Sodium valproate rescues expression of TRANK1 in iPSC-derived neural cells that carry a genetic variant associated with serious mental illness.

Biological characterization of genetic variants identified in genome-wide association studies (GWAS) remains a substantial challenge. Here we used human-induced pluripotent stem cells (iPSC) and their neural derivatives to characterize common variants on chromosome 3p22 that have been associated by GWAS with major mental illnesses. IPSC-derived neural progenitor cells carrying the risk allele of the single nucleotide polymorphism (SNP), rs9834970, displayed lower baseline TRANK1 expression that was rescued by chronic treatment with therapeutic dosages of valproic acid (VPA). VPA had the greatest effects on TRANK1 expression in iPSC, NPC, and astrocytes. Although rs9834970 has no known function, we demonstrated that a nearby SNP, rs906482, strongly affects binding by the transcription factor, CTCF, and that the high-affinity allele usually occurs on haplotypes carrying the rs9834970 risk allele. Decreased expression of TRANK1 perturbed expression of many genes involved in neural development and differentiation. These findings have important implications for the pathophysiology of major mental illnesses and the development of novel therapeutics.

PLS Subspace-Based Calibration Transfer for Near-Infrared Spectroscopy Quantitative Analysis.

In order to enable the calibration model to be effectively transferred among multiple instruments and correct the differences between the spectra measured by different instruments, a new feature transfer model based on partial least squares regression (PLS) subspace (PLSCT) is proposed in this paper. Firstly, the PLS model of the master instrument is built, meanwhile a PLS subspace is constructed by the feature vectors. Then the master spectra and the slave spectra are projected into the PLS subspace, and the features of the spectra are also extracted at the same time. In the subspace, the pseudo predicted feature of the slave spectra is transferred by the ordinary least squares method so that it matches the predicted feature of the master spectra. Finally, a feature transfer relationship model is constructed through the feature transfer of the PLS subspace. This PLS-based subspace transfer provides an efficient method for performing calibration transfer with only a small number of standard samples. The performance of the PLSCT was compared and assessed with slope and bias correction (SBC), piecewise direct standardization (PDS), calibration transfer method based on canonical correlation analysis (CCACT), generalized least squares (GLSW), multiplicative signal correction (MSC) methods in three real datasets, statistically tested by the Wilcoxon signed rank test. The obtained experimental results indicate that PLSCT method based on the PLS subspace is more stable and can acquire more accurate prediction results.

Chronic Opioid Usage in Surgical Patients in a Large Academic Center.

OBJECTIVE: The objective of this study is to investigate the prevalence and disparity of chronic opioid usage in surgical patients and the potential risk factors associated with chronic opioid usage. BACKGROUND: Chronic opioid usage is common in surgical patients; however, the characteristics of opioid usage in surgical patients is unclear. In this study, we hypothesize that the prevalence of chronic opioid usage in surgical patients is high, and that significant disparities may exist among different surgical populations. METHODS: Data of opioid usage in outpatients among different surgical services were extracted from the electronic medical record database. Patient demographics, clinical characteristics of sex, age, race, body mass index (BMI), specialty visited, duration of opioid use, and opioid type were collected. Chronic opioid users were defined as patients who had been recorded as taking opioids for at least 90 days determined by the first and last visit dates under opioid usage during the investigation. RESULTS: There were 79,123 patients included in this study. The average prevalence is 9.2%, ranging from 4.4% to 23.8% among various specialties. The prevalence in orthopedics (23.8%), neurosurgery (18.7%), and gastrointestinal surgery (14.4%) ranked in the top three subspecialties. Major factors influencing chronic opioid use include age, Ethnicitiy, Subspecialtiy, and multiple specialty visits. Approximately 75% of chronic users took opioids that belong to the category II Drug Enforcement Administration classification. CONCLUSIONS: Overall prevalence of chronic opioid usage in surgical patients is high with widespread disparity among different sex, age, ethnicity, BMI, and subspecialty groups. Information obtained from this study provides clues to reduce chronic opioid usage in surgical patients.

[Open construction of experimental abdominal aortic aneurysm swine models with Dacron patch for evaluating endovascular aneurysm repair techniques].

