Related mechanisms, current treatments, and new perspectives in meningioma.

Meningiomas are non-glial tumors that are the most common primary brain tumors in adults. Although meningioma can possibly be cured with surgical excision, variations in atypical/anaplastic meningioma have a high recurrence rate and a poor prognosis. As a result, it is critical to develop novel therapeutic options for high-grade meningiomas. This review highlights the current histology of meningiomas, prevalent genetic and molecular changes, and the most extensively researched signaling pathways and therapies in meningiomas. It also reviews current clinical studies and novel meningioma treatments, including immunotherapy, microRNAs, cancer stem cell methods, and targeted interventions within the glycolysis pathway. Through the examination of the complex landscape of meningioma biology and the highlighting of promising therapeutic pathways, this review opens the way for future research efforts aimed at improving patient outcomes in this prevalent intracranial tumor entity.

Ultrasound-based predictive indicators for treatment outcomes in pediatric vesicoureteral reflux.

PURPOSE: To evaluate the effectiveness of preoperative ultrasound (US) measurements in predicting pediatric vesicoureteral reflux (VUR) treatment outcomes. METHODS: This prospective study enrolled 35 patients (53 renal units) aged 1-16 years who underwent subureteric injection therapy for primary VUR between July 2020 and June 2022. Preoperative ultrasound examinations measured the bladder wall thickness at the ureteral orifice, ureteral submucosal tunnel length, distal ureteral diameter, patient demographics, VUR grade, presenting complaints, bladder-bowel dysfunction, and renal scarring, and the impact of these variables on treatment success was analyzed. RESULTS: Among the patients, 91.4% were female, with a mean age of 6.83 ± 3.84 years. A comparison between the treatment success and failure groups revealed no significant differences in the age, sex, VUR grade, laterality, bilaterality, presenting complaints, bladder-bowel dysfunction, bladder wall thickness, or distal ureteral diameter (p > 0.05). However, renal scarring occurred in 16 (38.1%) patients in the treatment success group and 10 (90.9%) in the treatment failure group (p = 0.002). The treatment failure group had shorter detrusor-to-ureteral orifice distances and smaller detrusor-ureteral orifice distance-to-distal ureteral diameter (D/U) ratios than that of the success group (p = 0.004 and p = 0.006, respectively). Patients with a detrusor-to-ureteral orifice distance < 7.4 mm had an 81.82% likelihood of treatment failure. CONCLUSION: Ultrasound measurements of the detrusor-to-ureteral orifice distance and D/U ratio proved reliable in predicting the success of endoscopic subureteric injection therapy for VUR.

Assessing the educational value of laparoscopic radical nephrectomy videos on YouTube®: A comparative analysis of short versus long videos.

INTRODUCTION: To evaluate the quality of laparoscopic radical nephrectomy videos and determine the extent to which they are informative and educational for healthcare professionals. PATIENTS AND METHODS: We used the YouTube® search engine to search for the term 'laparoscopic radical nephrectomy' with time filters of 4-20 min (Group 1) and >20 min (Group 2) and then sorted the results uploaded chronologically before January 2023. One hundred videos were analysed for each group. The reliability of the videos was assessed using the Journal of American Medical Association (JAMA) Benchmark Criteria and DISCERN questionnaire scores (DISCERN). Educational quality was assessed using the Global Quality Score (GQS) and a 20-item objective scoring system (OSS) for laparoscopic nephrectomy. The popularity of the videos was evaluated using the video power index (VPI). RESULTS: The mean video duration was 8.9 ± 4.3 min in Group 1 and 52.02 ± 31.09 min in Group 2 (P < 0.001). The mean JAMA (2.49 ± 0.61) and OSS scores (60 ± 12.3) were higher in Group 2 than in Group 1, while no significant difference was observed in the mean GQS (2.53 ± 0.7, 2.39 ± 0.88, respectively) between the groups (P < 0.001, P = 0.039, P = 0.131, respectively). CONCLUSION: While the standardisation of surgical videos published on YouTube® and the establishment of auditing mechanisms do not seem plausible, high total OSS, periprocedural OSS, and VPI scores, and high OSS, JAMAS, GQS and DISCERN scores in long videos indicate that such videos offer a greater contribution to education.

