975 resultados para Lower urinary tract dysfunction
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Background and aims: The selective SGLT2 inhibitor dapagliflozin (DAPA) reduces hyperglycaemia independently of insulin secretion or action by inhibiting renal glucose reabsorption. This study (MB102014) is a randomised double-blind, placebo (PBO)-controlled trial of DAPA added to metformin (MET) in T2DM (n=546) inadequately controlled with MET alone. Previously reported short-term data at week 24 showed significant mean reductions in the primary [HbA1c] and secondary [fasting plasma glucose (FPG) and weight] endpoints with DAPA compared to PBO. Here we report efficacy and safety results at week 102 of the long-term extension. Materials and methods: Patients aged 18-77 years with HbA1c 7-10% received DAPA 2.5 mg, 5 mg, 10 mg or PBO, plus open-label MET (≥1500mg/d). Exploratory endpoints at week 102 included changes from baseline in HbA1c, FPG and weight, and were analyzed by longitudinal repeated measures analysis. Results: Overall 71.2% of patients completed 102 weeks of the study; fewer on PBO (63.5%) than on DAPA 2.5 mg, 5 mg, and 10 mg (68.3%, 73.0%, 79.8%), due mainly to more patients on PBO discontinuing for lack of efficacy. At week 102, all DAPA groups showed greater mean reductions from baseline in HbA1c, FPG and weight compared to PBO (table), effects that were similar to those observed at week 24 and maintained throughout the trial. More patients at week 102 also achieved a therapeutic response of HbA1c<7% with DAPA 2.5 mg, 5 mg, and 10 mg (20.7%, 26.4%, 31.5%) than with PBO (15.4%). Adverse events (AEs), serious AEs and AEs leading to discontinuation were balanced across all groups. Signs and symptoms suggestive of genital infection (GenInf) were reported in 11.7%, 14.6%, 12.6% (DAPA 2.5 mg, 5 mg, 10 mg) and 5.1% (PBO) of patients, with 1 discontinuation due to GenInf. Signs and symptoms suggestive of urinary tract infection (UTI) were reported in 8.0%, 8.8%, 13.3% (DAPA 2.5 mg, 5 mg, 10 mg) and 8.0% (PBO), with 1 discontinuation due to UTI. No event of pyelonephritis was reported. Conclusion: In comparison to PBO, DAPA added to MET over 102 weeks demonstrated greater and sustained improvements in glycaemic control, clinically meaningful reduction in weight, and no increased risk of hypoglycaemia in patients with T2DM inadequately controlled with MET alone.
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Introduction : La néphro-urétérectomie radicale (NUR) représente le traitement primaire pour les patients atteints d’une tumeur des voies excrétrices supérieures (TVES) non métastatique. Une approche ouverte ou laparoscopique peut être considérée. Malgré la présence de plusieurs études comparant les résultats périopératoires et oncologiques entre ces deux approches, aucunes études se basent sur une cohorte populationnelle. Objectif : Notre but est d’évaluer la morbidité péri-opératoire entre la NUR ouverte et laparoscopique en utilisant une cohorte populationnelle. Méthode : Nous avons utilisé la base de donnée Nationwide Inpatient Sample (NIS) pour identifier tous les patients atteints d’une TVES non métastatique, traités par NUR ouverte ou laparoscopique, entre 1998 et 2009. Au total, 7401 (90,8%) et 754 (9,2%) patients ont subi une NUR ouverte et laparoscopique, respectivement. Dans le but de contrôler les différences inhérentes entre les deux groupes, nous avons utilisé une analyse par appariement sur les scores de propension. Ainsi, 3016 (80%) patients avec NUR ouverte étaient appariés à 754 (20%) patients avec NUR laparoscopique. Intervention : Tous les patients ont subi une NUR. Mesures : Les taux de complications intra-opératoires et post-opératoires, de transfusions sanguines, d’hospitalisation prolongée et de mortalité intrahospitalière ont été mesurés. Des analyses de régression logistique on été utilisées pour notre cohorte, après appariement sur les scores de propension. Résultats et Limitations : Pour les patients traités par approche ouverte vs. laparoscopique, les taux suivants furent calculés : transfusions sanguines : 15 vs. 10% (p<0,001); complications intra-opératoires : 4,7 vs. 2,1% (p=0,002); complications post-opératoires : 17 vs. 15% (p=0,24); durée d’hospitalisation prolongée (≥ 5 jours) : 47 vs. 28% (p<0,001); mortalité intra-hospitalière 1,3 vs. 0,7% (p=0,12). Sur les analyses par régression logistique, les patients ayant été traités par NUR laparoscopique avaient moins de chance de recevoir une transfusion sanguine (odds ratio [OR]: 0,6, p<0,001), de subir une complication intra-opératoire (OR: 0,4, p=0,002), et d’avoir une durée prolongée d’hospitalisation (OR: 0,4, p<0,001). Globalement les taux de complications postopératoires étaient équivalents. Toutefois, l’approche laparoscopique était associée à moins de complications pulmonaires (OR: 0,4, p=0,007). Cette étude est limitée par sa nature rétrospective. Conclusion: Après ajustement de potentiels biais de sélection, la NUR par approche laparoscopique est associée à moins de complications intraopératoires et péri-opératoires comparée à la NUR par approche ouverte.
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Essai doctoral présenté à la Faculté des études supérieures en vue de l’obtention du grade de Docteur en psychologie (D.Psy.), option clinique
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Essai doctoral présenté à la Faculté des études supérieures en vue de l’obtention du grade de Docteur en psychologie (D.Psy.), option clinique
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Introducción: La IVU es muy frecuenten en la (FCI - IC), Alrededor el 60% de los pacientes con diagnóstico de IVU nosocomial corresponden a gérmenes resistente, Desde el año 2010 el CLSI disminuyó los puntos de corte de sensibilidad en las enterobacteriaceae y removió la necesidad de tamizaje y confirmación de (BLEE), en el presente trabajo se pretende determinar el perfil epidemiológico de la formulación antibiótica en pacientes con IVU nosocomial. Diseño: Se realizó un estudio observacional analítico de corte transversal. Métodos: Se realizó un análisis univariado, bivariado y multivariado. El análisis bivariado y multivariado se realizó para determinar la medida de asociación teniendo en cuenta la formulación de Carbapenemico la variable dependiente, evaluándose mediante chi cuadrado. Resultados: Se revisaron 131 urocultivos, se incluyeron 116. Los aislamientos microbiológicos más frecuentemente encontrados fueron E. Coli y K. Pneumoniae, el 43.4% de los aislamientos, presentaron expresión de BLEE, 90% de los aislamientos fueron sensibles a Cefepime. La mayoría de los modelos obtenidos mostraron una fuerte asociación entre el reporte de BLEE en antibiograma con la formulación de carbapenémicos como terapia final OR 33,12 IC 95% (2,90 – 337,4). Conclusión: La epidemiologia de la IVU nosocomial en la FCI-IC no difiere de las referencias internacionales, no hay adherencia a las guías de manejo intrahospitalario y el reporte de la palabra BLEE en el antibiograma predice la formulación de antibiótico carbapenémico por el médico que lee el urocultivo
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Uropathogenic Escherichia coli (UPEC) accounts for approximately 85% of all urinary tract infections (UTIs), causing a global economic burden. E. coli is one of the pathogens mentioned in the ESKAPEE list drafted by OMS, meaning that the increasing antibiotic resistance acquired by UPEC is and will be a serious health problem in the future. Amongst the immunogenic antigens exposed on the surface of UPEC, FimH represent a potential target for vaccine development, since it is involved in the early stages of infection. As already demonstrated, immunizations with FimH elicit functional antibodies that prevent UPEC infections even though the number of doses required to elicit a strong immune response is not optimal. In this work, we aimed to stabilize FimH as a soluble recombinant antigen exploiting the donor strand complementation mechanism by generating different chimeric constructs constituted by FimH and FimG donor strand. To explore the potential of self-assembling nanoparticles to display FimH through genetic fusion, different constructs have been computationally designed and produced. In this work a structure-based design, using available crystal structures of FimH and three different NPs was performed to generate different constructs with optimized properties. Despite the different conditions tested, all the constructs designed (single antigen or chimeric NPs), resulted to be un-soluble proteins in E. coli. To overcome this issue a mammalian expression system has been tested. Soluble antigen expression was achieved for all constructs tested in the culture supernatants. Three novel chimeric NPs have been characterized by transmission electron microscopy (TEM) confirming the presence of correctly assembled NPs displaying UPEC antigen. In vivo study has shown a higher immunogenicity of the E. coli antigen when displayed on NPs surface compared to the single recombinant antigen. The antibodies elicited by chimeric NPs showed a higher functionality in the inhibition of bacterial adhesion.
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AIMS: The present is a retrospective evaluation of acute genito-urinary (GU) and gastro-intestinal (GI) toxicity, in addition to biochemical recurrence rate in 57 prostate cancer patients treated at our Institution with ultra-hypofractionated RT (UHRT) schedule. METHODS: From January 2021 to December 2022 we have treated 57 patients with prostate cancer, using an UHRT scheme of 5-fractions every other day for a total dose delivered of 36.25 Gy, according to the PACE-B trial treatment schedule. Good urinary function, assessed by International Prostate Symptom Score (IPSS), were required. The simulation CT scans were acquired in supine position and fused with MRI for CTVs definition for every patient. Each treatment was performed by Accuray's TomoTherapy with daily IGRT. The evaluation of the set-up was very restrictive before daily treatment delivery. RESULTS: According to RTOG toxicity scale, the acute GU toxicity at 3 months from RT, GU toxicity was G0 for 30 patients (52.6%), G1 for 26 (45.6%) and G2 for one only (1.75%); rectal toxicity was G0 for 56 patients (98.25%) and G1 for one only (1.75%). The median follow-up (FU) was 9 months (2-24 months). In the following FU months, we observed progressively lower urinary and rectal toxicity, except for one patient who showed G2 GU toxicity at 12 months. All but one patient had a progressive PSA value decrease. CONCLUSIONS: In our experience, UHRT appears to be safe and well tolerated even without the use of rectal spacer devices. A longer FU is necessary to evaluate late toxicity and disease control rate.
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This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r(2)>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.
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We described angiotensin-I-converting enzyme (ACE) isoforms with molecular masses of 190, 90, and 65 kDa in the urine of normotensive offspring of hypertensive subjects. Since they did not appear in equal amounts, we suggested that 90 kDa ACE might be a marker for hypertension. We evaluated the endothelial response in normotensive offspring with or without family history of hypertension and its association with the 90 kDa ACE in urine. Thirty-five normotensive subjects with a known family history of hypertension and 20 subjects without a family history of hypertension, matched for age, sex, body weight, and blood pressure, were included in the study. Endothelial function was assessed by ultrasound and a sample of urine was collected for determination of ACE isoforms. In the presence of a family history of hypertension and detection of 90 kDa ACE, we noted a maximal flow mediated dilation of 12.1 ± 5.0 vs 16.1 ± 6.0% in those without a previous history of hypertension and lacking urinary 90 kDa ACE (P < 0.05). In subjects with a family history of hypertension and presenting 90 kDa ACE, there were lower levels of HDL-cholesterol (P < 0.05) and higher levels of triglycerides (P < 0.05). Subjects with 90 kDa ACE irrespective of hypertensive history presented a trend for higher levels of triglycerides and HDL-cholesterol (P = 0.06) compared to subjects without 90 kDa ACE. Our data suggest that the 90 kDa ACE may be a marker for hypertension which may be related to the development of early atherosclerotic changes.
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Objective: Evaluation of selective decontamination of the digestive tract (SDD) on late mortality in ventilated trauma patients in an intensive care unit (ICU). Methods: A multicenter, randomized controlled trial was undertaken in 401 trauma patients with Hospital Trauma Index-Injury Severity Score of 16 or higher. Patients were randomized to control (n = 200) or SDD (n = 201), using polymyxin E, tobramycin, and amphotericin B in throat and gut throughout ICU treatment combined with cefotaxime for 4 days. Primary endpoint was late mortality excluding early death from hemorrhage or craniocerebral injury. Secondary endpoints were infection and organ dysfunction. Results: Mortality was 20.9% with SDD and 22.0% in controls. Overall late mortality was 15.3% (57/372) as 29 patients died from cerebral injury, 16 SDD and 13 control. The odds ratio (95% confidence intervals) of late mortality for SDD relative to control was 0.75 (0.40-1.37), corresponding to estimates of 13.4% SDD and 17.2% control. The overall infection rate was reduced in the test group (48.8% vs. 61.0%). SDD reduced lower airway infections (30.9% vs. 50.0%) and bloodstream infections due to aerobic Gram-negative bacilli (2.5% vs. 7.5%). No difference in organ dysfunction was found. Concluson: This study demonstrates that SDD significantly reduces infection in multiple trauma, although this RCT in 401 patients was underpowered to detect a mortality benefit.
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The present study was carried out to investigate the effects of copper (Cu) intake on lipid profile, oxidative stress and tissue damage in normal and in diabetic condition. Since diabetes mellitus is a situation of high-risk susceptibility to toxic compounds, we examined potential early markers of Cu excess in diabetic animals. Male Wistar rats, at 60-days-old were divided into six groups of eight rats each. The control(C) received saline from gastric tube, the no-diabetic(Cu-10), treated with 10 mg/kg of Cu(Cu(++)-CuSO(4), gastric tube), no-diabetic with Cu-60mg/kg(Cu-60), diabetic(D), diabetic low-Cu(DCu-10) and diabetic high-Cu(DCu-60). Diabetes was induced by an ip injection of streptozotocin (60mg/kg). After 30 days of treatments, no changes we're observed in serum lactate dehydrogenase, alanine transaminase and alkaline phosphatase; indicating no adverse effects on cardiac and hepatic tissues. D-rats had glucose intolerance and dyslipidemic profile. Cholesterol and LDL-cholesterol were higher in Cu-60 and DCu-60 than in C, Cu-10 and D and DCu-10 groups respectively. Cu-60 rats had higher lipid hydroperoxide (HP) and lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) serum activities than C and Cu-10 rats. LH was increased and GSH-Px was decreased, while no alterations were observed in SOD and catalase in serum of DCu-60 animals. DCu-60 rats had increased urinary glucose, creatinine and albumin. In conclusion, Cu intake at high concentration induced adverse effects on lipid profile, associated with oxidative stress and diminished activities of antioxidant enzymes. Diabetic animals were more susceptible to copper toxicity. High Cu intake induced dyslipidemic profile, oxidative stress and kidney dysfunction in diabetic condition. Copper renal toxicity was associated with oxidative stress and reduction at least, one of the antioxidant enzymes. (C) 2004 Elsevier Ltd. All rights reserved.
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BACKGROUND.: Urine is a potentially rich source of biomarkers for monitoring kidney dysfunction. In this study, we have investigated the potential of soluble human leukocyte antigen (sHLA)-DR in the urine for noninvasive monitoring of renal transplant patients. METHODS.: Urinary soluble HLA-DR levels were measured by sandwich enzyme-linked immunosorbent assay in 103 patients with renal diseases or after renal transplantation. sHLA-DR in urine was characterized by Western blotting and mass spectrometry. RESULTS.: Acute graft rejection was associated with a significantly elevated level of urinary sHLA-DR (P<0.0001), compared with recipients with stable graft function or healthy individuals. A receiver operating characteristic curve analysis showed the area under the curve to be 0.88 (P<0.001). At a selected threshold, the sensitivity was 80% and specificity was 98% for detection of acute renal transplant rejection. sHLA-DR was not exosomally associated and was of lower molecular weight compared with the HLA-DR expressed as heterodimer on the plasma membrane of antigen-presenting cells. CONCLUSIONS.: sHLA-DR excreted into urine is a promising indicator of renal transplant rejection.
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Colorectal cancer is a complex disease that is thought to arise when cells accumulate mutations that allow for uncontrolled growth. There are several recognized mechanisms for generating such mutations in sporadic colon cancer; one of which is chromosomal instability (CIN). One hypothesized driver of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, telomeres continuously shorten. Critically shortened telomeres are considered dysfunctional as they are recognized as sites of DNA damage and cells respond by entering into replicative senescence or apoptosis, a process that is p53-dependent and the mechanism for telomere-induced tumor suppression. Loss of this checkpoint and improper repair of dysfunctional telomeres can initiate a cycle of fusion, bridge and breakage that can lead to chromosomal changes and genomic instability, a process that can lead to transformation of normal cells to cancer cells. Mouse models of telomere dysfunction are currently based on knocking out the telomerase protein or RNA component; however, the naturally long telomeres of mice require multiple generational crosses of telomerase null mice to achieve critically short telomeres. Shelterin is a complex of six core proteins that bind to telomeres specifically. Pot1a is a highly conserved member of this complex that specifically binds to the telomeric single-stranded 3’ G-rich overhang. Previous work in our lab has shown that Pot1a is essential for chromosomal end protection as deletion of Pot1a in murine embryonic fibroblasts (MEFs) leads to open telomere ends that initiate a DNA damage response mediated by ATR, resulting in p53-dependent cellular senescence. Loss of Pot1a in the background of p53 deficiency results in increased aberrant homologous recombination at telomeres and elevated genomic instability, which allows Pot1a-/-, p53-/- MEFs to form tumors when injected into SCID mice. These phenotypes are similar to those seen in cells with critically shortened telomeres. In this work, we created a mouse model of telomere ysfunction in the gastrointestinal tract through the conditional deletion of Pot1a that recapitulates the microscopic features seen in severe telomere attrition. Combined intestinal loss of Pot1a and p53 lead to formation of invasive adenocarcinomas in the small and large intestines. The tumors formed with long latency, low multiplicity and had complex genomes due to chromosomal instability, features similar to those seen in sporadic human colorectal cancers. Taken together, we have developed a novel mouse model of intestinal tumorigenesis based on genomic instability driven by telomere dysfunction.
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In the general population, HDL cholesterol (HDL-C) is associated with reduced cardiovascular events. However, recent experimental data suggest that the vascular effects of HDL can be heterogeneous. We examined the association of HDL-C with all-cause and cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health study comprising 3307 patients undergoing coronary angiography. Patients were followed for a median of 9.9 years. Estimated GFR (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine-cystatin C (eGFRcreat-cys) equation. The effect of increasing HDL-C serum levels was assessed using Cox proportional hazard models. In participants with normal kidney function (eGFR>90 ml/min per 1.73 m(2)), higher HDL-C was associated with reduced risk of all-cause and cardiovascular mortality and coronary artery disease severity (hazard ratio [HR], 0.51, 95% confidence interval [95% CI], 0.26-0.92 [P=0.03]; HR, 0.30, 95% CI, 0.13-0.73 [P=0.01]). Conversely, in patients with mild (eGFR=60-89 ml/min per 1.73 m(2)) and more advanced reduced kidney function (eGFR<60 ml/min per 1.73 m(2)), higher HDL-C did not associate with lower risk for mortality (eGFR=60-89 ml/min per 1.73 m(2): HR, 0.68, 95% CI, 0.45-1.04 [P=0.07]; HR, 0.84, 95% CI, 0.50-1.40 [P=0.50]; eGFR<60 ml/min per 1.73 m(2): HR, 1.18, 95% CI, 0.60-1.81 [P=0.88]; HR, 0.82, 95% CI, 0.40-1.69 [P=0.60]). Moreover, Cox regression analyses revealed interaction between HDL-C and eGFR in predicting all-cause and cardiovascular mortality (P=0.04 and P=0.02, respectively). We confirmed a lack of association between higher HDL-C and lower mortality in an independent cohort of patients with definite CKD (P=0.63). In summary, higher HDL-C levels did not associate with reduced mortality risk and coronary artery disease severity in patients with reduced kidney function. Indeed, abnormal HDL function might confound the outcome of HDL-targeted therapies in these patients.
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Prostate cancer, the leading cause of cancer in men, has positive survival rates and constitutes a challenge to men with its side effects. Studies have addressed the bivaritate relationships between prostate cancer treatment side effects masculinity, partner relationship, and quality of life (QOL). However, few studies have highlighted the relationships among prostate cancer treatment side effects (i.e., sexual dysfunction, urinary incontinence), masculinity, and relationship with the partner together on QOL in men. Most studies were conducted with predominately Caucasian sample of men. Miami is a unique multiethnic setting that hosts Cuban, Columbian, Venezuelan, Haitian, other Latin American and Caribbean communities that were not represented in previous literature. The purpose of this study was to examine relative contributions of age, ethnicity, sexual dysfunction, urinary incontinence, masculinity, and perception of the relationship with the partner on the quality of life in men diagnosed with prostate cancer. Data were collected using self administered questionnaires measuring demographic variables, sexual and urinary functioning (UCLA PCI), masculinity (CMNI), partner relationship (DAS), and QOL (SF-36). A total of 117 partnered heterosexual men diagnosed with prostate cancer were recruited from four urology clinics in Miami, Florida. Men were 67.47 (SD = 8.42) years old and identified themselves to be of Hispanic origin (54.3 %, n = 63). Findings demonstrated that there was a significant moderate negative relationship between urinary and sexual functioning of men. There was a significant strong negative association between men's perceived relationship with partner and masculinity. There was a weak negative relationship between the partner relationship and QOL. Hierarchal multiple regression showed that the partner relationship (β = -.25, t (91) = -2.28, p = .03) significantly contributed overall to QOL. These findings highlight the importance of the relationship satisfaction in the QOL of men with prostate cancer. Nursing interventions to enhance QOL for these men should consider strengthening the relationship and involving the female partner as an active participant.^