Activation of Piezo1 channels enhances spontaneous contractions of isolated human bladder strips via acetylcholine release from the mucosa.

Enhanced spontaneous bladder contractions (SBCs) have been thought one of the important underlying mechanisms for detrusor overactivity (DO). Piezo1 channel has been demonstrated involved in bladder function and dysfunction in rodents. We aimed to investigate the modulating role of Piezo1 in SBCs activity of human bladder. Human bladder tissues were obtained from 24 organ donors. SBCs of isolated bladder strips were recorded in organ bath. Piezo1 expression was examined with reverse transcription-quantitative polymerase chain reaction and immunofluorescence staining. ATP and acetylcholine release in cultured human urothelial cells was measured. Piezo1 is abundantly expressed in the bladder mucosa. Activation of Piezo1 with its specific agonist Yoda1 (100 nM-100 µM) enhanced the SBCs activity in isolated human bladder strips in a concentration-dependent manner. The effect of Yoda1 mimicked the effect of a low concentration (30 nM) of carbachol, which can be attenuated by removing the mucosa, blocking muscarinic receptors with atropine (1 µM), and blocking purinergic receptors with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS, 30 µM), but not by tetrodotoxin (1 µM). Activation of urothelial Piezo1 with Yoda1 (30 µM) or hypotonic solution induced the release of ATP and acetylcholine in cultured human urothelial cells. In patients with benign prostatic hyperplasia, greater Piezo1 expression was observed in bladder mucosa from patients with DO than patients without DO. We conclude that upregulation and activation of Piezo1 may contribute to DO generation in patients with bladder outlet obstruction by promoting the urothelial release of ATP and acetylcholine. Inhibition of Piezo1 may be a novel therapeutic approach in the treatment of overactive bladder.

Functional Upregulation of TRPM3 Channels Contributes to Acute Pancreatitis-associated Pain and Inflammation.

Transient receptor potential melastatin M3 (TRPM3) channels have been recognized as a pain transducer in dorsal root ganglion (DRG) neurons in recent years. TRPM3 activation initiates neurogenic inflammation and is required for the development of inflammatory hyperalgesia. We aimed to evaluate the role of TRPM3 in pancreas sensory afferents in pancreatic nociception, neurogenic inflammation, and acute pancreatitis (AP)-associated pain. AP was induced by intraperitoneal (i.p.) injection of L-arginine in rats. TRPM3 expression in pancreatic DRG neurons, spontaneous or mechanical-stimulation-evoked pain behaviors, and the extent of inflammation were evaluated. We found that TRPM3 channels were expressed on pancreatic primary afferent nerve terminals containing calcitonin gene-related peptide (CGRP). Activation of TRPM3 in the pancreas by injection of its specific agonist CIM0216 (10 µM) induced pain, CGRP and substance P release, and neurogenic inflammation, as evidenced by edema, plasma extravasation, and inflammatory cell accumulation in the pancreas. Increased TRPM3 functional expression was detected in pancreatic DRG neurons from AP rats, and blocking TRPM3 activity with its antagonist (Primidone, 5 mg/kg, i.p.) attenuated AP-associated pain behaviors and pancreatic inflammation. Pre-incubation of pancreatic DRG neurons with nerve growth factor (NGF) enhanced the increase in intracellular Ca2+ induced by the TRPM3 agonist (CIM0216, 1 µM). Our findings indicate that, in addition to TRPV1 and TRPA1 channels, TRPM3 is another pain channel that has a critical role in pancreatic nociception, neurogenic inflammation, and AP-associated pain behaviors. TRPM3 may be a promising pharmaceutical target for AP pain treatment.

Comparison of sound touch elastography and quantification for assessing the renal pathologic changes in patients with proteinuria.

