Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance.

Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila, that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons.

The Abl pathway bifurcates to balance Enabled and Rac signaling in axon patterning in Drosophila.

The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. Although individual components are known, the relationships among them remain unresolved. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin-regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain. Finally, we show that a key target of Abl signaling in axons is the WAVE complex that promotes the formation of branched actin networks. Thus, we show that Abl constitutes a bifurcating network, suppressing Ena activity in parallel with stimulation of WAVE. We suggest that the balancing of linear and branched actin networks by Abl is likely to be central to its regulation of axon patterning.

Socioeconomic status and health-related quality of life among adults and older with overactive bladder.

OBJECTIVE: To study the effect of socioeconomic status (SES) on health-related quality of life (HRQoL) among persons with overactive bladder (OAB). DESIGN: A randomized HRQoL study was conducted from the year 2014 until the year 2016 based on the OAB pathology department of the regional clinical diagnostics center. SETTING: The medical institutions where the study was conducted had outpatient care. PARTICIPANTS: The simple response frequency was 81%. A total of 1893 men and women with OAB aged 35-85 (average 58.3 years) were selected by blind random sampling. Included into the group of examined individuals were persons who diagnosis provided after the examination was OAB. INTERVENTION: Evaluation of HRQoL was conducted using the SF-6D questionnaire. The OAB diagnosis was confirmed using the OAB-questionnaire and uroflowmetry. MAIN OUTCOME MEASURE(S): We hypothesized that the impact of SES on the HRQoL of patients with OAB has significant features. RESULTS: Described for the first time were HRQoL measures in various SES levels within different ages of people suffering from OAB. The strongest relationship was identified between education level, professional activity and HRQoL measures; meanwhile the weakest relationship was between income and HRQoL measures. We also confirmed the efficiency of evaluating HRQoL while using SF-6D and SRH as an external standard. CONCLUSION: The improvement of HRQoL in persons with OAB is contingent upon increment in their level of awareness about the methods of OAB treatment and the effectiveness of treatment for severe symptoms of LUT pathology, increased social support and, possibly, physical activity.

The Risk of Sexual Dysfunction and Effectiveness of Treatment of Benign Prostatic Hyperplasia With Severe Lower Urinary Tract Dysfunction With Combination of Dutasteride and Solifenacin.

INTRODUCTION: Correction of benign prostatic hyperplasia (BPH) with lower urinary tract (LUT) symptoms (LUTS) is treated with drugs of different pharmacological classes having side effects including suppression of sexual function. AIM: To assess the effect of simultaneous intake of dutasteride and solifenacin on the reversibility of severe LUTS and sexual function in men with BPH. METHODS: Patients from group A took dutasteride 0.5 mg/d, those from group В took dutasteride 0.5 mg/d and solifenacin 10 mg/d, and those from group С took dutasteride 0.5 mg/d and solifenacin 20 mg/d. The duration of the observation was 6 months. The sexual function was rated with the International Index of Erectile Function questionnaire and Men's Sexual Health Questionnaire-ejaculatory dysfunction. The functional status of LUT was rated with International Prostate Symptom Score, overactive bladder questionnaire-awareness tool, diary voiding, and uroflowmetry. MAIN OUTCOME MEASURE: The state of sexual function and function of the LUT in men improved. RESULTS: The erectile function in all men, having participated in the study, did not change [group A, 9.8 (1.6)/9.4 (3.8), P ≥ .05; group B, 10.1 (2.1)/10.5 (3.7), P ≥ .05; group C, 9.7 (1.5)/9.5 (2.6), P ≥ .05]. The ejaculator function significantly decreased in all groups. According to International Prostate Symptom Score, obstruction diminished in this group [incomplete emptying, 3.7 (0.7)/1.5 (0.3), P ≤ .05; intermittence, 3.5 (1.0)/3.5 (1.0), P ≤ .05; weak stream, 3.8 (0.6)/1.5 (0.4), P ≤ .05; straining, 3.4 (0.5)/0.7 (0.7), P ≤ .05] as did hyperactivity [urgency, 2.8 (0.7)/0.9 (0.7), P ≤ .05; nocturia, 2.8 (0.6)/1.2 (0.4), P ≤ .05]. All numbers in the manuscript are given in points unless otherwise stated. The values in parentheses are SD (unless otherwise specified). CLINICAL IMPLICATIONS: The information that a high dose of solifenacin administered concomitantly with dutasteride may contribute to increase in sexual satisfaction and preservation of erectile function at the baseline level can be useful and used by sexologists, urologists, and family doctors. STRENGTH & LIMITATIONS: The combination of dutasteride 0.5 mg/d and solifenacin 10 mg/d saves erectile function and improves sexual satisfaction. At the same time, the symptoms of obstruction and hyperactivity disappear or are reduced in most patients. Nevertheless, we did not study late results of the combined therapy. CONCLUSION: Suggested combination does not impact on erectile function but decreases ejaculator function; however, it does not affect a general high rating of sexual function by patients. Thus, overall sexual function in men with BPH and severe LUTS is not impaired by prolonged intake of double dosage of solifenacin combined with dutasteride. The combination of dutasteride and solifenacin is effective and safe to treat BPH and severe LUTS. Kosilov K, Kuzina I, Kuznetsov V, et al. The Risk of Sexual Dysfunction and Effectiveness of Treatment of Benign Prostatic Hyperplasia With Severe Lower Urinary Tract Dysfunction With Combination of Dutasteride and Solifenacin. J Sex Med 2018;15:1579-1590.

