Incidence of de novo stress urinary incontinence following minimally invasive sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the incidence and risk factors of postoperative de novo stress urinary incontinence (SUI) in stress-continent women following minimally invasive sacrocolpopexy without an anti-incontinence procedure. METHODS: We completed a multicenter, retrospective cohort study of women undergoing laparoscopic sacrocolpopexy without concurrent anti-incontinence procedures from October 2006 through January 2021. RESULTS: Of the 169 women who underwent minimally invasive sacrocolpopexy, 17.1% (n=30) developed de novo SUI, and 7.1% eventually underwent a midurethral sling placement. On logistic regression, BMI, preoperative urinary urgency, and history of transvaginal mesh repair were found to be significantly associated with and predictive of de novo SUI. When the concordance index (C-index) was calculated with the model published by Jelovsek et al. for women who developed de novo SUI within 12 months of the prolapse surgery, the current de novo SUI calculator was able to discriminate de novo SUI outcome (C-index = 0.71). CONCLUSIONS: The incidence of de novo SUI after minimally invasive sacrocolpopexy without anti-incontinence procedure correlates directly with higher BMI, preoperative urinary urgency, and transvaginal mesh history for POP. Preoperative counseling for minimally invasive sacrocolpopexy should include discussing the risk of de novo SUI and preoperative factors that may increase this risk.

Reproductive Justice: A Case-Based, Interactive Curriculum.

Introduction: Reproductive injustices such as forced sterilization, preventable maternal morbidity and mortality, restricted access to family planning services, and policy-driven environmental violence undermine reproductive autonomy and health outcomes, with disproportionate impact on historically marginalized communities. However, curricula focused on reproductive justice (RJ) are lacking in medical education. Methods: We designed a novel, interactive, case-based RJ curriculum for postclerkship medical students. This curriculum was created using published guidelines on best practices for incorporating RJ in medical education. The session included a prerecorded video on the history of RJ, an article, and four interactive cases. Students engaged in a 2-hour small-group session, discussing key learning points of each case. We evaluated the curriculum's impact with a pre- and postsurvey and focus group. Results: Sixty-eight students participated in this RJ curriculum in October 2020 and March 2021. Forty-one percent of them completed the presurvey, and 46% completed the postsurvey. Twenty-two percent completed both surveys. Ninety percent of respondents agreed that RJ was relevant to their future practice, and 87% agreed that participating in this session would impact their clinical practice. Most respondents (81%) agreed that more RJ content is needed. Focus group participants appreciated the case-based, interactive format and the intersectionality within the cases. Discussion: This interactive curriculum is an innovative and effective way to teach medical students about RJ and its relevance to clinical practice. Walking alongside patients as they accessed reproductive health care in a case-based curriculum improved students' comfort and self-reported knowledge on several RJ topics.

Ovarian stiffness increases with age in the mammalian ovary and depends on collagen and hyaluronan matrices.

Fibrosis is a hallmark of aging tissues which often leads to altered architecture and function. The ovary is the first organ to show overt signs of aging, including increased fibrosis in the ovarian stroma. How this fibrosis affects ovarian biomechanics and the underlying mechanisms are unknown. Using instrumental indentation, we demonstrated a quantitative increase in ovarian stiffness, as evidenced by an increase in Young's modulus, when comparing ovaries from reproductively young (6-12 weeks) and old (14-17 months) mice. This ovarian stiffness was dependent on collagen because ex vivo enzyme-mediated collagen depletion in ovaries from reproductively old mice restored their collagen content and biomechanical properties to those of young controls. In addition to collagen, we also investigated the role of hyaluronan (HA) in regulating ovarian stiffness. HA is an extracellular matrix glycosaminoglycan that maintains tissue homeostasis, and its loss can change the biomechanical properties of tissues. The total HA content in the ovarian stroma decreased with age, and this was associated with increased hyaluronidase (Hyal1) and decreased hyaluronan synthase (Has3) expression. These gene expression differences were not accompanied by changes in ovarian HA molecular mass distribution. Furthermore, ovaries from mice deficient in HAS3 were stiffer compared to age-matched WT mice. Our results demonstrate that the ovary becomes stiffer with age and that both collagen and HA matrices are contributing mechanisms regulating ovarian biomechanics. Importantly, the age-associated increase in collagen and decrease in HA are conserved in the human ovary and may impact follicle development and oocyte quality.

Low Molecular Weight Hyaluronan Induces an Inflammatory Response in Ovarian Stromal Cells and Impairs Gamete Development In Vitro.