OBJECTIVE: Sound touch elastography (STE) and sound touch quantification (STQ) are novel imaging methods to evaluate tissue stiffness. This study aims to investigate renal stiffness in patients with chronic kidney disease (CKD) by STE and STQ, using renal biopsy as 'gold standard'. METHODS: Between 2019 January and 2022 June, 60 patients who underwent renal biopsy for proteinuria (cases) and 45 healthy volunteers (controls) at our hospital were included in this study. The maximum and mean elastic modulus (Emax, Emean) of region of interest in right kidney were measured by STE and STQ techniques. Biochemical profiles and renal biopsy findings were recorded. RESULTS: Both Emax and Emean measured by STE were significantly different between cases and controls. ROC analysis of STE measurements revealed using a cutoff of 13.53 kPa for Emax and 10.16 kPa for Emean, the area under the curve (AUC) to distinguish nephropathy from healthy was 0.718 and 0.744. Analysis of ROC for STQ measurements showed that using a cutoff value of 15.87 kPa for Emax and 9.95 kPa for Emean, the AUC for the nephropathy was 0.612 and 0.569. Emax and Emean values were significantly different among CKD patients with mild, moderate and severe pathological stage. The Emax value for STE was positively related to Scr, ß2-MG (r = 0.257, 0.292, p < 0.05). CONCLUSION: Both STE and STQ are non-invasive, feasible methods to quantitatively evaluate renal stiffness. STE is more effective than STQ in the diagnosis of CKD patients with proteinuria. CRITICAL RELEVANCE STATEMENT: Sound touch elastography is more effective than sound touch quantification in the diagnosis of chronic kidney disease patients with proteinuria. KEY POINTS: • Emax and Emean measured by STE were different between cases and controls. • Emax and Emean were different among CKD patients with different pathological stages. • The Emax value for STE was positively related to serum creatinine, ß2-microglobulin.

Effects of mineral species and petroleum components on thermal desorption behavior of petroleum-contaminated soil.

Thermal desorption (TD) behavior of high-concentration petroleum-contaminated soil (PCS) is affected by soil composition, especially inorganic minerals. In this study, the TD behavior of petroleum-contaminated quartz (original mineral) and kaoline (clay mineral) were compared with those of pure petroleum (Petro-free); their "saturate, aromatic, resin, and asphaltenes" (SARA) fractions were investigated using thermogravimetry and differential thermogravimetry (TG-DTG). The modelling of the petroleum removal kinetics was also analyzed to provide insights into the mechanism. The results revealed that the limiting factor controlling the desorption of petroleum from quartz (Petro-Qtz) and kaoline (Petro-Kln) is the minerals, which increased the effective TD temperature by 200 °C and decreased TD efficiency by 2%. Compared to Petro-Qtz, Petro-Kln showed a lower desorption efficiency of 5% and the process was accomplished at a higher temperature of 100 °C. The investigation on SARA fractions indicated that polar fractions (i.e., aromatics, resins, and asphaltenes) were strongly captured by the minerals. The increment of the TD temperature of petroleum (resins-160 °C > aromatics-20 °C > saturates-5 °C) increased with the polarity of petroleum components. These results could be validated by thermogravimetry-gas chromatography/mass spectroscopy (TG-GC/MS) through the delayed desorption of naphthalene and acenaphthene. Furthermore, the increment of the TD temperature of SARA fractions on kaoline was higher than those on quartz. This makes sense because the kaoline decreased the diffusion of hydrocarbons due to its porosity features and higher specific surface area (kaoline 5.3300 m2 g-1, quartz 0.1153 m2 g-1). In addition, the analysis of the desorption kinetic models showed that the observed hysteresis was related to the diffusion barrier caused by chemisorption (n＜1). In consequence, the Petro-Kln showed a lower desorption efficiency, a slower desorption, and as a result, a higher energy consumption (0.476 kW h) for thermal remediation than Petro-Qtz (0.238 kW h).

[Protective effects of cordycepin on renal proximal tubular cells injury induced by lipopolysaccharide].

