The ability of CNS vital signs to detect coached sandbagging performance during concussion baseline testing: a randomized control trial.

Objective: Despite widespread use of baseline neurocognitive testing in concussion management, suboptimal performance due to sandbagging still readily occurs without detection. The purpose of this study is to determine CNS Vital Signs validity indicator accuracy in detecting coached sandbagging compared to controls.Method: We compared rates of invalidity and domain composite scores for neurocognitive test performance between two groups of twenty-five college-aged students (age = 20.8 ± 1.1 years, range 18-25, 48% female) completing CNS Vital Signs instructed to either 1) give their best effort (control) or, 2) give suboptimal performance (sandbag). The sandbagging group was given standardized instructions on how to sandbag without detection. All participants rated their effort after completing on a Visual Analog Scale (0-100 mm).Results: Built in invalidity indicators successfully identified 68.0% of sandbaggers, while only 12% in the control group presented with invalid scores. Participants in the sandbagging group on average reported significantly lower effort (sandbag: 51.0 ± 21.0, control: 86.0 ± 12.0, p < .001)Conclusions: Built-in CNS Vital Signs validity indicators have an overall high accuracy in identifying those attempting to purposefully sandbag and are comparable to other computerized neurocognitive tests. Given that 32% of intentional sandbaggers went undetected, clinicians should consider additional safeguards to detect these individuals at baseline.

A novel therapy, using Ghrelin with pegylated G-CSF, inhibits brain hemorrhage from ionizing radiation or combined radiation injury.

Medical treatment becomes challenging when complicated injuries arise from secondary reactive metabolic and inflammatory products induced by initial acute ionizing radiation injury (RI) or when combined with subsequent trauma insult(s) (CI). With such detrimental effects on many organs, CI exacerbates the severity of primary injuries and decreases survival. Previously, in a novel study, we reported that ghrelin therapy significantly improved survival after CI. This study aimed to investigate whether brain hemorrhage induced by RI and CI could be inhibited by ghrelin therapy with pegylated G-CSF (i.e., Neulasta®, an FDA-approved drug). B6D2F1 female mice were exposed to 9.5 Gy 60Co-γ-radiation followed by 15% total-skin surface wound. Several endpoints were measured at several days. Brain hemorrhage and platelet depletion were observed in RI and CI mice. Brain hemorrhage severity was significantly higher in CI mice than in RI mice. Ghrelin therapy with pegylated G-CSF reduced the severity in brains of both RI and CI mice. RI and CI did not alter PARP and NF-κB but did significantly reduce PGC-1α and ghrelin receptors; the therapy, however, was able to partially recover ghrelin receptors. RI and CI significantly increased IL-6, KC, Eotaxin, G-CSF, MIP-2, MCP-1, MIP-1α, but significantly decreased IL-2, IL-9, IL-10, MIG, IFN-γ, and PDGF-bb; the therapy inhibited these changes. RI and CI significantly reduced platelet numbers, cellular ATP levels, NRF1/2, and AKT phosphorylation. The therapy significantly mitigated these CI-induced changes and reduced p53-mdm2 mediated caspase-3 activation. Our data are the first to support the view that Ghrelin therapy with pegylated G-CSF is potentially a novel therapy for treating brain hemorrhage after RI and CI.

IAR3 encodes an auxin conjugate hydrolase from Arabidopsis.

Amide-linked conjugates of indole-3-acetic acid (IAA) are putative storage or inactivation forms of the growth hormone auxin. Here, we describe the Arabidopsis iar3 mutant that displays reduced sensitivity to IAA-Ala. IAR3 is a member of a family of Arabidopsis genes related to the previously isolated ILR1 gene, which encodes an IAA-amino acid hydrolase selective for IAA-Leu and IAA-Phe. IAR3 and the very similar ILL5 gene are closely linked on chromosome 1 and comprise a subfamily of the six Arabidopsis IAA-conjugate hydrolases. The purified IAR3 enzyme hydrolyzes IAA-Ala in vitro. iar 3 ilr1 double mutants are more resistant than either single mutant to IAA-amino acid conjugates, and plants overexpressing IAR3 or ILR1 are more sensitive than is the wild type to certain IAA-amino acid conjugates, reflecting the overlapping substrate specificities of the corresponding enzymes. The IAR3 gene is expressed most strongly in roots, stems, and flowers, suggesting roles for IAA-conjugate hydrolysis in those tissues.

Putative cytoplasmic amphiphilic domains in the nerve growth factor/tumour necrosis factor receptor superfamily.

Potential alpha-helical regions in cytoplasmic domains of the NGF/TNF receptor superfamily were searched to identify amphiphilic sequences favouring association with membrane surfaces, analogous to the predicted secondary structure of mastoparan (MP). Similar to MP, NGFR (rat, chick, human), human TNFR-1, and human 4-1BB have domains with putative surface membrane associating sequences. The circular dichroism spectra of mastoparan and a peptide homologous to the putative amphiphilic domain of NGFR were identical in an aqueous milieu, and both adopted an alpha-helical conformation in trifluoroethanol.