The ovarian stroma, the microenvironment in which female gametes grow and mature, becomes inflamed and fibrotic with age. Hyaluronan is a major component of the ovarian extracellular matrix (ECM), and in other aging tissues, accumulation of low molecular weight (LMW) hyaluronan fragments can drive inflammation. Thus, we hypothesized that LMW hyaluronan fragments contribute to female reproductive aging by stimulating an inflammatory response in the ovarian stroma and impairing gamete quality. To test this hypothesis, isolated mouse ovarian stromal cells or secondary stage ovarian follicles were treated with physiologically relevant (10 or 100 µg/mL) concentrations of 200 kDa LMW hyaluronan. In ovarian stromal cells, acute LMW hyaluronan exposure, at both doses, resulted in the secretion of a predominantly type 2 (Th2) inflammatory cytokine profile as revealed by a cytokine antibody array of conditioned media. Additional qPCR analyses of ovarian stromal cells demonstrated a notable up-regulation of the eotaxin receptor Ccr3 and activation of genes involved in eosinophil recruitment through the IL5-CCR3 signaling pathway. These findings were consistent with an age-dependent increase in ovarian stromal expression of Ccl11, a major CCR3 ligand. When ovarian follicles were cultured in 10 or 100 µg/mL LMW hyaluronan for 12 days, gametes with compromised morphology and impaired meiotic competence were produced. In the 100 µg/mL condition, LMW hyaluronan induced premature meiotic resumption, ultimately leading to in vitro aging of the resulting eggs. Further, follicles cultured in this LMW hyaluronan concentration produced significantly less estradiol, suggesting compromised granulosa cell function. Taken together, these data demonstrate that bioactive LMW hyaluronan fragments may contribute to reproductive aging by driving an inflammatory stromal milieu, potentially through eosinophils, and by directly compromising gamete quality through impaired granulosa cell function.

Tissue-specific Fixation Methods Are Required for Optimal In Situ Visualization of Hyaluronan in the Ovary, Kidney, and Liver.

Hyaluronan (HA) is a ubiquitous component of the extracellular matrix. The spatial-temporal localization of HA can be visualized in situ using biotinylated HA binding proteins (HABPs). This assay is sensitive to fixation conditions, and there are currently no best practices for HA detection. Thus, the goal of this study was to optimize fixation conditions for visualizing HA in the ovary, kidney, and liver through analysis of six commonly used fixatives for HA detection: Bouin's Solution, Carnoy's Solution, Ethanol-Formalin-Glacial Acetic Acid (EFG), Histochoice, Modified Davidson's Solution, and 10% Neutral Buffered Formalin. Organs were harvested from CB6F1 mice and fixed with one of the identified fixatives. Fixed organs were sectioned, and the HABP assay was performed on sections in parallel. Hematoxylin and eosin staining was also performed to visualize tissue architecture. HABP signal localization and intensity varied between fixatives. EFG and Carnoy's Solution best preserved the HA signal intensity in the ovary and liver, showing HA localization in various sub-organ structures. In the kidney, only Modified Davidson's Solution was less than optimal. Our findings demonstrate that fixation can alter the ability to detect HA in tissue macro- and microstructures, as well as localization in a tissue-specific manner, in situ.

Embedded Game Design as a Method for Addressing Social Determinants of Health.

This paper, describes the design, development, and evaluation of The Test, a theory-based mobile game prototype designed to promote HIV testing by providing information and influencing motivations, and behavioral intentions among YMSM. The Test was designed using embedded design, first described by Kaufman & Flanagan (2015), which diverges from traditional "educational game" design strategies by mixing on-message content with nonfocal content, in an attempt to make the overall experience more approachable and engaging. One challenge of embedded design is that it targets attitudes and actions that are not always proximate to a particular behavior. Games with embedded content forgo explicit takeaways, and their possible distal effects present a challenge to traditional tests of efficacy. The benefit of embedded design, however, is that its holistic or ecological design approach (which considers feelings, emotions, affects, social relations, and connections to broader communities) stands in close alignment with the social-ecological model.

Trust and Credibility in Web-Based Health Information: A Review and Agenda for Future Research.

