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OBJECTIVE To characterise the bladder microbiota of continent adult women. DESIGN Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data. SETTING US academic medical centre. POPULATION Well-characterised continent adult women. METHODS Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing. MAIN OUTCOME MEASURES Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen). RESULTS The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P

Germline DDX41 variants in myeloid neoplasms (MNs) are not uncommon, and we explored the prevalence and characterized the clinical and pathologic features in a cohort of 3132 unrelated adult MN patients. By targeted next-generation sequencing, we identified 28 patients (20 men and 8 women) with pathogenic germline DDX41 variants who developed acute myeloid leukemia (AML), in which only 3 (11%) had a family history (FH) of MNs. A subacute clinical course of cytopenia (mean duration of 11.2 months, range 0-72 months) prior to the initial AML diagnosis was accompanied by a low blast count (median at 30%, range 20-70%) in hypocellular marrows (93% of all patients), in vast contrast to the typical proliferative subtypes of AML in the elderly. Most patients had a normal karyotype (75%) and acquired a second DDX41 variant (69%). A favorable overall survival (OS) was observed in comparison to that of common subtypes of AML with wild-type DDX41 in age-matched patients. Our study demonstrated that the frequent germline pathogenic DDX41 variants characterized a clinically distinct AML entity. Features characteristic of DDX41-mutated AML include male predominance, often lack of FH, indolent course, low proliferative potential, frequent somatic DDX41 variants, and a favorable OS.

Prior research into the bacterium Gardnerella vaginalis has largely focused on its association with bacterial vaginosis (BV). However, G. vaginalis is also frequently found within the urinary microbiota of women with and without lower urinary tract symptoms as well as individuals with chronic kidney disease, interstitial cystitis, and BV., Gardnerella is a frequent member of the urogenital microbiota. Given the association between Gardnerella vaginalis and bacterial vaginosis (BV), significant efforts have been focused on characterizing this species in the vaginal microbiota. However, Gardnerella also is a frequent member of the urinary microbiota. In an effort to characterize the bacterial species of the urinary microbiota, we present here 10 genomes of urinary Gardnerella isolates from women with and without lower urinary tract symptoms. These genomes complement those of 22 urinary Gardnerella strains previously isolated and sequenced by our team. We included these genomes in a comparative genome analysis of all publicly available Gardnerella genomes, which include 33 urinary isolates, 78 vaginal isolates, and 2 other isolates. While once this genus was thought to consist of a single species, recent comparative genome analyses have revealed 3 new species and an additional 9 groups within Gardnerella. Based upon our analysis, we suggest a new group for the species. We also find that distinction between these Gardnerella species/groups is possible only when considering the core or whole-genome sequence, as neither the sialidase nor vaginolysin genes are sufficient for distinguishing between species/groups despite their clinical importance. In contrast to the vaginal microbiota, we found that only five Gardnerella species/groups have been detected within the lower urinary tract. Although we found no association between a particular Gardnerella species/group(s) and urinary symptoms, further sequencing of urinary Gardnerella isolates is needed for both comprehensive taxonomic characterization and etiological classification of Gardnerella in the urinary tract. IMPORTANCE Prior research into the bacterium Gardnerella vaginalis has largely focused on its association with bacterial vaginosis (BV). However, G. vaginalis is also frequently found within the urinary microbiota of women with and without lower urinary tract symptoms as well as individuals with chronic kidney disease, interstitial cystitis, and BV. This prompted our investigation into Gardnerella from the urinary microbiota and all publicly available Gardnerella genomes from the urogenital tract. Our work suggests that while some Gardnerella species can survive in both the urinary tract and vagina, others likely cannot. This study provides the foundation for future studies of Gardnerella within the urinary tract and its possible contribution to lower urinary tract symptoms.

Supplemental digital content is available in the text., Objective Multiple studies show cultivatable bacteria in urine of most women. The existence of these bacteria challenges interstitial cystitis (IC)/painful bladder syndrome (PBS) diagnosis, which presumes a sterile bladder. The aims of this study were (1) to compare the female bladder microbiomes in women with IC/PBS and unaffected controls and (2) to correlate baseline bladder microbiome composition with symptoms. Methods This cross-sectional study enrolled 49 IC/PBS and 40 controls. All provided catheterized urine samples and completed validated questionnaires. A subset of the IC/PBS cohort provided voided and catheterized urine samples. All samples from both cohorts were assessed by the expanded quantitative urine culture (EQUC) protocol; a subset was assessed by 16S rRNA gene sequencing. Results Of the IC/PBS cohort, 49.0% (24/49) were EQUC positive; in these EQUC-positive samples, the most common urotypes were Lactobacillus (45.8%) and Streptococcus (33.3%). Of the controls, 40.0% were EQUC positive; of these EQUC-positive samples, the most common urotype was Lactobacillus (50.0%). The urotype distribution was significantly different (P < 0.05), as 16% of the IC/PBS cohort, but 0% of controls, were Streptococcus urotype (P < 0.01). Symptom-free IC/PBS participants were less likely to be EQUC positive (12.5%) than IC/PBS participants with moderate or severe symptoms (68.8% and 46.2%) and the control cohort (60%; P < 0.05). Conclusion Lactobacillus was the most common urotype. However, the presence of Lactobacillus did not differ between cohorts, and it did not impact IC/PBS symptom severity. Bacteria were not isolated from most participants with active IC/PBS symptoms. These findings suggest that bacteria may not be an etiology for IC/PBS.

