Botucatu Medical School Research Articles

How anatomical impairments found on CT affect perfusion percentage assessed by SPECT/CT scan?

CT images can identify structural and opacity alterations of the lungs while nuclear medicine's lung perfusion studies show the homogeneity (or lack of) of blood perfusion on the organ. Therefore, the use of SPECT/CT in lung perfusion scintigraphies can help physicians to assess anatomical and functional alterations of the lungs and to differentiate between acute and chronic disease. To develop a computer-aided methodology to quantify the total global perfusion of the lungs via SPECT/CT images and to compare these results with parenchymal alterations obtained in CT images. 39 perfusion SPECT/CT images collected retrospectively from the Nuclear Medicine Facility of Botucatu Medical School's Clinics Hospital in São Paulo, Brazil, were analyzed. Anatomical lung impairments (emphysema, collapsed and infiltrated tissue) and the functional percentage of the lungs (blood perfusion) were quantified from CT and SPECT images, with the aid of the free, open-source software 3D Slicer. The results obtained with 3D Slicer (3D-TGP) were also compared to the total global perfusion of each patient's found on their medical report, obtained from visual inspection of planar images (2D-TGP). This research developed a novel and practical methodology for obtaining lungs' total global perfusion from SPECT/CT images in a semiautomatic manner. 3D-TGP versus 2D-TGP showed a bias of 7% with a variation up to 67% between the two methods. Perfusion percentage showed a weak positive correlation with infiltration (p = 0.0070 and ρ = 0.43) and collapsed parenchyma (p = 0.040 and ρ = 0.33). This research brings meaningful contributions to the scientific community because it used a free open-source software to quantify the lungs blood perfusion via SPECT/CT images and pointed that the relationship between parenchyma alterations and the organ's perfusion capability might not be so direct, given compensatory mechanisms.

Carnosine supplementation and retinal oxidative parameters in a high-calorie diet rat model

BackgroundTo assess oxidative effects induced by a high-calorie diet on the retina of Wistar rats and test the antioxidative effects of carnosine supplementation.MethodsWistar rats were randomly divided into the following groups: standard diet (SD), high-calorie diet (HcD), standard diet + carnosine (SD + Car), and high-calorie diet + carnosine (HcD + Car). The body weight, adiposity index, plasma glucose, total lipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid, creatinine, and triglycerides of the animals were evaluated. The retinas were analyzed for markers of oxidative stress. Hydrogen peroxide production was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCF) oxidation. The total glutathione (tGSH), total antioxidant capacity (TAC), protein carbonyl, and sulfhydryl groups of the antioxidant system were analyzed.ResultsTAC levels increased in the retinas of the SD + Car group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the HcD group (p < 0.05). The levels of GSH and the GSSH:GSSG ratio were increased in the HcD + Car group compared to the SD + Car group (p < 0.05). An increase in the retinal carbonyl content was observed in the HcD group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the SD + Car group (p < 0.05). A high-calorie diet (HcD) was also associated with a decrease in retinal sulfhydryl-type levels compared to the SD group (p < 0.05).ConclusionThe results suggest that feeding a high-calorie diet to rats can promote an increase in carbonyl content and a reduction in sulfhydryl groups in their retinas. The administration of carnosine was not effective in attenuating these oxidative markers.Trial registrationAnimal Ethics Committee of Botucatu Medical School - Certificate number 1292/2019.

Accessibility to manage the obstructive sleep apnea within the Brazilian Unified Health System

ObjectiveTo measure the average time for the diagnosis and for the therapeutic prescription of Continuous Positive Airway Pressure (CPAP) at a hospital in Botucatu Medical School - State University São Paulo, UNESP. MethodA retrospective observational study was carried out by collecting data from the electronic medical records of patients over 18-years of age, who had a diagnostic polysomnography testing scheduled between January and December 2017. ResultOf the 347 patients eligible for the study, 94 (27.1%) missed follow-up and 103 (29.7%) had a referral for CPAP use. Until February 2021, only 37 (35.9%) of these patients had already acquired and were using the device, the remaining 66 (64.1%) were waiting or gave up the therapy. The mean value of the waiting time interval between the referral of the diagnostic test and its performance was equivalent to 197 days (6.5 months). The mean time between diagnostic polysomnography and CPAP prescription was 440-days (14.5-months), with a total mean time of 624 days (21-months). ConclusionAs in other services, the diagnostic-therapeutic flow proved to be highly inefficient, with a long waiting period, difficult access to treatment and a high dropout rate. These findings highlight the need to establish new patient-centered strategies with measures that speed up the flow and facilitate access to CPAP, in order to reduce the morbidity and mortality associated with this condition. Level of evidenceLevel 3 - Non-randomized controlled cohort/follow-up study Recommendation B.

Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth.

Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women-15 preterm and 16 term-were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.

Reproducibility of double agar gel immunodiffusion test using stored serum and plasma from paracoccidioidomycosis patients.

Serological evaluation performed by double agar gel immunodiffusion test (DID) is used for diagnosis, evaluation of severity, management of paracoccidioidomycosis patients, and development of new clinical studies. For these reasons, the Botucatu Medical School of UNESP maintains a serum bank at the Experimental Research Unit with patient clinical data. This study aimed to evaluate the influence of the freeze-thaw cycle and different blood matrices on the titration of circulating antibodies. The study included 207 patients with confirmed (etiology-demonstrated) or probable (serology-demonstrated) paracoccidioidomycosis, and DID was performed with culture filtrate from Paracoccidioides brasiliensis B339 as antigen. First experiment: the antibody levels were determined in serum samples from 160 patients with the chronic form and 20 with the acute/subacute form, stored at -80oC for more than six months. Second experiment: titers of 81 samples of serum and plasma with ethylenediaminetetraacetic acid (EDTA) or heparin, from 27 patients, were compared according to matrix and effect of storage at -20oC for up to six months. Differences of titers higher than one dilution were considered discordant. First experiment: test and retest presented concordant results in serum stored for up to three years, and discordant titers in low incidence in storage for four to six years but high incidence when stored for more than six years, including conversion from reagent test to non-reagent retest. Second experiment: serum, plasma-EDTA and plasma-heparin samples showed concordant titers, presenting direct correlation, with no interference of storage for up to six months. Storage at -80oC for up to six years has no or little influence on the serum titers determined by DID, permitting its safe use in studies depending on this parameter. The concordant titrations in different blood matrices demonstrated that the plasma can be used for immunodiffusion test in paracoccidioidomycosis, with stability for at least six months after storage at -20oC.

Natural Language Processing to Extract Information from Portuguese-Language Medical Records

Studies that use medical records are often impeded due to the information presented in narrative fields. However, recent studies have used artificial intelligence to extract and process secondary health data from electronic medical records. The aim of this study was to develop a neural network that uses data from unstructured medical records to capture information regarding symptoms, diagnoses, medications, conditions, exams, and treatment. Data from 30,000 medical records of patients hospitalized in the Clinical Hospital of the Botucatu Medical School (HCFMB), São Paulo, Brazil, were obtained, creating a corpus with 1200 clinical texts. A natural language algorithm for text extraction and convolutional neural networks for pattern recognition were used to evaluate the model with goodness-of-fit indices. The results showed good accuracy, considering the complexity of the model, with an F-score of 63.9% and a precision of 72.7%. The patient condition class reached a precision of 90.3% and the medication class reached 87.5%. The proposed neural network will facilitate the detection of relationships between diseases and symptoms and prevalence and incidence, in addition to detecting the identification of clinical conditions, disease evolution, and the effects of prescribed medications.

