Effect of mesh anchoring technique in uterine prolapse repair surgery: A finite element analysis.

The female pelvic cavity involves muscles, ligaments, endopelvic fasciae and multiple organs where different pathologies may occur, namely the pelvic organ prolapse (POP). The synthetic implants are used for the reconstructive surgery of POP, but severe complications associated with their use have been reported, mainly related to their mechanical properties (e.g., implant stiffness) and microstructure. In this study, we mimicked a transvaginal reconstructive surgery to repair the apical ligaments (uterosacral ligaments (USLs) and cardinal ligaments (CLs)), by modeling, their impairment (90% and 50%) and/or total rupture. The implants to reinforce/replace these ligaments were built based on literature specifications and their mechanical properties were obtained through uniaxial tensile tests. The main aim of this study was to simulate the effect of mesh anchoring technique (simple stich and continuous stitch), and compare the displacement magnitude of the pelvic tissues, during Valsalva maneuver. The absence/presence of the synthetic implant was simulated when total rupture of the CLs and USLs occurs, causing a variation of the vaginal displacement (9% for the CLs and 27% for the USLs). Additionally, the simulations showed that there was a variation of the supero-inferior displacement of the vaginal wall between different anchoring techniques (simple stich and continuous stitch) being approximately of 10% for the simulation USLs and CLs implant. The computational simulation was able to mimic the biomechanical behavior of the USLs and CLs, in response to different anchoring techniques, which can be help improving the outcomes of the prolapse surgery.

Quality of life in enuretic children

ABSTRACT Introduction: Nocturnal enuresis is a highly incident chronic disorder that generates countless problems to the child and their parents. Bed-wetting has significant negative impacts on self-esteem and the performance of children. The aim of the current study is to assess the quality of life of enuretic children, as well as its association to sex and age. Patients and Methods: Thirty-nine enuretic children (23 boys) and 49 healthy children (27 boys) without any history of previous treatment for enuresis or voiding dysfunction were included. Age ranged between 6 and 11 years old. The "AUQEI" questionnaire was applied in a private environment to all children by the same researcher (psychologist) to evaluate quality of life. Results: Enuretic children displayed loss in quality of life when compared to non-enuretic (35.9% of enuretic x 16.3% of non-enuretic, p=0.035). They were mostly affected in their daily activities (p=0.02). No significant differences were found in the association of sex and gender with quality of life. These results suggest that, children with nocturnal enuresis have 2.87 times more chances of having loss in quality of life compared to non-enuretic. Conclusions: Enuresis has a great impact in quality of life of children. This impact is not related to the age or sex of the child.

Personal and familial factors associated with toilet training

ABSTRACT Purpose: Toilet training (TT) is an important marker in a child's physical and psychosocial development. The present study aimed to evaluate aspects associated to delayed TT. Material and Methods: We interviewed 372 parents of children who had completed TT up to 48 months before the interview. The questionnaires were applied at school exits when parents went to pick their children up and at public parks. Questions included demographics, aspects related to TT, dysfunction voiding symptom score and evaluation of constipation. Results: The interviews were performed at a mean of 15.3±10.4 (0 to 47) months after the end of TT. Girls accounted for 53% of the sample. The mean age at finishing TT was 31.6±9.3 months and similar in both genders (p=0.77). TT occurred before school entry in 45.7% of the children and medical advice for TT was sought only by 4.8% of the parents. No association was observed of age at completing TT and presence of lower urinary tract symptoms (LUTS) (p=0.57) and/or constipation (p=0.98). In the univariate analysis, prematurity (OR=2.7 [95% CI 2.3-3.1], p <0.0001) and mothers who work outside their household (OR=1.8 [95% CI 1.4-2.3], p <0.0001) were associated to delayed TT. Conclusion: Children completed TT at a mean of 2 years and 7 months of age. The age of completing TT was not related to LUTS and/or constipation. Premature children and those whose mothers work outside the home finish TT later.

Impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists

ABSTRACT Objectives To evaluate the impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists during the month of April 2020. Materials and Methods A 39-question, web-based survey was sent to all urologist members of the Brazilian Society of Urology. We assessed socio-demographic, professional, health and behavior parameters. The primary goal was to evaluate changes in urologists' clinical practice and income after two months of COVID-19. We also looked at geographical differences based on the incidence rates of COVID-19 in different states. Results Among 766 urologists who completed the survey, a reduction ≥ 50% of patient visits, elective and emergency surgeries was reported by 83.2%, 89.6% and 54.8%, respectively. An income reduction of ≥ 50% was reported by 54.3%. Measures to reduce costs were implemented by most. Video consultations were performed by 38.7%. Modifications in health and lifestyle included weight gain (32.9%), reduced physical activity (60.0%), increased alcoholic intake (39.9%) and reduced sexual activity (34.9%). Finally, 13.5% of Brazilian urologists were infected with SARS-CoV-2 and about one third required hospitalization. Urologists from the highest COVID-19 incidence states were at a higher risk to have a reduction of patient visits and non-essential surgeries (OR=2.95, 95% CI 1.86 - 4.75; p< 0.0001) and of being infected with SARS-CoV-2 (OR=4.36 95%CI 1.74-10.54, p=0.012). Conclusions COVID-19 produced massive disturbances in Brazilian urologists' practice, with major reductions in patient visits and surgical procedures. Distressing consequences were also observed on physicians' income, health and personal lives. These findings are probably applicable to other medical specialties.

10th European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals.

Therapeutic proteins and emerging gene and cell-based therapies are attractive therapeutic tools for addressing unmet medical needs or when earlier conventional treatment approaches failed. However, the development of an immune response directed against therapeutic agents is a significant concern as it occurs in a substantial number of cases across products and indications. The specific anti-drug antibodies that develop can lead to safety adverse events as well as inhibition of drug activity or accelerated clearance, both phenomena resulting in loss of treatment efficacy. The European Immunogenicity Platform (EIP) is a meeting place for experts and newcomers to the immunogenicity field, designed to stimulate discussion amongst scientists across industry and academia, encourage interactions with regulatory agencies and share knowledge and the state-of-the-art of immunogenicity sciences with the broader scientific community. Here we report on the main topics covered during the EIP 10th Open Symposium on Immunogenicity of Biopharmaceuticals held in Lisbon, 26-27 February 2019, and the 1-d training course on practical and regulatory aspects of immunogenicity held ahead of the conference. These main topics included immunogenicity testing, clinical relevance of immunogenicity, immunogenicity prediction, regulatory aspects, tolerance induction as a mean to mitigate immunogenicity and immunogenicity in the context of gene therapy.

Topical estradiol increases epidermal thickness and dermal collagen of foreskin prior to hypospadia surgery - Randomized double blinded controlled trial.

INTRODUCTION: The use of preoperative topical testosterone stimulation prior to hypospadias correction aims to increase penile size and achieve better surgical results. Topical estradiol has been shown to improve the quality of skin in other sites, but its use in boys with hypospadia has not yet been elucidated. OBJECTIVE: This study aims to evaluate the primary effects in epidermal thickness and collagen distribution of estradiol compared to testosterone and placebo in skin of prepuce before hypospadia surgery. MATHERIALS AND METHODS: Patients were randomized into three groups according to the topical hormone used: TG: Testosterone ointment; EG: Estradiol ointment; CG: Neutral base ointment. Fragments of foreskin were excised, fixed and then sectioned for histology. For each sample, epidermal thickness and dermal collagen expression was measured by specific computer analysis, P-values of <0.05. RESULTS: Thirty-three patients with a mean age of 4.01 ± 2.92 years were included. Hypospadia classification was similar in all three groups. Mean epidermal thickness and collagen type I expression in EG were greater than those of the other groups. Collagen type III expression was similar in all groups. DISCUSSION: Foreskin has a fundamental role in many techniques of hypospadias surgery and can be used either as a graft or a flap in the correction of the penile defect. Increase of epidermal thickness and dermal collagen observed in the present study has already been related to use of estradiol in other skin sites, but not yet in foreskin. Further studies are needed to evaluate the real significance of these findings in boys with hypospadias. CONCLUSION: Use of topical estradiol before hypospadias surgery lead to greater epidermal thickness and increases dermal collagen expression in foreskin.

