Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

Patterned Photonic Actuators with Dynamic Shape-Morphing and Color-Changing Capabilities Fabricated by Athermal Embossing Technology.

Stimuli-responsive patterned photonic actuators, characterized by their patterned nano/microscale structures and capacity to demonstrate synergistic color changes and shape morphing in response to external stimuli, have attracted intense scientific attention. However, traditional patterned photonic actuator systems still face limitations such as cumbersome and time-consuming preparation processes and small-scale deformations. Herein, we introduce a facile approach involving an athermal embossing technique to rapidly fabricate patterned photonic actuators based on near-infrared (NIR) light-responsive liquid crystal elastomers. The resulting patterned photonic actuators demonstrate remarkable features, including brilliant angle-dependent structural color, complex three-dimensional actuation, and good color durability under NIR light stimulation. As illustrative demonstrations of the proof-of-concept, we fabricate two light-fuelled patterned photonic soft actuators: a butterfly-inspired actuator that can produce wing-flapping dynamic changes in structural color, and an origami crane-shaped actuator with shape memory, structural color information storage, and dynamic display properties. This strategy provides distinct insights into the design and fabrication of various patterned photonic soft robotic devices and intelligent actuators.

Performance status, comorbidities, and cycles of methotrexate exert the greatest influence on outcomes of primary and secondary CNS lymphomas: the Lexington experience.

Primary central nervous system lymphoma (PCNSL) occurs primarily in older patients and has a worse prognosis than other extranodal lymphomas. Contemporary treatment is based on high-dose methotrexate (HD-MTX), which crosses the blood-brain barrier. Secondary CNS lymphoma (SCNSL) can occur concomitantly with systemic lymphoma or later at relapse and generally has a dismal outcome. We reviewed disease characteristics and outcomes of 103 patients (44 PCNSL and 59 SCNSL) treated at our center between 2015 and 2020. Median ages at diagnosis were 64 and 62 years, respectively. In both groups, diffuse large B cell lymphoma (DLBCL) was the major histologic type; in SCNSL, other types were also seen. SCNSL, in contrast with PCNSL, manifested with smaller tumors or cerebrospinal fluid positivity. For SCNSL the mean interval to brain involvement was 18 months (0-138). The overall survival had a trend to worse in SCNSL; median survival 11 months versus 61 months in PCNSL (p = 0.089). Progression-free survival was similar in both groups. A significant proportion of SCNSL patients with poor performance status could not obtain CNS-directed treatments. The strongest predictor of poor outcome was ECOG performance status 2 + at diagnosis for both groups. Charlson comorbidity index was predictive only for the PCNSL cohort. Tumor size was not prognostic for survival. The number of HD-MTX cycles correlated with survival, whereas the regimen itself and average cumulative dose of methotrexate did not play a role. Our study is in line with the recent literature and confirms ongoing challenges. We discuss how the outcomes of CNS lymphomas can be improved.

Selective inhibition of neurogenic, but not agonist-induced contractions by phospholipase A2 inhibitors points to presynaptic phospholipase A2 functions in contractile neurotransmission to human prostate smooth muscle.

BACKGROUND: Phospholipases A2 (PLA2 ) may be involved in α1 -adrenergic contraction by formation of thromboxane A2 in different smooth muscle types. However, whether this mechanism occurs with α1 -adrenergic contractions of the prostate, is still unknown. While α1 -adrenoceptor antagonists are the first line option for medical treatment of voiding symptoms in benign prostatic hyperplasia (BPH), improvements are limited, probably by nonadrenergic contractions including thromboxane A2 . Here, we examined effects of PLA2 inhibitors on contractions of human prostate tissues. METHODS: Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS) and by α1 -adrenergic agonists in an organ bath, after application of the cytosolic PLA2 inhibitors ASB14780 and AACOCF3, the secretory PLA2 inhibitor YM26734, the leukotriene receptor antagonist montelukast, or of solvent to controls. RESULTS: Frequency-dependent contractions of human prostate tissues induced by EFS were inhibited by 25% at 8 Hz, 38% at 16 Hz and 37% at 32 Hz by ASB14780 (1 µM), and by 32% at 16 Hz and 22% at 32 Hz by AACOCF3 (10 µM). None of both inhibitors affected contractions induced by noradrenaline, phenylephrine or methoxamine. YM26734 (3 µM) and montelukast (0.3 and 1 µM) neither affected EFS-induced contractions, nor contractions by α1 -adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM). CONCLUSIONS: Our findings suggest presynaptic PLA2 functions in prostate smooth muscle contraction, while contractions induced by α1 -adrenergic agonists occur PLA2 -independent. Lacking sensitivity to montelukast excludes an involvement of PLA2 -derived leukotrienes in promotion of contractile neurotransmission.

