Distribution of neurovascular structures within the prostate gland and their relationship to complications after radical prostatectomy.

BACKGROUND: Radical prostatectomy remains the main choice of treatment for prostate cancer. However, despite improvements in surgical techniques and neurovascular sparing procedures, rates of erectile dysfunction, and urinary incontinence remain variable. This is due, at least in part, to an incomplete understanding of neurovascular structures associated with the prostate. The objective of this study was to provide a comprehensive, detailed histological overview of the distribution of nerves and blood vessels within the prostate, facilitating subsequent correlation of prostatic neurovascular structures with patients' clinical outcomes after radical prostatectomy. METHODS: Neurovascular structures within the prostate were investigated in a total of 309 slides obtained from 15 patients who underwent non-nerve-sparing radical prostatectomy. Immunohistochemical staining was performed to identify and distinguish between parasympathetic and sympathetic nerves, whereas hematoxylin and eosin staining was used to identify blood vessels. The total number, density, and relative position of nerves and blood vessels were established using quantitative morphometry and illustrated using visualization approaches. Patient-specific outcome data were then used to establish whether the internal distribution of nerves and blood vessels within the prostate correlated with the nature and extent of complications after surgery. One-way analysis of variance tests and unpaired t tests were applied to establish statistically significant differences across the measured variables. RESULTS: Nerves and blood vessels were present across all prostatic levels and regions. However, their number and density varied considerably between regions. Assessment of the precise positioning of neurovascular structures revealed that the majority of nerve fibers were located within the dorsal and peripheral aspects of the gland. In contrast, blood vessels were predominantly located within ventral and dorsal midline regions. The number of intraprostatic nerves was found to be significantly lower in patients who recovered their continence within 12 months of surgery, compared to those whose recovery took 12 months or longer. CONCLUSION: We report an unexpected disconnect between the localization and positioning of nerve fibers and blood vessels within the prostate. Moreover, individual variability in the density of intraprostatic neurovascular structures appears to correlate with the successful recovery of urinary continence after radical prostatectomy, suggesting that differences in intrinsic neurovascular arrangements of the prostate influence postoperative outcomes.

Cost-effectiveness of quality improvement intervention to reduce time between CT-detection and ureteroscopic laser fragmentation in acute symptomatic ureteric stones management.

OBJECTIVE: To prospectively assess clinical and cost effectiveness of emergency ureteroscopic laser fragmentation of urinary stones causing symptoms or obstruction. PATIENTS AND METHODS: 100 consecutive patients with an average (median) age 55.6 (57.5) years and average (median) stone size of 8.2 mm (± 7 mm) between October 2018 and December 2021 who underwent emergency ureteroscopy and laser fragmentation formed the study cohort as part of a clinical service quality improvement. Primary outcome was single procedure stone-free rate and cost-effectiveness. The secondary outcomes were complications, re-admission and re-intervention. A decision analysis model was constructed to compare the cost-effectiveness of emergency ureteroscopy with laser fragmentation (EUL) and emergency temporary stenting followed by delayed ureteroscopy with laser fragmentation (DUL) using our results and success rates for modelling. RESULTS: Single procedure stone-free rates (SFR) for EUL and DUL were 85%. The re-intervention rate, re-admission and complication rates of the study cohort (EUL) were 9%, 18%, and 4%, respectively, compared to 15%, 20%, and 5%, respectively for the control cohort (DUL). The decision analysis modelling demonstrated that the EUL treatment option was more cost-efficient, averting £2868 (€3260) per patient for the UK health sector. Total cost of delayed intervention was £7783 (€8847) for DUL in contrast to £4915 (€5580) for EUL. CONCLUSIONS: Implementation of quality improvement project based on a reduction in CT detection-to-laser fragmentation time interval in acute ureteric obstruction or symptoms caused by stones had similar clinical effectiveness compared to delayed ureteroscopic management, but more cost-effective.

Bacteria populating freshly appeared supraglacial lake possess metals and antibiotic-resistant genes.

