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We compared the effect of commercial vaginal douching products on Lactobacillus crispatus, L. jensenii, L. gasseri, L. iners , E. coli , and immortalized vaginal epithelial cells (VK2). All studied douching products (vinegar, iodine and baking soda based) induced epithelial cell death, and all inhibited growth of E. coli . Co-culture of vaginal epithelial cells with any of the lactobacilli immediately following exposure to douching products resulted in a trend to less human cell death. However, co-culture of epithelial cells with L. iners was associated with higher production of IL6 and IL8, and lower IL1RA regardless of presence or type of douching solution. Co-culture with L. crispatus or L. jensenii decreased IL6 production in the absence of douches, but increased IL6 production after exposure to vinegar. Douching products may be associated with epithelial disruption and inflammation, and may reduce the anti-inflammatory effects of beneficial lactobacilli.

Vaginal microbiota composition affects many facets of reproductive health. Lactobacillus iners -dominated microbial communities are associated with poorer outcomes, including higher risk of bacterial vaginosis (BV), compared with vaginal microbiota rich in L. crispatus . Unfortunately, standard-of-care metronidazole therapy for BV typically results in dominance of L. iners , probably contributing to post-treatment relapse. Here we generate an L. iners isolate collection comprising 34 previously unreported isolates from 14 South African women with and without BV and 4 previously unreported isolates from 3 US women. We also report an associated genome catalogue comprising 1,218 vaginal Lactobacillus isolate genomes and metagenome-assembled genomes from >300 women across 4 continents. We show that, unlike L. crispatus , L. iners growth is dependent on l -cysteine in vitro and we trace this phenotype to the absence of canonical cysteine biosynthesis pathways and a restricted repertoire of cysteine-related transport mechanisms. We further show that cysteine concentrations in cervicovaginal lavage samples correlate with Lactobacillus abundance in vivo and that cystine uptake inhibitors selectively inhibit L. iners growth in vitro. Combining an inhibitor with metronidazole promotes L. crispatus dominance of defined BV-like communities in vitro by suppressing L. iners growth. Our findings enable a better understanding of L. iners biology and suggest candidate treatments to modulate the vaginal microbiota to improve reproductive health for women globally. l -cysteine is required for the growth of Lactobacillus iners , a vaginal microbiome species typically associated with adverse outcomes that lacks cysteine biosynthesis pathways and key uptake mechanisms present in other lactobacilli. Cystine uptake inhibitors can be used to suppress L. iners abundance in vitro in favour of L. crispatus , a species associated with favourable outcomes.

Up to 30% of women with vaginal symptoms are not assigned a diagnosis after standard diagnostic assessment. We compared premenopausal women with idiopathic vaginitis (IV) or vulvodynia (VVD) to healthy controls. Microbiota were characterized using rRNA sequencing. Cytokines/chemokines (IL-10, IL-1α, IL-1β, IL-6, IL-8, IL-2, IL-18, IL-4, IL-9, and IL-13) were measured in vaginal lavage fluid using the Meso Scale Discovery platform or ELISA (IL-1ra). Immunoglobulins were measured in vaginal lavage fluid using a bead-based immunoassay (Millipore). Cases and controls were compared using Kruskal-Wallis, analysis of variance, and linear regression or (for microbiome composition) the Bray-Curtis dissimilarity statistic. We compared 20 women with IV, 30 with VVD, and 52 controls. Most (80%) had greater than 90% 16S rRNA gene sequences from Lactobacillus crispatus, L. jensenii, L. gasseri, or L. iners. In analyses adjusted for age and hormonal contraception (HC), Gardnerella vaginalis was less prevalent and abundant in women with VVD (2/30, 7%) versus controls (16/52, 31%) or IV (5/20, 25%) (P = 0.030). Bray-Curtis dissimilarity was not significantly different between IV and controls or VVD. Fungal sequences were only detected in 5 participants: 2 control, 1 IV, 2 VVD. In univariate analysis, cytokines were not associated with diagnosis. Median vaginal concentration of IgE (but not other immunoglobulins) was lower in women with VVD (P = 0.006). Minimal differences in vaginal microbiota and inflammatory markers between women with IV, VVD or controls suggest no striking association between vaginal bacteria, fungi or inflammation and diagnosis in these women.

PurposeTo evaluate magnetic resonance imaging findings that differentiate among periurethral bulking agents (primarily collagen), urethral diverticulum, and periurethral cyst.MethodsWe searched our radiologic database retrospectively from 2001 to 2017 for periurethral cystic lesions, identifying a total of 50 patients with 68 lesions. Final diagnoses in 68 lesions were bulking agents (27), urethral diverticula (29), and periurethral cysts (12). Two abdominal radiologists, blinded to clinical history, independently evaluated T1, T2, and post-contrast images. The readers assessed number, morphological features, location, connection to urethra and mass effect, signal intensity, and enhancement for each lesion. Fisher exact test and logistic regression analysis were performed for each univariate significant feature. The operative and pathologic reports were the reference standard.ResultsMagnetic resonance imaging features found more often in bulking agents versus urethral diverticulum were multiple lesions (P = 0.011), upper or upper-mid-urethral location (P ≤ 0.0001), lack of internal fluid/fluid level (P = 0.002), no urethral connection (P = 0.005), T1 isointensity, and T2 mild hyperintensity compared to muscles but lower T2 signal than urine (P < 0.0001). Most cases of urethral diverticula and periurethral cysts were detected at mid- and lower urethra. Urethral diverticula were larger than bulking agents and periurethral cysts (P = 0.005 and P = 0.023) (mean diameter = 24, 16, 15 mm, respectively). Most bulking agents (93%) and urethral diverticula (90%) showed mass effect on urethra, while periurethral cysts (75%) did not (P < 0.0001).ConclusionSignal intensity and lesion characterization on magnetic resonance imaging can significantly differentiate bulking agent from urethral diverticulum and periurethral cyst. Radiologists should consider differential diagnosis of a bulking agent, especially when distinguishing characteristics described here are present to prevent incorrect diagnosis and ultimately unnecessary surgical intervention.