Quality and Quantity Assessment of Tomographic Exams That Can Be Performed on Existing Hybrid Equipment at Botucatu Medical School Nuclear Medicine Services

Computed Tomography (CT) has been one of the greatest innovations for medical diagnosis. Among the main features of CT is its ability to provide high-quality anatomical and functional images. Other important imaging modalities are the ones conducted in Nuclear Medicine (NM), which, with the use of radiotracers, makes it possible to obtain metabolic and molecular images in vivo. The union of NM and CT imaging modalities is possible through hybrid equipment. The purpose of this research is to evaluate the quality and quantity of tomographic exams that can be performed in hybrid equipment. To complete this research analyzes of the ability to perform CT exams in the room that holds a Single Photon Emission Computed Tomography/ Computed Tomography SPECT/CT equipment in an NM facility were carried out. The evaluation criteria were: equipment quality control, image quality assessment by a subjective method as per European Guidelines on Quality Criteria for Computed Tomography (EUR), and assessment of shielding of the room, as an indicator of how many exams can be performed. Considering the results of the barrier thickness, the Botucatu Medical School and Nuclear Medicine facility is capable of performing 100 tomography exams per week. According to information obtained in the facility, currently, approximately 20 scans are performed weekly, so there is an increased opportunity of up to 80 exams weekly. Therefore, the hybrid equipment is qualified to perform diagnostic tests with superior image quality, compared to those performed in CT equipment.

MicroRNAs expression influence in ulcerative colitis and Crohn's disease: A pilot study for the identification of diagnostic biomarkers.

BACKGROUNDInflammatory bowel disease (IBD) comprises two distinct diseases, Crohn’s disease (CD) and ulcerative colitis (UC), both of which are chronic, relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown etiology. The incidence and prevalence of IBD are continually increasing, indicating the need for further studies to investigate the genetic determinants of these diseases. Since microRNAs (miRNAs) regulate protein translation via complementary binding to mRNA, discovering differentially expressed miRNAs (DE) in UC or CD patients could be important for diagnostic biomarker identification, assisting in the appropriate disease differentiation progressing the understanding of IBD pathogenesis.AIMTo determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed miRNA. METHODSA total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University (Unesp). The diagnosis of UC or CD was based on clinical, endoscopic, radiologic, and histological criteria and confirmed by histopathological analysis at the time of selection. The TaqMan™ Array Human MicroRNA A+B Cards Set v3.0 (Applied Biosystems™) platform was used to analyze 754 miRNAs. Targets of DE-miRNAs were predicted using miRNA Data Integration Portal (mirDIP) and the miRNA Target Interaction database (MiRTarBase). All statistical analyses were conducted using GraphPad Prism software. Parametric and nonparametric data were analyzed using t-tests and Mann-Whitney U tests, respectively.RESULTSThe results showed that of the 754 miRNAs that were initially evaluated, 643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC; the remaining 111 miRNAs were not considered to be expressed in these patients. The expression levels of 28 miRNAs were significantly different between the CD and UC patients (P ≤ 0.05); 13 miRNAs demonstrated a fold-change in expression level greater than 1. Five miRNAs with a downregulated expression were selected for enrichment analysis. The miRNAs whose expression levels were significantly lower in UC patients than in CD patients were enriched in certain signaling pathways that were mostly correlated with cancer-related processes and respective biomarkers. CONCLUSIONMiRNAs could be used to differentiate UC from CD, and differently expressed miRNAs could help explain the distinct pathophysiology of each disease.

The impact of prediabetes in the first trimester of pregnancy on the incidence of gestational diabetes

