Natural compounds targeting miRNAs: a novel approach in oral cancer therapy.

Oral cancer (OC) is a significant global health issue, with high rates of both mortality and morbidity. Conventional treatments, including surgery, radiation, and chemotherapy, are commonly used, but they often come with serious side effects and may not fully eliminate cancer cells, resulting in recurrence and resistance to treatment. In recent years, natural products derived from plants and other biological sources have gained attention for their potential anticancer properties. These compounds offer advantages such as lower toxicity compared to traditional chemotherapy. Notable natural compounds like quercetin, berberine, curcumin, andrographolide, nimbolide, ovatodiolide, and cucurbitacin B have demonstrated effectiveness in inhibiting OC cell growth by targeting various signaling pathways involved in cancer progression. Recent breakthroughs in molecular biology have highlighted the crucial role of microRNAs (miRNAs) in the development of OC. Targeting dysregulated miRNAs with natural products offers a promising strategy for treating the disease. Natural compounds exert anticancer effects by influencing both altered cellular signaling pathways and miRNA expression profiles. This study aims to explore the role of miRNAs as potential molecular targets in OC and to investigate how natural products may regulate these miRNAs. Additionally, this review will shed light on the therapeutic potential of phytochemicals in modulating miRNA expression and their significance in OC treatment.

Phage-resistant Streptomyces abietis and its telomycin bioactive metabolite as a possible alternative to antibiotics.

Multidrug-resistant pathogens are now thought to be the primary global causes of disease and death. Therefore, it is imperative to develop new effective bioactive compounds from microbial sources, such as Streptomyces species. Nevertheless, the pharmaceutical industry suffered financial losses and low-quality end products as a result of Streptomyces bacteriophage contamination. To reduce the likelihood of phage-induced issues in the medical industry, it is crucial to develop a method for finding phage-resistant strains. Hence, we aimed to isolate and characterize Streptomyces spp. and Streptomyces phages from various rhizospheric soil samples in Egypt and to investigate their antibacterial activities. Moreover, we targeted development of a Streptomyces phage-resistant strain to extract its active metabolites and further testing its antibacterial activity. Herein, the antibacterial activities of the isolated 58 Streptomyces isolates showed that 10 (17.2 %) Streptomyces isolates had antibacterial activities against the tested bacteria including Listeria monocytogenes, E. coli O157, Acinetobacter baumannii, methicillin resistant-vancomycin-intermediate Staphylococcus aureus (MRSA-VISA) and Micrococcus luteus. Three lytic bacteriophages (ϕPRSC1, ϕPRSC2, and ϕPRSC4) belonging to the families Siphoviridae and Podoviridae were obtained from the rhizospheric soil samples using the most potent S. abietis isolate as the host strain. The three isolated Streptomyces phages were thermostable, ultraviolet stable, infectious, and had a wide range of hosts against the 10 tested Streptomyces isolates with antibacterial activities. The DNA of the ϕPRSC1 and ϕPRSC4 phages were resistant to digestion by EcoRI and HindIII, but the DNA of ϕPRSC2 was resistant to digestion by EcoRI and sensitive to digestion by HindIII. Of note, we developed a S. abietis strain resistant to the three isolated phages and its antibacterial activities were twice that of the wild strain. Finally, telomycin was recognized as an antibacterial metabolite extracted from phage-resistant S. abietis strain, which was potent against the tested Gram-positive bacteria including L. monocytogenes, MRSA-VISA, and M. luteus. Thus, our findings open new horizons for researching substitute antimicrobial medications for both existing and reemerging illnesses.

Side-specific factors for intraoperative hemodynamic instability in laparoscopic adrenalectomy for pheochromocytoma: a comparative study.

BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.

Identifying distinct phenotypes of patients with juvenile systemic lupus erythematosus: results from a cluster analysis by the Egyptian college of rheumatology (ECR) study group.

