A novel research definition of bladder health in women and girls: Implications for research and public health promotion

BACKGROUND:Bladder health in women and girls is poorly understood, in part, due to absence of a definition for clinical or research purposes. This article describes the process used by a National Institutes of Health funded transdisciplinary research team (The Prevention of Lower Urinary Tract Symptoms [PLUS] Consortium) to develop a definition of bladder health. METHODS:The PLUS Consortium identified currently accepted lower urinary tract symptoms (LUTS) and outlined elements of storage and emptying functions of the bladder. Consistent with the World Health Organization's definition of health, PLUS concluded that absence of LUTS was insufficient and emphasizes the bladder's ability to adapt to short-term physical, psychosocial, and environmental challenges for the final definition. Definitions for subjective experiences and objective measures of bladder dysfunction and health were drafted. An additional bioregulatory function to protect against infection, neoplasia, chemical, or biologic threats was proposed. RESULTS:PLUS proposes that bladder health be defined as: "A complete state of physical, mental, and social well-being related to bladder function and not merely the absence of LUTS. Healthy bladder function permits daily activities, adapts to short-term physical or environmental stressors, and allows optimal well-being (e.g., travel, exercise, social, occupational, or other activities)." Definitions for each element of bladder function are reported with suggested subjective and objective measures. CONCLUSIONS:PLUS used a comprehensive transdisciplinary process to develop a bladder health definition. This will inform instrument development for evaluation of bladder health promotion and prevention of LUTS in research and public health initiatives

The Prevention of Lower Urinary Tract Symptoms (PLUS) in girls and women: Developing a conceptual framework for a prevention research agenda

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146323/1/nau23787_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146323/2/nau23787.pd

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

IL22 regulates human urothelial cell sensory and innate functions through modulation of the acetylcholine response, immunoregulatory cytokines and antimicrobial peptides: assessment of an in vitro model.

Human urinary disorders are generally studied in rodent models due to limitations of functional in vitro culture models of primary human urothelial cells (HUCs). Current HUC culture models are often derived from immortalized cancer cell lines, which likely have functional characteristics differ from healthy human urothelium. Here, we described a simple explant culture technique to generate HUCs and assessed their in vitro functions. Using transmission electron microscopy, we assessed morphology and heterogeneity of the generated HUCs and characterized their intercellular membrane structural proteins relative to ex vivo urothelium tissue. We demonstrated that our cultured HUCs are free of fibroblasts. They are also heterogeneous, containing cells characteristic of both immature basal cells and mature superficial urothelial cells. The cultured HUCs expressed muscarinic receptors (MR1 and MR2), carnitine acetyltransferase (CarAT), immunoregulatory cytokines IL7, IL15, and IL23, as well as the chemokine CCL20. HUCs also expressed epithelial cell-specific molecules essential for forming intercellular structures that maintain the functional capacity to form the physiological barrier of the human bladder urothelium. A subset of HUCs, identified by the high expression of CD44, expressed the Toll-like receptor 4 (TLR4) along with its co-receptor CD14. We demonstrated that HUCs express, at the mRNA level, both forms of the IL22 receptor, the membrane-associated (IL22RA1) and the secreted soluble (IL22RA2) forms; in turn, IL22 inhibited expression of MR1 and induced expression of CarAT and two antimicrobial peptides (S100A9 and lipocalin-2). While the cellular sources of IL22 have yet to be identified, the HUC cytokine and chemokine profiles support the concept that IL22-producing cells are present in the human bladder mucosa tissue and that IL22 plays a regulatory role in HUC functions. Thus, the described explant technique is clearly capable of generating functional HUCs suitable for the study of human urinary tract disorders, including interactions between urothelium and IL22-producing cells

Uropathogenic <i>E. coli</i> strain NU14 adheres to HUCs.

<p>HUCs were exposed to NU14 (A), the isogenic <i>fimH</i> mutant NU14-1 (B) or media alone (C). After 2 h, the HUCs were washed and stained for the presence of adherent bacteria (green). Host cell actin (red) and nuclei (blue) were counterstained. Merged images show NU14 (A, arrows) adhering to urothelial cells. The percentage of urothelial cells with adherent bacteria was quantified (D) by scoring at least 200 urothelial cells from random fields of view for the presence of adherent bacteria. The percentage represents the number of urothelial cells with adherent bacteria divided by the total number of urothelial cells examined. Data are representative of at least three (A–C) or two (D) independent experiments performed with cells derived from independent biopsies. Between experiments, the average percentage of urothelial cells with adherent NU14 ranged from 8 to 23%. The errors bars represent the standard deviation of two coverslips per strain per experiment. Scale bars, 10 µm. *Indicates p<0.05, Student’s t-test.</p

Primer Sequences.

<p>Primer Sequences.</p

Antibodies Used in the Study.

#<p>A volume of 5 µL of the indicated dilution was used.</p><p>Antibodies Used in the Study.</p

Flow cytometric analysis of primary HUCs.

<p>Cells were stained with eight fluorochrome-conjugated monoclonal antibodies direct against cell surface makers. Cells were analyzed for the expression of: (A) HLA-ABC and CD54 (ICAM-1); (B) CD104 and EpCAM; (C) HLA-DR, and CD44– expression of CD44 shows two distinct populations of HUCs: CD44^lo and CD44^hi; (D, E) TLR and CD14. Representative data from 3 experiments performed with HUCs generated from 3 independent bladder biopsies.</p

Ultrastructures of primary HUCs.

<p>Cultured HUCs were analyzed by TEM. (A, B) a HUC with two nuclei (N) and many discoid fusiform vesicles (DVF) - *denotes lumens of DFV; B is a higher magnification of the square area identified in A - MVB denotes multivesicular body; (C) another example of MVB and DFV in a HUC; (D) presence of uroplakins plaques (Uro P, dark line) on the cell membrane of an umbrella cell; (E) formation of lateral interdigitation between two adjacent HUCs, a higher magnification of the identified was shown in F; (F) presence of numerous desmosomes (Des, arrowheads) within a well-formed lateral interdigitation of two adjacent HUCs. Bar scale is equal to 1 µm (in A, B, E and F) and 0.1 µm (in C and D).</p

Immunofluorescent staining of cultured HUCs.

<p>HUCs were fixed and double stained with anti-uroplakins (PE, Red) and keratin-20 (FITC, green). DAPI (blue) was used to stain the nucleus. Lower right panel is a negative control stained with mouse and rabbit IgG. Representative images from 3 experiments from 3 independent biopsies.</p