Aerococcus urinae is increasingly recognized as a potentially significant urinary tract bacterium. A. urinae has been isolated from urine collected from both males and females with a wide range of clinical conditions, including urinary tract infection (UTI), urgency urinary incontinence (UUI), and overactive bladder (OAB). A. urinae is of particular clinical concern because it is highly resistant to many antibiotics and, when undiagnosed, can cause invasive and life-threatening bacteremia, sepsis, or soft tissue infections. Previous genomic characterization studies have examined A. urinae strains isolated from patients experiencing UTI episodes. Here, we analyzed the genomes of A. urinae strains isolated as part of the urinary microbiome from patients with UUI or OAB. Furthermore, we report that certain A. urinae strains exhibit aggregative in vitro phenotypes, including flocking, which can be modified by various growth medium conditions. Finally, we performed in-depth genomic comparisons to identify pathways that distinguish flocking and nonflocking strains. IMPORTANCE Aerococcus urinae is a urinary bacterium of emerging clinical interest. Here, we explored the ability of 24 strains of A. urinae isolated from women with lower urinary tract symptoms to display aggregation phenotypes in vitro. We sequenced and analyzed the genomes of these A. urinae strains. We performed functional genomic analyses to determine whether the in vitro hyperflocking aggregation phenotype displayed by certain A. urinae strains was related to the presence or absence of certain pathways. Our findings demonstrate that A. urinae strains have different propensities to display aggregative properties in vitro and suggest a potential association between phylogeny and flocking.

Purpose The urinary microbiota in women with type 2 diabetes (T2DM) can have bacterial uropathogens which are more virulent. The primary objective was to describe and compare the characteristics of the microbiota in voided urine of women with and without T2DM. Methods Two cohorts of women: those with T2DM (n = 87) and those without T2DM (n = 49) were studied. Demographic data, hemoglobin A1c (HbA1c), fasting serum glucose, and voided urine were collected. To determine the characteristics of the microbiota in the urine, 16S rRNA gene sequencing was used. Results The genus Lactobacillus was more often present in women with T2DM (75.9%, n = 66) than in the controls (59.2%, n = 30) (p = 0.042), as was the family Enterobacteriaceae (12.6% T2DM versus 2.0% control, p = 0.055). There was evidence of an association between HbA1c and the relative abundance of the various bacteria in the total cohort. The relative abundance of Lactobacillus was positively associated (ρ = 0.19, 95% CI: 0.02, 0.34), while Corynebacterium (ρ = −0.26, 95% CI: −0.41, −0.10) and Prevotella (ρ = −0.23, 95% CI: −0.38, −0.06) were inversely associated with HbA1c. Conclusions Enterobacteriaceae (e.g. E. coli) predispose women to urinary tract infections and since T2DM increases this risk, further study is needed. The species of Lactobacillus and its impact needs exploration.

Women have a 20% risk of developing a urinary tract infection (UTI) following urogynecologic surgery. This study assessed the association of postoperative UTI with bacteria in preoperative samples of catheterized urine. Immediately before surgery, vaginal swabs, perineal swabs, and catheterized urine samples were collected, and the V4 region of the 16S ribosomal RNA (rRNA) gene was sequenced. The cohort was dichotomized in two ways: (1) standard day-of-surgery urine culture result (positive/negative), and (2) occurrence of postoperative UTI (positive/negative). Characteristics of bladder, vaginal, and perineal microbiomes were assessed to identify factors associated with postoperative UTI. Eighty-seven percent of the 104 surgical patients with pelvic organ prolapse/urinary incontinence (POP/UI) were white; mean age was 57 years. The most common genus was Lactobacillus, with a mean relative abundance of 39.91% in catheterized urine, 53.88% in vaginal swabs, and 30.28% in perineal swabs. Two distinct clusters, based on dispersion of catheterized urine (i.e., bladder) microbiomes, had highly significant (p

Viruses are the most abundant component of the human microbiota. Recent evidence has uncovered a rich diversity of viruses within the female bladder, including both bacteriophages and eukaryotic viruses. We conducted whole-genome sequencing of the bladder microbiome of 30 women: 10 asymptomatic ‘healthy’ women and 20 women with an overactive bladder. These metagenomes include sequences representative of human, bacterial and viral DNA. This analysis, however, focused specifically on viral sequences. Using the bioinformatic tool virMine, we discovered sequence fragments, as well as complete genomes, of bacteriophages and the eukaryotic virus JC polyomavirus. The method employed here is a critical proof of concept: the genomes of viral populations within the low-biomass bladder microbiota can be reconstructed through whole-genome sequencing of the entire microbial community.

Background Previous work has shown that the vaginal microbiome decreases in Lactobacillus predominance and becomes more diverse after menopause. It has also been shown that estrogen therapy restores Lactobacillus dominance in the vagina and that topical estrogen is associated with overactive bladder symptom improvement. We now know that the bladder contains a unique microbiome and that increased bladder microbiome diversity is associated with overactive bladder. However, there is no understanding of how quickly each pelvic floor microbiome responds to estrogen or if those changes are associated with symptom improvement. Objective This study aimed to determine if estrogen treatment of postmenopausal women with overactive bladder decreases urobiome diversity. Study Design We analyzed data from postmenopausal participants in 2 trials ( NCT02524769 and NCT02835846 ) who chose vaginal estrogen as the primary overactive bladder treatment and used 0.5 g of conjugated estrogen (Premarin cream; Pfizer, New York City, NY) twice weekly for 12 weeks. Baseline and 12-week follow-up data included the Overactive Bladder questionnaire, and participants provided urine samples via catheter, vaginal swabs, perineal swabs, and voided urine samples. Microbes were detected by an enhanced culture protocol. Linear mixed models were used to estimate microbiome changes over time. Urinary antimicrobial peptide activity was assessed by a bacterial growth inhibition assay and correlated with relative abundance of members of the urobiome. Results In this study, 12 weeks of estrogen treatment resulted in decreased microbial diversity within the vagina (Shannon, P=.047; Richness, P=.043) but not in the other niches. A significant increase in Lactobacillus was detected in the bladder (P=.037) but not in the vagina (P=.33), perineum (P=.56), or voided urine (P=.28). The change in Lactobacillus levels in the bladder was associated with modest changes in urgency incontinence symptoms (P=.02). The relative abundance of the genus Corynebacterium correlated positively with urinary antimicrobial peptide activity after estrogen treatment. Conclusion Estrogen therapy may change the microbiome of different pelvic floor niches. The vagina begins to decrease in diversity, and the bladder experiences a significant increase in Lactobacillus levels; the latter is correlated with a modest improvement in the symptom severity subscale of the Overactive Bladder questionnaire.