Impact of silencing eEF2K expression on the malignant properties of chordoma.

BACKGROUND: Eukaryotic elongation factor 2 kinase (eukaryotic elongation factor 2 kinase, eEF2K) is a calcium calmodulin dependent protein kinase that keeps the highest energy consuming cellular process of protein synthesis under check through negative regulation. eEF2K pauses global protein synthesis rates at the translational elongation step by phosphorylating its only kown substrate elongation factor 2 (eEF2), a unique translocase activity in ekaryotic cells enabling the polypeptide chain elongation. Therefore, eEF2K is thought to preserve cellular energy pools particularly upon acute development of cellular stress conditions such as nutrient deprivation, hypoxia, or infections. Recently, high expression of this enzyme has been associated with poor prognosis in an array of solid tumor types. Therefore, in a growing number of studies tremendous effort is being directed to the development of treatment methods aiming to suppress eEF2K as a novel therapeutic approach in the fight against cancer. METHODS: In our study, we aimed to investigate the changes in the tumorigenicity of chordoma cells in presence of gene silencing for eEF2K. Taking a transient gene silencing approach using siRNA particles, eEF2K gene expression was suppressed in chordoma cells. RESULTS: Silencing eEF2K expression was associated with a slight increase in cellular proliferation and a decrease in death rates. Furthermore, no alteration in the sensitivity of chordoma cells to chemotherapy was detected in response to the decrease in eEF2K expression which intriguingly promoted suppression of cell migratory and invasion related properties. CONCLUSION: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.

miRNAs as cell fate determinants of lateral and paraxial mesoderm differentiation from embryonic stem cells.

To date, the role of miRNAs on pluripotency and differentiation of ESCs into specific lineages has been studied extensively. However, the specific role of miRNAs during lateral and paraxial mesoderm cell fate decision is still unclear. To address this, we firstly determined miRNA profile of mouse ESCs differentiating towards lateral and paraxial lineages which were detected using Flk1 and PDGFαR antibodies, and of myogenic and hematopoietic differentiation potential of purified paraxial and lateral mesodermal cells within these populations. miRNAs associated with lateral and paraxial mesoderm, and their targets were identified using bioinformatics tools. The targets of the corresponding miRNAs were validated after transfection into mouse ESCs. The roles of the selected miRNAs in lateral, and paraxial mesoderm formation were assessed along with hematopoietic and myogenic differentiation capacity. Among the miRNAs, mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p, upregulated in lateral mesoderm cells, and mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p, upregulated in paraxial mesoderm cells. While transient co-transfection of mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p increased the number of lateral mesodermal cells, co-transfection of mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p increased the number of paraxial mesodermal cells. Moreover, differentiation potential of the lateral mesodermal cells into hematopoietic cell lineage increased upon co-transfection of mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p and differentiation potential of the paraxial mesodermal cells into skeletal muscle lineage were increased upon co-transfection of mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p. In conclusion, we determined the miRNA profile of lateral and paraxial mesodermal cells and co-transfection of miRNAs increased differentiation potential of both lateral and paraxial mesodermal cells transiently.

Long-term chronic caloric restriction alters miRNA profiles in the brain of ageing mice.