[Laser Techniques in the Treatment of Benign Prostatic Syndrome]. / Lasertechniken in der Behandlung des benignen Prostatasyndroms.

Laser Techniques in the Treatment of Benign Prostatic Syndrome Abstract: Lasers have a wide range of applications in endourological therapy. Not only in the treatment of stones, but also in the treatment of benign prostatic syndrome (BPS), their importance continues to grow. The endourological treatment of BPH with different laser techniques will be discussed in more detail in the following. The physical differences between the individual lasers will be explained first, followed by the treatment options that can be performed with a laser. The main focus will be on the concrete comparison of the treatment methods, especially in clinical contexts. In particular, the duration of surgery, length of hospitalisation, risk of post-operative bleeding, catheterisation duration, risk of urinary retention and risk of post-operative complications such as retrograde ejaculation, bladder neck sclerosis, urethra stricture and adenoma recurrence will be listed and compared for the most important methods. Nevertheless, the distribution of TURP to laser is still 30:1 in favour for TURP [1].

[Benign Prostate Hyperplasia - Current Medical Therapy, New Developments, and Side Effects]. / Benigne Prostatahyperplasie.

Benign Prostate Hyperplasia - Current Medical Therapy, New Developments, and Side Effects Abstract: Lower urinary tract symptoms (LUTS) consist of both voiding and storage symptoms. Urethral obstruction leading to voiding symptoms is most commonly attributed to benign prostatic hyperplasia (BPH), where hyperplastic growth and increased smooth muscle tone in the hyperplastic prostate may lead to benign prostate obstruction (BPO). Spontaneous contractions of the detrusor muscle may cause storage symptoms, which are referred to as overactive bladder (OAB). With a considerable proportion of patients suffering from "mixed LUTS", a combination of voiding and storage symptoms, LUTS affect a large portion of the population worldwide, with major impact on quality of life (QoL). A demographic shift in society, will lead to higher incidence and prevalence of LUTS, with a growing economic burden. Standard-of-care medical treatment for LUTS/BPO includes α1-adrenoceptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors, for reduction of prostate smooth muscle tone, and 5α-reductase inhibitors (5-ARI) to slow down disease progression. Medical therapy for LUTS/OAB includes muscarinic receptor antagonists, and ß3-agonists for relief of spontaneous bladder contractions. When left untreated, LUTS may cause considerable adverse events, ranging from acute urinary retention with kidney failure, and recurring infections, to social withdrawal, and depression.

A New Bacterial Adenosine-Derived Nucleoside as an Example of RNA Modification Damage.

The fields of RNA modification and RNA damage both exhibit a plethora of non-canonical nucleoside structures. While RNA modifications have evolved to improve RNA function, the term RNA damage implies detrimental effects. Based on stable isotope labelling and mass spectrometry, we report the identification and characterisation of 2-methylthio-1,N6-ethenoadenosine (ms2 ϵA), which is related to 1,N6-ethenoadenine, a lesion resulting from exposure of nucleic acids to alkylating chemicals in vivo. In contrast, a sophisticated isoprene labelling scheme revealed that ms2 ϵA biogenesis involves cleavage of a prenyl moiety in the known transfer RNA (tRNA) modification 2-methylthio-N6-isopentenyladenosine (ms2 i6 A). The relative abundance of ms2 ϵA in tRNAs from translating ribosomes suggests reduced function in comparison to its parent RNA modification, establishing the nature of the new structure in a newly perceived overlap of the two previously separate fields, namely an RNA modification damage.

The significance of a high preoperative PSA level for the detection of incidental prostate cancer in LUTS patients with large prostates.

PURPOSE: To evaluate the diagnostic value of a high preoperative PSA level for the detection of incidental prostate cancer (iPCa) in LUTS patients with very large prostates (> 100 cc). METHODS: We conducted a retrospective analysis of 1125 men treated for LUTS with holmium laser enucleation of the prostate (HoLEP). Patients were stratified according to a preoperative PSA level higher (high PSA; n = 365) or lower than 10 ng/ml (low PSA; n = 760). Preoperative and histopathological parameters were compared between both cohorts. Logistic regression models were used to identify independent predictors of iPCa. RESULTS: Demographic parameters were similar between both cohorts. The median PSA levels were 14.2 ng/ml (11.5-19.9) and 4 ng/ml (2.4-6.0). The prostate volume was significantly higher in the high PSA group (105 cc vs. 75 cc; p < 0.001). Correspondingly, the PSA density was significantly increased in the high PSA cohort compared to the low PSA cohort (0.14 vs. 0.05; p < 0.001). The overall detection rate of iPCa showed no difference between groups (9.5% vs. 9.9%). More preoperative prostate biopsies were performed in the high PSA group compared to the low PSA group (46.8% vs. 17.6%; p < 0.001). However, the rate of false negative results was comparable between groups (12.7% vs. 11.1%; p = 0.726). In logistic regression models all PSA-related parameters failed to predict iPCa. CONCLUSIONS: PSA-guided approaches to predict iPCa in LUTS patients with very large prostates are not accurate. This finding is useful in clinical practice for counselling our patients and to prevent unwarranted diagnostic procedures.