Update on complications of synthetic suburethral slings

ABSTRACT Synthetic suburethral slings have become the most widely used technique for the surgical treatment of stress urinary incontinence. Despite its high success rates, significant complications have been reported including bleeding, urethral or bladder injury, urethral or bladder mesh erosion, intestinal perforation, vaginal extrusion of mesh, urinary tract infection, pain, urinary urgency and bladder outlet obstruction. Recent warnings from important regulatory agencies worldwide concerning safety issues of the use of mesh for urogynecological reconstruction have had a strong impact on patients as well as surgeons and manufacturers. In this paper, we reviewed the literature regarding surgical morbidity associated with synthetic suburethral slings.

The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression.

Depression is a prevalent psychiatric disorder with an increasing impact in global public health. However, a large proportion of patients treated with currently available antidepressant drugs fail to achieve remission. Recently, antipsychotic drugs have received approval for the treatment of antidepressant-resistant forms of major depression. The modulation of adult neuroplasticity, namely hippocampal neurogenesis and neuronal remodeling, has been considered to have a key role in the therapeutic effects of antidepressants. However, the impact of antipsychotic drugs on these neuroplastic mechanisms remains largely unexplored. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 3 weeks of stress exposure, animals were treated with two different antipsychotics: haloperidol (a classical antipsychotic) and clozapine (an atypical antipsychotic). We demonstrated that clozapine improved both measures of depressive-like behavior (behavior despair and anhedonia), whereas haloperidol aggravated learned helplessness in the forced-swimming test and behavior flexibility in a cognitive task. Importantly, an upregulation of adult neurogenesis and neuronal survival was observed in animals treated with clozapine, whereas haloperidol promoted a downregulation of these processes. Furthermore, clozapine was able to re-establish the stress-induced impairments in neuronal structure and gene expression in the hippocampus and prefrontal cortex. These results demonstrate the modulation of adult neuroplasticity by antipsychotics in an animal model of depression, revealing that the atypical antipsychotic drug clozapine reverts the behavioral effects of chronic stress by improving adult neurogenesis, cell survival and neuronal reorganization.

Tau-dependent suppression of adult neurogenesis in the stressed hippocampus.

Stress, a well-known sculptor of brain plasticity, is shown to suppress hippocampal neurogenesis in the adult brain; yet, the underlying cellular mechanisms are poorly investigated. Previous studies have shown that chronic stress triggers hyperphosphorylation and accumulation of the cytoskeletal protein Tau, a process that may impair the cytoskeleton-regulating role(s) of this protein with impact on neuronal function. Here, we analyzed the role of Tau on stress-driven suppression of neurogenesis in the adult dentate gyrus (DG) using animals lacking Tau (Tau-knockout; Tau-KO) and wild-type (WT) littermates. Unlike WTs, Tau-KO animals exposed to chronic stress did not exhibit reduction in DG proliferating cells, neuroblasts and newborn neurons; however, newborn astrocytes were similarly decreased in both Tau-KO and WT mice. In addition, chronic stress reduced phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/glycogen synthase kinase-3ß (GSK3ß)/ß-catenin signaling, known to regulate cell survival and proliferation, in the DG of WT, but not Tau-KO, animals. These data establish Tau as a critical regulator of the cellular cascades underlying stress deficits on hippocampal neurogenesis in the adult brain.

Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression.