Since the discovery of the bladder microbiome (urobiome), interest has grown in learning whether urobiome characteristics have a role in clinical phenotyping and provide opportunities for novel therapeutic approaches for women with common forms of urinary incontinence.This study aimed to test the hypothesis that the bladder urobiome differs among women in the control cohort and women affected by urinary incontinence by assessing associations between urinary incontinence status and the cultured urobiome.With institutional review board oversight, urine specimens from 309 adult women were collected through transurethral catheterization. These women were categorized into 3 cohorts (continent control, stress urinary incontinence [SUI], and urgency urinary incontinence [UUI]) based on their responses to the validated Pelvic Floor Distress Inventory (PFDI) questionnaire. Among 309 women, 150 were in the continent control cohort, 50 were in the SUI cohort, and 109 were in the UUI cohort. Symptom severity was assessed by subscale scoring with the Urinary Distress Inventory (UDI), subscale of the Pelvic Floor Distress Inventory. Microbes were assessed by expanded quantitative urine culture protocol, which detects the most common bladder microbes (bacteria and yeast). Microbes were identified to the species level by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. Alpha diversity indices were calculated for culture-positive samples and compared across the 3 cohorts. The correlations of UDI scores, alpha diversity indices, and species abundance were estimated.Participants had a mean age of 53 years (range 22-90); most were whites (65%). Women with urinary incontinence were slightly older (control, 47; SUI, 54; UUI, 61). By design, UDI symptom scores differed (control, 8.43 [10.1]; SUI, 97.95 [55.36]; UUI, 93.71 [49.12]; P.001). Among 309 participants, 216 (70%) had expanded quantitative urine culture-detected bacteria; furthermore, the urinary incontinence cohorts had a higher detection frequency than the control cohort (control, 57%; SUI, 86%; UUI, 81%; P.001). In addition, the most frequently detected species among the cohorts were as follows: continent control, Lactobacillus iners (12.7%), Streptococcus anginosus (12.7%), L crispatus (10.7%), and L gasseri (10%); SUI, S anginosus (26%), L iners (18%), Staphylococcus epidermidis (18%), and L jensenii (16%); and UUI, S anginosus (30.3%), L gasseri (22%), Aerococcus urinae (18.3%), and Gardnerella vaginalis (17.4%). However, only Actinotignum schaalii (formerly Actinobaculum schaalii), A urinae, A sanguinicola, and Corynebacterium lipophile group were found at significantly higher mean abundances in 1 of the urinary incontinence cohorts when compared with the control cohort (Wilcoxon rank sum test; P.02), and no individual genus differed significantly between the 2 urinary incontinence cohorts. Both urinary incontinence cohorts had increased alpha diversity similar to continent control cohort with indices of species richness, but not evenness, strongly associated with urinary incontinence.In adult women, the composition of the culturable bladder urobiome is associated with urinary incontinence, regardless of common incontinence subtype. Detection of more unique living microbes was associated with worsening incontinence symptom severity. Culturable species richness was significantly greater in the urinary incontinence cohorts than in the continent control cohort.

OBJECTIVES: Persistent and de novo symptoms decrease satisfaction after urogynecologic surgery. We investigated whether the pre-operative bladder microbiome is associated with urinary symptoms prior to and after urogynecological surgery. METHODS: 126 participants contributed responses to the validated OABq symptom questionnaire. Catheterized (bladder) urine samples and vaginal and perineal swabs were collected immediately pre-operatively. Bacterial DNA in the urine samples and swabs was sequenced and classified. RESULTS: Pre-operative symptom severity was significantly worse in sequence-positive patients. Higher OABq Symptom Severity (OABqSS) scores (more symptomatic) were associated with higher abundance in bladder urine of two bacterial species: Atopobium vaginae and Finegoldia magna. The presence of Atopobium vaginae in bladder urine also was correlated with its presence in either the vagina or perineum. CONCLUSIONS: Two specific bacterial species detected in bladder urine, Atopobium vaginae and Finegoldia magna, are associated with pre-operative urinary symptoms severity in women undergoing POP/SUI surgery. The reservoir for Atopobium vaginae may be an adjacent pelvic floor niches. This observations should be validated in a larger cohort to determine whether there is a microbiological etiology for certain pre-operative urinary symptoms.

