Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Effects of short-term severe and long-term mild STZ-induced diabetes in urethral tissue of female rats.

AIMS: To estimate and compare the alterations in the urethral tissues of female rats with two diabetes models: short-term severe and long-term mild diabetes. METHODS: To induce mild diabetes (blood glucose levels between 120 and 300 mg/dl), female newborns received streptozotocin (100 mg/kg body weight, sc route), and to induce short-term severe diabetes (blood glucose levels > 300 mg/d), adult animals received streptozotocin (40 mg/kg, iv route). The rats were killed on day 133 of the experimental via an i.p. Thiopentax® injection of 80 mg/kg, and the urethrovaginal tissues were harvested. Morphometric, pathological, immunohistochemical, and ultrastructural analyses were conducted. RESULTS: In the long-term mild diabetes group, collagen deposition, severe fibrosis, lipid droplets and numerous subsarcolemmal, and intermyofibrillar mitochondria were observed. In the short-term severe diabetes group, centrally located myonuclei and a significantly reduced striated muscle area were noted. Both diabetic models exhibited similar immunohistochemistry patterns, with changes from fast to slow fibers and a decrease in the numbers of fast fibers. CONCLUSIONS: Either long-term mild hyperglycemia or short-term severe hyperglycemia have detrimental impacts on muscle health. They are both involved in the failure to maintain healthy skeletal muscle that may contribute to the development of pelvic floor dysfunctions via different pathways. These results have important implications for monitoring and prevention strategies for improving the quality of life of women with diabetes mellitus and pelvic floor muscle dysfunction. Neurourol. Urodynam. 36:574-579, 2017. © 2016 Wiley Periodicals, Inc.

Urethral striated muscle and extracellular matrix morphological characteristics among mildly diabetic pregnant rats: translational approach.

INTRODUCTION AND HYPOTHESIS: Diabetes mellitus (DM) during pregnancy is associated with high levels of urinary incontinence (UI) and pelvic floor muscle dysfunction. Mild DM can lead to changes in urethral striated muscle and extracellular matrix (ECM) in pregnant rats considering both structures as an entire system responsible for urinary continence. METHODS: Ninety-two female Wistar rats were distributed in four experimental groups: virgin, pregnant, diabetic, and diabetic pregnant. In adult life, parental nondiabetic female rats were mated with nondiabetic male rats to obtain newborns. At the first day of birth, newborns received citrate buffer (nondiabetic group) or streptozotocin 100 mg/kg body weight, subcutaneous route (mild DM group). At day 21 of the pregnancy, the rats were lethally anesthetized and the urethra and vagina were extracted as a unit. Urethral and vaginal sections were cut and analyzed by: (a) cytochemical staining for ECM and muscle structural components, (b) immunohistochemistry to identify fast- and slow-muscle fibers, and (c) transmission electron microscopy for ultrastructural analysis of urethral striated muscle. RESULTS: In comparison with the three control groups, variations in the urethral striated muscle and ECM from diabetic pregnant rats were observed including thinning, atrophy, fibrosis, increased area of blood vessels, mitochondria accumulation, increased lipid droplets, glycogen granules associated with colocalization of fast and slow fibers, and a steady decrease in the proportion of fast to slow fibers. CONCLUSIONS: Mild DM and pregnancy can lead to a time-dependent disorder and tissue remodeling in which the urethral striated muscle and ECM has a fundamental function.

Impact of Obesity and Hyperglycemia on Pregnancy-specific Urinary Incontinence.

OBJECTIVE: The lack of data on the impact of hyperglycemia and obesity on the prevalence of pregnancy-specific urinary incontinence (PSUI) led us to conduct a cross-sectional study on the prevalence and characteristics of PSUI using validated questionnaires and clinical data. METHODS: This cross-sectional study included 539 women with a gestational age of 34 weeks who visited a tertiary university hospital between 2015 and 2018. The main outcome measures were the prevalence of PSUI, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Incontinence Severity Index (ISI) questionnaires. The women were classified into four groups: normoglycemic lean, normoglycemic obese, hyperglycemic lean, and hyperglycemic obese. The differences between groups were tested using descriptive statistics. Associations were estimated using logistic regression analysis and presented as unadjusted and adjusted odds ratios. RESULTS: Prevalence rates of PSUI were no different between groups. However, significant difference in hyperglycemic groups worse scores for severe and very severe PSUI. When adjusted data for confound factors was compared with normoglycemic lean group, the hyperglycemic obese group had significantly higher odds for severe and very severe forms of UI using ICIQ-SF (aOR 3.157; 95% CI 1.308 to 7.263) and ISI (aOR 20.324; 95% CI 2.265 to 182.329) questionnaires and highest perceived impact of PSUI (aOR 4.449; 95% CI 1.591 to 12.442). CONCLUSION: Our data indicate that obesity and hyperglycemia during pregnancy significantly increase the odds of severe forms and perceived impact of PSUI. Therefore, further effective preventive and curative treatments are greatly needed.

