The impact of in-house pathology services on downstaging cervical cancer in Tanzania over an 18-year period.

PURPOSE: Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. METHODS: We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. RESULTS: Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). CONCLUSIONS: Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs.

Production and optimization of surfactin produced from locally isolated Bacillus halotolerans grown on agro-industrial wastes and its antimicrobial efficiency.

INTRODUCTION: Optimal exploitation of the huge amounts of agro-industrial residuals that are produced annually, which endangers the ecosystem and ultimately contributes to climate change, is one of the solutions available to produce value-added compounds. AIM AND OBJECTIVES: This study aimed at the economic production and optimization of surfactin. Therefore, the production was carried out by the microbial conversion of Potato Peel Waste (PPW) and Frying Oil Waste (FOW) utilizing locally isolated Bacillus halotolerans. Also, investigating its potential application as an antimicrobial agent towards some pathogenic strains. RESULTS: Screening the bacterial isolates for surfactin production revealed that the strain with the highest yield (49 g/100 g substrate) and efficient oil displacement activity was genetically identified as B. halotolerans. The production process was then optimized utilizing Central Composite Design (CCD) resulting in the amelioration of yield by 11.4% (from 49 to 55.3 g/100 g substrate) and surface tension (ST) by 8.3% (from 36 to 33 mN/m) with a constant level of the critical micelle concentration (CMC) at 125 mg/L. Moreover, the physiochemical characterization studies of the produced surfactin by FTIR, 1H NMR, and LC-MS/MS proved the existence of a cyclic lipopeptide (surfactin). The investigations further showed a strong emulsification affinity for soybean and motor oil (E24 = 50%), as well as the ability to maintain the emulsion stable over a wide pH (4-10) and temperature (10-100 °C) range. Interestingly, surfactin had a broad-spectrum range of inhibition activity against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, klebsiella pneumonia, and Candida albicans. CONCLUSION: Subsequently, the screening of the isolates and the utilized food-processing wastes along with the extraction technique resulted in a high yield of surfactin characterized by acceptable ST and CMC levels. However, optimization of the cultural conditions to improve the activity and productivity was achieved using Factor-At-A-Time (OFAT) and Central Composite Design (CCD). In contrast, surface activity recorded a maximum level of (33 mN/n) and productivity of 55.3 g/100 g substrate. The optimized surfactin had also the ability to maintain the stability of emulsions over a wide range of pH and temperature. Otherwise, the obtained results proved the promising efficiency of the surfactin against bacterial and fungal pathogens.

Protective effects of microbial biosurfactants produced by Bacillus halotolerans and Candida parapsilosis on bleomycin-induced pulmonary fibrosis in mice: Impact of antioxidant, anti-inflammatory and anti-fibrotic properties via TGF-ß1/Smad-3 pathway and miRNA-326.

Idiopathic pulmonary fibrosis (IPF) is an irreversible disease which considered the most fatal pulmonary fibrosis. Pulmonary toxicity including IPF is the most severe adverse effect of bleomycin, the chemotherapeutic agent. Based on the fact that, exogenous surfactants could induce alveolar stabilization in many lung diseases, the aim of this study was to explore the effects of low cost biosurfactants, surfactin (SUR) and sophorolipids (SLs), against bleomycin-induced pulmonary fibrosis in mice due to their antioxidant, and anti-inflammatory properties. Surfactin and sophorolipids were produced by microbial conversion of frying oil and potato peel wastes using Bacillus halotolerans and Candida parapsilosis respectively. These biosurfactants were identified by FTIR, 1H NMR, and LC-MS/MS spectra. C57BL/6 mice were administered the produced biosurfactants daily at oral dose of 200 mg kg-1 one day after the first bleomycin dose (35 U/kg). We evaluated four study groups: Control, Bleomycin, Bleomycin+SUR, Bleomycin+SLs. After 30 days, lungs from each mouse were sampled for oxidative stress, ELISA, Western blot, histopathological, immunohistochemical analyses. Our results showed that the produced SUR and SLs reduced pulmonary oxidative stress and inflammatory response in the lungs of bleomycin induced mice as they suppressed SOD, CAT, and GST activities also reduced NF-κß, TNF-α, and CD68 levels. Furthermore, biosurfactants suppressed the expression of TGF-ß1, Smad-3, and p-JNK fibrotic signaling pathway in pulmonary tissues. Histologically, SUR and SLs protected against lung ECM deposition caused by bleomycin administration. Biosurfactants produced from microbial sources can inhibit the induced inflammatory and fibrotic responses in bleomycin-induced pulmonary fibrosis.