Antibiotic resistance (AR) has been extensively studied in natural habitats and clinical applications. AR is mainly reported with the use and misuse of antibiotics; however, little is known about its presence in antibiotic-free remote supraglacial lake environments. This study evaluated bacterial strains isolated from supraglacial lake debris and meltwater in Dook Pal Glacier, northern Pakistan, for antibiotic-resistant genes (ARGs) and metal-tolerant genes (MTGs) using conventional PCR. Several distinct ARGs were reported in the bacterial strains isolated from lake debris (92.5%) and meltwater (100%). In lake debris, 57.5% of isolates harbored the blaTEM gene, whereas 58.3% of isolates in meltwater possessed blaTEM and qnrA each. Among the ARGs, qnrA was dominant in debris isolates (19%), whereas in meltwater isolates, qnrA (15.2%) and blaTEM (15.2%) were dominant. ARGs were widely distributed among the bacterial isolates and different bacteria shared similar types of ARGs. Relatively greater number of ARGs were reported in Gram-negative bacterial strains. In addition, 92.5% of bacterial isolates from lake debris and 83.3% of isolates from meltwater harbored MTGs. Gene copA was dominant in meltwater isolates (50%), whereas czcA was greater in debris bacterial isolates (45%). Among the MTGs, czcA (18.75%) was dominant in debris strains, whereas copA (26.0%) was greater in meltwater isolates. This presents the co-occurrence and co-selection of MTGs and ARGs in a freshly appeared supraglacial lake. The same ARGs and MTGs were present in different bacteria, exhibiting horizontal gene transfer (HGT). Both positive and negative correlations were determined between ARGs and MTGs. The research provides insights into the existence of MTGs and ARGs in bacterial strains isolated from remote supraglacial lake environments, signifying the need for a more detailed study of bacteria harboring ARGs and MTGs in supraglacial lakes.

Comparative Analysis of Enbloc or Piecemeal Removal After Enbloc Resection of Gastrointestinal Stromal Tumors.

OBJECTIVE: To investigate the safety and prognosis of enbloc or piecemeal removal after enbloc resection of a gastric GIST by comparing the clinical data of endoscopic en block resection and piecemeal removal (EP) and en block resection and complete removal (EC) of gastric GISTs. METHODS: A total of 111 (43 endoscopic piecemeal, and 68 complete removal) patients with gastric GIST's ≥ 2 cm in diameter who underwent endoscopic therapy from January 2016 to June 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. In all cases, it was ensured that the tumor was intact during the resection, however, it was divided into EP group and EC group based on whether the tumor was completely removed or was cut into pieces which were then removed. The patients' recurrence-free survival rate and recurrence-free survival (RFS) were recorded. RESULTS: There was no statistically significant difference in RFS rates between the two groups (P = 0.197). The EP group had relatively high patient age, tumor diameter, risk classification, and operation time. However, there was no statistically significant difference in the number of nuclear fission images, postoperative hospitalization time, postoperative fasting time, complication rate and complication grading between the two groups (P > 0.05). CONCLUSION: Endoscopic piecemeal removal after en block resection of gastric GIST is safe and effective and achieves similar clinical outcomes as complete removal after en block resection.

Predictive accuracy of boosted regression model in estimating risk of venous thromboembolism following minimally invasive radical surgery in pharmacological prophylaxis-naïve men with prostate cancer.

BACKGROUND: Venous thromboembolism (VTE) is a potentially life-threatening but preventable complication after urological surgery. Physicians are faced with the challenges of weighing the risks and benefits of thromboprophylaxis given scanty evidence for or against and practice variation worldwide. OBJECTIVE: The primary objective of the study was to explore the possibility of a risk-stratified approach for thromboembolism prophylaxis following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: A prospective database was accessed to cross-link venous thromboembolism events in 522 men who underwent minimally invasive prostatectomy between February 2010 and October 2021. A deterministic data linkage method was used to record events through electronic systems. Community Health Index (CHI) numbers were used to identify patients via electronic health records. Patient demographics and clinical characteristics such as age, comorbidities, Gleason staging, and readmission details accrued. OUTCOMES: VTE within 90 days and development of a risk-stratified scoring system. All statistical analysis was performed using R-Statistical Software and the risk of VTE within 90 days of surgery was estimated via gradient-boosting decision trees (BRT) model. RESULTS AND LIMITATIONS: 1.1% (6/522) of patients developed deep vein thrombosis or pulmonary embolism within 3 months post-minimally invasive prostatectomy. Statistical analysis demonstrated a significant difference in the body mass index (p = 0.016), duration of hospital stay (p < 0.001), and number of readmissions (p = 0.036) between patients who developed VTE versus patients who did not develop VTE. BRT analysis found 8 variables that demonstrated relative importance in predicting VTE. The receiver operating curves (ROC) were constructed to assess the discrimination power of a new model. The model showed an AUC of 0.97 (95% confidence intervals [CI]: 0.945,0.999). For predicting VTE, a single-center study is a limitation. CONCLUSIONS: The incidence of VTE post-minimally invasive prostatectomy in men who did not receive prophylaxis with low molecular weight heparin is low (1.1%). The proposed risk-scoring system may aid in the identification of higher-risk patients for thromboprophylaxis. In this report, we looked at the outcomes of venous thromboembolism following minimally invasive radical prostatectomy for prostate cancer in consecutive men. We developed a new scoring system using advanced statistical analysis. We conclude that the VTE risk is very low and our model, if applied, can risk stratify men for the development of VTE following radical surgery for prostate cancer.