Elastomeric nematic colloids, colloidal crystals and microstructures with complex topology.

Control of physical behaviors of nematic colloids and colloidal crystals has been demonstrated by tuning particle shape, topology, chirality and surface charging. However, the capability of altering physical behaviors of such soft matter systems by changing particle shape and the ensuing responses to external stimuli has remained elusive. We fabricated genus-one nematic elastomeric colloidal ring-shaped particles and various microstructures using two-photon photopolymerization. Nematic ordering within both the nano-printed particle and the surrounding medium leads to anisotropic responses and actuation when heated. With the thermal control, elastomeric microstructures are capable of changing from genus-one to genus-zero surface topology. Using these particles as building blocks, we investigated elastomeric colloidal crystals immersed within a liquid crystal fluid, which exhibit crystallographic symmetry transformations. Our findings may lead to colloidal crystals responsive to a large variety of external stimuli, including electric fields and light. Pre-designed response of elastomeric nematic colloids, including changes of colloidal surface topology and lattice symmetry, are of interest for both fundamental research and applications.

Baby bonus in Switzerland: Effects on fertility, newborn health, and birth-scheduling.

This paper studies the effect of birth allowances (so-called baby bonus) on fertility, newborn health, and birth-scheduling in Switzerland. Switzerland provides an optimal quasi-experiment: 11 out of 26 cantons introduced a baby bonus during the last 50 years at different points in time. To identify the effect of changes in the baby bonus, we employ an event study with control groups using several administrative data sets on births, stillbirths, and infant deaths in Switzerland from 1969 to 2017. While there is no evidence for birth-scheduling, we find, however, a sizable but only temporary increase in the fertility rate of 5.5% and a permanent but diminishing increase in the birth weight of 2.8%. The latter effect is particularly strong at the lower end of the birth weight distribution. Furthermore, we document substantial heterogeneity by citizenship of mothers.

Laparoscopic parastomal hernia repair delays recurrence relative to open repair.

BACKGROUND: Mesh repair of parastomal hernia is widely accepted as superior to non-mesh repair, yet the most favorable surgical approach is a subject of continued debate. The aim of this study was to compare the clinical outcomes of open versus laparoscopic parastomal hernia repair. METHODS: An IRB-approved retrospective review was conducted comparing laparoscopic (LPHR) or open (OPHR) parastomal hernia repair performed between 2009 and 2017 at our facilities. Patient demographics, preoperative characteristics, operative details, and clinical outcomes were compared by surgical approach. Subgroup analysis was performed by location of mesh placement. Repair longevity was measured using Kaplan-Meier method and Cox proportional hazards regression. Intention to treat analysis was used for this study based on initial approach to the repair. RESULTS: Sixty-two patients (average age of 61 years) underwent repair (31 LPHR, 31 OPHR). Patient age, gender, BMI, ASA Class, and comorbidity status were similar between OPHR and LPHR. Stoma relocation was more common in OPHR (32% vs 7%, p = .022). Open sublay subgroup was similar to LPHR in terms of wound class and relocation. Open "Other" and Sublay subgroups resulted in more wound complications compared to LPHR (70% and 48% vs 27%, p = .036). Operative duration and hospital length of stay were less with LPHR (p < .001). After adjustment for prior hernia repair, risk of recurrence was higher for OPHR (p = .022) and Open Sublay and Other subgroups compared to LPHR (p = .005 and p = .027, respectively). CONCLUSIONS: Laparoscopic repair of parastomal hernias is associated with shorter operative duration, decreased length of stay, fewer short-term wound complications, and increased longevity of repair compared to open repairs. Direct comparison of repair longevity between LPHR and OPHR with mesh using Kaplan-Meier estimate is unique to this study. Further study is warranted to better understand methods of parastomal hernia repair associated with fewer complications and increased durability.

