Germline mutations in BRCA1 and BRCA2 among Brazilian women with ovarian cancer treated in the Public Health System.

BACKGROUND: Germline mutations in BRCA1 and BRCA2 genes are among the main causes of hereditary ovarian cancer. Identifying these mutations may reduce cancer risk, facilitate early detection, and enable personalized treatment. However, genetic testing is limited in the Brazilian Public Health System, and data regarding germline mutations in many regions are scarce. Therefore, the study aimed to investigate the prevalence of germline mutations in BRCA1 and BRCA2 in women with ovarian cancer treated in the Public Health System in Pernambuco, Brazil. METHODS: A cross-sectional study was conducted in the Hereditary Cancer Program from two reference oncological centers in Pernambuco. Women (n = 45) with high-grade serous ovarian cancer underwent genetic counseling and DNA sequencing for BRCA1 and BRCA2 genes. RESULTS: The prevalence of deleterious mutations in the BRCA1 and BRCA2 genes was 33%. Of the 15 germline mutations found, 13 were in BRCA1 and 2 in BRCA2; two mutations of unknown clinical significance were also found in BRCA2. Mutations c.5266dupC and c.2215 A > T were the most frequent; each was mutation observed in three patients. Additionally, the mutations c.7645dupT and c.921dupT were reported for the first time. CONCLUSION: One in three women showed a pathogenic mutation, demonstrating a significant prevalence of germline mutations in this sample. Additionally, the small sample revealed an interesting number of mutations, indicating the need to explore more regions of the country.

Marketable 1,3-dimethylamylamine and caffeine-based thermogenic supplements: Regulatory genotoxicity assessment through in vitro and in silico approaches.

The consumption of dietary supplements to enhance physical performance has increased significantly in the last century, especially thermogenic pre-workout supplements. Nevertheless, this industry has faced criticism for inadequate safety measures surveillance in regulatory issues regarding their products. The aims of our study were to investigate two pre-workout supplements with respect to (1) mutagenicity utilizing Salmonella/microsome assay; (2) genotoxicity employing cytokinesis-block micronucleus (CBMN) assay protocols; and (3) hepatocytoxicity using WST cell proliferation, activities of lactate dehydrogenase (LDH) and alkaline phosphatase using human liver carcinoma (HepG2) and mouse fibroblast (F C3H) cells. Oxidative stress was determined through glutathione (GSH) measurement and in silico for predictions of pharmacokinetics and toxicity for the most abundant isolated substances present in these supplements. Both supplements induced mutagenicity in all examined bacterial strains, especially in the presence of exogenous metabolism. Further, tested supplements significantly elevated the formation of micronuclei (MN) as well as other cellular phenomena. Concentration- and time-dependent curves were observed for hepatotoxicity in both studied cell lines. In addition, both supplements decreased levels of intracellular and extracellular GSH. In silico predictions showed that the isolated individual compounds failed to induce the observed outcomes. Our findings provide contributions to the molecular mechanisms underlying two pre-workout supplement-induced toxicity and the need for surveillance.

Repercussion of inflammatory bowel disease on lung homeostasis: The role of photobiomodulation.

Inflammatory bowel diseases (IBD) are chronic and multifactorial diseases characterized by dysfunction of the intestinal mucosa and impaired immune response. Data show an important relationship between intestine and respiratory tract. The treatments of IBD are limited. Photobiomodulation (PBM) is an effective anti-inflammatory therapy. Our objective was to evaluate the repercussion of IBD as well as its treatment with PBM on pulmonary homeostasis. Male Wistar rats were submitted to IBD induction by acetic acid and treated or not with PBM. Rats were irradiated with red LED on both right and left sides of the ventral surface and beside the external anal region during 3 consecutive days (wavelenght 660 nm, power 100 mw, total energy 15 J and time of irradiation 150 s per point). Our results showed that IBD altered pulmonary homeostasis, since we observed an increase in the histopathological score, in myeloperoxidase activity (MPO), in mast cell degranulation, and in the release and gene expression of cytokines. We also showed that PBM treatment reduced biomarkers of IBD and reverted all augmented parameters in the lung, restoring its homeostasis. Thus, we confirm experimentally the important gut-lung axis and the role of PBM as a promising therapy.

Sensory and muscular functions of the pelvic floor in women with endometriosis - cross-sectional study.

PURPOSE: The aim of this study was to analyze the sensory and muscle functions of the pelvic floor in women with endometriosis, trying to improve overall knowledge/findings regarding pelvic floor muscle functions in patients with endometriosis. METHODS: Sample size calculated as 92 patients with endometriosis, aged between 18 and 45 years, not virgin, without other causes of pain and could not be pregnant. Patients underwent the Pelvic Floor Sensorial and Muscle Function Exam (EFSMAP). Descriptive data were recorded with mean and standard deviation, median (range), and absolute and relative frequency. The Kolmogorov-Smirnov test was used to observe the normality of quantitative variables. The significance level adopted for this study was 5%. RESULTS: Of 92 women assessed, 93.3% had pain and 75% had increased tone in the levator ani muscle; 50.4% had impaired pelvic floor relaxation with median strength of 3 by the Oxford scale and endurance of 2 s. CONCLUSIONS: The patients had a high prevalence of pain and dysfunction of the pelvic floor muscles, such as low muscle endurance and difficulty to relax. It shows that these patients should be referred to a pelvic floor physiotherapist, as soon as they have the diagnosis of endometriosis, to be assessed to prevent and/or treat pelvic floor impairments.

Intravascular laser irradiation of blood (ILIB) used to treat lung diseases: a short critical review.

Intravascular laser irradiation of blood (ILIB) was developed to treat cardiovascular diseases due to its rheological effects. In its original form, ILIB was applied by an intravenous optical fiber, restricting its application. However, this technique was modified to non-invasive irradiation through the radial artery, now called vascular photobiomodulation (VPBM). Many studies have used both, ILIB and VPBM, to treat lung diseases. It is well established that lung diseases affect more than 300 million people worldwide with high morbidity and mortality rates. In this short critical review, we discuss the potential benefits of photobiomodulation to treat lung diseases using these two approaches. The search was performed in the electronic database of MEDLINE (Medical Literature Analysis and Retrieval System Online) via PubMed. The data search was carried out from 1991 to 2017. We selected a total of 10 clinical studies using either ILIB or VPBM, in addition to 2 experimental studies in animals. The respiratory diseases treated in these studies included bronchitis, asthma, pneumonia, and tuberculosis. The results showed overall beneficial effects on lung diseases, characterized by a reduction in the inflammatory cascade and antioxidant effects, improvement of hemodynamic parameters, the efficiency of gas exchange, and reduction of hospitalization periods. In conclusion, all studies showed promising effects of ILIB in both animal and human studies. The studies did not discuss any disadvantages or contraindications. However, further studies are needed in order to understand the dosimetry, and the literature is lacking in randomized, controlled clinical trials. Thus, this review highlights the need for additional studies using this approach.

Comparison between local abdominal and transcutaneous tail vein photobiomodulation in experimental rat model of ulcerative colitis.

Ulcerative colitis (UC) is a chronic autoimmune disease that impacts the quality of life, but current pharmacological treatments are limited. Photobiomodulation (PBM) is a light-based treatment that can be applied either locally or systemically. Here, we compare the effects of local and vascular PBM (VPBM) in an experimental rat model of UC. Male Wistar rats were induced with UC by rectal instillation of acetic acid and treated with either local abdominal PBM or VPBM to the tail vein using a 660-nm LED. The findings indicated that local PBM but not VPBM reduced intestinal histological scores. Both local and VPBM increased mucus production, decreased mast cell degranulation, and modulated TNF-α and IL-1 ß levels in the intestines. Local PBM also affected the expression of the mRNAs for IL-6, TNF-α, and IFN-γ. In conclusion, we suggest that local PBM appears to be more promising than VPBM for treating UC. However, further research is needed to fully understand the mechanisms and to optimize the parameters of PBM for UC treatment.

Effects of photobiomodulation in the experimental acetic acid-induced colitis: comparison between male and female.

Ulcerative colitis (UC) is an important chronic and multifactorial disease, which alters the colon mucosal with a significant impact on life quality affecting both men and women. The difference between genders causes changes in the inflammatory processes, modulating the development of several diseases. The available drugs to treat UC exhibit limited outcomes and side effects; thus, new therapies are needed. Photobiomodulation (PBM) emerges as potential treatment by modulating the inflammatory process without side effects and low costs. The aim of this study was to evaluate the effects of PBM in acetic acid-induced UC comparing the responses between male and females. For this purpose, male and female Wistar rats (36) were submitted to induction of UC by rectal administration of 10% acetic acid (colitis group) and treated or not with PBM (colitis-PBM group) (LED, 660 nm, 100 mW, 150 s) in three points: right side and left of the ventral surface and in the external anal region. Non-manipulated rats were used as control (basal group). We investigated the disease activity index (DAI score), myeloperoxidase enzyme activity (MPO) and release of cytokines in the intestine homogenates, and histological analysis. PBM reduces DAI score, MPO activity, and mast cell degranulation while increased mucous production in both females and males. Moreover, PBM reduced histopathological score as well as the levels of IL-6 and IL-4 in the bowel only in males. We also showed reduced levels of IL-1beta and TNF-alpha after PBM in both males and females, while the levels of IL-10 and IFN-gamma were increased. In conclusion, despite our study has shown some differences between males and females, PBM attenuated the biomarkers of UC in both genders constituting a potential combined treatment that is non-invasive and low cost.

Respiratory deficits in a female rat model of Parkinson's disease.

NEW FINDINGS: What is the central question of this study? How does the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease model affect the respiratory response in female rats? What effect does ovariectomy have on that response? What is the main finding and its importance? The results suggest a protective effect of ovarian hormones in maintaining normal neuroanatomical integrity of the medullary respiratory nucleus in females. It was observed that ovariectomy alone reduced neurokinin-1 density in the pre-Bötzinger complex and Bötzinger complex, and there was an incremental effect of 6-OHDA and ovariectomy on retrotrapezoid nucleus neurons. ABSTRACT: Emerging evidence indicates that the course of Parkinson's disease (PD) includes autonomic and respiratory deficiencies in addition to the classical motor symptoms. The prevalence of PD is lower in women, and it has been hypothesized that neuroprotection by ovarian hormones can explain this difference. While male PD animal models present changes in the central respiratory control areas, as well as ventilatory parameters under normoxia and hypercapnia, little is known about sex differences regarding respiratory deficits in this disease background. This study aimed to explore the neuroanatomical and functional respiratory changes in intact and ovariectomized (OVX) female rats subjected to chemically induced PD via a bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). The respiratory parameters were evaluated by whole-body plethysmography, and the neuroanatomy was monitored using immunohistochemistry. It was found that dopaminergic neurons in the substantia nigra and neurokinin-1 receptor density in the rostral ventrolateral respiratory group, Bötzinger and pre-Bötzinger complex were reduced in the chemically induced PD animals. Additionally, reduced numbers of Phox2b neurons were only observed in the retrotrapezoid nucleus of PD-OVX rats. Concerning respiratory parameters, in OVX rats, the resting and hypercapnia-induced tidal volume (VT ) is reduced, and ventilation ( V ̇ E ${\dot V_{\rm{E}}}$ ) changes independently of 6-OHDA administration. Notably, there is a reduction in the number of retrotrapezoid nucleus Phox2b neurons and hypercapnia-induced respiratory changes in PD-OVX animals due to a 6-OHDA and OVX interaction. These results suggest a protective effect induced by ovarian hormones in neuroanatomical changes observed in a female experimental PD model.

Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling.

Combined fatty acid esterification and lipolysis, termed lipid cycling, is an ATP-consuming process that contributes to energy expenditure. Therefore, interventions that stimulate energy expenditure through lipid cycling are of great interest. Here we find that pharmacological and genetic inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes activates lipid cycling and energy expenditure, even in the absence of adrenergic stimulation. We show that the resulting increase in ATP demand elevates mitochondrial respiration coupled to ATP synthesis and fueled by lipid oxidation. We identify that glutamine consumption and the Malate-Aspartate Shuttle are required for the increase in Energy Expenditure induced by MPC inhibition in Brown Adipocytes (MAShEEBA). We thus demonstrate that energy expenditure through enhanced lipid cycling can be activated in brown adipocytes by decreasing mitochondrial pyruvate availability. We present a new mechanism to increase energy expenditure and fat oxidation in brown adipocytes, which does not require adrenergic stimulation of mitochondrial uncoupling.