Cognitive functions and health-related quality of life in men with benign prostatic hyperplasia and symptoms of overactive bladder when treated with a combination of tamsulosin and solifenacin in a higher dosage.

AIM: To study the cognitive functions and health-related quality of life (HRQoL) in individuals taking a combination of tamsulosin and solifenacin in a higher dosage. METHODS: All patients (n = 262) were assigned to group A (N = 93, tamsulosin 0.4 mg + solifenacin 10 mg per day), group B (N = 83, tamsulosin 0.4 mg + solifenacin 20 mg), and control group C (N = 86; tamsulosin 0.4 mg + placebo). The lower urinary tract (LUT) condition was assessed on the scales International Prostate Symptom Score, Over Active Bladder Awareness Tool and uroflowmetry. The state of cognitive status was assessed on the scales Mini-mental State Examination, Controlled Oral Word Association Test, Wechsler Adult Intelligence Scale-Revised, Wechsler III, Color Trails Test, California Verbal Learning Test. RESULTS: The values of cognitive function indicators in the individuals from all groups after treatment did not significantly differ from the respective values at the baseline (p > .05). The values of most HRQoL parameters of the functional state of the LUT significantly improved in groups A and B. A significant correlation between the state of cognitive status and HRQoL, as well as LUT was absent (r <0.3). CONCLUSION: The combination of solifenacin in a double dosage along with tamsulosin can be recommended for elderly benign prostatic hyperplasia patients with overactive bladder symptoms.

The effective tool for self-assessment of adherence to treatment in patients with benign prostatic obstruction and overactive bladder symptoms.

PURPOSE: Study of validity of the Medication Adherence Self-Report Inventory (MASRI) for use in clinical practice to treat patients with benign prostatic obstruction (BPO) accompanied with overactive bladder (OAB) symptoms. METHODS: During 12 weeks of the randomized study, 452 patients with BPO and OAB symptoms (mean age of 61.3 (12.7)) were studied for adherence to the treatment with Tamsulosin, Solifenacin and Trospium using the MASRI. External monitoring instruments included the Brief Medication Questionnaire (BMQ) and the visual remaining pill count. The state of the prostate gland and the lower urinary tract was monitored using questionnaires I-PSS, OAB Awareness Tool, uroflowmetry and voiding diaries. RESULT: Correlation between the percentage of men non-adherent to treatment (MASRI) and the percentage of patients having a belief barrier on the screen of the BMQ was r = 0.89, p ≤0.05, r = 0.92, p ≤0.01, r = 0.85, p ≤0.05, a number of missed doses on the Regimen Screen of the BMQ was r = 0.79; p ≤0.05; r = 0.81; p ≤0.05; r = 0.75, p ≤0.05, a number of non-adherent patients according to the BMQ was r = 0.83 (p ≤0.05), r = 0.88 (p ≤0.05), r = 0.79, p ≤0.05, the results of the pill count were r = 0.65-0.76; p ≤0.05-0.01. These data confirm high validity of the MASRI. CONCLUSION: The MASRI is a valid tool for rapid assessment of adherence to treatment of patients with BPO and OAB receiving Tamsulosin and antimuscarinic drugs and may be recommended for use in clinical practice.

