Host-bacteria interactions : Host cell responses and bacterial pathogenesis

Helicobacter pylori colonizes the human stomach, where it causes gastritis that may develop into peptic ulcer disease or cancer when left untreated. Neisseria gonorrhoeae colonizes the urogenital tract and causes the sexually transmitted disease gonorrhea. In contrast, Lactobacillus species are part of the human microbiota, which is the resident microbial community, and are considered to be beneficial for health. The first host cell types that bacteria encounter when they enter the body are epithelial cells, which form the border between the inside and the outside, and macrophages, which are immune cells that engulf unwanted material.       The focus of this thesis has been the interaction between the host and bacteria, aiming to increase our knowledge of the molecular mechanisms that underlie the host responses and their effects on bacterial pathogenicity. Understanding the interactions between bacteria and the host will hopefully enable the development of new strategies for the treatment of infectious disease. In paper I, we investigated the effect of N. gonorrhoeae on the growth factor amphiregulin in cervical epithelial cells and found that the processing and release of amphiregulin changes upon infection. In paper II, we examined the expression of the transcription factor early growth response-1 (EGR1) in epithelial cells during bacterial colonization. We demonstrated that EGR1 is rapidly upregulated by many different bacteria. This upregulation is independent of the pathogenicity, Gram-staining type and level of adherence of the bacteria, but generally requires viable bacteria and contact with the host cell. The induction of EGR1 is mediated primarily by signaling through EGFR, ERK1/2 and β1-integrins. In paper III, we described the interactions of the uncharacterized protein JHP0290, which is secreted by H. pylori, with host cells. JHP0290 is able to bind to several cell types and induces apoptosis and TNF release in macrophages. For both of these responses, signaling through Src family kinases and ERK is essential. Apoptosis is partially mediated by TNF release. Finally, in paper IV, we showed that certain Lactobacillus strains can reduce the colonization of H. pylori on gastric epithelial cells. Lactobacilli decrease the gene expression of SabA and thereby inhibit the binding mediated by this adhesin.

Polymer optical fibre sensors for endoscopic optoacoustic imaging

Opto-acoustic imaging (OAI) shows particular promise for in-vivo biomedical diagnostics. Its applications include cardiovascular, gastrointestinal and urogenital systems imaging. Opto-acoustic endoscopy (OAE) allows the imaging of body parts through cavities permitting entry. The critical parameter is the physical size of the device, allowing compatibility with current technology, while governing flexibility of the distal end of the endoscope based on the needs of the sensor. Polymer optical fibre (POF) presents a novel approach for endoscopic applications and has been positively discussed and compared in existing publications. A great advantage can be obtained for endoscopy due to a small size and array potential to provide discrete imaging speed improvements. Optical fibre exhibits numerous advantages over conventional piezo-electric transducers, such as immunity from electromagnetic interference and a higher resolution at small sizes. Furthermore, micro structured polymer optical fibres offer over 12 times the sensitivity of silica fibre. We present a polymer fibre Bragg grating ultrasound detector with a core diameter of 125 microns. We discuss the ultrasonic signals received and draw conclusions on the opportunities and challenges of applying this technology in biomedical applications.

Em Algorithm for MLE of a Probit Model for Multiple Ordinal Outcomes

The correlated probit model is frequently used for multiple ordered data since it allows to incorporate seamlessly different correlation structures. The estimation of the probit model parameters based on direct maximization of the limited information maximum likelihood is a numerically intensive procedure. We propose an extension of the EM algorithm for obtaining maximum likelihood estimates for a correlated probit model for multiple ordinal outcomes. The algorithm is implemented in the free software environment for statistical computing and graphics R. We present two simulation studies to examine the performance of the developed algorithm. We apply the model to data on 121 women with cervical or endometrial cancer. Patients developed normal tissue reactions as a result of post-operative external beam pelvic radiotherapy. In this work we focused on modeling the effects of a genetic factor on early skin and early urogenital tissue reactions and on assessing the strength of association between the two types of reactions. We established that there was an association between skin reactions and polymorphism XRCC3 codon 241 (C>T) (rs861539) and that skin and urogenital reactions were positively correlated. ACM Computing Classification System (1998): G.3.

Epidemiologic Features of Vulvovaginal Candidiasis among Reproductive-Age Women in India

Background. Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (<19%). We did not find strong evidence for associations between sociodemographic characteristics and the prevalence of vulvovaginal candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8) compared to women assessed to be negative for bacterial vaginosis (Prevalence 6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal candidiasis were not observed by the presence or absence of laboratory-confirmed bacterial vaginosis. Conclusions. For correct diagnosis of vulvovaginal candidiasis, laboratory confirmation of infection with Candida is necessary as well as assessment of whether the discharge has been caused by bacterial vaginosis. Studies are needed of women infected with Candida yeast species to determine the risk factors for yeast’s overgrowth.

Are stress and mixed urinary incontinence associated with impaired executive control in community-dwelling older women?

Objectives: To assess whether stress or mixed urinary incontinence (UI) is associated with deficits in executive functioning among community-dwelling women. Design: An observational study comparing the performance, using multivariate analyses of variance (MANOVAs) and Bonferroni post hoc test, of continent women and women with stress or mixed UI during executive control tasks. Setting: The research center of the Institut universitaire de gériatrie de Montréal. Participants: One hundred and fifty-five community-dwelling women aged 60 and older participated in the study. Measurements: Based on the Urogenital Distress Inventory (UDI), participants were split into three groups: 35 continent women, 43 women with stress UI, and 78 women with mixed UI. Participants completed a battery of neuropsychological tests and a computerized dual-task test. Results: Women with mixed UI showed poorer performances than continent and stress UI women in executive control functions. Deficits were specific to tests involving switching and sharing/dividing attention between two tasks. Conclusion: Results of this study suggest that mixed UI can be associated with executive control deficits in community-dwelling older women. Future intervention studies in the treatment of UI should take the higher risk of an executive control deficit in women with UI under consideration.

Physiotherapy for persistent postnatal stress urinary incontinence : a randomized controlled trial

OBJECTIVE: The aim of this study was to compare the effectiveness of multimodal supervised physiotherapy programs with the absence of treatment among women with persistent postnatal stress urinary incontinence. METHODS: This was a single-blind randomized controlled trial. Sixty-four women with stress urinary incontinence were randomly assigned to 8 weeks of either multimodal pelvic floor rehabilitation (n = 21), multimodal pelvic floor rehabilitation with abdominal muscle training (n = 23), or control non–pelvic floor rehabilitation (n = 20). The primary outcome measure consisted of a modified 20-minute pad test. The secondary outcome measures included a Visual Analog Scale describing the perceived burden of incontinence, the Urogenital Distress Inventory, the Incontinence Impact Questionnaire, and pelvic floor muscle function measurements. RESULTS: Two patients dropped out, leaving 62 for analysis. At follow-up, more than 70% of the women in the treatment groups (14/20 in the pelvic floor and 17/23 in the pelvic floor plus abdominal group) were continent on pad testing compared with 0% of women in the control group. Scores on the pad test, Visual Analog Scale, Urogenital Distress Inventory, and Incontinence Impact Questionnaire improved significantly in both treatment groups (all P < .002), whereas no changes were observed in the control group. Pelvic floor muscle function, however, did not improve significantly in either active group. CONCLUSION: Multimodal supervised pelvic floor physiotherapy is an effective treatment for persistent postnatal stress urinary incontinence.

Are stress and mixed urinary incontinence associated with impaired executive control in community-dwelling older women?

Objectives: To assess whether stress or mixed urinary incontinence (UI) is associated with deficits in executive functioning among community-dwelling women. Design: An observational study comparing the performance, using multivariate analyses of variance (MANOVAs) and Bonferroni post hoc test, of continent women and women with stress or mixed UI during executive control tasks. Setting: The research center of the Institut universitaire de gériatrie de Montréal. Participants: One hundred and fifty-five community-dwelling women aged 60 and older participated in the study. Measurements: Based on the Urogenital Distress Inventory (UDI), participants were split into three groups: 35 continent women, 43 women with stress UI, and 78 women with mixed UI. Participants completed a battery of neuropsychological tests and a computerized dual-task test. Results: Women with mixed UI showed poorer performances than continent and stress UI women in executive control functions. Deficits were specific to tests involving switching and sharing/dividing attention between two tasks. Conclusion: Results of this study suggest that mixed UI can be associated with executive control deficits in community-dwelling older women. Future intervention studies in the treatment of UI should take the higher risk of an executive control deficit in women with UI under consideration.

Physiotherapy for persistent postnatal stress urinary incontinence : a randomized controlled trial

OBJECTIVE: The aim of this study was to compare the effectiveness of multimodal supervised physiotherapy programs with the absence of treatment among women with persistent postnatal stress urinary incontinence. METHODS: This was a single-blind randomized controlled trial. Sixty-four women with stress urinary incontinence were randomly assigned to 8 weeks of either multimodal pelvic floor rehabilitation (n = 21), multimodal pelvic floor rehabilitation with abdominal muscle training (n = 23), or control non–pelvic floor rehabilitation (n = 20). The primary outcome measure consisted of a modified 20-minute pad test. The secondary outcome measures included a Visual Analog Scale describing the perceived burden of incontinence, the Urogenital Distress Inventory, the Incontinence Impact Questionnaire, and pelvic floor muscle function measurements. RESULTS: Two patients dropped out, leaving 62 for analysis. At follow-up, more than 70% of the women in the treatment groups (14/20 in the pelvic floor and 17/23 in the pelvic floor plus abdominal group) were continent on pad testing compared with 0% of women in the control group. Scores on the pad test, Visual Analog Scale, Urogenital Distress Inventory, and Incontinence Impact Questionnaire improved significantly in both treatment groups (all P < .002), whereas no changes were observed in the control group. Pelvic floor muscle function, however, did not improve significantly in either active group. CONCLUSION: Multimodal supervised pelvic floor physiotherapy is an effective treatment for persistent postnatal stress urinary incontinence.