PURPOSE: Juvenile systemic lupus erythematosus (J-SLE) is a complex, heterogeneous disease affecting multiple organs. However, the classification of its subgroups is still debated. Therefore, we investigated the aggregated clinical features in patients with J-SLE using cluster analysis. METHODS: Patients (≤ 16 years) diagnosed using the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were identified from the clinical database of the Egyptian College of Rheumatology (ECR) SLE study group. Demographic data, clinical characteristics, laboratory features, and current therapies were selected. A cluster analysis was performed to identify different clinical phenotypes. RESULTS: Overall, 404 patients, of whom 355 (87.9%) were female, had a mean age at diagnosis of 11.2 years and a mean disease duration of 2.3 years. We identified four distinct subsets of patients. Patients in cluster 1 (n = 103, 25.5%) were characterized predominantly by mucocutaneous and neurologic manifestations. Patients in cluster 2 (n = 101, 25%) were more likely to have arthritis and pulmonary manifestations. Cluster 3 (n = 71, 17.6%) had the lowest prevalence of arthritis and lupus nephritis (LN), indicative of mild disease intensity. Patients in cluster 4 (n = 129, 31.9%) have the highest frequency of arthritis, vasculitis, and LN. Cluster 1 and 4 patients had the highest disease activity index score and were less likely to use low-dose aspirin (LDA). The SLE damage index was comparable across clusters. CONCLUSIONS: Four identified J-SLE clusters express distinct clinical phenotypes. Attention should be paid to including LDA in the therapeutic regimen for J-SLE. Further work is needed to replicate and clarify the phenotype patterns in J-SLE.

Transphyseal Hemiepiphysiodesis: Is it Truly Reversible?

BACKGROUND: Although numerous studies reported the efficacy of percutaneous epiphysiodesis using transphyseal screws (PETS) in correcting angular knee deformities, many surgeons refrained from using it in younger children because of a lack of objective evidence of reversibility. Our hypothesis is that PETS is both truly reversible and effective. METHODS: Twenty-one patients aged 8 to 13 years (36 lower limbs LL) with coronal plane knee deformity were enrolled into this prospective case series from January 2021 to September 2023. Besides the routine monitoring of PETS efficacy, low dose CT knee of 32 treated physes was done 6 months after screw removal. In addition, lower limb length, mechanical lateral distal femur angle (mLDFA), and medial proximal tibial angle (MPTA) were recorded preoperatively and 6 to 17 months after screw removal for 24 LL to investigate physis behavior, technique reversibility, and resumption of bone growth after screw removal. RESULTS: The mean mechanical axis deviation (MAD) correction rate was 3.46 mm/mo and 1.78 mm/mo for genu valgum and genu varum patients, respectively. No physeal bony bars could be detected 6 months after screw removal for all patients. Out of 24 physis that underwent computerized radiography (CR) of the whole lower limb, 12 LL resumed their growth, 4 were stationary, while 8 were excluded due to inadequate calibration. A single physis showed rebound deformity, and another showed overcorrection in the genu valgum group. CONCLUSIONS: In addition to being a highly effective method of hemiepiphysiodesis, PETS was found to be reproducible, safe, and reversible when used in the juvenile and early adolescent pediatric population. LEVEL OF EVIDENCE: IV-Prospective case series.

Systematic Evaluation of Regiochemistry and Lipidation of Aryl Trehalose Mincle Agonists.