OBJECTIVE: To construct an experimental abdominal aortic aneurysm (AAA) swine model with Dacron patch for evaluating endovascular aneurysm repair (EVAR) technique. METHODS: The experimental pigs were generally anesthetized for the open procedure of an aneurysm model creation with Dacron and subsequent arteriography and EVAR with stent graft. Repeat arteriography was performed after 3-month follow-up. RESULTS: AAA models were successfully constructed in all 10 experimental pigs. The average aneurysm diameter was (26.3±3.1)mm, increasing by (15.7±3.1)mm comparing to the primary aorta diameter (10.5±0.4)mm. The aorta diameter before and after the experiment showed significant difference (P<0.001). All the animals were survived after the procedure. One swine died 24 hours after the subsequent EVAR because the covering of both renal arteries by the stent graft. The rest 9 animals survived well after the whole operation and 3-month follow-up. The surviving rates at 1 month and 3 months after the operation were both 90%. One type 2 endoleak (10%) was observed after the EVAR, which disappeared at 3-month follow-up. CONCLUSIONS: Open construction of experimental AAA swine models with Dacron patch is safe and feasible. The model can be used in the developing new EVAR techniques and implant training.

Off-policy two-dimensional reinforcement learning for optimal tracking control of batch processes with network-induced dropout and disturbances.

In this paper, a new off-policy two-dimensional (2D) reinforcement learning approach is proposed to deal with the optimal tracking control (OTC) issue of batch processes with network-induced dropout and disturbances. A dropout 2D augmented Smith predictor is first devised to estimate the present extended state utilizing past data of time and batch orientations. The dropout 2D value function and Q-function are further defined, and their relation is analyzed to meet the optimal performance. On this basis, the dropout 2D Bellman equation is derived according to the principle of the Q-function. For the sake of addressing the dropout 2D OTC problem of batch processes, two algorithms, i.e., the off-line 2D policy iteration algorithm and the off-policy 2D Q-learning algorithm, are presented. The latter method is developed by applying only the input and the estimated state, not the underlying information of the system. Meanwhile, the analysis with regard to the unbiasedness of solutions and convergence is separately given. The effectiveness of the provided methodologies is eventually validated through the application of a simulated case during the filling process.

A qualitative exploration of e-cigarette prevention advertisements' effectiveness among college students in China.

INTRODUCTION: The rapid growth of e-cigarette usage among youth and young people has emerged as a significant public health concern. It is imperative to initiate effective vaping prevention campaigns and undertake relevant research to address this pressing issue. This research seeks to identify effective video advertisements to deter young people from starting to use e-cigarettes. It aims to offer evidence-based insights and recommendations for creating communication materials and designing messages for youth e-cigarette prevention efforts. METHODS: College students aged 18-24 years (n=40) participated in focus groups within this qualitative study. After viewing four stimulus videos, participants discussed what they perceived as effective and ineffective video characteristics, as well as suggestions for future videos. RESULTS: Effective video characteristics included the use of real-life testimonials, displaying specific health hazards, revealing harmful chemical ingredients and the deceptive nature of flavors, and positively perceived effectiveness. Participants generally found that videos with strong visual impact and graphics were more engaging and that approaches using fear and emotion were more effective. Ineffective characteristics included complex and exaggerated information, lack of empathy and irrelevance, insufficiently specific information, extreme and death-themed content, industry messages, as well as preachy tones, animations, metaphors, dull formats, excessive length, and scenes of e-cigarette use. CONCLUSIONS: Developing anti-e-cigarette campaign materials for youth necessitates target audience-focused qualitative research. This helps in deeply exploring and identifying effective themes and messages, as well as video characteristics and details while avoiding ineffective or even misleading messages and themes from young people's perspectives outside the United States. Future development of e-cigarette prevention videos for Chinese college students may consider incorporating localized real-life testimonial cases to convey specific harms, including self-efficacy information, and utilizing fear and emotional appeals.

Phenolic Constituents from Black Quinoa Alleviate Insulin Resistance in HepG2 Cells via Regulating IRS1/PI3K/Akt/GLUTs Signaling Pathways.