OBJETIVO: A falta de dados sobre o impacto da hiperglicemia e obesidade na prevalência de incontinência urinária específica da gravidez (IAPS) nos levou a realizar um estudo transversal sobre a prevalência e características da IAPS usando questionários validados e dados clínicos. MéTODOS: Este estudo transversal incluiu 539 mulheres com idade gestacional de 34 semanas que visitaram um hospital universitário terciário entre 2015 e 2018. As principais medidas de desfecho foram a prevalência de PSUI, o formulário curto do International Consultation on Incontinence Questionnaire (ICIQ-SF) e os questionários do Incontinence Severity Index (ISI). As mulheres foram classificadas em quatro grupos: magras normoglicêmicas, obesas normoglicêmicas, magras hiperglicêmicas e obesas hiperglicêmicas. As diferenças entre os grupos foram testadas por meio de estatística descritiva. As associações foram estimadas usando análise de regressão logística e apresentadas como odds ratio não ajustadas e ajustadas. RESULTADOS: As taxas de prevalência de PSUI não foram diferentes entre os grupos. No entanto, houve diferença significativa nos grupos hiperglicêmicos com piores escores para PSUI grave e muito grave. Quando os dados ajustados para fatores de confusão foram comparados ao grupo magro normoglicêmico, o grupo obeso hiperglicêmico teve chances significativamente maiores de formas graves e muito graves de IU usando ICIQ-SF (aOR 3,157; IC 95% 1,308 a 7,263) e ISI (aOR 20,324; 95% CI 2,265 a 182,329) questionários e maior impacto percebido de PSUI (aOR 4,449; 95% CI 1,591 a 12,442). CONCLUSãO: Nossos dados indicam que a obesidade e a hiperglicemia durante a gravidez aumentam significativamente as chances de formas graves e o impacto percebido da PSUI. Portanto, tratamentos preventivos e curativos mais eficazes são extremamente necessários.

In vivo genotoxicity assessment of nerolidol.

Nerolidol is a sesquiterpenoid component of essential oil used as a flavor and aroma enhancer. It has also been studied as a topical skin penetration enhancer, and has inhibitory activities against S. aureus and E. coli, among other activities. The objective of this study was to evaluate the ability of a single nerolidol treatment to induce DNA damage in peripheral blood and liver cells of mice and micronuclei in polychromatic erythrocytes of bone marrow cells of the same animals. In the dose range-finding assays, the maximum tolerated dose was higher than 2000 mg kg(-1) . The doses used in the experiments were 250, 500 and 2000 mg kg(-1) , administered by gavage in a single dose. Peripheral blood cells were collected 4 and 24 h after the treatments and liver cells 24 h after. At least 100 nucleoids per cell type/animal were analyzed to determine the DNA damage scores and 2000 PCEs per animal for micronuclei in PCEs. The positive control was N-nitroso-N-ethylurea 50 mg kg(-1) . Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE:NCE ratio). The results showed that nerolidol induced weak levels of dose-related DNA damage in both types of cells analyzed, and enhanced the average number of micronucleated cells in the two high doses tested. The PCE:NCE ratio showed no cytotoxicity for the three doses of the compound. The data obtained support the view that nerolidol induces clastogenicity and very weak genotoxicity in the mouse cells tested.

Pregnancy-specific urinary incontinence in women with gestational hyperglycaemia worsens the occurrence and severity of urinary incontinence and quality of life over the first year post partum.

OBJECTIVE: To determine the occurrence and severity of pregnancy-specific urinary incontinence (PSUI) in women with gestational hyperglycaemia, and its impact on quality of life (QoL) over the first year post partum. STUDY DESIGN: Three hundred and eighty-eight pregnant women with PSUI were distributed into two groups (normoglycaemic and hyperglycaemic) and analysed at five timepoints during pregnancy and the first year post partum. Gestational hyperglycaemia was defined according to the criteria of the American Diabetes Association and the glucose profile test. Relationships with outcome were analysed using Chi-squared test for categorical variables and Student's t-test for quantitative variables. RESULTS: The overall prevalence rate of PSUI was 54.1 %, with prevalence rates of 43.3 % and 56.7 % in normoglycaemic and hyperglycaemic Brazilian pregnant women, respectively. Women with gestational hyperglycaemia had a higher amount of urine loss (p < 0.0027), frequency of UI (p < 0.0014), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0003) and total scores on the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-SF) and Incontinence Severity Index (ISI) (p<0.0001) at the two timepoints during pregnancy; and a higher amount of urine loss (p = 0.0079), frequency of UI (p = 0.0382), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0053) and questionnaire scores (p < 0.0001 for ICIQ-SF and p = 0.003 for ISI) over the first year post partum. CONCLUSIONS: PSUI in women with gestational hyperglycaemia worsens the occurrence and severity of UI, and the impact of UI on QoL over the first year post partum. These results emphasize the interaction between PSUI, gestational hyperglycaemia and long-term maternal outcome.