Introduction: Prediabetes (PD) outside of pregnancy is a condition reflecting a significant loss of glucose tolerance, characterized in the laboratory by fasting glucose between 100 and 125 mg/dL or 2 hour glucose in the 75 g Oral Glucose Tolerance Test (OGTT) between 140 and 199 mg/dL or by HbA1c levels between 5.7%-6.4% and is associated with an increased risk of developing type 2 diabetes. The development of gestational diabetes mellitus (GDM) during pregnancy, characterized by a fasting blood glucose between 92 and 125 mg/dL or an impaired OGTT value of 75 g between 24th and 28th weeks, is another condition that increases the risk of perinatal complications such as preeclampsia, cesarean section rate, macrosomia, and also the development of type 2 diabetes after delivery. Determining the prevalence of women diagnosed with prediabetes at the beginning of prenatal care and its association with the diagnosis of GDM is therefore of great importance for clinical, gynecological and obstetric care. Objective: the aim of the study is to determine the prevalence and association of prediabetes in the first trimester of pregnancy with the development of gestational diabetes&#x0D; Methodology: It was carried out in the Clinical Hospital of Botucatu Medical School. Retrospective cohort study involving eligible pregnant women who underwent fasting glucose test (FG) and glycated hemoglobin (HbA1c) test up to the 14 th week of gestation without previous diagnosis of diabetes mellitus, and who underwent 75 g oral glucose tolerance test (between the 24th and 28th week). We excluded cases in which FG was between 92 mg/dL and 125 mg/dL, which were considered GDM, and cases with FG ≥ 126 mg/dL and/or HbA1c ≥ 6.5 % (overt diabetes). One thousand electronic medical records from between 2013 and 2021 were reviewed and a database was created. The partial results were presented as percentage and 95 Confidence Interval (95% CI). The association between HbA1c and GDM was presented as relative risk and 95% CI. Results: Among pregnant women with normal fasting glucose levels and HbA1c &lt;5.7%, the incidence of GDM, diagnosed by OGTT, was 8.5% (6.4-11.3), while in the group with PD was 14.3% (5.8%-29.8%). The relative risk (RR) for developing GDM among the PD group was 1.7 (0.7-3.9). Discussion and conclusion: The association between prediabetes and gestational diabetes was not confirmed. However, these results are preliminary, and we need to reach the sample size calculated before starting the study to better understand these results. Furthermore, nonpregnant women with prediabetes are monitored and eventually treated, therefore, further studies are needed to evaluate the benefit of treating these pregnant women as recommended for the general population

Translation of a Brazilian educational booklet concerning hydrocephalus into Spanish as spoken in Spain

PurposeA booklet for children with hydrocephalus and their parents was presented. This study translated the Brazilian version of the booklet “Laura's diary: knowing hydrocephalus and its treatment” into Spanish as spoken in Spain. MethodologyThis methodological study conducted in Spain (Universidad de Santiago de Compostela) and Brazil (Botucatu Medical School) undertook the following translation steps: translation, using two Brazilian translators fluent in Spanish; synthesis, involving a Spanish nurse with experience in education; and back-translation, using a Brazilian translator and nurse fluent in Spanish. FindingsThe two versions of the initial translation were similar, with few amendments necessary during the consensus meeting between the researchers to achieve synthesis of the translations. The two versions of the back-translation were very similar to the original. ConclusionA free Spanish booklet was presented to minimize the negative effects of surgery, empower families, and aid future research between Brazil and Spain. Mismanagement of a disease can affect a child's quality of life. Communication is essential for health education to help ensure greater participation of patients and families in care plans.

Mejoramiento del tiempo y el espacio en la gestión de un centro quirúrgico: el caso de Botucatu, Brasil

This study aims to the creation of an indicator framework for monitoring, general evaluation and control of the operation of the Surgical Center of the Clinical Hospital of the Botucatu Medical School (HCFMB), to optimize time and better use the space available. The article consists of a qualitative case study, using a questionnaire, distributed to the team of the HCFMB Surgical Center. Data was collected through a focus group to confirm which indicators fit the Botucatu HC Surgical Center. After the meeting, some indicators that did not fit the reality of the hospital were eliminated. Time usage indicators were more relevant than performance related ones. The main contribution consists in the elaboration of a proposal, as there is very little research on the subject, being a very important and costly area for hospitals.