Quantifying the association of sperm DNA fragmentation with assisted reproductive technology outcomes: An umbrella review.

BACKGROUND: Systematic reviews and meta-analyses are instrumental in shaping clinical practice. However, their findings can sometimes be marred by discrepancies and potential biases, thereby diluting the strength of the evidence presented. Umbrella reviews serve to comprehensively assess and synthesise these reviews, offering a clearer insight into the quality of the evidence presented. In the context of the relationship between sperm DNA fragmentation (SDF) and assisted conception outcomes, there is a divergence in the literature. Some reviews suggest a clear cause-and-effect linkage, whereas others present conflicting or inconclusive results. OBJECTIVES: In this umbrella review we aimed to synthesise the evidence collated in systematic reviews and meta-analyses summarising the association of SDF with assisted reproductive technology (ART) outcomes. SEARCH STRATEGY: After preregistration (https://doi.org/10.17605/OSF.IO/6JHDP), we performed a comprehensive search of the PubMed, Scopus, Cochrane Library, Web of Science and Embase databases. We conducted a search for systematic reviews on the association between SDF and ART without any restrictions on language or publication date. SELECTION CRITERIA: Systematic reviews and meta-analyses assessing the association between SDF and ART outcomes were eligible. DATA COLLECTION AND ANALYSIS: We assessed the quality of the included reviews using AMSTAR 2 and ROBIS, and determined the degree of overlap of primary studies between reviews estimating the corrected covered area (CCA), adjusted for structural missingness. We evaluated the most recent reviews assessing the association of SDF with live birth, pregnancy, miscarriage, implantation, blastulation and fertilisation. The synthesis of evidence was harmonised across all included quantitative syntheses, re-estimating the odds ratio (eOR) in random-effects meta-analyses with 95% confidence intervals (95% CIs) and 95% prediction intervals (95% PIs). We categorised the evidence strength into convincing, highly suggestive, suggestive, weak or nonsignificant, according to the meta-analysis re-estimated P-value, total sample size, I2 statistic for heterogeneity, small study effect, excess significance bias and the largest study significance. MAIN RESULTS: We initially captured and screened 49 332 records. After excluding duplicate and ineligible articles, 22 systematic reviews, 15 of which were meta-analyses, were selected. The 22 reviews showed a moderate degree of overlap (adjusted CCA 9.2%) in their included studies (overall n = 428, with 180 unique studies). The 15 meta-analyses exhibited a high degree of overlap (adjusted CCA = 13.6%) in their included studies (overall n = 274, with 118 unique studies). AMSTAR 2 categorised the quality of evidence in 18 reviews as critically low and the quality of evidence in four reviews as low. ROBIS categorised all the reviews as having a high risk of bias. The re-estimated results showed that the association of SDF with live birth was weak in one and nonsignificant in four meta-analyses. Similarly, the association of SDF with pregnancy, miscarriage, implantation, blastulation and fertilisation was also weak or nonsignificant. The association of high SDF with different ART outcomes was also weak or nonsignificant for different interventions (IVF, ICSI and IUI) and tests. CONCLUSIONS: This umbrella review did not find convincing or suggestive evidence linking SDF with ART outcomes. Caution should be exercised in making any claims, policies or recommendations concerning SDF.