The Macrophage-Inducible C-type Lectin receptor (Mincle) plays a critical role in innate immune recognition and pathology, and therefore represents a promising target for vaccine adjuvants. Innovative trehalose-based Mincle agonists with improved pharmacology and potency may prove useful in the development of Th17-mediated adaptive immune responses. Herein, we report on in vitro and in silico investigations of specific Mincle ligand-receptor interactions required for the effective receptor engagement and activation of Th17-polarizing cytokines. Specifically, we employed a library of trehalose benzoate scaffolds, varying the degree of aryl lipidation and regiochemistry that produce inflammatory cytokines in a Mincle-dependent fashion. In vitro interleukin-6 (IL-6) cytokine production by human peripheral blood mononuclear cells (hPBMCs) indicated that the lipid regiochemistry is key to potency and maximum cytokine output, with the tri-substituted compounds inducing higher levels of IL-6 in hPBMCs than the di-substituted derivatives. Additionally, IL-6 production trended higher after stimulation with compounds that contained lipids ranging from five to eight carbons long, compared to shorter (below five) or longer (above eight) carbon chains, across all the substitution patterns. An analysis of the additional cytokines produced by hPBMCs revealed that compound 4d, tri-substituted and five carbons long, induced significantly greater levels of interleukin-1ß (IL-1ß), tumor necrosis factor- α (TNF-α), interleukin-23 (IL-23), and interferon- γ (IFN-γ) than the other compounds tested in this study. An in silico assessment of 4d highlighted the capability of this analogue to bind to the human Mincle carbohydrate recognition domain (CRD) efficiently. Together, these data highlight important structure-activity findings regarding Mincle-specific cytokine induction, generating a lead adjuvant candidate for future formulations and immunological evaluations.

Sedative and behavioral effects of atomized intranasal midazolam in comparison with nebulized midazolam for children undergoing dental treatment: A randomized clinical trial.

BACKGROUND: Fear and anxiet are significant barriers of dental care in children. Sedation emerged as a valuable behaviour guidance technique to manage uncooperative children. AIM: To evaluate the sedative and behavioral effectiveness of midazolam administered via nebulizer in comparison with intranasal atomizer in the behavior management of anxious children during dental treatment. STUDY DESIGN: Two-arm randomized clinical trial with 68 children (3-5 years) assigned to receive nebulized midazolam (NEB MDZ) and atomized intranasal midazolam (AIN MDZ) during dental treatment. The onset time, sedation levels, and behavior of children were documented. The data were analyzed using the Wilcoxon signed-rank test and Mann-Whitney U tests. RESULTS: Significant differences between the two groups in terms of onset time, sedation level, and behavior of children during the dental treatment. AIN MDZ was associated with a significantly faster onset time compared with NEB MD, (p < .001). Children who received NEB MDZ exhibited deeper levels of sedation compared with AIN MDZ group (p = .02). During the administration of local anesthesia, notable statistical differences were observed between the behavior of the two groups (p = .02). CONCLUSIONS: Midazolam administered via either nebulizer or intranasal atomizer was the effective route of administration and proved effective in the management of anxious children undergoing dental treatment. AIN MDZ, however, exhibited a faster onset time, whereas children receiving NEB MDZ demonstrated superior behavior compared with those receiving AIN MDZ.

Oral health status of Egyptian children with lysosomal storage diseases: An evaluation of dental indices, salivary cytokines level, and bacterial bioburden.

BACKGROUND: Lysosomal storage diseases (LSDs), a group of inborn errors of metabolism, include various subtypes, for example, mucopolysaccharidosis (MPS) and Gaucher disease (GD). Besides the physical/mental disabilities, they suffer from several oral deteriorations. AIM: To evaluate the oral health status of Egyptian children with LSD. DESIGN: Thirty LSD children and thirty non-LSD children were enrolled for this study according to the inclusion and exclusion criteria. Dental indices were used to assess caries prevalence and periodontal status. Saliva samples were collected from all enrolled children to estimate interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and protein levels as well as Streptococcus mutans and Lactobacilli colony counts. RESULTS: Children with MPS and GD showed non-significant differences in decayed, missing, or filled teeth (DMFT) scores (p = .115). Scores of dmft showed a significant increase in MPS, but not in GD children (p = .020, p = .127). Children with LSD showed significantly increased Modified Gingival Index (MGI), Plaque Index (PI), Oral Hygiene Index (OHI-s) scores (p < .001) and salivary IL-6 and TNF-α (p = .007, p = .001, p < .0001, p = .002, respectively) and salivary total proteins (p = .001) levels. Unexpectedly, non-significant differences were observed in salivary Streptococcus mutans or Lactobacilli counts in children with MPS and GD (p = .058, p = .420, p = .502, p = .053, respectively). CONCLUSION: To our knowledge, this is the first article that evaluates Egyptian children with LSD. We demonstrated high caries prevalence in primary teeth, not permanent teeth, in children with MPS and poor gingival/hygiene status in children with MPS and GD, which triggered a state of inflammation. The daily supplement intake prevented oral bacterial growth. The most probable cause of oral alterations is decreased salivary flow rate, as deduced from a significantly increased salivary protein.