BACKGROUND: Internet sources are becoming increasingly important in seeking health information, such that they may have a significant effect on health care decisions and outcomes. Hence, given the wide range of different sources of Web-based health information (WHI) from different organizations and individuals, it is important to understand how information seekers evaluate and select the sources that they use, and more specifically, how they assess their credibility and trustworthiness. OBJECTIVE: The aim of this study was to review empirical studies on trust and credibility in the use of WHI. The article seeks to present a profile of the research conducted on trust and credibility in WHI seeking, to identify the factors that impact judgments of trustworthiness and credibility, and to explore the role of demographic factors affecting trust formation. On this basis, it aimed to identify the gaps in current knowledge and to propose an agenda for future research. METHODS: A systematic literature review was conducted. Searches were conducted using a variety of combinations of the terms WHI, trust, credibility, and their variants in four multi-disciplinary and four health-oriented databases. Articles selected were published in English from 2000 onwards; this process generated 3827 unique records. After the application of the exclusion criteria, 73 were analyzed fully. RESULTS: Interest in this topic has persisted over the last 15 years, with articles being published in medicine, social science, and computer science and originating mostly from the United States and the United Kingdom. Documents in the final dataset fell into 3 categories: (1) those using trust or credibility as a dependent variable, (2) those using trust or credibility as an independent variable, and (3) studies of the demographic factors that influence the role of trust or credibility in WHI seeking. There is a consensus that website design, clear layout, interactive features, and the authority of the owner have a positive effect on trust or credibility, whereas advertising has a negative effect. With regard to content features, authority of the author, ease of use, and content have a positive effect on trust or credibility formation. Demographic factors influencing trust formation are age, gender, and perceived health status. CONCLUSIONS: There is considerable scope for further research. This includes increased clarity of the interaction between the variables associated with health information seeking, increased consistency on the measurement of trust and credibility, a greater focus on specific WHI sources, and enhanced understanding of the impact of demographic variables on trust and credibility judgments.

Students' trust judgements in online health information seeking.

As one of the most active groups of Internet users, students and other young people are active users of digital health information. Yet, research into young people's evaluation of health information is limited, and no previous studies have focused on trust formation. In addition, prior studies on adults' use of digital information do not reach a consensus regarding the key factors in trust formation. This study seeks to address this gap. A questionnaire-based survey was used to collect data from undergraduate students studying a variety of disciplines in one UK university. The Trust in Online Health Information Scale is proposed, and it includes the following dimensions: authority, style, content, usefulness, brand, ease of use, recommendation, credibility, and verification. In addition, inspection of responses to specific items/questions provides further insights into aspects of the information that were of specific importance in influencing trust judgements.

Substrate specificity of prostate-specific membrane antigen.

A series of putative dipeptide substrates of prostate-specific membrane antigen (PSMA) was prepared that explored alpha- and beta/gamma-linked acidic residues at the P1 position and various chromophores at the P2 position, while keeping the P1' residue constant as L-Glu. Four chromophores were examined, including 4-phenylazobenzoyl, 1-pyrenebutyryl, 9-anthracenylcarboxyl-gamma-aminobutyryl, and 4-nitrophenylbutyryl. When evaluating these chromophores, it was found that a substrate containing 4-phenylazobenzoyl at the P2 position was consumed most efficiently. Substitution at the P1 position with acidic residues showed that only gamma-linked L-Glu and D-Glu were recognized by the enzyme, with the former being more readily proteolyzed. Lastly, binding modes of endogenous substrates and our best synthetic substrate (4-phenylazobenzoyl-Glu-gamma-Glu) were proposed by computational docking studies into an X-ray crystal structure of the PSMA extracellular domain.

Optimizing phenylethylphosphonamidates for the inhibition of prostate-specific membrane antigen.

A series of eight N-2-phenylethylphosphonyl derivatives of glutamic acid was prepared to determine if the inhibitory potency of a phenylethylphosphonyl derivative of glutamic acid against prostate-specific membrane antigen (PSMA) could be improved through rational substitutions on the phenyl ring. The design of these eight analogs was based upon the Topliss batchwise approach. Of the inhibitors from the first generation, the 3,4-dichlorophenyl analog exhibited the greatest improvement over the lead compound which was an unsubstituted phenyl derivative, while the 4-methoxyphenyl analog was essentially void of inhibitory potency against PSMA in single-dose studies. From the potency ranking order of the first generation, the parameter most important to the pharmacophore was determined to be pi + sigma. Attempts to optimize further the potency of inhibitors by preparing a second generation of compounds did not result in structures with greater potency than that of the 3,4-dichlorophenyl analog from the first generation. Based upon K(i) values, the 3,4-dichlorophenyl analog represented a potency improvement of nearly one order of magnitude. These results confirm further the usefulness of the Topliss approach to analog development when large library synthesis cannot be achieved readily.

Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates.

To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K(i) values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (1f, n=5 and 1g, n=6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA.