Contained specimen morcellation during robotics-assisted laparoscopic supracervical hysterectomy for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Robotics-assisted laparoscopic supracervical hysterectomy (RALSH) with concomitant apical robotics-assisted POP repair provides advantages of minimally invasive procedures; however specimen removal without intraperitoneal spillage of potential pathology remains challenging. The primary aim of our study is to determine the factors affecting contained manual morcellation (CMM) of specimens during RALSH for POP surgery. The secondary aim of the study is to report complications associated with CMM and on specimen pathology. METHODS: A total of 67 sequential patients underwent RALSH with concomitant robotics-assisted sacrocolpopexy or uterosacral vaginal suspension. Factors analyzed to affect CMM were specimen weight, length of skin and fascia incisions, patient age, body mass index (BMI), and estimated blood loss (EBL). RESULTS: Median CMM time was 11 min (1 to 46) and specimen weight 62 g (19 to 711). Median patient age was 56 years (36 to 83), and patient BMI was 28 (18 to 44). Median EBL was 50 ml (10 to 150). Median skin and fascial incision lengths were 3 cm (1.5 to 7), and 3.5 cm (1.5 to 8). CMM time was significantly dependent on specimen weight (p < 0.0001) and length of rectus fascia incision (p < 0.0126). There was no gross tissue spillage or bag ruptures. Uterine pathology revealed normal tissue (26%), leiomyoma (47%), adenomyosis (49%), and endometriosis (14%). 4.5% of specimens had evidence of microscopic neoplasm, and 5 years after surgery patients were cancer free. CONCLUSION: Contained manual extraction of the uterus and/or adnexae at the time of RALSH for POP surgery is a viable, safe, and efficient method of specimen removal.

Impact of microbiota and host immunologic response on the efficacy of anticholinergic treatment for urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Studies within the past decade have suggested associations among composition of the urinary microbiota, local immune responses, and urinary incontinence symptoms. To investigate these relationships, we evaluated the structure of the urinary microbiome, local inflammatory markers, and patient responses prior to and at 6-weeks after treatment with anticholinergic medication for urgency urinary incontinence (UUI). METHODS: Using a prospective pilot study, we enrolled women who presented with UUI symptoms and were prescribed treatment with anticholinergics. Catheterized urine samples were collected from participants at their baseline and 6-week follow-up visits for microbiological (standard and 16S rRNA gene phylotyping analyses) and cytokine analysis along with the UDI-6 questionnaire and 2-day bladder diary. RESULTS: Patients were Caucasian, post- menopausal, with a median age of 64 and median BMI of 30.1 kg/m2. Among the patients, 75% had UUI symptoms for less than 2 years, but with a frequency of at least a few times a week or every day. Most women were prescribed 10 mg oxybutynin ER daily at enrollment. Patients had varied urinary microbiota by culture and 16S phylotyping, with species of Lactobacillus being the most common, in six samples, in addition to taxa associated with Enterococcus, Staphylococcus, and mixed flora. Cytokine levels showed no differences before and after treatment with anticholinergics, nor correlation with urinary bacteria or microbiome composition. CONCLUSIONS: Our pilot study suggests factors in addition to the urinary microbiome and local immune responses may be involved in patients' response to anticholinergics for UUI.

Perioperative use of pain medications in vaginal versus laparoscopic pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: There has been renewed interest in the management of postoperative pain after benign gynecological surgery. The purpose of the study was to determine if the use of intraoperative and immediate postoperative pain medication differs between vaginal and laparoscopic surgery in women with pelvic organ prolapse. METHODS: The study included women who had undergone pelvic organ prolapse repair between 2014 and 2019 in two tertiary care hospitals. We collected demographic data and pain medication used during and after surgery, including opioids, local anesthetics, gabapentin, ketorolac, ibuprofen, and acetaminophen. Data analyses were performed using STATA Version 16.1. A p value <0.05 was considered to indicate statistical significance. RESULTS: A total of 195 women were included in the study, with 98 in the vaginal and 97 in the laparoscopic group. Intraoperative opioid use in the two groups was similar (25 morphine milligram equivalent [MME], p = 0.34). However, women in the laparoscopic group received significantly more intravenous and local anesthesia (lidocaine: 60 vs 40 mg; bupivacaine 49.6 vs 20 ml, p < 0.001). Postoperatively, although women in the vaginal group required almost twice as many narcotics as those in the laparoscopy group (MME = 28 vs 15, p < 0.001), after controlling for confounders in the multivariate analysis, there were no differences in postoperative pain requirements between the two groups. Recovery time had a significant impact on opioid and acetaminophen use (p < 0.05). CONCLUSION: Use of pain medication was similar in the intraoperative and immediate postoperative period after pelvic organ prolapse surgery when comparing the vaginal and laparoscopic approaches after controlling for potential confounding factors.

A Novel Method of Endotoxins Removal from Chitosan Hydrogel as a Potential Bioink Component Obtained by CO2 Saturation.

The article presents a new approach in the purification of chitosan (CS) hydrogel in order to remove a significant amount of endotoxins without changing its molecular weight and viscosity. Two variants of the method used to purify CS hydrogels from endotoxins were investigated using the PyroGene rFC Enzymatic Cascade assay kit. The effect of the CS purification method was assessed in terms of changes in the dynamic viscosity of its hydrogels, the molecular weight of the polymer, microbiological purity after refrigerated storage and cytotoxicity against L929 cells based on the ISO 10993-5:2009(E) standard. The proposed purification method 1 (M1) allows for the removal of significant amounts of endotoxins: 87.9-97.6% in relation to their initial concentration in the CS hydrogel without affecting the solution viscosity. Moreover, the final solutions were sterile and microbiologically stable during storage. The M1 purification method did not change the morphology of the L929 cells.

Antifungal Effect of Penicillamine Due to the Selective Targeting of L-Homoserine O-Acetyltransferase.

Due to the apparent similarity of fungal and mammalian metabolic pathways, the number of established antifungal targets is low, and the identification of novel ones is highly desirable. The results of our studies, presented in this work, indicate that the fungal biosynthetic pathway of L-methionine, an amino acid essential for humans, seems to be an attractive perspective. The MET2 gene from Candida albicans encoding L-homoserine O-acetyltransferase (CaMet2p), an enzyme catalyzing the first step in that pathway, was cloned and expressed as the native or the oligo-His-tagged fusion protein in Escherichia coli. The recombinant enzymes were purified and characterized for their basic molecular properties and substrate specificities. The purified MET2 gene product revealed the appropriate activity, catalyzed the conversion of L-homoserine (L-Hom) to O-acetyl-L-homoserine (OALH), and exhibited differential sensitivity to several L-Hom or OALH analogues, including penicillamine. Surprisingly, both penicillamine enantiomers (L- and D-Pen) displayed comparable inhibitory effects. The results of the docking of L- and D-Pen to the model of CaMet2p confirmed that both enantiomeric forms of the inhibitor are able to bind to the catalytic site of the enzyme with similar affinities and a similar binding mode. The sensitivity of some fungal cells to L-Pen, depending on the presence or absence of L-Met in the medium, clearly indicate Met2p targeting. Moreover, C. glabrata clinical strains that are resistant to fluconazole displayed a similar susceptibility to L-Pen as the wild-type strains. Our results prove the potential usefulness of Met2p as a molecular target for antifungal chemotherapy.

Targeting DNA Topoisomerase II in Antifungal Chemotherapy.

Topoisomerase inhibitors have been in use clinically for the treatment of several diseases for decades. Although those enzymes are significant molecular targets in antibacterial and anticancer chemotherapy very little is known about the possibilities to target fungal topoisomerase II (topo II). Raising concern for the fungal infections, lack of effective drugs and a phenomenon of multidrug resistance underlie a strong need to expand the range of therapeutic options. In this review paper, we discussed the usefulness of fungal topo II as a molecular target for new drug discovery. On the basis of previously published data, we described structural and biochemical differences between fungal and human enzymes as well as a molecular basis of differential sensitivity to known anticancer drugs targeting the latter. This review focuses especially on highlighting the differences that may underlie the selectivity of action of new inhibitors. Distinct sites within fungal topo II in comparison with human counterparts are observed and should be further studied to understand the significance of those sites and their possible usage in design of new drugs.

Pelvic organ prolapse after 3 modes of hysterectomy: long-term follow-up.

BACKGROUND: There are various indications and approaches for hysterectomy; yet, the difference in long-term risk of subsequent prolapse after surgery is not well studied. OBJECTIVE: To assess the risk of prolapse after abdominal, vaginal, and laparoscopic or robotic hysterectomy for up to 17 years from surgery. STUDY DESIGN: A retrospective chart review study of women undergoing hysterectomy across all indications (benign and malignant) between 2001 and 2008 was conducted. An equivalent random sample of hysterectomy patients was selected each year. We compared demographic and other surgical characteristics data including age, race, parity, body mass index, indication and year of hysterectomy, blood loss, cervix removal, cuff suspension, and complications using chi-square, Kruskal-Wallis test, and Fisher's exact across the 3 groups. Presence and treatment of subsequent prolapse (based on patient symptoms, pelvic exam, International Classification of Diseases, Ninth Revision diagnosis, and current procedural terminology pessary or surgical codes) were compared with Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: Of the 2158 patients, 1459, 375, and 324 underwent open, vaginal, and laparoscopic or robotic hysterectomy, respectively. The vaginal group (56) was older than the abdominal (52) or laparoscopic or robotic (49) groups, with a P value of <.05. Most patients were White with a mean body mass index of 30 kg/m2. The main indication was cancer for abdominal (33%) and laparoscopic or robotic hysterectomy (25%) and prolapse for vaginal hysterectomy (60%). Time to prolapse was shortest after vaginal surgery (27 months) and longest after laparoscopic or robotic surgery (71 months). After controlling for confounders, including surgery indication, the hazard ratio for subsequent prolapse was no different among vaginal (hazard ratio=1.36 [0.77-2.45]), laparoscopic or robotic (hazard ratio=1.47 [0.80-2.69]), or open (reference) hysterectomy. Prolapse grade was similar across the 3 groups. About 50% of women with recurrent prolapse received physical therapy, pessary, or surgical treatment. CONCLUSION: At the 17-year follow-up, the route of hysterectomy is not associated with a difference in recurrence, grade, or subsequent treatment of prolapse when the indication for hysterectomy is considered. Prolapse, as an indication for hysterectomy, increases risk for recurrence. Women planning a hysterectomy should be counseled appropriately about the risk of subsequent prolapse.

A new 1-nitro-9-aminoacridine derivative targeting yeast topoisomerase II able to overcome fluconazole-resistance.

