ErbB2 receptor tyrosine kinase plays a role in neuregulin signaling and is expressed in the developing nervous system. We genetically rescued the cardiac defect of erbB2 null mutant embryos, which otherwise died at E11. These rescued erbB2 mutant mice die at birth and display a severe loss of both motor and sensory neurons. Motor and sensory axons are severely defasciculated and aberrantly projected within their final target tissues. Schwann cells are completely absent in the peripheral nerves. Schwann cell precursors are present within the DRG and proliferate normally, but their ability to migrate is decreased. Acetylcholine receptors cluster within the central band of the mutant diaphragm muscle. However, these clusters are dispersed and morphologically different from those in control muscle. Our results reveal an important role for erbB2 during normal peripheral nervous system development.

The prevalence rates of Mycoplasma genitalium infections and coinfections with other sexually transmitted organisms and the frequency of a macrolide antibiotic resistance phenotype were determined in urogenital specimens collected from female and male subjects enrolled in a multicenter clinical study in the United States. Specimens from 946 subjects seeking care from seven geographically diverse clinical sites were tested for M. genitalium and for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Sequencing was used to assess macrolide antibiotic resistance among M. genitalium-positive subjects. M. genitalium prevalence rates were 16.1% for females and 17.2% for males. Significant risk factors for M. genitalium infections were black race, younger age, non-Hispanic ethnicity, and female symptomatic status. Female M. genitalium infections were significantly more prevalent than C. trachomatis and N. gonorrhoeae infections, while the M. genitalium infection rate in males was significantly higher than the N. gonorrhoeae and T. vaginalis infection rates. The macrolide-resistant phenotype was found in 50.8% of females and 42% of males. These results show a high prevalence of M. genitalium single infections, a lower prevalence of coinfections with other sexually transmitted organisms, and high rates of macrolide antibiotic resistance in a diverse sample of subjects seeking care across a wide geographic area of the United States.

Trichomoniasis is a common sexually transmitted disease associated with preterm birth, low birth weight, and increased susceptibility to infection with other pathogenic sexually transmitted microorganisms. Nucleic acid amplification tests for Trichomonas vaginalis have improved sensitivity for detecting infected individuals compared to existing culture-based methods. This prospective, multicenter U.S. clinical trial evaluated the performance of the automated Aptima T. vaginalis assay for detecting T. vaginalis in 1,025 asymptomatic and symptomatic women. Vaginal swab, endocervical swab, ThinPrep PreservCyt, and urine specimens were collected. Subject infection status was determined by wet-mount microscopy and culture. Aptima T. vaginalis assay performance was determined for each specimen type by comparison to subject infection status. Of 933 subjects analyzed, 59.9% were symptomatic. Aptima T. vaginalis clinical sensitivity and specificity were, respectively, 100% and 99.0% for vaginal swabs, 100% and 99.4% for endocervical swabs, 100% and 99.6% in ThinPrep samples, and 95.2% and 98.9% in urine specimens. Aptima T. vaginalis performance levels were similar in asymptomatic and symptomatic subjects. This study validates the clinical performance of the Aptima T. vaginalis assay for screening asymptomatic and symptomatic women for T. vaginalis infection.Trichomoniasis, a common sexually transmitted disease (STD) caused by the protozoan Trichomonas vaginalis, affects approximately 180 million persons per year worldwide, making it the most common nonviral STD agent in the world. An estimated 7.4 million new cases occur annually in the United States (1), and the disease has an overall prevalence of 3.1% (24). Both women and men can be infected, although symptoms are more common in women. Symptomatic women have a diffuse, malodorous, yellow-green vaginal discharge with vulvar irritation which may be confused with bacterial vaginosis. Infected men may temporarily have urethral irritation, mild discharge, or slight burning after urination or ejaculation (5). Many infections do not produce symptoms and when left untreated may lead to preterm birth, low birth weight, and pelvic inflammatory disease (5). T. vaginalis infection also increases susceptibility to infection with HIV (14,22,23). Effective and inexpensive antibiotic therapy for T. vaginalis infection is readily available, and detection and treatment of T. vaginalis in symptomatic or asymptomatic women with a high risk of STD are important to prevent disease acquisition, transmission, and associated complications.Currently, the gold standard for the diagnosis of T. vaginalis infection is culture; however, the sensitivity of commercially available culture has been reported to be 75% to 89% compared to amplified methods (13,20). Tests with improved sensitivity are needed to diagnose this prevalent STD. The Aptima Trichomonas vaginalis assay, an FDA-cleared, fully automated nucleic acid amplification test, has demonstrated high sensitivity and specificity compared to c...

dUrinary tract infections (UTIs) and sexually transmitted infections (STIs) are commonly diagnosed in emergency departments (EDs). Distinguishing between these syndromes can be challenging because of overlapping symptomatology and because both are associated with abnormalities on urinalysis (UA). We conducted a 2-month observational cohort study to determine the accuracy of clinical diagnoses of UTI and STI in adult women presenting with genitourinary (GU) symptoms or diagnosed with GU infections at an urban academic ED. For all urine specimens, UA, culture, and nucleic acid amplification testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis were performed. Of 264 women studied, providers diagnosed 175 (66%) with UTIs, 100 (57%) of whom were treated without performing a urine culture during routine care. Combining routine care and study-performed urine cultures, only 84 (48%) of these women had a positive urine culture. Sixty (23%) of the 264 women studied had one or more positive STI tests, 22 (37%) of whom did not receive treatment for an STI within 7 days of the ED visit. Fourteen (64%) of these 22 women were diagnosed with a UTI instead of an STI. Ninety-two percent of the women studied had an abnormal UA finding (greater-than-trace leukocyte esterase level, positive nitrite test result, or pyuria). The positive and negative predictive values of an abnormal UA finding were 41 and 76%, respectively. In this population, empirical therapy for UTI without urine culture testing and overdiagnosis of UTI were common and associated with unnecessary antibiotic exposure and missed STI diagnoses. Abnormal UA findings were common and not predictive of positive urine cultures. U rinary tract infections (UTIs) are diagnosed in over 1 million emergency department (ED) visits each year in the United States (1). Sexually transmitted infections (STIs) are also commonly diagnosed in the ED. The Centers for Disease Control and Prevention estimates that nearly 20 million new STIs occur annually, many of which go undiagnosed and unreported (2). Lower UTIs and many STIs have overlapping symptomatology, including the traditional UTI symptoms of dysuria, frequency, and urgency. In addition, abnormal urinalysis (UA) findings of positive leukocyte esterase and pyuria are common in both UTIs and STIs (3-6). Thus, distinguishing between these infections can be challenging.Previous studies in ED settings evaluating women diagnosed with UTIs have demonstrated that only about 50% will have a positive urine culture and 10 to 50% will have an STI (5, 7-10). These studies suggest that UTIs are overdiagnosed and STIs are underdiagnosed in the ED. However, previous studies in the ED setting have several limitations. First, some studies (5, 8) used a cutoff of Ն10 4 CFU/ml of a single uropathogen to define a positive urine culture, which may be inappropriately high for some organisms and populations (11, 12). Thus, the incidence of UTI may have been underestimated. Second, some studies may have underdiagnosed STIs b...

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