Analyzing energetics and dynamics of hepatitis C virus polymerase interactions with marine bacterial compounds: a computational study.

Hepatitis C Virus (HCV) is a significant health concern affecting a large portion of the global population and is a major cause of acute liver diseases, including cirrhosis. The variability in the HCV genome mainly results from the rapid replication facilitated by the NS5B polymerase, making it a prime target for anti-HCV drug development. This study explores potential compounds from marine bacteria that could inhibit the HCV NS5B polymerase by virtual screening, analyzing the energetics, and dynamic behavior of target-compound complexes. Virtual screening with the Lipinski filter was employed to select compounds from the marine bacteria database that demonstrated strong binding affinity to NS5B. The top four (CMNPD27216, CMNPD21066, CMNPD21065, and CMNPD27283) compounds, ranked by their re-docking scores, underwent additional evaluation. Molecular dynamics simulations for 200 ns were conducted to assess the dynamic stability of these complexes in a solvent environment. Furthermore, methods such as MM-GBSA, PCA, and free energy landscape analysis were used to analyze the system's energetics and identify stable conformations by locating transition states. The findings suggest that these compounds exhibit promising binding capabilities to HCV polymerase and could be considered for future experimental validation.

Peritoneal B Cells Play a Role in the Production of Anti-polyethylene Glycol (PEG) IgM against Intravenously Injected siRNA-PEGylated Liposome Complexes.

Polyethylene glycol (PEG)-modified (PEGylated) cationic liposomes are frequently used as delivery vehicles for small interfering RNA (siRNA)-based drugs because of their ability to encapsulate/complex with siRNA and prolong the circulation half-life in vivo. Nevertheless, we have reported that subsequent intravenous (IV) injections of siRNA complexed with PEGylated cationic liposomes (PLpx) induces the production of anti-PEG immunoglobulin M (IgM), which accelerates the blood clearance of subsequent doses of PLpx and other PEGylated products. In this study, it is interesting that splenectomy (removal of spleen) did not prevent anti-PEG IgM induction by IV injection of PLpx. This indicates that B cells other than the splenic version are involved in anti-PEG IgM production under these conditions. In vitro and in vivo studies have shown that peritoneal cells also secrete anti-PEG IgM in response to the administration of PLpx. Interleukin-6 (IL-6) is a glycoprotein that is secreted by peritoneal immune cells and has been detected in response to the in vivo administration of PLpx. These observations indicate that IV injection of PLpx stimulates the proliferation/differentiation of peritoneal PEG-specific B cells into plasma cells via IL-6 induction, which results in the production of anti-PEG IgM from the peritoneal cavity of mice. Our results suggest the mutual contribution of peritoneal B cells as a potent anti-PEG immune response against PLpx.

Sinefungin analogs targeting VP39 methyltransferase as potential anti-monkeypox therapeutics: a multi-step computational approach.

The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds-CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.

Long-Term Costs of Minimally Invasive Sacral Colpopexy Compared to Native Tissue Vaginal Repair With Concomitant Hysterectomy.