Fungal resistance remains a significant threat and a leading cause of death worldwide. Thus, overcoming microbial infections have again become a serious clinical problem. Although acridine derivatives are widely analyzed as anticancer agents, only a few reports have demonstrated their antifungal activity. In an effort to develop biologically active antifungals, twelve novel C-857 (9-(2'-hydroxyethylamino)-1-nitroacridine) and C-1748 (9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine) derivatives were synthesized. The evaluation of biological properties suggests that starting compounds: C-1748, C-857 and IE3 (2-[(4-methyl-1-nitroacridin-9-yl)amino]ethyl lysinate), IE4 (2-[(1-nitroacridin-9-yl)amino]ethyl lysinate) antifungal mode of action differ from that determined for IE5 (N'-{3-[(4-methyl-1-nitroacridin-9-yl)amino]propyl}lysinamide), IE6 (N'-{3-[(1-nitroacridin-9-yl)amino]propyl}lysinamide) and IE10 (3,3'-Bis-(1-nitroacridin-9-ylamino)-aminoethylaminoethylaminoethylamine). Although MIC values determined for the latter were higher, in contrast to C-857 and C-1748, newly synthesized IE5, IE6 and IE10 reduced C. albicans hyphal growth in different inducing media. Those compounds also exhibited antibiofilm activity, whereas IE10 was the most effective. Moreover, only IE6 exhibited antifungal activity against fluconazole resistant C. albicans strains with MICs values in the range of 16-64 µg mL-1. Our results also indicate that, in contrast to other analyzed derivatives, novel synthetized compounds IE6 and IE10 with antifungal activity target yeast topoisomerase II activity.

The Effect of Conjugation with Octaarginine, a Cell-Penetrating Peptide on Antifungal Activity of Imidazoacridinone Derivative.

Acridine cell-penetrating peptide conjugates are an extremely important family of compounds in antitumor chemotherapy. These conjugates are not so widely analysed in antimicrobial therapy, although bioactive peptides could be used as nanocarriers to smuggle antimicrobial compounds. An octaarginine conjugate of an imidazoacridinone derivative (Compound 1-R8) synthetized by us exhibited high antifungal activity against reference and fluconazole-resistant clinical strains (MICs ≤ 4 µg mL-1). Our results clearly demonstrate the qualitative difference in accumulation of the mother compound and Compound 1-R8 conjugate into fungal cells. Only the latter was transported and accumulated effectively. Microscopic and flow cytometry analysis provide some evidence that the killing activity of Compound 1-R8 may be associated with a change in the permeability of the fungal cell membrane. The conjugate exhibited low cytotoxicity against human embryonic kidney (HEK-293) and human liver (HEPG2) cancer cell lines. Nevertheless, the selectivity index value of the conjugate for human pathogenic strains remained favourable and no hemolytic activity was observed. The inhibitory effect of the analysed compound on yeast topoisomerase II activity suggested its molecular target. In summary, conjugation with R8 effectively increased imidazoacridinone derivative ability to enter the fungal cell and achieve a concentration inside the cell that resulted in a high antifungal effect.

Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics.

Three aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans→ all trans photochemical isomerization. The obtained all-trans isomers demonstrated substantially improved in vitro selective toxicity in the Candida albicans cells: human erythrocytes model. This effect was mainly due to the diminished hemotoxicity. The molecular modeling studies on interactions between original antibiotics and their photoisomers with ergosterol and cholesterol revealed some difference in free energy profiles of formation of binary antibiotic/sterol complexes in respective membrane environments. Moreover, different geometries of heptaene: sterol complexes and variations in polyene macrolide molecule alignment in cholesterol-and ergosterol-containing membranes were found. None of these effects are of the crucial importance for the observed improvement of selective toxicity of aromatic heptaene antifungals but each seems to provide a partial contribution.

'Acridines' as New Horizons in Antifungal Treatment.

Frequent fungal infections in immunocompromised patients and mortality due to invasive mycosis are important clinical problems. Opportunistic pathogenic Candida species remain one of the leading causes of systemic mycosis worldwide. The repertoire of antifungal chemotherapeutic agents is very limited. Although new antifungal drugs such as lanosterol 14α-demethylase and ß-glucan synthase inhibitors have been introduced into clinical practice, the development of multidrug resistance has become increasingly significant. The urgency to expand the range of therapeutic options for the treatment of fungal infections has led researchers in recent decades to seek alternative antifungal targets to the conventional ones currently used. Among them, many compounds containing an acridine scaffold have been synthesized and tested. In this review, the applicability of acridines and their functional analogues acridones as antifungal agents is described. Acridine derivatives usage in photoantifungal chemotherapy, interactions with fungal transporters resulting in modulation of efflux/influx pumps and the effect of acridine derivatives on fungal topoisomerases are discussed. This article explores new perspectives on the mechanisms of antifungal acridine-peptide conjugates and acridine-based hybrid molecules to effectively combat fungal infections.

