Epigenetic programing of cancer stemness by transcription factors-non-coding RNAs interactions.

Cancer 'stemness' is fundamental to cancer existence. It defines the ability of cancer cells to indefinitely perpetuate as well as differentiate. Cancer stem cell populations within a growing tumor also help evade the inhibitory effects of chemo- as well as radiation-therapies, in addition to playing an important role in cancer metastases. NF-κB and STAT-3 are representative transcription factors (TFs) that have long been associated with cancer stemness, thus presenting as attractive targets for cancer therapy. The growing interest in non-coding RNAs (ncRNAs) in the recent years has provided further insight into the mechanisms by which TFs influence cancer stem cell characteristics. There is evidence for a direct regulation of TFs by ncRNAs, such as, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) as well as circular RNAs (circRNAs), and vice versa. Additionally, the TF-ncRNAs regulations are often indirect, involving ncRNA-target genes or the sponging of other ncRNA species by individual ncRNAs. The information is rapidly evolving and this review provides a comprehensive review of TF-ncRNAs interactions with implications on cancer stemness and in response to therapies. Such knowledge will help uncover the many levels of tight regulations that control cancer stemness, providing novel opportunities and targets for therapy in the process.

Assessing the predictive validity of pre-admission criteria on dental students' academic performance: a cross-sectional study.

BACKGROUND: This study examines the multifaceted factors influencing academic performance among dental students in Saudi Arabia, exploring the complex relationships between demographic, educational, and psychological variables and students' Grade Point Averages (GPAs) to enhance global dental education admission strategies. METHODS: Data on demographics, academic performance indicators (including GPA, high school grades, test scores), accommodation type, parental education, suspension history, and English proficiency were collected through an English-language electronic questionnaire from 900 dental students across multiple institutions in Riyadh. The study employed Pearson's correlation analysis to examine relationships between GPA and various academic and demographic factors. A detailed regression analysis, using a stepwise selection based on Akaike's information criteria (AIC), identified significant GPA predictors and evaluated the average marginal effects of pre-admission variables on GPA, alongside rigorous diagnostic checks to validate the model's robustness. RESULTS: The study revealed a complex interplay of factors impacting GPA among dental students. High school grades, achievement, and aptitude test scores showed moderate positive correlations with GPA, while negative correlations were observed with age and number of times suspended. Regression analysis highlighted age, marital status, high school grades, and test scores as key predictors, with complex interaction effects demonstrating the layered influences of these factors. For instance, the negative impact of age on GPA was moderated by high school grade and aptitude test score. The analysis also highlighted the significant marginal effects of various pre-admission variables on GPA, such as the negative average impact of age and the positive impact of high school grades. CONCLUSIONS: This study provides valuable insights into the multifaceted determinants of academic success in dental education. Our findings underscore the significant roles of high school grades, achievement, and aptitude test scores, as well as the nuanced influence of age and marital status on GPA. These results advocate for a holistic approach in evaluating candidates for dental programs and have broader implications for global dental education, emphasizing the need for comprehensive admission strategies.

Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine.

Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-ß) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-ß mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.

New Succinimide-Thiazolidinedione Hybrids as Multitarget Antidiabetic Agents: Design, Synthesis, Bioevaluation, and Molecular Modelling Studies.

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue's resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide-thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a-e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.

Exploring DSSC Efficiency Enhancement: SQI-F and SQI-Cl Dyes with Iodolyte Electrolytes and CDCA Optimization.