STUDY OBJECTIVE: To determine the long-term costs of hysterectomy with minimally invasive sacrocolpopexy (MISCP) versus uterosacral ligament suspension (USLS) for primary uterovaginal prolapse repair. DESIGN: A hospital-based decision analysis model was built using TreeAge Pro (TreeAge Software Inc, Williamstown, MA). Those with prolapse were modeled to undergo either vaginal hysterectomy with USLS or minimally invasive total hysterectomy with sacrocolpopexy (MISCP). We modeled the chance of complications of the index procedure, prolapse recurrence with the option for surgical retreatment, complications of the salvage procedure, and possible second prolapse recurrence. The primary outcome was cost of the surgical strategy. The proportion of patients living with prolapse after treatment was the secondary outcome. SETTING: Tertiary center for urogynecology. PATIENTS: Female patients undergoing surgical repair by the same team for primary uterovaginal prolapse. INTERVENTIONS: Comparison analysis of estimated long-term costs was performed. MEASUREMENTS AND MAIN RESULTS: Our primary outcome showed that a strategy of undergoing MISCP as the primary index procedure cost $19 935 and that undergoing USLS as the primary index procedure cost $15 457, a difference of $4478. Furthermore, 21.1% of women in the USLS group will be living with recurrent prolapse compared to 6.2% of MISCP patients. Switching from USLS to MISCP to minimize recurrence risk would cost $30 054 per case of prolapse prevented. Additionally, a surgeon would have to perform 6.7 cases by MISCP instead of USLS in order to prevent 1 patient from having recurrent prolapse. CONCLUSION: The higher initial costs of MISCP compared to USLS persist in the long term after factoring in recurrence and complication rates, though more patients who undergo USLS live with prolapse recurrence.

Impact of the universal health insurance benefits on cervical cancer mortality in Colombia.

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.

Mass Spectrometry Applications to Study Human Microbiome.

Microbiotas are an adaptable component of ecosystems, including human ecology. Microorganisms influence the chemistry of their specialized niche, such as the human gut, as well as the chemistry of distant surroundings, such as other areas of the body. Metabolomics based on mass spectrometry (MS) is one of the primary methods for detecting and identifying small compounds generated by the human microbiota, as well as understanding the functional significance of these microbial metabolites. This book chapter gives basic knowledge on the kinds of untargeted mass spectrometry as well as the data types that may be generated in the context of microbiome study. While data analysis remains a barrier, the emphasis is on data analysis methodologies and integrative analysis, particularly the integration of microbiome sequencing data. Mass spectrometry (MS)-based techniques have resurrected culture methods for studying the human gut microbiota, filling in the gaps left by high-throughput sequencing methods in terms of culturing minor populations.

Applications of Proteomics in Probiotics Having Anticancer and Chemopreventive Properties.

Proteomics has grown in importance in molecular sciences because it gives vital information on protein identification, expression levels, and alteration. Cancer is one of the world's major causes of death and is the major focus of much research. Cancer risk is determined by hereditary variables as well as the body's immunological condition. Probiotics have increasing medical importance due to their therapeutic influence on the human body in the prevention and treatment of numerous chronic illnesses, including cancer, with no adverse effects. Several anticancer, anti-inflammatory, and chemopreventive probiotics are studied using different proteomic approaches like two-dimensional gel electrophoresis, liquid chromatography-mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. To gain relevant information about probiotic characteristics, data from the proteomic analysis are evaluated and processed using bioinformatics pipelines. Proteomic studies showed the significance of different proteomic approaches in characterization, comparing strains, and determination of oxidative stress of different probiotics. Moreover, proteomic approaches identified different proteins that are involved in glucose metabolism and the formation of cell walls or cell membranes, and the differences in the expression of critical enzymes in the HIF-1 signaling pathway, starch, and sucrose metabolism, and other critical metabolic pathways.

Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors.

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N'-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = -8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19.

Prognostic impact of MYD88 and TP53 mutations in diffuse large B Cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of lymphoma. It is a highly heterogeneous lymphoid neoplasm, with variations in gene expression profiles and genetic alterations. MYD88 and TP53 genes are common to be expressed and mutated in DLBCL patients with controversy regarding their role in prognosis and survival. This study aims to determine the predictive and prognostic role of MYD88 and TP53 gene mutation in DLBCL. A prospective cohort study was conducted on 50 patients who were diagnosed with DLBCL and 30 healthy individuals to assess the sensitivity and specificity of MYD88 and TP53 genetic mutations. MYD88 and TP53 gene mutations were more sensitive, specific, and accurate in predicting overall mortality and disease progression in comparison with the international prognostic index. Mutant MYD88 and TP53 showed their prognostic importance for worse objective response rates and survival outcomes. Both mutant MYD88 and TP53 were associated with worse ORR. There was a significant statistical difference for both MYD88 and TP53 with regard to 2-year PFS and 2-year OS rate. Hence, both mutant MYD88 and TP53 can be used in predicting disease progression and overall mortality.