Ηyper-sinh-Convolutional Neural Network for Early Detection of Parkinson’s Disease from Spiral Drawings

Modern developments in the state-of-the-art open-source activation functions for Convolutional Neural Networks (CNNs) have broadened the selection of benchmark activations for Deep Learning (DL)-aided classification. Nevertheless, achieving discrimination of non-linear input image data in CNN is still not straightforward and it is unclear how such novel activation functions can have translational applications with tangible impact. hyper-sinh, made freely available in TensorFlow and Keras, was demonstrated as a benchmark activation function on five (N=5) datasets in its ground-breaking paper. Measuring the value from deploying this activation in a specific application is pivotal to supply the required evidence of its performance on real-life supervised DL-based image classification tasks. In this study, a CNN was for the first time combined with hypersinh to aid early detection of Parkinson’s Disease (PD) from discriminating pathophysiological patterns extracted from spiral drawings. Thus, the hyper-sinh activation was deployed to maximise the separability of the input features from spiral drawings via automated pattern recognition. We demonstrate the accuracy and reliability of hyper-sinh-CNN to aid early diagnosis of PD, evaluated against other gold standard activation functions, including the recent Quantum ReLU (QReLU) and the modified Quantum ReLU (m-QReLU) that solved the ‘dying ReLU’ problem for the first time in the literature of DL. Two (N=2) benchmark datasets from the database of the Botucatu Medical School, São Paulo State University in Brazil, scaled to be in 28 by 28 pixels as the MNIST benchmark data, were used to discriminate between input image patterns of 158 subjects (53 healthy controls and 105 patients with PD) from spirals drawn on graphics tablets. Overtraining was avoided via early stopping and the models were developed and tested in TensorFlow and Keras (Python 3.6). The supervised model (hyper-sinh-CNN) could detect early Parkinson’s Disease with 81% and 91% classification accuracy from the two datasets respectively (F1-scores: 73% and 91% correspondingly). Furthermore, the model achieved high sensitivity (81% and 91%). Thus, this study validates the application of hyper-sinh to aid real-life supervised DL-based image classification, in particular early diagnosis of PD from spiral drawings.

Paracoccidioimycosis and white individuals: Susceptibility and biogeographic aspects in an important endemic area in Brazil.

Paracoccidioidomycosis (PCM) is a neglected mycosis most commonly occurring in Latin America. The etiologic agents are thermo dimorphic fungi of the genus Paracoccidioides, and cause an important granulomatous response in affected tissues. The Botucatu Medical School, from São Paulo State University (UNESP), is a PCM study pole, located in São Paulo State Midwest region, which is classified as a hyperendemic area in the Southeast region in Brazil. This study aimed to perform a retrospective epidemiological, geographical, and clinical analysis by the information available in medical records. It was listed as socio-demographic data along with clinical characteristics from patients diagnosed and treated during a 10-year period in Botucatu, totaling 177 patients with Paracoccidioidomycosis confirmed by the histopathological test. It was observed that the main clinical presentation was the chronic type (76,3%), most commonly identified in white male individuals over the age of 29 years old, smokers, and alcoholics, providing evidences for the first time that white individuals were more affected by the disease, in comparison to non-white individuals that may be more resistant to infection. This data opens new avenues for study within ancestry, resistance and susceptibility in paracoccidioidomycosis.

Symphysis-Fundal Height Curve in Pregnancies Complicated by Maternal Hyperglycemia: Comparison with Curves of Nondiabetic Pregnant Women.

