Improving the Interprofessional Relationship between Nurses and Speech-Langauge Pathologists - Expansion of a Project

The research presented on this poster explored the impact of extraprofessional education on undergraduate nursing and speech-language pathology students with an overall goal of improving the interprofessional relationship between the two fields. Utilizing quantitative and qualitative methods in the form of a pre-test, educational materials, live guided observation, and post-tests, the researchers found an increase in the nursing students ability to identify the role of the speech-language pathologist in a medical setting. There was also an increase in the speech-language pathology student’s ability to understand how and when to communicate with nurses in a medical setting

Genome-wide MicroRNA profiling of mantle cell lymphoma reveal a distinct subgroup with poor prognosis

MicroRNA (miRNA) deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1- positive MCL (n=30) and cyclin D1-negative MCL (n=7) and compared them with small lymphocytic leukemia/lymphoma (SLL, n=12), aggressive B-cell lymphomas (n=138), normal B-cell subsets and stromal cells. We identified a 19-miRNA classifier which included six upregulated miRNAs (miR-135a, miR-708, miR-150, miR-363, miR-184, miR-342-5p) and 13 downregulated miRNAs, that was able to distinguish MCL from other aggressive lymphomas with \u3e90% probability. Some of these upregulated miRNAs are highly expressed in naïve B-cells. MicroRNA classifier showed consistent results in FFPE tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from SLL, dominated by 23 upregulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL cases demonstrated a cluster characterized by high expression of miRNAs from polycistronic miR17~92 cluster and its paralogs miR-106a-363 and miR-106b-25, which was distinct from the other clusters showing enrichment of stroma associated miRNAs. The corresponding gene-expressionprofiling (GEP) data showed that the former cluster of MCL had significantly higher proliferation genesignature (PS), while the other subsets had higher expression of stroma associated genes. Clinical outcome analysis suggests that miRNAs can serve as prognosticators

Loss of signalling via Gα13 in germinal center B-cell-derived lymphoma

Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined1,2. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells3,4. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma

Genome-wide miRNAprofiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis

miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1–positive MCL (n = 30) and cyclin D1–negative MCL (n =7) and compared them with small lymphocytic leukemia/ lymphoma (n =12), aggressive B-cell lymphomas (n =138), normal B-cell subsets, and stromal cells.We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1–negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators

Improving the Interprofessional Relationship between Nurses and Speech-Langauge Pathologists - Expansion of a Project

The research presented on this poster explored the impact of extraprofessional education on undergraduate nursing and speech-language pathology students with an overall goal of improving the interprofessional relationship between the two fields. Utilizing quantitative and qualitative methods in the form of a pre-test, educational materials, live guided observation, and post-tests, the researchers found an increase in the nursing students ability to identify the role of the speech-language pathologist in a medical setting. There was also an increase in the speech-language pathology student’s ability to understand how and when to communicate with nurses in a medical setting

Characterization of the discrepancies between four-dimensional phase-contrast magnetic resonance imaging and in-silico simulations of cerebrospinal fluid dynamics

The purpose of the present study was to compare subject-specific magnetic resonance imaging (MRI)-based computational fluid dynamics (CFD) simulations with time-resolved three-directional (3D) velocity-encoded phase-contrast MRI (4D PCMRI) measurements of the cerebrospinal fluid (CSF) velocity field in the cervical spinal subarachnoid space (SSS). Three-dimensional models of the cervical SSS were constructed based on MRI image segmentation and anatomical measurements for a healthy subject and patient with Chiari I malformation. CFD was used to simulate the CSF motion and compared to the 4D PCMRI measurements. Four-dimensional PCMRI measurements had much greater CSF velocities compared to CFD simulations (1.4 to 5.6 x greater). Four-dimensional PCMRI and CFD both showed anterior and anterolateral dominance of CSF velocities, although this flow feature was more pronounced in 4D PCMRI measurements compared to CFD. CSF flow jets were present near the nerve rootlets and denticulate ligaments (NRDL) in the CFD simulation. Flow jets were visible in the 4D PCMRI measurements, although they were not clearly attributable to nerve rootlets. Inclusion of spinal cord NRDL in the cervical SSS does not fully explain the differences between velocities obtained from 4D PCMRI measurements and CFD simulations

An MRI-Compatible Hydrodynamic Simulator of Cerebrospinal Fluid Motion in the Cervical Spine

Goal: Develop and test an MRI-compatible hydrodynamic simulator of cerebrospinal fluid (CSF) motion in the cervical spinal subarachnoid space. Four anatomically realistic subject-specific models were created based on a 22-year-old healthy volunteer and a five-year-old patient diagnosed with Chiari I malformation. Methods: The in vitro models were based on manual segmentation of high-resolution T2-weighted MRI of the cervical spine. Anatomically realistic dorsal and ventral spinal cord nerve rootlets (NR) were added. Models were three dimensional (3-D) printed by stereolithography with 50-mu m layer thickness. A computer controlled pump system was used to replicate the shape of the subject specific in vivo CSF flow measured by phase-contrast MRI. Each model was then scanned by T2-weighted and 4-D phase contrast MRI (4D flow). Results: Cross-sectional area, wetted perimeter, and hydraulic diameter were quantified for each model. The oscillatory CSF velocity field (flow jets near NR, velocity profile shape, and magnitude) had similar characteristics to previously reported studies in the literature measured by in vivo MRI. Conclusion: This study describes the first MRI-compatible hydrodynamic simulator of CSF motion in the cervical spine with anatomically realistic NR. NR were found to impact CSF velocity profiles to a great degree. Significance: CSF hydrodynamics are thought to be altered in craniospinal disorders such as Chiari I malformation. MRI scanning techniques and protocols can be used to quantify CSF flow alterations in disease states. The provided in vitro models can be used to test the reliability of these protocols across MRI scanner manufacturers and machines

Cerebellar tonsil ectopia measurement in type I Chiari malformation patients show poor inter-operator reliability

BackgroundType 1 Chiari malformation (CM-I) has been historically defined by cerebellar tonsillar position (TP) greater than 3-5mm below the foramen magnum (FM). Often, the radiographic findings are highly variable, which may influence the clinical course and patient outcome. In this study, we evaluate the inter-operator reliability (reproducibility) of MRI-based measurement of TP in CM-I patients and healthy controls.MethodsThirty-three T2-weighted MRI sets were obtained for 23 CM-I patients (11 symptomatic and 12 asymptomatic) and 10 healthy controls. TP inferior to the FM was measured in the mid-sagittal plane by seven expert operators with reference to McRae's line. Overall agreement between the operators was quantified by intraclass correlation coefficient (ICC).ResultsThe mean and standard deviation of cerebellar TP measurements for asymptomatic (CM-Ia) and symptomatic (CM-Is) patients in mid-sagittal plane was 6.382.19 and 9.57 +/- 2.63mm, respectively. TP measurements for healthy controls was 0.48 +/- 2.88mm. The average range of TP measurements for all data sets analyzed was 7.7mm. Overall operator agreement for TP measurements was relatively high with an ICC of 0.83.ConclusionThe results demonstrated a large average range (7.7mm) of measurements among the seven expert operators and support that, if economically feasible, two radiologists should make independent measurements before radiologic diagnosis of CM-I and surgery is contemplated. In the future, an objective diagnostic parameter for CM-I that utilizes automated algorithms and results in smaller inter-operator variation may improve patient selection