Self-assessment of treatment compliance with antimuscarinic drugs and lower urinary tract condition among women with urinary incontinence.

AIM: Our aim was to determine the efficiency of the Medication Compliance Self-Report Inventory (MASRI) in self-reporting antimuscarinic drug treatment compliance among women with urinary incontinence (UI). MATERIALS AND METHODS: The study assessed 347 women aged 18-65 (averaging 49.7) years with more than one urinary incontinence (UI) episode per day. Treatment compliance was tested at the beginning and at weeks 4, 8, and 12 using the MASRI, the Brief Medication Questionnaire (BMQ), and visual pill counts. The MASRI's constructive, concurrent, and discriminate validity was studied in comparison with an external standard that uses the chi-square and Spearman coefficient. Receiver operating characteristic (ROC) analysis was performed to identify optimum MASRI cutoffs that would predict noncompliance. Furthermore, the functional condition of the lower urinary tract was tested using voiding diaries, uroflowmetry, and cystometry. RESULT: The correlation between the percentage of noncompliant women according to the MASRI, and individuals with a belief barrier with respect to the BMQ screen was r = 0.81 (p ≤0.05), r = 0.84 (p ≤0.05), and r = 0.79 (p ≤0.05). The correlation between the percentage of noncompliant women according to the MASRI and of women who missed >20% of their doses according to the Regimen Screen of the BMQ was r = 0.79, p ≤0.05, r = 0.82, p ≤0.01, r = 0.77, and p ≤0.05 at the control points. Finally, the percentage of noncompliant patients who self-reported correctly according to the MASRI data compared with the BMQ was 95.6%, 95.7%, and 96.6% at the control points. CONCLUSION: The MASRI entails acceptable validity for accurately predicting treatment compliance with antimuscarinic drugs among women who have had UI for >3 months.

Cdk5 regulates developmental remodeling of mushroom body neurons in Drosophila.

BACKGROUND: During metamorphosis, axons and dendrites of the mushroom body (MB) in the Drosophila central brain are remodeled extensively to support the transition from larval to adult behaviors. RESULTS: We show here that the neuronal cyclin-dependent kinase, Cdk5, regulates the timing and rate of mushroom body remodeling: reduced Cdk5 activity causes a delay in pruning of MB neurites, while hyperactivation accelerates it. We further show that Cdk5 cooperates with the ubiquitin-proteasome system in this process. Finally, we show that Cdk5 modulates the first overt step in neurite disassembly, dissolution of the neuronal tubulin cytoskeleton, and provide evidence that it also acts at additional steps of MB pruning. CONCLUSIONS: These data show that Cdk5 regulates the onset and extent of remodeling of the Drosophila MB. Given the wide phylogenetic conservation of Cdk5, we suggest that it is likely to play a role in developmental remodeling in other systems, as well. Moreover, we speculate that the well-established role of Cdk5 in neurodegeneration may involve some of the same cellular mechanisms that it uses during developmental remodeling.

How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS.