Calorie restriction (CR) has been shown to be one of the most effective methods in alleviating the effects of ageing and age-related diseases. Although the protective effects of CR have been reported, the exact molecular mechanism still needs to be clarified. This study aims to determine differentially expressed (DE) miRNAs and altered gene pathways due to long-term chronic (CCR) and intermittent (ICR) CR in the brain of mice to understand the preventive roles of miRNAs resulting from long-term CR. Ten weeks old mice were enrolled into three different dietary groups; ad libitum, CCR or ICR, and fed until 82 weeks of age. miRNAs were analysed using GeneChip 4.1 microarray and the target of DE miRNAs was determined using miRNA target databases. Out of a total 3,163 analysed miRNAs, 55 of them were differentially expressed either by different CR protocols or by ageing. Brain samples from the CCR group had increased expression levels of mmu-miR-713 while decreasing expression levels of mmu-miR-184-3p and mmu-miR-351-5p compared to the other dietary groups. Also, current results indicated that CCR showed better preventive effects than that of ICR. Thus, CCR may perform its protective effects by modulating these specific miRNAs since they are shown to play roles in neurogenesis, chromatin and histone regulation. In conclusion, these three miRNAs could be potential targets for neurodegenerative and ageing-related diseases and may play important roles in the protective effects of CR in the brain.

Clinical preferences and treatment attitudes among urologists, gynecologists, and geriatricians: An independent online questionnaire survey for comparison of treatment choices in the management of overactive bladder.

OBJECTIVE: Overactive bladder (OAB) is a common clinical problem with associated morbidities both in men and women. Although real-life management strategies have been examined among urologists (URO), treatment choices may differ between different specialties. In the present study, an online survey was conducted to determine and compare the management strategies and clinical preferences of UROs, obstetricians/gynecologists (OB/GYN), and geriatricians (GER) in the treatment of OAB in their daily practices. METHODS: Between December 2020 and February 2021, an online questionnaire was sent to URO, OB/GYN, and GER specialists/residents. Current strategies and attitudes toward treatment of OAB in patients <65 years were compared between URO and OB/GYN, whereas the responses were compared between all three specialties in patients ≥65 years. RESULTS: A total of 733 specialists/physicians (433 URO, 236 OB/GYN, and 64 GER) completed the online survey. Patients with OAB were more likely to present to URO compared to OB/GYN and GER (p = 0.001). A combination of behavioral modification and pharmacotherapy (antimuscarinics and/or beta-3 agonists) were chosen for the initial treatment of patients with OAB in both specialties with a significantly higher proportion by URO than by OB/GYN (51.9% vs. 38.1%; p = 0.001). Antimuscarinics were the most frequently prescribed medications by both the URO and OB/GYN specialties (81.8% vs. 78.4%; p = 0.27). Combination therapy with antimuscarinics was preferred more often by URO (91.5% vs. 77.1%; p = 0.001) when no or an inadequate response after initial treatment occurred. Multiple medication use, comorbidities, and risk of cognitive side effects affected medication preference by all specialists, especially by GER (p = 0.018). CONCLUSIONS: Patients with OAB present to UROs, OB/GYN and GER more frequently compared to other specialities. Although antimuscarinics and beta-3 adrenoceptor agonists are equally recommended as first-line pharmacotherapy for OAB, antimuscarinics were preferred for most patients as the initial molecule by all specialties. Beta-3 agonists are increasingly preferred for elderly patients.

Distinctive role of dysregulated miRNAs in chordoma cancer stem-like cell maintenance.

Chordoma is a rare, slow-growing tumor thought to arise from remnants of embryonic notochord associated with an aggressive outcome. Cancer stem-like cells (CSCs) are related to tumorigenesis, recurrence, and resistance in cancers. Therefore, chordoma CSCs are possible targets for chordoma treatment. In this study, dysregulated miRNAs were determined in chordoma CSCs and identified their role in chordoma. Dysregulated miRNAs were determined via miRNA microarray and validated through qPCR. miRNAs were transiently transfected to the chordoma cell lines and their roles in proliferation, apoptosis, migration and invasion capacities and stem-like properties were identified. Finally, a relationship between clinicopathological features and dysregulated miRNAs has been evaluated among 21 chordoma patients. CD133+CD15+ cells exhibited CSC phenotype with increased CSC- and Epithelial-Mesenchymal Transition (EMT)-related gene expression, invasion, migration, tumorosphere- and colony-forming abilities. In addition, WNT5A, TGF-α, BTG2 and MYCBP genes involved in CSC-related pathways, were targets of miR-140-3p, miR-148a-3p, miR-210-5p and miR-574-5p, respectively. Transfection of CSC-related miRNAs also increased migration and invasion along with stem cell phenotype. Finally, we determined that miR-140-3p and miR-148a-3p expressions correlated with Ki67 while miR-140-3p and TGF-α expressions were correlated with p53. Moreover, MYCBP expression was positively correlated with tumor volume, and metastasis was associated with the expression of miR-210-5p and TGF-α in our patient cohort. Through these findings, we conclude that chordoma CSCs have distinctive miRNA profile, which can regulate stem-like properties of chordoma CSCs.