Women with idiopathic vulvovaginal symptoms had no differences in bacteria, fungi, or vaginal cytokines/chemokines compared with healthy controls, suggesting symptoms are not due to occult infection. Supplemental digital content is available in the text. Background Up to 30% of women with vaginal symptoms are not assigned a diagnosis after standard diagnostic assessment. Methods We compared premenopausal women with idiopathic vaginitis (IV) or vulvodynia (VVD) to healthy controls. Microbiota were characterized using rRNA sequencing. Cytokines/chemokines (IL-10, IL-1α, IL-1β, IL-6, IL-8, IL-2, IL-18, IL-4, IL-9, and IL-13) were measured in vaginal lavage fluid using the Meso Scale Discovery platform or ELISA (IL-1ra). Immunoglobulins were measured in vaginal lavage fluid using a bead-based immunoassay (Millipore). Cases and controls were compared using Kruskal-Wallis, analysis of variance, and linear regression or (for microbiome composition) the Bray-Curtis dissimilarity statistic. Results We compared 20 women with IV, 30 with VVD, and 52 controls. Most (80%) had greater than 90% 16S rRNA gene sequences from Lactobacillus crispatus, L. jensenii, L. gasseri, or L. iners. In analyses adjusted for age and hormonal contraception (HC), Gardnerella vaginalis was less prevalent and abundant in women with VVD (2/30, 7%) versus controls (16/52, 31%) or IV (5/20, 25%) (P = 0.030). Bray-Curtis dissimilarity was not significantly different between IV and controls or VVD. Fungal sequences were only detected in 5 participants: 2 control, 1 IV, 2 VVD. In univariate analysis, cytokines were not associated with diagnosis. Median vaginal concentration of IgE (but not other immunoglobulins) was lower in women with VVD (P = 0.006). Conclusions Minimal differences in vaginal microbiota and inflammatory markers between women with IV, VVD or controls suggest no striking association between vaginal bacteria, fungi or inflammation and diagnosis in these women.

Calibration and testing of the instruments on the Integrated Science Instrument Module (ISIM) of the James Webb Space Telescope (JWST) is being performed by the use of a cryogenic, full-field, optical simulator that was constructed for this purpose. The Pupil Select Mechanism (PSM) assembly is one of several mechanisms and optical elements that compose the Optical Telescope Element SIMulator, or OSIM. The PSM allows for several optical elements to be inserted into the optical plane of OSIM, introducing a variety of aberrations, distortions, obscurations, and other calibration states into the pupil plane. The following discussion focuses on the details of the design evolution, analysis, build, and test of this mechanism along with the challenges associated with creating a sub arc-minute positioning mechanism operating in an extreme cryogenic environment. In addition, difficult challenges in the control system design will be discussed including the incorporation of closed-loop feedback control into a system that was designed to operate in an open-loop fashion.

Calibration and testing of the instruments on the Integrated Science Instrument Module (ISIM) of the James Webb Space Telescope (JWST) is being performed by the use of a cryogenic, full-field, optical simulator that was constructed for this purpose. The Pupil Select Mechanism (PSM) assembly is one of several mechanisms and optical elements that compose the Optical Telescope Element SIMulator, or OSIM. The PSM allows for several optical elements to be inserted into the optical plane of OSIM, introducing a variety of aberrations, distortions, obscurations, and other calibration states into the pupil plane. The following discussion focuses on the details of the design evolution, analysis, build, and test of this mechanism along with the challenges associated with creating a sub arc-minute positioning mechanism operating in an extreme cryogenic environment. In addition, difficult challenges in the control system design will be discussed including the incorporation of closed-loop feedback control into a system that was designed to operate in an open-loop fashion.

This paper describes the design of a unique suite of mechanisms that make up the Deployment and Pointing System (DAPS) for the Neutron Star Interior Composition Explorer (NICER/SEXTANT) instrument, an X-Ray telescope, which will be mounted on the International Space Station (ISS). The DAPS system uses four stepper motor actuators to deploy the telescope box, latch it in the deployed position, and allow it to track sky targets. The DAPS gimbal architecture provides full-hemisphere coverage, and is fully re-stowable. The compact design of the mechanism allowed the majority of total instrument volume to be used for science. Override features allow DAPS to be stowed by ISS robotics.

Vaginal microbiota composition affects several important reproductive health outcomes. Lactobacillus crispatus-dominant bacterial communities have favorable associations whereas anaerobe-dominant communities deficient of lactobacilli are linked to poor outcomes, including bacterial vaginosis (BV). Lactobacillus iners, the most abundant vaginal species worldwide, has adverse associations compared to L. crispatus, but standard metronidazole treatment for BV promotes L. iners-dominance, likely contributing to post-treatment relapse. L. iners is under-studied because it fails to grow in standard Lactobacillus media in vitro. Here we trace this in vitro phenotype to a species-specific cysteine requirement associated with limitations in cysteine-related transport mechanisms and show that vaginal cysteine concentrations correlate with Lactobacillus abundance in vivo. We demonstrate that cystine uptake inhibitors selectively impede L. iners growth and that combining an inhibitor with metronidazole thus promotes L. crispatus dominance of defined BV-like communities. These findings identify a novel target for therapeutic vaginal microbiota modulation to improve reproductive health.