Bacterial viruses (bacteriophages) play a significant role in microbial community dynamics. Within the human gastrointestinal tract, for instance, associations among bacteriophages (phages), microbiota stability, and human health have been discovered. In contrast to the gastrointestinal tract, the phages associated with the urinary microbiota are largely unknown. Preliminary metagenomic surveys of the urinary virome indicate a rich diversity of novel lytic phage sequences at an abundance far outnumbering that of eukaryotic viruses. These surveys, however, exclude the lysogenic phages residing within the bacteria of the bladder. To characterize this phage population, we examined 181 genomes representative of the phylogenetic diversity of bacterial species within the female urinary microbiota and found 457 phage sequences, 226 of which were predicted with high confidence. Phages were prevalent within the bladder bacteria: 86% of the genomes examined contained at least one phage sequence. Most of these phages are novel, exhibiting no discernible sequence homology to sequences in public data repositories. The presence of phages with substantial sequence similarity within the microbiota of different women supports the existence of a core community of phages within the bladder. Furthermore, the observed variation between the phage populations of women with and without overactive bladder symptoms suggests that phages may contribute to urinary health. To complement our bioinformatic analyses, viable phages were cultivated from the bacterial isolates for characterization; a novel coliphage was isolated, which is obligately lytic in the laboratory strain Escherichia coli C. Sequencing of bacterial genomes facilitates a comprehensive cataloguing of the urinary virome and reveals phage-host interactions. IMPORTANCE Bacteriophages are abundant within the human body. However, while some niches have been well surveyed, the phage population within the urinary microbiome is largely unknown. Our study is the first survey of the lysogenic phage population within the urinary microbiota. Most notably, the abundance of prophage exceeds that of the bacteria. Furthermore, many of the prophage sequences identified exhibited no recognizable sequence homology to sequences in data repositories. This suggests a rich diversity of uncharacterized phage species present in the bladder. Additionally, we observed a variation in the abundances of phages between bacteria isolated from asymptomatic “healthy” individuals and those with urinary symptoms, thus suggesting that, like phages within the gut, phages within the bladder may contribute to urinary health.

Purpose To examine the characteristics of the midstream urine microbiome in adults with stage 3–5 non-dialysis-dependent chronic kidney disease (CKD). Methods Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate [eGFR] 50% reads) by the genera Corynebacterium (n = 11), Staphylococcus (n = 9), Streptococcus (n = 7), Lactobacillus (n = 7), Gardnerella (n = 7), Prevotella (n = 4), Escherichia_Shigella (n = 3), and Enterobacteriaceae (n = 2); the rest lacked a dominant genus. The samples had high levels of diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)]. Diversity measures were generally higher in participants with urgency urinary incontinence and higher estimated glomerular filtration rate (eGFR). After controlling for demographics and diabetes status, microbiome diversity was significantly associated with estimated eGFR (P

Metagenomic analyses have indicated that the female bladder harbors an indigenous microbiota. However, there are few cultured reference strains with sequenced genomes available for functional and experimental analyses. Here we isolate and genome-sequence 149 bacterial strains from catheterized urine of 77 women. This culture collection spans 78 species, representing approximately two thirds of the bacterial diversity within the sampled bladders, including Proteobacteria, Actinobacteria, and Firmicutes. Detailed genomic and functional comparison of the bladder microbiota to the gastrointestinal and vaginal microbiotas demonstrates similar vaginal and bladder microbiota, with functional capacities that are distinct from those observed in the gastrointestinal microbiota. Whole-genome phylogenetic analysis of bacterial strains isolated from the vagina and bladder in the same women identifies highly similar Escherichia coli, Streptococcus anginosus, Lactobacillus iners, and Lactobacillus crispatus, suggesting an interlinked female urogenital microbiota that is not only limited to pathogens but is also characteristic of health-associated commensals.

To assess urinary symptoms associated with urinary tract infection (UTI) in a urogynecologic population of women.In this cohort study, we enrolled 150 urogynecologic patients who completed the validated UTI Symptom Assessment questionnaire and contributed transurethral catheterized urine samples. The primary measure (UTI diagnosis) was defined in three ways. Self-report (a nonculture-based UTI diagnosis) was defined by a yes or no response to the query "Do you think you have a UTI?" Two culture-based UTI diagnoses also were analyzed: standard urine culture (10 colony-forming units [CFU]/mL or greater) and enhanced quantitative urine culture (10 CFU/mL or greater) of any uropathogen. Statistical analyses were performed on patient demographics and urinary symptom prevalence among patient groups.Although the presence of the urinary symptoms of frequency and urgency (respectively) differ somewhat between UTI-positive and UTI-negative women (self-report [P=.005 and P.001], standard urine culture [P=.038 and P=.044], or enhanced quantitative urine culture [P=.059 and P=.098]), the presence of dysuria (pain or burning) during urination was significantly more prevalent in UTI-positive women for all UTI definitions (self-report P.001, standard urine culture P.001, and enhanced quantitative urine culture P=.010). Furthermore, women reporting dysuria had higher severity and bother scores for all other urinary symptoms assessed by the UTI Symptom Assessment questionnaire compared with women not reporting dysuria (frequency P=.001, urgency P=.006, dysuria P.001).Our findings show that, in women seeking urogynecologic care, the presence of frequency and urgency of urination does not confirm a culture-based UTI diagnosis. Instead, clinicians can more readily detect UTI using the presence of dysuria, which more effectively discriminates UTI-positive and UTI-negative individuals, regardless of the culture-based method used to diagnose UTI.

This case describes an injury to a 40-year-old woman, employed as a softball team coach, who presented to an emergency department (ED) after sustaining a line drive hit to the right side of the face with a softball during practice. Upon arrival to the ED, the patient complained of moderate pain, swelling, and bruising over the right side of her midface area. After evaluation in the ED, the patient received a diagnosis of a zygomatic arch fracture that was further managed by an occupational medicine nurse practitioner, a plastic surgeon, and an ear, nose, and throat (ENT) physician specialist. Language: en

Enhanced quantitative urine culture (EQUC) detects live microorganisms in the vast majority of urine specimens reported as “no growth” by the standard urine culture protocol. Here, we evaluated an expanded set of EQUC conditions (expanded-spectrum EQUC) to identify an optimal version that provides a more complete description of uropathogens in women experiencing urinary tract infection (UTI)-like symptoms. One hundred fifty adult urogynecology patient-participants were characterized using a self-completed validated UTI symptom assessment (UTISA) questionnaire and asked “Do you feel you have a UTI?” Women responding negatively were recruited into the no-UTI cohort, while women responding affirmatively were recruited into the UTI cohort; the latter cohort was reassessed with the UTISA questionnaire 3 to 7 days later. Baseline catheterized urine samples were plated using both standard urine culture and expanded-spectrum EQUC protocols: standard urine culture inoculated at 1 μl onto 2 agars incubated aerobically; expanded-spectrum EQUC inoculated at three different volumes of urine onto 7 combinations of agars and environments. Compared to expanded-spectrum EQUC, standard urine culture missed 67% of uropathogens overall and 50% in participants with severe urinary symptoms. Thirty-six percent of participants with missed uropathogens reported no symptom resolution after treatment by standard urine culture results. Optimal detection of uropathogens could be achieved using the following: 100 μl of urine plated onto blood (blood agar plate [BAP]), colistin-nalidixic acid (CNA), and MacConkey agars in 5% CO 2 for 48 h. This streamlined EQUC protocol achieved 84% uropathogen detection relative to 33% detection by standard urine culture. The streamlined EQUC protocol improves detection of uropathogens that are likely relevant for symptomatic women, giving clinicians the opportunity to receive additional information not currently reported using standard urine culture techniques.

Background The role of calcium oxalate crystals and deposits in UTI pathogenesis has not been established. The objectives of this study were to identify bacteria present in pediatric urolithiasis and, using in vitro and in vivo models, to determine the relevance of calcium oxalate deposits during experimental pyelonephritis. Methods Pediatric kidney stones and urine were collected and both cultured and sequenced for bacteria. Bacterial adhesion to calcium oxalate was compared. Murine kidney calcium oxalate deposits were induced by intraperitoneal glyoxalate injection and kidneys were transurethrally inoculated with uropathogenic Escherichia coli to induce pyelonephritis Results E. coli of the family Enterobacteriaceae was identified in patients by calcium oxalate stone culture. Additionally Enterobacteriaceae DNA was sequenced from multiple calcium oxalate kidney stones. E. coli selectively aggregated on and around calcium oxalate monohydrate crystals. Mice inoculated with glyoxalate and uropathogenic E. coli had higher bacterial burdens, increased kidney calcium oxalate deposits and an increased kidney innate immune response compared to mice with only calcium oxalate deposits or only pyelonephritis. Conclusions In a murine model, the presence of calcium oxalate deposits increases pyelonephritis risk, likely due to preferential aggregation of bacteria on and around calcium oxalate crystals. When both calcium oxalate deposits and uropathogenic bacteria were present, calcium oxalate deposit number increased along with renal gene transcription of inner stone core matrix proteins increased. Therefore renal calcium oxalate deposits may be a modifiable risk factor for infections of the kidney and urinary tract. Furthermore, bacteria may be present in calcium oxalate deposits and potentially contribute to calcium oxalate renal disease.

Many adult women have resident urinary bacteria (urinary microbiome/microbiota). In adult women affected by urinary urgency incontinence (UUI), the etiologic and/or therapeutic role of the urinary microbiome/microbiota remains unknown. We hypothesized that microbiome/microbiota characteristics would relate to clinically relevant treatment response to UUI medication per os. Adult women initiating medication treatment orally for UUI and a comparator group of unaffected women were recruited in a tertiary care health-care system. All participants provided baseline clinical data and urine samples. Women with UUI were given 5 mg solifenacin, with potential dose escalation to 10 mg for inadequate UUI symptom control at 4 weeks. Additional data and urine samples were collected from women with UUI at 4 and 12 weeks. The samples were assessed using 16S ribosomal RNA (rRNA) gene sequencing and enhanced quantitative urine culturing. The primary outcome was treatment response as measured by the validated Patient Global Symptom Control (PGSC) questionnaire. Clinically relevant UUI symptom control was defined as a 4 or 5 score on the PGSC. Diversity and composition of the urinary microbiome/microbiota of women with and without UUI differed at baseline. Women with UUI had more bacteria and a more diverse microbiome/microbiota. The clinical response to solifenacin in UUI participants was related to baseline microbiome/microbiota, with responders more likely to have fewer bacteria and a less diverse community at baseline. Nonresponders had a more diverse community that often included bacteria not typically found in responders. Knowledge of an individual’s urinary microbiome/microbiota may help refine UUI treatment. Complementary tools, DNA sequencing, and expanded urine culture provide information about bacteria that appear to be related to UUI incontinence status and treatment response in this population of adult women.

The purpose of this study was to characterize the urinary microbiota in women who are planning treatment for urgency urinary incontinence and to describe clinical associations with urinary symptoms, urinary tract infection, and treatment outcomes.Catheterized urine samples were collected from multisite randomized trial participants who had no clinical evidence of urinary tract infection; 16S ribosomal RNA gene sequencing was used to dichotomize participants as either DNA sequence-positive or sequence-negative. Associations with demographics, urinary symptoms, urinary tract infection risk, and treatment outcomes were determined. In sequence-positive samples, microbiotas were characterized on the basis of their dominant microorganisms.More than one-half (51.1%; 93/182) of the participants' urine samples were sequence-positive. Sequence-positive participants were younger (55.8 vs 61.3 years old; P = .0007), had a higher body mass index (33.7 vs 30.1 kg/m(2); P = .0009), had a higher mean baseline daily urgency urinary incontinence episodes (5.7 vs 4.2 episodes; P.0001), responded better to treatment (decrease in urgency urinary incontinence episodes, -4.4 vs -3.3; P = .0013), and were less likely to experience urinary tract infection (9% vs 27%; P = .0011). In sequence-positive samples, 8 major bacterial clusters were identified; 7 clusters were dominated not only by a single genus, most commonly Lactobacillus (45%) or Gardnerella (17%), but also by other taxa (25%). The remaining cluster had no dominant genus (13%).DNA sequencing confirmed urinary bacterial DNA in many women with urgency urinary incontinence who had no signs of infection. Sequence status was associated with baseline urgency urinary incontinence episodes, treatment response, and posttreatment urinary tract infection risk.