Course of Urological Problems in Children with Spinal Dysraphism: Long-Term Follow-Up Results.

BACKGROUND/AIMS: We aimed to evaluate the course of urinary problems in children with spinal dysraphism. METHODS: This multicenter study evaluated data on pediatric patients diagnosed with spinal dysraphism between 2010 and 2019. The neurological and urological conditions of the patients were examined retrospectively. This study focused on the course of urological problems. Urodynamic examinations including urodynamic bladder capacity, bladder pressure in maximal capacity, compliance, detrusor hyperactivity, uroflowmetry, and residual urine amount were evaluated. All patients underwent urinary system ultrasonography, urinalysis, hemogram and biochemical tests, and urodynamics at admission and follow-ups. RESULTS: A total 62 patients (35 males, 27 females) with a mean age of 7.50 ± 4.01 years and age range of 1-16 years were included in the study. Ultrasonographic evaluation revealed normal results in 32 patients and abnormal findings, including moderate-to-severe calyceal dilatation, parenchymal thinning, and residual urine, in 30 patients. At the time of diagnosis, culture-positive urinary tract infection was detected in 22 patients, and leukocyte and/or bacterial positivity was detected in 18 patients. The differences between bladder capacity, bladder pressure at maximal capacity, compliance, and detrusor hyperactivity at first admission and post-treatment were statistically significant (p < 0.05). Vesicoureteral reflux was also detected in 25 patients. Thirty patients underwent oral anticholinergic and antibiotic prophylaxis, while 17 additionally underwent clean intermittent catheterization. Five patients underwent intravesical Botox injection, clean intermittent catheterization, and medical treatment, and 10 patients underwent augmentation cystoplasty. CONCLUSION: The prevalence of urinary tract problems is high in patients with spinal dysraphism for whom early diagnosis is very important for both urologic and neurosurgical considerations. Early follow-up of urodynamics should be performed, and treatment should be carried out if necessary. Regular follow-up and appropriate treatment have positive effects on the quality of life of these patients and may also prevent the occurrence of severe renal dysfunction.

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells.

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fibroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.

Smooth muscle cell differentiation from rabbit amniotic cells.

Amniotic fluid (AF) is the liquid layer that provides mechanical support and allows movement of the fetus during embryogenesis. Mesenchymal stem cells (MSCs), which have differentiation capacity, are also found in AF-derived cells at a low ratio. Smooth muscle cells (SMCs) play an important role in organ function and are frequently used in tissue engineering. We examined the differentiation of AF-derived MSCs (AMSCs) into SMCs. AMSCs were sorted from cultured amniotic cells and differentiated into SMCs using differentiation agents, including platelet-derived growth factor BB (PDGF-BB) and tumor growth factor ß (TGF-ß). Characterization of differentiated SMCs was confirmed morphologically, molecularly (via quantitative polymerase chain reaction [qPCR] and immunocytochemistry [ICC]), and functionally (using a contractile assay and fluo-4 calcium signaling assay). Poly(lactide-co-glycolide) (PLGA) scaffolds were fabricated, and the attachment capacity of AMSCs was assessed via scanning electron microscopy. AMSCs were successfully differentiated into SMCs. Our results indicate that AMSCs change their morphology and exhibit increased expression of ACTA2 and MYH11, which was confirmed via qPCR and ICC. Furthermore, functional experiments revealed that differentiated SMCs had both contraction ability and increased Ca2 concentration in the cytoplasm. Finally, PLGA scaffolds were prepared and AMSCs were successfully planted onto the scaffolds. The AMSCs fully differentiated into functional SMCs, and the PLGA polymer is a suitable scaffold material for AMSCs. With further clinical trials, AF-derived MSC-based SMC engineering may become a highly efficient treatment option.