OBJECTIVE: To investigate the protective effect and potential mechanism of cordycepin on renal proximal tubular cells injury induced by lipopolysaccharide (LPS). METHODS: Renal proximal tubular cells NRK-52E were incubated on a cell culture plated at a density of 1×105/mL for experiment, then divided into control group (Ctrl group), LPS group (cells were stimulated with 1 mg/L LPS), 10 µmol/L or 20 µmol/L cordycep in intervention groups (LPS+C 10 group and LPS+C 20 group). Cell viability was measured using cell counting kit-8 (CCK-8) reagent. The level of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining. The protein expressions of inflammatory factors intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1ß (IL-1ß), and nuclear factor-κB (NF-κB) were detected by Western blotting. RESULTS: Compared with the Ctrl group, LPS significantly inhibited NRK-52E cell viability, increased intracellular ROS, and up-regulated the expressions of ICAM-1, VCAM-1, IL-1ß and NF-κB. Compared with LPS group, after treated with 10 µmol/L or 20 µmol/L cordycepin, NRK-52E cell viability was significantly increased (Ctrl group as 1: 0.717±0.017, 0.916±0.036 vs. 0.554±0.046) and intracellular ROS level was significantly decreased (Ctrl group as 1: 1.527±0.165, 1.098±0.168 vs. 2.543±0.127), meanwhile the expressions of ICAM-1, VCAM-1, IL-1ß and NF-κB were significantly down-regulated [Ctrl group as 1, ICAM-1/GAPDH: 2.364±0.097, 1.561±0.074 vs. 3.101±0.121; VCAM-1/GAPDH: 2.866±0.135, 1.920±0.098 vs. 4.170±0.119; IL-1ß/GAPDH: 2.358±0.107, 1.563±0.179 vs. 3.301±0.210; phosphorylation NF-κB p65 (NF-κB p-p65)/GAPDH: 2.559±0.166, 1.596±0.148 vs. 3.183±0.098], the differences were statistically significant (all P < 0.05). Compared with the LPS+C 10 group, the cell activity of LPS+C 20 group was more significant (0.916±0.036 vs. 0.717±0.017, P < 0.01), and the expressions of ICAM-1, VCAM-1, IL-1ß, NF-κB were down-regulated more significantly (ICAM-1/GAPDH: 1.561±0.074 vs. 2.364±0.097, VCAM-1/GAPDH: 1.920±0.098 vs. 2.866±0.135, IL-1ß/GAPDH: 1.563±0.179 vs. 2.358±0.107, NF-κB p-p65/GAPDH: 1.596±0.148 vs. 2.559±0.166, all P < 0.05). CONCLUSIONS: Cordycepin could significantly increase the survival rate of NRK-52E cells, reduce intracellular ROS level, and inhibit inflammation, and the anti-inflammation effect can be related with NF-κB pathway.

Independent Variables for Determining the Cumulative Live Birth Rates of Aged Patients with Polycystic Ovary Syndrome or Tubal Factor Infertility: A Retrospective Cohort Study.

Objective: To assess whether women of advanced age (≥35 years) with polycystic ovary syndrome (PCOS) have the same cumulative live birth rate (CLBR) as their age-matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs of aged women. Design: A retrospective cohort study. Setting and Population: A total of 160 women of advanced age (≥35 years) with PCOS and 1073 women with tubal factor infertility were included in our study. All patients underwent their first fresh cycles and subsequent frozen cycles within in one year in our centre from 2015 to 2020. Methods: To determine independent influencing factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR according to the transfer cycle type was constructed. Main outcome measure(s): CLBRs. Result: The Cox regression model of the CLBRs indicated that there was no significant difference between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.95; 95% CI, 0.71-1.27, P=0.732). The CLBR significantly decreased for women of advanced reproductive age up to 37 years of age (HR, 0.46; 95% CI, 0.39-0.56, P<0.001). The CLBR increased by 63% when more than ten oocytes were retrieved (HR, 1.63; 95% CI, 1.34-1.98, P<0.001). Patients with an AMH level above 32.13pmol/l were likely to have a 72%(HR, 1.72; 95% CI, 1.08-2.73, = 0.023) and 34% (HR, 1.34; 95% CI, 1.07-1.68, P=0.010)improvement in CLBR compared to those with an AMH below 7.85pmol/l and 7.85-32.12pmol/l, respectively. Conclusion: Despite the higher number of oocytes retrieved in PCOS patients, the reproductive window is not extended for PCOS patients compared with tubal factor infertility patients. Age, AMH and the number of oocytes retrieved play crucial roles in the CLBRs of patients of advanced age (≥35 years).

Nurses' ethical challenges caring for people with COVID-19: A qualitative study.

