Candidiasis, Bacterial Vaginosis, Trichomoniasis and Other Vaginal Conditions Affecting the Vulva

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Psychosocial Stress, Cortisol Levels, and Maintenance of Vaginal Health

Stress stimuli are ubiquitous and women do not enjoy any exemptions. The physiologic “fight-or-flight” response may be deleterious to the female lower genital tract microbiome if the stress stimuli persist for longer than necessary. Persistent exposure to psychosocial stress and stimulation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes, and associated hormones are risk factors for several infections including genitourinary tract infections. Though this could be due to a dysregulated immune response, a cortisol-induced inhibition of vaginal glycogen deposition may be involved especially in the instance of vaginal infection. The estrogen-related increased vaginal glycogen and epithelial maturation are required for the maintenance of a healthy vaginal ecosystem (eubiosis). The ability of cortisol to disrupt this process as indicated in animal models is important in the pathogenesis of vaginal dysbiosis and the subsequent development of infection and inflammation. This phenomenon may be more crucial in pregnancy where a healthy Lactobacillus-dominated vaginal microbiota is sacrosanct, and there is local production of more corticotropin-releasing hormone (CRH) from the decidua, fetal membranes and placenta. To highlight the relationship between the stress hormone cortisol and the vaginal microbiomial architecture and function, the potential role of cortisol in the maintenance of vaginal health is examined

Energy and charge control in mass spectrometry of synthetic polymers

Synthetic polymers are the products of humans’ attempts to imitate nature’s gigantic molecular chain architectures. The extended variety of building blocks and reaction mechanisms resulted in a plethora of different polymeric architectures. The biggest challenge for polymer chemists is to develop an understanding of the relation between the chemical structure of polymers and their physicochemical and mechanical properties. Mass spectrometry (MS) can provide detailed information about the elemental composition, monomer unit and end-group structure of polymeric systems. However, it also has its limitations. The analysis of high molar mass and/or disperse and/or structurally complicated synthetic polymers remains a big challenge. This thesis tries to address this challenge by controlling the charge state and energy of synthetic polymers during MS. Chapter 2 gives a general introduction to polymer analysis and MS. Besides this introduction, Chapter 2 presents some examples of current practical state-of-the-art MS, and liquid chromatography coupled to MS, methods for the analysis of synthetic polymers. Chapter 3 provides an example of the current performance of LC coupled to tandem MS (MS/MS) in the analysis of structurally complicated polymers, such as vegetable oil ethoxylates. Chapter 4 presents the method development to achieve an accurate and reproducible control of the applied excitation energy in a quadrupole ion trap. The method is checked by studying the required excitation energy for fragmentation of poly(ethylene glycol)s as a function of their size. This dependence is shown to be linear and in agreement with other MS instruments where the applied excitation energy can be controlled in a more accurate way. In Chapter 5, the methodology for accurate and reproducible control of the applied excitation energy is used to discriminate between different polymer classes. It is shown that discrimination is achieved by determining a “characteristic” parameter (i.e., the characteristic collision voltage (CCV)), which is related to the polymer’s structure and expresses the stability of the respective polymer ion upon excitation. The determination of the CCV is then used in the analysis of a mixture of a structurally complicated copolymer system and various, nominally isobaric, homopolymers, which cannot be discriminated by conventional MS and MS/MS methods. Chapters 6, 7 and 8 present the study of non-covalent complex ions of high molar mass synthetic polymers and molecules containing ammonium functionalities. These complex ions appear to have a preference for low charge states. Chapter 6 and 7 present the investigations of the parameters that influence the formation of these low charge state adducts ions. Chapter 8 presents the behavior of these non-covalent complex ions upon activation at both low and relatively high collision regimes. The amount and type of fragments ions is strongly influenced by the structure of the ammonium ion. The results show that MS/MS of these non-covalent complex ions can be used as a source of polymer structural informatio

Mullerian dysgenesis: a critical review of the literature

Purpose: To present an update of the genetic, clinical, diagnostic, and therapeutic aspects of Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome. Methods: Studies were considered eligible if they have evaluated patients with MRKH syndrome. Eligible articles were identified by a search of MEDLINE bibliographical database from 1950 to August 2016. A purely descriptive approach was adopted concerning all outcomes examined by the individual studies. Results: MRKH syndrome is defined as congenital aplasia of the upper vagina and impairment of uterine development in normal 46XX females. Accounting for 1:4500 women, MRKH is the second most common cause of primary amenorrhea following gonadal dysgenesis. Potential association of MRKH syndrome to specific genes has been the focus of recent research. Null-association results of HOXA genes and Wnt5a, Wnt7a, and Wnt9a have been reported, while point mutations of the WNT4 gene point mutations have been associated with an MRKH-like syndrome characterized by Mullerian duct regression and hyperandrogenism. Ultrasound and Magnetic Resonance Imaging (MRI) are the main techniques to establish an accurate diagnosis of the syndrome. Several non-surgical and surgical procedures have been reported for the creation of a functional neovagina; in general, non-surgical treatment should be the first initially pursued. Along with psychological support, recent developments in assisted reproductive technologies of IVF techniques and the availability of gestational surrogacy, as well as the recent breakthrough of successful uterus transplantation, enable women with MRKH syndrome to attain their own genetic child. Conclusion(s): MRKH syndrome is a medical modality with important social, legal, and ethical projections that require a multi-disciplinary approach. © 2017, Springer-Verlag Berlin Heidelberg

Alpha Amylase Levels In Vaginal Fluid And Its Relation To Anti-bacterial And Membrane Degradation Mediators.

221309A310

A population-based analysis of a rare oncologic entity: Malignant pancreatic tumors in children

Purpose: To examine the clinicopathological characteristics and prognosis of pediatric patients with malignant pancreatic tumors in a population-based cohort. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was utilized to identify all pediatric patients with malignant pancreatic tumors, diagnosed between 1973 and 2013. Kaplan–Meier analysis was performed to determine median and five-year overall survival (OS) rates. Univariate survival analysis was executed using the log-rank test. Cox proportional hazards model was used to identify variables independently associated with mortality. Results: A total of 114 patients with pancreatic malignancies were identified. Median patient age was 16 years and the majority of patients were white (64%) females (61.4%). The most prevalent histologic subtype was neuroendocrine tumors (35.1%), whereas pancreatoblastoma was more common during the first decade of life (P < 0.001). Distant metastases were noted in 41.7% of the patients, while 33.3% and 25% had localized and regional disease respectively. Five-year OS rates were 77%, 66.4% and 64.8% for patients with pancreatoblastoma, neuroendocrine and epithelial tumors respectively. No death was observed in the solid pseudopapillary tumor group. Only history of having cancer-directed surgery (CDS) was significantly associated with lower overall mortality (HR: 5.1, 95% CI: 2.1, 12.4). Conclusion: Pancreatic malignancies are rare in children. Their prognosis is variable and only CDS was independently associated with superior survival. Evidence rating/classification: Prognosis study, Level II. © 2017 Elsevier Inc

α-amylase In Vaginal Fluid: Association With Conditions Favorable To Dominance Of lactobacillus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Vaginal glycogen is degraded by host -amylase and then converted to lactic acid by Lactobacilli. This maintains the vaginal pH at 4.5 and prevents growth of other bacteria. Therefore, host -amylase activity may promote dominance of Lactobacilli. We evaluated whether the -amylase level in vaginal fluid is altered in women with bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) and whether its concentration was associated with levels of lactic acid isomers and host mediators. Vaginal fluid was obtained from 43 women with BV, 50 women with VVC, and 62 women with no vulvovaginal disorders. Vaginal fluid concentrations of -amylase, secretory leukocyte protease inhibitor (SLPI), hyaluronan, hyaluronidase-1, -defensin, and elafin were measured by enzyme-linked immunosorbent assay (ELISA). Vaginal concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP) 8, and d- and l-lactic acid levels in these patients were previously reported. The median vaginal fluid -amylase level was 1.83 mU/mL in control women, 1.45 mU/mL in women with VVC, and 1.07 mU/mL in women with BV. Vaginal levels of -amylase were correlated with d-lactic acid (P = .003) but not with l-lactic acid (P > .05) and with SLPI (P < .001), hyaluronidase-1 (P < .001), NGAL (P = .001), and MMP-8 (P = .005). The exfoliation of glycogen-rich epithelial cells into the vaginal lumen by hyaluronidase-1 and MMP-8 may increase glycogen availability and promote -amylase activity. The subsequent enhanced availability of glycogen breakdown products would favor proliferation of Lactobacilli, the primary producers of d-lactic acid in the vagina. Concomitant production of NGAL and SLPI would retard growth of BV-related bacteria.221113931398Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPESP [2011/19960-9]CAPES [4889-13-14