Effect of Dexmedetomidine with or without Midazolam during procedural dental sedation in children: a randomized controlled clinical trial.

BACKGROUND: Dental anxiety is a global problem in the realm of pediatric dentistry. The use of procedural sedation is recommended to avoid substandard or unsafe dental treatment in preschoolers. This study aimed to compare the effect sedation with Dexmedetomidine with or without Midazolam in terms of sedation level, analgesic effect and ease of treatment completion in preschool children. METHODS: A triple blind randomized controlled clinical trial comprised 72 healthy uncooperative children, 4-6 years old, were randomly allocated into three groups of 24 patients each: Group I patients were sedated with nebulized 5 µg/kg Dexmedetomidine (DEX), Group II with nebulized 3 µg/kg DEX followed by nebulized 0.3 mg/kg Midazolam (MID), and Group III with nebulized 0.5 mg/kg MID. Along the session, the three regimens were assessed and compared during the sedation level (children responsiveness) using the Modified Observer's Assessment of Alertness/Sedation Scale, the analgesic effect using the Face, Leg, Activity, Cry, Consolability scale and ease of treatment completion using a separate 5-point scale. Vital signs were recorded before and during sedation, until full recovery. RESULTS: A significant difference was detected regarding children responsiveness during operative procedure in favour of DEX in comparison to MID and DEX/MID groups (P = 0.045). Within the DEX group, a significant difference was recorded regarding children responsiveness at optimum sedation and during the operative procedure (P = 0.04). Although, the analgesic effects of sedative drugs showed no statistically significant difference among the study groups (P = 0.20), the ease of treatment completion was statistically higher in the DEX than MID and DEX/MID groups (P = 0.03). CONCLUSION: Dexmedetomidine provides a moderate level of sedation, that allowed better patient cooperation, and easy completion of performed dental procedures.

Forgotten Biliary Plastic Stents: Complications, Management, and Clinical Outcomes.

Background and Objectives: Endoscopic biliary plastic stenting is a safe and effective temporary therapeutic modality used in various benign biliary disorders. Long-term indwelling stents for more than one year without retrieval are termed "forgotten biliary stents". In clinical practice, the forgotten stents are underestimated and the majority of data were obtained from case reports. The aim of this study was to determine the forgotten-biliary-plastic-stent-related complications, their management, and the patients' clinical outcomes. Materials and Methods: This retrospective study was performed at three hospitals during the period from January 2021 to December 2023. In total, 577 patients with biliary plastic stents-inserted for a variety of benign biliary conditions-were included. They were divided into two groups, as follows: group 1 included 527 patients who had biliary stents removed within 3 months, and group 2 included 50 patients with biliary stents retrieved after one year of their deployment. The stent-related complications (e.g., acute cholangitis, stent clogging, distal stent migration, new common bile duct (CBD) stone formation, and proximal stent migration) and the endoscopic management success rate were evaluated. Results: Irretrievable CBD stones were the main indication for biliary plastic stenting in both groups. The stent-related complications, number of endoscopic sessions, and hospital admissions were significantly higher in the patients with forgotten biliary stents than those with stent removal within 3 months. All the study patients were successfully managed endoscopically with uneventful outcomes. Conclusions: Based on this retrospective study, non-adherence to the endoscopists' instructions is the main reason for retained biliary stents for more than one year. The patients with forgotten stents had significantly higher complication rates, a higher number of endoscopic sessions, and a higher number of hospital admissions than those with stents that were retrieved in the scheduled time. All patients were managed endoscopically with a technical success rate of 100%, and with no complication-related mortality.