Quinoa is a nutrient-rich pseudocereal with a lower glycemic index and glycemic load. However, its therapeutic potency and underlying mechanism against insulin resistance (IR) have not been fully elucidated. In this work, network pharmacology was applied to screen IR targets and their related pathways. The efficacy and mechanism of black quinoa polyphenols (BQP) on IR improvement were evaluated and uncovered based on the IR model in vitro combined with molecular docking. Ten phenolic constituents of BQP were detected, and the network pharmacology results show that PI3K/Akt pathways are the main pathways in BQP against IR. The in vitro assay proved that BQP increases the glucose consumption and glycogen synthesis via upregulating insulin receptor substrate 1 (IRS1)/PI3K/Akt/glucose transporters (GLUTs) signaling pathways to alleviate IR. Rutin, resveratrol, and catechin show lower binding energy docking with IRS1, PI3K, Akt, and GLUT4 proteins, indicating better interactions. It might be an effective constituent against IR. Hence, BQP could become a potential functional food source for blood glucose management among insulin-resistant people.

Unveiling alkali metal poisoning of CrMn catalyst for selective catalytic reduction of NOx with NH3: An experimental and theoretical study.

Alkali metal poisoning has been an intricate and unsolved issue confining the catalytic activity of NH3-SCR catalysts up to now. Herein, the effect of NaCl and KCl on catalytic activity of CrMn catalyst for NH3-SCR of NOx was systematically investigated to clarify the alkali metal poisoning by combined experiments and theoretical calculations. It unveiled that NaCl/KCl could deactivate CrMn catalyst due to the decrease in specific surface area, electron transfer (Cr5++Mn3+↔Cr3++Mn4+), redox ability and oxygen vacancy and NH3/NO adsorption. In addition, NaCl cut off E-R mechanism reactions by inactivating surface Brønsted/Lewis acid sites. DFT calculations revealed that (1) Na and K could weaken MnO bond, (2) competitive adsorption between Cl and NH3 was a main reason weakening Lewis acid, (3) Cl adsorption was also a major cause diminishing Brønsted acid and oxygen vacancy, (4) Both Na and K seriously impeded NO adsorption/activation, (5) NaCl/KCl increased the reaction heat of H2O desorption (rate-determining step) in E-R mechanism reactions and KCl elevated its energy barrier in L-H mechanism reactions. Thus, this study provides the deep understanding of alkali metal poisoning and a well strategy to synthesize NH3-SCR catalysts with outstanding alkali metal resistance.

Upconverting Nanoparticle-Based Photoactive Probes for Highly Efficient Labeling and Isolation of Target Proteins.

Photoaffinity labeling (PAL) has blossomed into a powerful and versatile tool for capture and identification of biomolecular targets. However, low labeling efficiency for specific targets such as lectins, the tedious process for protein purification, inevitable cellular photodamage, and less tissue penetration of UV light are significant challenges. Herein, we reported a near-infrared (NIR) light-driven photoaffinity labeling approach using upconverting nanoparticle (UCNP)-based photoactive probes, which were constructed by assembling photoactive groups and ligands onto NaYF4:Yb,Tm nanoparticles. The novel probes were easily prepared and functionalized, and the labeled proteins can be isolated and purified through simple centrifugation and washing. The advantages of this approach were demonstrated by labeling and isolation of peanut agglutinin (PNA), asialoglycoprotein receptor (ASGPR), and human carbonic anhydrase II (hCAII) from mixed proteins or cell lysates with good selectivity and efficiency, especially for PNA and ASGPR, two lectins that showed low binding affinity to their ligands. More importantly, successful labeling of PNA through pork tissues and ASGPR in mice strongly proved the good tissue penetrating capacity of NIR light and the application potential of UCNP-based photoactive probes for protein labeling in vivo. Biosafety of this approach was experimentally validated by enzyme, cell, and animal work, and we demonstrated that NIR light caused minimal photodamage to enzyme activity compared to UV light, and the UCNP-based photoactive probe presents good biosafety both in vitro and in vivo. We believe that this novel PAL approach will provide a promising tool for study of ligand-protein interactions and identification of biomolecular targets.

