Fine structure and molecular characterization of two new parabasalid species that naturally colonize laboratory mice, Tritrichomonas musculus and Tritrichomonas casperi.

Tritrichomonas muris is a common flagellated protist isolated from the cecum of wild rodents. This commensal protist has been shown previously to alter immune phenotypes in laboratory mice. Other trichomonads, referred to as Tritrichomonas musculis and Tritrichomonas rainier, also naturally colonize laboratory mice and cause immune alterations. This report formally describes two new trichomonads, Tritrichomonas musculus n. sp., and Tritrichomonas casperi n. sp., at the ultrastructural and molecular level. These two protists were isolated from laboratory mice and were differentiated by their size and the structure of their undulating membrane and posterior flagellum. Analysis at the 18S rRNA and trans-ITS genetic loci supported their designation as distinct species, related to T. muris. To assess the true extent of parabasalid diversity infecting laboratory mice, 135 mice bred at the National Institutes of Health (NIH) were screened using pan-parabasalid primers that amplify the trans-ITS region. Forty-four percent of mice were positive for parabasalids, encompassing a total of eight distinct sequence types. Tritrichomonas casperi and Trichomitus-like protists were dominant. T. musculus and T. rainier were also detected, but T. muris was not. Our work establishes a previously underappreciated diversity of commensal trichomonad flagellates that naturally colonize the enteric cavity of laboratory mice.

Esophageal Dysmotility Is Associated With Disease Severity in Eosinophilic Esophagitis.

BACKGROUND & AIMS: An association of eosinophilic esophagitis (EoE) with esophageal dysmotility has been described, however, the related mechanism remains unclear. We aimed to evaluate clinical and physiologic characteristics, including esophageal distensibility, associated with secondary peristalsis in patients with EoE. METHODS: A total of 199 consecutive adult patients with EoE (age, 18-78 y; 32% female) who completed a 16-cm functional luminal imaging probe (FLIP) during endoscopy were evaluated in a cross-sectional study. FLIP panometry contractile response (CR) patterns were classified as normal CR or borderline CR if antegrade contractions were present, and abnormal CRs included impaired/disordered CR, absent CR, or spastic-reactive CR. The distensibility plateau of the esophageal body and esophagogastric junction distensibility was measured with FLIP. RESULTS: FLIP CR patterns included 68 (34%) normal CR, 65 (33%) borderline CR, 44 (22%) impaired/disordered CR, 16 (8%) absent CR, and 6 (3%) spastic-reactive CR. Compared with normal CRs, abnormal CRs more frequently had reduced esophageal distensibility (distensibility plateau <17 mm in 56% vs 32%), greater total EoE reference scores (median, 5; interquartile range [IQR], 3-6 vs median, 4; IQR, 3-5) with more severe ring scores, and a greater duration of symptoms (median, 10 y; IQR, 4-23 y vs median, 7 y; IQR, 3-15 y). Mucosal eosinophil density, however, was similar between abnormal CRs and normal CRs (median, 34 eosinophils/high-power field [hpf]; IQR, 14-60 eosinophils/hpf vs median, 25 eosinophils/hpf; IQR, 5-50 eosinophils/hpf). CONCLUSIONS: Although normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.

Diagnostic accuracy of sentinel node identification is maintained with the addition of local lidocaine and subareolar radioactive colloid injection.

Preoperative sentinel node localization (SNL) using a subareolar injection of radiotracer technetium-99m-sulfur colloid (Tc(99m)SC) is associated with significant pain. Lidocaine use during SNL is not widely adopted partly due to a concern that it can obscure sentinel node identification and reduce its diagnostic accuracy. We prospectively identified women with a biopsy-proven infiltrating breast cancer who were awaiting a SNL. The women completed the McGill pain questionnaire, Visual Analog Scale, and Wong-Baker FACES Pain Rating Scale prior to and following SNL. We identified a retrospective cohort of women with similar demographic and tumor characteristics who did not receive lidocaine before SNL. We compared sentinel lymph node identification rates in the two cohorts. We used Wilcoxon rank sum tests to compare continuous measures and Fisher's exact test for categorical measures. Between January 2011 to July 2012, 110 women consented, and 105 were eligible for and received lidocaine prior to Tc(99m)SC injection. The post-lidocaine identification rate of SNL was 95 % with Tc(99m)SC, and 100 % with the addition of intraoperative methylene blue dye/saline. Pain range prior to and following the SNL was unchanged (P = 0.703). We identified 187 women from 2005 to 2009 who did not receive lidocaine during preoperative SNL. There was no significant difference in the success rate of SNL, with or without lidocaine (P = 0.194). The administration of lidocaine during SNL prevents pain related to isotope injection while maintaining the success rate. We have changed our practice at our center to incorporate the use of lidocaine during all SNL.

Using a Nationwide Virtual Radiology Student Interest Group to Expand Medical Students' General Awareness, Drive Greater Interest, and Achieve Uniform National Messaging in the Field of Radiology.

RATIONALE AND OBJECTIVES: Many medical schools offer minimal exposure to radiology, leading to a decreased understanding of the field and negative perceptions among medical students. The purpose of this study was to examine the effects of a radiology intensive series piloted by a novel virtual radiology interest group. Specifically, we were interested in how radiologists and medical educators can expand students' general awareness, drive greater interest in the field, and achieve more uniform national messaging across all trainees. MATERIALS AND METHODS: We launched a national/international interest group called Radiology Student Interest Group (RadSIG) and piloted the RadSIG Intensive, a series of five events aimed at increasing awareness and dispelling misconceptions among preclinical medical students. Validated pre-intensive and post-intensive surveys were used to ascertain the students' baseline and changed perspectives, respectively. A separate faculty survey was also distributed to understand how they perceived our events. Statistical analysis was carried out on the collected data to identify trends and assess the utility of our programming. RESULTS: 205 students completed the pre-intensive survey, and 61 students completed the post-intensive survey. Of the pre-intensive survey respondents, 51.7% (106/205) indicated that they had a limited understanding of what a career in radiology entails. Of those who completed the entire RadSIG Intensive, average 5-point Likert scale scores for understanding of a radiology career rose from 3.30 to 4.38 respectively pre- to post-completion. A Wilcoxon signed-rank test revealed that this difference was statistically significant (Z=-5.95, p<0.001), and that the RadSIG Intensive significantly improved perceptions of radiologists across every single question measured, except for perception of long hours worked (Z=-0.20, p=0.841). The results also showed increased student comfort in reaching out to radiology attendings (Z=-4.30, p<0.001) and residents (Z=-5.12, p<0.001). Faculty survey results indicated positive perceptions of the series. CONCLUSION: Our results show that the RadSIG Intensive was effective in increasing students' understanding of radiology as a field and a potential career. Online outreach can also lower the resistance and improve student comfort in reaching out for mentorship, which may provide a new pathway to reach underserved students with a unifying message. By furthering a platform based on voluntary and supplemental resources, we see a far greater potential of impacting the perception and known role of the imager in patient care among our next generation of physicians.

Measuring esophageal compliance using functional lumen imaging probe to assess remodeling in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is associated with fibrostenotic remodeling that can be objectively assessed using the functional lumen imaging probe (FLIP). This is typically done using a metric called distensibility plateau (DP). We aimed to describe a novel measure of compliance of the esophageal body and evaluate the associated clinical characteristics in EoE. METHODS: One hundred seventy-one adult patients with EoE (mean (SD) age 38 (12) years), 31% female and 35 healthy, asymptomatic controls who completed 16-cm functional luminal imaging probe (FLIP) during endoscopy, were evaluated in a cross-sectional study. The esophageal body DP and compliance were measured using a customized analysis program, with compliance calculated as (Δ esophageal body volume)/(Δ pressure) between two FLIP-filled volumes. RESULTS: In controls, the median (5-95th percentile) DP was 19.8 mm (17.9-21) and esophageal body compliance was 0.37 ml/mmHg (0.18-1.1), which was greater than in EoE (DP 19 (11-21)), compliance 0.19 (0.02-0.71), p-values <0.001. Among EoE patients, 70 (41%) had normal compliance (>0.2 ml/mmHg) and normal DP (>17 mm); 11 (6%) had normal compliance and reduced DP; 34 (20%) had reduced compliance and normal DP; and 56 (33%) had reduced compliance and reduce DP. Patients with both reduced compliance and DP had the greatest proportion of severe rings (61% with EREFS score 2-3) and stricture (100%). CONCLUSION: FLIP provides an objective evaluation of biomechanical properties of the esophageal wall that appears enhanced by complementary application of metrics of DP and esophageal body compliance.

Potential Prognostic Value of Native T1 in Pulmonary Hypertension Patients.

Native T1, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE) characterize myocardial tissue and relate to patient prognosis in a variety of diseases, including pulmonary hypertension. The purpose of this study was to evaluate if left ventricle (LV) fibrosis measurements have prognostic value for cardiac outcomes in pulmonary hypertension subgroups. 54 patients with suspected pulmonary hypertension underwent right-heart catheterization and were classified into pulmonary hypertension subgroups: pre-capillary component (PreCompPH) and isolated post-capillary (IpcPH). Cardiac magnetic resonance imaging (MRI) scans were performed with the acquisition of balanced cine steady-state free precession, native T1, and LGE pulse sequences to measure cardiac volumes and myocardial fibrosis. Associations between cardiac events and cardiac MRI measurements were analyzed within PreCompPH and IpcPH patients. IpcPH: LV native T1 was higher in patients who experienced a cardiac event within two years vs. those who did not. In patients with LV native T1 > 1050 ms, the rate of cardiac events was higher. ECV and quantitative LGE did not differ between groups. PreCompPH: native T1, ECV, and quantitative/qualitative LGE did not differ between patients who experienced a cardiac event within two years vs. those who did not. LV native T1 may have potential value for forecasting cardiac events in IpcPH, but not in PreCompPH, patients.

Ultrastructural identification and molecular characterization of two new parabasalid species that naturally colonize laboratory mice, Tritrichomonas musculus and Tritrichomonas casperi.

Tritrichomonas muris is a flagellated protist isolated from the cecum of wild mice in the Czech Republic. This commensal protist has been shown previously to alter immune phenotypes in laboratory mice. Other trichomonads, previously referred to as Tritrichomonas musculis and Tritrichomonas rainier , also naturally colonize laboratory mice and cause immune alterations. This report formally describes two new trichomonads, Tritrichomonas musculus n. sp., and Tritrichomonas casperi n. sp., at the ultrastructural and molecular level. These two protists were isolated from laboratory mice, and were differentiated by their size and the structure of their undulating membrane and posterior flagellum. Analysis at the 18S rRNA and trans- ITS genetic loci supported their designation as distinct species, related to T. muris . To further assess the true extent of parabasalid diversity infecting laboratory mice, 135 mice were screened at the NIH using pan-parabasalid primers that amplify the trans- ITS region. Forty-four percent of mice were positive for parabasalids, encompassing a total of 8 distinct sequence types. Tritrichomonas casperi and Trichomitus- like protists were dominant. T. musculus and T. rainier were also detected, but T. muris was not. Our work establishes a previously underappreciated diversity of commensal trichomonad protists that naturally colonize the enteric cavity of laboratory mice.

Gene Methylation and Cytological Atypia in Random Fine-Needle Aspirates for Assessment of Breast Cancer Risk.

Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density and obtained random fine-needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole-genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (P < 0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number, and body mass index. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus, CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. Cancer Prev Res; 9(8); 673-82. ©2016 AACR.