STEVEN SOL WITKIN
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- The vaginal microbiome in pregnant women: knowledge gaps in relation to clinical relevance(2021) WITKIN, S. S.; MORON, A. F.; LINHARES, I. M.; SKUPSKI, D. W.
- Influence of recurrent vulvovaginal candidiasis on quality of life issues(2019) I, Eiko Fukazawa; WITKIN, Steven S.; ROBIAL, Renata; VINAGRE, Joao G.; BARACAT, Edmund C.; LINHARES, Iara M.Purpose More than 370 million women will experience recurrent vulvovaginal candidiasis (RVVC) during their lifetime. However, RVVC is often trivialized as clinically insignificant and not worthy of research funding. We evaluated the influence of RVVC on the quality of life in affected women. Methods The validated World Health Organization Quality of Life Abbreviated Assessment (WHOQOL-Bref) questionnaire was administered to 100 women with RVVC and to 101 epidemiologically matched women with no history of vulvovaginal candidiasis. RVVC was defined as at least four episodes of clinical and culture-positive vaginal candidiasis within a 1 year period. Data were analyzed by Chi square, Student t test and analysis of variance. Internal consistency of responses to questions was evaluated by Cronbach alpha. Results The Cronbach alpha coefficient was > 0.80 for responses to generalized questions and > 0.65 for answers to more specific questions, indicating substantial internal consistency. Perception of quality of life and satisfaction with their health was greatly reduced in the RVVC group (p < 0.001). Diminished responses to physical and psychological well-being were also reported by women with RVVC (p < 0.001). Various aspects of social relations including sexual activity were similarly reduced (p < 0.001) as were satisfaction with issues such as home environment, financial resources and employment (p < 0.001). Conclusion RVVC affects multiple aspects of a woman's well-being. Women with this condition deserve serious attention from clinicians and research into susceptibility, prevention and treatment of this infection deserves much greater emphasis.
- Influence of Lactobacillus crispatus, Lactobacillus iners and Gardnerella vaginalis on bacterial vaginal composition in pregnant women(2021) WITKIN, Steven S.; MORON, Antonio F.; LINHARES, Iara M.; FORNEY, Larry J.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.
- Identification of bacteriophages in the vagina of pregnant women: a descriptive study(2021) COSTA, A. C. da; MORON, A. F.; FORNEY, L. J.; LINHARES, I. M.; SABINO, E.; COSTA, S. F.; MENDES-CORREA, M. C.; WITKIN, S. S.Objective To determine the presence and identity of extracellular bacteriophage (phage) families, genera and species in the vagina of pregnant women. Design Descriptive, observational cohort study. Setting Sao Paulo, Brazil. Population Pregnant women at 21-24 weeks' gestation. Methods Vaginal samples from 107 women whose vaginal microbiome and pregnancy outcomes were previously determined were analysed for phages by metagenomic sequencing. Main outcome measures Identification of phage families, genera and species. Results Phages were detected in 96 (89.7%) of the samples. Six different phage families were identified: Siphoviridae in 69.2%, Myoviridae in 49.5%, Microviridae in 37.4%, Podoviridae in 20.6%, Herelleviridae in 10.3% and Inviridae in 1.9% of the women. Four different phage families were present in 14 women (13.1%), three families in 20 women (18.7%), two families in 31 women (29.1%) and one family in 31 women (29.1%). The most common phage species detected wereBacillusphages in 48 (43.6%),Escherichiaphages in 45 (40.9%),Staphylococcusphages in 40 (36.4%),Gokushovirusin 33 (30.0%) andLactobacillusphages in 29 (26.4%) women. In a preliminary exploratory analysis, there were no associations between a particular phage family, the number of phage families present in the vagina or any particular phage species and either gestational age at delivery or the bacterial community state type present in the vagina. Conclusions Multiple phages are present in the vagina of most mid-trimester pregnant women. Tweetable abstract Bacteriophages are present in the vagina of most pregnant women.
- Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus(2020) RUDGE, Marilza V. C.; SOUZA, Fatima P.; ABBADE, Joelcio F.; HALLUR, Raghavendra L. S.; MARCONDES, Joao Paulo C.; PICULO, Fernanda; MARINI, Gabriela; VESENTINI, Giovana; THABANE, Lehana; WITKIN, Steven S.; CALDERON, Iracema M. P.; BARBOSA, Angelica M. P.; RUDGE, M. V.; BARBOSA, A. M. P.; CALDERON, I. M. P.; SOUZA, F. P.; ABBADE, J. F.; HALLUR, L. S. R.; PICULO, F.; MARINI, G.; VESENTINI, G.; THABANE, L.; PALMA, M. S.; GRAEFF, C. F. O.; ARNI, R. K.; HERCULANO, R. D.; SALVADORI, D. F.; MATEUS, S.; SILVA, M. Dal Pai; MAGALHAES, C. G.; COSTA, R. A.; LIMA, S. A. M.; FELISBINO, S. L.; BARBOSA, W.; ATALLAH, A.; GIRAO, M. J. B.; BELLA, Z. Di; UCHOA, S. M.; PAYAO, S.; HIJAS, A.; BERGHMAN, B.; BIE, R. De; SOBREVIA, L.; JUNGINGER, B.; ALVES, F. C. B.; ROSSIGNOLI, P. S.; PRUDENCIO, C. B.; ORLANDI, M. I. G.; GONCALVES, M. I.; NUNES, S. K.; CATINELLI, B. B.; QUIROZ, S.; SARMENTO, B. V.; PINHEIRO, F. A.; SARTORAO, C. I.; LUCAS, R. R.; REYES, D. R. A.; QUIROZ, S. B. C. V.; ENRIQUEZ, E. M. A.; OLIVEIRA, R. G.; FLORIANO, J. F.; MARCONDES, J. P. C.; BARNEZE, S.; DANGIO, T. D.; PASCON, T.; ROSSIGNOLI, P.; FREITAS, J. V.; TAKANO, L.; REIS, F.; CALDEIRAO, T. D.; FERNANDES, J. N.; CARR, A. M.; GAITERO, M. V. C.; CORRENTE, J. E.; NUNES, H. R. C.; CANDIDO, A. F.; COSTA, S. M. B.; DANGIO, T. D.; PASCON, T.; MELO, J. V. F.; TAKANO, L.; REIS, F. V. D. S.; CALDEIRAO, T. D.; CARR, A. M.; GARCIA, G. A.; RABADAN, G. B.; BASSIN, H. C. M.; SUYAMA, K. S.; DAMASCENO, L. N.; TAKEMOTO, M. L. S.; MENEZES, M. D.; BUSSANELI, D. G.; NOGUEIRA, V. K. C.; LIMA, P. R.; LOURENCO, I. O.; SA, J. Marostica de; MEGID, R. A.; CARUSO, I. P.; RASMUSSEN, L. T.; PRATA, G. M.; PICULO, F.; VESENTINI, G.; ARANTES, M. A.; FERRAZ, G. A. R.; CAMARGO, L. P.; KRON, M. R.; CORRENTE, J. E.; NUNES, H. R. C.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 (Sao 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.
- An exploratory study of associations with spontaneous preterm birth in primigravid pregnant women with a normal cervical length(2022) SARMENTO, Stephanno G. P.; MORON, Antonio F.; FORNEY, Larry J.; HATANAKA, Alan R.; CARVALHO, Francisco H. C.; FRANCA, Marcelo S.; HAMAMOTO, Tatiana K.; MATTAR, Rosiane; LINHARES, Iara M.; MINIS, Evelyn; SANUDO, Adriana; SABINO, Ester; RUDGE, Marilza V. C.; WITKIN, Steven S.Background: Predictors of spontaneous preterm birth in primigravid women remain undetermined. Aim: We evaluated whether biomarkers in vaginal secretions and/or differences in the dominant bacterium in the vaginal microbiome predicted the risk for spontaneous preterm birth in primigravid women with a cervical length >25mm. Study design: In a prospective study, 146 second trimester pregnant women with their first conception and a cervix >25mm were enrolled. The vaginal microbiome composition was characterized by analysis of 16S ribosomal RNA gene sequences. The concentrations of d- and l-lactic acid, matrix metalloproteinase (MMP) 2, 8 and 9 and tissue inhibitor of metalloproteinase (TIMP) 1 and 2 in vaginal secretions were measured by ELISA. Cervical length was determined by vaginal ultrasonography. Pregnancy outcome data were subsequently collected. There was a spontaneous preterm birth (SPTB) in 13 women (8.9%) while in an additional 8 women (5.5%) preterm delivery was medically indicated. Lactobacillus iners was the dominant vaginal bacterium in 61.5% of women with a SPTB but only in 31.2% of those who delivered at term (p = .0354). The vaginal concentration of TIMP-1 (p = .0419) and L-lactic acid (p = .0495) was higher in women with a SPTB as compared to those who delivered at term. Lactobacillus iners dominance was associated with elevated levels of TIMP-1 (p = .0434) and TIMP-2 (p = .0161) and lower levels of D-lactic acid (p < .0001) compared to when L. crispatus was dominant. Conclusion: In this exploratory study of primigravid women, elevations in vaginal TIMP-1 and L- lactic acid and L. iners dominance in the vaginal microbiome are associated with an increased occurrence of SPTB.
- Influence of a mannose-binding lectin gene polymorphism and exposure to Chlamydia trachomatis on fallopian tube obstruction in Brazilian woman(2019) VINAGRE, Joao G.; WITKIN, Steven S.; RIBEIRO, Sergio C.; ROBIAL, Renata; I, Eiko Fukazawa; ORTOLANI, Carla C.; BARACAT, Edmund C.; LINHARES, Iara M.Purpose Factors influencing fallopian tube occlusion in women with a lower genital tract infection remain incompletely elucidated. We evaluated whether a polymorphism in the mannose-binding lectin (MBL) gene at codon 54 influences the occurrence of fallopian tube blockage in relation to exposure to Chlamydia trachomatis. Methods In a case-control study at The Hospital das Clinicas, University of Sao Paulo, Brazil, 75 women with hysterosalpingography-documented tubal occlusion and 75 women with patent fallopian tubes were analyzed for detection of single-nucleotide polymorphism in codon 54 of the MBL gene and for IgG anti-C. trachomatis antibodies in their sera. Both groups were matched for age, race, and sexual variables. Results Prior exposure to C. trachomatis, as evidenced by the presence of IgG antibodies, was comparable in both groups. Detection of the polymorphic MBL allele was more prevalent in women with blocked tubes (p < 0.01), regardless of whether or not there was evidence of prior chlamydial exposure. Conclusion The level of MBL-related innate immunity influences the consequences of infection by C. trachomatis or other microbes.
- Torquetenovirus Titer in Vaginal Secretions from Pregnant and Postpartum Women: Association with Absence ofLactobacillus crispatusand Levels of Lactic Acid and Matrix Metalloproteinase-8(2020) TOZETTO-MENDOZA, Tania R.; BONGIOVANNI, Ann Marie; MINIS, Evelyn; LINHARES, Iara M.; BOESTER, Allison; FREIRE, Wilton S.; LIMA, Silvia H.; OLIVEIRA, Natan P. G. de; MENDES-CORREA, Maria C.; FORNEY, Larry J.; WITKIN, Steven S.Vaginal samples from women with term deliveries were tested for torquetenovirus (TTV) by gene amplification, matrix metalloproteinase (MMP)-8 and D- and L-lactic acid by ELISA, and microbiome composition by analysis of the bacterial 16S ribosomal RNA gene. TTV was detected in 43.2%, 31.5%, and 41.4% of first trimester, third trimester, and postpartum samples, respectively. The viral titer was higher in postpartum than in the first (p = 0.0018) or third (p = 0.0013) trimester. The mean gestational age at delivery was lower in women positive for TTV in their first trimester (p = 0.0358). In the first and third trimester, the MMP-8 level was higher if TTV was also present (p < 0.0091). The D-lactic acid level was lower in first trimester samples if TTV was present (p = 0.0334).Lactobacillus crispatusdominance in first and third trimester samples was higher when TTV was absent (p < 0.0033). We conclude that TTV is present in the vagina in many women with normal pregnancy outcomes and that its occurrence is associated with a lack ofL. crispatusdominance, an increase in vaginal MMP-8 and a decrease in D-lactic acid.
- Changes in the Vaginal Microbiome during the Pregnancy to Postpartum Transition(2021) NUNN, Kenetta L.; WITKIN, Steven S.; SCHNEIDER, G. Maria; BOESTER, Allison; NASIOUDIS, Dimitrios; MINIS, Evelyn; GLINIEWICZ, Karol; FORNEY, Larry J.Substantial changes in the composition of the vaginal microbiome occur following the end of pregnancy. To identify potential drivers of microbiome changes in individual women during the pregnancy to postpartum transition, we evaluated vaginal samples from 48 pregnant women during their first and third trimesters and postpartum. We determined the species composition of vaginal communities and the vaginal fluid levels of compounds involved in mediating changes in host physiology and the immune system at each time point. We used linear mixed-effects models to characterize associations. Consistent with previous reports, but with a larger sample size, a US population, and variations in the dominant bacteria, the vaginal microbiome was found to be more diverse during the postpartum period. There was a lower abundance of Lactobacillus and significantly higher proportions of Streptococcus anginosus and Prevotella bivia. Moreover, we uniquely demonstrated that postpartum vaginal secretions were also altered postpartum. There were elevated levels of hyaluronan and Hsp70 and decreased levels of the D- and L-lactic acid isomers. We posit that these variations are consequences of alterations in the vagina after delivery that profoundly alter the host environment and, thus, lead to changes in the capability of different bacterial species to survive and proliferate.
- The Medium Is the Message: Defining a ""Normal"" Vaginal Microbiome in Healthy Reproductive-Age Women(2023) WITKIN, Steven S.; LINHARES, Iara MorenoThe microbial composition of the human vagina differs from that of all other mammals, likely as a consequence of the unique composition of vaginal constituents that promote the selective maintenance and proliferation of distinct bacterial species. Similarly, variations between individual healthy women in genetic, environmental, and medical variables also modify the vaginal lumen composition. The direction and magnitude of immune reactions to microorganisms present in the vagina, responses to stress and non-infectious stimuli, coupled with medical and pregnancy history and environmental exposures, can greatly differ between women. Adaptations to both internal and external pressures will determine the ability of select resident vaginal bacteria to numerically dominate and, therefore, the definition of a ""normal"" vaginal microbiota will substantially differ between individual healthy women.