Small airway resistance in obese and nonobese patients with obstructive sleep apnea syndrome using impulse oscillometry.

Background/aim: There is limited information on the pathologic changes in the small airways among obese and nonobese patients with obstructive sleep apnea syndrome (OSAS). Impulse oscillometry (IOS) measures airway resistance and reactance independently of patient effort. This study aimed to compare airway resistance in small airways using IOS between obese and nonobese patients with OSAS. Materials and methods: In this real-life cross-sectional study, demographic information was collected from obese and nonobese subjects diagnosed with moderate and severe OSAS without any other underlying diseases. Spirometry and IOS measurements were conducted, and the values of both groups were statistically analyzed. Results: The nonobese group had a mean age of 45.6 ± 11.7 years (median 45), while the obese group had a mean age of 48.4 ± 9.5 years (median 47.5). The mean body mass index (BMI) for the nonobese group was 26.2 ± 2.1 kg/m2 (median 27 kg/m2), and for the obese group, it was 35.6 ± 6.4 kg/m2 (median 33 kg/m2). Statistically significant differences were observed between the two groups in R5 - R20 percentage, reactance area (AX), and resonant frequency (Fres) values (p < 0.05). Conclusion: Among obese OSAS patients, there is an increase in resistance in small airways as indicated by IOS values. IOS shows promise as a potential screening tool for diagnosing OSAS.

Erectile and voiding function outcomes after buccal mucosa graft urethroplasty for long-segment bulbar urethral stricture: ventral versus dorsal onlay technique.

PURPOSE: To compare the impact of dorsal versus ventral onlay buccal mucosa graft bulbar urethroplasty on postoperative erectile function status. MATERIALS AND METHODS: We retrospectively reviewed the records for 232 patients who underwent dorsal and ventral onlay buccal mucosa graft bulbar urethroplasty from March 2012 to April 2021. Outcomes were urinary and erectile function status as assessed by IIEF5-15 score at preoperative, three months, and 12 months post-urethroplasty. We compared the dorsal and ventral only techniques at the different follow-up visits using difference-in-differences analysis. RESULTS: 165 patients met our inclusion criteria; the overall success rate was 87.9% after a mean follow-up of 52.3 ± 18.5 months. Of the patients, 17.6% experienced a 90-day complication. When comparing dorsal and ventral only techniques, there were no significant differences in terms of success rate (88.3% vs. 87.1%, Mantel-Cox test p = 0.68) or postoperative complications (15.5% Vs. 19.4%, p = 0.3). Likewise, there was no significant difference between both techniques regarding postoperative erectile function as assessed by IIEF5-15 score after three months (26.28 ± 2.53 Vs. 26.37 ± 2.41; p = 0.836) and twelve months (26.88 ± 2.45 Vs. 26.48 ± 1.98; p = 0.532). We detected a post-urethroplasty transient ED in (3.9% vs. 1.6%; p = 0.41), and permanent ED in (1.9% vs. 3.2%; p = 0.6) for dorsal and ventral onlay, respectively. CONCLUSIONS: Onlay Buccal mucosa graft urethroplasty is a highly effective surgery in treating long-segment bulbar urethral stricture. The dorsal and ventral only techniques were comparable regarding urinary and erectile function outcomes. Additionally, both techniques have no significant negative impact on post-urethroplasty erectile function status.

Urethral advancement and glanuloplasty versus tubularized incised plate urethroplasty for distal hypospadias repair: a prospective randomized study.