Alterations in the structural characteristics of rectus abdominis muscles caused by diabetes and pregnancy: A comparative study of the rat model and women.

BACKGROUND AND OBJECTIVE: In the present study, we compared the effect of diabetic pregnancy on the rectus abdominis muscle (RAM) in humans and rats. We hypothesized that our animal model could provide valuable information about alterations in the RAM of women with Gestational Diabetes (GDM). METHOD: Newborns female rats (n = 10/group) were administered streptozotocin (100 mg/kg body weight) subcutaneously and were mated on reaching adulthood, to develop the mild hyperglycemic pregnant (MHP) rat model. At the end of pregnancy, the mothers were sacrificed, and the RAM tissue was collected. Pregnant women without GDM (non-GDM group; n = 10) and those diagnosed with GDM (GDM group; n = 8) and undergoing treatment were recruited, and RAM samples were obtained at C-section. The RAM architecture and the distribution of the fast and slow fibers and collagen were studied by immunohistochemistry. RESULTS: No statistically significant differences in the maternal and fetal characters were observed between the groups in both rats and women. However, significant changes in RAM architecture were observed. Diabetes in pregnancy increased the abundance of slow fibers and decreased fast fiber number and area in both rats and women. A decrease in collagen distribution was observed in GDM women; however, a similar change was not observed in the MHP rats. CONCLUSION: Our results indicated that pregnancy- associated diabetes- induced similar structural adaptations in the RAM of women and rats with slight alterations in fiber type number and area. These findings suggest that the MHP rat model can be used for studying the effects of pregnancy-associated diabetes on the fiber structure of RAM.

Deleterious effects of gestational diabetes mellitus on the characteristics of the rectus abdominis muscle associated with pregnancy-specific urinary incontinence.

AIMS: To evaluate the effects of gestational diabetes mellitus (GDM) on the structural characteristics of the rectus abdominis muscle (RAM) and its indirect effects on pregnancy-specific urinary incontinence (PSUI). METHODS: A total of 92 pregnant women were divided into four groups, according to their clinical conditions: non-GDM continent, non-GDM associated PSUI, GDM continent and GDM associated PSUI. The muscle morphometry (histochemistry and immunohistochemistry) for the fiber types and collagen fiber distribution, the ultrastructural analysis (transmission electron microscopy), the protein expression of fiber types and calcium signaling (Western blotting), and the content of types I and III collagen fiber (ELISA) in RAM collected at delivery were assessed. RESULTS: The GDM groups presented a significantly increased number of slow fibers and slow-twitch oxidative fiber expression; decreased fiber area, number of fast fibers, and area of collagen; an increase in central nuclei; ultrastructural alterations with focal lesion areas such as myeloid structures, sarcomere disorganization, and mitochondrial alteration. The PSUI groups presented a considerable decrease in types I and III collagen contents and the localization of collagen fiber. CONCLUSIONS: Our data reveal that GDM causes morphological, biochemical and physiological changes in the RAM, and this might predispose women to PSUI.

Pelvic floor and abdominal muscle cocontraction in women with and without pelvic floor dysfunction: a systematic review and meta-analysis.

There is an ongoing discussion regarding abdominal muscle (AbM) and pelvic floor muscle (PFM) synergism. Therefore, this study aimed to investigate the cocontraction between AbMs and PFMs in women with or without pelvic floor dysfunction (PFD). The following databases were searched up to December 21, 2018: MEDLINE, EMBASE, LILACS, PEDro and CENTRAL. We included any study that assessed the cocontraction between PFMs and AbMs in women with and without PFD. Two reviewers independently screened eligible articles and extracted data. The outcomes were extracted and analyzed as continuous variables with random effect models. Twenty studies were included. A meta-analysis did not show differences in women with and without PFD. However, a sensitivity analysis suggested cocontraction of the transversus abdominis (TrA) during PFM contraction in healthy women (standardized mean difference (SMD) -1.02 [95% confidence interval (CI) -1.90 to -0.14], P=0.02; I2= not applicable; very low quality of evidence). Women with PFD during contraction of PFMs showed cocontraction of the obliquus internus (OI) (SMD 1.10 [95% CI 0.27 to 1.94], P=0.01; I2= not applicable; very low quality of evidence), and obliquus externus (OE) (SMD 2.08 [95% CI 1.10 to 3.06], P<0.0001; I2 = not applicable; very low quality of evidence). Increased cocontraction of the TrA may be associated with maximal contraction of PFMs in women without PFD. On the other hand, there is likely an increased cocontraction with the OI and OE in women with PFD.