Crystal structures of aminotransferases Aro8 and Aro9 from Candida albicans and structural insights into their properties.

Aminotransferases catalyze reversibly the transamination reaction by a ping-pong bi-bi mechanism with pyridoxal 5'-phosphate (PLP) as a cofactor. Various aminotransferases acting on a range of substrates have been reported. Aromatic transaminases are able to catalyze the transamination reaction with both aromatic and acidic substrates. Two aminotransferases from C. albicans, Aro8p and Aro9p, have been identified recently, exhibiting different catalytic properties. To elucidate the multiple substrate recognition of the two enzymes we determined the crystal structures of an unliganded CaAro8p, a complex of CaAro8p with the PLP cofactor bound to a substrate, forming an external aldimine, CaAro9p with PLP in the form of internal aldimine, and CaAro9p with a mixture of ligands that have been interpreted as results of the enzymatic reaction. The crystal structures of both enzymes contains in the asymmetric unit a biologically relevant dimer of 55 kDa for CaAro8 and 59 kDa for CaAro9p protein subunits. The ability of the enzymes to process multiple substrates could be related to a feature of their architecture in which the active site resides on one subunit while the substrate-binding site is formed by a long loop extending from the other subunit of the dimeric molecule. The separation of the two functions to different chemical entities could facilitate the evolution of the substrate-binding part and allow it to be flexible without destabilizing the conservative catalytic mechanism.

Versatility of putative aromatic aminotransferases from Candida albicans.

Amino acids constitute the key sources of nitrogen for growth of Candida albicans. In order to survive inside the host in different and rapidly changing environments, this fungus must be able to adapt via its expression of genes for amino acid metabolism. We analysed the ARO8, ARO9, YER152C, and BNA3 genes with regards to their role in the nutritional flexibility of C. albicans. CaAro8p is undoubtedly the most versatile enzyme among the aminotransferases investigated. It is involved in the catabolism of histidine, lysine, and aromatic amino acids as well as in l-Lys, Phe and Tyr biosynthesis. CaAro9p participates in the catabolism of aromatic amino acids and lysine at high concentrations of these compounds, with no biosynthetic role. Conversely, the CaYer152Cp catalytic potential for aromatic amino acid catabolism observed in vitro appears to be of little importance in vivo. Neither biosynthetic nor catabolic roles of CaBan3p were observed for any proteinogenic amino acid. Finally, none of the analysed aminotransferases was solely responsible for the catabolism of a single particular amino acid or its biosynthesis.

Non-invasive therapeutic use of High-Intensity Focused Ultrasound (HIFU) with 3 Tesla Magnetic Resonance Imaging in women with symptomatic uterine fibroids.

Benign uterine fibroids are common female genital tract tumors and if symptomatic often require extensive surgery. When tumors are multiple and large or unusually located, the operative treatment may lead to significant morbidity and compromise quality of life. Recovery period after surgical treatment may be complicated by patient's medical condition and wound healing problems. Currently used other non-surgical treatment modalities usually provide only a temporal symptoms relief and may not be efficient in all affected women. In the last decade, minimally invasive treatment of uterine fibroids called Magnetic Resonance guided High-Intensity Focused Ultrasound (MRI HIFU) was introduced. This technique uses thermal ablation simultaneously with MRI imaging of the mass and tissue temperature measurements during the procedure where a focused ultrasound beam is applied externally to destroy tumors located in the human body. Successful application of MRI HIFU has been recently described in patients with various malignancies, such as breast, prostate and hepatocellular cancers as well as soft tissue and bone tumors. This technique is innovative and has been proven to be safe and effective but there are several limitations for treatment. The article highlights the relative advantages and disadvantages of MRI guided HIFU in women with uterine fibroids. The authors also describe high-resolution MRI technique on 3T MRI, along with the approach to interpretation of HIFU results applied to uterine fibroids that has been experienced at one institution.

