Transcriptional and Histone Acetylation Changes Associated with CRE Elements Expose Key Factors Governing the Regulatory Circuit in the Early Stage of Huntington's Disease Models.

Huntington's disease (HD) is a disorder caused by an abnormal expansion of trinucleotide CAG repeats within the huntingtin (Htt) gene. Under normal conditions, the CREB Binding Protein interacts with CREB elements and acetylates Lysine 27 of Histone 3 to direct the expression of several genes. However, mutant Htt causes depletion of CBP, which in turn induces altered histone acetylation patterns and transcriptional deregulation. Here, we have studied a differential expression analysis and H3K27ac variation in 4- and 6-week-old R6/2 mice as a model of juvenile HD. The analysis of differential gene expression and acetylation levels were integrated into Gene Regulatory Networks revealing key regulators involved in the altered transcription cascade. Our results show changes in acetylation and gene expression levels that are related to impaired neuronal development, and key regulators clearly defined in 6-week-old mice are proposed to drive the downstream regulatory cascade in HD. Here, we describe the first approach to determine the relationship among epigenetic changes in the early stages of HD. We determined the existence of changes in pre-symptomatic stages of HD as a starting point for early onset indicators of the progression of this disease.

Mechanical stretch increases L-type calcium channel stability in cardiomyocytes through a polycystin-1/AKT-dependent mechanism.

The L-type calcium channel (LTCC) is an important determinant of cardiac contractility. Therefore, changes in LTCC activity or protein levels could be expected to affect cardiac function. Several studies describing LTCC regulation are available, but only a few examine LTCC protein stability. Polycystin-1 (PC1) is a mechanosensor that regulates heart contractility and is involved in mechanical stretch-induced cardiac hypertrophy. PC1 was originally described as an unconventional Gi/o protein-coupled receptor in renal cells. We recently reported that PC1 regulates LTCC stability in cardiomyocytes under stress; however, the mechanism underlying this effect remains unknown. Here, we use cultured neonatal rat ventricular myocytes and hypo-osmotic stress (HS) to model mechanical stretch. The model shows that the Cavß2 subunit is necessary for LTCC stabilization in cardiomyocytes during mechanical stretch, acting through an AKT-dependent mechanism. Our data also shows that AKT activation depends on the G protein-coupled receptor activity of PC1, specifically its G protein-binding domain, and the associated Gßγ subunit of a heterotrimeric Gi/o protein. In fact, over-expression of the human PC1 C-terminal mutant lacking the G protein-binding domain blunted the AKT activation-induced increase in Cav1.2 protein in cardiomyocytes. These findings provide novel evidence that PC1 is involved in the regulation of cardiac LTCCs through a Gißγ-AKT-Cavß2 pathway, suggesting a new mechanism for regulation of cardiac function.

Pharmacokinetics of ivermectin in sheep following pretreatment with Escherichia coli endotoxin.

The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 µg LPS/kg bw at -24, -16, and -0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non-compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half-life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day-1 ml-1 ), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.

Plasma disposition kinetics of moxidectin after subcutaneous administration to pregnant sheep.

The plasma kinetic profile of moxidectin (MXD) in ewes during the last third of pregnancy was studied after the subcutaneous dose of 0.2 mg/kg of body weight (bw). Two groups of sheep (n = 7) that were equally balanced in body weight were used. Group I (control) was maintained unmated, while Group II (pregnant) was estrous-synchronized and mated with fertile rams. Both groups were maintained under similar conditions regarding management and feeding. When the ewes from Group II fulfilled 120 days of pregnancy, both groups were treated with a subcutaneous injection of 0.2 mg of MXD/kg bw. Blood samples were collected at different set times between 1 h and 40 days post-treatment. After plasma extraction and derivatization, the samples were analyzed using high-performance liquid chromatography with fluorescence detection. A noncompartmental pharmacokinetic analysis was performed, and the data were compared using Student's t-test. The mean pharmacokinetic parameters, including Cmax , Tmax , and the area under the concentration-time curve (AUC), were similar for both groups of sheep. The average of elimination half-life was significantly lower (P = 0.0023) in the pregnant (11.49 ± 2.2 days) vs. the control (17.89 ± 4.84 days) sheep. Similarly, the mean residence time (MRT) for the pregnant group (20.6 ± 3.8 days) was lower (P = 0.037) than that observed in the control group (27.4 ± 9.1 days). It is concluded that pregnancy produces a significant decrease in mean values of half-life of elimination of MXD, indicating that pregnancy can increase the rate of elimination of the drug reducing their permanence in the body.

Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis.

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1-/- mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD.

Characteristics of hospitalised patients with 2009 H1N1 influenza in Chile.

As the pandemic of 2009 H1N1 influenza A virus progressed, more patients required hospitalisation. The objective of this study is to describe the characteristics and clinical course of hospitalised patients with 2009 H1N1 virus infection in Chile. This was a prospective, observational study of 100 consecutive hospitalised patients with RT-PCR-confirmed 2009 H1N1 influenza A, admitted to Puerto Montt General Hospital (Puerto Montt, Chile). Information was obtained regarding contact history, demographics, laboratory values and clinical course. The primary reason for hospitalisation was pneumonia, in 75% of patients. Rapid influenza A test was positive in 51% of patients. Prior exposure to 2009 H1N1 virus was documented in 21% of patients. Clinical failure, documented in 18% of cases, was characterised by respiratory failure and acute respiratory distress syndrome. Failure was more common in patients with obesity, tachypnoea, confusion and multilobar infiltrates. When evaluating a patient hospitalised with influenza-like illness, a negative rapid test for influenza A or negative contact with a suspected case should not alter physicians' considerations regarding the likelihood of 2009 H1N1 virus infection. Patients with 2009 H1N1 virus infection with obesity, tachypnoea, confusion and multilobar infiltrates should be closely monitored since they are at high risk for clinical failure.

Coronavirus Optimization Algorithm: A Bioinspired Metaheuristic Based on the COVID-19 Propagation Model.

This study proposes a novel bioinspired metaheuristic simulating how the coronavirus spreads and infects healthy people. From a primary infected individual (patient zero), the coronavirus rapidly infects new victims, creating large populations of infected people who will either die or spread infection. Relevant terms such as reinfection probability, super-spreading rate, social distancing measures, or traveling rate are introduced into the model to simulate the coronavirus activity as accurately as possible. The infected population initially grows exponentially over time, but taking into consideration social isolation measures, the mortality rate, and number of recoveries, the infected population gradually decreases. The coronavirus optimization algorithm has two major advantages when compared with other similar strategies. First, the input parameters are already set according to the disease statistics, preventing researchers from initializing them with arbitrary values. Second, the approach has the ability to end after several iterations, without setting this value either. Furthermore, a parallel multivirus version is proposed, where several coronavirus strains evolve over time and explore wider search space areas in less iterations. Finally, the metaheuristic has been combined with deep learning models, to find optimal hyperparameters during the training phase. As application case, the problem of electricity load time series forecasting has been addressed, showing quite remarkable performance.

A low temperature scanning tunneling microscope for electronic and force spectroscopy.

In this article, we describe and test a novel way to extend a low temperature scanning tunneling microscope with the capability to measure forces. The tuning fork that we use for this is optimized to have a high quality factor and frequency resolution. Moreover, as this technique is fully compatible with the use of bulk tips, it is possible to combine the force measurements with the use of superconductive or magnetic tips, advantageous for electronic spectroscopy. It also allows us to calibrate both the amplitude and the spring constant of the tuning fork easily, in situ and with high precision.

Mooren's ulcer: 30 years of follow-up. / Úlcera de Mooren: 30 años de seguimiento.

CASE REPORT: A 33-year-old Caucasian female presented with epiphora, ocular pain, and foreign body sensation in both eyes for one month. Examination revealed bilateral peripheral corneal ulcers. The patient had been treated with immunomodulators, and she was treated in the left eye with peripheral semi-circular keratoplasty, penetrating keratoplasty, conjunctival-corneal-scleroplasty, buccal mucosal graft, tibial osteo-keratoprosthesis and finally, retinal detachment. DISCUSSION: Mooren's ulcer is an immunological corneal disease. This lesion must be treated initially with immunomodulators. Surgical treatment should be considered when a risk of corneal perforation is present, when the perforation appears, or under acute necrosis.

Similarities between the Binding Sites of SB-206553 at Serotonin Type 2 and Alpha7 Acetylcholine Nicotinic Receptors: Rationale for Its Polypharmacological Profile.