The effect of piezoelectric shockwave lithotripsy with 2- and 8-mm focus sizes on stone disintegration and renal injury.

OBJECTIVES: To compare the efficacy and safety of shockwave lithotripsy (SWL) using a narrow focus or wide focus for renal stones. PATIENTS AND METHODS: A double-blind randomised trial included adult patients with a solitary radio-opaque renal pelvic stone of 1-2 cm. Patients were randomised into two groups: narrow-focus (2 mm) SWL and wide-focus (8 mm) SWL. The stone-free rate (SFR) and presence of complications such as haematuria, fever, pain, and peri-renal haematoma were evaluated. Pre- and postoperative urinary markers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule 1 [KIM-1]) concentrations were compared to assess renal injury. RESULTS: A total of 135 patients were recruited for this study. The SFR after the first SWL session was 79.2% and 69.1% in narrow- and wide-focus groups, respectively. There was a comparable rise in the median 2-h NGAL concentration in both groups (P = 0.62). However, the rise in the median (interquartile range [IQR]) 2-h KIM-1 concentration was significantly higher in the narrow-focus group at 4.9 (4.6, 5.8) ng/mL compared with the wide-focus group at 4.4 (3.2, 5.7) ng/mL (P = 0.02). Nevertheless, the 3-day NGAL and KIM-1 urinary marker concentrations were significantly improved (P = 0.263 and P = 0.963, respectively). The overall SFR after three sessions was 86.6% and 86.8% in the narrow- and wide-focus groups, respectively (P = 0.77). Both groups were comparable for complications, apart from the median pain score and the percentage of high-grade haematuria, which were significantly higher in the narrow-focus group (P < 0.001 and P = 0.03, respectively). CONCLUSION: Narrow- and wide-focus SWL were associated with comparable outcomes and re-treatment rates. However, narrow-focus SWL was associated with significantly higher morbidity in terms of pain and haematuria.

Evaluation of ultrathin semirigid ureteroscopy in terms of efficiency and cost compared to flexible ureteroscopy in treating proximal ureteric stones: a prospective randomized multicenter study.

PURPOSE: To investigate the outcome and cost-effectiveness of ultrathin 6-7.5-Fr semirigid ureteroscopy in treating proximal ureteric stones compared to flexible ureteroscopy. METHODS: Two hundred and twenty patients with a solitary proximal ureteric stone were eligible for ureteroscopy (stone size = 1-2 cm). Patients were randomly subdivided into two groups: Group I included 105 patients who underwent ultrathin semirigid ureteroscopy and group II included 115 patients who underwent flexible ureteroscopy. Both groups were compared regarding successful stone access, operation time, reoperation rates, the financial cost to stone-free, complications, and stone clearance at 4 and 8 weeks. RESULTS: Groups I and II had no significant differences regarding patient demographics, stone criteria, and hospitalization time. In contrast, the mean operative time was significantly longer in group II (p < 0.001). The overall scope-to-stone access rate was 89.5%. It was 87.6% compared to 91.3% (p = 0.32), while the stone-free rate was 81.9% versus 87.8% (p = 0.22) for groups I and II, respectively. Intraoperative and postoperative complications were statistically insignificant between the study groups. The cost/person in Egyptian pounds was 8619 ± 350 in group I, compared to 17,620 ± 280 in group II (p < 0.001); similarly, the cost to attain the stone-free rate was 8950 ± 720 in group I compared to 17,950 ± 500 in group II. CONCLUSION: Ultrathin semirigid ureteroscopy is safe, durable, and considered a cost-effective method for treating upper ureteric calculi compared to the flexible ureteroscopy and could be considered a first treatment option in developing countries.