CPAP promotes timely cilium disassembly to maintain neural progenitor pool.

A mutation in the centrosomal-P4.1-associated protein (CPAP) causes Seckel syndrome with microcephaly, which is suggested to arise from a decline in neural progenitor cells (NPCs) during development. However, mechanisms ofNPCs maintenance remain unclear. Here, we report an unexpected role for the cilium inNPCs maintenance and identifyCPAPas a negative regulator of ciliary length independent of its role in centrosome biogenesis. At the onset of cilium disassembly,CPAPprovides a scaffold for the cilium disassembly complex (CDC), which includes Nde1, Aurora A, andOFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutatedCPAPfails to localize at the ciliary base associated with inefficientCDCrecruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re-entry leading to premature differentiation of patientiPS-derivedNPCs. AberrantCDCfunction also promotes premature differentiation ofNPCs in SeckeliPS-derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control.

Plasma-Induced Polymerizations: A New Synthetic Entry in Liquid Crystal Elastomer Actuators.

The research on soft actuators including liquid crystal elastomers (LCEs) becomes more and more appealing at a time when the expansion of artificial systems is blooming. Among the various LCE actuators, the bending deformation is often in the origin of many actuation modes. Here, a new strategy with plasma technology is developed to prepare single-layer main-chain LCEs with thermally actuated bending and contraction deformations. Two distinct reactions, plasma polymerization and plasma-induced photopolymerization, are used to polymerize in one step the nematic monomer mixture aligned by magnetic field. The plasma polymerization forms cross-linked but disoriented structures at the surface of the LCE film, while the plasma-induced photopolymerization produces aligned LCE structure in the bulk. The actuation behaviors (bending and/or contraction) of LCE films can be adjusted by plasma power, reaction time, and sample thickness. Soft robots like crawling walker and flower mimic are built by LCE films with bending actuation.

Double methylation of tRNA-U54 to 2'-O-methylthymidine (Tm) synergistically decreases immune response by Toll-like receptor 7.

Sensing of nucleic acids for molecular discrimination between self and non-self is a challenging task for the innate immune system. RNA acts as a potent stimulus for pattern recognition receptors including in particular human Toll-like receptor 7 (TLR7). Certain RNA modifications limit potentially harmful self-recognition of endogenous RNA. Previous studies had identified the 2'-O-methylation of guanosine 18 (Gm18) within tRNAs as an antagonist of TLR7 leading to an impaired immune response. However, human tRNALys3 was non-stimulatory despite lacking Gm18. To identify the underlying molecular principle, interferon responses of human peripheral blood mononuclear cells to differentially modified tRNALys3 were determined. The investigation of synthetic modivariants allowed attributing a significant part of the immunosilencing effect to the 2'-O-methylthymidine (m5Um) modification at position 54. The effect was contingent upon the synergistic presence of both methyl groups at positions C5 and 2'O, as shown by the fact that neither Um54 nor m5U54 produced any effect alone. Testing permutations of the nucleobase at ribose-methylated position 54 suggested that the extent of silencing and antagonism of the TLR7 response was governed by hydrogen patterns and lipophilic interactions of the nucleobase. The results identify a new immune-modulatory endogenous RNA modification that limits TLR7 activation by RNA.

Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C-terminal domain.

Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non-24-hour sleep-wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT1 and MT2 , belonging to the G protein-coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT1 and MT2 . Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT1 and MT2 by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT1 or MT2 . None of the mABs cross-reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR-KO mice as control. MT2 expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta-cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies.

Implementation of a Trauma Quality Improvement Program Communications Package Decreases Time-to-Operation for Facial Trauma.

INTRODUCTION: Facial trauma is common and carries significant morbidity and cost. Suboptimal interdisciplinary communication is associated with negative health outcomes. This study evaluates the clinical impact of implementation of American College of Surgeons Trauma Quality Improvement Program (TQIP) interdisciplinary communication guidelines between facial surgery and trauma teams. METHODS: Patients with facial trauma presenting to our level 1 trauma center between May and December 2017 were included (N = 812) and split into 3 groups, each anonymously representing a service that treats facial trauma. Services 1 and 2 were controls, and service 3 adopted TQIP communication guidelines. Mean and slope of time-to-operation (TTO) and mean length of stay were assessed 106 days before (n = 95) and 107 days after (n = 77) implementation. RESULTS: For service 3, mean TTO decreased significantly from 6.2 to 2.9 days (P = 0.005) after implementation of the communication intervention. There was no significant difference in mean TTO preimplementation versus postimplementation in either control cohort, including service 1 (4.6 vs 4.9 days; P = 0.59) and service 2 (4.2 vs 4.5 days; P = 0.62). Average length of stay did not differ significantly between the preintervention versus postintervention in any service (service 1: 9.0 vs 8.3 days, P = 0.43; service 2: 4.6 vs 6.6 days, P = 0.85; service 3: 6.7 vs 6.4 days, P = 0.45). CONCLUSION: Our study demonstrates that cost-free TQIP-guided improvement in interdisciplinary communication between the trauma service and a consulting surgical specialist decreases TTO for patients with operative facial trauma. Health care providers should develop strong well-defined communication channels between collaborating teams involved in patient care to optimize patient clinical outcomes.