Impact of Obesity and Hyperglycemia on Pregnancy-specific Urinary Incontinence / Impacto da obesidade e hiperglicemia na incontinência urinária específica da gravidez

Abstract Objective The lack of data on the impact of hyperglycemia and obesity on the prevalence of pregnancy-specific urinary incontinence (PSUI) led us to conduct a cross-sectional study on the prevalence and characteristics of PSUI using validated questionnaires and clinical data. Methods This cross-sectional study included 539 women with a gestational age of 34 weeks who visited a tertiary university hospital between 2015 and 2018. The main outcome measures were the prevalence of PSUI, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Incontinence Severity Index (ISI) questionnaires. The women were classified into four groups: normoglycemic lean, normoglycemic obese, hyperglycemic lean, and hyperglycemic obese. The differences between groups were tested using descriptive statistics. Associations were estimated using logistic regression analysis and presented as unadjusted and adjusted odds ratios. Results Prevalence rates of PSUI were no different between groups. However, significant difference in hyperglycemic groups worse scores for severe and very severe PSUI. When adjusted data for confound factors was compared with normoglycemic lean group, the hyperglycemic obese group had significantly higher odds for severe and very severe forms of UI using ICIQ-SF (aOR 3.157; 95% CI 1.308 to 7.263) and ISI (aOR 20.324; 95% CI 2.265 to 182.329) questionnaires and highest perceived impact of PSUI (aOR 4.449; 95% CI 1.591 to 12.442). Conclusion Our data indicate that obesity and hyperglycemia during pregnancy significantly increase the odds of severe forms and perceived impact of PSUI. Therefore, further effective preventive and curative treatments are greatly needed.

Resumo Objetivo A falta de dados sobre o impacto da hiperglicemia e obesidade na prevalência de incontinência urinária específica da gravidez (IAPS) nos levou a realizar um estudo transversal sobre a prevalência e características da IAPS usando questionários validados e dados clínicos. Métodos Este estudo transversal incluiu 539 mulheres com idade gestacional de 34 semanas que visitaram um hospital universitário terciário entre 2015 e 2018. As principais medidas de desfecho foram a prevalência de PSUI, o formulário curto do International Consultation on Incontinence Questionnaire (ICIQ-SF) e os questionários do Incontinence Severity Index (ISI). As mulheres foram classificadas em quatro grupos: magras normoglicêmicas, obesas normoglicêmicas, magras hiperglicêmicas e obesas hiperglicêmicas. As diferenças entre os grupos foram testadas por meio de estatística descritiva. As associações foram estimadas usando análise de regressão logística e apresentadas como odds ratio não ajustadas e ajustadas. Resultados As taxas de prevalência de PSUI não foram diferentes entre os grupos. No entanto, houve diferença significativa nos grupos hiperglicêmicos com piores escores para PSUI grave e muito grave. Quando os dados ajustados para fatores de confusão foram comparados ao grupo magro normoglicêmico, o grupo obeso hiperglicêmico teve chances significativamente maiores de formas graves e muito graves de IU usando ICIQ-SF (aOR 3,157; IC 95% 1,308 a 7,263) e ISI (aOR 20,324; 95% CI 2,265 a 182,329) questionários e maior impacto percebido de PSUI (aOR 4,449; 95% CI 1,591 a 12,442). Conclusão Nossos dados indicam que a obesidade e a hiperglicemia durante a gravidez aumentam significativamente as chances de formas graves e o impacto percebido da PSUI. Portanto, tratamentos preventivos e curativos mais eficazes são extremamente necessários.

The influence of hyperglycemia on the remodeling of urethral connective tissue in pregnant rats.

OBJECTIVE: To analyze the distribution and quantification of the key structural extracellular matrix components of the urethral tissue in a rat model of hyperglycemia and pregnancy. STUDY DESIGN: A total of 120 female Wistar rats were distributed into the following four experimental groups: virgin, pregnant, hyperglycemic and hyperglycemic + pregnant groups. The urethra was harvested for histochemical, morphometric, immunohistochemical, Western blot and glycosaminoglycan analyses. All protocols were approved by the Institutional Animal Care and Use Committee of Botucatu Medical School (process number 828-2010). RESULTS: The hyperglycemic + pregnant group showed significantly increased stiffness in urethral tissue. The total striated muscle was decreased, with increased deposition of collagen fibers around the muscle fibers and a change in the organization of the collagen fibrils. An increase in the relative collagen type I/III ratio and a decrease in total glycosaminoglycans were also observed. CONCLUSIONS: This study provides the first line of experimental evidence supporting a metabolic relationship between hyperglycemia and urethral remodeling of connective tissue in pregnant rats. The different organization of the collagen fibrils and the profile of glycosaminoglycans found in urethral samples suggest that the pathology of the urethral fibromuscular system could be related to hyperglycemia-induced pelvic floor dysfunction in women, which has direct clinical implications with the possibility to develop new multidisciplinary treatments for improving the health care of these women.

