Tissue factor as a novel diagnostic target for early detection of ovarian cancer using ultrasound microbubbles.

INTRODUCTION: Ovarian cancer (OC) is the deadliest gynecologic malignancy, with an overall 5-year survival rate of less than 30%. The existing paradigm for OC detection involves a serum marker, CA125, and ultrasound examination, neither of which is sufficiently specific for OC. This study addresses this deficiency through the use of a targeted ultrasound microbubble directed against tissue factor (TF). METHODS: TF expression was examined in both OC cell lines and patient-derived tumor samples via western blotting and IHC. In vivo microbubble ultrasound imaging was analyzed using high grade serous ovarian carcinoma orthotopic mouse models. RESULTS: While TF expression has previously been described on angiogenic, tumor-associated vascular endothelial cells (VECs) of several tumor types, this is first study to show TF expression on both murine and patient-derived ovarian tumor-associated VECs. Biotinylated anti-TF antibody was conjugated to streptavidin-coated microbubbles and in vitro binding assays were performed to assess the binding efficacy of these agents. TF-targeted microbubbles successfully bound to TF-expressing OC cells, as well as an in vitro model of angiogenic endothelium. In vivo, these microbubbles bound to the tumor-associated VECs of a clinically relevant orthotopic OC mouse model. CONCLUSION: Development of a TF-targeted microbubble capable of successfully detecting ovarian tumor neovasculature could have significant implications towards increasing the number of early-stage OC diagnoses. This preclinical study shows potential for translation to clinical use, which could ultimately help increase the number of early OC detections and decrease the mortality associated with this disease.

Development and assessment of an integrated anatomy mobile app.

Curricular hours for anatomical sub-disciplines (gross anatomy, embryology, histology, and neuroanatomy) continue to decline, while medical schools are simultaneously transitioning to systems-based, vertically integrated curricula. This requires students to learn and integrate all basic science content for a learning block prior to the summative assessment. Currently, no educational technology resource exists that integrates the four anatomical sub-disciplines into a single resource to supplement integrated curricula. The objective of this study was to assess a novel integrated anatomical sciences mobile app for medical students. The 4natomy mobile app was developed to integrate the four sub-disciplines for a single topic, the spinal cord. The app was distributed to first-year medical students during the neurological disorders learning. Following the learning block, assessment of the student acceptance and experience with the app was conducted through a technology acceptance model (TAM) framework survey. The results indicated that students found the app to be useful (p < 0.001) and easy to use (p < 0.05), predicting continued future usage of the app. Students requested expanded anatomy content for the entire learning block, as well as more clinical correlations, videos, and animations. The integrated anatomy mobile app developed in this study was useful and easy to use, indicating continued use within an integrated medical curriculum. This was the first study to utilize the TAM as a conceptual framework for technology assessment in medical education, suggesting that future studies that develop new technologies should adapt the TAM for user testing.

Histologic Investigation of the Salpingopharyngeus.

PURPOSE: The purpose of this study was to characterize the histologic contents of the salpingopharyngeal fold. The primary objective was to observe the presence of salpingopharyngeus (SP) muscle fibers, particularly at the section near the muscle origin at the torus tubarius (TT). METHOD: Histologic samples of the salpingopharyngeal fold from 10 cadavers (six females and four males) were analyzed. Following a head bisection, a tissue sample measuring 5 mm in length along the course of the salpingopharyngeal fold was collected from one side (i.e., right or left). The tissue sample was taken from the estimated base of the TT to a point 5 mm inferiorly. Slides were prepared using a standard histological approach and basic pathological staining and analyzed via bright-field microscopy. RESULTS: Skeletal muscle fibers were identified in eight of the 10 tissue blocks of the salpingopharyngeal fold, with dense connective tissue identified in the remaining two tissue blocks. Glandular material was also identified in all 10 tissue blocks. CONCLUSIONS: Skeletal muscle fibers and/or dense connective tissue can be consistently identified in the section of the salpingopharyngeal fold near the TT. Glandular material is also consistently present in this same region of the salpingopharyngeal fold. These findings are discussed in relation to possible functional roles of the salpingopharyngeal fold contents, including the SP muscle.

A Cadaveric and Magnetic Resonance Imaging Investigation of the Salpingopharyngeus.

Purpose The aim of the study was to update our information regarding the salpingopharyngeus (SP) muscle using cadaveric and in vivo magnetic resonance imaging (MRI) data. Primary objectives were to (a) observe the presence/absence of the muscle and (b) quantify and describe its dimensions and course. Method SP specimens from 19 cadavers (10 women, nine men) were analyzed. Following head bisection, measurements of SP, including width of the cartilaginous attachment (CW) and width of the superior muscle base (SMW), were taken before and after removal of the overlying mucosa. In addition, SP was analyzed in 15 healthy subjects (eight men, seven women) using high-resolution three-dimensional MRI data. CW and SMW measures were replicated in the paraxial MRI view. Results The presence of the salpingopharyngeal fold and muscle was confirmed bilaterally in all cadaveric and living subjects. Following mucosa removal, mean cadaveric CW and SMW measurements were 5.6 and 3.8 mm, respectively. Mean in vivo CW and SMW were 6.1 and 3.7 mm, respectively. Results from the hierarchical regression analyses revealed that, in both cadaveric and living groups, SMW is dependent on the relationship between age and body weight, after controlling for sex. Conclusions The salpingopharyngeal fold and SP muscle are always present bilaterally and can be quantified at the superior origin using both cadaveric and in vivo three-dimensional MRI data. Though both the superior origin and inferior course of SP are highly variable, the size of the SP muscle is dependent on characteristics known to affect muscle fibers, such as the relationship between age and body weight. Given the consistent and quantifiable presence of the SP muscle, its potential role in velopharyngeal function for speech and swallowing is reconsidered. Supplemental Material https://doi.org/10.23641/asha.14347859.

Contracted Extravelar Segments of the Levator Veli Palatini Muscle: A Magnetic Resonance Imaging Morphometric Study.

OBJECTIVES: To provide detailed descriptions of contraction-induced morphometric changes in the extravelar segments of the levator veli palatini (LVP) muscle using 3-dimensional (3-D) magnetic resonance imaging (MRI). DESIGN: Three-dimensional MRI data were acquired at rest and during "silent /i/" from 4 singers. During silent /i/, participants voluntarily sustained velar elevation while breathing orally for the entire scan time. Focusing on the extravelar segments, LVP length, angle of the muscle origin, and cross-sectional area (CSA), measurements were obtained and compared between tasks. RESULTS: Three of the 4 participants exhibited the expected patterns of change following concentric contraction of the LVP muscle. Consistent changes from the resting to the contracted state included reductions in LVP length by 13.5% and angle of the muscle origin by 9.8%, as well as increases in CSAs by 22.1%, on average. CONCLUSIONS: This study presented high-resolution data of the LVP muscle behavior with the first in vivo 3-D measurements of the contracted LVP muscle, which can be useful for the validation of computational models that aim at describing biomechanical properties of the LVP muscle in future research. The active behavior of the extravelar LVP muscle also provides some insight on optimal LVP muscle geometry to consider during cleft palate repair.

A Novel Approach to Gross Dissection of the Human Pelvis and Perineum.

Progressive curricular changes in medical education over the past two decades have resulted in the diaspora of gross anatomy content into integrated curricula while significantly reducing total contact hours. Despite the development of a wide range of alternative teaching modalities, gross dissection remains a critical component of medical education. The challenge posed to modern anatomists is how to maximize and integrate the time spent dissecting under the current curricular changes. In this study, an alternative approach to the dissection of the pelvis and perineum is presented in an effort to improve content delivery and student satisfaction. The approach involves removal of the perineum en bloc from the cadaver followed by excision of the pubic symphysis, removal and examination of the bladder and associated structures, examination and bisection of the midline pelvic organs in situ, and midsagittal hemisection of the pelvis for identification of the neurovasculature. Results indicate that this novel dissecting approach increases the number of structures identified by 46% ± 14% over current dissecting methods. Survey results indicate that students were better able to integrate lecture and laboratory concepts, understand the concepts, and successfully identify more structures using the new approach (P < 0.05). The concept of anatomic efficiency is introduced and proposed as a standard quantitative measure of gross dissection proficiency across programs and institutions. These findings provide evidence that innovative solutions to anatomy education can be found that help to maintain critical content and student satisfaction in a modern medical curriculum.

What type of learner are your students? Preferred learning styles of undergraduate gross anatomy students according to the index of learning styles questionnaire.

Students learn and process information in many different ways. Learning styles are useful as they allow instructors to learn more about students, as well as aid in the development and application of useful teaching approaches and techniques. At the undergraduate level there is a noticeable lack of research on learning style preferences of students enrolled in gross anatomy courses. The Index of Learning Styles (ILS) questionnaire was administered to students enrolled in a large enrollment undergraduate gross anatomy course with laboratory to determine their preferred learning styles. The predominant preferred learning styles of the students (n = 505) enrolled in the gross anatomy course were active (54.9%), sensing (85.1%), visual (81.2%), and sequential (74.4%). Preferred learning styles profiles of particular majors enrolled in the course were also constructed; analyses showed minor variation in the active/reflective dimension. An understanding of students' preferred learning styles can guide course design but it should not be implemented in isolation. It can be strengthened (or weakened) by concurrent use of other tools (e.g., flipped classroom course design). Based on the preferred learning styles of the majority of undergraduate students in this particular gross anatomy course, course activities can be hands on (i.e., active), grounded in concrete information (i.e., sensing), utilize visual representation such as images, figures, models, etc. (i.e., visual), and move in small incremental steps that build on each topic (i.e., sequential). Anat Sci Educ 11: 358-365. © 2017 American Association of Anatomists.

Severe hyponatraemia with absence of hyperkalaemia in rapidly progressive Addison's disease.

We present a case of rapidly progressing Addison's disease in adrenal crisis with severe hyponatraemia and absence of hyperkalaemia in a 10-year-old girl. She presented with 2 weeks of vomiting, fatigue and weight loss. Her serum electrolytes obtained 1 week prior to presentation were normal, except for mild hyponatraemia at 131 mmol/L, which dropped to 112 mmol/L on admission. She had normal serum potassium, low-serum osmolality, with elevated urine sodium and osmolality, indistinguishable from syndrome of inappropriate antidiuretic hormone (SIADH). Subsequently, Addison's disease was diagnosed on the basis of gingival hyperpigmentation and undetectable cortisol on adrenocorticotropic hormone stimulation test. She rapidly responded to stress dose hydrocortisone, followed by hydrocortisone and fludrocortisone replacement therapy. The absence of hyperkalaemia in the presence of severe hyponatraemia cannot rule out Addison's disease in children. The mechanism of hypo-osmolar hyponatraemia in primary adrenal insufficiency and clinical clues to differentiate it from SIADH are discussed.