Evidence from systems biology indicates that promiscuous drugs, i.e. those that act simultaneously at various protein targets, are clinically better in terms of efficacy, than those that act in a more selective fashion. This has generated a new trend in drug development called polypharmacology. However, the rational design of promiscuous compounds is a difficult task, particularly when the drugs are aimed to act at receptors with diverse structure, function and endogenous ligand. In the present work, using docking and molecular dynamics methodologies, we established the most probable binding sites of SB-206553, a drug originally described as a competitive antagonist of serotonin type 2B/2C metabotropic receptors (5-HT2B/2CRs) and more recently as a positive allosteric modulator of the ionotropic α7 nicotinic acetylcholine receptor (nAChR). To this end, we employed the crystal structures of the 5-HT2BR and acetylcholine binding protein as templates to build homology models of the 5-HT2CR and α7 nAChR, respectively. Then, using a statistical algorithm, the similarity between these binding sites was determined. Our analysis showed that the most plausible binding sites for SB-206553 at 5-HT2Rs and α7 nAChR are remarkably similar, both in size and chemical nature of the amino acid residues lining these pockets, thus providing a rationale to explain its affinity towards both receptor types. Finally, using a computational tool for multiple binding site alignment, we determined a consensus binding site, which should be useful for the rational design of novel compounds acting simultaneously at these two types of highly different protein targets.

Forceps and vacuum injuries to the cornea: histopathologic features of twelve cases and review of the literature.

Histopathologic and ultrastructural features were examined from 11 cases of corneal injury from obstetrical forceps and one case from vacuum extraction. Four major types of histopathologic features were observed. Type I (n = 4) included large tears of Descemet's membrane with a fragment of Descemet's membrane extending into the anterior chamber at one end of the tear and scroll formation at the other end. Type II (n = 6) consisted of scrolls of Descemet's membrane at each margin of the original break. Type III (n = 2) included those with small breaks in Descemet's membrane and healing by fibrosis at and posterior to the original tear. Type IV (n = 1) contained a small break in Descemet's membrane with minimal fibrosis. Transmission electron microscopy revealed Descemet's scrolls and retrocorneal fibrous tissue. Scanning electron microscopy revealed folds in Descemet's membrane and attenuation or absence of endothelium. Spindle- and stellate-shaped cells and pigment granules were present in the area of the tear in most cases. A review of the literature is presented.

Case report: Conservative management of an arteriovenous fistula of the inferior epigastric artery.

We present a case of pseudoaneurysm and arteriovenous fistula of the inferior epigastric artery secondary to the placement of a drain during a surgical intervention. We stress the utility of colour Doppler ultrasound and arteriography embolisation in diagnosis and treatment, respectively.

[Blastocystosis and other intestinal protozoan infections in human riverside communities of the Valdivia River basin, Chile]. / Blastocistosis y otras infecciones por protozoos intestinales en comunidades humanas ribereñas de la cuenca del Río Valdivia, Chile.

Between March and October 1987, the prevalence of infection by Blastocystis hominis and other intestinal protozoan, their relationship with the age and sex of the hosts, and the percentage of infected persons in family groups were determined in riverside communities of Valdivia River Basin, Chile. One or more intestinal protozoan species were determined in 72.5% of the examined persons. The prevalence was greater for B. hominis (61.8%). The prevalences of B. hominis, Endolimax nana and Entamoeba coli were greater in relation to the age of the host. The sex of the host and prevalence of infections by B. hominis and other species of intestinal protozoans did not show association. Prevalence of B. hominis was greater in persons from houses with no sanitary faeces disposal. Over 60% of the members of family groups showed infection by B. hominis in 53.1% of the groups compared to 2.4%-21.8% of infections by other protozoan species. Faecal samples of 45 pigs revealed 22.2% of infection by Blastocystis.

Evolutionary learning of hierarchical decision rules.

This paper describes an approach based on evolutionary algorithms, hierarchical decision rules (HIDER), for learning rules in continuous and discrete domains. The algorithm produces a hierarchical set of rules, that is, the rules are sequentially obtained and must therefore be tried until one is found whose conditions are satisfied. Thus, the number of rules may be reduced because the rules could be inside of one another. The evolutionary algorithm uses both real and binary coding for the individuals of the population. We tested our system on real data from the UCI repository, and the results of a ten-fold cross-validation are compared to C4.5s, C4.5Rules, See5s, and See5Rules. The experiments show that HIDER works well in practice.

Esophageal candidiasis in HIV-negative patients.