Score Establishment and Brazilian Portuguese version of the Pregnancy Sexual Response Inventory (PSRI).

OBJECTIVE: To establish the Pregnancy Sexual Response Inventory (PSRI) scores for each domain before and during pregnancy, and to publish the Brazilian Portuguese version of the PSRI. METHODS: Pregnant women were recruited during antenatal care; the PSRI was administered to 244 women prenatally at Faculdade de Medicina de Botucatu, at Universidade do Estado de São Paulo (UNESP, in the Portuguese acronym). The PSRI scores were estimated based on the Kings Health Questionnaire (KHQ) and the Medical Outcomes Study 36-item short form survey (SF-36). The raw scale type was used to standardize the minimal value and amplitude of each domain. For each domain, the score varied from 0 to 100, and the composite score was obtained as the domain average. The composite score before and during pregnancy was determined by the sum of the scores of all specific domains for each divided by the full domain number. The categorization of the scale into quartiles was established when all PSRI-specific and composite scores were combined. RESULTS: The composite and specific scores for each domain were categorized into quartiles: 0 < 25 as "very bad;" 25 < 50 as "bad;" 50 < 75 as "good" and 75 to 100 as "excellent." The mean scores were lower during pregnancy than before pregnancy in 8 of the 10 domains. The Brazilian Portuguese PSRI version is presented. CONCLUSION: This study allowed the establishment of the PSRI composite and specific scores for each domain, and the categorization of scores into quartiles: very bad, bad, good and excellent. In addition, the Brazilian Portuguese version of the PSRI is presented in full for application in the Brazilian population.

OBJETIVO: Estabelecer os escores do Inventário da Resposta Sexual na Gestação (PSRI) para cada domínio antes e durante a gravidez, e publicar a versão do PSRI em português brasileiro. MéTODOS: Gestantes foram recrutadas durante o cuidado pré-natal; o PSRI foi administrado a 244 mulheres no pré-natal na Faculdade de Medicina de Botucatu da Universidade do Estado de São Paulo (UNESP). Os escores do PSRI foram estimados com base no Kings Health Questionnaire (KHQ) e Medical Outcomes Study36-item short form survey (SF-36). O tipo de escala bruta foi utilizado para padronizar o valor mínimo e a amplitude de cada domínio. Para cada domínio, a pontuação variou de 0 a 100, e o escore composto foi obtido pela média do domínio. O escore composto antes e durante a gravidez foi determinado pela somatória dos escores de todos os domínios específicos para cada período dividido pelo número total do domínio. A escala de categorização em quartil foi estabelecida quando todos os escores específicos e compostos do PSRI foram reunidos. RESULTADOS: Os escores compostos e específicos para cada domínio foram categorizados em quartis: 0 < 25 como "muito ruim;" 25 < 5 0 como "ruim;" 50 < 75 como "bom" e 75 a 100 como "excelente." As médias dos escores foram menores durante a gravidez do que antes da gravidez em 8 dos 10 domínios. Foi apresentada a versão PSRI em português brasileiro. CONCLUSãO: Este estudo permitiu o estabelecimento dos escores compostos e específicos do PSRI para cada domínio e a categorização dos escores em quartis: muito ruim, ruim, bom e excelente. Além disso, a versão em português do PSRI é apresentada integralmente para aplicação na população brasileira.

Gene expression profile of whole blood cells differs in pregnant women with positive screening and negative diagnosis for gestational diabetes.

OBJECTIVE: To evaluate the gene expression profile of whole blood cells in pregnant women without diabetes (with positive screening and negative diagnosis for gestational diabetes mellitus (GDM)) compared with pregnant women with negative screening for GDM. RESEARCH DESIGN AND METHODS: Pregnant women were recruited in the Diabetes Perinatal Research Centre-Botucatu Medical School-UNESP and Botucatuense Mercy Hospital (UNIMED). Distributed into 2 groups: control (n=8), women with negative screening and non-diabetic (ND, n=13), with positive screening and negative diagnosis of GDM. A peripheral blood sample was collected for glucose, glycated hemoglobin, and microarray gene expression analyses. RESULTS: The evaluation of gene expression profiles showed significant differences between the control group and the ND group, with 22 differentially expressed gene sequences. Gene networks and interaction tables were generated to evaluate the biological processes associated with differentially expressed genes of interest. CONCLUSIONS: In the group with positive screening, there is an apparent regulatory balance between the functions of the differentially expressed genes related to the pathogenesis of diabetes and a compensatory attempt to mitigate the possible etiology. These results support the 'two-step Carpenter-Coustan' strategy because pregnant women with negative screening do not need to continue on diagnostic investigation of gestational diabetes, thus reducing the cost of healthcare and the medicalization of pregnancy. Although not diabetic, they do have risk factors, and thus attention to these genes is important when considering disease evolution because this pregnant women are a step toward developing diabetes compared with women without these risk factors.

Prevalence of urinary incontinence and pelvic floor muscle dysfunction in primiparae two years after cesarean section: cross-sectional study.

CONTEXT AND OBJECTIVE: There is uncertainty in the literature regarding the theory that obstetric events and pelvic floor injuries give rise to lower risk of subsequent urinary incontinence among women delivering via cesarean section than among women delivering vaginally. The objective of this study was to assess the two-year postpartum prevalence of urinary incontinence and pelvic floor muscle dysfunction and the factors responsible for them. DESIGN AND SETTING: Cross-sectional study, conducted in a public university. METHODS: 220 women who had undergone elective cesarean section or vaginal childbirth two years earlier were selected. Their urinary incontinence symptoms were investigated, and their pelvic floor muscle dysfunction was assessed using digital palpation and a perineometer. RESULTS: The two-year urinary incontinence prevalences following vaginal childbirth and cesarean section were 17% and 18.9%, respectively. The only risk factor for pelvic floor muscle dysfunction was weight gain during pregnancy. Body mass index less than 25 kg/m 2 and normal pelvic floor muscle function protected against urinary incontinence. Gestational urinary incontinence increased the risk of two-year postpartum urinary incontinence. CONCLUSION: Gestational urinary incontinence was a crucial precursor of postpartum urinary incontinence. Weight gain during pregnancy increased the subsequent risk of pelvic floor muscle dysfunction, and elective cesarean section did not prevent urinary incontinence.

[Translational research in gestational diabetes mellitus and mild gestational hyperglycemia: current knowledge and our experience]. / Pesquisa translacional em diabetes melito gestacional e hiperglicemia gestacional leve: conhecimento atual e nossa experiência.

Maternal diabetes constitutes an unfavorable environment for fetal-placental and embryonic development. It is has important repercussion in modern obstetrics, since it is associated to an increased risk of neonatal and maternal morbidity, and it still is a significant medical challenge. The increased occurrence of diabetes worldwide, the increase in diabetes type 2 in women at reproductive age and the crossed generation of intrauterine programming for diabetes type 2 are the bases for the growing interest in utilization of diabetic experimental samples, with the aim to acquire knowledge about the mechanisms that induce development alterations in gestational diabetes. Several studies have shown the benefits of diabetes prevention, with interventions in lifestyle, metabolic improvement and control of cardiovascular risk factors to substantially prevent the complications of this devastating disease. Despite these findings, the recent revolution in the scientific knowledge, and the infinite number of new therapies for diabetes, there is still a large gap between what was learned through research and what is really done in public, clinical and community health. The negative economic impact of this complacency in people, families, and national economies is alarming. It is expected that translational research in the binomial diabetes and pregnancy are implemented in centers of excellence, in both basic and applied research, and complemented by multicenter clinical studies, conducted in a pragmatic way to increase the level of scientific evidence with more reliable diagnostic and propaedeutic resources.

Score establishment and brazilian portuguese version of the pregnancy sexual response inventory (PSRI) / Definição de escores e versão em português brasileiro do inventário da resposta sexual na gestação (PSRI)

Abstract Objective To establish the Pregnancy Sexual Response Inventory (PSRI) scores for each domain before and during pregnancy, and to publish the Brazilian Portuguese version of the PSRI. Methods Pregnant women were recruited during antenatal care; the PSRI was administered to 244 women prenatally at Faculdade de Medicina de Botucatu, at Universidade do Estado de São Paulo (UNESP, in the Portuguese acronym). The PSRI scores were estimated based on the Kings Health Questionnaire (KHQ) and the Medical Outcomes Study 36-item short form survey (SF-36). The raw scale type was used to standardize the minimal value and amplitude of each domain. For each domain, the score varied from 0 to 100, and the composite score was obtained as the domain average. The composite score before and during pregnancy was determined by the sum of the scores of all specific domains for each divided by the full domain number. The categorization of the scale into quartiles was established when all PSRI-specific and composite scores were combined. Results The composite and specific scores for each domain were categorized into quartiles: 0 < 25 as "very bad;" 25 < 50 as "bad;" 50 < 75 as "good" and 75 to 100 as "excellent." The mean scores were lower during pregnancy than before pregnancy in 8 of the 10 domains. The Brazilian Portuguese PSRI version is presented. Conclusion This study allowed the establishment of the PSRI composite and specific scores for each domain, and the categorization of scores into quartiles: very bad, bad, good and excellent. In addition, the Brazilian Portuguese version of the PSRI is presented in full for application in the Brazilian population.