This investigation delves into the potential use of halogen bonding to enhance both the short-circuit current (JSC) and overall efficiency of dye-sensitized solar cells (DSSCs). Specifically, we synthesized two distinct dyes, SQI-F and SQI-Cl, and characterized them using FT-IR, 1HNMR, 13C NMR, and mass spectroscopy. These dyes are based on the concept of incorporating halogen atoms within unsymmetrical squaraine structures with a donor-acceptor-donor (D-A-D) configuration. This strategic design aims to achieve optimal performance within DSSCs. We conducted comprehensive assessments using DSSC devices and integrated these synthesized dyes with iodolyte electrolytes, denoted as Z-50 and Z-100. Further enhancements were achieved through the addition of CDCA. Remarkably, in the absence of CDCA, both SQI-F and SQI-Cl dyes displayed distinct photovoltaic characteristics. However, through sensitization with three equivalents of CDCA, a significant improvement in performance became evident. The peak of performance was reached with the SQI-F dye, sensitized with three equivalents of CDCA, and paired with iodolyte Z-100. This combination yielded an impressive DSSC device efficiency of 6.74%, an open-circuit voltage (VOC) of 0.694 V, and a current density (JSC) of 13.67 mA/cm2. This substantial improvement in performance can primarily be attributed to the presence of a σ-hole, which facilitates a robust interaction between the electrolyte and the dyes anchored on the TiO2 substrate. This interaction optimizes the critical dye regeneration process within the DSSCs, ultimately leading to the observed enhancement in efficiency.

Nurses' readiness to prescribe under supervision in Saudi Arabia: A cross-sectional study.

Aim: To explore nurses' readiness to prescribe medications under supervision and identify associations between prescribing practices under supervision and demographic characteristics in Saudi Arabia. Design: A cross-sectional study. Methods: Using convenience sampling, this study used a 32-item survey to collect data on nurses prescribing medications under supervision between December 2022 and March 2023. Results: A total of 379 nurses were recruited from different regions in Saudi Arabia. Approximately 7% (n = 30) of the participants were prescribing medications independently, and 70% (n = 267) expressed their likelihood of becoming prescribers. The highest motivating factors to become prescribers were improvement of patient care (52.2%) and contribution to the multidisciplinary team (52.0%). Most participants (60%-81%) agreed that prescribing medications under supervision would improve potential outcomes at the system, nurse, and patient levels. Availability of appropriate mentors or supervisors (72.9%) was the highest rated facilitating factor, followed by support of nursing colleagues (72%). Based on demographic characteristics, findings revealed significant differences in the: a) likelihood and motivators of becoming prescribers; b) required minimum qualification, years of experience, and continuing professional education hours to become prescribers; and c) type of organizations delivering educational programs for nurse prescribing. Conclusion: Majority of nurses in Saudi Arabia favored becoming prescribers, and motivating factors were mostly relevant to optimizing patient care outcomes. Having the proper supervision was rated as the most facilitating factor for nurse prescribing. Nurses' views on potential outcomes, facilitating factors, and possible motivators varied based on nurses' demographical characteristics. Implications for the professional and/or patient care: Nurses favored prescribing under supervision to improve patient care outcomes, which is an opportunity to expand the benefits of health services, including easy access to healthcare. Impact: Results revealed that nurses support the implementation of prescribing practice under supervision. Thus, the findings may inform practice change in Saudi Arabia to allow prescribing under supervision, which was perceived to have a positive impact on patient care outcomes. Reporting Method: This study adhered to STROBE guidelines.

The ameliorative effect of bergamot oil nano-emulsion in stressed rabbit bucks: Influence on blood biochemical parameters, redox status, immunity indices, inflammation markers, semen quality, testicular changes and the expression of HSPs genes.

This work explored the activities of bergamot oil nano-emulsion (NBG) in modulating blood biochemical parameters, redox status, immunity indices, inflammation markers, semen quality, testicular changes and the expression of HSPs genes in stressed rabbit bucks. Twenty-four mature rabbit bucks (5 months) were randomly divided into three groups; control group (NBG0) received 1 ml of distilled water, while the other two groups received NBG orally at doses of 50 and 100 mg/kg (bw) twice a week. The present study's findings revealed that treated groups had lower values of total and direct bilirubin, triglyceride, lactate dehydrogenase, and creatinine compared with NBG0 group (p < 0.05). NBG100 group recorded the greatest of total protein, albumin, GPx, T3 and T4 values as well as the lowest values of uric acid, MDA, and indirect bilirubin. Both treated groups showed significantly reduced 8-OhDG, Amyloid A, TLR 4, while significantly increased nitric oxide, IgA, IgM, TAC, and SOD levels. Semen characteristics such as volume, sperm count, sperm motility, normal sperm, and vitality were significantly higher in the NBG100 group compared to the NBG50 and NBG0 groups, whereas sperm abnormalities and dead sperm were significantly reduced. HSP70, HSP72, and HSPA9 gene overexpression showed that testicular integrity was maintained after buck received oral doses of 50 or 100 mg/kg of NBG. Existing findings indicate that oral administration of NBG improves heat tolerance in rabbit bucks primarily as e result of its antioxidant and anti-inflammatory effects.

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats.

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

Comparison of diagnostic criteria for significant anal sphincter defects between endoanal and transperineal ultrasound.

OBJECTIVE: To evaluate the agreement between three-dimensional endoanal ultrasound (EAUS) and four-dimensional transperineal ultrasound (TPUS) in measuring anal sphincter defect angle. METHODS: This was a secondary analysis of the PERINEAL study, which evaluated the effect of perineal wound infection on anal sphincter integrity. Women were reviewed once a week, until their perineal wound had healed or for up to a maximum of 16 weeks. At each visit, both EAUS and TPUS (the latter at rest and on maximum pelvic floor muscle contraction (PFMC)) were performed to evaluate the presence of external (EAS) and internal (IAS) anal sphincter defect and measure the defect size. The largest angle size of a defect at the same sphincter level was analyzed. A defect was deemed significant if it was > 30°. Kappa coefficient (κ), intraclass correlation coefficient and standard error of measurement (SEM) were calculated, using EAUS as the reference standard. RESULTS: In 73 women scanned at weekly intervals, a total of 250 EAUS and 250 TPUS scans were performed. An EAS defect was found in 55 (22.0%) EAUS images and 47 (18.8%) TPUS images. An IAS defect was found in 26 (10.4%) images on both modalities. There was excellent agreement (κ = 0.87) between TPUS and EAUS in diagnosing the presence of an EAS defect and perfect agreement (κ = 1.00) in diagnosing the presence of an IAS defect. TPUS performed at rest had poor and moderate agreement with EAUS in measuring EAS and IAS defect size, respectively, with respective SEMs of ± 16.1° and ± 27.9°. TPUS performed during maximum PFMC had poor and moderate agreement with EAUS in measuring EAS and IAS defect size, respectively, with respective SEMs of ± 16.5° and ± 26.4°. Based on the SEMs, if the diagnostic cut-off of 30° for defect size on TPUS was used, an incorrect diagnosis of significant EAS defect could occur in approximately 9-36% of women and an incorrect diagnosis of a significant IAS defect could occur in approximately 4-15% of women, using EAUS as the reference. CONCLUSIONS: This is the first study to compare directly anal sphincter defect angle measurements obtained on EAUS and TPUS. A cut-off angle of 30° should not be used for the diagnosis of a significant residual anal sphincter defect during TPUS examination. Further research is required to determine the optimal defect cut-off angle for TPUS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic test accuracy of magnetic resonance imaging and pelvic floor ultrasound for diagnosis of levator ani muscle avulsion.

OBJECTIVE: To estimate the diagnostic test accuracy of magnetic resonance imaging (MRI) and pelvic floor ultrasound for levator ani muscle (LAM) avulsion in a general parous population, with view to establishing if ultrasound could substitute for MRI to diagnose LAM avulsion. METHODS: This was a cross-sectional study of 135 women 4 years after their first delivery. Signs and symptoms of pelvic floor dysfunction were assessed using validated methods. All women underwent four-dimensional transperineal ultrasound (TPUS), three-dimensional endovaginal ultrasound (EVUS) and MRI. Images were acquired at rest, on pelvic floor muscle contraction (PFMC) and on maximum Valsalva maneuver, and analyzed by two blinded observers. Predefined cut-off values were used to diagnose LAM avulsion. In the absence of a reference standard, latent class analysis (LCA) was used to establish diagnostic test characteristics for LAM avulsion as the primary outcome measure. Secondary outcomes were kappa (κ) agreement between imaging techniques, intraclass correlation coefficients (ICC) for hiatal measurements at rest, on PFMC and on maximum Valsalva maneuver, and the association of LAM avulsion with signs and symptoms of pelvic floor dysfunction. RESULTS: The prevalence of LAM avulsion was 23.0% for MRI, 11.1% for TPUS and 17.8% for EVUS. The prevalence of LAM avulsion using LCA was 15.7%. The sensitivity for LAM avulsion of TPUS (71% (95% CI, 50-90%)) and EVUS (91% (95% CI, 74-100%)) was lower than that of MRI (100% (95% CI, 84-100%)). The specificity of TPUS (100% (95% CI, 97-100%)) and EVUS (95% (95% CI, 91-99%)) was higher than that of MRI (91% (95% CI, 85-97%)). MRI and EVUS had high predictive values for the assessment of major LAM avulsion (positive predictive value (PPV), 95% and negative predictive value (NPV), 100%; PPV, 100% and NPV, 98%, respectively), while TPUS had high predictive values for minor LAM avulsion (PPV, 100% and NPV, 95%). Major LAM avulsion on MRI and EVUS was associated with anterior vaginal wall prolapse, which was not found for TPUS. The agreement in the diagnosis of LAM avulsion (κ, 0.69) and hiatal measurements (ICC, 0.60-0.81) was highest between MRI and EVUS. CONCLUSIONS: Pelvic floor ultrasound can be implemented as a triage test to assess parous women for LAM avulsion because of its high specificity. Ultrasound cannot substitute for MRI because of its lower sensitivity. The predictive ability of ultrasound is moderate for the presence, and very good for the absence, of LAM avulsion. A positive test should be confirmed by a different observer or imaging technique. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Prebiotics can restrict Salmonella populations in poultry: a review.

Antibiotics were over the years, the common supplement used for poultry production. There is a global trend to lessen antibiotics' use due to the contamination of consumed meat with antibiotic residues. Also, there is a concern that human treatments might be jeopardized due to the emergence of antibiotic-resistant bacteria. Prebiotics are attractive supplements, particularly in poultry production, because of the diversity of their effects, including pH amendments, production of short-chain fatty acids (SCFA) and the inhibition of pathogens' growth. The commonly used prebiotics are carbohydrate sources that cannot be easily broken down by chickens. However, they can efficiently be utilized by the intestinal tract's microflora. Oligosaccharides, polysaccharides and lactose are non-digestible carbohydrate sources that are typically used in poultry diets as prebiotics. This review covers current applications and prospects for using prebiotics to improve poultry performance and reduce pathogens, particularly Salmonella, in gastrointestinal tract.

α-Glucosidase, α-Amylase and Antioxidant Evaluations of Isolated Bioactives from Wild Strawberry.

Diabetes mellitus is a metabolic disorder and is a global challenge to the current medicinal chemists and pharmacologists. This research has been designed to isolate and evaluate antidiabetic bioactives from Fragaria indica. The crude extracts, semi-purified and pure bioactives have been used in all in vitro assays. The in vitro α-glucosidase, α-amylase and DPPH free radical activities have been performed on all plant samples. The initial activities showed that ethyl acetate (Fi.EtAc) was the potent fraction in all the assays. This fraction was initially semi-purified to obtain Fi.EtAc 1-3. Among the semi-purified fractions, Fi.EtAc 2 was dominant, exhibiting potent IC50 values in all the in vitro assays. Based on the potency and availability of materials, Fi.EtAc 2 was subjected to further purification to obtain compounds 1 (2,4-dichloro-6-hydroxy-3,5-dimethoxytoluene) and 2 (2-methyl-6-(4-methylphenyl)-2-hepten-4-one). The two isolated compounds were characterized by mass and NMR analyses. The compounds 1 and 2 showed excellent inhibitions against α-glucosidase (21.45 for 1 and 15.03 for 2 µg/mL), α-amylase (17.65 and 16.56 µg/mL) and DPPH free radicals (7.62 and 14.30 µg/mL). Our study provides baseline research for the antidiabetic bioactives exploration from Fragaria indica. The bioactive compounds can be evaluated in animals-based antidiabetic activity in future.

Curcumin and ustekinumab cotherapy alleviates induced psoriasis in rats through their antioxidant, anti-inflammatory, and antiproliferative effects.

INTRODUCTION: Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects. OBJECTIVE: The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model. MATERIALS AND METHODS: Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis. RESULTS: Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (p < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant (p < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3. CONCLUSIONS: Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Neutrophil-to-lymphocyte ratio (NLR) variations in relationship with childhood maltreatment in patients with anorexia nervosa: a retrospective cohort study.

PURPOSE: Anorexia nervosa (AN) is a serious mental illness. It is frequently accompanied by a history of childhood maltreatment (CM) that may constitute a specific ecophenotype in patients with eating disorders necessitating special assessment and management. This retrospective study tested whether in patients with AN, CM-related chronic stress may manifest through low-grade inflammation reflected by an increase in white blood cell ratios (neutrophil-to-lymphocyte ratio, NLR, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio). METHODS: Participants (N = 206) were enrolled at an eating disorder daycare unit in Montpellier, France, from March 2013 and January 2020. CM was assessed using the childhood trauma questionnaire (CTQ). The Eating Disorder Examination Questionnaire (EDE-Q) and the MINI were used to assess AN severity and the other clinical characteristics, respectively. RESULTS: NLR was higher in patients with AN and history of CM (p = 0.029) and in patients with AN and history of emotional abuse (p = 0.021), compared with patients with AN without history of CM. In multivariate analysis, emotional abuse (ß = 0.17; p = 0.027) contributed significantly to NLR variability. CONCLUSION: In patients with AN, NLR is a low-grade inflammation marker that is influenced by various sociodemographic, clinical and biological factors. It is more directly affected by some CM types, especially emotional abuse, than by the presence/absence of CM history. Future studies should focus on mediators between CM and increased inflammation, such as interoceptive awareness, emotional dysregulation, food addiction, and stress sensitization. LEVEL OF EVIDENCE: III. Evidence obtained from well-designed cohort or case-control analytic studies.

Association between 3D endovaginal and 2D perineal pelvic floor ultrasound findings and symptoms in women presenting with mid-urethral sling complications.

OBJECTIVES: To present the characteristics of women attending a tertiary urogynecology pelvic floor scan clinic with mid-urethral sling (MUS) complications and examine the association between patient symptoms and findings on two-dimensional (2D) perineal and three-dimensional (3D) endovaginal ultrasound. METHODS: This was a cross-sectional study of all women with MUS complications referred to a specialist pelvic floor ultrasound clinic between October 2016 and October 2018. Detailed history was obtained regarding their symptoms and time of onset. All patients underwent 2D perineal and 3D endovaginal ultrasound assessment. The association between patient symptoms and ultrasound findings was evaluated using logistic regression analysis. Only symptomatic women with a single MUS, without other pelvic floor mesh, prior mesh excision or bulking agents, were included in the regression analysis. RESULTS: A total of 311 women with a history of MUS surgery were seen during the study period. Vaginal and/or non-vaginal pain was reported by 80% of patients and this was the primary presenting complaint in 59% of the patients. One-third of the patients reported symptoms starting within 4 weeks after surgery. The data of 172 patients were included in the regression analysis. MUS position within the rhabdosphincter was significantly associated with voiding dysfunction (odds ratio (OR), 10.6 (95% CI, 2.2-50.9); P = 0.003). Voiding dysfunction was highest in those with C-shaped MUS both at rest and on Valsalva maneuver (OR, 3.2 (95% CI, 1.3-7.6); P < 0.001). MUS position in the distal third of the urethra was significantly associated with a higher rate of recurrent urinary tract infection (OR, 2.9 (95% CI, 1.3-6.3); P = 0.01). CONCLUSIONS: Pelvic floor ultrasound can provide insight into the position and shape of the MUS, which could explain some patient symptoms and guide management or surgical planning. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Transperineal and endovaginal ultrasound for evaluating suburethral masses: comparison with magnetic resonance imaging.

OBJECTIVE: To evaluate the utility of pelvic floor ultrasound (US) in the detection and evaluation of suburethral masses, using magnetic resonance imaging (MRI) as the reference standard. METHODS: This was a retrospective analysis of US and MRI scans of all women with a suburethral mass on clinical examination at a single urogynecology clinic over a 13-year period (February 2007 to March 2020). All women were examined using two-dimensional transperineal US (2D-TPUS) with or without three-dimensional endovaginal US (3D-EVUS). All patients underwent unenhanced T1-weighted and T2-weighted MRI, which was considered the reference standard in this study. Presence of a suburethral mass and its size, location, connection with the urethral lumen and characteristics were evaluated on both pelvic floor US and MRI. Agreement between pelvic floor US and MRI was assessed using intraclass correlation coefficients (ICC; 3,1). RESULTS: Forty women suspected of having a suburethral mass on clinical examination underwent both MRI and US (2D-TPUS with or without 3D-EVUS). MRI detected a suburethral mass in 34 women, which was also detected by US. However, US also identified a suburethral mass in the remaining six women. Thus, the agreement between US and MRI for detecting a suburethral mass was 85% (95% CI, 70.2-94.3%). The ICC analysis showed good agreement between MRI and 2D-TPUS for the measured distance between the suburethral mass and the bladder neck (ICC, 0.89; standard error of measurement (SEM), 3.64 mm) and excellent agreement for measurement of the largest diameter of the mass (ICC, 0.93; SEM, 4.31 mm). Good agreement was observed between MRI and 3D-EVUS for the measured distance from the suburethral mass to the bladder neck (ICC, 0.88; SEM, 3.48 mm) and excellent agreement for the largest diameter of the suburethral mass (ICC, 0.94; SEM, 4.68 mm). CONCLUSIONS: 2D-TPUS and 3D-EVUS are useful in the imaging of suburethral masses. US shows good-to-excellent agreement with MRI in identifying and measuring suburethral masses; therefore, the two modalities can be used interchangeably depending on availability of equipment and expertise. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Natural history of levator ani muscle avulsion 4 years following childbirth.

OBJECTIVES: The primary aim was to evaluate prospectively the natural history of levator ani muscle (LAM) avulsion 4 years following first delivery and its correlation with signs and symptoms of pelvic floor dysfunction (PFD). The secondary aim was to investigate the effect of a second vaginal delivery on the incidence of LAM avulsion and PFD. METHODS: This was a prospective longitudinal study of nulliparous women recruited antenatally, who were assessed at 36 weeks' gestation and 3 months, 1 year and 4 years postpartum for signs and symptoms of PFD and presence of LAM avulsion. Pelvic floor muscle strength was assessed by digital palpation, and pelvic organ prolapse (POP) was assessed using the POP quantification (POP-Q) system. Validated questionnaires were used to evaluate urinary, bowel and sexual function and symptoms of POP. Transperineal ultrasound was performed to assess LAM integrity and hiatal biometry. Differences in signs and symptoms of PFD over time were evaluated using a linear mixed model, separately in women who had had one delivery and in those who had two or more deliveries during the study period. RESULTS: Of 269 women recruited, 147 (55%) attended the 4-year follow-up and were examined at a mean interval of 3.8 ± 0.4 years after their first delivery. Of these, 74 (50%) had a subsequent delivery. The prevalence of LAM avulsion 4 years after a first vaginal delivery was 13%, with no difference between women who had one and those who had two or more vaginal deliveries. Women with an intact LAM and one or more deliveries showed no change in signs and symptoms of PFD at 4 years compared with the previous assessments. Of women with one vaginal delivery who were diagnosed with LAM avulsion 3 months or 1 year postpartum, those in whom the LAM avulsion was no longer evident at 4 years (42%) showed worsening of POP-Q measurements, whereas those with persistent LAM avulsion (58%) showed significant worsening in pelvic floor muscle strength and hiatal area on ultrasound. After a second vaginal delivery, no new avulsions were diagnosed, however, previous LAM avulsion became more extensive in 44% of women and hiatal area increased in women with persistent LAM avulsion. CONCLUSIONS: The first vaginal delivery carries the greatest risk for LAM avulsion, with impact on signs of PFD 4 years later. A second vaginal delivery could result in deterioration of LAM avulsion, but no new avulsions were found. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Visnagin prevents isoproterenol-induced myocardial injury by attenuating oxidative stress and inflammation and upregulating Nrf2 signaling in rats.

Oxidative tissue injury and inflammatory responses play major roles in cardiovascular diseases and heart failure. Visnagin (VIS) is a natural bioactive component of Ammi visnaga, with promising radical scavenging and anti-inflammatory activities. This study explored the protective effect of VIS against isoproterenol (ISO)-induced acute myocardial injury and oxidative stress in rats. VIS was supplemented for 14 days, and the rats received ISO (100 mg/kg) twice at an interval of 24 h. ISO-induced myocardial injury was characterized by elevated serum CK-MB, LDH, and troponin-I associated with increased heart weight and several histopathological changes. ISO increased reactive oxygen species (ROS), malondialdehyde (MDA), NF-κB p65, TNF-α, IL-6, and decreased glutathione and antioxidant enzymes in rats' hearts. VIS prevented myocardial injury and ameliorated the cardiac function markers, ROS, MDA, NF-κB p65, and pro-inflammatory cytokines in ISO-intoxicated rats. In addition, VIS decreased Bax mRNA and caspases, and upregulated Nrf2, HO-1, Bcl-2, and PPARγ. Molecular docking simulations revealed the binding method of VIS to NF-κB, Keap1, and PPARγ. In conclusion, VIS protects against ISO-induced acute myocardial injury by attenuating oxidative tissue injury and reducing key inflammatory and apoptosis markers. In vivo and in silico results showed that activation of Nrf2/HO-1 signaling and PPARγ mediates the cardioprotective effect of VIS.

A New CDK2 Inhibitor with 3-Hydrazonoindolin-2-One Scaffold Endowed with Anti-Breast Cancer Activity: Design, Synthesis, Biological Evaluation, and In Silico Insights.

BACKGROUND: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. METHODS: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. RESULTS: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of HI 5 was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides, HI 5 blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (syn and anti) is responsible for binding affinity and intrinsic activity of HI 5. However, the molecular dynamic studies have confirmed that the syn-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity. DISCUSSION: These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.

Clinical Efficacy of Single Use of Three Different Mouthrinses on the Level of Streptococcus mutans in Saliva.

AIM AND OBJECTIVE: The aim of this cross-sectional population-based clinical study was to assess the effect of single use of three different mouthrinses on the level of salivary Streptococcus mutans of 8 to 10-year-old Saudi children. MATERIALS AND METHODS: Convenient samples of 52 Saudi children aged 8-10 years were randomly allocated into four groups of 13 each. Saliva samples were collected to assess the level of S. mutans at baseline before rinsing with the assigned mouthrinse or control. Three mouthrinses, Avalon Avohex, Listerine Miswak, and Optima Aloe Dent Mouthrinse, were randomly distributed to the children. Each participant was instructed to rinse for 2 minutes using 10 mL of the assigned mouthrinse. Saliva samples were collected after rinsing and colony forming unit (CFU) of S. mutans per mL of saliva was calculated. Statistical analysis was performed to compare S. mutans count at baselines and postintervention values of each experimental group and control using paired t-test and one-way ANOVA. All statistical analyses were set at a significance level of p < 0.05. RESULTS: All test groups showed a reduction in salivary S. mutans compared to that at baseline. Statistically significant reduction (p > 0.05) in bacterial count was seen in Avalon Avohex group. CONCLUSION: A single-time rinse of chlorhexidine extract mouthrinse for 2 minutes effectively reduced the number of S. mutans of 8 to 10-year-old Saudi children. CLINICAL SIGNIFICANCE: Rinsing with chlorhexidine extract mouthrinse should be considered as a potential method in prevention of dental caries in children.