Efficacy of spontaneous pushing with pursed lips breathing compared with directed pushing in maternal and neonatal outcomes.

This is a quasi-randomised clinical trial, with 62 low-risk pregnant women in the second stage of labour. They were randomly allocated in control (CG) (n = 31) and intervention (IG) (n = 31) groups. The IG performed spontaneous pushing with pursed lips breathing while the CG was oriented to perform directed pushing associated with Valsalva Manoeuvre (VM). There was no difference between the groups regarding the occurrence of episiotomy (RR 1,1; 95%IC 1,0 to 1,2). However, there was a decrease in the duration of the maternal pushing by 3.2 min (MD 3,2; 95%CI 1,4 to 5,1) and a difference in maternal anxiety (Md (IQR) IG 46 (35-52), CG 51 (44-56) p:0,049), both favouring the IG. Spontaneous pushing was effective in reducing the duration of the pushing and showed a difference in maternal anxiety but did not decrease the maternal and neonatal outcomes. Brazilian Clinical Trials Registry (ReBEC) under the identifier: RBR-556d22IMPACT STATEMENTWhat is already known on the subject? Spontaneous pushing reduces the duration of pushing time when compared to directed pushing with VM but has no effect on other maternal and neonatal outcomes, based on a low quality of evidence.What do the results of this study add? No subject has been published on the subject. Our results suggest that the use spontaneous pushing with pursed lips breathing reduces the duration of the pushing by 3.2 min, also showing a difference in maternal anxiety. This result may indicate its use for emotional control when compared to the directed pushing.What are the implications of these findings for clinical practice and/or further research? These findings may signal an attitude in decision-making about guiding the breathing pattern in the expulsive stage.

Assessment of the strength and electrical activity of the pelvic floor muscles of male-to-female transgender patients submitted to gender-affirming surgery: A case series.

AIMS: To assess the strength and electrical activity of the pelvic floor muscles (PFMs) of male-to-female transgender individuals submitted to gender-affirming surgery (GAS). METHODS: A case series study was conducted from October 2016 to August 2018. Transgender women, who were scheduled for GAS, participated in the study. The volunteers were submitted to a clinical evaluation of the PFM followed by digital palpation (PERFECT method) and electromyography in the preoperative, 15, and 30 days after GAS. They responded to the International Consultation on Incontinence Questionnaire-Urinary Incontinence (UI)-Short Form to evaluate the effect of UI on quality of life and to questions related to the urinary, anorectal, and sexual symptoms. Fifteen days after the GAS, patients were instructed to perform perineal exercises at home, twice a day. RESULTS: The study sample consisted of 15 transgender women with an average age of 30.6 (SD = 6.7) years. There was a decline in median strength and sustained muscle contraction duration (PERFECT), in the electrical muscle activity (RMSmean and RMSmax) between pre-GAS and 15 days after GAS (p < 0.05). However, there was an increase in these parameters between 15 and 30 days after GAS (p < 0.05). Moreover, six patients exhibited pre-GAS UI, which continued after surgery, with a worsening of urgency symptoms and improvement in nocturia and postmicturition leakage. CONCLUSION: Strength, sustained muscle contraction duration, and PFM electrical activity may decline 15 days after GAS, returning to pre-GAS values in the first month after surgery.

Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: Effect on conventional coagulation tests and thrombomodulin-modified thrombin generation.