Resumo Objetivo Estabelecer os escores do Inventário da Resposta Sexual na Gestação (PSRI) para cada domínio antes e durante a gravidez, e publicar a versão do PSRI emportuguês brasileiro. Métodos Gestantes foram recrutadas durante o cuidado pré-natal; o PSRI foi administrado a 244 mulheres no pré-natal na Faculdade de Medicina de Botucatu da Universidade do Estado de São Paulo (UNESP). Os escores do PSRI foram estimados com base no Kings Health Questionnaire (KHQ) e Medical Outcomes Study 36-item short form survey (SF-36). O tipo de escala bruta foi utilizado para padronizar o valor mínimo e a amplitude de cada domínio. Para cada domínio, a pontuação variou de 0 a 100, e o escore composto foi obtido pelamédia do domínio. O escore composto antes e durante a gravidez foi determinado pela somatória dos escores de todos os domínios específicos para cada período dividido pelo número total do domínio. A escala de categorização em quartil foi estabelecida quando todos os escores específicos e compostos do PSRI foram reunidos. Resultados Os escores compostos e específicos para cada domínio foram categorizados em quartis: 0 < 25 como "muito ruim;" 25 < 5 0 como "ruim;" 50 < 75 como "bom" e 75 a 100 como "excelente." As médias dos escores foram menores durante a gravidez do que antes da gravidez em 8 dos 10 domínios. Foi apresentada a versão PSRI em português brasileiro. Conclusão Este estudo permitiu o estabelecimento dos escores compostos e específicos do PSRI para cada domínio e a categorização dos escores emquartis:muito ruim, ruim, bom e excelente. Além disso, a versão em português do PSRI é apresentada integralmente para aplicação na população brasileira.

Pesquisa translacional em diabetes melito gestacional e hiperglicemia gestacional leve: conhecimento atual e nossa experiência / Translational research in gestational diabetes mellitus and mild gestational hyperglycemia: current knowledge and our experience

O diabetes materno constitui um ambiente desfavorável para o desenvolvimento embrionário e feto-placentário. É uma repercussão de importância na obstetrícia moderna, visto que está associado a um risco aumentado de morbidade materna e neonatal e continua a ser um desafio médico significativo. O aumento mundial na incidência do diabetes, o aumento do diabetes tipo 2 em mulheres em idade reprodutiva e a geração cruzada da programação intrauterina do diabetes tipo 2 são as bases para o interesse crescente na utilização de modelos experimentais diabéticos, a fim de obter conhecimento sobre os mecanismos que induzem as alterações de desenvolvimento no diabetes gestacional. Vários estudos têm demonstrado os benefícios da prevenção do diabetes com intervenções no estilo de vida, melhora metabólica e controle de fator de risco cardiovascular para evitar substancialmente as complicações devastadores da doença. Apesar desses achados e a revolução recente no conhecimento científico e infinidade de novas terapias do diabetes, continua a haver uma grande lacuna entre o que foi aprendido por meio da pesquisa e o que é feito na prática da saúde pública, clínica e comunitária. O iminente impacto econômico negativo dessa complacência nos indivíduos, nas famílias e nas economias nacionais é alarmante. Espera-se que a pesquisa translacional no binômio diabetes-gravidez seja implementada em centros de excelência tanto de pesquisa básica como aplicada e complementada por estudos clínicos multicêntricos, conduzidos de forma pragmática para aumentar o nível de evidência científica com recursos diagnósticos e propedêuticos mais confiáveis.

Maternal diabetes constitutes an unfavorable environment for fetal-placental and embryonic development. It is has important repercussion in modern obstetrics, since it is associated to an increased risk of neonatal and maternal morbidity, and it still is a significant medical challenge. The increased occurrence of diabetes worldwide, the increase in diabetes type 2 in women at reproductive age and the crossed generation of intrauterine programming for diabetes type 2 are the bases for the growing interest in utilization of diabetic experimental samples, with the aim to acquire knowledge about the mechanisms that induce development alterations in gestational diabetes. Several studies have shown the benefits of diabetes prevention, with interventions in lifestyle, metabolic improvement and control of cardiovascular risk factors to substantially prevent the complications of this devastating disease. Despite these findings, the recent revolution in the scientific knowledge, and the infinite number of new therapies for diabetes, there is still a large gap between what was learned through research and what is really done in public, clinical and community health. The negative economic impact of this complacency in people, families, and national economies is alarming. It is expected that translational research in the binomial diabetes and pregnancy are implemented in centers of excellence, in both basic and applied research, and complemented by multicenter clinical studies, conducted in a pragmatic way to increase the level of scientific evidence with more reliable diagnostic and propaedeutic resources.

Prevalence of urinary incontinence and pelvic floor muscle dysfunction in primiparae two years after cesarean section: cross-sectional study / Prevalência de incontinência urinária e disfunção muscular do assoalho pélvico em primíparas dois anos após parto cesárea: estudo transversal

CONTEXT AND OBJECTIVE There is uncertainty in the literature regarding the theory that obstetric events and pelvic floor injuries give rise to lower risk of subsequent urinary incontinence among women delivering via cesarean section than among women delivering vaginally. The objective of this study was to assess the two-year postpartum prevalence of urinary incontinence and pelvic floor muscle dysfunction and the factors responsible for them. DESIGN AND SETTING Cross-sectional study, conducted in a public university. METHODS 220 women who had undergone elective cesarean section or vaginal childbirth two years earlier were selected. Their urinary incontinence symptoms were investigated, and their pelvic floor muscle dysfunction was assessed using digital palpation and a perineometer. RESULTS The two-year urinary incontinence prevalences following vaginal childbirth and cesarean section were 17% and 18.9%, respectively. The only risk factor for pelvic floor muscle dysfunction was weight gain during pregnancy. Body mass index less than 25 kg/m 2 and normal pelvic floor muscle function protected against urinary incontinence. Gestational urinary incontinence increased the risk of two-year postpartum urinary incontinence. CONCLUSION Gestational urinary incontinence was a crucial precursor of postpartum urinary incontinence. Weight gain during pregnancy increased the subsequent risk of pelvic floor muscle dysfunction, and elective cesarean section did not prevent urinary incontinence. .

CONTEXTO E OBJETIVO É ainda controversa na literatura a teoria de que eventos obstétricos e traumas no assoalho pélvico representariam menor risco para mulheres submetidas ao parto cesárea do que para aquelas submetidas a parto vaginal, no tocante a subsequente incontinência urinária. O objetivo do estudo foi avaliar a prevalência de incontinência urinária e disfunção muscular do assoalho pélvico dois anos após o parto e os fatores responsáveis por elas. TIPO DE ESTUDO E LOCAL Estudo transversal conduzido em universidade pública. MÉTODOS Foram selecionadas 220 mulheres dois anos após parto cesáreo eletivo ou parto vaginal. Foram avaliados sintomas de incontinência urinária e disfunção muscular do assoalho pélvico por palpação digital e perineômetro. RESULTADOS A prevalência de incontinência urinária dois anos após parto vaginal e cesárea foi de 17% e 18,9% respectivamente. O único fator de risco para disfunção muscular do assoalho pélvico foi o ganho de peso durante a gestação. Índice de massa corporal inferior a 25 kg/m 2 e disfunção muscular do assoalho pélvico normal foram fatores de proteção contra incontinência urinária. Incontinência urinária na gestação aumentou o risco de incontinência urinária dois anos pós-parto. CONCLUSÃO Incontinência urinária gestacional foi um precursor crucial de incontinência urinária pós-parto. O ganho de peso durante a gestação aumentou o risco posterior de disfunção muscular do assoalho pélvico e o parto cesárea eletivo não foi uma ação de prevenção para a ...

Importância do modelo animal para testar hipóteses sobre a fisiopatologia do binômio diabetes e incontinência urinária feminina / Importance of animal model to test hypotheses about the pathophysiology of the binomial diabetes and female urinary incontinence

Objetivos: discutir a importância do estudo de modelos animais para testar hipóteses sobre os mecanismos de continência urinária e fisiopatologia do binômio diabetes incontinência urinária.Fonte de Dados: foi realizada revisão de literatura no PubMed e SciELO. Os descritores utilizados foram diabetes, urinary incontinence, urethra, human e rats.Síntese dos Dados: existe forte correlação entre a gênese da incontinência urinária e o diabetes mellitus. Devido à similaridade entre a distribuição normal da musculatura estriada e da neuroanatomia da uretra em mulheres e em ratas, estes modelos animais vêm sendo cada vez mais utilizados nas pesquisas sobre esses distúrbios.Conclusões: o uso de ratas como modelo animal é apropriado para estudos experimentais que testam hipóteses sobre os mecanismos de continência e a fisiopatologia do binômio diabetes mellitus e incontinência urinária, possibilitando assim, soluções de grande valia na prática clínica.

Aims: To discuss the importance of studying animal models to test hypotheses about the mechanisms of urinary continence and pathophysiology of diabetes and urinary incontinence.Source of Data: A literature review was conducted in PubMed and SciELO. The key words used were diabetes, urinary incontinence, urethra, human and rats.Summary of Findings: There is a strong relation between the genesis of urinary incontinence and diabetes mellitus. Due to the similarity of normal distribution of skeletal muscle and urethra anatomy between humans and rats, these animal models have been used in current research about these disorders.Conclusions: The use of rats as an animal model is suitable for experimental studies that test hypotheses about the mechanisms of continence and pathophysiology of the binomial diabetes mellitus and urinary incontinence, thus enabling solutions of great value in clinical practice.