Radiogenomics Map-Based Molecular and Imaging Phenotypical Characterization in Localised Prostate Cancer Using Pre-Biopsy Biparametric MR Imaging.

To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer.

HMG co-reductase expression and response to intravesical Bacillus Calmette-Guérin in patients with high grade non-muscle invasive urinary bladder cancer receiving statins.

BACKGROUND: Cardiovascular disease affects over 7 million people in the UK and statins are often prescribed to mitigate cardiovascular risks. The effect of statins on a number of cancers is debated and their effect on Bacillus Calmette-Guérin (BCG) responsiveness in non-muscle invasive urinary bladder cancer (NMIBC) is not fully understood. AIMS: This study aims to explore the difference in HMG Co-A reductase (HMGCR) expression in NMIBC on immunochemistry in BCG responders and non-responders while on statins. METHOD: Three hundred and thirty-two cases of intravesical BCG treatment for high-risk NMIBC between November 2003 and December 2017 were identified. Patients taking statins for at least 12 months before the diagnosis of NIMBC and with a follow-up of at least 5 years were included. They were divided into BCG responders and non-responders. Tumour tissue from these patients was immunohistochemically stained and quantitative image analysis carried out to assess and compare HMGCR expression in the groups. RESULTS & CONCLUSION: This study showed a differential expression of HMGCR in responders vs. non-responders to BCG for high-risk NMIBC on statins. This data should form the basis of a further research and multi-centre study in a larger cohort, using HMGCR as a biomarker of response in patients on statins.

Validation of the updated Bosniak classification (2019) in pathologically confirmed CT-categorised cysts.

INTRODUCTION: The updated Bosniak classification in 2019 (v2019) addresses vague imaging terms and revises the criteria with the intent to categorise a higher proportion of cysts in lower-risk groups and reduce benign cyst resections. The aim of the present study was to compare the diagnostic accuracy and inter-observer agreement rate of the original (v2005) and updated classifications (v2019). METHOD: Resected/biopsied cysts were categorised according to Bosniak classifications (v2005 and v2019) and the diagnostic accuracy was assessed with reference to histopathological analysis. The inter-observer agreement of v2005 and v2019 was determined. RESULTS: The malignancy rate of the cohort was 83.6% (51/61). Using v2019, a higher proportion of malignant cysts were categorised as Bosniak ≥ III (88.2% vs 84.3%) and a significantly higher percentage were categorised as Bosniak IV (68.9% vs 47.1%; p = 0.049) in comparison to v2005. v2019 would have resulted in less benign cyst resections (13.5% vs 15.7%). Calcified versus non-calcified cysts had lower rates of malignancy (57.1% vs 91.5%; RR,0.62; p = 0.002). The inter-observer agreement of v2005 was higher than that of v2019 (kappa, 0.70 vs kappa, 0.43). DISCUSSION: The updated classification improves the categorisation of malignant cysts and reduces benign cyst resection. The low inter-observer agreement remains a challenge to the updated classification system.

Multicenter Randomized Trial Assessing MRI and Image-guided Biopsy for Suspected Prostate Cancer: The MULTIPROS Study.

