Identifying intrinsic and extrinsic determinants that regulate internal initiation of translation mediated by the FMR1 5' leader

<p>Abstract</p> <p>Background</p> <p>Regulating synthesis of the Fragile X gene (FMR1) product, FMRP alters neural plasticity potentially through its role in the microRNA pathway. Cap-dependent translation of the FMR1 mRNA, a process requiring ribosomal scanning through the 5' leader, is likely impeded by the extensive secondary structure generated by the high guanosine/cytosine nucleotide content including the CGG triplet nucleotide repeats in the 5' leader. An alternative mechanism to initiate translation – internal initiation often utilizes secondary structure to recruit the translational machinery. Consequently, studies were undertaken to confirm and extend a previous observation that the FMR1 5' leader contains an internal ribosomal entry site (IRES).</p> <p>Results</p> <p>Cellular transfection of a dicistronic DNA construct containing the FMR1 5' leader inserted into the intercistronic region yielded significant translation of the second cistron, but the FMR1 5' leader was also found to contain a cryptic promoter possibly confounding interpretation of these results. However, transfection of dicistronic and monocistronic RNA <it>ex vivo </it>or <it>in vitro </it>confirmed that the FMR1 5' leader contains an IRES. Moreover, inhibiting cap-dependent translation <it>ex vivo </it>did not affect the expression level of endogenous FMRP indicating a role for IRES-dependent translation of FMR1 mRNA. Analysis of the FMR1 5' leader revealed that the CGG repeats and the 5' end of the leader were vital for internal initiation. Functionally, exposure to potassium chloride or intracellular acidification and addition of polyinosinic:polycytidylic acid as mimics of neural activity and double stranded RNA, respectively, differentially affected FMR1 IRES activity.</p> <p>Conclusion</p> <p>Our results indicate that multiple stimuli influence IRES-dependent translation of the FMR1 mRNA and suggest a functional role for the CGG nucleotide repeats.</p

The sonographic digital portfolio: a longitudinal ultrasound image tracking program

BACKGROUND: Ultrasonography (US) at the medical student level is developing. As clinical skills and simulation centers expand, US equipment miniaturizes, and more students are exposed to ultrasound; a digital portfolio comprised of US images and videos may be useful in demonstrating experience and possibly competency. METHODS: Medical students participated in US curricula consisting of didactics and hands-on training. From 1 July 2006 to 30 June 2008, student images and videos were saved. Total images and videos were evaluated and catalogued. RESULTS: A total of 10,074 images and 1,227 videos were saved during the 2-year period. For the academic year 2006 to 2007, 159 medical students obtained 3,641 of the images (84.9%) and 270 of the videos (86.0%). First year students obtained 778 images and 20 videos; second year students, 1,174 images and 64 videos; third year students, 211 images and 20 videos; and fourth year students, 1,478 images and 166 videos. For the academic year 2007 to 2008, 222 medical students obtained 4,340 images (75%) and 619 videos (67.8%). First year students obtained 624 images and 109 videos; second year students, 555 images and 81 videos; third year students, 132 images and 14 videos; and fourth year students, 3,029 images and 415 videos. CONCLUSIONS: The ultrasound digital portfolio allows medical students to collate and document their ultrasound experience. Currently, there is no requirement for ultrasound training, documentation of competency, or minimum numbers of US exams for medical education. The ultrasound digital portfolio may be a useful tool in documenting ultrasound proficiency

The sonographic digital portfolio: a longitudinal ultrasound image tracking program

Abstract Background: Ultrasonography (US) at the medical student level is developing. As clinical skills and simulation centers expand, US equipment miniaturizes, and more students are exposed to ultrasound; a digital portfolio comprised of US images and videos may be useful in demonstrating experience and possibly competency. First year students obtained 624 images and 109 videos; second year students, 555 images and 81 videos; third year students, 132 images and 14 videos; and fourth year students, 3,029 images and 415 videos. Conclusions: The ultrasound digital portfolio allows medical students to collate and document their ultrasound experience. Currently, there is no requirement for ultrasound training, documentation of competency, or minimum numbers of US exams for medical education. The ultrasound digital portfolio may be a useful tool in documenting ultrasound proficiency

Inflammatory myofibroblastic tumors-A retrospective analysis of the Cooperative Weichteilsarkom Studiengruppe

BACKGROUND Inflammatory myofibroblastic tumors (IMTs) are a rare subgroup of soft tissue tumors. The outcome of patients with IMT has been reported as favorable when the tumor is completely resected. If surgical resection is not possible, systemic therapy has to be considered. However, the best systemic treatment and response rates are currently unclear. METHODS Thirty-eight patients under the age of 21, who were registered between 2000 and 2014 with a primary diagnosis of IMT, were analyzed. RESULTS IMT was typically localized intra-abdominally or in the pelvis. In 20 patients, the tumor was resected without further therapy; 17 patients were in complete remission at last evaluation and two patients were in partial remission. Eighteen patients received systemic therapy, 15 of whom had macroscopically incomplete resection. Systemic therapy most commonly consisted of regimens with dactinomycin, ifosfamide or cyclophosphamide, and vincristine, with or without doxorubicin, and it seemed to reduce tumor extension in individual cases. Five-year event-free survival was 74 ± 14% and 5-year overall survival was 91 ± 10% for all patients. The patients who died due to the disease were those with incomplete resection (n = 3). CONCLUSIONS Surgery without further systemic therapy was a feasible and acceptable therapeutic option for every second patient with IMT. Standard chemotherapy for pediatric soft tissue sarcoma produced favorable results in individual cases and was able to shrink the tumor enough to enable resection. Superior efficacy of new targeted therapies such as anaplastic lymphoma kinase-inhibitors compared to standard chemotherapy has to be proven in the future