Background Reference symphysis-fundal height (SFH) curves for pregnancies complicated by maternal hyperglycemia are not available. Objective To build an SFH curve according to gestational age for pregnant women with hyperglycemia-type 2 diabetes (T2DM), gestational diabetes mellitus (GDM), or mild gestational hyperglycemia (MGH) and compare it with three other curves in use in Brazil. Methods Prospective cohort study of 422 pregnant women with hyperglycemia attending the Perinatal Diabetes Research Center (PDRC) of Botucatu Medical School, São Paulo State University/UNESP. Between 13 and 41 weeks of pregnancy, 2470 SFH measurements were obtained (mean 5.85 per woman). For the assessment of glycemic control, 2074 glucose level measurements were taken and the glycemic mean (GM) at each gestational week was estimated. Results GM was adequate (<120 mg/dL) in 94.9% and inadequate (≥120 mg/dL) in 5.1% of the cases. The equation applied for SFH prediction was expressed as SFH = 1.082 + 0.966∗week (r2 = 84.6%). At visual analysis, P10 and P90 SFH measurements were higher in the study curve than in the three other curves. Statistical analysis confirmed that SFH median values in this study were higher than those in the reference curve of habitual risk pregnancies, especially after 19 weeks of pregnancy. Conclusion Taking into account that the maternal hyperglycemia was at strict control, our unedited results suggest that the current SFH curve can be a useful tool in prenatal care of T2DM, GDM, and MGH pregnant women.

Survival and prognostic factors of patients with breast cancer in the state of São Paulo

Abstract Introduction Breast cancer is a public health problem worldwide, being the most common malignant neoplasm in the female population. Objectives To estimate 5- and 10-year breast cancer-specific survival probabilities of patients included in the hospital-based cancer registry (HBCR) of the Fundação Oncocentro de São Paulo (FOSP, in Portuguese) and to assess the prognostic factors for this neoplasm. Methods Historical cohort study that included women with breast cancer included in HBCR-FOSP and diagnosed between 2002 and 2012. The event of interest was breast cancer-specific mortality. Living cases at the end of follow-up (December 31, 2017), loss to follow-up and death other than that due to breast cancer were considered censored on the date of the last contact or date of death. Descriptive analysis and survival analysis were performed using the Kaplan-Meyer method. Survival curves were compared using the log-rank test. Hazard ratios (HR) and their 95%CI were estimated using Cox's proportional hazards model. The study was approved by the Human Research Ethics Committee of the Botucatu Medical School, São Paulo State University, Brazil. Results 53,146 cases of invasive breast cancer were registered at HBCR-FOSP between 2002-2012. The median age at diagnosis was 55.9 years. By the end of the follow-up, 20,683 patients died, and 71.4% were due to breast cancer. The 5- and 10-year breast cancer-specific survival for the entire cohort was 76.1% (95%CI 75.7-76.5%) and 64.8% (95% CI 64.2-65.3%), respectively. In the multivariate analysis, the factors associated with prognosis were age at diagnosis, year of diagnosis, educational level, clinical stage, and histological type. Conclusions These findings may contribute to the development of policies for the identification of breast tumors at earlier stages. Key messages Breast cancer is an important public health problem in Brazil and worldwide. The findings of this study may contribute to the development of public policies for the control of breast cancer in the state of São Paulo.

Translation of a Brazilian educational booklet concerning hydrocephalus into Spanish as spoken in Spain

PurposeA booklet for children with hydrocephalus and their parents was presented. This study translated the Brazilian version of the booklet “Laura's diary: knowing hydrocephalus and its treatment” into Spanish as spoken in Spain. MethodologyThis methodological study conducted in Spain (Universidad de Santiago de Compostela) and Brazil (Botucatu Medical School) undertook the following translation steps: translation, using two Brazilian translators fluent in Spanish; synthesis, involving a Spanish nurse with experience in education; and back-translation, using a Brazilian translator and nurse fluent in Spanish. FindingsThe two versions of the initial translation were similar, with few amendments necessary during the consensus meeting between the researchers to achieve synthesis of the translations. The two versions of the back-translation were very similar to the original. ConclusionA free Spanish booklet was presented to minimize the negative effects of surgery, empower families, and aid future research between Brazil and Spain. Mismanagement of a disease can affect a child's quality of life. Communication is essential for health education to help ensure greater participation of patients and families in care plans.

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

BackgroundPelvic 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.MethodsThe 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.DiscussionTo 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.

Breast cancer in women: characterization of cases included in the hospital cancer records of the state of São Paulo and factors associated with advanced stadiums

Introduction: Breast cancer is a worldwide public health problem, being the most common malignancy in the female population. It is a potentially curable disease if diagnosed early. The advanced stage at the time of diagnosis is associated with increased morbidity and low survival of these women. Objectives: To describe the sociodemographic, clinical, and anatomopathological characteristics of breast cancer cases in women included in the São Paulo State hospital cancer database (registros hospitalares de câncer de São Paulo – RHC-SP), established in 2000 and maintained by the Fundação Oncocentro de São Paulo (FOSP) and to investigate the factors associated with the clinical stage at the time of diagnosis. Material and methods: The study design was a series of cases. The sample consisted of women with breast cancer diagnosed between 2000-2014 and included in the RHC-FOSP. The outcome variable was the clinical stage (stage 0-II versus III-IV). The explanatory variables were: age at diagnosis and education level. This study was approved by the Human Research Ethics Committee of the Botucatu Medical School, UNESP. Results: The study included 84,987 women with in situ and invasive breast cancer diagnosed between 2000-2014. The mean age of women at diagnosis was 56.7 years (95%CI 56.6–56.8 years). Sixty-five percent of the cases have complete elementary school or less and the most frequent histological type was ductal carcinoma (77.2%). During the study period, there was a small decrease in the proportion of tumors in more advanced stages, from 39.8% in 2000 to 32.6% in 2014. There was a statistically significant association between the variables age at diagnosis and level of education with the clustered clinical stage of women. Women of older age and those with a higher level of education had reduced odds ratios for tumors in more advanced stages at the time of diagnosis. Conclusion: These findings may contribute to the development of policies for the identification of breast tumors at an earlier stage.

Influence of single nucleotide polymorphisms (SNPs) in immunoregulatory genes in the morbidity of preterm newborns

Background Prematurity is the main cause of perinatal and neonatal morbidity and mortality worldwide. Single nucleotide polymorphisms (SNPs) have been associated with the pathogenesis of morbidities in preterm neonates. We aimed to investigate the association between SNPs in regulatory genes of innate immune response IL1B, IL6, IL6R, IL10, TNFA, TNFRII, TLR2 and TLR4 and neonatal/infant morbidities in preterm newborns. Methods Oral swabs were collected from 272 newborns (91 preterm and 181 at term) seen at Botucatu Medical School, Unesp, between 2013 and 2014 and SNPs were identified using Taqman® Genotyping Assays. Medical records were examined to obtain data regarding neonatal/infant morbidity. Stepwise binomial logistic regression models were used to explain the morbidities. Results Minor neonatal morbidity was influenced by the clinical parameters of maternal age and newborn weight at birth and by the presence of the allele IL6R2 C (rs2228145) while major neonatal morbidity was only influenced by gestational age. Minor infant morbidity was associated with the allele TLR2 T (rs4696480) and major infant morbidity was associated with gestational age and presence of IL6R2 C. Conclusion The presence of SNPs that exacerbate the inflammatory response increases the susceptibility to neonatal and infant morbidity.

Tissue microarrays of bone marrow aspirate clot allow assessment of multiple samples

Time optimization and cost reduction without quality loss is fundamental for scientific production. The TMA technique allows large-scale analysis of paraffin-embedded and fixed tissues using non-decalcified bone marrow specimens. Cytoinclusion samples (n = 264) were selected from patients diagnosed with monoclonal gammopathy (n = 189) at Botucatu Medical School, São Paulo State University. Slides were cut from the TMA block and stained with H&E and immunohistochemical markers. Of the 276 fragments included in the receptor block, 45 core detachments were observed, thus 84% of the samples remained viable. The representative material allowed for adequate analysis of isolated cells, which showed nuclear, cytoplasmic and membrane staining. Thus, we verified that inclusion of bone marrow aspirate clot is a valid alternative for TMA histological and immunohistochemical analyses.