Depression is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in emotional and cognitive domains. Neuroplastic phenomena are increasingly considered central to the etiopathogenesis of and recovery from depression. Nevertheless, a high number of remitted patients experience recurrent episodes of depression, remaining unclear how previous episodes impact on behavior and neuroplasticity and/or whether modulation of neuroplasticity is important to prevent recurrent depression. Through re-exposure to an unpredictable chronic mild stress protocol in rats, we observed the re-appearance of emotional and cognitive deficits. Furthermore, treatment with the antidepressants fluoxetine and imipramine was effective to promote sustained reversion of a depressive-like phenotype; however, their differential impact on adult hippocampal neuroplasticity triggered a distinct response to stress re-exposure: while imipramine re-established hippocampal neurogenesis and neuronal dendritic arborization contributing to resilience to recurrent depressive-like behavior, stress re-exposure in fluoxetine-treated animals resulted in an overproduction of adult-born neurons along with neuronal atrophy of granule neurons, accounting for an increased susceptibility to recurrent behavioral changes typical of depression. Strikingly, cell proliferation arrest compromised the behavior resilience induced by imipramine and buffered the susceptibility to recurrent behavioral changes promoted by fluoxetine. This study shows that previous exposure to a depressive-like episode impacts on the behavioral and neuroanatomical changes triggered by subsequent re-exposure to similar experimental conditions and reveals that the proper control of adult hippocampal neuroplasticity triggered by antidepressants is essential to counteract recurrent depressive-like episodes.

Lower urinary tract symptoms in children and adolescents with Williams-Beuren syndrome.

INTRODUCTION: Williams-Beuren syndrome (WBS) is a genetic condition caused by a microscopic deletion in the chromosome band 7q11.23. Individuals with WBS may present with congenital cardiovascular defects, neurodevelopmental disturbances and structural abnormalities of the urinary tract. Lower urinary tract symptoms (LUTS) seem to be frequent in this population, but studies on this topic are scarce and based on small case series. OBJECTIVE: To systematically evaluate the prevalence of lower urinary tract symptoms (LUTS) and the acquisition of bladder control in a large population with WBS. STUDY DESIGN: A cross-sectional study evaluating 87 consecutive patients with WBS; there were 41 girls and 46 boys. Genetic studies confirmed WBS in all patients. Subjects were clinically evaluated with: a history of LUTS obtained from the parents and child, a structured questionnaire of LUTS, a 3-day urinary frequency-volume chart, a quality of life question regarding LUTS, and physical examination. A history regarding the acquisition of bladder control was directly evaluated from the parents. RESULTS: Mean age of patients was 9.0 ± 4.2 years, ranging from 3 to 19 years. Based on the symptoms questionnaire and the frequency-volume chart, 70 patients (80.5%) were symptomatic. The most common symptom was urgency, affecting 61 (70.1%) patients, followed by increased urinary frequency in 60 (68.9%) patients, and urge-incontinence in 53 (60.9%), as shown in Summary Fig. More than half of the children reported nocturnal enuresis, including 61% of the girls and 52% of the boys. Twenty-three patients (25.6%) had a history of urinary tract infections. The mean age for acquisition of dryness during the day was 4.4 ± 1.9 years. Parents of 61 patients (70.1%) acknowledged that LUTS had a significant impact on the quality of life of their children. DISCUSSION: A high prevalence of LUTS was confirmed with a significant negative impact on quality of life in a large population of children and adolescents with WBS. It was shown for the first time that the achievement of daytime bladder control is delayed in children with WBS. Although LUTS are not recognized as one of the leading features of the syndrome, it is believed that it should be considered as a significant characteristic of the clinical diagnosis of WBS. CONCLUSIONS: LUTS are highly prevalent in children and adolescents with WBS and have a significant negative impact on patient's quality of life.

Assay for transposase-accessible chromatin and circularized chromosome conformation capture, two methods to explore the regulatory landscapes of genes in zebrafish.