BACKGROUND: About one in 200 to one in 300 male births has hypospadias. The prevalence of this congenital anomaly varies worldwide. The meatus is located distally in approximately 70% of cases. Several surgical techniques were described for distal hypospadias repair; despite this, there is no ideal approach. This study compares urethral advancement &glanuloplasty, and TIP techniques in terms of feasibility, duration of operation, and complications. Patients and. METHODS: This prospective randomized comparative study was conducted at Al-Azhar University Hospitals from April 2022 to October 2022. Fifty-seven cases with different types of hypospadias were assessed for eligibility. Among them, seven cases were excluded due to the presence of severe chordee (n = 3), proximal variant (n = 2), and recurrent cases of hypospadias (n = 2). Fifty cases were randomly divided into two groups using a 1:1 ratio (computer-generated randomization). Twenty-five cases were subjected to urethral advancement and glanuloplasty, and the rest were subjected to tubularized incised plate (TIP) urethroplasty. RESULTS: The mean age of all studied cases was 4.2 years. Approximately 52% had coronal or sub-coronal meatus, whereas 48% had glandular meatus. Both groups were matched according to age and meatus location (p > 0.05). No statistically significant difference was observed between the two groups regarding duration of operation, postoperative pain, and postoperative hospital stay. In addition, both groups did not differ significantly in late complications (meatal stenosis, meatal retraction, fistula, and glans dehiscence). CONCLUSIONS: Both urethral advancement &glanuloplasty, and TIP urethroplasty have comparable short-term outcomes. Urethral advancement and glanuloplasty is preferred in certain conditions, especially in circumcised children or those with a narrow urethral plate. TRIAL REGISTRATION: The study protocol was approved by the Pan African Clinical Trials Registry (number for the registry is: PACTR202211757905870) on (29/11/2022). All procedures were performed per the Helsinki Declaration.

Value of preoperative ureteral wall thickness in prediction of impaction of ureteric stones stratified by size in laser ureteroscopic lithotripsy.

OBJECTIVES: To evaluate the role of preoperative UWT in the prediction of impaction of ureteral stones stratified according to stone size in ureteroscopic laser lithotripsy. PATIENT AND METHODS: This study included 154 patients submitted to URSL for ureteral stones. Radiological data comprised the presence of hydronephrosis, anteroposterior pelvic diameter (PAPD), proximal ureteric diameter (PUD), and maximum UWT at the stone site. Collected stone characteristics were stone size, side, number, site, and density. RESULTS: The study included 154 patients subjected to URSL. They comprised 74 patients (48.1%) with impacted stones and 80 (51.9%) with non-impacted stones. Patients were stratified into those with stone size ≤ 10 mm and others with stone size > 10 mm. In the former group, we found that stone impaction was significantly associated with higher PAPD, PUD, and UWT. In patients with stone size > 10 mm, stone impaction was related to higher UWT, more stone number, and higher frequency of stones located in the lower ureter. ROC curve analysis revealed good power of UWT in discrimination of stone impaction in all patients [AUC (95% CI) 0.65 (0.55-0.74)] at a cut-off of 3.8 mm, in patients with stone size ≤ 10 mm [AUC (95% CI) 0.76 (0.61-0.91)] at a cut-off of 4.1 mm and in patients with stone size > 10 mm [AUC (95% CI) 0.72 (0.62-0.83)] at a cut-off of 3.0 mm. CONCLUSIONS: Stratifying ureteric stones according to size would render UWT a more practical and clinically-oriented approach for the preoperative prediction of stone impaction.

Super pulsed thulium fiber laser outcomes in retrograde intrarenal surgery for ureteral and renal stones: a systematic review and meta-analysis.