Elucidating the facet-dependent reactivity of CrMn catalyst for selective catalytic reduction of NOx with NH3.

The facet-dependent reactivity of CrMn catalysts was still unclear, hindering the further enhancement of their low-temperature SCR performance. Herein, the facet-dependent reactivity of CrMn1.5O4 catalyst for NH3-SCR of NOx was innovatively illustrated by numerous characterizations and density functional theory (DFT) calculations. Exposed (100) facet of CrMn1.5O4 catalyst exhibited best low-temperature SCR activity with ≥90 % NO conversion within 148-296 °C and 2.86 × 10-3 mol/(g·s) reaction rate within 160-240 °C. The characterizations revealed that (100) facet could induce the increase of BET specific area, electron transfer, concentration of Mn4+ and Oα, surface acidity, redox ability, NH3 and NOx adsorption/activation capacity. Subsequently, DFT calculations demonstrated that (100) facet exhibited the strongest affinity for NH3 and NO due to its unique 3O3c-Mn5c-2O4c bond and abundant charges transfer near the active adsorption sites, and Brønsted acid and oxygen vacancies were most easily formed on (100) facet. Furthermore, H2O formation as the rate determining step easily occurred on (100) facet. Eventually, we successfully improved the low-temperature SCR activity of CrMn1.5O4 catalyst by further tailoring highly active (100) facet from 0.754 to 0.865. This work provides the deeper understanding of facet-dependent reactivity and a good strategy to improve the catalytic activity of the catalysts.

Staphylococcus aureus increases Prostaglandin E2 secretion in cow neutrophils by activating TLR2, TLR4, and NLRP3 inflammasome signaling pathways.

Introduction: In clinical settings, dairy cows are often attacked by pathogenic bacteria after delivery, especially Staphylococcus aureus (S. aureus). Neutrophils have long been regarded as essential for host defense against S. aureus. Prostaglandin E2 (PGE2) can additionally be used as an inflammatory mediator in pathological conditions to promote the repair of inflammatory injuries. However, whether S. aureus can promote the accumulation of PGE2 after the infection of neutrophils in cows and its mechanism remain unclear. Lipoprotein is an important immune bioactive ingredient of S. aureus. Methods: In this study, the changes in neutrophils were monitored in dairy cows infected with wild-type S. aureus (SA113) and an S. aureus lipoprotein-deficient strain (Δlgt); meanwhile, we established whether pattern recognition receptors mediate this process and whether S. aureus lipoproteins are necessary for causing the release of PGE2 from cow neutrophils. Results: The results showed that Δlgt was less effective than SA113 in inducing the production of IL-1ß, IL-6, IL-8, IL-10, and PGE2 within neutrophils; furthermore, TLR2, TLR4, and NLRP3 receptors were found to mediate the inducible effect of lipoprotein on the above inflammation mediators and cytokines, which depended on MAPK and Caspase-1 signaling pathways. In addition, TLR2, TLR4, and NLRP3 inhibitors significantly inhibited PGE2 and cytokine secretion, and PGE2 was involved in the interaction of S. aureus and neutrophils in dairy cows, which could be regulated by TLR2, TLR4, and NLRP3 receptors. We also found that S. aureus was more likely to be killed by neutrophils when it lacked lipoprotein and TLR2, TLR4, and NLRP3 were involved, but PGE2 seemed to have no effect. Discussion: Taken together, these results suggest that lipoprotein is a crucial component of S. aureus in inducing cytokine secretion by neutrophils as well as killing within neutrophils, which could be accomplished by the accumulation of PGE2 by activating MAPK and the Caspase-1 signaling pathways through TLR2, TLR4, and NLRP3 receptors. These results will contribute to a better understanding of the interaction between S. aureus and host immune cells in dairy cows.

A resource of induced pluripotent stem cell (iPSC) lines including clinical, genomic, and cellular data from genetically isolated families with mood and psychotic disorders.

Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.

Dance emotion recognition based on linear predictive Meir frequency cepstrum coefficient and bidirectional long short-term memory from robot environment.

Dance emotion recognition is an important research direction of automatic speech recognition, especially in the robot environment. It is an important research content of dance emotion recognition to extract the features that best represent speech emotion and to construct an acoustic model with strong robustness and generalization. The dance emotion data set is small in size and high in dimension. The traditional recurrent neural network (RNN) has the problem of long-range dependence disappearance, and due to the focus on local information of convolutional neural network (CNN), the mining of potential relationships between frames in the input sequence is insufficient. To solve the above problems, this paper proposes a novel linear predictive Meir frequency cepstrum coefficient and bidirectional long short-term memory (LSTM) for dance emotion recognition. In this paper, the linear prediction coefficient (LPC) and Meier frequency cepstrum coefficient (MFCC) are combined to obtain a new feature, namely the linear prediction Meier frequency cepstrum coefficient (LPMFCC). Then, the combined feature obtained by combining LPMFCC with energy feature is used as the extracted dance feature. The extracted features are input into the bidirectional LSTM network for training. Finally, support vector machine (SVM) is used to classify the obtained features through the full connection layer. Finally, we conduct experiments on public data sets and obtain the better effectiveness compared with the state-of-art dance motion recognition methods.

Novel data-driven two-dimensional Q-learning for optimal tracking control of batch process with unknown dynamics.

In view that the previous control methods usually rely too much on the models of batch process and have difficulty in a practical batch process with unknown dynamics, a novel data-driven two-dimensional (2D) off-policy Q-learning approach for optimal tracking control (OTC) is proposed to make the batch process obtain a model-free control law. Firstly, an extended state space equation composing of the state and output error is established for ensuring tracking performance of the designed controller. Secondly, the behavior policy of generating data and the target policy of optimization as well as learning is introduced based on this extended system. Then, the Bellman equation independent of model parameters is given via analyzing the relation between 2D value function and 2D Q-function. The measured data along the batch and time directions of batch process are just taken to carry out the policy iteration, which can figure out the optimal control problem despite lacking systematic dynamic information. The unbiasedness and convergence of the designed 2D off-policy Q-learning algorithm are proved. Finally, a simulation case for injection molding process manifests that control effect and tracking effect gradually become better with the increasing number of batches.

Deep transcriptome sequencing of subgenual anterior cingulate cortex reveals cross-diagnostic and diagnosis-specific RNA expression changes in major psychiatric disorders.

Despite strong evidence of heritability and growing discovery of genetic markers for major mental illness, little is known about how gene expression in the brain differs across psychiatric diagnoses, or how known genetic risk factors shape these differences. Here we investigate expressed genes and gene transcripts in postmortem subgenual anterior cingulate cortex (sgACC), a key component of limbic circuits linked to mental illness. RNA obtained postmortem from 200 donors diagnosed with bipolar disorder, schizophrenia, major depression, or no psychiatric disorder was deeply sequenced to quantify expression of over 85,000 gene transcripts, many of which were rare. Case-control comparisons detected modest expression differences that were correlated across disorders. Case-case comparisons revealed greater expression differences, with some transcripts showing opposing patterns of expression between diagnostic groups, relative to controls. The ~250 rare transcripts that were differentially-expressed in one or more disorder groups were enriched for genes involved in synapse formation, cell junctions, and heterotrimeric G-protein complexes. Common genetic variants were associated with transcript expression (eQTL) or relative abundance of alternatively spliced transcripts (sQTL). Common genetic variants previously associated with disease risk were especially enriched for sQTLs, which together accounted for disproportionate fractions of diagnosis-specific heritability. Genetic risk factors that shape the brain transcriptome may contribute to diagnostic differences between broad classes of mental illness.

Successful repair for a ruptured venous aneurysm: an unusual complication of venous arterialization in Buerger's disease.

We report a ruptured venous aneurysm, an unusual complication of venous arterialization for lower limb ischemia in Buerger's disease. Arteriovenous shunt ligation and aneurysm resection were performed successfully, with the distal limb perfusion preserved. By our very limited experience, venous arterialization may be ineffective on improving lower limb ischemia with Buerger's disease.

[Premedication with oral midazolam in children receive sevoflurane general anesthesia].