Characterization of recombinant homocitrate synthase from Candida albicans.

LYS21 and LYS22 genes from Candida albicans encoding isoforms of homocitrate synthase (HCS), an enzyme catalyzing the first committed step in the l-lysine biosynthetic pathway, were cloned and expressed as N-oligoHistagged fusion proteins in Escherichia coli. The purified gene products revealed HCS activity, i.e. catalyzed the condensation of α-ketoglutarate with acetyl-coenzyme A to yield homocitrate. The recombinant enzymes were purified to homogeneity and characterized for their physical properties and substrate specificities. As determined by size-exclusion chromatography (SEC) and native page electrophoresis, both isoenzymes adopt multiple quaternary structures, with the homotetrameric one being the most abundant. The KM (acetyl-CoA)=0.8±0.15mM and KM (α-ketoglutarate)=0.113±0.02mM for His6CaLys21p and KM (acetyl-CoA)=0.48±0.09mM and KM (α-ketoglutarate)=0.152±0.03mM values for His6CaLys22p were determined. Both enzyme versions were inhibited by l-Lys, i.e. the end product of the α-aminoadipate pathway but Lys22p was more sensitive than Lys21p, with Ki (L-Lys)=128±8µM for His6CaLys21p and Ki (L-Lys)=4.37±0.68µM for His6CaLys22p. The isoforms of C. albicans HCS exhibited differential sensitivity to several l-Lys analogues. Most notably, dl-α-difluoromethyllysine strongly inhibited His6CaLys22p (IC50 32±3µM) but was not inhibitory at all towards His6CaLys21p. Differential sensitivity of recombinant C. albicans Δlys21/LYS22, LYS21/Δlys22 and Δlys21/Δlys22 mutant strains to lysine analog, 2-aminoethyl-l-cysteine and biochemical properties of homocitrate synthase isoforms suggest different roles of two HCS isoenzymes in α-aminoadipate pathway.

Inhibitors of amino acids biosynthesis as antifungal agents.

Fungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit growth defect or at least reduced virulence under in vivo conditions. Several chemical compounds inhibiting activity of one of these enzymes exhibit good antifungal in vitro activity in minimal growth media, which is not always confirmed under in vivo conditions. This article provides a comprehensive overview of the present knowledge on pathways of amino acids biosynthesis in fungi, with a special emphasis put on enzymes catalyzing particular steps of these pathways as potential targets for antifungal chemotherapy.

Phenotypic consequences of LYS4 gene disruption in Candida albicans.

A BLAST search of the Candida Genome Database with the Saccharomyces cerevisiae LYS4 sequence known to encode homoaconitase (HA) revealed ORFs 19.3846 and 19.11327. Both alleles of the LYS4 gene were sequentially disrupted in Candida albicans BWP17 cells using PCR-based methodology. The null lys4Δ mutant exhibited lysine auxotrophy in minimal medium but was able to grow in the presence of l-Lys and α-aminoadipate, an intermediate of the α-aminoadipate pathway, at millimolar concentrations. The presence of d-Lys and pipecolic acid did not trigger lys4Δ growth. The C. albicans lys4Δ mutant cells demonstrated diminished germination ability. However, their virulence in vivo in a murine model of disseminated neonatal candidiasis appeared identical to that of the wild-type strain. Moreover, there was no statistically significant difference in fungal burden of infected tissues between the strains.

Oncofertility as an Essential Part of Comprehensive Cancer Treatment in Patients of Reproductive Age, Adolescents and Children.

The number of children, adolescents and young adults diagnosed with cancer has been rising recently. Various oncological treatments have a detrimental effect on female fertility, and childbearing becomes a major issue during surveillance after recovery. This review discusses the impact of oncological treatments on the ovarian reserve with a thorough explanation of oncologic treatments' effects and modes of oncofertility procedures. The aim of this review is to help clinicians in making an informed decision about post-treatment fertility in their patients. Ultimately, it may lead to improved overall long-term outcomes among young populations suffering from cancer.

Prevalence of urinary incontinence and prolapse after hysterectomy for benign disease versus gynecologic malignancy.

OBJECTIVES: To estimate the prevalence of UI and POP after hysterectomy for benign disease and gynecologic malignancy. This is a retrospective cohort chart review study. Two major urban tertiary care centers between 2006-2010. Women ≥ 18 years undergoing hysterectomy for benign or malignant indications. MATERIAL AND METHODS: Presence of UI and POP was based on patient report in clinic notes, ICD-9 UI and POP diagnosis codes, and CPT codes for treatment. Prevalence of UI and POP after hysterectomy and time to development of UI and POP after hysterectomy. RESULTS: 1363 (55%) women underwent hysterectomy for benign disease while 1107 (45%) had a hysterectomy for malignancy. Postoperative prevalence of UI and POP in the benign versus the malignant group was 15.1% vs 11.1% (p = 0.001), and 12.1% vs 2.8%, (p < 0.001), respectively. The median time to development of UI in the subset of patients without preoperative UI was 3.5 years in the benign group vs 3 years in the malignant group (p < 0.001). The median time to development of POP in the subset of patients without preoperative POP was 5 years in the benign group and 3.5 years in the malignant group (p < 0.001). There was no significant difference in the risk of developing UI or POP between groups after adjusting for confounders or when accounting for pre-hysterectomy UI or POP. CONCLUSIONS: When pre-hysterectomy UI or POP is taken into consideration, there is no difference in the prevalence of post-hysterectomy UI or POP.

Smartphone-Assisted and Optical Quantification of Copper and Glucose Using Palm Wine-Tailored Carbon Dots and Their Multiple Logic Gate Application.

In this work, potassium, sulfur, nitrogen, and chlorine self-doped carbon dots (CDs) were hydrothermally synthesized using palm wine as a carbon source. The palm wine-derived CDs (PW-CDs) are amorphous in nature and displayed an average particle size of 4.19 ± 0.89 nm. The as-synthesized CDs are used to fabricate a photoluminescent sensing probe to simultaneously detect Cu2+ and glucose via the "Turn ON-OFF-ON" mechanism. The PL quenching mechanism of PW-CDs enables the selective and sensitive detection of Cu2+ ions with a detection limit (LOD) of 0.8 ppb (4.7 nM). The sensing probe quantified Cu2+ in tap water, drinking water, and e-waste samples to prove its viability. Using CDs to quantify copper in e-waste leachate samples is a novel approach as no prior instances of such application have been reported. The system's performance is considered to be highly reproducible due to the relative standard deviation being <6.64%, along with excellent recoveries within the range of 93.24-109.86%. The quenched PL can be recovered by introducing glucose into the PW-CD + Cu2+ system; this strategy is employed to quantify glucose with a LOD of 0.11 ppm (0.61 µM). The feasibility of this sensor was confirmed by the determination of glucose in actual human plasma specimens of diabetic patients. It is to be noted that these samples were neither diluted nor spiked with glucose. The developed PW-CD + Cu2+ sensing system yields satisfactory recoveries of 93.45-107.37%. This probe was also incorporated into a smartphone-based sensing platform to detect Cu2+ and glucose with desirable recoveries. The proposed smartphone-based sensing platform is flexible, reliable, and accurate, making it suitable for resource-constrained areas. Furthermore, based on the effect of Cu2+ ions and glucose on the PL response and absorbance spectra of PW-CDs, four logic gates (YES, IMPLICATION, NOT, and OR) were designed, and PW-CDs were also used for cell imaging applications.