The prevalence and risk factors of occult stress urinary incontinence in women undergoing genitourinary prolapse surgery

De novo stress urinary incontinence (SUI) may occur in up to 80% of clinically continent women following genitourinary prolapse surgery. This had resulted in an increase in the rate of concurrent continence surgery during prolapse repair from 38% in 2001 to 47% in 2009 in the United States. To date, there is no local data available to estimate the prevalence of occult SUI (OSUI) among Malaysian women awaiting surgery. Therefore, this study was conducted to elicit the prevalence of occult SUI and its associated risks factors in patients awaiting prolapse surgery. We retrospectively studied the records of 296 consecutive women with significant pelvic organ prolapse awaiting reconstructive repair. All patients attended the Urogynaecology Unit in Hospital Kuala Lumpur Malaysia between October 2007 and September 2011. They had undergone standardized interviews, clinical examinations and urodynamic studies. During the urodynamic testings, all prolapses were reduced using ring pessaries to elicit OSUI. Primary outcome was the prevalence of OSUI with prolapse reduction to predict possibility of developing de novo SUI following prolapse surgery. Secondary outcome was the assessment of potential risk factors for OSUI. Among the 296 women studied, 121 (40.9%) were found to have OSUI. The risk factors associated with OSUI included age, BMI, numbers of SVD, recurrent UTI, reduction of urinary flow symptoms and grade 2 to 4 central compartment prolapses. We concluded that preoperative urodynamic testing with reduction of prolapse is useful to identify women with OSUI. This is important for preoperative counselling as well as planning for one step approach of prophylactic concomitant anti-incontinence procedures during prolapse surgery in order to avoid postoperative de novo SUI

Exposure to Stress and Air Pollution from Bushfires during Pregnancy: Could Epigenetic Changes Explain Effects on the Offspring?

Due to climate change, bushfires are becoming a more frequent and more severe phenomenon which contributes to poor health effects associated with air pollution. In pregnancy, environmental exposures can have lifelong consequences for the fetus, but little is known about these consequences in the context of bushfire smoke exposure. In this review we summarise the current knowledge in this area, and propose a potential mechanism linking bushfire smoke exposure in utero to poor perinatal and respiratory outcomes in the offspring. Bushfire smoke exposure is associated with poor pregnancy outcomes including reduced birth weight and an increased risk of prematurity. Some publications have outlined the adverse health effects on young children, particularly in relation to emergency department presentations and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero. Prenatal stress is likely to occur as a result of catastrophic bushfire events, and stress is known to be associated with poor perinatal and respiratory outcomes. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire events to explore this further, and to design appropriate mitigation interventions, in this area of global public health importance.Vanessa Murphy is supported by an Investigator Grant from the Medical Research Future Fund (grant ID 1196252)

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases

Immunosuppressive Lymphocyte Factors: Characterization of the IDS-Producing Cell in the Experimental Model of Antigenic Competition

Inhibitor of DNA synthesis, is a soluble, protein lymphocyte factor which nonspecifically suppresses in vitro lymphocyte responses to antigens or mitogens. It is secreted in large amounts in vivo in some experimentally induced immunological paralysis. Here, we have defined the cell secreting IDS in one experimental model of non-specific immune-suppression, ie., that of antigenic competition.Lymphocytes of rats injected with a large dose of ovalbumin intravenously, show no immunologic response to the same or other antigens or mitogens 24hr later. At this time, spleen cells of these rats secrete large amounts of the inhibitor into culture supernatants. However spleen cell supernates of T-depleted rats do not contain the activity. Further, maximal inhibitor concentrations are obtained in the first 2 days of culture when more than 65% of cultured cells are large blasts actively synthesizing protein. As the number of actively metabolizing blast cells decrease in subsequent days of culture inhibitor concentration falls. Finally thymocytes of rats pretreated with hydrocortisone acetate, to deplete thymus cortex cells are unable to secrete inhibitor in culture.These findings reveal that the cells producing inhibitory DNA synthesis in an animal made tolerant with a supra-optimal dose of antigen is an active blast transformed T cell (present in the spleen and thymus). In the thymus the cell making inhibitor appears to reside in the thymus cortex. Previous experiments have confirmed that an identical cell causes nonspecific immune-suppression in vitro. We suggest that this cell produces in vivo tolerance in antigenic competition through the release of inhibitor to DNA synthesis