Development of the segmented central nerve cords of vertebrates and invertebrates requires connecting successive neuromeres. Here, we show both how a pathway is constructed to guide pioneer axons between segments of the Drosophila CNS, and how motility of the pioneers along that pathway is promoted. First, canonical Notch signaling in specialized glial cells causes nearby differentiating neurons to extrude a mesh of fine projections, and shapes that mesh into a continuous carpet that bridges from segment to segment, hugging the glial surface. This is the direct substratum that pioneer axons follow as they grow. Simultaneously, Notch uses an alternate, non-canonical signaling pathway in the pioneer growth cones themselves, promoting their motility by suppressing Abl signaling to stimulate filopodial growth while presumably reducing substratum adhesion. This propels the axons as they establish the connection between successive segments.

Corrigendum to "Efficacy of a combination of dutasteride, tadalafil, and solifenacin in the treatment of previously unsuccessful patients" [Asian J Urol 9 (2022) 42-50].

[This corrects the article DOI: 10.1016/j.ajur.2021.04.002.].

Efficacy of a combination of dutasteride, tadalafil, and solifenacin in the treatment of previously unsuccessful patients.

OBJECTIVE: To evaluate the efficacy and safety of simultaneous administration of dutasteride, tadalafil and solifenacin in the treatment of benign prostatic hyperplasia (BPH) with overactive bladder symptoms and lower urinary tract obstruction in previously unsuccessfully treated men. METHODS: Patients in Group A (n=97) received dutasteride 0.5 mg/day, tadalafil 2.5 mg/day, and solifenacin 2.5 mg/day; Group B (n=95) received dutasteride 0.5 mg/day, tadalafil 5 mg/day, and solifenacin 5 mg/day; Group C (n=103) received dutasteride 0.5 mg/day, tadalafil 20 mg/day, and solifenacin 10 mg/day. The functional status of the lower urinary tract was assessed using the International Prostate Symptom Score (I-PSS), Overactive Bladder Questionnaire (OABq), International Index of Erectile Function (IIEF), and Male Sexual Health Questionnaire Ejaculatory Dysfunction (MSHQ-EjD) as well as uroflowmetry. RESULTS: The total score of the sexual function remained unchanged in Group B of patients 81.3 points vs. 80.2 points (p>0.05) according to MSHQ-EjD, 61.4 points vs. 51.2 points (p>0.05) according to IIEF data. The total assessment of symptoms of hyperactivity significantly decreased in Group C according to OABq data after the 4th week of the study (17.5 points vs. 26.1 points, p<0.05) and remained below the baseline until the end of the study (15.2 points). CONCLUSIONS: The simultaneous administration of standard doses of dutasteride, solifenacin, and tadalafil for 3 months is safe, effective, and can be recommended for patients with BPH to reduce symptoms of obstruction and hyperactivity of the bladder and maintain sexual function.

Inflammatory Mechanisms of Diabetes and Its Vascular Complications.

The main cause of death in patients with type 2 DM is cardiovascular complications resulting from the progression of atherosclerosis. The pathophysiology of the association between diabetes and its vascular complications is complex and multifactorial and closely related to the toxic effects of hyperglycemia that causes increased generation of reactive oxygen species and promotes the secretion of pro-inflammatory cytokines. Subsequent oxidative stress and inflammation are major factors of the progression of type 2 DM and its vascular complications. Data on the pathogenesis of the development of type 2 DM and associated cardiovascular diseases, in particular atherosclerosis, open up broad prospects for the further development of new diagnostic and therapeutic approaches.

The Impact of Variable Factors on the Health-Related Quality of Life in the Elderly in Japan and Russia.

AIM: The study of the impact of socio-economic, demographic factors and polymorbidity on the quality of life associated with health (HRQoL) in elderly people from Japan and Russia. BACKGROUND: Factors affecting the quality of life of the elderly in both countries are poorly understood. OBJECTIVE: Make a comparative analysis of factors affecting the quality of life of the elderly of both sexes in Japan and Russia. METHODS: The age range in this study is 65-95 years old. For the study of HRQoL, a questionnaire Health Status Survey-Short Form 36v2 was used, including two main domains: physical and mental health. The level of polymorbidity was studied using CIRS-G. The linear regression model of the influence of variables upon HRQoL was calculated for SES, demographic characteristics, and morbidity. RESULT: Strong associations with HRQoL in the combined sample had a living together with relatives (r=6.94 (5.17-8.72) p<0,05), the incidence rate (r=8.50 (5.51-11.49), p<0.01) and the older age (r=5.39 (2.63-8.16), p<0,01.). The elderly inhabitants of Japan had a higher self-assessment for physical health in the age ranges 65-74 and over 85 years old (p<0.05), and a higher selfassessment of mental health at the age of 75-84 years old. Sixty-eight elderly Japanese and 48% Russians estimated their physical health as normal. CONCLUSION: The effect of living together, morbidity and age upon HRQoL is manifested equally strongly both among the inhabitants of Japan and among the Russians. The elderly Japanese estimate the state of physical and mental health as a whole higher than their Russian peers.

The Analysis of the Effects of Executive Functions, Working Memory and Other Factors on Medication Adherence in Elderly Men with Benign Prostatic Hyperplasia and Overactive Bladder Symptoms.

AIM: Evaluation of the executive function and working memory influence, as well as the general state of memory, on adherence to Benign Prostatic Hyperplasia (BPH) and overactive bladder symptoms treatment in elderly men. BACKGROUND: The influence of the executive function and working memory on treatment adherence in older men with BPH has not been studied enough. OBJECTIVE: To determine the level of influence of various factors on the treatment adherence in older men with BPH. METHODS: The executive function and working memory evaluation, as well as a general memory assessment, were carried out using the Wisconsin Test, the Wechsler Memory Scale, and the California Verbal Test. Hierarchical and simultaneous regressions were calculated to study the effect of executive function and working memory. RESULTS: After the end of the study, the symptoms of hyperactive bladder significantly decreased, the symptoms of evacuation did not change significantly, and the cognitive status of the patients remained unchanged. The predictor variables significantly influencing adherence of elderly men to BPH and overactive bladder (OAB) treatment are executive function and working memory composite (ß = .33, p < .05), severe symptoms of lower urinary tract (-.34, p < .05), and age (-.27, p < .05). CONCLUSION: The status of executive function and working memory, as well as the age and severity of the pathological symptoms of the lower urinary tract, should be taken into account when predicting the risks of rejecting BPH and OAB treatment in elderly patients.

Improvement of the symptoms of lower urinary tract and sexual dysfunction with tadalafil and solifenacin after the treatment of benign prostatic hyperplasia with dutasteride.

BACKGROUND: The aim of this research is to study the influence of simultaneous taking of tadalafil and solifenacin in standard and double dosage on the lower urinary tract symptoms (LUTS) and sexual dysfunction in men with benign prostatic hyperplasia after the course of dutasteride. MATERIALS AND METHODS: The research included 326 patients older than 50 years with benign prostatic hyperplasia coupled with LUTS and sexual dysfunction having undergone the course of treatment with dutasteride. After random division into three groups, patients from the Group A (n = 107) got tadalafil 5 mg/d as monotherapy, from the Group В (n = 107) got tadalafil 5 mg/d and solifenacin 10 mg/d, and from the Group С (n = 112) got tadalafil 5 mg/d and solifenacin 20 mg/d. The duration of treatment was 12 weeks. The rating of sexual function was made with the questionnaires International Index of Erectile Function and other. RESULTS: The results of rating of sexual function with the questionnaires MSHQ-EjD and International Index of Erectile Function correlated among themselves. According to MSHQ-EjD, overall rating of the sexual function increased in each of the three groups (A: 67.9 (12.4)/91.5 (10.4), P ≤ 0.05; B: 72.4 (14.5)/102.6 (16.9), P ≤ 0.05; C: 76.6 (16.3)/109.6 (15.6), P ≤ 0.05). The level of hyperactivity symptoms decreased in Groups В and С (В: urgency -2.9 (0.7)/1.1 (0.6), P ≤ 0.05; nocturia 2.7 (1.0)/0.7 (0.5), P ≤ 0.05; C: urgency -2.5 (0.5)/0.8 (0.6), P ≤ 0.05; nocturia -2.8 (0.6)/1.0 (0.5), P ≤ 0.05), and it did not change in the Group A. CONCLUSIONS: The use of tadalafil as monotherapy significantly improves the sexual function but does not affect overactive bladder symptoms. The combination therapy of tadalafil and solifenacin leads to dramatic improvement of sexual function and reversibility of detrusor hyperactivity symptoms.