BACKGROUND: Ethical challenges are common in clinical nursing practice, and an infectious environment could put nurses under ethical challenges more easily, which may cause nurses to submit to negative emotions and psychological pressure, damaging their mental health. PURPOSE: To examine the ethical challenges encountered by nurses caring for patients with the novel coronavirus pneumonia (COVID-19) and to provide nurses with suggestions and support regarding promotion of their mental health. RESEARCH DESIGN AND METHOD: A qualitative study was carried out using a qualitative content analysis. The participants were 18 nurses who agreed to attend an interview and describe their own experiences of providing care to COVID-19 patients in China. They were purposively sampled, and structured, in-depth interviews were performed. Data were iteratively collected and analyzed from February to March 2020. ETHICAL CONSIDERATIONS: The proposal was approved by the Research Ethics Committee of the Second Hospital of Shandong University, China. FINDINGS: The findings revealed three main themes and 10 categories. The themes were the following: (1) ethical challenges (people with COVID-19, inequality, professional ethics, and job competency); (2) coping styles (active control and planning, seeking support as well as catharsis, and staying focused); and (3) impacts on career (specialized nursing skills, scientific research ability, and management skills). CONCLUSION: Nurses faced ethical challenges on multiple fronts in caring for COVID-19 patients. The results may help nurses with more safety, ethics, and humanistic care in nursing practice.

Real-time transrectal ultrasound-guided seminal vesiculoscopy for the treatment of patients with persistent hematospermia: A single-center, prospective, observational study.

This study aimed to describe endoscopic anatomy of the seminal tract and summarize our experience of transutricular seminal vesiculoscopy (TSV) guided by real-time transrectal ultrasonography (TRUS) in managing persistent hematospermia. A total of 281 consecutive patients with persistent hematospermia who underwent TSV with or without real-time TRUS were enrolled in this single-center, prospective, observational study. The median follow-up period was 36.5 (range: 8.0-97.5) months. TSV was successfully performed in 272 (96.8%) patients. The approach of a 4.5/6 F rigid vesiculoscope entering the seminal tract was categorized into four types on the basis of endoscopic presentation of the ejaculatory duct orifice and verumontanum. Seven (2.6%), 74 (27.2%), 64 (23.5%), and 127 (46.7%) patients had Types I (through the ejaculatory duct in the urethra), II (through the ejaculatory duct in the prostatic utricle), III (transutricular fenestration through a thin membrane), and IV (real-time transrectal ultrasound-guided transutricular fenestration) approach, respectively. In patients who successfully underwent surgery, bleeding occurred in the seminal vesicle in 249 (91.5%) patients. Seminal vesiculitis, calculus in the prostatic utricle, calculus in the ejaculatory duct, calculus in the seminal vesicle, prostatic utricle cysts, and seminal vesicle cysts were observed in 213 (78.3%), 96 (35.3%), 22 (8.1%), 81 (29.8%), 25 (9.2%), and 11 (4.0%) patients, respectively. Hematospermia was alleviated or disappeared in 244 (89.7%) patients 12 months after surgery. Fifteen patients had recurrent hematospermia, and the median time to recurrence was 7.5 (range: 2.0-18.5) months. TSV guided by TRUS may contribute to successful postoperative outcomes in managing persistent hematospermia.

Neonatal outcomes of singleton live births with vanishing twin syndrome following double embryos transfer in assisted reproductive technology: a retrospective cohort study.

BACKGROUND: Women with vanishing twin syndrome are associated with increased risks of adverse neonatal outcomes, such as preterm birth (PTB) and low birthweight (LBW), compared with those in singleton live births following single embryo transfer (SET) in assisted reproductive technology (ART). METHODS: Anonymized data on all cycles performed in China were obtained from the Reproductive Medicine Department at the Third Affiliated Hospital of Zhengzhou University, which had involved 127597 cycles following double embryos transfer (DET), including 54585 fresh embryos transfer (ET) cycles and 73012 frozen embryos transfer (FET) cycles. In addition, the obstetric outcomes, such as gestation age, PTB, small for gestation age (SGA), birthweight (BW), LBW, congenital malformation, pediatric admission and Neonatal Intensive Care Unit (NICU) admission in the fresh ET and FET cycles, were analyzed. Moreover, logistic regression analysis was performed to adjust the confounders, including age of women, body weight index (BMI), value of AMH, infertile years, current cycle, antral follicles, cause of infertility, number of oocytes retrieved, endometrial thickness at the date of transplantation, number of high-quality embryos, and embryo stage. RESULTS: In the fresh ET cycles, the BW and gestational age in study group were lower than those in control group, which were (2962.4 ± 563.1vs. 3104.9 ± 498. 5, p = 0.000) and (262.8 ± 8.4 vs. 268.9 ± 13.9, p = 0.000), respectively. Relative to control group, the study group was linked with increased risks of PTB (adjusted odds ratio (aOR) 2.45, 95% CI:1.98-3.03, adjusted p = 0.000), LBW (aOR2.11, 95% CI:1.67-2.65, adjusted p = 0.000), pediatric admission (aOR 2.55, 95% CI2.07-3.13, adjusted p = 0.000), and NICU admission (aOR 1.98, 95% CI1.32-2.96, adjusted p = 0.001), but there were no statistically significant differences in the risks of SGA (aOR 1.09, 95% CI0.82-1.45, adjusted p = 0.960) and congenital malformation (aOR 0.94, 95% CI0.53-1.68, adjusted p = 0.640) between the two groups. In the FET cycles, the gestational age and BW in study group were lower than those in control group, which were (263.0 ± 15.7vs. 273.0 ± 10.5, p = 0.000) and (3099 ± 662.1vs. 3352 ± 671.5), respectively. The study group was associated with increased risks of PTB (aOR2. 45, 95% CI: 2.23-3.43, adjusted p = 0.000), LBW (aOR 2.67, 95% CI: 2.13-3.34, adjusted p = 0.000), pediatric admission (aOR2.62, 95% CI2.14-3.21, adjusted p = 0.000), and NICU admission (aOR 2.22, 95% CI1.43, 3.46, adjusted p = 0.001) compared with those in control group, but differences in the risks of SGA (aOR 0.98, 95% CI0.71-1.36, adjusted p = 0.730) and congenital malformation (aOR 0.99, 95% CI 0.60,1.63, adjusted p = 0.940) between the two groups were not statistically significant. CONCLUSIONS: Our study finds that singleton live births with VTS have higher risks of LBW, PTB, pediatric admission and NICU admission than those without VTS in both the fresh and frozen cycles, even after adjusting for confounders. However, no increased risks of SGA or congenital malformation are observed in singleton live births in both the fresh and frozen ART cycles following DET.

Mean platelet volume might be an effective indicator of arterial erectile dysfunction.

The aim of our study was to investigate the role of platelet parameters including mean platelet volume (MPV) and platelet count (PC) in the pathogenesis of penile arteriogenic erectile dysfunction (ED) and to evaluate the association between the platelet parameters and arteriogenic ED. There were 244 patients with ED (based on the International Index of Erectile Function [IIEF]-5 ≤21) and 60 healthy controls (IIEF-5 >21) enrolled. All participants were asked to undergo a laboratory examination, and penile vascular function was evaluated using penile color Doppler ultrasonography (pDUS). Among these ED patients, 24 patients with no abnormality on nocturnal penile tumescence (NPT) and 84 with normal vasculature or mixed vascular abnormalities were excluded. The other patients were classified into three groups as follows: control (n = 60), arteriogenic ED (n = 99), and venous leakage (n = 37) groups. MPV and PC were significantly higher in the arteriogenic ED group compared with the venous and control groups (P < 0.05). Receiver operating characteristic curve analysis revealed that the area under the curve for MPV to predict arteriogenic ED was 0.707. MPV ≥9.65 fl was recognized as a cut-off value for potential arteriogenic ED (sensitivity: 47.5%; specificity: 91.7%). A significant inverse correlation was detected between MPV and 10-min peak systolic velocity (PSV) (r = -0.34; P < 0.001) in the arteriogenic ED group. These findings suggest that the MPV might be a powerful indicator to predict and diagnose arteriogenic ED, and MPV may be a marker for ED when using pDUS.

Uretero-fallopian fistula after hysteroscopy fallopian tube embolization: a case report.

BACKGROUND: Uretero-fallopian fistula (UFF) is a very rare surgery complication which usually happens after surgeries of fallopian tube or ureter. There has been no report of interventional operations of fallopian tube causing UFF. CASE PRESENTATION: A 41-year-old female received fallopian tube embolization for birth control. After that she noticed "clear vaginal discharge". She neglected that symptom for 7 years, until a sudden onset of abdominal pain brought her to the ER. Retrograde ureterogram confirmed UFF and revealed severe hydronephrosis of the left kidney. She received left nephrectomy afterwards and recovered well, with no urine leakage from her vagina. CONCLUSION: UFF could be caused by interventional operations of fallopian tube, and could lead to severe consequences. The application of fallopian tube embolization should be carefully controlled.

Recellularization of well-preserved decellularized kidney scaffold using adipose tissue-derived stem cells.

To establish a recellularization kidney model by using adipose tissue-derived stem cells (ADSCs) as seeding cells and to investigate the growth and differentiation of ADSCs in decellularized kidney scaffolds. ADSCs were isolated using a modified method and then identified using flow cytometry analysis. Osteogenesis and adipogenesis differentiation were performed. Rat kidneys were decellularized using 0.5% sodium dodecyl sulfate. Immunofluorescence, immunohistochemistry, and scanning electron microscope were conducted to examine the scaffold microstructure. The decellularized kidney scaffold was seeded with ADSCs antegrade through the artery or retrograde through the ureter and cultured for 5-10 days. Hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry were applied to assess growth and differentiation of seeding cells within the scaffold. ADSCs populated within the glomerular, vascular, and tubular area of kidney scaffolds. Cells differentiated toward endothelial or tubular cells. Stromal cell-derived factor 1 promoted cell attachment in the scaffold. These findings suggest that ADSCs can be used as an additional new source of seeding cells within decellularized kidney scaffold. This combination may offer an alternative to donor kidney transplant. In this way, autologous ADSCs can be utilized as seeding cells in cell-scaffold kidney regeneration for further clinical transplantation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 805-814, 2018.

Transcutaneous electrical stimulation of somatic afferent nerves in the foot relieved symptoms related to postoperative bladder spasms.

BACKGROUND: Bladder spasm is a common side effect of urological surgery. Main treatment modalities include opioids or anticholinergic medication; however, bladder spasms still occur even after these interventions. Recent studies indicate that transcutaneous stimulation of the foot can result in 50% increase in bladder capacity in healthy adults, and inhibit bladder detrusor overactivity in spinal cord injured patients. In this study, we examined the effects of transcutaneous electrical stimulation of the foot on bladder spasms related symptoms. METHODS: Sixty-six male patients who underwent prostate or bladder surgeries due to benign prostatic hyperplasia or bladder diseases were randomly divided into two groups: the control group (n = 36) and the treatment group (n = 30). The control group received the routine postoperative care. The treatment group received daily transcutaneous electrical stimulation of the foot during 3 days after surgery; each time lasted for 60 min. All patients were evaluated by the Visual Analogue Scale for pain sensation, frequency of bladder spasm episodes, and a total score of bladder spasms symptoms. RESULTS: In the control group, the patients with bladder surgery had a higher Visual Analogue Scale score than patients with prostate surgery (P = 0.024). In both treatment and control groups, the Visual Analogue Scale score, spasm frequency, and total score of bladder spasm symptoms decreased from day 1 to day 3 (P <0.001). The Visual Analogue Scale score at day 2, total score of bladder spasm symptoms at day 2 and day 3 were significantly lower in the treatment group than in the control group (P <0.05). CONCLUSION: These results provided preliminary evidence suggesting beneficial effects of stimulating somatic afferent nerves in the foot on postoperative bladder spasms. TRIAL REGISTRATION: The study was registered with Chinese Clinical Trial Registry on June 13 2016 ( http://www.chictr.org.cn/ ) (Identifier: ChiCTR-INR-16008635).

Post-stimulation block of frog sciatic nerve by high-frequency (kHz) biphasic stimulation.

This study determined if high-frequency biphasic stimulation can induce nerve conduction block that persists after the stimulation is terminated, i.e., post-stimulation block. The frog sciatic nerve-muscle preparation was used in the study. Muscle contraction force induced by low-frequency (0.5 Hz) nerve stimulation was recorded to indicate the occurrence and recovery of nerve block induced by the high-frequency (5 or 10 kHz) biphasic stimulation. Nerve block was observed during high-frequency stimulation and after termination of the stimulation. The recovery from post-stimulation block occurred in two distinct phases. During the first phase, the complete block induced during high-frequency stimulation was maintained. The average maximal duration for the first phase was 107 ± 50 s. During the second phase, the block gradually or abruptly reversed. The duration of both first and second phases was dependent on stimulation intensity and duration but not frequency. Stimulation of higher intensity (1.4-2 times block threshold) and longer duration (5 min) produced the longest period (249 ± 58 s) for a complete recovery. Post-stimulation block can be induced by high-frequency biphasic stimulation, which is important for future investigations of the blocking mechanisms and for optimizing the stimulation parameters or protocols in clinical applications.

A modified natural cycle results in higher live birth rate in vitrified-thawed embryo transfer for women with regular menstruation.

There is no consensus regimen for the optimal endometrial preparation for cryopreservation and vitrified-thawed embryo transfer cycles. This is largely caused by the lack of sufficient investigation and analyses on the respective pregnancy and perinatal outcomes by different regimens. This study aimed to compare both pregnancy and perinatal outcomes between the modified natural and artificial cycles in vitrified-thawed day three embryo transfer for women with regular menstruation. A total of 1,482 vitrified-thawed day three embryo transfer cycles were reviewed including 427 modified natural cycles (NC), 132 ovulation induction cycles (OC), 794 artificial cycles (AC), and 129 GnRH agonist artificial cycles (GAC). The primary outcome that was evaluated was live birth rate. The NC regimen demonstrated a higher rate of ongoing pregnancy (43.8% vs. 30.2%, P = 0.002) and a lower rate of late abortion (2.8% vs. 14.0%, P = 0.003) than the GAC regimen as well as a higher implantation rate (31.9% vs. 27.1%, P = 0.008) and live birth rate (43.1% vs. 34.1%, P = 0.002) than the AC regimen. A significantly higher peak endometrial thickness before transfer was observed in patients using the NC and GAC regimens (10.0 ± 1.7, 9.9 ± 2.4) compared to the AC regimens (9.2 ± 1.5, P = 0.000). Multivariate logistic regression showed that the NC protocol was associated with a higher live birth rate. There were no significant differences in rates of pregnancy complications, neonatal mortality, birth defects, mean birth weight, and other perinatal outcomes among the regimens. Modified natural cycle endometrial preparation regimen for vitrified-thawed day three embryo transfer is associated with superior live birth pregnancy outcomes compared to artificial cycles. Future studies are warranted to investigate the underlying biologic mechanisms of these findings. Abbreviations ART: assisted reproductive technology; BMI: body mass index; FET: frozen-thawed embryo transfer; HCG: human chorionic gonadotropin; IVF: in-vitro fertilization; IVF-ET: in-vitro fertilization and embryo transfer; OHSS: ovarian hyperstimulation syndrome; RCTs: randomized controlled trials.

Role of glycine in nociceptive and non-nociceptive bladder reflexes and pudendal afferent inhibition of these reflexes in cats.

AIM: This study examined the role of glycinergic transmission in nociceptive and non-nociceptive bladder reflexes and in inhibition of these reflexes by pudendal nerve stimulation (PNS). METHODS: Cystometrograms (CMGs) were performed in α-chloralose anesthetized cats by intravesical infusion of saline or 0.25% acetic acid (AA) to trigger, respectively, non-nociceptive or nociceptive bladder reflexes. PNS at 2 or 4 times threshold (T) intensity for inducing anal twitch was used to inhibit the bladder reflexes. Strychnine (a glycine receptor antagonist) was administered in cumulative doses (0.001-0.3 mg/kg, i.v.) at 60-120 min intervals. RESULTS: Strychnine at 0.001-0.3 mg/kg significantly (P < 0.05) increased bladder capacity and reduced contraction amplitude during saline CMGs but did not change these parameters during AA CMGs except at the 0.3 mg/kg dose which increased bladder capacity. Strychnine did not alter PNS inhibition during saline CMGs except at the highest dose at 2T intensity, but significantly (P < 0.05) suppressed PNS inhibition during AA CMGs after 0.001-0.003 mg/kg doses at 2T and 4T intensities. During AA CMGs strychnine (0.3 mg/kg) also unmasked a post-PNS excitatory effect that significantly reduced bladder capacity after termination of PNS. CONCLUSIONS: Glycinergic inhibitory neurotransmission in the central nervous system plays an unexpected role to tonically enhance the magnitude and reduce the bladder volume threshold for triggering the non-nociceptive bladder reflex. This is attributable to inhibition by glycine of another inhibitory mechanism. Glycine also has a minor role in PNS inhibition of the nociceptive bladder reflex. Neurourol. Urodynam. 35:798-804, 2016. © 2015 Wiley Periodicals, Inc.