Comparative study between antegrade flexible ureteroscopy and reterograde intrarenal surgery in the management of impacted upper ureteric stones 1.5 cm or larger.

OBJECTIVE: To prospectively investigate the safety and efficacy of antegrade flexible ureteroscopy (FURS) with the following criteria (supine, ultrasonic guided puncture through lower calyx with 14 fr tract, tubeless) versus retrograde intrarenal surgery (RIRS) in the management of large impacted upper ureteric stones ≥ 1.5 cm. PATIENTS AND METHODS: This study recruited 61 patients with single large impacted upper ureteric stone of ≥ 1.5 cm. The patients were randomly allocated to two groups. Group A, included 31 patients who treated by antegrade FURS, all patients were put in supine modified galadako Valdivia position and the renal access is reached by ultrasonic guided puncture through the lower calyx with dilatation upto 14 fr to insert ureteric access sheath and all cases were tubless with JJ stent insertion. Group B, included 30 patients who were treated by RIRS with JJ stent insertion. Stone fragmentation was done by holmium laser in both group. RESULTS: Group A was significantly associated with higher proportion of SFR (90.3%) compared to Group B (70%) (p = 0.046). Group B was significantly associated with shorter operative time and fluoroscopy time in comparison with Group A (p < 0.001). No significant differences were found between studied groups regarding bleeding (p = 0.238). Urosepsis showed significantly higher proportion associated with retrograde approach when compared to antegrade approach (p = 0.024). CONCLUSION: This study showed that antegrade FURS is safe and more effective than RIRS for the management of large impacted upper ureteric stones ≥ 1.5 cm.

Production and optimization of novel Sphorolipids from Candida parapsilosis grown on potato peel and frying oil wastes and their adverse effect on Mucorales fungal strains.

BRIEF INTRODUCTION: Mucormycosis disease, which has recently expanded with the Covid 19 pandemic in many countries, endangers patients' lives, and treatment with common drugs is fraught with unfavorable side effects. AIM AND OBJECTIVES: This study deals with the economic production of sophorolipids (SLs) from different eight fungal isolates strains utilizing potato peels waste (PPW) and frying oil waste (FOW). Then investigate their effect against mucormycetes fungi. RESULTS: The screening of the isolates for SLs production revealed the highest yield (39 g/100 g substrate) with most efficiency was related to a yeast that have been identified genetically as Candida parapsilosis. Moreover, the characterizations studies of the produced SLs by FTIR, 1H NMR and LC-MS/MS proved the existence of both acidic and lactonic forms, while their surface activity was confirmed by the surface tension (ST) assessment. The SLs production was optimized utilizing Box-Behnken design resulting in the amelioration of yield by 30% (55.3 g/100 g substrate) and ST by 20.8% (38mN/m) with constant level of the critical micelle concentration (CMC) at 125 mg/L. The studies also revealed the high affinity toward soybean oil (E24 = 50%), in addition to maintaining the emulsions stability against broad range of pH (4-10) and temperature (10-100℃). Furthermore, the antifungal activity against Mucor racemosus, Rhizopus microsporus, and Syncephalastrum racemosum proved a high inhibition efficiency of the produced SLs. CONCLUSION: The findings demonstrated the potential application of the SLs produced economically from agricultural waste as an effective and safer alternative for the treatment of infection caused by black fungus.

Potential anti-obesity/inflammatory flavonoid-derived biomolecules against Obesity to prevent WAT differentiation by targeting a DNA-binding protein inhibitor, ID-1.