Background The optimal diagnostic pathway for prostate cancer (PCa) is evolving, requiring further evaluation in a randomized controlled trial. Purpose To assess the diagnostic accuracy of prebiopsy multiparametric MRI in the identification of clinically significant PCa (csPCa) using radical prostatectomy (RP) specimens as the reference standard, and to test the diagnostic accuracy of combined US and MRI fusion-targeted biopsy with systematic biopsies. Materials and Methods In a prospective randomized controlled trial including university hospitals, men with suspected PCa were recruited between January 2015 and August 2020 to assess the diagnostic accuracy of multiparametric MRI before biopsy in detection of csPCa at biopsy and RP histopathologic structure (primary outcome). Men with lesions suspicious for cancer (Prostate Imaging and Reporting Data System [PI-RADS] ≥3) at multiparametric MRI were first randomized to either systematic random prostate biopsies alone (control group) or US and MRI fusion-targeted biopsies with systematic random prostate biopsies (intervention group) at a one-to-one ratio to compare the diagnostic accuracy of systematic random versus combined fusion with systematic random biopsies (secondary outcome). A subset of recruited participants (n = 89) underwent RP and histologic sectioning. Results There were 582 participants who were eligible to undergo multiparametric MRI (mean age, 65 years ± 6 [SD]). In total, 413 had a PI-RADS score of at least 3 and were randomized into either the intervention group (207 of 413; 50.1%) or control group (206 of 413; 49.9%). The csPCa detection rate in the intervention group was higher, with an adjusted odds ratio of 1.79 (95% CI: 1.14, 2.79; P = .01). A subgroup of 89 men underwent RP (21.5%; 89 of 413). Multiparametric MRI helped correctly identify 131 of 182 csPCa foci in 89 men (sensitivity, 72%; 95% CI: 65, 78). The specificity, positive predictive value, and negative predictive value were 71% (91 of 128), 78% (131 of 168), and 64% (91 of 142), respectively. Conclusion Prebiopsy multiparametric MRI was accurate in the depiction of clinically significant PCa. Combining US and MRI fusion-targeted biopsies with systematic biopsies helped detect more clinically significant lesions than did systematic biopsies alone. Clinical trial registration no. NCT02745496 © RSNA, 2023 Supplemental material is available for this article.

Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults.

BACKGROUND: Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic drugs are commonly used to treat this condition. This is an update of a Cochrane Review first published in 2002 and last updated in 2006. OBJECTIVES: To assess the effects of anticholinergic drugs compared with placebo or no treatment for treating overactive bladder syndrome in adults. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 14 January 2020), and the reference lists of relevant articles. We updated this search on 3 May 2022, but these results have not yet been fully incorporated. SELECTION CRITERIA: We included randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug alone with placebo treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and extracted data from the included studies, including an assessment of the risk of bias. We assessed the certainty of the body of evidence using the GRADE approach. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included 104 studies, 71 of which were new or updated for this version of the review. Although 12 studies did not report the number of participants, there were 47,106 people in the remainder of the included studies. The majority of the studies had insufficient information to allow judgement of risk of bias and we judged them to be unclear for all domains. Nine anticholinergic drugs were included in these studies: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium. No studies were found that compared anticholinergic drugs to no treatment. At the end of the treatment period, anticholinergics may slightly increase condition-specific quality of life (mean difference (MD) 4.41 lower, 95% confidence interval (CI) 5.28 lower to 3.54 lower (scale range -100 to 0); 12 studies, 6804 participants; low-certainty evidence). Anticholinergics are probably better than placebo in terms of patient perception of cure or improvement (risk ratio (RR) 1.38, 95% CI 1.15 to 1.66; 9 studies, 8457 participants; moderate-certainty evidence), and the mean number of urgency episodes per 24-hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, 16,875 participants; moderate-certainty evidence). Compared to placebo, anticholinergics may result in an increase in dry mouth adverse events (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, 38,368 participants; low-certainty evidence), and may result in an increased risk of urinary retention (RR 3.52, 95% CI 2.04 to 6.08; 17 studies, 7862 participants; low-certainty evidence). Taking anticholinergics may be more likely to lead to participants withdrawing from the studies due to adverse events (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, 36,943 participants; low-certainty evidence). However, taking anticholinergics probably reduces the mean number of micturitions per 24-hour period compared to placebo (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, 19,395 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of anticholinergics are sustained during long-term treatment or after treatment stops.