Accurate transcriptional control of genes is fundamental for the correct functioning of organs and developmental processes. This control depends on the interplay between the promoter of genes and other noncoding sequences, whose interaction is mediated by 3D chromatin arrangements. Thus, the detailed description of transcriptional regulatory landscapes is essential to understand the mechanisms of transcriptional regulation. However, to achieve that, two important challenges have to be faced: (1) the identification of the noncoding sequences that contribute to gene transcription and (2) the association of these sequences to the respective genes they control. In this chapter, we describe two protocols that allow overcoming these important challenges: the assay for transposase-accessible chromatin using sequencing (ATAC-seq) and circularized chromosome conformation capture (4C-seq). ATAC-seq is a very efficient technique that, using a very low number of cells as starting material, allows the identification of active chromatin regions genome wide, whereas 4C-seq detects the subset of sequences that interact specifically with the promoter of a given gene. When combined, both techniques provide a comprehensive snapshot of the regulatory landscapes of developmental genes. The protocols we present here have been optimized for teleost fish samples, zebrafish and medaka, allowing the in-depth study of transcriptional regulation in these two emerging animal models. Given the amenability and easy genetic manipulation of these two experimental systems, we anticipate that they will be important in revealing general principles of the vertebrate regulatory genome.

Cinética de secagem e difusividade efetiva em folhas de jenipapo (Genipa americana L. ) / Drying kinetics and effective diffusivity in jenipapo sheets (Genipa americana L. )

RESUMO O jenipapo (Genipa americana L.) é uma espécie nativa com importância medicinal, sendo amplamente utilizada no Brasil. Em função da necessidade de conhecimento à cerca do pré-processamento desta espécie, este trabalho foi desenvolvido com o objetivo de avaliar a cinética de secagem de folhas de jenipapo (G. americana L.), bem como determinar a difusividade efetiva da água durante o processo. As folhas foram coletadas com teor de água inicial de 2,30±0,05 (decimal b.s.), e submetidas à secagem em três condições de temperatura do ar (35,3; 46,0 e 65,0°C) até atingirem o teor de água de equilíbrio. Aos dados experimentais, ajustaram-se doze modelos matemáticos, recomendados para representar o processo de secagem de produtos agrícolas. As magnitudes do coeficiente de determinação (R2), do erro médio relativo (P), do erro médio estimado (SE) e do teste do qui-quadrado (χ2), foram utilizadas para verificar o grau de ajuste dos modelos. Os modelos de Henderson e Pabis modificado e Midilli apresentaram ajustes adequados aos dados experimentais, sendo o modelo de Midilli, em função de sua simplicidade, escolhido para representar a cinética de secagem das folhas de jenipapo. Aumentando a temperatura do ar de secagem de 35,3 para 46,0 e 65,0ºC houve redução no tempo de secagem das folhas de jenipapo de 91,1 para 62,5 e 24,2 horas, respectivamente. O coeficiente de difusão efetivo aumenta com a elevação da temperatura, e esta relação é descrita pela equação de Arrhenius, que apresenta energia de ativação para a difusão líquida de 33,9 kJ mol-1.

ABSTRACT The jenipapo (Genipa americana L.) is a native species with medicinal importance and is widely used in Brazil. Due to the need for knowledge about the preprocessing of this species, this work was developed to evaluate the drying kinetics of the jenipapo leaves (G. americana L.), and also to determine the effective diffusivity of water during the process. The leaves were collected with an initial moisture content of 2.30 ± 0.05 (decimal db), and dried in three conditions of air temperature (35.3, 46.0 and 65.0°C) until they reach the equilibrium moisture content. The experimental data set were twelve mathematical models, recommended to represent the drying process of agricultural products. The magnitudes of the coefficient of determination (R2), the mean relative error (P), the average estimated error (SE) and the chi-square (X2), were used in order to verify the adequacy level of the models. The Henderson, modified Pabis and Midilli models presented appropriate adjustments to the experimental data, with the model Midilli, due to its simplicity, chosen to represent the drying kinetics of the jenipapo leaves. By increasing the temperature of the drying air from 35.3 to 46.0 and 65.0ºC, there was a reduction in the drying time of the jenipapo leaves, from 91.1 to 62.5 and to 24.2 hours, respectively. The effective diffusion coefficient increases with the temperature’s raise, and this relationship is described by the Arrhenius equation, which shows activation energy for liquid diffusion of 33.9 kJ mol-1.