Influence of current state of executive function and working memory on adherence to antimuscarinic therapy in older women with OAB.

AIM: Evaluation of the executive function and working memory influence, as well as the general state of memory, on adherence to treatment with antimuscarinic drugs in elderly women with overactive bladder (OAB). BACKGROUND: Antimuscarinic are effective and safe for the treatment of OAB, but adherence to treatment remains low. Demographic, socioeconomic, and medical factors which influence the medication adherence have been explored; however, the impact of executive function and working memory on adherence has not been evaluated yet. METHODS: In total 417 women from 65 to 88 years old with the diagnosis overactive bladder were selected to participate in the study. They were prescribed AM drugs: trospium 15 mg / day (n = 138), or Solifenacin 5 mg / day (n = 132), or Darifenacin 7.5 mg / day (n = 147). The observation was carried out for 12 weeks. The urodynamic state was investigated using the questionnaire OABq-SF, uroflowmetry was performed at the start and end of the study, voiding diary - during the whole time of observation. The state of mental health was investigated using MMSE and GDS. The assessment of executive function and working memory, as well as general memory estimation, was carried out using the Wisconsin Card Sorting Test, Wechsler Memory Scale subscale, and the California Verbal Learning Test. Hierarchical and simultaneous regressions were calculated to study the effect of executive function and working memory on medication adherence. RESULTS: The urodynamic state of patients significantly improved after the treatment, the cognitive functions did not change. The analysis of hierarchical and simultaneous regressions made it possible to establish that the predictor variables significantly influencing medication adherence of elderly women with OAB to AM treatment are executive function and working memory composite (ß = .39, p < .05), severe symptoms of lower urinary tract (ß =. -. 31, p < .05), and age (ß =. -. 25, p < .05). CONCLUSION: The status of executive function and working memory, as well as the age and severity of the pathological symptoms of lower urinary tract should be considered when predicting adherence to AM treatment in elderly patients with OAB.

Hyperactive Innate Immunity Causes Degeneration of Dopamine Neurons upon Altering Activity of Cdk5.

Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. Here, we identify a molecular pathway that links innate immunity to age-dependent loss of dopaminergic neurons in Drosophila. We find, first, that altering the expression of the activating subunit of the Cdk5 protein kinase (Cdk5α) causes severe disruption of autophagy. Second, this disruption of autophagy is both necessary and sufficient to cause the hyperactivation of innate immunity, particularly expression of anti-microbial peptides. Finally, it is the upregulation of immunity that induces the age-dependent death of dopaminergic neurons. Given the dysregulation of Cdk5 and innate immunity in human neurodegeneration and the conserved role of the kinase in the regulation of autophagy, this sequence is likely to have direct application to the chain of events in human neurodegenerative disease.

Expression of a Fragment of Ankyrin 2 Disrupts the Structure of the Axon Initial Segment and Causes Axonal Degeneration in Drosophila.

Neurodegenerative stimuli are often associated with perturbation of the axon initial segment (AIS), but it remains unclear whether AIS disruption is causative for neurodegeneration or is a downstream step in disease progression. Here, we demonstrate that either of two separate, genetically parallel pathways that disrupt the AIS induce axonal degeneration and loss of neurons in the central brain of Drosophila. Expression of a portion of the C-terminal tail of the Ank2-L isoform of Ankyrin severely shortens the AIS in Drosophila mushroom body (MB) neurons, and this shortening occurs through a mechanism that is genetically separate from the previously described Cdk5α-dependent pathway of AIS regulation. Further, either manipulation triggers morphological degeneration of MB axons and is accompanied by neuron loss. Taken together, our results are consistent with the hypothesis that disruption of the AIS is causally related to degeneration of fly central brain neurons, and we suggest that similar mechanisms may contribute to neurodegeneration in mammals.