Efficacy and safety of onabotulinumtoxinA injection in patients with refractory overactive bladder: First multicentric study in Turkish population.

AIMS: To investigate the efficacy and safety of intradetrusor onabotulinumtoxinA (onaBoNT-A) injection in patients with overactive bladder (OAB) refractory to antimuscarinic treatment. METHODS: A total of 80 patients with OAB symptoms were enrolled in this prospective multicenter study and received 100 U intradetrusor onaBoNT-A injection.The changes from baseline in the frequency of voiding, urge urinary incontinence (UI) and urge episodes, mean and maximum bladder capacities, uroflowmetry, post-void residual urine volume (PVR), quality of life score, and treatment benefit scale score were assessed. The need for a second injection,and treatment-related adverse events were also examined postoperatively. RESULTS: OnaBoNT-A injection significantly decreased the UI episodes(P = 0.0001), the mean voiding frequency (P = 0.0001), and the urgency episodes (P = 0.0001) in the third month compared to baseline. Similarly, the mean bladder capacity, and maximal bladder capacity were increased (P < 0,05). The quality of life scores improved by 57.1% compared to the pre-treatment rate (P = 0,0001). No significant change was observed in the PVR or maximum flow rate. Urinary retention developed in 3 (3.75%) patients and urinary infection and transient hematuria were observed in five patients (6.25%) each. The UI episodes, voiding frequency and urgency episodes were significantly lower at the 9th month than at baseline (all P = 0.0001). Overall 67% of the patients continued to experience benefits from the injection. Sixteen patients (20%) required a second injection in the third month. Eight patients were lost to follow-up at the last visit in the 9th month, and 34 of the remaining 56 patients required a second injection at the 9th month. Cumulatively, 50 (63%) patients needed re-injections. CONCLUSIONS: Our results demonstrated that the onaBoNT-A injection produced significant improvement in all OAB symptoms with a low incidence of treatment related adverse events.

Characterization of stem-like cells in a new astroblastoma cell line.

Cell lines established from tumors are the most commonly used models in cancer research, and their use in recent years has enabled a greater understanding of the biology of cancer and the means to develop effective treatment strategies. Astroblastomas are uncommon neuroepithelial tumors of glial origin, predominantly affecting young people, mainly teenagers and children, predominantly females. To date, only a single study has reported that astroblastomas contain a large number of neural stem-like cells, which had only a partial proliferation capacity and differentiation. Our objective was to establish an astroblastoma cell line to investigate the presence of astroblastic cells and cancer stem-like cells. The migratory and invasion abilities of the cells were quantified with invasion and migration assays and compared to a glioblastoma cell line. The presence of stem cells was detected with surface-marker analysis by using flow cytometry, and measuring the differentiation ability with a differentiation assay and the self-renewal capacity with a sphere-forming assay. These characteristics may determine whether this novel cell line is a model for astroblastomas that may have stem-cell characteristics. With this novel cell line, scientists can investigate the molecular pathways underlying astroblastomas and develop new therapeutic strategies for patients with these tumors.

Comparison of the Kelly's plication and TOT simultaneously with vaginal hysterectomy, on the incontinence, and sexual functions.

PURPOSE: To compare the effect of vaginal hysterectomy-anterior/posterior colporrhaphy with Kelly's plication(VH-KP), versus vaginal hysterectomy-anterior/posterior colporrhaphy-transobturator tape(VH-TOT) surgeries on incontinence, quality of life, and sexual functions in patients with pelvic organ prolapse(POP), and concurrent obvious stress urinary incontinence(SUI). MATERIALS AND METHODS: Between 2013 and 2017, fifty patients treated with VH-KP(n = 25), and VH-TOT(n = 25) due to POP and SUI, were evaluated prospective consecutively. Age, parity, duration of urinary incontinence,and the daily pad use were recorded. Patients were filled "rinary Distress Inventory-6(UDI-6)", "Incontinence Impact Questionnaire 7(IIQ-7)" and "Index of Female Sexual Function(IFSI)" questionnaire forms at preoperatively,and postoperative 6th month. No usage of pads was accepted as subjective cure rate.Intraoperative,and postoperative complications were noted. RESULTS: There was no statistically significant difference between two groups, for the mean age of the patients, parity, duration of SUI, and the daily pad use, preoperatively (p > 0.05). Decreased UDI-6 scores, IIQ-7 scores and daily pad usage, and increased IFSF scores were found statistical significantly in each group, at the postoperative 6 th month (p < 0.05). However, VH-TOT group had higher improvement rates, on UDI-6 scores (69.5% vs 63.0%, p = 0.04). In addition, it was notable that the the rates of the patients had IFSF scores ≥ 25 was higher in VH-KP group (p = 0.05). Four (16%) patients had recurrent SUI in the VH-KP group (p = 0.039) and vaginal extrusion occurred in 2 (8%) patients in the VH-TOT group (p = 0.153), postoperatively. CONCLUSIONS: Although the effects of VH-TOT surgery are superior to conventional methods for incontinence and quality of life; negative effects on sexual functions are notable. In addition, although recurrence rates of TOT are low, complications such as vaginal extrusion are accompanied by drawbacks of mesh usage.

Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3 and miR-29c.

BACKGROUND: Although meningioma is a common disease, there is a lack of understanding of the underlying molecular mechanisms behind its initiation and progression. We used combined miRNA-mRNA transcriptome analysis to discover dysregulated genes and networks in meningiomas. METHODS: Fourteen fresh-frozen meningioma samples and one human meningeal cell line were analyzed by using miRNA and whole transcriptome microarray chips. Data was filtered and analyzed. Candidate miRNAs and mRNAs were selected for validation in fifty-eight patient samples. miRNA and target mRNA relationships were assessed by inhibiting miRNA in meningioma cells. Apoptosis and viability assays were also used as functional tests. RESULTS: With the whole transcriptome microarray, 3753 genes were found to be dysregulated, and 891 miRNAs were found to be dysregulated as a result of miRNA microarray. Results were combined and analyzed with bioinformatics tools. Top differential pathways included those of inflammation, cancer, and cellular growth and survival. The oncosupressor PTX3 was constitutively low in meningioma samples. Moreover, PTX3 negatively correlated with miR-29c in our samples. Inhibiting miR-29c upregulated the PTX3 level, induced apoptosis of meningioma cells, and decreased cell viability. CABIN1, miR-29c, TMOD1, PTX3, RPL22, SPARCL1 and RELA were correlated with clinicopathological features in patient samples. CONCLUSIONS: Our results present the first integrated mRNA-miRNA analysis in meningiomas. miR-29c-3p and PTX3 are inversely correlated in tissues and meningioma cells, hinting that PTX3 can be regulated by miR-29c-3p. Furthermore, we determined potential clinicopathological markers.

Boron nitride nanotubes for gene silencing.

BACKGROUND: Non-viral gene delivery is increasingly investigated as an alternative to viral vectors due to low toxicity and immunogenicity, easy preparation, tissue specificity, and ability to transfer larger sizes of genes. METHODS: In this study, boron nitride nanotubes (BNNTs) are functionalized with oligonucleotides (oligo-BNNTs). The morpholinos complementary to the oligonucleotides attached to the BNNTs (morpholino/oligo-BNNTs) are hybridized to silence the luciferase gene. The morpholino/oligo-BNNTs conjugates are administered to luciferase-expressing cells (MDA-MB-231-luc2) and the luciferase activity is monitored. RESULTS: The luciferase activity is decreased when MDA-MB-231-luc2 cells were treated with morpholino/oligo-BNNTs. CONCLUSIONS: The study suggests that BNNTs can be used as a potential vector to transfect cells. GENERAL SIGNIFICANCE: BNNTs are potential new nanocarriers for gene delivery applications.