Female urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described.We sought to study the cross-sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery.Preoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models.The majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P = .02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P = .04); and hormonal status (P.001). No associations were detected with stress urinary incontinence symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone-negative women.Women undergoing stress urinary incontinence surgery have detectable urinary microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms.

Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this study, we used 16S rRNA gene sequencing to classify bacterial DNA and expanded quantitative urine culture (EQUC) techniques to isolate live bacteria in urine collected by using a transurethral catheter from women with UUI and, in comparison, a cohort without UUI. For these cohorts, we demonstrated that the UUI and non-UUI urinary microbiomes differ by group based on both sequence and culture evidences. Compared to the non-UUI microbiome, sequencing experiments revealed that the UUI microbiome was composed of increased Gardnerella and decreased Lactobacillus . Nine genera ( Actinobaculum , Actinomyces , Aerococcus , Arthrobacter , Corynebacterium , Gardnerella , Oligella , Staphylococcus , and Streptococcus ) were more frequently cultured from the UUI cohort. Although Lactobacillus was isolated from both cohorts, distinctions existed at the species level, with Lactobacillus gasseri detected more frequently in the UUI cohort and Lactobacillus crispatus most frequently detected in controls. Combined, these data suggest that potentially important differences exist in the urinary microbiomes of women with and without UUI, which have strong implications in prevention, diagnosis, or treatment of UUI. IMPORTANCE New evidence indicates that the human urinary tract contains microbial communities; however, the role of these communities in urinary health remains to be elucidated. Urgency urinary incontinence (UUI) is a highly prevalent yet poorly understood urinary condition characterized by urgency, frequency, and urinary incontinence. Given the significant overlap of UUI symptoms with those of urinary tract infections, it is possible that UUI may have a microbial component. We compared the urinary microbiomes of women affected by UUI to those of a comparison group without UUI, using both high-throughput sequencing and extended culture techniques. We identified statistically significant differences in the frequency and abundance of bacteria present. These differences suggest a potential role for the urinary microbiome in female urinary health.

Background: Although many treatment modalities are available for Morton’s neuroma (MN), studies looking at the long-term effectiveness of most forms of treatment are scarce. The injection of MN with alcohol has gained popularity over the past 10 years with widespread media coverage. Many surgeons have anecdotally questioned the long-term effectiveness of this treatment. We reviewed a cohort of patients at an average 5-year follow-up to assess the medium-term results of alcohol injection. Methods: We used the modified Johnson score and visual analogue scales to assess 45 of the original cohort of patients with an average follow-up of 61 months (range, 33-73 months). Any complications from the procedure were also noted. Results: Our results indicated that by 5 years, 16 of 45 patients had undergone surgical treatment and a further 13 patients had return of symptoms. Only 29% (13/45) remained symptom free. The visual analog scale and modified Johnson scores showed statistically significant deterioration in patients’ symptoms at 5 years following alcohol injection. Conclusion: Injection with alcohol sclerosant for MN has been marketed as a definitive management option comparable to surgical excision. Our investigation illustrated that although short-term results are encouraging, alcohol injection does not offer permanent resolution of symptoms for most patients and can be associated with considerable morbidity. Our investigation provides the only long-term data for alcohol injection treatment of MN. Level of Evidence: Level II, prospective case series.

Scintillation camera renography with Tc-DTPA was performed before and after pyeloplasty on 16 kidneys with urographic signs of pelviurctcric obstruction causing hydronephrosis. Regional parenchymal renograms were generated, and the passage of Tc-DTPA through the parenchyma was measured and correlated to the change in separate glomerular filtration rate. Preoperative parenchymal passage of DTPA was significantly slower (p = 0.02) in kidneys with improved glomerular filtration rate after pyeloplasty than in those without such improvement. Postoperative passage of DTPA in parenchyma was almost identical with that in a reference series. This method seems to be clinically useful for evaluating cases of hydronephrosis and for predicting the outcome of pyeloplasty.

The most recent wave of interviews in a longitudinal study spanned the terrorist attacks of September 11, 2001. This unintended "natural experiment" allows examination of effects of traumatic events in ways impossible in studies conducted solely after the event and in populations not previously studied.Participants were 610 members of the randomly selected Children in the Community cohort studied longitudinally for over 25 years and between ages 27 and 38 at the time of the current in-home interviews. Symptoms of generalized anxiety, post-traumatic stress disorder, panic disorder, agoraphobia, dissociation, and depression were assessed with an adaptation of the Structured Clinical Interview for Diagnosis. Changes in self-reported symptoms from an assessment 10 years earlier were related to the date of interview between 7/2001 and 12/2003 by polynomial regression methods, including demographic and design controls. Diagnoses based on clinical follow-up were also examined.In contrast to other data on this cohort where timing effects were absent, levels of symptoms were related to time of interview. The months following 9/11/2001 and the two anniversary periods in 2002 and 2003 showed significant elevation in anxiety symptoms (t = 2.50, df = 608, P = 0.013) with some evidence of elevated anxiety disorder as well (Fisher's exact test P = 0.096). Similar patterns were seen for specific anxiety and depressive symptom groups. Effects of religious participation, patriotism, having offspring, and media exposure on anxiety symptoms tended to differ by season, but the effect of community involvement did not. Proximity to New York City was not significantly related to symptoms.Study findings suggest that young Americans showed symptomatic and, possibly, diagnostic anxiety reactions to the events of 9/11 that persisted in response to heightened awareness of ongoing threat during anniversary periods.

In a recent Scottish Appeal Court opinion ( Kim Louise Scarsbrook or Galbraith v. Her Majesty's Advocate, 2001) it was successfully argued by the appellant that her conviction of murder was unsound inter-alia on the basis of overly restrictive pre-existing definitions of diminished responsibility in Scottish law resulting in unduly narrow directions being given by the trial judge to the jury in her case. We felt it timely to present a revised overview of the defence of diminished responsibility in Scotland and to consider the issues surrounding its applicability in cases of clinical depression. The psychiatric literature regarding depression and homicide is reviewed.

This retrospective case note review describes the demographic, forensic and psychiatric backgrounds of 14 in-patient suicides in a maximum secure hospital. The majority were schizophrenic with chronic treatment-resistant illnesses, who had committed proportionally more violent offences, had a history of serious self-injury but no recognized clear depressive episodes. This profile is markedly different from that reported in general psychiatric inpatients, out-patients and suicides in prison, but is similar to that described in a maximum secure hospital in the United States and in long-stay patients in Canada. Many of the patients had continued to experience significantly subjective distress over many years. The clinical relevance of this series is discussed in the context of the assessment of suicidal intent in psychotic patients. We speculate that the decrease in in-patient suicides in the State Hospital may be due to a less restrictive ward milieu, increased staff/patient ratios, or the introduction of Clozapine.

The effect of drug-induced Parkinsonism and of the topography of the dyskinetic movements on the psychological consequences of tardive dyskinesia was assessed in 20 schizophrenic subjects and 20 non-dyskinetic schizophrenic controls matched for age, sex, the presence of anticholinergic medication, and the presence and severity of drug-induced Parkinsonism. Limb–truncal subscale scores but not orofacial scores had a significant correlation with cognitive impairment and with negative symptoms. Drug-induced Parkinsonism was found to be a powerful confounding variable.

Criticism of the Papanicolaou smear in the lay press and recent federal legislation regulating cytology laboratories indicate a need to reappraise cervical cancer screening programs. This study directly compares three potential screening tests, used alone or in combination. A total of 1012 women aged 18 to 35 years were screened by cytologic testing, cervicography, and hybridization for human papillomavirus deoxyribonucleic acid, with discrepancies being referred by the last two authors. After findings from the entire lower genital tract were combined, 116 women (11.5%) showed definite clinical abnormalities (either exophytic vulvovaginal condylomas or cervical squamous intraepithelial lesions). Another 72 (7.2%) had positive Southern blot hybridizations without accompanying viral expression, yielding a cumulative frequency for established disease or latent infection of 18.6%. When associated vulvovaginal condylomas are disregarded, final groupings with regard to cervical pathologic classification were: 23 high-grade and 71 low-grade squamous intraepithelial lesions, 164 cases of equivocal atypia (34 of which had detectable human papillomavirus deoxyribonucleic acid), and 754 cases with negative results (38 of which had detectable human papillomavirus deoxyribonucleic acid). Cervical screening tests were compared principally by plotting increasingly liberal recall criteria onto receiver operating characteristic curves (i.e., graphs of true-positive results on the Y axis versus false-positive results on the X axis). Used individually, each screening test was valid, but none was substantially better than the others. No matter how liberal the recall criteria, no single test was able to detect all of the 23 definite precursors in this sample. Applying conventional recall criteria (i.e., high- or low-grade lesion suspected), cytologic testing alone detected 12 high-grade squamous intraepithelial lesions (52.2%), at a cost of having to perform colposcopy in 8.7% of the sample. Combining all three tests and setting the end point as just a high-positive result by at least one test, 19 high-grade squamous intraepithelial lesions (83%) were detected, with a recall of 7%. Optimal test performance (96% sensitivity, 4% recall) would have been attained by recalling all patients with high-grade cytologic results or positive cervicography results, plus any patients with low-grade morphologic atypia in which hybridization detected an oncogenic human papillomavirus type. Our conclusions are as follows: (1) Cytologic detection rates are markedly improved by a second or third test; (2) increased screening costs could be offset by not recalling patients with minor lesions with no apparent potential for progression.

We report our experience of myocardial scintigraphy with 201thallium (201Tl) in 52 children, aged 4 days to 18 years, in which 80 studies were made primarily to demonstrate or exclude impaired myocardial perfusion. For analysis, the patients were divided into the following eight groups: group I, coronary artery malformations (five patients); group II, Kawasaki's syndrome (six patients); group III, arterial switch operation (seven patients); group IV, dilated cardiomyopathy (18 patients); group V, hypertrophic cardiomyopathy (four patients); group VI, myocardial dysfunction after surgery for congenital heart disease (five patients); group VII, pulmonary atresia (three patients); and group VIII, miscellaneous (four patients). Myocardial scintigraphy was performed with a planar or tomographic technique at rest or after exercise (four patients). Isotope-uptake defects, indicating impaired myocardial perfusion, were present in 14 patients, including small infants. Defects were seen in all groups except those with hypertrophic cardiomyopathy and pulmonary atresia. The absence of such defects in several of the patients with Kawasaki's syndrome was particularly valuable as it made coronary angiography unnecessary. In the other groups of patients myocardial scintigraphy was a valuable adjunct to other investigations.

Splenectomy was performed in 7 patients on regular hemodialysis treatment who had disabling anemia. All patients had a short 51Cr red cell survival time and an increased splenic uptake of red cells verified by external counting and computer-aided scintigraphy. The need for blood-transfusions was eliminated in all except one. In all patients the hemoglobin concentration rose after splenectomy. This was probably an effect of a reduced plasma volume and the removal of a large pool of non-circulating red cells. No consistent changes in the red blood cell survival time or the red cell volume were observed. The white cell and the platelet counts in the blood rose to twice the preoperative value. No adverse effect of the splenectomy was observed.

1. 14C-L-histidine was given i.v. to one normal subject and two patients with chronic myelocytic leukaemia. Urinary excretion of histamine and two of its metabolites methylhistamine and methylimidazoleacetic acid, total as well as 14C-labelled, was measured, as well as blood 14C-histamine. In addition the total urinary and pulmonary elimination of 14C was followed. 2. Total 14C elimination was high during the first days, then declined slowly except for a plateau at the 10th-14th day in the two patients. There was a measurable elimination even after some months. 3. 14C-histamine appeared in the blood of the leukaemic patient, whereas in the normal subjects the values were hardly measurable. 4. The leukaemic patients excreted much more of the two 14C-labelled histamine metabolites than the normal subject. The difference in excretion of the 14C-labelled metabolites was largest around the 12th day after the infusion of 14C-L-histidine. 5. The results indicate that the leukaemic patients formed at least 20 times more histamine daily than the normal subject.

26 patients were studied to assess the association between iron deficiency and akathisia. 13 akathisic patients were matched with 13 non-akathisic controls. Serum iron and percentage saturation were significantly decreased in the akathisic group, whereas total iron-binding capacity was significantly increased. A negative correlation between serum iron and akathisia rating (r S = -0·42) was also found.

Some ventilatory and circulatory parameters were studied in 17 very obese patients before and after weight reduction following jejunoileal bypass. A low vital capacity and signs of impaired lung function with intrapulmonary shunting, increased alveolar-arterial Po2 difference and low Pao2 were found. Although the spirometric values improved significantly after weight reduction, the ventilatory disturbance persisted. A normal response to inhalation of CO2 was seen. The total blood volume was high and did not change after weight reduction. However, if calculated as blood volume per kg body weight, the values were lower than normal, and they increased as a consequence of weight reduction. Cardiac output was slightly lower than normal in relation to oxygen consumption. Total peripheral resistance was normal. Arterial blood pressure, which was in the high normal range preoperatively, decreased significantly after weight reduction. Total doses of intravenous anaesthetic agents and muscle relaxants were the same as for patients of normal weight. The importance of preoperative evaluation and of respiratory care of obese patients undergoing elective surgery is stressed.

Myocardial 201Tl emission computed tomography was performed on 25 normal subjects and 27 patients with angiographically significant coronary artery disease. A semi-automatic computer program was designed to define the left ventricular myocardial volume in all short axis sections. Within this volume the relative mean myocardial pixel count was calculated. This parameter was found to separate the 2 patient groups with a sensitivity of at least 81% at a specificity of 100%.

A young Thai immigrant presented with a mass in the left hip, pain, and difficulty in ambulation. At operation, the mass was found to be a group of cysts containing bizarre, fungus-like structures like those first described in Africa and recently in St. Louis. The cause of this condition may be iatrogenic, resulting from a peculiar reaction to intramuscular injection.

Total and separate renal function, renal parenchymal thickness and dilatation of the upper urinary tract were studied in 40 patients preoperatively and 24 to 67 months after urinary diversion, using 51Cr-EDTA clearance test, scintillation camera renography and urography. In ten patients a continent caecal reservoir was used for diversion. In the other patients, an ileal or a colonic conduit (15 patients with each method) was used, one ureter being implanted with an anti-reflux method and the other with direct technique. Renal function following urinary diversion showed little or no deterioration in most patients. The functional outcome was not related to the method of diversion or, in the conduit groups, to the mode of ureteral implantation. Serum creatinine tests and urography were not adequate for determining loss of renal function. Radionuclide studies proved to be valuable for assessing renal function after urinary diversion.

To evaluate the influence of conduit type (ileal or colonic) and method of ureterointestinal anastomosis (refluxing or antirefluxing) on renal function in patients with urinary diversion, a prospective randomized trial was conducted in 1977-1984. During these years urinary diversion via a continent caecal reservoir emerged as an alternative to conduit diversion at our hospital, and these patients with continent reservoir were also included in the study. Total and separate glomerular filtration rate (GFR) were measured, the latter with scintillation camera renography, preoperatively and at follow-up in 70 patients. Measurements 2-10 years postoperatively showed slight to moderate decrease of GFR in all groups, with no significant difference between values according to conduit type or caecal reservoir or between refluxing and antirefluxing ureterointestinal anastomosis. Almost all of the anastomotic strictures involved the ureter that had been brought beneath the sigmoid mesentery, indicating that ischemia secondary to extensive ureteral mobilization is a likely cause of stricture in these cases.

Most patients with chronic myelocytic leukaemia (12 cases in this material) excreted much larger quantities (up to twenty times normal) of histamine metabolites in the urine than healthy individuals and patients with other forms of leukaemia. This indicated an increased rate of formation of histamine in chronic myelocytic leukaemia. The site and mechanism of this increased histamine formation is discussed in relation the metabolic pattern found.