Menin determines K-RAS proliferative outputs in endocrine cells

Endocrine cell proliferation fluctuates dramatically in response to signals that communicate hormone demand. The genetic alterations that override these controls in endocrine tumors often are not associated with oncogenes common to other tumor types, suggesting that unique pathways govern endocrine proliferation. Within the pancreas, for example, activating mutations of the prototypical oncogene KRAS drive proliferation in all pancreatic ductal adenocarcimomas but are never found in pancreatic endocrine tumors. Therefore, we asked how cellular context impacts K-RAS signaling. We found that K-RAS paradoxically suppressed, rather than promoted, growth in pancreatic endocrine cells. Inhibition of proliferation by K-RAS depended on antiproliferative RAS effector RASSF1A and blockade of the RAS-activated proproliferative RAF/MAPK pathway by tumor suppressor menin. Consistent with this model, a glucagon-like peptide 1 (GLP1) agonist, which stimulates ERK1/2 phosphorylation, did not affect endocrine cell proliferation by itself, but synergistically enhanced proliferation when combined with a menin inhibitor. In contrast, inhibition of MAPK signaling created a synthetic lethal interaction in the setting of menin loss. These insights suggest potential strategies both for regenerating pancreatic β cells for people with diabetes and for targeting menin-sensitive endocrine tumors.     

Rare Variant of Vastus Medialis Detected in vivo by Ultrasound and Confirmed by High-resolution MRI

[Purpose] This report describes an unusual incidental finding during ultrasound investigation of the vastus medialis muscle. Volunteers underwent ultrasound scanning as part of an on-going investigation into the architecture of the vastus medialis muscle. [Subjects and Methods] The distal thighs of forty-one subjects were scanned using the Philips iU22 US system. An unusual muscle morphology was detected bilaterally in one subject, who then underwent a 3T Magnetic Resonance Imaging (MRI) scan in order to further investigate the muscle morphology. The subject in question was a 32 year-old female who suffers from recurrent bilateral patellar dislocations. [Results] The MRI scan confirmed the ultrasound findings, and indicated the presence of the vastus medialis in two layers, with the VML continuing deep, separate from the VMO. [Conclusion] Although this rare variant has been been reported in previous cadaveric studies, we believe this to be the first report in the literature of this morphology in vivo. The biomechanical implications of this muscle arrangement are unknown, but it may not be without significance that this individual suffers from recurrent patellar dislocations.Key words: Vastus medialis, Ultrasound, MRI     

A comprehensive review of COVID-19 biology,diagnostics, therapeutics,and disease impacting the central nervous system

Journal of NeuroVirology - The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible disease. SARS-CoV-2 is estimated to have...     

Changes in aphasic discourse after contrasting treatments for anomia

Background: Discourse analysis is a key element in determining treatment effects. However, it is extremely labour intensive, requiring in‐depth knowledge of linguistics and aphasiology; thus, it is often neglected in the analysis of treatment outcomes. A clinically practical method of discourse analysis would be beneficial for evaluation and determination of treatment efficacy.

Aims: The current study investigates changes in discourse content following contrasting treatments for anomia using grammatical analysis. In addition, we pilot the use of a new information measure.

Methods & Procedures: We compare discourse changes after a gestural + verbaltreatment and a semantic‐phonologic treatment for nouns and verbs on two groups of individuals with aphasia. Analyses compared discourse samples from 14 participants taken at baseline, post‐phase 1, and post‐phase 2. In addition to traditional measures such as number of nouns, verbs, and sentence types, a new measure of information is introduced, the Utterance with New Information (UNI). The UNI is designed to assess content in non‐propositional, impaired speech in open‐ended discourse.

Outcomes & Results: Noun production increased in participants of both treatments, whereas grammatical sentences increased only in participants of the semantic‐phonologic treatment. Production of UNIs increased in participants of both treatments as well as over time.

Conclusions: This study demonstrates that a few easily counted measures of discourse production can provide clinically useful information for the clinician. Moreover, these findings suggest discourse analysis is a viable method of determining treatment outcomes especially given that improving discourse is the ultimate goal of all aphasia treatments.