A concoction of unhealthy eating, inactivity, and the adverse effects of specific drugs brings on obesity. The primary cause of Obesity is the storage of too much energy and triglycerides in adipocytes, particularly white adipose tissue (WAT). In addition to modifying one's lifestyle, anti-obesity medicines are increasingly used as adjuvant therapy. Flavonoids are the major class of compounds having significant biological impacts and health-improving properties. To find novel flavonoid compounds that fight obesity using computational drug design techniques. This work targets 1DI protein to predict new flavonoid compounds that fight obesity. The study uses computational approaches to anticipate potential anti-obesity/inflammatory flavonoid compounds against obesity to prevent WAT differentiation by targeting ID-1, a DNA-binding protein inhibitor. Our study led to the identification of the protein target inhibitor lead CID: 5280443, which was found to be a potent inhibitor of the receptor. According to the findings of this study, this bio-active molecule may be used as a lead for the development of drugs that preferentially fight obesity without interfering with the functions of the human proteasome. The scientific community will benefit from these discoveries, which could aid in the creation of new medications that treat obesity more successfully.

Financial analysis of minimally invasive sacrocolpopexy compared with native tissue vaginal repair with concomitant hysterectomy.

INTRODUCTION: Minimally invasive sacrocolpopexy (MISCP) is increasingly used for uterovaginal prolapse, but comparative cost data of MISCP versus native tissue vaginal repair (NTR) are lacking. The objective was to determine the cost difference, from a hospital perspective, between MISCP and NTR performed with hysterectomy for uterovaginal prolapse. METHODS: This was a retrospective cohort study at a tertiary care center of women who underwent NTR or MISCP with concomitant hysterectomy in 2021. Hospital charges, direct and indirect costs, and operating margin (revenue minus costs) were obtained from Strata Jazz and compared using SPSS. RESULTS: A total of 82 women were included, 33 MISCP (25 robotic, 8 laparoscopic) versus 49 NTR. Demographic and surgical data were similar, except that MISCP had younger age (50.5 vs 61.1 years, p<0.01). Same-day discharge and estimated blood loss were similar, but operative time was longer for MISCP (204 vs 161 min, p<0.01). MISCP total costs were higher (US$17,422 vs US$13,001, p<0.01). MISCP had higher direct costs (US$12,354 vs US$9,305, p<0.01) and indirect costs (US$5,068 vs US$3,696, p<0.01). Consumable supply costs were higher with MISCP (US$4,429 vs US$2,089, p<0.01), but the cost of operating room time and staff was similar (US$7,926 vs US$7,216, p=0.07). Controlling for same-day discharge, anti-incontinence procedures and smoking, total costs were higher for MISCP (adjusted beta = US$4,262, p<0.01). Mean charges (US$102,060 vs US$97,185, p=0.379), revenue (US$22,214 vs US$22,491, p=0.929), and operating margin (US$8,719 vs US$3,966, p=0.134) were not statistically different. CONCLUSION: Minimally invasive sacrocolpopexy had higher costs than NTR; however, charges, reimbursement, and operating margins were not statistically significantly different between the groups.

Targeting Breast Cancer Signaling via Phytomedicine and Nanomedicine.

BACKGROUND: The development of breast cancer (BC) and how it responds to treatment have both been linked to the involvement of inflammation. Chronic inflammation is critical in carcinogenesis, leading to elevated DNA damage, impaired DNA repair machinery, cell growth, apoptosis, angiogenesis, and invasion. Studies have found several targets that selectively modulate inflammation in cancer, limit BC's growth, and boost treatment effectiveness. Drug resistance and the absence of efficient therapeutics for metastatic and triple-negative BC contribute to the poor outlook of BC patients. SUMMARY: To treat BC, small-molecule inhibitors, phytomedicines, and nanoparticles are conjugated to attenuate BC signaling pathways. Due to their numerous target mechanisms and strong safety records, phytomedicines and nanomedicines have received much attention in studies examining their prospects as anti-BC agents by such unfulfilled demands. KEY MESSAGES: The processes involved in the affiliation across the progression of tumors and the spread of inflammation are highlighted in this review. Furthermore, we included many drugs now undergoing clinical trials that target cancer-mediated inflammatory pathways, cutting-edge nanotechnology-derived delivery systems, and a variety of phytomedicines that presently address BC.