Fiber Bundle Image Reconstruction Using Convolutional Neural Networks and Bundle Rotation in Endomicroscopy.

Fiber-bundle endomicroscopy has several recognized drawbacks, the most prominent being the honeycomb effect. We developed a multi-frame super-resolution algorithm exploiting bundle rotation to extract features and reconstruct underlying tissue. Simulated data was used with rotated fiber-bundle masks to create multi-frame stacks to train the model. Super-resolved images are numerically analyzed, which demonstrates that the algorithm can restore images with high quality. The mean structural similarity index measurement (SSIM) improved by a factor of 1.97 compared with linear interpolation. The model was trained using images taken from a single prostate slide, 1343 images were used for training, 336 for validation, and 420 for testing. The model had no prior information about the test images, adding to the robustness of the system. Image reconstruction was completed in 0.03 s for 256 × 256 images indicating future real-time performance is within reach. The combination of fiber bundle rotation and multi-frame image enhancement through machine learning has not been utilized before in an experimental setting but could provide a much-needed improvement to image resolution in practice.

Urinary bladder recurrences following ureteroscopic biopsies of upper tract urothelial cancers: a multi-centre observational study with genomic assessment for clonality.

BACKGROUND AND AIMS: Urinary bladder recurrences (UBRs) after radical nephroureterectomy (RNUx) are a known challenge in patients with upper-tract urothelial cancers (UTUCs). We aim to assess factors associated with UBR and clonal-relatedness with resected UTUC. METHODS: Patients who underwent RNUx for UTUC between 1998 and 2015 in five institutions were identified. Clonal relatedness between primary UTUC and subsequent UBR in a sub-cohort was assessed using next-generation sequencing. A Kaplan-Meier curve was used to assess differences in UBR between two groups (with or without ureteroscopic biopsy). RESULTS: Of 267 patients with complete records, 73 (27.3%) had UBR during follow-up. The five-year UBR-free survival in all patients was 64.7%. The five-year UBR-free-survival was inferior in patients who underwent URS biopsy compared with patients who did not undergo ureteroscopic biopsy (49.9% vs 76.4%, p < 0.001). History of bladder tumour (HR, 95% CI; 2.94, 1.73-5.00, p < 0.001), ureteroscopic biopsy (HR, 95% CI; 2.21, 1.38-3.53, p = 0.001) and preoperative urine cytology ≥C3 (HR, 95% CI; 2.06, 1.24-3.40, p = 0.005) were independently associated with UBR. Patients with ureteroscopic biopsy (n = 3/5) showed identical mutational changes for common genes (TP53 and FGFR3) between primary UTUC and subsequent UBR. CONCLUSIONS: Ureteroscopic biopsy of UTUC is a significant risk factor for UBR. Qualitative clonality assessment showed identical mutational signatures between primary UTUC and UBR.

Fabrication of novel BiVO4/Bi2O3heterostructure with superior visible light induced photocatalytic properties.

Heterostructure BiVO4/Bi2O3nanocomposites with enhanced visible light activity are effectively synthesized through an easiest and single step hydrothermal route, using bismuth subnitrate and ammonium meta-vanadate as main raw materials in existence of citric acid. The phase and surface structure, topography and optical properties of synthesized composites are characterized by XRD, SEM, EDX, FTIR, UV-Visible and PL spectroscopy. It was found that 5%BiVO4/Bi2O3(BOBV-5) nanocomposite exhibit excellent photocatalytic performance for rhodamine B dye degradation and tetracyclic under irradiation of visible light as compared to single component i.e. BiVO4. The increased photocatalytic activity should be ascribed for making p-n heterojunction among p-type Bi2O3and n-type BiVO4. This p-n heterojunction successfully reduce the recombination of photogenerated charge carriers. Furthermore, the BOBV-5 novel photocatalyst shows good stability in constructive five cycles and photocatalytic activity is best for conquering photo corrosion of a photocatalysts. To explain charge migration route, whole photocatalytic mechanism was described in terms of energy band structures. Furthermore, the present work is helpful effort for design of new visible light photocatalytic materials with heterojunction structures.

The trend in delayed childbearing and its potential consequences on pregnancy outcomes: a single center 9-years retrospective cohort study in Hubei, China.

BACKGROUND: Due to the advancement of modern societies, the proportion of women who delay childbearing until or beyond 30 years has dramatically increased in the last three decades and has been linked with adverse maternal-neonatal outcomes. OBJECTIVE: To determine the trend in delayed childbearing and its negative impact on pregnancy outcomes. MATERIAL AND METHODS: A tertiary hospital-based retrospective study was conducted in Wuhan University Renmin Hospital, Hubei Province, China, during the years 2011-2019. The joinpoint regression analysis was used to find a trend in the delayed childbearing and the multiple binary logistic regression model was used to estimate the association between maternal age and pregnancy outcomes. RESULTS: Between 2011 and 2019, the trend in advanced maternal age (AMA ≥35 years) increased by 75% [AAPC 7.5% (95% CI: - 10.3, 28.9)]. Based on maternal education and occupation, trend in AMA increased by 130% [AAPC 11.8% (95% CI: 1.1, 23.7)] in women of higher education level, and 112.5% [AAPC 10.1% (95% CI: 9.4, 10.9)] in women of professional services. After adjusting for confounding factors, AMA was significantly associated with increased risk of gestational hypertension (aOR 1.5; 95% CI: 1.2, 2.1), preeclampsia (aOR 1.6; 95% CI: 1.4, 1.9), sever preeclampsia (aOR 1.7; 95% CI: 1.1, 2.6), placenta previa (aOR 1.8; 95% CI: 1.5, 2.2), gestational diabetes mellitus (aOR 2.5; 95% CI: 2.3, 2.9), preterm births (aOR 1.6; 95% CI: 1.4, 1.7), perinatal mortality (aOR 1.8; 95% CI: 1.3, 2.3), and low birth weight (aOR 1.3; 95% CI: 1.2, 1.4) compared with women aged < 30 years. CONCLUSION: Our findings show a marked increase in delayed childbearing and its negative association with pregnancy outcomes.

Morphometric and Myelin Basic Protein Expression Changes in Arcuate Nucleus Kisspeptin Neurons Underlie Activation of Hypothalamic Pituitary Gonadal-axis in Monkeys (Macaca Mulatta) during the Breeding Season.

INTRODUCTION: Kisspeptin is involved in the hypothalamic pituitary gonadal-axis' seasonal regulation in rodents and sheep. Studies of kisspeptin signaling in regulating the transition between breeding and nonbreeding seasons have focused on kisspeptin expression, myelin basic protein (MBP) expression around kisspeptin-ir cells, and quantifying the synaptic connections between kisspeptin and gonadotropin-releasing hormone (GnRH) neurons in various animal models; however, the role of kisspeptin in regulating the seasonal breeding of primates has not been explored yet. OBJECTIVE: This study investigated changes in kisspeptin signaling during breeding and a non-breeding season in a non-human primate model, the rhesus monkey. METHODS: Three adult male monkeys (n = 3) from the breeding season and two monkeys (n = 2) from the non-breeding season were used in this study. After measuring the testicular volume and collecting a single blood sample, all animals were humanely euthanized under controlled conditions, and their hypothalami were collected and processed. Two 20 µm thick hypothalamic sections (mediobasal hypothalamus) from each animal were processed for kisspeptin-MBP and kisspeptin-GnRH immunohistochemistry (IHC). One section from each animal was used as a primary antibody omitted control to check the nonspecific binding in each IHC. RESULTS: Compared to the non-breeding season, plasma testosterone levels and testicular volumes were significantly higher in monkeys during the breeding season. Furthermore, compared to the non-breeding season, increased kisspeptin expression and a higher number of synaptic contacts between kisspeptin fibers and GnRH cell bodies were observed in the arcuate nucleus of the breeding season monkeys. In contrast, enlarged kisspeptin soma and higher MBP expression were observed in non-breeding monkeys. CONCLUSION: Our results indicated enhanced kisspeptin signaling in primate hypothalamus during the breeding season. These findings support the idea that kisspeptin acts as a mediator for the seasonal regulation of the reproductive axis in higher primates.

De Novo Transcriptome Assembly and Analysis of Longevity Genes Using Subterranean Termite (Reticulitermes chinensis) Castes.

The longevity phenomenon is entirely controlled by the insulin signaling pathway (IIS-pathway). Both vertebrates and invertebrates have IIS-pathways that are comparable to one another, though no one has previously described de novo transcriptome assembly of IIS-pathway-associated genes in termites. In this research, we analyzed the transcriptomes of both reproductive (primary kings "PK" and queens "PQ", secondary worker reproductive kings "SWRK" and queens "SWRQ") and non-reproductive (male "WM" and female "WF" workers) castes of the subterranean termite Reticulitermes chinensis. The goal was to identify the genes responsible for longevity in the reproductive and non-reproductive castes. Through transcriptome analysis, we annotated 103,589,264 sequence reads and 184,436 (7G) unigenes were assembled, GC performance was measured at 43.02%, and 64,046 sequences were reported as CDs sequences. Of which 35 IIS-pathway-associated genes were identified, among 35 genes, we focused on the phosphoinositide-dependent kinase-1 (Pdk1), protein kinase B2 (akt2-a), tuberous sclerosis-2 (Tsc2), mammalian target of rapamycin (mTOR), eukaryotic translation initiation factor 4E (EIF4E) and ribosomal protein S6 (RPS6) genes. Previously these genes (Pdk1, akt2-a, mTOR, EIF4E, and RPS6) were investigated in various organisms, that regulate physiological effects, growth factors, protein translation, cell survival, proliferation, protein synthesis, cell metabolism and survival, autophagy, fecundity rate, egg size, and follicle number, although the critical reason for longevity is still unclear in the termite castes. However, based on transcriptome profiling, the IIS-pathway-associated genes could prolong the reproductive caste lifespan and health span. Therefore, the transcriptomic shreds of evidence related to IIS-pathway genes provide new insights into the maintenance and relationships between biomolecular homeostasis and remarkable longevity. Finally, we propose a strategy for future research to decrypt the hidden costs associated with termite aging in reproductive and non-reproductive castes.

Ti3C2Tx-Modified PEDOT:PSS Hole-Transport Layer for Inverted Perovskite Solar Cells.

PEDOT: PSS is a commonly used hole-transport layer (HTL) in inverted perovskite solar cells (PSCs) due to its compatibility with low-temperature solution processing. However, it possesses lower conductivity than other conductive polymers and metal oxides, along with surface defects, limiting its photovoltaic performance. In this study, we introduced two-dimensional Ti3C2Tx (MXene) as an additive in the PEDOT:PSS HTL with varying doping concentrations (i.e., 0, 0.03, 0.05, and 0.1 wt.%) to tune the electrical conductivity of PEDOT:PSS and to modify the properties of the perovskite film atop it. We noted that the grain size of the CH3NH3PbI3 (MAPI3) perovskite layer grown over an optimal concentration of MXene (0.03 wt.%)-doped PEDOT:PSS increased from 250 nm to 400 nm, reducing charge recombination due to fewer grain boundaries. Ultraviolet photoelectron spectroscopy (UPS) revealed increased work function (WF) from 4.43 eV to 4.99 eV with 0.03 wt.% MXene doping, making the extraction of holes easier due to a more favorable energy level alignment with the perovskite. Quantum chemical investigations based on density functional theory (DFT) were conducted at the ωB97XD/6-311++G(d,p) level of theory to provide more insight into the stability, bonding nature, and optoelectronic properties of the PEDOT:PSS-MXene system. The theoretical investigations revealed that the doping of PEDOT:PSS with Ti3C2Tx could cause a significant effect on the electronic properties of the HTL, as experimentally demonstrated by an increase in the electrical conductivity. Finally, the inverted PSCs employing 0.03 wt.% MXene-doped PEDOT:PSS showed an average power conversion efficiency (PCE) of 15.1%, up from 12.5% for a reference PSC employing a pristine PEDOT:PSS HTL. The champion device with a 0.03 wt.% MXene-PEDOT:PSS HTL achieved 15.5% PCE.

Extra-peritoneal Laparoscopic Resection of Benign Prostate Adenoma >150 CC with preservation of posterior wall of prostatic urethra: Dundee Technique and early outcomes.