UNLABELLED: Candida esophagitis is the most frequent esophageal infection in HIV seropositive as well as in seronegative patients. AIM: this retrospective study was designed to determine the characteristics of this disease in HIV negative patients in a general hospital. DESIGN: clinical records of all HIV negative patients with Candida esophagitis, which was endoscopically diagnosed and microscopically confirmed (biopsy and/or cytology of esophageal mucosa), were studied. RESULTS: thirty-one patients (23 men, 8 women, mean age: 65.4 +/- 14.3 years, median 71) fulfilled the criteria (0.56% of the diagnostic esophagogastroduodenal endoscopies). The most common clinical symptoms were dysphagia with or without odynophagia and pain (retrosternal, epigastric or xiphoid). Fourteen patients (45%) had no esophageal signs; in nine of them (29%) the disease was diagnosed in the course of an endoscopic exam to investigate the sources of acute or chronic anaemia. The most frequent predisposing factors were diabetes mellitus, oral or aerosolized corticotherapy, malignancies, treatment with broad-spectrum antibiotics and liver cirrhosis. Nine patients (29%) presented no known predisposing factors. The most common endoscopic appearance was grade II (51%). Sixty-one per cent of the patients exhibited at least one other esophagogastroduodenal endoscopic lesion associated with the mycosis. Three patients died of their underlying diseases within one week of the diagnosis of the candidiasis. Only one patient presented persistence of candidiasis one week after initiating treatment with oral nystatine. CONCLUSIONS: esophageal candidiasis is infrequent and does not always present with suspicious symptoms or known predisposing factors. Aerosolized corticotherapy may be a risk factor for the development of esophageal candidiasis.

[Epidemiology of diphyllobothriasis in the Valdivia river basin, Chile]. / Epidemiología de la difilobotriasis en la cuenca del Río Valdivia, Chile.

In the Valdivia (Chile) river basin 1,295 inhabitants of 6 riverside districts were examined between March and October 1987 and showed a 1.2% of prevalence by Diphyllobothrium in the districts of Riñihue and Las Huellas. Prevalence of 5.3% and 9.8% respectively were registered in dogs of the districts of Riñihue and Malihue. No cat or pig infection was observed in the different districts. The parasites recovered after the treatment were identified as Diphyllobothrium latum. Human infection by D. latum in the districts affected results from the consumption of smoked or insufficiently cooked fish. The investigation of 1,450 fish (4 exotic species and 11 autochthonous ones), caught in the Valdivia river basin in 1986 and 1987, showed the existence of plerocercoids of D. latum and/or Diphyllobothrium dendriticum in Salmo gairdneri and Salmo trutta among exotic fish and in some autochthonous species. Prevalence and mean intensity in the infection of fish as well as the degree of aggregation in the infrapopulations varied in the different districts. Some species of fish would act as intermediary hosts and others as paratenic hosts in the life cycles of Diphyllobothrium spp. in the Valdivia river basin. An improvement in the conditions of basic sanitation, in sanitary education and in the treatment of infected persons is proposed as a means for the control of diphyllobothriasis in the districts affected.

[Severe isolated pulmonary hypertension as main manifestation of Crest syndrome]. / Hipertensión pulmonar aislada severa como manifestación principal del síndrome Crest.

Interstitial pulmonary fibrosis is the leading cause of secondary pulmonary hypertension in systemic sclerosis, and it occurs in either limited or diffuse cutaneous scleroderma subset. Isolated pulmonary hypertension, without pulmonary disease, occurs primarily in patients with limited cutaneous scleroderma (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia [CREST] variant) although it is an unusual feature in this subset, with a worse prognosis in the short term. We present a previously undiagnosed patient with the CREST syndrome, with severe isolated pulmonary hypertension and secondary respiratory failure as major feature of its connective tissue disease. Clinical, prognostic and therapeutical aspects are commented.

Forensic paleoradiology: identification of a public figure murdered in 1837.

Two unidentified graves were found during construction of a new crypt at the Metropolitan Cathedral in Santiago, Chile. One of the bodies was sent to the Teaching Hospital of the University of Chile for forensic identification. The fully mummified corpse was suspected to be that of Diego Portales, a prominent Chilean politician who was assassinated in 1837. The condition of the corpse determined that the best way to establish a positive identification was by means of a multislice CT scan, since the body had been autopsied and embalmed using unknown substances. This paper presents the results of the virtual autopsy of the remains and compares these results with the original autopsy report of 1837. The embalming method is also discussed, based on chemical analysis using inductively coupled mass spectroscopy (ICP-MS) and cold vapour atomic absorption spectrometry (HG-CVAAS).

[Study of sociodemographic and psychopathological risk factors in suicide attempts. 2008-2010]. / Análisis de los intentos de autolisis en un área de salud. 2008-2010.

OBJECTIVE: The aim of this study is to determine the sociodemographic and psychopathological features and risk factors associated with suicide attempts. DESIGN: A descriptive cross-sectional study based on medical records. Emergency Primary Care Centres (Jumilla, Yecla) and Hospital Emergency Departments (Yecla, Murcia, Spain). RESULTS: The suicide attempt rate increases in younger people (average of 36.4 years old). Suicide attempts are higher among women (67%). In terms of psychopathological data, suicide attempts were characterised by a higher prevalence of depression and anxiety disorder (30%), and substance abuse (13%). The percentage of patients who had made a previous suicide attempt was 37%. Self-poisoning was the most recurrent method of suicide attempt, present in at least 80% of the cases. Gender was a significant factor in the cause of suicide attempt (P=.042) and psychopathology (P=.011). The geographic origin of the patient is significantly associated with the suicide method used (P=.000). CONCLUSIONS: Suicide treatment protocols and suicide prevention programs must be developed, as well as recording the risk factors in the patient history.

Cirugías de afirmación de género en mujeres trans: resultados estéticos, sexuales y urinarios de una serie inicial de vaginoplastias / Gender affirmation surgeries in transgender women: Aesthetic, sexual, and urinary results of an initial series of vaginoplasties

Introducción y objetivos: La disforia de género se asocia a elevada comorbilidad de salud mental, como depresión y suicidio. Las «cirugías de afirmación de género» mejoran la sexualidad y el bienestar psicosocial. El objetivo de la vaginoplastia es que los genitales se asemejen en forma y función a una vagina con una profundidad de al menos 11cm y un clítoris sensible. Además, la uretra debe acortarse y permitir la micción en posición sentada. Nuestro objetivo es describir los resultados estéticos, sexuales y urinarios.Pacientes y métodoEstudio retrospectivo de todas las pacientes operadas de genitoplastia feminizante en el Hospital Sótero del Río entre 2018 y 2019 que cumplían requisitos de WPATH. Se evaluaron dimensiones vaginales, sensibilidad del neoclítoris, conformidad estética y sexual de la neovagina, cuestionarios Índice de Función Sexual Femenina (FSFI) y la Escala de Autoimagen Genital Femenina (FGSIS), IPSS-QoL, uroflujometría y residuo posmiccional.ResultadosSe identificaron 10 mujeres operadas de genioplastia feminizante. La profundidad promedio neovaginal fue de 14,2cm. No hubo lesión rectal ni reoperación. Hubo 100% de sensibilidad del neoclítoris y 88% de conformidad con el ancho neovaginal. La FGSIS promedió 25,4 puntos y el FSFI promedió 16 puntos. El IPSS fue de 6,7 puntos, el Qmax promedio fue de 22ml/s y el residuo posmiccional promedio fue de 22ml. No hubo estenosis del neomeato.ConclusionesLa genitoplastia feminizante es una cirugía compleja, exigente y no completamente estandarizada. Sin embargo, es un procedimiento relativamente seguro que logra adecuados resultados estéticos, sexuales y urinarios. (AU)

Introduction and objectives: Gender dysphoria is associated with mental health comorbidity, such as depression and suicide. “Gender affirming surgeries” improve sexuality and psychosocial well-being. The goal of vaginoplasty is for the genitalia to resemble in form and function to a biological vagina with a depth of at least 11 cm and a sensitive clitoris. In addition, the urethra must be shortened and allow voiding in a sitting position. Our objective is to describe the aesthetic, sexual and urinary results.Patients and methodRetrospective study of all patients undergoing feminizing genitoplasty, at Hospital Sótero del Río between 2018 and 2019, that met WPATH requirements. Vaginal dimensions, neo-clitoral sensitivity, aesthetic and sexual satisfaction of the neovagina, questionnaires Female Sexual Function Index (FSFI) and the Female Genital Self-Image Scale (FGSIS), IPSS-QoL, uroflowmetry and post-void residue were evaluated.Results10 women who underwent feminizing genitoplasty were identified. The neovaginal depth average was 14.2 cm. There was no rectal injury or reoperation. There was 100% of Neoclitoris sensitivity and 88% satisfaction with the neovaginal width.The FGSIS averaged 25.4 points and the FSFI averaged 16 points. The IPSS was 6.7 points, the average Qmax was 22 ml/s and post-void residual volume average was 22 ml. There was no neomeatal stenosis.ConclusionsFeminizing Genitoplasty is a complex, demanding and not completely standardized surgery. However, it is a relatively safe procedure that achieves adequate aesthetic, sexual and urinary results. (AU)