Serotonin 2C receptor antagonists induce fast-onset antidepressant effects.

Current antidepressants must be administered for several weeks to produce therapeutic effects. We show that selective serotonin 2C (5-HT2C) antagonists exert antidepressant actions with a faster-onset (5 days) than that of current antidepressants (14 days) in mice. Subchronic (5 days) treatment with 5-HT2C antagonists induced antidepressant behavioral effects in the chronic forced swim test (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy paradigm. This treatment regimen also induced classical markers of antidepressant action: activation of cAMP response element-binding protein (CREB) and induction of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). None of these effects were induced by subchronic treatment with citalopram, a prototypical selective serotonin reuptake inhibitor (SSRI). Local infusion of 5-HT2C antagonists into the ventral tegmental area was sufficient to induce BDNF in the mPFC, and dopamine D1 receptor antagonist treatment blocked the antidepressant behavioral effects of 5-HT2C antagonists. 5-HT2C antagonists also activated mammalian target of rapamycin (mTOR) and eukaryotic elongation factor 2 (eEF2) in the mPFC, effects recently linked to rapid antidepressant action. Furthermore, 5-HT2C antagonists reversed CMS-induced atrophy of mPFC pyramidal neurons. Subchronic SSRI treatment, which does not induce antidepressant behavioral effects, also activated mTOR and eEF2 and reversed CMS-induced neuronal atrophy, indicating that these effects are not sufficient for antidepressant onset. Our findings reveal that 5-HT2C antagonists are putative fast-onset antidepressants, which act through enhancement of mesocortical dopaminergic signaling.

Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens.

There is accumulating evidence that the nucleus accumbens (NAc) has an important role in the pathophysiology of depression. As the NAc is a key component in the neural circuitry of reward, it has been hypothesized that anhedonia, a core symptom of depression, might be related to dysfunction of this brain region. Neuronal morphology and expression of plasticity-related molecules were examined in the NAc of rats displaying anhedonic behavior (measured in the sucrose-consumption test) in response to chronic mild stress. To demonstrate the relevance of our measurements to depression, we tested whether the observed changes were sensitive to reversal with antidepressants (imipramine and fluoxetine). Data show that animals displaying anhedonic behavior display an hypertrophy of medium spiny neurons in the NAc and, in parallel, have increased expression of the genes encoding for brain-derived neurotrophic factor, neural cell adhesion molecule and synaptic protein synapsin 1. Importantly, the reversal of stress-induced anhedonia by antidepressants is linked to a restoration of gene-expression patterns and dendritic morphology in the NAc. Using an animal model of depression, we show that stress induces anhedonic behavior that is associated with specific changes in the neuronal morphology and in the gene-expression profile of the NAc that are effectively reversed after treatment with antidepressants.

Cell genesis and dendritic plasticity: a neuroplastic pas de deux in the onset and remission from depression.

Brain neuroplasticity is increasingly considered to be an important component of both the pathology and treatment of depressive spectrum disorders. Recent studies shed light on the relevance of hippocampal cell genesis and cortico-limbic dendritic plasticity for the development and remission from depressive-like behavior. However, the neurobiological significance of neuroplastic phenomena in this context is still controversial. Here we summarize recent developments in this topic and propose an integrative interpretation of data gathered so far.

Perceived Stress in Obsessive-Compulsive Disorder is Related with Obsessive but Not Compulsive Symptoms.

