Overweight/Obesity and HIV Disease Progression in HIV+ Adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.

Effects of pelvic floor muscle rehabilitation on PFM function and morphology in older women

Aims The purpose of this study was to examine the effect of a pelvic floor muscle (PFM) rehabilitation program on incontinence symptoms, PFM function, and morphology in older women with SUI. Methods Women 60 years old and older with at least weekly episodes of SUI were recruited. Participants were evaluated before and after a 12-week group PFM rehabilitation intervention. The evaluations included 3-day bladder diaries, symptom, and quality of life questionnaires, PFM function testing with dynamometry (force) and electromyography (activation) during seven tasks: rest, PFM maximum voluntary contraction (MVC), straining, rapid-repeated PFM contractions, a 60 sec sustained PFM contraction, a single cough and three repeated coughs, and sagittal MRI recorded at rest, during PFM MVCs and during straining to assess PFM morphology. Results Seventeen women (68.9 ± 5.5 years) participated. Following the intervention the frequency of urine leakage decreased and disease-specific quality of life improved significantly. PFM function improved significantly: the participants were able to perform more rapid-repeated PFM contractions; they activated their PFMs sooner when coughing and they were better able to maintain a PFM contraction between repeated coughs. Pelvic organ support improved significantly: the anorectal angle was decreased and the urethrovescial junction was higher at rest, during contraction and while straining. Conclusions This study indicated that improvements in urine leakage were produced along with improvements in PFM co-ordination (demonstrated by the increased number of rapid PFM contractions and the earlier PFM activation when coughing), motor-control, pelvic organ support.

Virtual reality rehabilitation as a treatment approach for older women with mixed urinary incontinence : a feasibility study

Background Motivated patients are more likely to adhere to treatment resulting in better outcomes. Virtual reality rehabilitation (VRR) is a treatment approach that includes video gaming to enhance motivation and functional training. Aims The study objectives were (1) to evaluate the feasibility of using a combination of pelvic floor muscles (PFM) exercises and VRR (PFM/VRR) to treat mixed urinary incontinence (MUI) in older women, (2) to evaluate the effectiveness of the PFM/VRR program on MUI symptoms, quality of life (QoL), and (3) gather quantitative information regarding patient satisfaction with this new combined training program. Methods Women 65 years and older with at least 2 weekly episodes of MUI were recruited. Participants were evaluated two times before and one time after a 12-week PFM/VRR training program. Feasibility was defined as the participants' rate of participation in and completion of both the PFM/VRR training program and the home exercise. Effectiveness was evaluated through a bladder diary, pad test, symptom and QoL questionnaire, and participant's satisfaction through a questionnaire. Results Twenty-four women (70.5 ± 3.6 years) participated. The participants complied with the study demands in terms of attendance at the weekly treatment sessions (91%), adherence to home exercise (92%) and completion of the three evaluations (96%). Post-intervention, the frequency and quantity of urine leakage decreased and patientreported symptoms and QoL improved significantly. Most participants were very satisfied with treatment (91%). Conclusion A combined PFM/VRR program is an acceptable, efficient, and satisfying functional treatment for older women with MUI and should be explore through further RCTs.

Vesicoureteral reflux and the extracellular matrix connection.

Primary vesicoureteral reflux (VUR) is a common pediatric condition due to a developmental defect in the ureterovesical junction. The prevalence of VUR among individuals with connective tissue disorders, as well as the importance of the ureter and bladder wall musculature for the anti-reflux mechanism, suggest that defects in the extracellular matrix (ECM) within the ureterovesical junction may result in VUR. This review will discuss the function of the smooth muscle and its supporting ECM microenvironment with respect to VUR, and explore the association of VUR with mutations in ECM-related genes.

Spatial Relationships among Hydroacoustic, Hydrographic and Top Predator Patterns: Cetacean Distributions in the Mid-Atlantic Bight

Effective conservation and management of top predators requires a comprehensive understanding of their distributions and of the underlying biological and physical processes that affect these distributions. The Mid-Atlantic Bight shelf break system is a dynamic and productive region where at least 32 species of cetaceans have been recorded through various systematic and opportunistic marine mammal surveys from the 1970s through 2012. My dissertation characterizes the spatial distribution and habitat of cetaceans in the Mid-Atlantic Bight shelf break system by utilizing marine mammal line-transect survey data, synoptic multi-frequency active acoustic data, and fine-scale hydrographic data collected during the 2011 summer Atlantic Marine Assessment Program for Protected Species (AMAPPS) survey. Although studies describing cetacean habitat and distributions have been previously conducted in the Mid-Atlantic Bight, my research specifically focuses on the shelf break region to elucidate both the physical and biological processes that influence cetacean distribution patterns within this cetacean hotspot.