Inhibition of smooth muscle contraction and ARF6 activity by the inhibitor for cytohesin GEFs, secinH3, in the human prostate.

Prostate smooth muscle contraction is critical for etiology and treatment of male lower urinary tract symptoms (LUTS) and is promoted by small monomeric GTPases (RhoA and Rac). GTPases may be activated by guanosine nucleotide exchange factors (GEFs). GEFs of the cytohesin family may indirectly activate Rac, or ADP ribosylation factor (ARF) GTPases directly. Here we investigated the expression of cytohesin family GEFs and effects of the cytohesin inhibitor Sec7 inhibitor H3 (secinH3) on smooth muscle contraction and GTPase activities in human prostate tissues. Of all four cytohesin isoforms, cytohesin-1 and -2 showed the highest expression in real-time PCR. Western blot and fluorescence staining suggested that cytohesin-2 may be the predominant isoform in prostate smooth muscle cells. Contractions induced by norepinephrine, the α1-adrenoceptor agonist phenylephrine, the thromboxane A2 analog U-46619 , and endothelin-1 and -3, as well as neurogenic contractions induced by electric field stimulation (EFS), were reduced by secinH3 (30 µM). Inhibition of EFS-induced contractions appeared to have efficacy similar to that of inhibition by the α1-adrenoceptor antagonist tamsulosin (300 nM). Combined application of secinH3 plus tamsulosin caused larger inhibition of EFS-induced contractions than tamsulosin alone. Pull-down assays demonstrated inhibition of the small monomeric GTPase ARF6 by secinH3, but no inhibition of RhoA or Rac1. In conclusion, we suggest that a cytohesin-ARF6 pathway takes part in smooth muscle contraction. This may open attractive new possibilities in medical treatment of male LUTS.

A Vastly Increased Chemical Variety of RNA Modifications Containing a Thioacetal Structure.

Recently discovered new chemical entities in RNA modifications have involved surprising functional groups that enlarge the chemical space of RNA. Using LC-MS, we found over 100 signals of RNA constituents that contained a ribose moiety in tRNAs from E. coli. Feeding experiments with variegated stable isotope labeled compounds identified 37 compounds that are new structures of RNA modifications. One structure was elucidated by deuterium exchange and high-resolution mass spectrometry. The structure of msms2 i6 A (2-methylthiomethylenethio-N6-isopentenyl-adenosine) was confirmed by methione-D3 feeding experiments and by synthesis of the nucleobase. The msms2 i6 A contains a thioacetal, shown in vitro to be biosynthetically derived from ms2 i6 A by the radical-SAM enzyme MiaB. This enzyme performs thiomethylation, forming ms2 i6 A from i6 A in a first turnover. The new thioacetal is formed by a second turnover. Along with the pool of 36 new modifications, this work describes a new layer of RNA modification chemistry.

Effects of vaginal conjugated equine estrogens and ospemifene on the rat vaginal wall and lower urinary tract.

Although the positive effects of vaginal estrogens and the selective estrogen receptor modulator, ospemifene (OS), on the vaginal epithelium are well recognized, less is known regarding the effects of these therapies on the lower urinary tract or vaginal muscularis. Clinical evidence suggests that vaginally administered estrogen may improve overactive bladder-related symptoms. The objective of this study was to compare the effects of OS, vaginal conjugated equine estrogens (CEE), or both on the vaginal wall and lower urinary tract in a rat model of menopause. Contractile force of the bladder neck, dome, and external urethral sphincter at optimal field stimulation did not differ significantly among treatment groups. Pharmacologic responses to atropine, carbachol, and potassium chloride were similar among groups. Vaginal epithelial thickness and differentiation were differentially regulated by CEE or OS. Ospemifene altered epithelial differentiation pathways in vaginal epithelium in a unique way, and these effects were additive with local CEE. Unless contraindicated, the beneficial effects of vaginal CEE on the vaginal wall outweigh those of OS.