The influence of the menstrual cup on female pelvic floor muscles variables: a prospective case series.

The aim was to assess and report the effects of menstrual cup on pelvic floor muscles (PFM) function and tone, as well as check the acceptability after a period of three menstrual cycles in healthy young women. The data collected in assessments and reassessments included the International Consultation on Incontinence Questionnaire - Vaginal Symptoms (ICIQ-VS) questionnaire, evaluation of PFM function through PERFECT Scheme, PFM muscle tone, and PFM manometry (Peritron 9300®). A diary regarding the overall colletor acceptability and satisfaction was collected. Ten healthy young women completed the study. There was an improvement in the mean values of maximal voluntary contraction (MVC) (p = 0.032), a decrease in the vaginal resting pressure (VRP) (p = 0.05), and an increase in the number of repetitions of sustained muscle contractions (p = 0.042). Seven women reported some discomfort while using the vaginal cup only in the first cycle while three revealed discomfort during the whole experiment. This study provides preliminary case-based evidence that the use of the vaginal cup for a period of three menstrual cycles changes the VRP, MVC, and PFM tone, as well as improves the repetitions of PFM assessed by digital palpation. Moreover, the women reported the use of vaginal cup as a positive experience.

Adaptive temporal processing of odor stimuli.

The olfactory system translates chemical signals into neuronal signals that inform behavioral decisions of the animal. Odors are cues for source identity, but if monitored long enough, they can also be used to localize the source. Odor representations should therefore be robust to changing conditions and flexible in order to drive an appropriate behavior. In this review, we aim at discussing the main computations that allow robust and flexible encoding of odor information in the olfactory neural pathway.

Characterizing the Biomechanical Properties of the Pubovisceralis Muscle Using a Genetic Algorithm and the Finite Element Method.

To better understand the disorders in the pelvic cavity associated with the pelvic floor muscles (PFM) using computational models, it is fundamental to identify the biomechanical properties of these muscles. For this purpose, we implemented an optimization scheme, involving a genetic algorithm (GA) and an inverse finite element analysis (FEA), in order to estimate the material properties of the pubovisceralis muscle (PVM). The datasets of five women were included in this noninvasive analysis. The numerical models of the PVM were built from static axial magnetic resonance (MR) images, and the hyperplastic Mooney-Rivlin constitutive model was used. The material parameters obtained were compared with the ones established through a similar optimization scheme, using Powell's algorithm. To validate the values of the material parameters that characterize the passive behavior of the PVM, the displacements obtained via the numerical models with both methods were compared with dynamic MR images acquired during Valsalva maneuver. The material parameters (c1 and c2) were higher for the GA than for Powell's algorithm, but when comparing the magnitude of the displacements in millimeter of the PVM, there was only a 5% difference, and 4% for the principal logarithmic strain. The GA allowed estimating the in vivo biomechanical properties of the PVM of different subjects, requiring a lower number of simulations when compared to Powell's algorithm.

On the Stiffness of the Mesh and Urethral Mobility: A Finite Element Analysis.

Midurethral slings are used to correct urethral hypermobility in female stress urinary incontinence (SUI), defined as the complaint of involuntary urine leakage when the intra-abdominal pressure (IAP) is increased. Structural and thermal features influence their mechanical properties, which may explain postoperative complications, e.g., erosion and urethral obstruction. We studied the effect of the mesh stiffness on urethral mobility at Valsalva maneuver, under impairment of the supporting structures (levator ani and/or ligaments), by using a numerical model. For that purpose, we modeled a sling with "lower" versus "higher" stiffness and evaluated the mobility of the bladder and urethra, that of the urethrovesical junction (the α-angle), and the force exerted at the fixation of the sling. The effect of impaired levator ani or pubourethral ligaments (PUL) alone on the organs displacement and α-angle opening was similar, showing their important role together on urethral stabilization. When the levator ani and all the ligaments were simulated as impaired, the descent of the bladder and urethra went up to 25.02 mm, that of the bladder neck was 14.57 mm, and the α-angle was 129.7 deg, in the range of what was found in women with SUI. Both meshes allowed returning to normal positioning, although at the cost of higher force exerted by the mesh with higher stiffness (3.4 N against 2.3 N), which can relate to tissue erosion. This finite element analysis allowed mimicking the biomechanical response of the pelvic structures in response to changing a material property of the midurethral synthetic mesh.

Urinary Incontinence in Physically Active Young Women: Prevalence and Related Factors.

This cross-sectional survey aims to (1) verify the prevalence of urinary incontinence and its impact on the quality of life among nulliparous fit women, and to (2) analyze whether urinary incontinence is influenced by the intensity of the sport (high- vs. low-impact) or by the volume of physical activity (minutes per week) performed. Two hundred forty-five nulliparous women (18-40 years) completed the International Consultation on Incontinence Questionnaire-Short Form, the Kings Health Questionnaire and a questionnaire regarding demographic and training variables. Overall 22.9% of the participants self-reported urinary incontinence, and among them, 60.7% had stress urinary incontinence. Incontinent women demonstrated worse quality of life than continent females (p=0.000). Women practicing high-impact sports presented higher frequency in loss of urine than those practicing low-impact sports (p=0.004). Regardless the intensity of the sport, the volume of exercise showed positive association with the frequency of loss of urine (p=0.005, r=0.475). In conclusion, almost one fourth of the women enrolled in this study reported symptoms of urinary incontinence and worse quality of life than those who were continent. Women who practice high-impact sports or who have higher volume of training should be aware of the symptoms associated with pelvic floor dysfunction, since they seem to predispose to urine leakage.

Breast DWI at 3 T: influence of the fat-suppression technique on image quality and diagnostic performance.

AIM: To evaluate two fat-suppression techniques: short tau inversion recovery (STIR) and spectral adiabatic inversion recovery (SPAIR) regarding image quality and diagnostic performance in diffusion-weighted imaging (DWI) of breast lesions at 3 T. MATERIALS AND METHODS: Ninety-two women (mean age 48 ± 12.1 years; range 21-78 years) underwent breast MRI. Two DWI pulse sequences, with b-values (50 and 1000 s/mm(2)) were performed with STIR and SPAIR. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), suppression homogeneity, and apparent diffusion coefficient (ADC) values were quantitatively assessed for each technique. Values were compared between techniques and lesion type. Receiver operating characteristics (ROC) analysis was used to evaluate lesion discrimination. RESULTS: One hundred and fourteen lesions were analysed (40 benign and 74 malignant). SNR and CNR were significantly higher for DWI-SPAIR; fat-suppression uniformity was better for DWI-STIR (p < 1 × 10(-4)). ADC values for benign and malignant lesions and normal tissue were 1.92 × 10(-3), 1.18 × 10(-3), 1.86 × 10(-3) s/mm(2) for DWI-STIR and 1.80 × 10(-3), 1.11 × 10(-3), 1.79 × 10(-3) s/mm(2) for SPAIR, respectively. Comparison between fat-suppression techniques showed significant differences in mean ADC values for benign (p = 0.013) and malignant lesions (p = 0.001). DWI-STIR and -SPAIR ADC cut-offs were 1.42 × 10(-3) and 1.46 × 10(-3) s/mm(2), respectively. Diagnostic performance for DWI-STIR versus SPAIR was: accuracy (81.6 versus 83.3%), area under curve (87.7 versus 89.2%), sensitivity (79.7 versus 85.1%), and specificity (85 versus 80%). Positive predictive value was similar. CONCLUSION: The fat-saturation technique used in the present study may influence image quality and ADC quantification. Nevertheless, STIR and SPAIR techniques showed similar diagnostic performances, and therefore, both are suitable for use in clinical practice.

Improving malignancy prediction in breast lesions with the combination of apparent diffusion coefficient and dynamic contrast-enhanced kinetic descriptors.

AIM: To assess how the joint use of apparent diffusion coefficient (ADC) and kinetic parameters (uptake phase and delayed enhancement characteristics) from dynamic contrast-enhanced (DCE) can boost the ability to predict breast lesion malignancy. MATERIALS AND METHODS: Breast magnetic resonance examinations including DCE and diffusion-weighted imaging (DWI) were performed on 51 women. The association between kinetic parameters and ADC were evaluated and compared between lesion types. Models with binary outcome of malignancy were studied using generalized estimating equations (GEE), (GEE), and using kinetic parameters and ADC values as malignancy predictors. Model accuracy was assessed using the corrected maximum quasi-likelihood under the independence confidence criterion (QICC). Predicted probability of malignancy was estimated for the best model. RESULTS: ADC values were significantly associated with kinetic parameters: medium and rapid uptake phase (p<0.001) and plateau and washout curve types (p=0.004). Comparison between lesion type showed significant differences for ADC (p=0.001), early phase (p<0.001), and curve type (p<0.001). The predicted probabilities of malignancy for the first ADC quartile (≤1.17×10(-3) mm(2)/s) and persistent, plateau and washout curves, were 54.6%, 86.9%, and 97.8%, respectively, and for the third ADC quartile (≥1.51×10(-3) mm(2)/s) were 3.2%, 15.5%, and 54.8%, respectively. The predicted probability of malignancy was less than 5% for 18.8% of the lesions and greater than 33% for 50.7% of the lesions (24/35 lesions, corresponding to a malignancy rate of 68.6%). CONCLUSION: The best malignancy predictors were low ADCs and washout curves. ADC and kinetic parameters provide differentiated information on the microenvironment of the lesion, with joint models displaying improved predictive performance.

Volume of training and the ranking level are associated with the leakage of urine in young female trampolinists.

OBJECTIVES: The aim of this study was to investigate in young nulliparous female trampolinists the hypothetical associations between the level of athletic performance and the volume of training with urine leakage. DESIGN: Cross-sectional cohort study. SETTING: Professional trampolinists. PARTICIPANTS: Twenty-two female athletes participating in a trampoline national championship were included in this study. ASSESSMENT OF RISK FACTORS: The associations for player-related performance variables were evaluated using Spearman rank correlation and Kruskal-Wallis H test verified the differences between the tertiles. MAIN OUTCOME MEASURES: Rate of urinary incontinence (UI) among young athletes and the relationship with the athletic performance. Screening was performed through a questionnaire. This included the demographic sample characterization, the assessment of training volume, and the athletes' ranking in the championship. Additionally, it included the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-UI-SF) to assess the leakage. RESULTS: About 72.7% of the participants reported that they experienced urine leakage during trampoline practice and described that the episodes of leakage started after the beginning of the trampoline. Significant associations between the athletic performance and the training volume were observed with the severity of incontinence. Dividing the sample in tertiles of training volume, it was observed that the third tertile was the one with greatest impact of incontinence on their quality of life (ICIQ score). CONCLUSIONS: The results confirm a high frequency of UI in young trampolinists and reveal a clear identification of the athletes' ranking and the training volume as risk factors to develop and worsen urine loss. CLINICAL RELEVANCE: Special attention from team physicians and trainers is required for this athletes' problem that is often hidden by shame. In addition, female athletes practicing high-impact sports should be informed about the risk to develop pelvic floor muscles dysfunction and should be encouraged to seek help from health professionals to minimize or even eliminate the urine incontinence.

Fat suppression techniques (STIR vs. SPAIR) on diffusion-weighted imaging of breast lesions at 3.0 T: preliminary experience.

PURPOSE: The aim of this work was to perform a qualitative and quantitative comparison of the performance of two fat suppression techniques on breast diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Fifty-one women underwent clinical breast magnetic resonance imaging, including DWI with short TI inversion recovery (STIR) and spectral attenuated inversion recovery (SPAIR). Four were excluded from the analysis due to image artefacts. Rating of fat suppression uniformity and lesion visibility were performed. Agreement between the two sequences was evaluated. Additionally, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values for normal gland, benign and malignant lesions were compared. Receiver operating characteristic analysis was also performed. RESULTS: From the 52 lesions found, 47 were detected by both sequences. DWI-STIR evidenced more homogeneous fat suppression (p = 0.03). Although these lesions were seen with both techniques, DWI-SPAIR evidenced higher score for lesion visibility in nine of them. SNR and CNR were comparable, except for SNR in benign lesions (p < 0.01), which was higher for DWI-SPAIR. Mean ADC values for lesions were similar. ADC for normal fibroglandular tissue was higher when using DWI-STIR (p = 0.006). Sensitivity, specificity, accuracy and area under the curve values were alike: 84.0 % for both; 77.3, 71.4 %; 80.9, 78.3 %; 82.5, 81.3 % for DWI-SPAIR and DWI-STIR, respectively. CONCLUSION: DWI-STIR showed superior fat suppression homogeneity. No differences were found for SNR and CNR, except for SNR in benign lesions. ADCs for lesions were comparable. Findings in this study are consistent with previous studies at 1.5 T, meaning that both fat suppression techniques are appropriate for breast DWI at 3.0 T.

Application of the diffusion kurtosis model for the study of breast lesions.

OBJECTIVES: To evaluate diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in the differentiation and characterisation of breast lesions. METHODS: Thirty-six women underwent breast magnetic resonance imaging (MRI) including a DWI sequence with multiple b-values (50-3,000 s/mm(2)). Mean values for apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) were calculated by lesion type and histological subtype. Differences and correlation between parameters were determined. RESULTS: Forty-four lesions were found. There were significant differences between benign and malignant lesions for all parameters (ADC, p = 0.017; MD, p = 0.028; MK, p = 0.017). ADC and MD were higher for benign (1.96 ± 0.41 × 10(-3) and 2.17 ± 0.42 × 10(-3) mm(2)/s, respectively) than for malignant lesions (1.33 ± 0.18 × 10(-3) and 1.52 ± 0.50 × 10(-3) mm(2)/s). MK was higher for malignant (0.61 ± 0.27) than benign lesions (0.37 ± 0.18). We found differences between invasive ductal carcinoma (IDC) and fibroadenoma (FA) for all parameters (ADC, MD and MK): p = 0.016, 0.022 and 0.016, respectively. FA and fibrocystic change (FC) showed differences only in MK (p = 0.016). CONCLUSIONS: Diffusion in breast lesions follows a non-Gaussian distribution. MK enables differentiation and characterisation of breast lesions, providing new insights into microstructural complexity. To confirm these results, further investigation in a broader sample should be performed.

Effects of Croton rhamnifolioides essential oil on Aedes aegypti oviposition, larval toxicity and trypsin activity.

Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its effects on oviposition and survival of larvae of the dengue fever mosquito Aedes aegypti. In addition, we have established a possible mechanism of action for the larvicidal activity of the essential oil. GC-MS analyses revealed marked differences in the composition of oil that had been freshly isolated and that of a sample that had been stored in a sealed amber-glass vial under refrigeration for three years. However, both fresh and stored oil exhibited substantial larvicidal activities with LC50 values of 122.35 and 89.03 ppm, respectively, and oviposition deterrent effects against gravid females at concentrations of 50 and 100 µg·mL-1. These results demonstrate that the larvicidal effect of the essential oil was unchanged during three years of storage even though its chemical composition altered. Hence, the essential oil could be used in the preparation of commercial products. In addition, we observed that the trypsin-like activity of mosquito larvae was inhibited in vitro by the essential oil of C. rhamnifolioides, suggesting that the larvicidal effect may be associated with inhibition of this enzyme.

Moment of inertia as a means to evaluate the biomechanical impact of pelvic organ prolapse.

OBJECTIVES: To present an alternative measure (moment of inertia) to describe the anatomical features of the pelvic organ prolapse. METHODS: A total of 30 women (21 diagnosed as having pelvic organ prolapse and 9 as controls) were evaluated by clinical scales and magnetic resonance imaging. Imaging biometric measures were carried out. Moment of inertia, pubovisceral muscle thickness and area, and levator hiatus anterior-to-posterior and lateral measures were compared by means of non-parametric tests, as well as their correlation with demographic features of the two sample groups. RESULTS: Moment of inertia, muscle area and levator hiatus diameters were statistically different between patients and controls. Furthermore, they were also well correlated with prolapse-associated factors, such as the number of vaginal deliveries and age, as well as Pelvic Organ Prolapse Quantification system and imaging staging of levator ani defects. CONCLUSIONS: Moment of inertia can be used as a new parameter to evaluate pelvic floor damage resulting from prolapse.

The Metabolic Fingerprint of Doxorubicin-Induced Cardiotoxicity in Male CD-1 Mice Fades Away with Time While Autophagy Increases.

The cardiotoxicity of doxorubicin (DOX) may manifest at the beginning/during treatment or years after, compromising patients' quality of life. We intended to study the cardiac pathways one week (short-term, control 1 [CTRL1] and DOX1 groups) or five months (long-term, CTRL2 and DOX2 groups) after DOX administration in adult male CD-1 mice. Control groups were given saline, and DOX groups received a 9.0 mg/Kg cumulative dose. In the short-term, DOX decreased the content of AMP-activated protein kinase (AMPK) while the electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) increased compared to CTRL1, suggesting the upregulation of fatty acids oxidation. Moreover, mitofusin1 (Mfn1) content was decreased in DOX1, highlighting decreased mitochondrial fusion. In addition, increased B-cell lymphoma-2 associated X-protein (BAX) content in DOX1 pointed to the upregulation of apoptosis. Conversely, in the long-term, DOX decreased the citrate synthase (CS) activity and the content of Beclin1 and autophagy protein 5 (ATG5) compared to CTRL2, suggesting decreased mitochondrial density and autophagy. Our study demonstrates that molecular mechanisms elicited by DOX are modulated at different extents over time, supporting the differences on clinic cardiotoxic manifestations with time. Moreover, even five months after DOX administration, meaningful heart molecular changes occurred, reinforcing the need for the continuous cardiac monitoring of patients and determination of earlier biomarkers before clinical cardiotoxicity is set.

Cardiac Molecular Remodeling by Anticancer Drugs: Doxorubicin Affects More Metabolism While Mitoxantrone Impacts More Autophagy in Adult CD-1 Male Mice.

Doxorubicin (DOX) and mitoxantrone (MTX) are classical chemotherapeutic agents used in cancer that induce similar clinical cardiotoxic effects, although it is not clear if they share similar underlying molecular mechanisms. We aimed to assess the effects of DOX and MTX on the cardiac remodeling, focusing mainly on metabolism and autophagy. Adult male CD-1 mice received pharmacologically relevant cumulative doses of DOX (18 mg/kg) and MTX (6 mg/kg). Both DOX and MTX disturbed cardiac metabolism, decreasing glycolysis, and increasing the dependency on fatty acids (FA) oxidation, namely, through decreased AMP-activated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) content and decreased free carnitine (C0) and increased acetylcarnitine (C2) concentration. Additionally, DOX heavily influenced glycolysis, oxidative metabolism, and amino acids turnover by exclusively decreasing phosphofructokinase (PFKM) and electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH) content, and the concentration of several amino acids. Conversely, both drugs downregulated autophagy given by the decreased content of autophagy protein 5 (ATG5) and microtubule-associated protein light chain 3 (LC3B), with MTX having also an impact on Beclin1. These results emphasize that DOX and MTX modulate cardiac remodeling differently, despite their clinical similarities, which is of paramount importance for future treatments.

Insights on the molecular targets of cardiotoxicity induced by anticancer drugs: A systematic review based on proteomic findings.

Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents, but in fact, the specific modulation is not completely elucidated. Thus, this systematic review aims to provide an integrative perspective of the molecular mechanisms underlying the toxicity of anticancer agents on heart muscle while using a high-throughput technology, mass spectrometry (MS)-based proteomics. A literature search using PubMed database led to the selection of 27 studies, of which 13 reported results exclusively on animal models, 13 on cardiomyocyte-derived cell lines and only one included both animal and a cardiomyocyte line. The reported anticancer agents were the proteasome inhibitor carfilzomib, the anthracyclines daunorubicin, doxorubicin, epirubicin and idarubicin, the antimicrotubule agent docetaxel, the alkylating agent melphalan, the anthracenedione mitoxantrone, the tyrosine kinase inhibitors (TKIs) erlotinib, lapatinib, sorafenib and sunitinib, and the monoclonal antibody trastuzumab. Regarding the MS-based proteomic approaches, electrophoretic separation using two-dimensional (2D) gels coupled with tandem MS (MS/MS) and liquid chromatography-MS/MS (LC-MS/MS) were the most common. Overall, the studies highlighted 1826 differentially expressed proteins across 116 biological processes. Most of them were grouped in larger processes and critically analyzed in the present review. The selection of studies using proteomics on heart muscle allowed to obtain information about the anticancer therapy-induced modulation of numerous proteins in this tissue and to establish connections that have been disregarded in other studies. This systematic review provides interesting points for a comprehensive understanding of the cellular cardiotoxicity mechanisms of different anticancer drugs.

Thalamic volumetric abnormalities in type 1 diabetes mellitus and 'peripheral' neuropathy.

We hypothesized that thalamic volumes of patients with type 1 diabetes mellitus (DM) and nonpainful diabetic peripheral neuropathy (DPN) would be reduced relative to thalamic volumes of patients with type 1 DM and painful DPN. We calculated the standardized thalamic volumetric difference between these groups in a pilot sample to obtain a statistical power of 80% at a 5% significance level. Hence, we measured thalamic volumes from 15 patients with nonpainful DPN (10 women, mean age = 49 years, standard deviation [SD] = 11.5) and from 13 patients with painful DPN (8 women, mean age = 43 years, SD = 12.5) by using a manual segmentation approach. A volumetric difference of approximately 15% was found between the nonpainful (mean = 5072 mm3, SD = 528.1) and painful (mean = 5976 mm3, SD = 643.1) DPN groups (P < 0.001). Curiously, a volumetric difference between the left (mean = 5198 mm3, SD = 495.0) and the right (mean = 4946 mm3, SD = 590.6) thalamus was also found in patients with nonpainful DPN (P < 0.01), but not in patients with painful DPN (P = 0.97). Patients with nonpainful DPN have lower thalamic volumes than those with painful DPN, especially in the right thalamus.

Exploring the contribution of mitochondrial dynamics to multiple acyl-CoA dehydrogenase deficiency-related phenotype.

Mitochondrial fatty acid ß-oxidation disorders (FAOD) are among the diseases detected by newborn screening in most developed countries. Alterations of mitochondrial functionality are characteristic of these metabolic disorders. However, many questions remain to be clarified, namely how the interplay between the signaling pathways harbored in mitochondria contributes to the disease-related phenotype. Herein, we overview the role of mitochondria on the regulation of cell homeostasis through the production of ROS, mitophagy, apoptosis, and mitochondrial biogenesis. Emphasis is given to the signaling pathways involving MnSOD, sirtuins and PGC-1α, which seem to contribute to FAOD phenotype, namely to multiple acyl-CoA dehydrogenase deficiency (MADD). The association between phenotype and genotype is not straightforward, suggesting that specific molecular mechanisms may contribute to MADD pathogenesis, making MADD an interesting model to better understand this interplay. However, more work needs to be done envisioning the development of novel therapeutic strategies.

Exploring the aging effect of the anticancer drugs doxorubicin and mitoxantrone on cardiac mitochondrial proteome using a murine model.

Current cancer therapies are successfully increasing the lifespan of cancer patients. Nevertheless, cardiotoxicity is a serious chemotherapy-induced adverse side effect. Doxorubicin (DOX) and mitoxantrone (MTX) are cardiotoxic anticancer agents, whose toxicological mechanisms are still to be identified. This study focused on DOX and MTX's cardiac mitochondrial damage and their molecular mechanisms. As a hypothesis, we also sought to compare the cardiac modulation caused by 9 mg/kg of DOX or 6 mg/kg of MTX in young adult mice (3 months old) with old control mice (aged control, 18-20 months old) to determine if DOX- and MTX-induced damage had common links with the aging process. Cardiac homogenates and enriched mitochondrial fractions were prepared from treated and control animals and analyzed by immunoblotting and enzymatic assays. Enriched mitochondrial fractions were also characterized by mass spectrometry-based proteomics. Data obtained showed a decrease in mitochondrial density in young adults treated with DOX or MTX and aged control, as assessed by citrate synthase (CS) activity. Furthermore, aged control had increased expression of the peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1α) and manganese superoxide dismutase (MnSOD). Regarding the enriched mitochondrial fractions, DOX and MTX led to downregulation of proteins related to oxidative phosphorylation, fatty acid oxidation, amino acid metabolic process, and tricarboxylic acid cycle. MTX had a greater impact on malate dehydrogenase (MDH2) and pyruvate dehydrogenase E1 component subunit α (PDHA1). No significant proteomic changes were observed in the enriched mitochondrial fractions of aged control when compared to young control. To conclude, DOX and MTX promoted changes in several mitochondrial-related proteins in young adult mice, but none resembling the aged phenotype.

Pubovisceralis Muscle Fiber Architecture Determination: Comparison Between Biomechanical Modeling and Diffusion Tensor Imaging.

Biomechanical analysis of pelvic floor dysfunction requires knowledge of certain biomechanical parameters, such as muscle fiber direction, in order to adequately model function. Magnetic resonance (MR) diffusion tensor imaging (DTI) provides an estimate of overall muscle fiber directionality based on the mathematical description of water diffusivity. This work aimed at evaluating the concurrence between pubovisceralis muscle fiber representations obtained from DTI, and the maximum principal stress lines obtained through the finite element method. Seven datasets from axial T2-weighted images were used to build numerical models, and muscle fiber orientation estimated from the DT images. The in-plane projections of the first eigenvector of both vector fields describing muscle fiber orientation were extracted and compared. The directional consistency was evaluated by calculating the angle between the normalized vectors for the entire muscle and also for the right and left insertions, middle portions, and anorectal area. The values varied between 28° ± 6 (right middle portion) and 34° ± 9 (anorectal area), and were higher than the angular precision of the DT estimates, evaluated using wild bootstrapping analysis. Angular dispersion ranged from 17° ± 4 (left middle portion) to 23° ± 5 (anorectal area). Further studies are needed to examine acceptability of these differences when integrating the vectors estimated from DTI in the numerical analysis.

Biomechanical study on the bladder neck and urethral positions: simulation of impairment of the pelvic ligaments.

Excessive mobility of the bladder neck and urethra are common features in stress urinary incontinence. We aimed at assessing, through computational modelling, the bladder neck position taking into account progressive impairment of the pelvic ligaments. Magnetic resonance images of a young healthy female were used to build a computational model of the pelvic cavity. Appropriate material properties and constitutive models were defined. The impairment of the ligaments was simulated by mimicking a reduction in their stiffness. For healthy ligaments, valsalva maneuver led to an increase in the α angle (between the bladder neck-symphysis pubis and the main of the symphysis) from 91.8° (at rest) to 105.7°, and 5.7 mm of bladder neck dislocation, which was similar to dynamic imaging of the same woman (α angle from 80° to 103.3°, and 5mm of bladder neck movement). For 95% impairment, they enlarged to 124.28° and 12 mm. Impairment to the pubourethral ligaments had higher effect than that of vaginal support (115° vs. 108°, and 9.1 vs. 7.3mm). Numerical simulation could predict urethral motion during valsalva maneuver, for both healthy and impaired ligaments. Results were similar to those of continent women and women with stress urinary incontinence published in the literature. Biomechanical analysis of the pubourethral ligaments complements the biomechanical study of the pelvic cavity in urinary incontinence. It may be useful in young women presenting stress urinary incontinence without imaging evidence of urethral and muscle lesions or organ descend during valsalva, and for whom fascial damage are not expected.