BACKGROUND: Laser lithotripsy using a thulium fiber laser (TFL) has become an effective treatment option for small renal stones with low complication rates. TFL has a higher absorption coefficient, smaller fibers, and better pulse rate capability. METHODS: We conducted a systematic review and meta-analysis to evaluate the published evidence regarding TFL's lithotripsy performance in retrograde intrarenal surgery (RIRS), for which we primarily assessed the outcomes of stone-free rate, operation time, and complications. We searched different databases from inception to April 2023. We assessed the methodological quality and risk of bias using the Cochrane Risk of Bias tool for randomized trials and the ROBINS-I tool for non-randomized studies. We used a random-effects model for meta-analysis and assessed heterogeneity using the I2 statistic. RESULTS: Twelve published studies evaluated the efficacy of RIRS using a TFL for treating renal and ureteral stones. The meta-analysis revealed a predicted stone-free rate of 89.37% (95% CI: 83.93% to 93.12%), indicating that, on average, approximately 89.37% of patients achieved a stone-free state after treatment. The substantial heterogeneity among the studies was evident, as shown by a Q-value of 33.1174 and a p-value of 0.0003. The I2 value of 69.80% (95% CI: 25.91% to 92.02%) highlighted the proportion of variability attributed to genuine heterogeneity across the studies. Moreover, the H2 value 3.31 (95% CI: 1.35 to 12.53) indicated significant heterogeneity beyond random chance. The estimated overall effect size (logit-transformed) of 2.1289 was highly statistically significant (z = 8.7648, p < 0.0001) with a confidence interval of 1.6528 to 2.6049. The reported complications varied across studies, encompassing Clavien grade I-II complications in most cases, with a subset experiencing more severe Clavien grade III-V complications. Additionally, other studies noted a range of complications, such as haematuria, fever, transient creatinine elevation, and postoperative issues like bleeding, pain, and sepsis. CONCLUSION: This meta-analysis suggests that RIRS using TFL is an effective and safe treatment option for renal and ureteral stones, with high stone-free and low complication rates. The included studies exhibited a low risk of bias and were of high quality. However, more extensive randomized controlled trials with extended follow-up periods are needed to investigate this technique's efficacy and safety.

Erectile function after different techniques of bulbar urethroplasty: does urethral transection make a difference?

PURPOSE: We aimed to compare the impact of urethral transection after different techniques of bulbar urethroplasty on erectile function outcome. MATERIALS AND METHODS: We retrospectively reviewed the records for 245 patients who underwent different urethroplasty techniques for bulbar urethral stricture between February 2013 and January 2021. The comparison between the transecting and non-transecting cohorts included patients' demographics, clinicopathological features of the urethral stricture, post-urethroplasty erectile function, and success of urethroplasty. Outcomes were erectile function status verified by IIEF5-15 score at preoperative, three months, and 12 months post-surgery. We defined Post-urethroplasty ED as a decrease of 5 points or more. RESULTS: The urethroplasty success rate of the entire cohort was 86.9% after a mean follow-up of 45.59 ± 21 months. Out of 245 patients, 18 (7.3%) experienced 90-day complications. Transecting bulbar urethroplasty techniques were performed in 74 patients (30.2%), while non-transecting techniques were performed in 171 patients (69.8%). there were no differences between the cohorts regarding urethroplasty success (87.8% Vs. 86.5%, Mantel-Cox test p = 0.93) or postoperative complications (8.1% Vs. 7%, p = 0.73). Transient ED was evident in the transecting cohort as reported in 8.1% compared to 2.9% for the non-transecting (p = 0.07).Still, but de novo permanent ED was comparable (4.1% Vs. 2.9%, p = 0.65), for transecting and non-transecting, respectively. CONCLUSIONS: Unfortunately, some patients who undergo transecting techniques of bulbar urethroplasty experience transient erectile dysfunction that can improve within the first post- urethroplasty year; however, de novo permanent erectile dysfunction is uncommon after different techniques of bulbar urethroplasty and is not predisposed by urethral transection.

Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance.

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

Design, synthesis, and antitumor efficacy of novel 5-deazaflavin derivatives backed by kinase screening, docking, and ADME studies.

Novel 5-deazaflavins were designed as potential anticancer candidates. Compounds 4j, 4k, 5b, 5i, and 9f demonstrated high cytotoxicity against MCF-7 cell line with IC50 of 0.5-190nM. Compounds 8c and 9g showed preferential activity against Hela cells (IC50: 1.69 and 1.52 µM respectively). However, compound 5d showed notable potency against MCF-7 and Hela cell lines of 0.1 nM and 1.26 µM respectively. Kinase profiling for 4e showed the highest inhibition against a 20 kinase panel. Additionally, ADME prediction studies exhibited that compounds 4j, 5d, 5f, and 9f have drug-likeness criteria to be considered promising antitumor agents deserving of further investigation. SAR study showed that substitutions with 2-benzylidene hydra zino have a better fitting into PTK with enhanced antiproliferative potency. Noteworthy, the incorporation of hydrazino or ethanolamine moieties at position 2 along with small alkyl or phenyl at N-10, respectively revealed an extraordinary potency against MCF-7 cells with IC50 values in the nanomolar range.

High-Reynolds-number fractal signature of nascent turbulence during transition.

Transition from laminar to turbulent flow occurring over a smooth surface is a particularly important route to chaos in fluid dynamics. It often occurs via sporadic inception of spatially localized patches (spots) of turbulence that grow and merge downstream to become the fully turbulent boundary layer. A long-standing question has been whether these incipient spots already contain properties of high-Reynolds-number, developed turbulence. In this study, the question is posed for geometric scaling properties of the interface separating turbulence within the spots from the outer flow. For high-Reynolds-number turbulence, such interfaces are known to display fractal scaling laws with a dimension [Formula: see text], where the 1/3 excess exponent above 2 (smooth surfaces) follows from Kolmogorov scaling of velocity fluctuations. The data used in this study are from a direct numerical simulation, and the spot boundaries (interfaces) are determined by using an unsupervised machine-learning method that can identify such interfaces without setting arbitrary thresholds. Wide separation between small and large scales during transition is provided by the large range of spot volumes, enabling accurate measurements of the volume-area fractal scaling exponent. Measurements show a dimension of [Formula: see text] over almost 5 decades of spot volume, i.e., trends fully consistent with high-Reynolds-number turbulence. Additional observations pertaining to the dependence on height above the surface are also presented. Results provide evidence that turbulent spots exhibit high-Reynolds-number fractal-scaling properties already during early transitional and nonisotropic stages of the flow evolution.

Development of machine learning models for detection of vision threatening Behçet's disease (BD) using Egyptian College of Rheumatology (ECR)-BD cohort.

BACKGROUND: Eye lesions, occur in nearly half of patients with Behçet's Disease (BD), can lead to irreversible damage and vision loss; however, limited studies are available on identifying risk factors for the development of vision-threatening BD (VTBD). Using an Egyptian college of rheumatology (ECR)-BD, a national cohort of BD patients, we examined the performance of machine-learning (ML) models in predicting VTBD compared to logistic regression (LR) analysis. We identified the risk factors for the development of VTBD. METHODS: Patients with complete ocular data were included. VTBD was determined by the presence of any retinal disease, optic nerve involvement, or occurrence of blindness. Various ML-models were developed and examined for VTBD prediction. The Shapley additive explanation value was used for the interpretability of the predictors. RESULTS: A total of 1094 BD patients [71.5% were men, mean ± SD age 36.1 ± 10 years] were included. 549 (50.2%) individuals had VTBD. Extreme Gradient Boosting was the best-performing ML model (AUROC 0.85, 95% CI 0.81, 0.90) compared with logistic regression (AUROC 0.64, 95%CI 0.58, 0.71). Higher disease activity, thrombocytosis, ever smoking, and daily steroid dose were the top factors associated with VTBD. CONCLUSIONS: Using information obtained in the clinical settings, the Extreme Gradient Boosting identified patients at higher risk of VTBD better than the conventional statistical method. Further longitudinal studies to evaluate the clinical utility of the proposed prediction model are needed.