The clinical effect of Dienogest on urinary and sexual symptoms in endometriosis patients.

BACKGROUND: To evaluate the effect on urinary symptoms and sexual functioning of Dienogest within a 6-month period of follow-up. METHODS: A total of 22 women who were diagnosed as having endometriosis with pelvic pain and irritative urinary symptoms were recruited in this study. The participating patients took a daily dose of 2 mg DNG and underwent outpatient visits at the beginning, 1, 2, 3 and 6 months following treatment. RESULTS: Our data showed a significant improvement of the VAS score since the 1st month till the 6th month after treatment of DNG. OABSS, UDI-6 and IIQ-7 were significantly improved after the treatment of DNG. Besides, serum estradiol was also decreased. Our data also showed that DNG treatment for 6 months did not affect FSFI score. Some patients with heavy menstruation were also improved; however, some patients with regular periods missed or dropped a period after DNG treatment, while other adverse effects were also shown. CONCLUSION: Our study demonstrated that DNG could not only alleviate endometriosis pelvic pain but reduce urinary symptoms within the 6-month follow-up as well. DNG did not affect sexual function in FSFI score, although some adverse effects were recorded.

Comorbid Attention Deficit Hyperactivity Disorder in Women with Premenstrual Dysphoric Disorder.

Background: This study evaluated the associations between inattention, impulsivity, and attention deficit hyperactivity disorder (ADHD) in women with premenstrual dysphoric disorder (PMDD) across the menstrual cycle. Methods: This study enrolled 58 women with PMDD and 50 controls. Symptoms were assessed using the Attention and Performance Self-Assessment Scale and the Dickman Impulsivity Inventory during the pre-ovulatory (PO), mid-luteal (ML), and late luteal (LL) phases of the menstrual cycle. Results: The chi-square analysis revealed a significant association between ADHD and PMDD. Women with PMDD experienced a greater increase in scores of prospective everyday memory problems and difficulties maintaining focused attention from the PO phase to LL phase than the controls; in addition, they had higher scores in dysfunctional impulsivity during the LL phase than the controls. Among women in the PMDD group, those with ADHD had higher scores in prospective everyday memory problems and dysfunctional impulsivity during the PO and ML phases than those without ADHD. Women in the PMDD group without ADHD had a greater increase in scores of prospective everyday memory problems, difficulties maintaining focused attention, and dysfunctional impulsivity from the PO phase to the LL phase than the controls. Conclusion: Our study demonstrated that women with PMDD were more likely to have comorbid ADHD and higher levels of inattention across the menstrual cycle. PMDD was associated with increased impulsivity during the LL phase, independent of ADHD, but it was not associated with a persistent elevation of impulsivity. Furthermore, PMDD women with comorbid ADHD experienced higher inattention and impulsivity during the PO and ML phases than those without it. Thus, ADHD comorbidity should be assessed when assessing or intervening in the symptoms of inattention and impulsivity in women with PMDD.

Ni-Catalyzed Csp2 and Csp3 Coupling for Divergent Bisboronic Ester Synthesis.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

Estrogen, progesterone, cortisol, brain-derived neurotrophic factor, and vascular endothelial growth factor during the luteal phase of the menstrual cycle in women with premenstrual dysphoric disorder.

The interplay between ovarian hormones, stress, and inflammatory markers in developing premenstrual dysphoric disorder (PMDD) remains inadequately understood. This study investigated the associations of dynamic changes in the levels of estrogen, progesterone, cortisol, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) with PMDD during the luteal phase of the menstrual cycle. A total of 58 women with PMDD and 50 healthy women were recruited in this study. These women's estrogen, progesterone, cortisol, BDNF, and VEGF levels were evaluated during the preovulation (PO), mid-luteal (ML), and late-luteal (LL) phases. Furthermore, the severity of P MDD symptoms, depressive symptoms, perceived stress, inattention, craving for sweet foods, and fatigue was assessed. The findings revealed that women with PMDD with higher levels of progesterone during the ML or LL phase or a greater increase (ML-PO) or higher sum (ML + LL) of luteal progesterone level exhibited a greater increase in PMDD symptoms during the luteal phase than did the healthy controls. Furthermore, women with PMDD exhibited higher cortisol levels during the LL phase than did the controls. The BDNF level was negatively correlated with PMDD severity. Furthermore, BDNF and VEGF levels were negatively correlated with inattention and craving for sweet foods among women with PMDD. These results suggest an association between progesterone and the exacerbation of PMDD symptoms during the LL phase. Women with PMDD have relatively high cortisol levels during the LL phase. Future investigations with experimental designs or larger sample sizes are warranted to verify the roles of progesterone and cortisol in the development of PMDD.

The Neuroprotective Effect of Isotetrandrine on Parkinson's Disease via Anti-Inflammation and Antiapoptosis In Vitro and In Vivo.

Parkinson's disease (PD) is one of the most influential diseases in the world, and the current medication only can relieve the clinical symptoms but not slow the progression of PD. Therefore, we intend to examine the neuroprotective activity of plant-derived compound isotetrandrine (ITD) in vitro and in vivo. In vitro, cells were cotreated with ITD and LPS to detect the inflammatory-related protein and mRNA. In vivo, zebrafish were pretreated with ITD and inhibitors prior to 6-OHDA treatment. Then, the behavior was monitored at 5 dpf. Our result showed ITD inhibited LPS-induced upregulation of iNOS, COX-2 protein expression, and iL-6, inos, cox-2, and cd11b mRNA expression in BV2 cells. The data in zebrafish also demonstrated a significant improvement of ITD on the 6-OHDA-induced locomotor deficiency. ITD also improved 6-OHDA-induced apoptosis in zebrafish PD. We also pharmacologically validated the mechanism with three inhibitors, including LY294002, PI3K inhibitor; LY32141996, ERK inhibitor, SnPP, and HO-1 inhibitors. All of these inhibitors could abolish the neuroprotective effect of ITD partially in locomotor activity. Besides, the molecular level also showed the same trend. Treatment of these inhibitors could significantly abolish ITD-induced antineuroinflammatory and antioxidative stress effects in zebrafish PD. Our study showed ITD possessed a neuroprotective activity in zebrafish PD. The mRNA level also supported our arguments. The neuroprotection of ITD might be through antineuroinflammation and antiapoptosis pathways via PI3K, ERK, and HO-1.

Effect of pelvic floor muscles exercises by extracorporeal magnetic innervations on the bladder neck and urinary symptoms.

BACKGROUND: This study aimed to investigate the changes in the bladder neck (BN) and urinary symptoms using extracorporeal magnetic innervation (ExMI) therapy before and after performing passive pelvic floor exercises. METHODS: Twenty women with stress urinary incontinence (SUI) were assessed by transperineal ultrasound and questionnaires before and after the ExMI therapy from January 2011 to February 2021. RESULTS: The incidence of urinary frequency and SUI were significantly decreased after the therapy (McNemar test, p < 0.01). The therapeutic efficacy of SUI was 75%. A significant decrease was noted in pad test results (paired t test, p < 0.05). At the same time, there was a considerable difference in Urinary Distress Inventory-6 scale measures (paired t test, p < 0.001). However, results for the Incontinence Impact Questionnaire-7 showed a marginally significant difference (paired t test, p = 0.066). Three domains of lubrication, orgasm, and satisfaction in the Female Sexual Function Index showed significant differences (paired t test, p < 0.05). Transperineal ultrasound found that BN mobility and Q-tip straining angle were not statistically significant (paired t test, p > 0.05). CONCLUSION: The ExMI is effective for SUI by strengthening the pelvic floor muscle without significantly decreasing BN mobility.

Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers.

Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell-targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells.

Emission Wavelength-Tunable Bicyclic Dioxetane Chemiluminescent Probes for Precise In Vitro and In Vivo Imaging.

Chemiluminescent probes have become increasingly popular in various research areas including precise tumor imaging and immunofluorescence analysis. Nevertheless, previously developed chemiluminescence probes are mainly limited to studying oxidation reaction-associated biological events. This study presents the first example of bioimaging applicable bicyclic dioxetane chemiluminescent probes with tunable emission wavelengths that range from 525 to 800 nm. These newly developed probes were able to detect the analytes of ß-Gal, H2O2, and superoxide with high specificity and a limit of detection of 77 mU L-1, 96, and 28 nM, respectively. The bioimaging application of the probes was verified in ovarian and liver cancer cells and macrophage cells, allowing the detection of the content of ß-Gal, H2O2, and superoxide inside the cells. The high specificity allowed us to image the xenografted tumor in mice. We expect that our probes will receive extensive applications in recording complex biomolecular events using noninvasive imaging techniques.

Relationship between Q-Tip Test and Urethral Hypermobility on Perineal Ultrasound.

BACKGROUND: The aim of this study was to assess the correlation between the overall rest-stress distance measured by transperineal ultrasound (TPUS) and Q-tip test angle in women with urodynamic stress incontinence (USI), and determine a cut-off value of rest-stress distance for predicting urethral hypermobility (UH). METHODS: Women with USI scheduled for mid-urethral sling surgery were retrospectively recruited. UH was defined as a Q-tip angle more than or equal to 30 degrees. Ultrasonic measurement of the overall rest-stress distance was defined as the linear distance of bladder-neck position change from resting status to maximal strain. RESULTS: Among the 132 enrolled women, the Pearson correlation coefficient between the overall rest-stress distance in TPUS and Q-tip test angle was 0.9104 (95% CI, 0.8758-0.9357, p < 0.001). In receiver-operating-characteristic-curve analysis, a rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH (sensitivity = 76.47%, specificity = 93.3%; area = 0.937, 95% confidence interval: 0.881-0.972). CONCLUSIONS: The overall rest-stress distance in TPUS correlated well with the Q-tip test angle, indicating that it can be an alternative method for the assessment of USI. A rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH in women with USI.

Tape-Releasing Suture with "Long Loop" on Mid-Urethral Sling: A Novel Procedure for Management of Iatrogenic Urethral Obstruction.

BACKGROUND: To report our experiences of a tape-releasing suture with "long-loop" in women with iatrogenic urethral obstruction following the mid-urethral sling procedure. METHODS: A total of 149 women underwent a tape-releasing suture with "Long Loop" during the operation. Post-void residual volume was evaluated after Foley removal. Lower urinary tract symptoms and urodynamic studies were assessed before and six months postoperatively. RESULTS: Nine women out of 149 who underwent mid-urethral sling surgery were found to have iatrogenic urethral obstruction post-operatively based on their urinary symptoms and ultrasound findings. There was no apparent difference between tested groups in mid-urethral sling products and concomitant procedures. 77.8% had successful releases after the first Long-loop manipulation procedure, and 22.2% required two or more releases. However, the SUI cure rate is similar in groups receiving the Long-loop manipulation or not (88.9% and 87.1%, respectively). CONCLUSIONS: We are convinced of the practicability and efficacy of the tape-releasing suture "Long-loop." We adopted subjective and objective means to evaluate both groups before and after a six-month follow-up. The Long-loop manipulation procedure can successfully resolve the iatrogenic urethral obstruction without compromising the effectiveness of mid-urethral sling for the treatment of SUI.

Ni-Catalyzed Protecting Group Free Diphenic Acid Analog Synthesis.

Severe side effects and drug resistance are major drawbacks of Pt-based chemotherapy in clinical practice, leading to the search for new Pt-based drugs through the tuning of coordination ligands. Therefore, seeking appropriate ligands has attracted significant interest in this area. In this study, we report a Ni-catalyzed coupling strategy for the divergent synthesis of diphenic acid derivatives and the application of these newly prepared acids in Pt(II) agent synthesis.

Favorable cervical cancer mortality-to-incidence ratios of countries with good human development index rankings and high health expenditures.

BACKGROUND: Cervical cancer is highly preventable. The mortality-to-incidence ratio (MIR) is a marker that reflects the available screening interventions and clinical outcomes of cancer treatments. The association between the MIR for cervical cancer and cancer screening disparities among countries is an interesting issue but rarely investigated. The present study sought to understand the association between the cervical cancer MIR and the Human Development Index (HDI). METHODS: Cancer incidence and mortality rates were obtained from the GLOBOCAN database. The MIR was defined as the ratio of the crude mortality rate to the incidence rate. We used linear regression to analyze the correlation of MIRs with the HDI and current health expenditure (CHE) in 61 countries selected based on data quality. RESULTS: The results showed lower incidence and mortality rates and MIRs in more developed regions. In terms of regional categories, Africa had the highest incidence and mortality rates and MIRs. The incidence and mortality rates and MIRs were lowest in North America. Furthermore, favorable MIRs were correlated with a good HDI and high CHE as a percentage of gross domestic product (CHE/GDP) (both p < 0.0001). CONCLUSIONS: The MIR variation for cervical cancer is associated with the ranking of the health system and health expenditure, which further supports the role of cancer screening and treatment disparities in clinical outcomes. The promotion of cancer screening programs can reduce the cervical cancer global incidence and mortality rates and MIRs.

Zinc Finger Protein 90 Knockdown Promotes Cisplatin Sensitivity via Nrf2/HO-1 Pathway in Ovarian Cancer Cell.

Our study discussed the role of Zfp90 in ovarian cancer (OC) cell lines' sensitivity to cisplatin. We used two OC cell lines, SK-OV-3 and ES-2, to evaluate their role in cisplatin sensitization. The protein levels of p-Akt, ERK, caspase 3, Bcl-2, Bax, E-cadherin, MMP-2, MMP-9 and other drug resistance-related molecules, including Nrf2/HO-1, were discovered in the SK-OV-3 and ES-2 cells. We also used a human ovarian surface epithelial cell to compare the effect of Zfp90. Our outcomes indicated that cisplatin treatment generates reactive oxygen species (ROS) that modulate apoptotic protein expression. The anti-oxidative signal was also stimulated, which could hinder cell migration. The intervention of Zfp90 could greatly improve the apoptosis pathway and block the migrative pathway to regulate the cisplatin sensitivity in the OC cells. This study implies that the loss of function of Zfp90 might promote cisplatin sensitization in OC cells via regulating the Nrf2/HO-1 pathway to enhance cell apoptosis and inhibit the migrative effect in both SK-OV-3 and ES-2 cells.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder.

PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.

A time-frame comparison study of surgical volume shifts on female primary stress urinary incontinence surgery.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the surgical volume shifts for primary female stress urinary incontinence (SUI) over a 20-year period (1999-2018) in Taiwan. METHODS: This was a retrospective cohort study based on Taiwan's National Health Insurance Research Database. We divided the time-frame into four periods: first period (1999-2003), second period (2004-2008), third period (2009-2013), and fourth period (2014-2018). The variables included major surgical types for SUI (retropubic urethropexy, pubovaginal sling, midurethral sling, etc.), surgeon gender, specialty, surgical volume (high ≥30, median 5-29, low <5), and hospital accreditation level. Reoperation rates within 1 year were analyzed as an outcome measurement. RESULTS: A total of 51,018 patients were identified. Major surgical types increased significantly during the first three periods and slightly decreased during the fourth period. The proportion of surgical volume shifted from high- to medium-, and low-volume, but it reversed during the fourth period. The proportion of SUI surgeries decreased in medical centers, whereas it increased in regional and local hospitals. The proportion of SUI surgeries by female surgeons increased. Similar phenomena occurred in MUS. As for surgeon specialty, major surgical types were performed by gynecologists and urologists equally, whereas MUS were performed more by gynecologists than by urologists. Unexpectedly, 1-year reoperation rates were higher in high-volume surgeons. CONCLUSIONS: The surgical trend of SUI surgeries shifted from high- to medium-, and low-volume surgeons, medical centers to regional and local hospitals during the study periods. This implied surgical skills and performance spreading, which may have a great influence on patient and healthcare provider choice of treatment.

The Clinical Effects of Pixel CO2 Laser on Bladder Neck and Stress Urinary Incontinence.

Background: Our study aims to assess Pixel CO2 laser efficacy for female stress urinary incontinence (SUI). Methods: In the study, 25 women with SUI were included and scheduled for vaginal Pixel CO2 Laser (FemiLift™, Alma Lasers, Israel) treatment. All subjects had a baseline and 6-month post-treatment assessment that included three-dimensional perineal ultrasound and validated questionnaires. Results: Data showed that monthly three-session vaginal Pixel CO2 Laser treatment significantly improved SUI symptoms, as evidenced by validated questionnaires, including UDI-6, IIQ-7, ICIQ, and vaginal laxity questionnaire (p < 0.05). The Pixel CO2 Laser efficacy in vaginal treatment was 20/25 (80%), and the perineal sonography showed that laser treatment significantly decreased bladder neck mobility and middle urethral area (during resting and straining). Permanent adverse events were not found. Conclusions: The results of our study suggested that for the treatment of mild to moderate SUI symptoms, Pixel CO2 Laser is effective and safe; however, more studies and a longer follow-up should be conducted to confirm its efficacy and durability.