Efficacy of onabotulinum toxin A injection in pediatric patients with non-neurogenic detrusor overactivity.

AIMS: To evaluate the effectiveness and reliability of onabotulinum toxin A (onaBoNT-A) injections in pediatric patients with non-neurogenic detrusor overactivity (NNDO). METHODS: Between January 2010 and February 2016, 39 patients underwent onaBoNT-A injections for NNDO, and were evaluated retrospectively. Three-day voiding diary was filled at baseline, and at the postoperative 9th month. The voiding frequency, incontinence episodes, and the cystometric capacity were noted. Vesicoureteral reflux (VUR) associated with NNDO, and presence of nocturia were recorded. Additional injection requirements were also stated. RESULTS: We reached the data of 33 patients on 9th month. The mean age was determined as 8.75 ± 3.01 (5-16) years. Initially, the mean bladder capacity was calculated as 114.66 ± 35.23 mL on the voiding diary, and 153.15 ± 47.40 mL on the baseline urodynamic study. After the procedures, the mean bladder capacity increased to 140.84 ± 45.61 mL (P = 0.0011), the mean daily voiding frequency decreased from 10.36 ± 1.05 to 7.42 ± 0.83 (P = 0.01), and the mean incontinence episodes decreased from 2.72 ± 1.87 to 1.18 ± 1.13 (P = 0.001), on voiding diary. VUR associated with NNDO was determined in 10 (30.3%) patients. The degree of VUR decreased three in patients, and VUR disappeared in five patients following the injections (P = 0.011). Fourteen (42.4%) patients had nocturia, and after the injections, nocturia disappeared in five (15.15%) patients (P = 0.151). Additional injections were required in 10 (30.3%) patients at the 9th month. CONCLUSIONS: OnaBoNT-A injections can be used in the pediatric patients with NNDO as an effective and reliable procedure by decreasing voiding frequency, incontinence episodes, and increasing bladder capacity, with negligible side effects and complications.

A neural network - based algorithm for predicting stone - free status after ESWL therapy.

OBJECTIVE: The prototype artificial neural network (ANN) model was developed using data from patients with renal stone, in order to predict stone-free status and to help in planning treatment with Extracorporeal Shock Wave Lithotripsy (ESWL) for kidney stones. MATERIALS AND METHODS: Data were collected from the 203 patients including gender, single or multiple nature of the stone, location of the stone, infundibulopelvic angle primary or secondary nature of the stone, status of hydronephrosis, stone size after ESWL, age, size, skin to stone distance, stone density and creatinine, for eleven variables. Regression analysis and the ANN method were applied to predict treatment success using the same series of data. RESULTS: Subsequently, patients were divided into three groups by neural network software, in order to implement the ANN: training group (n=139), validation group (n=32), and the test group (n=32). ANN analysis demonstrated that the prediction accuracy of the stone-free rate was 99.25% in the training group, 85.48% in the validation group, and 88.70% in the test group. CONCLUSIONS: Successful results were obtained to predict the stone-free rate, with the help of the ANN model designed by using a series of data collected from real patients in whom ESWL was implemented to help in planning treatment for kidney stones.

The molecular aspects of chordoma.

Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

Overexpression of miR-145-5p inhibits proliferation of prostate cancer cells and reduces SOX2 expression.

We aimed to perform functional analysis of miR-145-5p in prostate cancer (PCa) cells and to identify targets of miR-145-5p for understanding its role in PCa pathogenesis. PC3, DU145, LNCaP PCa, and PNT1a nontumorigenic prostate cell lines were utilized for functional analysis of miR-145-5p. Its overexpression caused inhibition of proliferation through apoptosis and reduced migration in PCa cells. SOX2 expression was significantly decreased in both mRNA and protein level in miR-145-5p-overexpressed PCa cells. We proposed that miR-145-5p, being an important regulator of SOX2, carries a crucial role in PCa tumorigenesis.