Influence of the Short-term Intake of High Doses of Solifenacin and Trospium on Cognitive Function and Health-Related Quality of Life in Older Women With Urinary Incontinence.

PURPOSE: The aim of this study was to investigate the safety and the effects of elevated doses of solifenacin and trospium on cognitive function and health-related quality of life (HRQoL) in elderly women receiving treatment for urinary incontinence. METHODS: The study included 312 women aged 60-83 years (mean age, 69.4 years). All participants had scored at least 24 points on the Mini-Mental State Examination (MMSE) scale, and all of them had been diagnosed with urge urinary incontinence (UUI) or mixed urinary incontinence (MUI). The women were randomly assigned to 3 groups: group A, individuals who were simultaneously administered solifenacin at a high dosage of 20 mg per day and trospium at a high dosage of 60 mg per day; group B, persons taking solifenacin and trospium at the usual dosage of 10 and 30 mg per day, respectively; and group C, persons who received a placebo. Participants' cognitive status was assessed by the MMSE, Controlled Oral Word Association Test, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale III, Colour Trails Test, and California Verbal Learning Test scales. The HRQoL assessment was performed using the Medical Outcomes Study 36-Item Health Survey. RESULTS: The cognitive function parameters did not differ at the start and end of the study across the groups (P>0.05). Additionally, the cognitive function parameters did not differ significantly within each group between the start and end of the study (P>0.05). The values of most HRQoL parameters regarding the functional state of the lower urinary tract (LUT) after the termination of treatment significantly improved in groups A and B (P<0.05). A significant correlation between cognitive status and HRQoL or LUT parameters was absent (r<0.3), while the correlations between HRQoL and LUT parameters were r=0.31-0.83, P<0.05. CONCLUSIONS: The use of elevated doses of solifenacin and trospium did not increase the risk of cognitive impairment in women with UUI and MUI. The combination of solifenacin and trospium at a double dosage may be recommended to elderly women with treatment-resistant symptoms of UUI and MUI. However, the safety of combining antimuscarinic drugs in women with an increased volume of residual urine requires further study.

Effectiveness of a new tool for self-evaluation of adherence to antimuscarinic drug treatment in older patients of both sexes with urge incontinence.

AIM: The present study was a comparison of the validity of the Medication Adherence Self-Report Inventory (MASRI) questionnaire with other methods of assessing adherence to antimuscarinic drugs treatment in older patients with urge incontinence. METHODS: The experiment involved 733 men and women aged >65 years who had noted no less than one urge incontinence episode per day. At the beginning of the experiment, and after 4, 8 and 12 weeks, their adherence to treatment was monitored using the MASRI. RESULTS: The construct validity of the tool was confirmed by data on the correlation of the percentage of non-adherent patients according to the MASRI and the percentage of patients having a belief barrier on the Brief Medication Questionnaire screen (r = 0.89, P ≤ 0.01; r = 0.91, P ≤ 0.01; and r = 0.91, P ≤ 0.05 at the 4th, 8th and 12th week of the follow up). The hypothesis of competitive validity was supported by comparing the percentage of non-adherent patients according to the MASRI and the number of missed doses on the Brief Medication Questionnaire screen (r = 0.94, P ≤ 0.01; r = 0.85, P ≤ 0.05; and r = 0.7, P ≤ 0.05), and according to a visual count of pills. The area under the curve at the 4th, 8th , and 12th week was 0.95 ± 0.04, 0.92 ± 0.03 and 0.94 ± 0.04, respectively. CONCLUSION: The MASRI questionnaire has high validity, and is effective for evaluating adherence to treatment among older patients with urge incontinence taking antimuscarinic drugs. Using the MASRI would imply lower costs and greater availability of diagnostics, and it is the tool of choice in clinical practice. Geriatr Gerontol Int 2018; 18: 115-122.