OBJECTIVE: To investigate the effect of oral midazolam on sedation, on perioperative emotion and on behavior in children with sevoflurane general anesthesia. METHODS: 48 children undergoing cataract surgeries were randomly divided into two groups and respectively received 0.5 mg/kg oral midazolam (Group I)and placebo (Group II) 30 minutes before the operation. Perioperative behavior and emotion status were assessed. RESULTS: Satisfactory sedation ratio in group I was better than that in group II (58.3% vs 12.5%, P < 0.05). There were no differences in emergence time, PACU stay and incidence of emergence agitation between two groups (P > 0.05). CONCLUSION: 0.5 mg/kg oral midazolam before sevoflurane general anesthesia in children is safe. It is effective on anxious relief, however it does not decrease the incidence of emergence agitation.

BHLHB2 controls Bdnf promoter 4 activity and neuronal excitability.

Brain-derived neurotrophic factor (BDNF), via activation of TrkB receptors, mediates vital physiological functions in the brain, ranging from neuronal survival to synaptic plasticity, and has been implicated in the pathophysiology of neurodegenerative disorders. Although transcriptional regulation of the BDNF gene (Bdnf) has been extensively studied, much remains to be understood. We discovered a sequence within Bdnf promoter 4 that binds the basic helix-loop-helix protein BHLHB2 and is a target for BHLHB2-mediated transcriptional repression. NMDA receptor activation de-repressed promoter 4-mediated transcription and correlated with reduced occupancy of the promoter by BHLHB2 in cultured hippocampal neurons. Bhlhb2 gene -/- mice showed increased hippocampal exon 4-specific Bdnf mRNA levels compared with +/+ littermates under basal and activity-dependent conditions. Bhlhb2 knock-out mice also showed increased status epilepticus susceptibility, suggesting that BHLHB2 alters neuronal excitability. Together, these results support a role for BHLHB2 as a new modulator of Bdnf transcription and neuronal excitability.

Lower extremity arterial occlusive disease as a rare complication of Crohn's disease.

OBJECTIVE: To investigate the clinical characteristics and treatment strategy of lower extremity arterial occlusive disease in patients with Crohn's disease (CD). METHODS: Clinical information of 9 cases suffering from lower extremity arterial occlusion and CD was investigated retrospectively. RESULTS: All the cases were less than 50 years old and the most were females (8/9). Arterial occlusions occurred in either active (5/9) or inactive (4/9) stage of CD. Besides the arteries of lower extremities, other arteries could also be involved such as aorta, iliac artery, renal artery or mesentery artery. Seven cases had atherosclerotic imaging findings (4 had aortic plaques and 6 had iliac artery stenoses). Embolectomy or thromboendarterectomy were mostly performed. Four (44.4%) cases had recurrent lower limb ischemia. CONCLUSIONS: Arterial occlusive disease is a rare extraintestinal manifestation of CD. A thorough inspection of aorta is necessary. Embolectomy is mostly preferred. Anticoagulation treatment is highly recommended after the operation.

Neuropeptide Y expression in vaginal epithelium of women with pelvic organ prolapse and stress urinary incontinence.

OBJECTIVES: To determine the role of neuropeptide Y (NPY) in anterior and posterior vaginal epithelium in the etiologic development of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). METHODS: Forty biopsy specimens from anterior and posterior vaginal epithelium were obtained from 40 POP/SUI patients and controls. The specimens were stained using hematoxylin and eosin and NPY immunohistochemical staining. NPY was measured semiquantitatively and NPY mRNA expression was assessed using DNA hybridization in situ. RESULTS: There were no significant differences in NPY between anterior and posterior vaginal epithelium. NPY profiles in posterior vaginal epithelium in the SUI group were significantly lower than in the POP (P<0.05) and control (P<0.05) groups. In the POP group, the NPY profile correlated negatively with advancing age and years post menopause. CONCLUSION: The reduction in NPY in the anterior and posterior vaginal wall epithelium might be related to nerve damage or degeneration, resulting in a change in blood flow, atrophy, and pelvic floor laxity in patients with POP and SUI, especially post menopause and with advancing age.