BACKGROUND & AIMS: The efficacy of fresh frozen plasma (FFP) transfusion in enhancing thrombin generation in patients with cirrhosis and impaired conventional coagulation tests has not been sufficiently explored. Thus, we aimed to assess the effect of FFP transfusion on thrombin generation in these patients. METHODS: Fifty-three consecutive patients receiving a standard dose of FFP to treat bleeding and/or before invasive procedures - if international normalized ratio (INR)/prothrombin time (PT) ratio were ≥1.5 - were prospectively enrolled. The primary endpoint was the amelioration of endogenous thrombin potential (ETP) with thrombomodulin (ETP-TM) after transfusion, which corresponds to the total amount of generated thrombin. INR/PT ratio and activated partial thromboplastin time (aPTT) were also assessed before and after transfusion. RESULTS: FFP enhanced ETP-TM by 5.7%, from 973 (731-1,258) to 1,028 (885-1,343 nM × min; p = 0.019). Before transfusion, evidence of normal or high ETP-TM was found in 94% of patients, even in those with bacterial infections. Only 1 (1.9%) patient had ETP-TM values reverting to the normal range after transfusion. Notably, no patients with low ETP-TM had bleeding. The median decrease in ETP-TM was 8.3% and the mean was 12.8% in 18 (34%) patients after transfusion (from 1,225 [1,071-1,537] to 1,124 [812-1,370] nM × min; p ≤0.0001). Similar responses to FFP transfusion were observed in patients with compensated and acute decompensated cirrhosis, acute-on-chronic liver failure, infection or shock. FFP significantly ameliorated INR and aPTT values (p <0.0001), but in a minority of patients the values were reduced to less than the cut-off point of 1.5. CONCLUSIONS: FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, and slightly decreased thrombin generation in 34% of cases. LAY SUMMARY: Transfusion of fresh frozen plasma in patients with cirrhosis only slightly improves coagulation test values in a limited number of patients and even appears to worsen them in a third of cases. Transfusion for the purpose of preventing or treating bleeding events could cause inherent risks and costs without clear benefits.

Assessment of mitochondrial physiology of murine white adipose tissue by mechanical permeabilization and lipid depletion.

White adipose tissue (WAT) represents a major site of triacylglycerol energy storage and is directly associated with metabolic disorders. Mitochondria regulate cellular energy expenditure and are active in WAT. Although isolated mitochondria have been classically used to assess their functions, several artifacts can be introduced by this approach. Furthermore, important limitations exist in the available methods to determine mitochondrial physiology in permeabilized WAT. Here, we established and validated a method for functional evaluation of mice mesenteric WAT (mWAT) mitochondria by using MEchanical Permeabilization and LIpid DEpletion (MEPLIDE) coupled to high-resolution respirometry. We observed that mild stirring of mWAT for 20 min at room temperature with 4% fatty acid-free albumin (FAF-BSA) followed by 50 min without FAF-BSA selectively permeabilized white adipocytes plasma membrane. In these conditions, mWAT mitochondria were intact, exhibiting succinate-induced respiratory rates that were sensitive to classical oxidative phosphorylation modulators. Finally, the respiratory capacity of mWAT in female mice was significantly higher than in males, an observation that agrees with reported data. Therefore, the functional assessment of mWAT mitochondria through MEPLIDE coupled to high resolution respirometry proposed here will contribute to a better understanding of WAT biology in several pathophysiological contexts.

Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms.

Butyrate is a short-chain fatty acid derived from the metabolism of indigestible carbohydrates by the gut microbiota. Butyrate contributes to gut homeostasis, but it may also control inflammatory responses and host physiology in other tissues. Butyrate inhibits histone deacetylases, thereby affecting gene transcription, and also signals through the metabolite-sensing G protein receptor (GPR)109a. We produced an mAb to mouse GPR109a and found high expression on podocytes in the kidney. Wild-type and Gpr109a-/- mice were induced to develop nephropathy by a single injection of Adriamycin and treated with sodium butyrate or high butyrate-releasing high-amylose maize starch diet. Butyrate improved proteinuria by preserving podocyte at glomerular basement membrane and attenuated glomerulosclerosis and tissue inflammation. This protective phenotype was associated with increased podocyte-related proteins and a normalized pattern of acetylation and methylation at promoter sites of genes essential for podocyte function. We found that GPR109a is expressed by podocytes, and the use of Gpr109a-/- mice showed that the protective effects of butyrate depended on GPR109a expression. A prebiotic diet that releases high amounts of butyrate also proved highly effective for protection against kidney disease. Butyrate and GPR109a play a role in the pathogenesis of kidney disease and provide one of the important molecular connections between diet, the gut microbiota, and kidney disease.-Felizardo, R. J. F., de Almeida, D. C., Pereira, R. L., Watanabe, I. K. M., Doimo, N. T. S., Ribeiro, W. R., Cenedeze, M. A., Hiyane, M. I., Amano, M. T., Braga, T. T., Ferreira, C. M., Parmigiani, R. B., Andrade-Oliveira, V., Volpini, R. A., Vinolo, M. A. R., Mariño, E., Robert, R., Mackay, C. R., Camara, N. O. S. Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms.

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation.

BACKGROUND: Thrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices. However, elevated von Willebrand factor (VWF) in cirrhosis improves platelet function and could decrease this risk. Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation (EVL). METHODS: The assessment consisted of platelet count, antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity, and a platelet adhesion and aggregation test simulating vascular flow in vivo (Impact-RⓇ) prior to EVL. RESULTS: Totally 111 patients were divided into three groups according to platelet count: (1) < 50 × 109/L (n = 38, 34.2%); (2) 50 × 109/L to 100 × 109/L (n = 47, 42.3%); and (3) > 100 × 109/L (n = 26, 23.4%). No statistically significant difference was found in the aggregate size of platelets [group 1: 41.0 (31.8-67.3) µm2; group 2: 47.0 (33.8-71.3) µm2; and group 3: 47.0 (34.0-66.0) µm2; P = 0.60] and no significant correlation was found between aggregate size and platelet count (Spearman r = 0.07; P = 0.47). Surface coverage was 4.1% (2.8%-6.7%), 8.5% (4.0%-10.0%), and 9.0% (7.1%-12.0%) (P < 0.001) in groups 1, 2 and 3, respectively and correlated with platelet count (Spearman r = 0.39; P < 0.0001). There was no significant difference between groups in VWF or ADAMTS-13. Post-EVL bleeding occurred in six (5.4%) patients (n = 2 in group 1, n = 1 in group 2, and n = 3 in group 3; P = 0.32). Patients with bleeding had higher MELD scores [15.0 (11.3-20.3) versus 12.0 (10.0-15.0); P = 0.025], but no difference was demonstrated for platelet function parameters. CONCLUSION: Platelet function is preserved even in the presence of thrombocytopenia, including in the patients with post-EVL bleeding.

Modulation of mitochondrial metabolism as a biochemical trait in blood feeding organisms: the redox vampire hypothesis redux.

Hematophagous organisms undergo remarkable metabolic changes during the blood digestion process, increasing fermentative glucose metabolism, and reducing respiratory rates, both consequence of functional mitochondrial remodeling. Here, we review the pathways involved in energy metabolism and mitochondrial functionality in a comparative framework across different hematophagous species, and consider how these processes regulate redox homeostasis during blood digestion. The trend across distinct species indicate that a switch in energy metabolism might represent an important defensive mechanism to avoid the potential harmful interaction of oxidants generated from aerobic energy metabolism with products derived from blood digestion. Indeed, in insect vectors, blood feeding transiently reduces respiratory rates and oxidant production, irrespective of tissue and insect model. On the other hand, a different scenario is observed in several unrelated parasite species when exposed to blood digestion products, as respiratory rates reduce and mitochondrial oxidant production increase. The emerging picture indicates that re-wiring of energy metabolism, through reduced mitochondrial function, culminates in improved tolerance to redox insults and seems to represent a key step for hematophagous organisms to cope with the overwhelming and potentially toxic blood meal.

Vaginal laxity: what does this symptom mean?

INTRODUCTION AND HYPOTHESIS: Vaginal laxity is a poorly understood symptom of pelvic floor dysfunction. The purpose of this study was to investigate associations between the symptom of vaginal laxity and its bother on the one hand, and demographic data, other symptoms, and findings on examination on the other hand. METHODS: This was a retrospective observational study at a tertiary urogynecological unit. A total of 337 patients were seen for a standardized interview, clinical examination (ICS POP-Q) and 4D translabial ultrasonography. Stored imaging data were analyzed offline to evaluate functional pelvic floor anatomy and investigate associations with symptoms and other findings. RESULTS: Of the 337 women seen during the study period, 13 were excluded due to missing data, leaving 324. Vaginal laxity was reported by 24% with a mean bother of 5.7. In a univariate analysis, this symptom was associated with younger age, vaginal parity, POP symptoms and bother, clinically and sonographically determined POP and hiatal area on Valsalva maneuver. CONCLUSIONS: Vaginal laxity or 'looseness' is common in our urogynecology service at a prevalence of 24%. The associated bother is almost as high as the bother associated with conventional prolapse symptoms. It is associated with younger age, vaginal parity, symptoms of prolapse, prolapse bother and objective prolapse on POP-Q examination and imaging, suggesting that vaginal laxity may be considered a symptom of prolapse. The strongest associations were found with gh + pb and hiatal area on Valsalva maneuver, suggesting that vaginal laxity is a manifestation of levator ani hyperdistensibility.

Association between vaginal parity and rectocele.

INTRODUCTION AND HYPOTHESIS: Rectocele is common in parous women but also seen in nulliparae. This study was designed to investigate the association between vaginal parity and descent of the rectal ampulla/rectocele depth as determined by translabial ultrasound (TLUS). METHODS: This retrospective observational study involved 1296 women seen in a urogynaecological centre. All had undergone an interview, clinical examination and 4D ultrasound (US) imaging supine and after voiding. Offline analysis of volume data was undertaken blinded against other data. Rectal ampulla position and rectocele depth were measured on Valsalva. A pocket depth of 10 mm was used as a cutoff to define rectocele on imaging. RESULTS: Most women presented with prolapse (53%, n = 686); 810 (63%) complained of obstructed defecation (OD). Clinically, 53% (n = 690) had posterior-compartment prolapse with a mean Bp of -1 [standard deviation (SD)1.5; -3 to 9 cm]. Mean descent of the rectal ampulla was 10 mm below the symphysis (SD 15.8; -50 to 41). A rectocele on imaging was found in 48% (n = 618). On univariate analysis, OD symptoms were strongly associated with rectal descent, rectocele depth and rectocele on imaging (all P < 0.001). The prevalence of a rectocele seen on imaging increased with vaginal parity (P < 0.001). One-way analysis of variance (ANOVA) of vaginal parity against rectal descent and rectocele depth showed a dose-response relationship (both P < 0.001). CONCLUSIONS: Vaginal parity was strongly associated with descent of the rectal ampulla and rectocele depth. This relationship approximated dose-response characteristics, with the greatest effect due to the first vaginal delivery.

Pelvic organ support several years after a first birth.

INTRODUCTION AND HYPOTHESIS: Female pelvic organ prolapse is highly prevalent and childbirth has been shown to be an important risk factor. The study was carried out to observe if pelvic organ support deteriorates over time following a first birth. METHODS: This is a retrospective review using archived data sets of women seen in the context of two prospective perinatal imaging studies. All subjects had undergone a standardised interview, a clinical examination and 4D translabial ultrasound, 3 months and 2-5 years post-partum. Main outcome measures were pelvic organ descent and hiatal area at maximum Valsalva manoeuvre. Means at the two time points were compared using paired Student's t test. Predictors of change over time in continuous variables were explored using linear modelling methods. RESULTS: A total of 300 women had at least two postnatal follow-ups. They were first seen on average 0.39 (SD 0.2, range 0.2-2.1) years and again 3.1 (SD 1.5, range 1.4-8) years after the index delivery, with a mean interval of 2.71 (SD 1.5, range 0.7-7.7) years, providing a total of 813 (300 × 2.71) woman-years of observation. On univariate analysis, there was a significant decrease in mobility over time of the bladder neck, bladder, and rectal ampulla (P = < 0.004) and hiatal area (P = 0.012). The degree of improvement was less marked in women with levator avulsion. CONCLUSIONS: A significant reduction in pelvic organ descent and hiatal area was noted over a mean of 2.7 years after a first birth.

High dose of formaldehyde exposure during pregnancy increases neutrophils lung influx evoked by ovalbumin in the offspring.

OBJECTIVE: Considering that asthma might have their onset in the intrauterine life and the exposure to FA during pregnancy interferes in the immune system of offspring, here we hypothesized that high dose of FA exposure during pregnancy could to contribute for development and severity of asthma in the offspring. METHODS: Pregnant Wistar rats were submitted to FA inhalation (6.13 mg/m(3), 1 h/day, 5 days/week, for 21 days) or vehicle (distillated water). After 30 days of birth, the offspring was sensitized with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge, the analyses were performed. Non-manipulated rats were used as basal parameters. RESULTS: Our data show that the exposure to high dose of FA during pregnancy predisposes the development of neutrophilic lung inflammation in the offspring, as observed by the profile of cells and cytokines in the lung. CONCLUSION: This study contributes to the understanding of effects of pollution on the development of lung diseases.