Obsessive-compulsive disorder (OCD) is achronic psychiatric disorder characterized by recurrent intrusive thoughts and/or repetitive compulsory behaviors. This psychiatric disorder is known to be stress responsive, as symptoms increase during periods of stress but also because stressful events may precede the onset of OCD. However, only a few and inconsistent reports have been published about the stress perception and the stress-response in these patients. Herein, we have characterized the correlations of OCD symptoms with basal serum cortisol levels and scores in a stress perceived questionnaire (PSS-10). The present data reveals that cortisol levels and the stress scores in the PSS-10 were significantly higher in OCD patients that in controls. Moreover, stress levels self-reported by patients using the PSS-10 correlated positively with OCD severity in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Interestingly, PSS-10 scores correlated with the obsessive component, but not with the compulsive component, of Y-BOCS. These results confirm that stress is relevant in the context of OCD, particularly for the obsessive symptomatology.

Sustained remission from depressive-like behavior depends on hippocampal neurogenesis.

Impairment of hippocampal neurogenesis has been associated with the expression of depressive-like symptoms and some studies have suggested neurogenesis as a critical factor in the normalization of behavior by antidepressant (AD) drugs. This study provides robust evidence that ongoing neurogenesis is essential for the maintenance of behavioral homeostasis and that its pharmacological arrest precipitates symptoms commonly found in depressed patients. Further, the incorporation of newly born neurons and astrocytes into the preexisting hippocampal neurocircuitry is shown to be necessary for the spontaneous recovery from the adverse effects of stress and for long-term benefits of AD treatments.

Early postoperative pelvic-floor biofeedback improves erectile function in men undergoing radical prostatectomy: a prospective, randomized, controlled trial.

Erectile dysfunction (ED) and urinary incontinence are common complications following radical prostatectomy (RP). Although pelvic-floor biofeedback training (PFBT) may improve urinary continence following RP, its effects on the recovery of potency are unknown. Fifty-two patients selected for RP were prospectively randomized for a treatment group (n=26) receiving PFBT once a week for 3 months and home exercises or a control group (n=26), in which patients received verbal instructions to contract the pelvic floor. Erectile function (EF) was evaluated with the International Index of Erectile Function-5 (IIEF-5) before surgery and 1, 3, 6 and 12 months postoperatively. Patients were considered potent when they had a total IIEF-5 score>20. Continence status was assessed and defined as the use of no pads. Groups were comparable in terms of age, body mass index, diabetes, pathological tumor stage and neurovascular bundle preservation. A significant reduction in IIEF-5 scores was observed after surgery in both groups. In the treatment group, 8 (47.1%) patients recovered potency 12 months postoperatively, as opposed to 2 (12.5%) in the control group (P=0.032). The absolute risk reduction was 34.6% (95% confidence interval (CI): 3.8-64%) and the number needed to treat was 3 (95% CI: 1.5-17.2). A strong association between recovery of potency and urinary continence was observed, with continent patients having a 5.4 higher chance of being potent (P=0.04). Early PFBT appears to have a significant impact on the recovery of EF after RP. Urinary continence status was a good indicator of EF recovery, with continent patients having a higher chance of being potent.

The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling.

The mechanisms underlying the initiation/onset of, and the recovery from, depression are still largely unknown; views that neurogenesis in the hippocampus may be important for the pathogenesis and amelioration of depressive symptoms have gained currency over the years although the original evidence has been challenged. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 2 weeks of stress exposure, animals were treated with the antidepressants fluoxetine, imipramine, CP 156,526 or SSR 1494515, alone or combined with methylazoxymethanol, a cytostatic agent used to arrest neurogenesis. We found that antidepressants retain their therapeutic efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked. Instead, our experiments suggest re-establishment of neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus and prefrontal cortex, rather than neurogenesis, as the basis for the restoration of behavioral homeostasis by antidepressants.