabilis with MIC values of 0.83 and 0.5 mg/mL, respectively, compared to ciprofloxacin (0.312 µg/mL). The radical scavenging activity results indicated that tephrosin (3), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6) showed potent DPPH scavenging activity with IC50 values of 10.97, 10.43 and 10.73 µg/mL, respectively, compared to ascorbic acid (IC50 of 5.83 µg/mL). The docking prediction results revealed that 6a, 12a-dehydro-deguelin (2) displayed the best binding energy of -8.1 kcal/mol towards pyruvate kinase of S. aureus (PDB ID: 3T07) and -7.9 kcal/mol towards P. mirabilis urease (PDB ID: 1E9Y) and DNA gyrase B of Escherichia coli (PDB: 4F86) receptors compared to ciprofloxacin (-7.2 to -8.0 kcal/mol). Maackiain (4) and obovatin (5) displayed the minimum binding energy of -7.9 and -8.2 kcal/mol towards the LasR protein of P. aeruginosa (PDB: ID 2UV) and S. epidermidis FtsZ (PDB: ID 4M8I), respectively. The SwissADME drug-likeness and Pro Tox II toxicity prediction results indicated that compounds (2-6) obeyed Lipinski's rule of five with 0 violations and none of them were found to be hepatotoxic, mutagenic, and cytotoxic, respectively. The in vitro assessment results supported by the in silico analysis revealed that crude extracts and isolated compounds showed promising antibacterial and antioxidant activity, which proves the therapeutic potential of the roots of T. vogelii.

Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.

BACKGROUND: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. METHODS: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. FINDINGS: We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. INTERPRETATION: The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

Genetic heterogeneity of chicken anemia virus isolated in selected Egyptian provinces as a preliminary investigation.

Chicken anemia virus (CAV) is a widespread and economically significant pathogen in the poultry industry. In this study 110 samples were collected from various poultry farms in selected Egyptian provinces during 2021-2022 and were tested against CAV by Polymerase Chain Reaction (PCR), revealing 22 positive samples with 20% incidence rate. Full sequence analysis of five selected CAV strains revealed genetic variations in VP1, VP2, and VP3 genes. Phylogenetic analysis grouped the Egyptian strains with reference viruses, mainly in group II, while vaccines like Del-Rose were categorized in group III. Recombination events were detected between an Egyptian strain (genotype II) and the Del-Rose vaccine strain (genotype III), indicating potential recombination between live vaccine strains and field isolates. To evaluate pathogenicity, one Egyptian isolate (F883-2022 CAV) and Del-Rose vaccine were tested in Specific Pathogen Free (SPF) chicks. Chicks in the positive group displayed clinical symptoms, including weakness and stunted growth, with postmortem findings consistent with CAV infection. The vaccine group showed milder symptoms and less severe postmortem changes. This study provides important insights into the genetic diversity of CAV in selected Egyptian poultry farms showing recombination event between field strain and vaccine strains, highlighting the need for advanced vaccination programs, especially for broilers.

Hydrogen energy systems: Technologies, trends, and future prospects.

This review critically examines hydrogen energy systems, highlighting their capacity to transform the global energy framework and mitigate climate change. Hydrogen showcases a high energy density of 120 MJ/kg, providing a robust alternative to fossil fuels. Adoption at scale could decrease global CO2 emissions by up to 830 million tonnes annually. Despite its potential, the expansion of hydrogen technology is curtailed by the inefficiency of current electrolysis methods and high production costs. Presently, electrolysis efficiencies range between 60 % and 80 %, with hydrogen production costs around $5 per kilogram. Strategic advancements are necessary to reduce these costs below $2 per kilogram and push efficiencies above 80 %. Additionally, hydrogen storage poses its own challenges, requiring conditions of up to 700 bar or temperatures below -253 °C. These storage conditions necessitate the development of advanced materials and infrastructure improvements. The findings of this study emphasize the need for comprehensive strategic planning and interdisciplinary efforts to maximize hydrogen's role as a sustainable energy source. Enhancing the economic viability and market integration of hydrogen will depend critically on overcoming these technological and infrastructural challenges, supported by robust regulatory frameworks. This comprehensive approach will ensure that hydrogen energy can significantly contribute to a sustainable and low-carbon future.

Anticancer diterpenes of African natural products: Mechanistic pathways and preclinical developments.

BACKGROUND: The African continent is home to five biodiversity hotspots, boasting an immense wealth of medicinal flora, fungi and marine life. Diterpenes extracted from such natural products have compelling cytotoxic activities that warrant further exploration for the drug market, particularly in cancer therapy, where mortality rates remain elevated worldwide. PURPOSE: To demonstrate the potential of African natural products on the global stage for cancer therapy development and provide an in-depth analysis of the current literature on the activity of cancer cytotoxic diterpenes from African natural sources (to our knowledge, the first of its kind); not only to reveal the most promising candidates for clinical development, but to demonstrate the importance of preserving the threatened ecosystems of Africa. METHODS: A comprehensive search by means of the PRISMA strategy was conducted using electronic databases, namely Web of Science, PubMed, Google Scholar and ScienceDirect. The search terms employed were 'diterpene & mechanism & cancer' and 'diterpene & clinical & cancer'. The selection process involved assessing titles in English, Portuguese and Spanish, adhering to predefined eligibility criteria. The timeframe for inclusion spanned from 2010 to 2023, resulting in 218 relevant papers. Chemical structures were visualized using ChemDraw 21.0, PubChem was utilized to search for CID numbers. RESULTS: Despite being one of the richest biodiverse zones in the world, African natural products are proportionally underreported compared to Asian countries or otherwise. The diterpenes andrographolide (Andrographis paniculata), forskolin (Coleus forskohlii), ent-kauranes from Isodon spp., euphosorophane A (Euphorbia sororia), cafestol & kahweol (Coffea spp.), macrocylic jolkinol D derivatives (Euphorbia piscatoria) and cyathane erinacine A (Hericium erinaceus) illustrated the most encouraging data for further cancer therapy exploration and development. CONCLUSIONS: Diterpenes from African natural products have the potential to be economically significant active pharmaceutical and medicinal ingredients, specifically focussed on anticancer therapeutics.

The impact of incorporating dried cafeteria leftover food on growing APRI rabbits productivity, profitability and meat quality.

This study was conducted to investigate the effect of dried cafeteria leftover food (DCLF) incorporation in growing APRI rabbit diets on nutrient digestibility, live body weight, body weight gain, carcass traits, meat quality, blood parameters, and economic efficiency. Thirty-six APRI rabbits (6 weeks of age), after weaning, were randomly divided into three groups (12 rabbits/group, 613 ± 5 g). During the experiment, rabbits aged 6-14 weeks participated in the experiment. An approximate isocaloric and isonitrogenous composition was achieved in three pelleted experimental diets. For the rabbit groups D1 (as the control), D2, and D3, DCLF was added at doses of 0%, 17.5%, and 35%, respectively. Digestibility trails were carried out at the end of the feeding experiment to evaluate the nutritional and feeding values of the experimental diets. To examine the characteristics of the carcasses, the quality of the meat, the histopathological analysis, and the blood plasma parameters, three rabbits were slaughtered from each group. The results showed that the feeding values (TDN and DE), which had the greatest values, as well as the digesting coefficients for dry matter, organic matter, crude fiber, and ether extract between the D1 and D3 groups were significantly different (p < 0.05). On the contrary, the curde protein, nitrogen-free extract, and digestible crude protein of the examined diets showed no signifcant differences compared with the control diet. The level of DCLF incorporation in diets significantly (p < 0.05) increased the live body weight at 14 weeks; with D3 recording the highest values (2130.9 g) when compared to the D1 and D2 groups. A similar pattern was observed for both daily increase and total body gain (6-14 weeks). Feed conversion recorded insignificant differences among the experimental diets respecting the period 6-14 weeks of age. DCLF levels had a significant effect on dressing and giblet percentages. The chemical composition and color parameters of rabbit meat were similar (p > 0.05), except for fat%, which had the highest value in the D3 group (p < 0.05) compared to the D1 and D2 groups. Economic efficiency was improved by using DLCF up to 35% in terms of gross margin and feed cost/kg gain. In conclusion, using DCLF in the feeding system of rabbits could enhance productive performance, carcass traits, meat quality, and physiological function, as well as improve economic efficiency.

Green Biocatalyst for Ultrasound-Assisted Thiazole Derivatives: Synthesis, Antibacterial Evaluation, and Docking Analysis.

The catalytic activity of chitosan (Cs) and grafted Cs led to the preparation of terephthalohydrazide Cs Schiff's base hydrogel (TCsSB), which was then investigated as an eco-friendly biocatalyst for synthesizing novel thiazole derivatives. TCsSB exhibited greater surface area and higher thermal stability compared to Cs, making it a promising eco-friendly biocatalyst. We synthesized two novel series of thiazoles via the reaction of 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothioamide with various hydrazonoyl chlorides and 2-bromo-1-arylethan-1-ones, employing ultrasonic irradiation and using TCsSB as a catalyst. A comparative study between Cs and TCsSB revealed higher yields than TCsSB. The methodology offered advantages such as mild reaction conditions, quick reaction times, and high yields. TCsSB could be reused multiple times without a significant loss of potency. The chemical structures of the newly synthesized compounds were verified through IR, 1H NMR, 13C NMR, and MS analyses. Six synthesized compounds were assessed for their in vitro antibacterial effectiveness by establishing the minimum inhibitory concentration against four distinct bacterial strains. The docking analyses revealed favorable binding scores against several amino acids within the selected protein (PDB Code-1MBT) for these compounds, with compound 4c exhibiting particularly noteworthy binding properties. Additionally, the in silico ADME parameter estimation for all compounds indicated favorable pharmacological properties for these compounds.

Effect of urea-treated rice straw, mixed with faba bean straw, on nutrient digestibility, blood metabolites and performance of growing lambs.

The present study aimed to use poor quality roughages, such as rice and faba bean straw, treated with or without urea, and their impacts on digestibility, rumen fermentation, some blood parameters, and growth performance of lambs. Twenty crossbred male lambs (1/4 Finland ×¾ Ossimi, 25±1.13kg live body weight) were chosen and divided into four groups. All lambs were fed rations of concentrated feed mixture at 2% of live weight with the following roughages ad libitum: URS (control group, untreated rice straw), TRS (urea-treated rice straw), FBS (faba bean straw), and TRS+FBS (mixture of TRS and FBS, 1:1). Nutrient digestibility and feeding values improved (P<0.05) with TRS+FBS lambs versus FBS, TRS and URS lambs. The highest numerical values of ruminal total volatile fatty acid (VFA) concentration in TRS lambs were recorded 23.9 ml.eq/dl followed by TRS+FBS, URS and FBS. Regarding to the ruminal parameters, there were no differences (P>0.05) among evaluated groups except for NH3-N, the highest concentration (P<0.05) was recorded in TRS lambs at 3 h post-feeding. Lambs of TRS, FBS and TRS+FBS showed faster growth (P<0.05) than those of the control (i.e., URS). Intakes of dry matter, total digestible nutrients, and digestible crude protein were numerically increased for TRS, FBS, and TRS+FBS. Feed conversion, as kg dry matter/kg gain, was improved for TRS, FBS, and TRS+FBS lambs versus URS. Daily gain of lambs increased (P<0.05) with lambs of TRS, FBS, and TRS+FBS but URS lambs showed a decrease (P<0.05) in daily gain. Feed conversion as kg dry matter intake/kg gain was improved (P<0.05) by feeding on TRS, FBS and TRS+FBS rations versus URS. The TRS+FBS lambs tended to have the highest economic efficiency versus URS, TRS and FBS lambs. It was concluded that urea-treated rice straw could be used as sole roughage or mixed with faba bean straw (1:1) in growing lambs' ration to improve their performance and economic efficiency without adversely affecting their health.The present study aimed to use poor quality roughages, such as rice and faba bean straw, treated with or without urea, and their impacts on digestibility, rumen fermentation, some blood parameters, and growth performance of lambs. Twenty crossbred male lambs (1/4 Finland ×¾ Ossimi, 25±1.13kg live body weight) were chosen and divided into four groups. All lambs were fed rations of concentrated feed mixture at 2% of live weight with the following roughages ad libitum: URS (control group, untreated rice straw), TRS (urea-treated rice straw), FBS (faba bean straw), and TRS+FBS (mixture of TRS and FBS, 1:1). Nutrient digestibility and feeding values improved (P<0.05) with TRS+FBS lambs versus FBS, TRS and URS lambs. The highest numerical values of ruminal total volatile fatty acid (VFA) concentration in TRS lambs were recorded 23.9 ml.eq/dl followed by TRS+FBS, URS and FBS. Regarding to the ruminal parameters, there were no differences (P>0.05) among evaluated groups except for NH3-N, the highest concentration (P<0.05) was recorded in TRS lambs at 3 h post-feeding. Lambs of TRS, FBS and TRS+FBS showed faster growth (P<0.05) than those of the control (i.e., URS). Intakes of dry matter, total digestible nutrients, and digestible crude protein were numerically increased for TRS, FBS, and TRS+FBS. Feed conversion, as kg dry matter/kg gain, was improved for TRS, FBS, and TRS+FBS lambs versus URS. Daily gain of lambs increased (P<0.05) with lambs of TRS, FBS, and TRS+FBS but URS lambs showed a decrease (P<0.05) in daily gain. Feed conversion as kg dry matter intake/kg gain was improved (P<0.05) by feeding on TRS, FBS and TRS+FBS rations versus URS. The TRS+FBS lambs tended to have the highest economic efficiency versus URS, TRS and FBS lambs. It was concluded that urea-treated rice straw could be used as sole roughage or mixed with faba bean straw (1:1) in growing lambs' ration to improve their performance and economic efficiency without adversely affecting their health.

Green Synthesis of Gold Nanoparticles Using Liquiritin and Other Phenolics from Glycyrrhiza glabra and Their Anti-Inflammatory Activity.

Phenolic compounds are the main phytochemical constituents of many higher plants. They play an important role in synthesizing metal nanoparticles using green technology due to their ability to reduce metal salts and stabilize them through physical interaction/conjugation to the metal surface. Six pure phenolic compounds were isolated from licorice (Glycyrrhiza glabra) and employed in synthesizing gold nanoparticles (AuNPs). The isolated compounds were identified as liquiritin (1), isoliquiritin (2), neoisoliquiritin (3), isoliquiritin apioside (4), liquiritin apioside (5), and glabridin (6). The synthesized AuNPs were characterized using UV, zeta sizer, HRTEM, and IR and tested for their stability in different biological media. The phenolic isolates and their corresponding synthesized NP conjugates were tested for their potential in vitro cytotoxicity. The anti-inflammatory effects were investigated in both normal and inflammation-induced settings, where inflammatory biomarkers were stimulated using lipopolysaccharides (LPSs) in the RAW 264.7 macrophage cell line. LPS, functioning as a mitogen, promotes cell growth by reducing apoptosis, potentially contributing to observed outcomes. Results indicated that all six pure phenolic isolates inhibited cell proliferation. The AuNP conjugates of all the phenolic isolates, except liquiritin apioside (5), inhibited cell viability. LPS initiates inflammatory markers by binding to cell receptors and setting off a cascade of events leading to inflammation. All the pure phenolic isolates, except isoliquiritin, neoisoliquiritin, and isoliquiritin apioside inhibited the inflammatory activity of RAW cells in vitro.

Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway.

Introduction: Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing. Methods: This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line. Results and Discussion: We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 µg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.

Management of placenta accreta spectrum in low- and middle-income countries.

Placenta accreta spectrum (PAS) can be associated massive intra- and post-operative hemorrhage which when not controlled can lead to maternal death. Important advances have occurred in understanding the pathophysiology and therapeutic options for this condition. The prevalence of PAS at birth is direct association with the cesarean delivery (CD) rate in the corresponding population and is increasing worldwide. Limited health infrastructure in low- and middle-income countries increases the morbidity and mortality of patients with PAS at birth. In many cases, obstetricians working in limited resources settings cannot follow some of the international guideline's recommendations and have to opt for low-cost management procedures. In this review, we describe the particularities of managing PAS care in low- and middle-income countries from of prenatal evaluation of patients at risk of PAS at birth, therapeutic options, and inter-institutional collaboration. We also propose a management protocol based on training of the local obstetric teams rather than on sophisticated technological resources that are almost never available in low-resource scenarios.

Perceived Social Stigma of Cutaneous Leishmaniasis in Hubuna, Saudi Arabia.

Background: Cutaneous Leishmaniasis (CL) is a vector-borne skin infection that remains prevalent in regions with poor socioeconomic conditions. Stigmatization occurs when individuals with physical or psychological disorders interact with societal stereotypes. The aim of this study was to explore the perceived social stigma surrounding CL among people residing in Hubuna, Saudi Arabia. Methods: This cross-sectional community-based survey recruited 618 individuals aged 18 years and above using the snowball sampling technique to reach hidden cases within the target population. Data was collected using a self-administered questionnaire and the Explanatory Model Interview Catalogue for Perceived Social Stigma (EMIC-SS-12) was used to assess the level of perceived social stigma. It includes questions on demographic variables, behaviors, and experiences. The analysis was performed using SPSS. Results: The study included 618 participants, the majority of whom were women and girls (54.2%), with a mean age of 28 ± 12.7 years. The median score for perceived social stigma was 26.0. Only 2.1% (n = 13) of participants had the highest EMIC-SS-12 score of 36, while 7.6% (n = 47) scored zero. The mean score for overall perceived social stigma was 1.89 ± 0.91, while the mean score for experienced stigma was 1.99 ± 1.02. Univariate analysis showed that sex, employment, location of lesions, and number of lesions were insignificantly associated with stigmatization (P-value < 0.05), because these associations were uncertain because the CI includes or very close to 1. Conclusion: The study reveals insights into stigmatization associated with CL in the Habuna area of Saudi Arabia. It found that the median of perceived social stigma was 26. Factors such as sex, employment status, and location of the lesion are uncertainly associated with stigma. It is crucial to explore negative behaviors and perceptions and develop suitable health education programs.

Cognitive performance in aged rats is associated with differences in distinctive neuronal populations in the ventral tegmental area and altered synaptic plasticity in the hippocampus.

Introduction: Deterioration of cognitive functions is commonly associated with aging, although there is wide variation in the onset and manifestation. Albeit heterogeneity in age-related cognitive decline has been studied at the cellular and molecular level, there is poor evidence for electrophysiological correlates. The aim of the current study was to address the electrophysiological basis of heterogeneity of cognitive functions in cognitively Inferior and Superior old (19-20 months) rats in the ventral tegmental area (VTA) and the hippocampus, having Young (12 weeks) rats as a control. The midbrain VTA operates as a hub amidst affective and cognitive facets, processing sensory inputs related to motivated behaviours and hippocampal memory. Increasing evidence shows direct dopaminergic and non-dopaminergic input from the VTA to the hippocampus. Methods: Aged Superior and Inferior male rats were selected from a cohort of 88 animals based on their performance in a spatial learning and memory task. Using in vivo single-cell recording in the VTA, we examined the electrical activity of different neuronal populations (putative dopaminergic, glutamatergic and GABAergic neurons). In the same animals, basal synaptic transmission and synaptic plasticity were examined in hippocampal slices. Results: Electrophysiological recordings from the VTA and hippocampus showed alterations associated with aging per se, together with differences specifically linked to the cognitive status of aged animals. In particular, the bursting activity of dopamine neurons was lower, while the firing frequency of glutamatergic neurons was higher in VTA of Inferior old rats. The response to high-frequency stimulation in hippocampal slices also discriminated between Superior and Inferior aged animals. Discussion: This study provides new insight into electrophysiological information underlying compromised cerebral ageing. Further understanding of brain senescence, possibly related to neurocognitive decline, will help develop new strategies towards the preservation of a high quality of life.

Emergency Decompression of Orbital Emphysema, a Sight-Saving Tool in a Patient With Precious Eye.

A woman, 19 years old, with a history of falling from a height with resulting zygomatico-maxillar complex fracture on the right side, a mandibular fracture on the left side for which she underwent repair with plate insertion, and traumatic optic atrophy in her right eye, presented 9 months later with eye facial swelling, proptosis, and acute rapid loss of vision in the left eye. The diagnosis was done immediately aided by radiology assistance and a decision was taken to admit the patient to undergo urgent decompression to save the vision and the patient did recover well. This case presented here and the associated literature review focus on severe orbital emphysema with compressive optic neuropathy and orbital compartment syndrome as a morbidity that can exist with delayed presentation after trauma and not elicited by sneezing or forced blowing, as well as the drastic importance of brisk intervention, to save vision and prevent visual complications if left untreated.