BACKGROUND: There are limited options for men with large benign prostates (>150cc) and bladder outflow obstruction due to benign prostatic hyperplasia (BPH). Management options include surgery (open or minimal access) and endoscopic procedures. There is a paucity of literature on outcomes for prostates >150cc. METHODS: In this case series we describe a step-by-step, illustrated, modified extra-peritoneal technique of laparoscopic prostatectomy with preservation of the posterior prostatic urethra. This involves creation of extra-peritoneal space, transverse incision of prostate capsule, progressive adenoma dissection, resection, and closure of the capsule. RESULTS: Ten patients underwent this procedure between 2015 and 2019. The mean age was 72.4 years and mean prostate size was 215.5cc. Mean procedure duration was 200 min and there were no intraoperative complications. Most patients were discharged on postoperative day 1. Mean intraoperative blood loss was 120 ml with no patient requiring blood transfusion. At follow up (mean 37 months) no patients had residual symptoms of BPH. CONCLUSION: We describe a novel extraperitoneal laparoscopic technique for benign prostates of >150cc with very good outcomes. The transferability of this technique to centres with laparoscopic expertise at minimal extra cost and future adaptability in the robotic setting are some of the advantages of this technique.

Global Assessment of Urological Endoscopic Skills (GAUES): development and validation of a novel assessment tool to evaluate endourological skills.

OBJECTIVE: To develop and evaluate an assessment tool for endourological skills during simulation including cystoscopy, ureteroscopy (URS) and transurethral resection (TUR) procedures. METHODS: We designed a Global Assessment of Urological Endoscopic Skills (GAUES) tool, comprised of nine endourology task-specific and two global-rating skills items. The tool was developed through two rounds of the Delphi process. The GAUES tool was used to assess acquisition of URS and TUR skills of novices (Year 2 core surgical trainees, CT2) and intermediate level trainees (residents at the start of the UK higher surgical training programme in Urology, Speciality Trainee Year 3, ST3) at the Urology Simulation Boot Camp (USBC) between 2016 and 2018. Validity was evaluated by comparing scores between trainees with different levels of urological experience. Inter-rater reliability was also assessed. RESULTS: We evaluated 130 residents, 52% of trainees were at an intermediate stage of training and 39% were novices. In all, 9% of the anonymous forms were missing demographics. The completion rate of the GAUES tool during the USBC for URS and TUR was 85% and 89%, respectively. Our analysis demonstrated a significant difference in all domains between intermediates and novices at assessment in URS, except for one domain more suited to clinical assessment (P = 0.226). There was excellent intraclass correlation (ICC) overall between the two experts' judgements, ICC = 0.841 (95% confidence interval 0.767-0.893; P < 0.001, n = 88). CONCLUSIONS: We have developed the novel GAUES tool for cystoscopic, URS and TUR skills. Overall, we demonstrated good face, content and construct validity and excellent reliability, suggesting that the GAUES tool can be useful for endourological skills assessment.

Endoscopic surgical simulation using low-fidelity and virtual reality transurethral resection simulators in urology simulation boot camp course: trainees feedback assessment study.

OBJECTIVES: The objective of our study was to study trainees' feedback and rating of models for training transurethral resection of bladder lesions (TURBT) and prostate (TURP) during simulation. METHODS: The study was performed during the ''Transurethral resection (TUR) module" at the boot camp held in 2019. Prior to the course, all trainees were required to evaluate their experience in performing TURBT and TURP procedures. Trainees simulated resection on two different models; low-fidelity tissue model (Samed, GmBH, Dresden, Germany) and virtual reality simulator (TURPMentor, 3D Systems, Littleton, US). Following the completion of the module, trainees completed a questionnaire using a 5-point Likert scale to evaluate their assessment of the models for surgical training. RESULTS: In total, 174 simulation assessments were performed by 56 trainees (Samed Bladder-40, Prostate-45, TURPMentor Bladder-51, Prostate-37). All trainees reported that they had performed < 50 TUR procedures. The Samed model median scores were for appearance (4/5), texture (5/5), feel (5/5) and conductibility (5/5). The TURPMentor median score was for appearance (4/5), texture and feel (4/5) and conductibility (4/5). The most common criticism of the Samed model was that it failed to mimic bleeding. In contrast, trainees felt that the TURPMentor haptic feedback was inadequate to allow for close resection and did not calibrate movements accurately. CONCLUSIONS: Our results demonstrate that both forms of simulators (low-fidelity and virtual reality) were rated highly by urology trainees and improve their confidence in performing transurethral resection and in fact complement each other in providing lower tract endoscopic resection simulation.