Characterization of CRESS-DNA viruses in human vaginal secretions: An exploratory metagenomic investigation.

The Phylum Cressdnaviricota consists of a large number of circular Rep-encoding single-stranded (CRESS)-DNA viruses. Recently, metagenomic analyzes revealed their ubiquitous distribution in a diverse range of eukaryotes. Data relating to CRESS-DNA viruses in humans remains scarce. Our study investigated the presence and genetic diversity of CRESS-DNA viruses in human vaginal secretions. Vaginal swabs were collected from 28 women between 29 and 43 years old attending a fertility clinic in New York City. An exploratory metagenomic analysis was performed and detection of CRESS-DNA viruses was confirmed through analysis of near full-length sequences of the viral isolates. A phylogenetic tree was based on the REP open reading frame sequences of the CRESS-DNA virus genome. Eleven nearly complete CRESS-DNA viral genomes were identified in 16 (57.1%) women. There were no associations between the presence of these viruses and any demographic or clinical parameters. Phylogenetic analysis indicated that one of the sequences belonged to the genus Gemycircularvirus within the Genomoviridae family, while ten sequences represented previously unclassified species of CRESS-DNA viruses. Novel species of CRESS-DNA viruses are present in the vaginal tract of adult women. Although they be transient commensal agents, the potential clinical implications for their presence at this site cannot be dismissed.

Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5'UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Changes in cytokine and sequestosome-1 levels during twin pregnancy progression: Association with outcome.

BACKGROUND: Twin pregnancies are associated with complications and adverse outcomes. The number of twin pregnancies has increased in the last decades, due to the use of assisted reproductive techniques and delayed childbearing. Analysis of changes that occur during twin pregnancy progression and their association with outcome will lead to improved clinical interventions. OBJECTIVE: We evaluated if the plasma concentration of select cytokines and the level of sequestosome-1 (p62) in peripheral blood mononuclear cells (PBMCs) during each trimester of twin gestations was predictive of pregnancy outcome. STUDY DESIGN: This prospective, observational study was conducted at Careggi University Hospital, Florence, Italy. Plasma from 82 women with twin pregnancies was collected in each trimester for measurement of interleukin (IL)-1ß, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α. The intracellular PBMC concentration of p62, a protein involved in autophagy, kinase activity and cell differentiation, was also determined. RESULTS: IL-1ß (p < 0.001), IL-6 (p < 0.001), TNF-α (p < 0.001) and p62 (p < 0.05) increased from the 1st to the 2nd to the 3rd trimester. The TNF-α level was correlated with the IL-1ß concentration in the 1st and 3rd trimesters p < 0.01) and with the IL-6 concentration in each of the three trimesters (p < 0.01). The intracellular p62 level in PBMCs was negatively correlated with the concentration of IL-1ß in the 2nd trimester (p < 0.05) and negatively correlated with the IL-6 level in the 3rd trimester (p < 0.05). The TNF-α level was significantly higher in the 2nd (p < 0.05) and 3rd (p < 0.001) trimester in women with a spontaneous preterm delivery. The TNF-α concentrations in the 2nd (p < 0.05) and 3rd (p < 0.01) trimester, respectively, and 3rd trimester IL-6 (p < 0.01), were negatively associated with gestational age at delivery. The concentration of IL-6 was highest in the 2nd (p < 0.05) and 3rd (p < 0.05) trimesters in women who utilized assisted reproductive technologies. An elevated IL-1ß level in the 3rd trimester was associated with gestational diabetes mellitus (p < 0.05). CONCLUSION: Variations in cytokine levels between individual women during the three trimesters of twin gestations are predictive of spontaneous preterm delivery and the onset of gestational diabetes.

Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with Haemophilus influenzae Meningitis in a Newborn.

Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology.

Does the addition of electrical stimulation or kinesiotherapy improve outcomes of amitriptyline treatment for women with vulvodynia? A randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: Women diagnosed with provoked vulvodynia frequently report a great deal of frustration in achieving symptomatic relief. Physical therapy and drug treatment are among the interventions most indicated by guidelines; however, whether those modalities are effective when combined remains unclear. The objective was to evaluate the effectiveness of adding a physical therapy modality compared with amitriptyline alone for the treatment of vulvodynia. METHODS: Eighty-six women with vulvodynia were randomized to (G1) 25 mg amitriptyline, once a day (n=27), (G2) amitriptyline + electrical stimulation therapy (n=29) or (G3) amitriptyline + kinesiotherapy (n=30). All treatment modalities were administered for 8 weeks. The primary endpoint was the reduction in vestibular pain. Secondary measurements focused on sexual pain, frequency of vaginal intercourse, Friedrich score, and overall sexual function. Data were analyzed using intention-to-treat. RESULTS: All treatment modalities resulted in a significant decrease in vestibular pain (p<0.001), sexual pain (p<0.05), Friedrich score (p<0.001), and an increase in the frequency of sexual intercourse (p<0.05). G3 was more effective than G1 at reducing sexual pain (G1: 5.3±3.3 vs G3: 3.2±2.7; p=0.01) and at improving sexual function (G1: 18.8±9.8 vs G3: 23.9±7.8; p=0.04). CONCLUSION: Kinesiotherapy and electrotherapy additions to amitriptyline administration as well as amitriptyline alone, were effective at improving vestibular pain in women with vulvodynia. Women receiving physical therapy had the greatest improvement in sexual function and frequency of intercourse at post-treatment and follow-up.

Improved detection of hepatitis C virus-positive blood donors and determination of infection status.

BACKGROUND: In low-risk populations, variability in the sensitivity of current serological tests for Hepatitis C virus (HCV) blood donor screening may lead to the presence of false-positive results. This contributes to the unnecessary loss of blood donor samples as well as to difficulty in accurate donor counselling. The present study determined the optimal cut-off value of a chemiluminescent immunoassay for identification of HCV-reactive blood donors. STUDY DESIGN AND METHODS: In a retrospective cross-sectional analysis of 193 973 blood donations, 578 samples that were positive for HCV antibody in a chemiluminescent immunoassay and/or RNA screening tests were identified. Blood from 379 of these positive samples was available for retesting by a second confirmatory HCV immunoassay followed by a receiver operating characteristic (ROC) curve analysis. Donors were also recalled for a new analysis. RESULTS: Only 71 (18.7%) blood samples remained HCV-positive upon retesting, while 233 (61.5%) now tested negative and 75 (19.8%) yielding indeterminate results. A signal to cutoff ratio ≥4.32 was determined as the best differential threshold between a positive and negative result, increasing the positive predictive value from 27.3% to 66.7%. CONCLUSION: Using a higher threshold for an HCV-positive blood sample enhances the chemiluminescent immunoassay screening test´s accuracy and helps to improve donor counselling and notification processes.

Differences in Placental Histology Between Zika Virus-infected Teenagers and Older Women.

In pregnant women, Zika virus (ZIKV) is associated with a congenital syndrome, most frequently involving damage to embryo brain formation and the development of microcephaly. The mechanism(s) by which ZIKV enters the maternal-fetal interface and is transmitted to the fetus remains incompletely determined. We sought to evaluate histologic changes in the placenta of ZIKV-infected pregnant women and to determine if this varied by maternal age. Placental samples were obtained from 66 women, 33 of whom were positive for ZIKV. Histologic evaluations were performed on 4 areas of the placenta: fetal surface, maternal surface, umbilical cord, and membranes. Samples were analyzed by the tissue microarray technique and tested for CD4, CD8, CD20, CD68, FOXP3, and cyclooxygenase-2 expression. Data were evaluated using Fisher exact test. ZIKV infection was more frequent in women less than 18 yr of age (9/11, 81.8%) than in women above 18 yr old (24/55, 43.6%) (P=0.0440). ZIKV detection was associated with neutrophilic chorioamnionitis (P=0.0332) and with septal (P=0.0244) and villous (P=0.0534) calcification. Hofbauer cell hyperplasia (P=0.0260) and cyclooxygenase-2 expression (P=0.0346) were more prevalent in ZIKV-positive women aged 18 yr and below than in the older ZIKV-positive women. ZIKV infection during pregnancy occurs more frequently in adolescents and induces higher rates of damage at the maternal-fetal interface than in older women.

Survival among children and adults treated with granulocyte transfusions: Twenty years' experience at a Brazilian blood center.

BACKGROUND: It remains controversial whether granulocyte transfusions as a supportive treatment improve survival in patients with febrile neutropenia or granulocyte dysfunctions. We describe survival rates subsequent to granulocyte transfusions in pediatric and adults patients treated at a major blood center in Brazil. MATERIAL AND METHODS: We retrospectively reviewed the clinical charts of pediatric and adult patients treated with granulocyte transfusions at our institution from January 2000 to October 2019. We assessed demographic characteristics, clinical features, indications for transfusion, units transfused, dose of granulocytes administered and survival rates 30 and 100 days after the initial transfusion. RESULTS: We identified 64 pediatric and 67 adult patients treated with 262 granulocyte transfusions. An optimal dose (> 0.6 × 109 granulocytes per kilogram per transfused unit) was available for transfusion in 80.4 % of pediatric patients but in only 19.6 % of adults (p = 0.017). Thirty days after their first granulocyte transfusion, 38 (59.4 %) pediatric and 61 (91 %) adult patients had died. Patients receiving the optimal dose of granulocytes had better survival outcomes, but even among this sub-group, adults were more likely to die than were children either at 30 days (OR = 8.67, 95 %CI 2.69-34.9) or 100 days (OR = 6.27, 95 %CI 1.86-25.9) after their initial granulocyte transfusion. CONCLUSION: Survival rates following granulocyte transfusion varied by the dose transfused and were higher in children than in adults.

Comparative measurement of D- and L-lactic acid isomers in vaginal secretions: association with high-grade cervical squamous intraepithelial lesions.

PURPOSE: Identification of low-cost protocols to identify women at elevated susceptibility to develop cervical intra-epithelial abnormalities would aid in more individualized monitoring. We evaluated whether quantitation of the D- and L-lactic acid isomers in vaginal secretions could differentiate women with normal cervical epithelia from those with a low (LSIL) or high (HSIL) grade squamous intraepithelial lesion or with cervical cancer. METHODS: Vaginal samples, collected from 78 women undetgoing cervical colposcopy and biopsy, were tested for pH, bacterial composition by Gram stain (Nugent score) and concentrations of D- and L-lactic acid by a colorimetric assay. RESULTS: Subsequent diagnosis was 23 women with normal cervical epithelium, 10 with LSIL, 43 with HSIL and 2 with cervical cancer. Vaginal pH and Nugent score were comparable in all subject groups. The concentration of L-lactic acid, but not D-lactic acid, as well as the L/D-lactic acid ratio, were significantly elevated (p < 0.01) in women with HSIL and cervical cancer. CONCLUSION: Comparative measurement of vaginal D- and L-lactic acid isomers may provide a low-cost alternative to identification of women with an elevated susceptibility to cervical abnormalities.

Transcriptomic Profiling of Rectus Abdominis Muscle in Women with Gestational Diabetes-Induced Myopathy: Characterization of Pathophysiology and Potential Muscle Biomarkers of Pregnancy-Specific Urinary Incontinence.

Gestational diabetes mellitus (GDM) is recognized as a "window of opportunity" for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.

Prolonged presence of replication-competent SARS-CoV-2 in mildly symptomatic individuals: A report of two cases.

It has been estimated that individuals with COVID-19 can shed replication-competent virus up to a maximum of 20 days after initiation of symptoms. The majority of studies that addressed this situation involved hospitalized individuals and those with severe disease. Studies to address the possible presence of SARS-CoV-2 during the different phases of COVID-19 disease in mildly infected individuals, and utilization of viral culture techniques to identify replication-competent viruses, have been limited. This report describes two patients with mild forms of the disease who shed replication-competent virus for 24 and 37 days, respectively, after symptom onset.

Influence of unreported HIV prophylaxis on the kinetics of post-blood donation HIV seroconversion.

BACKGROUND: In 2020, of 110,000 blood donors screened for HIV exposure two individuals were identified who were viral RNA-positive but seronegative. One of the donors, borderline negative in a pooled screening test for HIV RNA, utilized antiretroviral drugs as post-exposure, pre-donation prophylaxis. The kinetics of subsequent HIV seropositivity in both donors are described. STUDY DESIGN AND METHODS: Both donors were recalled and interviewed, and blood was obtained at intervals for HIV antibodies and RNA testing. RESULTS: One donor used antiretroviral prophylaxis for 30 days due to a relationship with an HIV-positive partner. In follow-up samples, seroconversion was noted at 70 days, and viral RNA was detected at 105 days, after blood donation. In contrast, the other donor seroconverted in <25 days and the appearance and titer of HIV RNA was in accordance with the typical pre-seroconversion window. CONCLUSION: The use of anti-viral prophylaxis by blood donors in the acute phase of HIV infection delays seroconversion. A 6-month deferral in blood donation after HIV prophylaxis, as currently recommended in Brazil, would have been sufficient in this case to mitigate the risk of transfusion-transmitted HIV. Ultimately, improvement in donor compliance with selection procedures for blood donation is needed to optimize blood safety.

Occult and active hepatitis B virus detection in donated blood in São Paulo, Brazil.

BACKGROUND: The present study determined the HBV antigen, antibody, and DNA status in blood donations deemed to be HBV positive. Individuals with an occult HBV infection (OBI), defined as being positive for HBV DNA but negative for HBV surface antigen (HBsAg), as well as those with active infection (HBsAg-positive), were identified and characterized. STUDY DESIGN AND METHODS: From a total pool if 198,363 blood donations, we evaluated in a cross-sectional study, 1106 samples that were positive in screening tests for antibody to HBV core antigen (HBcAb), HBsAg, and/or HBV DNA by nucleic acid testing (NAT-HBV). The presence of genetic variants in the HBV pol/S gene in individuals with an active HBV infection was also determined. RESULTS: OBIs were detected in six of 976 samples (0.6%) that were positive only for HBcAb. The rate of HBV active infection was 0.024% (48/198,363) and there was a predominance of HBV sub-genotype A1 (62.2%, 28/45), followed by D3 (17.8%, 8/45). Mutations in the S gene were found in 57.8% (26/45) and immune escape mutations in 37.8% (17/45) of active HBV-infected donors. Among them, T123N, G145A, and D144G high-impact immune escape mutations were identified. CONCLUSION: Highly sensitive molecular tests improve the capacity to detect OBIs. When NAT is performed in pooled samples, HBcAb test has value in the detection of donors with OBI and improves transfusion safety. Mutations in the S gene are frequent in HBsAg-positive blood, including those associated with diagnostic failure and vaccine escape mutations.

Human astrovirus types 1, 4 and 5 circulating among children with acute gastroenteritis in a rural Brazilian state, 2010-2016.

This study combined conventional epidemiology of human astroviruses. From 2010 to 2016, 232 stool samples from children under 5 years of age were screened using NGS and conventional RT-PCR followed by genetic analysis in order to investigate the genotypic diversity of classical human astrovirus (HAstV) circulating in Tocantins State, Brazil. HAstV was detected in 16 cases (6.9%). Seven specimens (43.7%; 7/16) were positive according RT-PCR and next-generation sequencing (NGS) to investigate the molecular to both NGS and RT-PCR. NGS and RT-PCR individually revealed six (37.5%; 6/16) and three (18.8%; 3/16) additional positive samples, respectively. Sequencing of the HAstV-positive samples revealed HAstV-1a (9/16), HAstV-4c (3/16), and HAstV-5c (4/16) lineages.

The influence of race on cervical length in pregnant women in Brazil.

OBJECTIVES: Short cervical length is a predictor of preterm birth. We evaluated if there were racial differences in variables associated with cervical length in pregnant Brazilian women. METHODS: Cervical length was determined by vaginal ultrasound in 414 women at 21 weeks gestation. All women were seen at the same clinic and analyzed by the same investigators. Women found to have a short cervix (≤25 mm) received vaginal progesterone throughout gestation. Composition of the vaginal microbiome was determined by analysis of the V1-V3 region of the gene coding for bacterial 16S ribosomal RNA. Demographic, clinical and outcome variables were determined by chart review. Subjects were 53.4% White, 37.2% mixed race and 9.4% Black. RESULTS: Pregnancy, medical history and education level were similar in all groups. Mean cervical length was shorter in Black women (28.4 mm) than in White (32.4 mm) or mixed race (32.8 mm) women (p≤0.016) as was the percentage of women with a short cervix (23.1, 12.2, 7.8% in Black, White, mixed race respectively) (p≤0.026). Mean cervical length increased with maternal age in White (p=0.001) and mixed race (p=0.045) women but not Black women. There were no differences in bacterial dominance in the vaginal microbiota between groups. Most women with a short cervix delivered at term. CONCLUSIONS: We conclude that Black women in Brazil have a shorter cervical length than White or mixed race women independent of maternal age, pregnancy and demographic history or composition of the vaginal microbiome.

Influence of Lactobacillus crispatus, Lactobacillus iners and Gardnerella vaginalis on bacterial vaginal composition in pregnant women.

PURPOSE: To investigate associations between bacterial species in the vagina in mid-trimester pregnant women from Brazil. METHODS: The vaginal microbiome in 613 subjects was identified by analysis of the V1-V3 region of bacterial 16S ribosomal RNA and the relative prevalence of individual bacteria were determined. RESULTS: The bacterial species present in the greatest number of women were Lactobacillus crispatus (306 women), L. iners (298 women) and Gardnerella vaginalis (179 women). When present in the vagina, L. crispatus was the most abundant bacterium more than 85% of the time. In contrast, L. iners and G. vaginalis were most abundant in 63% and 41% of women who were positive for these microorganisms, respectively (p < 0.0001 vs. L. crispatus). The proportion of L. crispatus was negatively associated with the proportions of L. iners, L. jensenii, L. gasseri, G. vaginalis, Megasphaera, Atopobium vaginae and Prevotella (p < 0.0001). In contrast, the proportion of G. vaginalis was positively associated with levels of Megasphaera, A. vaginae and Prevotella (p < 0.0001) while L. iners proportion was unrelated to the proportion of L. jensenii, G. vaginalis, Megasphaera, A. vaginae or Prevotella. CONCLUSION: The composition of the vaginal microbiota in mid-trimester pregnant women is influenced by the relative concentrations of L. crispatus, L. iners and G. vaginalis.

Detection of Zika virus in paired urine and amniotic fluid samples from symptomatic and asymptomatic women and their babies during a disease outbreak: association with neurological symptoms in newborns.

Paired maternal and newborn urine and amniotic fluid from 138 subjects collected during a Zika virus (ZIKV) outbreak was analyzed for ZIKV by gene amplification (RT-qPCR), and the findings were correlated with clinical symptoms and neurological anomalies in the babies. ZIKV was detected in 1 of 9 symptomatic women (11.1%) and in 19 of 129 asymptomatic women (14.7%). Neurological manifestations were present in 19 babies (13.7%), 10 of 20 (50%) positive and 9 of 119 (7.6%) negative (p < 0.001) for ZIKV. Twelve (8.6%) urines collected during gestation were ZIKV-positive; only 2 remained positive for ZIKV postpartum. Six (4.1%) newborn urines collected within 1 day of delivery were ZIKV-positive cases. In 3 of these cases, ZIKV was detected in mother's urine pre- and postpartum and in both mother's urine and babies' urine. Four of the amniotic fluid samples (2.9%) were ZIKV-positive. Among ZIKV-negative babies with neurological sequel, 87.5% were female; in contrast, 72.7% ZIKV-positive babies with neurological abnormalities were male (p = 0.019). We conclude that during a ZIKV outbreak, clinical symptoms and ZIKV detection in biological fluids are poor predictors of infection and adverse neurologic sequel in newborns.

Mycoplasma genitalium, a stealth female reproductive tract.

Mycoplasma genitalium was first isolated from the urethral swabs of two symptomatic men with urethritis in 1980. It is a sexually transmitted bacterium associated with a number of urogenital conditions in women like cervicitis, endometritis, pelvic inflammatory disease, infertility, and susceptibility to human immunodeficiency virus (HIV). However, M. genitalium may also act like a stealth pathogen at female reproductive tract, giving no symptoms. Its prevalence varies between different groups, with the average being 0.5-10% in the general population and 20-40% in women with sexually transmitted infections. The recommended treatment of this infection is azithromycin as a single 1-g dose. However, in recent years, macrolide resistance has increased which is significantly lowering the cure rate, being less than 50% in some studies. New treatment regimens need to be investigated due to increasing drug resistance. The discussion and suggestion of an algorithm for management of this infection is the highlight of this paper.

Histopathologic Changes in Placental Tissue Associated With Vertical Transmission of Zika Virus.

Zika virus (ZIKV) is highly neurotropic after crossing the placenta, inducing teratogenic effects that result in delayed development and microcephaly in infants. The available evidence for vertical transmission of this infection is based on placental studies showing alterations in trophoblastic tissue. However, complete characterization of ZIKV-infected placenta and involved pathways has yet to be fully clarified. This case report of placental ZIKV infection describes morphologic and molecular changes in the placenta. Hyperplasia of placental Hofbauer cells in chorionic villi and numerous histiocyte-like cells in the decidua were observed. The decidua, fibroblasts, and chorion, as well as circulating cells in the intravascular compartment stained positive for ZIKV envelop protein. Deciduitis was present on the maternal surface of the placenta, with a prevalence of lymphocytes associated with vasculitis. A high level of uncommitted CD3 T lymphocytes were present, in addition to CD4 and CD8 cells. Elevated expression of the apoptosis inhibitor, Bcl-2, was observed in syncytiotrophoblasts. These parameters may promote the persistence of ZIKV in placental tissue and transmission to the fetus.

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.