Role of µ, κ, and δ opioid receptors in tibial inhibition of bladder overactivity in cats.

In α-chloralose anesthetized cats, we examined the role of opioid receptor (OR) subtypes (µ, κ, and δ) in tibial nerve stimulation (TNS)-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative i.v. doses of selective OR antagonists (cyprodime for µ, nor-binaltorphimine for κ, or naltrindole for δ ORs) was tested. Naloxone (1 mg/kg, i.v., an antagonist for µ, κ, and δ ORs) was administered at the end of each experiment. AA caused bladder overactivity and significantly (P < 0.01) reduced bladder capacity to 21.1% ± 2.6% of the saline control. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement significantly (P < 0.01) restored bladder capacity to 52.9% ± 3.6% or 57.4% ± 4.6% of control, respectively. Cyprodime (0.3-1.0 mg/kg) completely removed TNS inhibition without changing AA control capacity. Nor-binaltorphimine (3-10 mg/kg) also completely reversed TNS inhibition and significantly (P < 0.05) increased AA control capacity. Naltrindole (1-10 mg/kg) reduced (P < 0.05) TNS inhibition but significantly (P < 0.05) increased AA control capacity. Naloxone (1 mg/kg) had no effect in cyprodime pretreated cats, but it reversed the nor-binaltorphimine-induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pretreated cats. These results indicate a major role of µ and κ ORs in TNS inhibition, whereas δ ORs play a minor role. Meanwhile, κ and δ ORs also have an excitatory role in irritation-induced bladder overactivity.

Outcomes of Microscopic Subinguinal Varicocelectomy With and Without the Assistance of Doppler Ultrasound: A Randomized Clinical Trial.

OBJECTIVE: To compare the surgical outcomes and complications between microscopic subinguinal varicocelectomy (MV) and intraoperative vascular Doppler ultrasound-assisted microscopic subinguinal varicocelectomy (IVDU-MV) for infertile patients with varicoceles. MATERIALS AND METHODS: One hundred seventy-two infertile patients with varicoceles were randomly divided into IVDU-MV group (n = 85) and MV group (n = 87). We assessed patients' operative and postoperative parameters, semen parameters, and the pregnancy rate. The mean follow-up period was 21 months (range, 13-34 months). RESULTS: The operative time was significantly shorter in the IVDU-MV group than MV group (41.9 ± 13.6 vs 52.7 ± 14.1 minutes, P <.05). The number of intraoperative arteries spared was significantly greater in the IVDU-MV group than the MV group (1.9 ± 0.8 vs 1.3 ± 0.7, P <.05). In addition, the average number of spermatic veins ligated was significantly greater in the IVDU-MV group (7.8 ± 2.1 vs 7.0 ± 1.9, P <.05). Lymphatic spared showed no significant difference (P >.05). The postoperative hospital stay showed no significant difference. Sperm concentration, sperm motility, and the percentage of grade a+b sperm were significantly increased in both groups at 3, 6, and 12 months after surgery (P <.05), and the sperm motility was higher in IVDU-MV than MV group (43.98 ± 7.64 vs 36.98 ± 5.10, P <.05) in 12 months after surgery. Sperm morphology was comparable between the 2 groups. The pregnancy rate showed no significant difference (36.8% of the MV vs 34.1% of the IVDU-MV, P >.05). CONCLUSION: Our study demonstrated that both MV and IVDU-MV are effective methods for the improvement of semen parameters in infertile men with varicocele, with a natural conception rate of 35% over a mean follow-up of 21 months. Compared with MV, IVDU-MV is superior in shortening operative time, increasing the number of spermatic arteries spared, spermatic veins ligated, and sperm motility after surgery. IVDU should be routinely used as an effective tool to improve outcomes and safety of varicocelectomy.

Role of the brain stem in tibial inhibition of the micturition reflex in cats.

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P < 0.05) increased bladder capacity to 30-60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300-900 µg) eliminated acute TNS inhibition and significantly (P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes.