Thesis (Ph. D.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains viii, 88 p. Includes abstract. Includes bibliographical references (p. 52-59).

Objectives: To study recovery after hysterectomy under Enhanced Recovery After Surgery (ERAS) care, and in relation to different operation techniques. Materials and Methods: An observational study was conducted comparing 85 patients undergoing hysterectomy with ERAS care to 120 patients immediately before establishing ERAS. In a prospective cohort study of 121 consecutive patients undergoing hysterectomy, the outcome was compared for patients with malignant versus benign indications. The main outcome measure was length of stay (LOS). A randomised controlled trial (RCT) of 20 women scheduled for hysterectomy compared robot-assisted laparoscopic with abdominal hysterectomy in terms of the development of insulin resistance, inflammatory reactions, and clinical recovery, and examined the relation to hormonal status. All studies were conducted in 2011--2015, at the Department of Obstetrics and Gynaecology, Örebro University Hospital, Sweden. Results: Implementation of a structured ERAS protocol significantly reduced LOS compared to non-ERAS care. The effect was similar between patients with malignant and benign indications for surgery. No difference in complications was found. There was no difference in development of insulin resistance between robotic and abdominal technique, but clinical outcomes and inflammatory responses significantly favoured robot-assisted hysterectomy. Female sex hormone status was associated with the development of insulin resistance. Conclusions: Recovery after hysterectomy can be influenced. ERAS care seems to be effective and safe. Clinical outcome can also be influenced by operational technique. Hysterectomy triggers a stress reaction in both the metabolic and the inflammatory system. It remains unclear why the reduced inflammatory reaction and favourable clinical outcome in robotic surgery were not mirrored by less insulin resistance. This could not be explained by female sex hormone status.

The natural history of hepatitis C virus infection differs between women and men. Women demonstrate a slow rate of disease progression until menopause. Older women are more likely to develop fibrosis and are less responsive than younger women to pegylated interferon and ribavirin. Women of childbearing age have higher rates of sustained virologic response, but current therapies are contraindicated during pregnancy. Vertical transmission of hepatitis C virus occurs, but data supporting recommendations for prevention of mother-to-infant transmission are limited.

The natural history of hepatitis C virus infection differs between women and men. Women demonstrate a slow rate of disease progression until menopause. Older women are more likely to develop fibrosis and are less responsive than younger women to pegylated interferon and ribavirin. Women of childbearing age have higher rates of sustained virologic response, but current therapies are contraindicated during pregnancy. Vertical transmission of hepatitis C virus occurs, but data supporting recommendations for prevention of mother-to-infant transmission are limited.

Magister Public Health - MPH / HIV/AIDS remains a major public health issue that is affecting all population groups and communities in Zambia. Among the most affected groups are key populations (KPs) such as female sex workers. KPs are considered at high risk of contracting HIV but have limited access to HIV services and retention in care due to internalized stigma, discrimination, criminalization, and negative attitudes towards HIV treatment. Under the USAID Open Doors project in Zambia, KPs access comprehensive HIV prevention, care and treatment services. The test and treat strategy is implemented by the project in support of the UNAIDS 90-90-90 targets by 2020 to diagnose 90% of people living with HIV, put 90% of them on treatment, and for 90% of them to have suppressed viral load.

Although women constitute more than half of the estimated 34-40 million people living with HIV/AIDS worldwide, little is known about the early events of HIV-1 infection in the female genital tract (FGT). Genital epithelial cells (GECs) line the FGT and act as intrinsic barriers providing mechanical protection against foreign microbes. GECs are also sentient and are capable of sensing and immunologically responding to various types of pathogens including sexually transmitted infections (STIs). These responses play a central role in preventing disease and also help mobilize both innate and adaptive immune cells against invading threats. While it is well understood that GECs exert important physical and immunological protective roles in the FGT, little is known regarding the role of GECs and GEC inflammatory responses in HIV infection. It is estimated that 40% of all new HIV infections are established each year in the FGT. Our understanding of the early events following HIV transmission in the FGT remains particularly elusive in the context of endogenous or exogenous factors found in the genital microenvironment that may influence susceptibility to HIV-1. Inflammation is known to play a critical role in increasing HIV susceptibility, replication as well as initiating and maintaining chronic immune activation, a hallmark of disease progression. Among the key factors in the FGT that are known to or that could influence inflammation are sexually transmitted co-infections and female sex hormones. The work summarized in this thesis examines how GEC innate immune responses to co-infecting microbes or female sex hormones impact HIV infection and replication in the FGT. Our results show that GEC innate immune response against herpes simplex virus type 2 (HSV-2), a common HIV co-infecting agent, consists of elevated proinflammatory cytokines and chemokines in addition to biologically active interferon-β. Furthermore, our results show that these responses require potent viral HSV-2 replication and that proinflammatory cytokine and chemokine responses are enhanced in the absence of the HSV-2 virus host shutoff protein. Based on this work, we decided to investigate whether GEC inflammatory responses to common STIs played a role in regulating HIV replication in T-cells. We found that HIV co-infecting microbes, specifically HSV-1, HSV-2 and Neisseria gonorrhoeae, directly induced HIV replication in T-cells, and caused primary GECs to upregulate inflammatory responses that indirectly increased HIV replication in T-cells. Next we examined a translational aspect of the aforementioned studies by examining whether blocking inflammatory pathways, using the broad anti-inflammatory compound curcumin, could provide prophylactic or therapeutic protection against HIV. We found that curcumin pre-treatment a) protected the genital epithelial barrier against HIV-1-mediated disruption and inflammation, b) prevented the gp120-mediated upregulation of chemokines by GECs that recruit HIV target cells to the FGT, c) blocked GEC innate inflammatory responses to co-infecting microbes and indirect activation of the HIV promoter in T-cells, d) decreased HIV amplification in chronically infected T-cells and e) blocked HSV-2 viral replication in GECs by a mechanism that likely involves NFκB. Lastly, it has long been speculated that female sex hormones can regulate inflammatory responses, and numerous lines of evidence suggest that they may also regulate susceptibility to HIV-1. Thus, we investigated how female sex hormones and the hormonal contraceptive medroxyprogesterone acetate (MPA), used by more than 100 million women worldwide, regulated HIV infection and replication in GECs and whether inflammation played an important role in this regulation. Our results showed that progesterone and in particular MPA increased uptake of HIV-1 and transcytosis, but not replication, across GECs – in the absence of a proinflammatory milieu - and that this enhanced transcytosis resulted in increased infection of HIV target cells. These results demonstrate that sex hormones and co-infection both play an important role in regulating HIV-1 infection and replication in the FGT. Furthermore, our results suggest that anti-inflammatory compounds such as curcumin may offer paradigm shifting prophylactic or therapeutic strategies against HIV-1 infection and future research should investigate its potential benefit in vivo. / Thesis / Doctor of Philosophy (Medical Science)

Females suffer anterior cruciate ligament (ACL) injuries at a 2 to 10-fold greater rate compared to male athletes participating in similar sports. Altered movement patterns and inadequate knee stiffness are two interrelated factors that may increase ACL injury risk. Onset of these neuromuscular risk factors may coincide with the rapid adolescent growth that results in the divergence of a multitude of neuromuscular parameters between sexes. The overall purpose of this dissertation was to determine if neuromuscular ACL injury risk factors in female athletes increase following rapid growth and development compared to males. Male and female athletes were tested with three-dimensional motion analysis techniques during a drop vertical jump over two consecutive years to determine if ACL injury risk factors increased. Pubertal females showed a significant longitudinal increase in knee abduction angle compared to post-pubertal females and both male groups. The increase in knee abduction angle appeared to remain consistent, as the post pubertal female cohort had greater overall knee abduction compared to post-pubertal males. Similar results were found with a greater magnitude of knee abduction moment in post-pubertal females compared to males. Males and females increased ankle, knee and hip active stiffness from the first to second year of testing. Ankle and hip stiffness were increased significantly more in the pubertal group compared to post-pubertal. Sex and maturational group differences were found in hip and ankle joint stiffness. Post-pubertal males had significantly greater hip stiffness than the other groups (even when normalized to body mass). This indicates that post-pubertal males utilized a different neuromuscular strategy during landing. Males had a significantly greater increase from year to year in vertical jump height compared to females. Vertical jump height is often related to a measure of whole body power and indicates that males had a significant neuromuscular spurt compared to females. Early puberty appears to be a critical phase related to the divergence of increased ACL injury risk factors. Injury prevention programs that focus on neuromuscular training may be beneficial to help address the development of ACL injury risk factors that occur in female athletes during maturation.

In this paper-based thesis, I describe the findings of my ethnographic research conducted among the intimate partners of female sex workers and adolescent boys in Northern Karnataka. By highlighting the contradictory and relational nature of masculinity, my study aims to contribute to the larger scholarship on masculinity in South Asia. In the first manuscript, I examine the intimate partners’ perceptions and practices to shed light on the common occurrence of intimate partner violence and how local ideologies of manhood—and the social and structural conditions that shape these ideologies—perpetuate intimate partner violence. In an attempt to destabilize hierarchical gender orders, the second manuscript builds on Connell’s theory of “hegemonic masculinity” by developing the notion of incipient masculinity. From a public health perspective, the findings of these studies are expected to inform the ongoing structural interventions in Northern Karnataka that aim to prevent violence against female sex workers. / October 2016

Lesão pulmonar aguda é caracterizada por infiltrado de neutrófilos no pulmão, edema, lesão alveolar difusa e alteração da reatividade das vias aéreas. Evidências clínicas e experimentais sugerem que os hormônios sexuais femininos (HSF) modulam a inflamação. Nesse estudo camundongos fêmeas C57BL/6 foram ovariectomizados (OVx) ou falsamente operados, com ovários mantidos (Sham). Após 7 dias foi realizada instilação nasal de LPS (ou salina como controle). Após 4 ou 24 h os experimentos foram conduzidos. Os resultados obtidos 24 h após o LPS mostram aumento de neutrófilos, IL-1b e de óxido nítrico (NO) e redução de IL-10 no pulmão dos animais OVx em relação aos Sham. Também foi observada redução da reatividade traqueal e da resistência e elastância pulmonar dos animais OVx. O tratamento dos animais OVx com 17b-estradiol ou progesterona antes do LPS reverteram esses efeitos. Os dados mostram que 4 h após o LPS a OVx não altera a inflamação e a reatividade das vias aéreas. Pode-se concluir nesse modelo experimental que os HSF exerçam papel de proteção ao organismo. / Acute lung injury is characterized by lung neutrophil infiltration, edema, diffuse alveolar damage and changes in airway reactivity. Clinical and experimental evidences suggest that the female sex hormones (FSH) modulate the inflammation. In this study, female mice C57BL/6 were ovariectomized (OVx) or not (Sham). After 7 days, LPS or saline (as control) were intranasally instillated. After 4 or 24 h the experiments were carried. We observed, 24 h after LPS, increase in neutrophil, IL-1b and nitric oxide (NO) and reduction of IL-10 in the lungs of OVx compared to Sham. We also noted reduced tracheal reactivity and lung resistance and elastance in OVx animals. Treatment of OVx with 17b-estradiol or progesterone before LPS reversed these effects. The data show that 4 h after LPS, the OVx does not promote inflammation and airway reactivity. We can conclude that in our experimental model, FSH exert protective role.

A asma traz remodelamento das vias aéreas por deposição de colágeno, hiperplasia mucoide, hipertrofia celular lisa e hipertrofia epitelial além de afetar a reatividade das vias aéreas. Camundongos C57Bl/6 ovariectomizadas (OVx) foram sensibilizadas e desafiadas com OVA por inalação 3 vezes por semana durante 3 ou 7 semanas. Passadas 120h pós desafio avaliou-se: reatividade traqueal, histologia, MMPs 2 e 9 e mecânica pulmonar. O grupo OVx alérgico teve a reatividade traqueal à MCh e a quantificação de muco, colágeno e músculo liso reduzida em comparação ao grupo controle (sham OVx). O tratamento com estrógeno aumentou MMP2 e o tratamento com progesterona aumentou MMP9. A mecânica ventilatória não diferiu entre os grupos. Nossos dados sugerem que o remodelamento brônquico pode ser modulado por HSFs. / Asthma is characterized by remodeling and increased airway responsiveness. Remodeling is recognized by sub-epithelial fibrosis, bronchial glands hypertrophy and goblet cell hyperplasia. We investigated role of HSF in airway remodeling and in tracheal responsiveness in a model of chronic lung inflammation. Mice were ovariectomized (OVx), sensitized and OVA challenged. Elapsed 120h of the last challenge, histological assessment and contractile response of trachea to methacholine (MCh) was performed. Total lung resistance (R) and elastance (E) were measured under mechanical ventilation. Control group consisted of Sham OVx allergic mice. Airway remodeling were significantly lower of OVx mice compared with Sham OVx allergic counterparts. OVx allergic mice showed lower tracheal responsiveness than Sham OVx. R and E were the same between groups.