In Chapter One I review biologically important areas for cetaceans in the Atlantic waters of the United States. I describe the study area, the shelf break region of the Mid-Atlantic Bight, in terms of the general oceanography, productivity and biodiversity. According to recent habitat-based cetacean density models, the shelf break region is an area of high cetacean abundance and density, yet little research is directed at understanding the mechanisms that establish this region as a cetacean hotspot.

In Chapter Two I present the basic physical principles of sound in water and describe the methodology used to categorize opportunistically collected multi-frequency active acoustic data using frequency responses techniques. Frequency response classification methods are usually employed in conjunction with net-tow data, but the logistics of the 2011 AMAPPS survey did not allow for appropriate net-tow data to be collected. Biologically meaningful information can be extracted from acoustic scattering regions by comparing the frequency response curves of acoustic regions to theoretical curves of known scattering models. Using the five frequencies on the EK60 system (18, 38, 70, 120, and 200 kHz), three categories of scatterers were defined: fish-like (with swim bladder), nekton-like (e.g., euphausiids), and plankton-like (e.g., copepods). I also employed a multi-frequency acoustic categorization method using three frequencies (18, 38, and 120 kHz) that has been used in the Gulf of Maine and Georges Bank which is based the presence or absence of volume backscatter above a threshold. This method is more objective than the comparison of frequency response curves because it uses an established backscatter value for the threshold. By removing all data below the threshold, only strong scattering information is retained.

In Chapter Three I analyze the distribution of the categorized acoustic regions of interest during the daytime cross shelf transects. Over all transects, plankton-like acoustic regions of interest were detected most frequently, followed by fish-like acoustic regions and then nekton-like acoustic regions. Plankton-like detections were the only significantly different acoustic detections per kilometer, although nekton-like detections were only slightly not significant. Using the threshold categorization method by Jech and Michaels (2006) provides a more conservative and discrete detection of acoustic scatterers and allows me to retrieve backscatter values along transects in areas that have been categorized. This provides continuous data values that can be integrated at discrete spatial increments for wavelet analysis. Wavelet analysis indicates significant spatial scales of interest for fish-like and nekton-like acoustic backscatter range from one to four kilometers and vary among transects.

In Chapter Four I analyze the fine scale distribution of cetaceans in the shelf break system of the Mid-Atlantic Bight using corrected sightings per trackline region, classification trees, multidimensional scaling, and random forest analysis. I describe habitat for common dolphins, Risso’s dolphins and sperm whales. From the distribution of cetacean sightings, patterns of habitat start to emerge: within the shelf break region of the Mid-Atlantic Bight, common dolphins were sighted more prevalently over the shelf while sperm whales were more frequently found in the deep waters offshore and Risso’s dolphins were most prevalent at the shelf break. Multidimensional scaling presents clear environmental separation among common dolphins and Risso’s dolphins and sperm whales. The sperm whale random forest habitat model had the lowest misclassification error (0.30) and the Risso’s dolphin random forest habitat model had the greatest misclassification error (0.37). Shallow water depth (less than 148 meters) was the primary variable selected in the classification model for common dolphin habitat. Distance to surface density fronts and surface temperature fronts were the primary variables selected in the classification models to describe Risso’s dolphin habitat and sperm whale habitat respectively. When mapped back into geographic space, these three cetacean species occupy different fine-scale habitats within the dynamic Mid-Atlantic Bight shelf break system.

In Chapter Five I present a summary of the previous chapters and present potential analytical steps to address ecological questions pertaining the dynamic shelf break region. Taken together, the results of my dissertation demonstrate the use of opportunistically collected data in ecosystem studies; emphasize the need to incorporate middle trophic level data and oceanographic features into cetacean habitat models; and emphasize the importance of developing more mechanistic understanding of dynamic ecosystems.

Experiences of Internalized and Enacted Stigma among Women with Obstetric Fistula in Tanzania

Background: Obstetric fistula is the development of a necrosis between the bladder and the vagina and/or the bladder and the rectum as a result of prolonged obstructed labor, resulting in urinary or fecal incontinence. In Tanzania surgical repair for obstetric fistula is provided freely by the government but it is estimated that there are over 25,000 women living with an untreated fistula. These women experience high degrees of psycho-social stresses exacerbated by the stigma surrounding their condition. There is a dire need to explore stigma within this population in order to better understand its impact, as stigma affects both treatment seeking behavior as well as long term recovery of those who access surgical repair.

Study Aims: This study aims to understand the experiences of stigma among women with obstetric fistulas by examining both internalized and enacted stigma, and by identifying pertinent correlates of internalized stigma.

Methods: This mixed-methods study utilized both quantitative and qualitative data collected in two related studies at a single hospital in Moshi, Tanzania. All study participants were women receiving surgical repair for an obstetric fistula. In the quantitative portion, cross-sectional survey data were collected from 52 patients. The primary outcome was fistula-related stigma, measured using an adaptation of the HASI-P stigma scale, which included constructs of both internalized and enacted stigma. In the qualitative portion, 45 patients participated in a semi-structured in-depth interview, which explored topics such as stressors caused by the fistula, coping mechanisms, and available support. The transcripts were analyzed using analytic memos and an iterative process of thematic coding using the framework of content analysis.

Results: Expressions of internalized stigma were common in the sample, with a median score of 2.1 on a scale of 0 – 3. Internalized was significantly correlated with negative religious coping, social participation, impact of incontinence and enacted stigma. Qualitative analysis was consistent and demonstrated widespread themes of shame and embarrassment. Experiences of enacted stigma were not as common (median score of 0), although some items, like those pertaining to mockery and blame, were endorsed by up to 25% of the study sample. Themes of anticipated stigma (isolation and non-disclosure due to the possibility of stigmatization) were also evident in the qualitative sample and may explain the low enacted stigma scores observed.

Conclusion: In this sample of women receiving surgical repair for an obstetric fistula, stigma was evident, with internalized stigma resulting in psychological impacts for patients. Experiences of both anticipated and enacted stigma were also observed. There is a need to explore interventions that would decrease stigma while also increasing support for these women, as stigma may be a barrier towards accessing surgical repair and reintegration following surgery.

Keywords: Tanzania, obstetric fistula, stigma, maternal health

Why Serological Responses during Cystitis are Limited.

The high frequency of urinary tract infections (UTIs), some of which appear to be endogenous relapses rather than reinfections by new isolates, point to defects in the host's memory immune response. It has been known for many decades that, whereas kidney infections evoked an antibody response to the infecting bacteria, infections limited to the bladder failed to do so. We have identified the existence of a broadly immunosuppressive transcriptional program associated with the bladder, but not the kidneys, during infection of the urinary tract that is dependent on bladder mast cells. This involves the localized secretion of IL-10 and results in the suppression of humoral immune responses in the bladder. Mast cell-mediated immune suppression could suggest a role for these cells in critically balancing the needs to clear infections with the imperative to prevent harmful immune reactions in the host.

Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (Oryzias latipes) embryos.

This study examined developmental toxicity of different mercury compounds, including some used in traditional medicines. Medaka (Oryzias latipes) embryos were exposed to 0.001-10 µM concentrations of MeHg, HgCl2, α-HgS (Zhu Sha), and β-HgS (Zuotai) from stage 10 (6-7 hpf) to 10 days post fertilization (dpf). Of the forms of mercury in this study, the organic form (MeHg) proved the most toxic followed by inorganic mercury (HgCl2), both producing embryo developmental toxicity. Altered phenotypes included pericardial edema with elongated or tube heart, reduction of eye pigmentation, and failure of swim bladder inflation. Both α-HgS and β-HgS were less toxic than MeHg and HgCl2. Total RNA was extracted from survivors three days after exposure to MeHg (0.1 µM), HgCl2 (1 µM), α-HgS (10 µM), or β-HgS (10 µM) to examine toxicity-related gene expression. MeHg and HgCl2 markedly induced metallothionein (MT) and heme oxygenase-1 (Ho-1), while α-HgS and β-HgS failed to induce either gene. Chemical forms of mercury compounds proved to be a major determinant in their developmental toxicity.

Effects of pelvic floor muscle rehabilitation on PFM function and morphology in older women

Aims The purpose of this study was to examine the effect of a pelvic floor muscle (PFM) rehabilitation program on incontinence symptoms, PFM function, and morphology in older women with SUI. Methods Women 60 years old and older with at least weekly episodes of SUI were recruited. Participants were evaluated before and after a 12-week group PFM rehabilitation intervention. The evaluations included 3-day bladder diaries, symptom, and quality of life questionnaires, PFM function testing with dynamometry (force) and electromyography (activation) during seven tasks: rest, PFM maximum voluntary contraction (MVC), straining, rapid-repeated PFM contractions, a 60 sec sustained PFM contraction, a single cough and three repeated coughs, and sagittal MRI recorded at rest, during PFM MVCs and during straining to assess PFM morphology. Results Seventeen women (68.9 ± 5.5 years) participated. Following the intervention the frequency of urine leakage decreased and disease-specific quality of life improved significantly. PFM function improved significantly: the participants were able to perform more rapid-repeated PFM contractions; they activated their PFMs sooner when coughing and they were better able to maintain a PFM contraction between repeated coughs. Pelvic organ support improved significantly: the anorectal angle was decreased and the urethrovescial junction was higher at rest, during contraction and while straining. Conclusions This study indicated that improvements in urine leakage were produced along with improvements in PFM co-ordination (demonstrated by the increased number of rapid PFM contractions and the earlier PFM activation when coughing), motor-control, pelvic organ support.