A New Panel of Blood Biomarkers for the Diagnosis of Mild Traumatic Brain Injury/Concussion in Adults.

No routine tests currently exist to objectively diagnose mild traumatic brain injury (mTBI)/concussion. Previously reported biomarkers for mTBI represented proteins released from damaged neurons or glia. However, low levels of these proteins, and/or the complexity of assays used for their detection, limits implementation of these biomarkers in routine practice. Here, we sought to identify proteins whose synthesis is altered post-mTBI and whose blood levels could be measured using standard immunoassays. Adult patients sustaining a concussion within the past 24 h were enrolled. Controls were uninjured subjects and patients with orthopedic injury (OI). Four candidate biomarkers were identified: copeptin; galectin 3 (LGALS3); matrix metalloproteinase 9 (MMP9); and occludin (OCLN). A 3.4-fold decrease (p<0.0001) in plasma concentration of copeptin was found in mTBI patients within 8 h after accident, compared to uninjured controls. Plasma levels of LGALS3, MMP9, and OCLN increased 3.6- to 4.5-fold (p<0.0001) within the same time frame postinjury. Levels of at least two biomarkers were altered beyond their respective cut-off values in 90% of mTBI patients, whereas in none of uninjured controls were levels of two biomarkers simultaneously changed. A positive correlation (r=0.681; p<0.001) between plasma levels of LGALS3 and OCLN was also found in mTBI patients, whereas in OI patients or uninjured subjects, these variables did not correlate. This panel of biomarkers discerns, with high accuracy, patients with isolated concussion from uninjured individuals within the first 8 h after accident. These biomarkers can also aid in diagnosing concussion in the presence of OI.

Emergency physicians' and nurses' attitudes towards alcohol-intoxicated patients.

BACKGROUND: Emergency physicians and nurses are frequently dissatisfied professionally when treating alcohol-intoxicated patients, and have negative attitudes towards this patient population and alcohol rehabilitation. STUDY OBJECTIVES: The goal of this study is to examine differences in attitudes between emergency physicians and nurses towards alcohol-intoxicated patients. METHODS: This single-site survey study evaluated emergency physicians' and nurses': 1) attitudes of personal professional satisfaction and dissatisfaction when caring for intoxicated patients; 2) attitudes towards the difficulty in caring for alcohol-intoxicated patients; 3) attitudes towards respect of the alcohol-intoxicated patient; 4) attitudes towards the adequacy of training in caring for intoxicated patients; 5) attitudes towards rehabilitation and counseling of alcohol-intoxicated patients. RESULTS: Physicians were less satisfied and more dissatisfied than nurses when caring for alcohol-intoxicated patients. Physicians found treating alcohol-intoxicated patients more difficult than nurses did. Physicians were more likely to agree that alcohol-intoxicated patients should be treated with respect. Physicians felt more adequately trained than nurses in caring for alcohol-intoxicated patients. Nurses were more likely to believe that alcohol-related rehabilitation is ineffective compared with physicians. Both nurses and physicians refer alcohol-intoxicated patients to rehabilitation to a similar extent. CONCLUSIONS: Emergency physicians and nurses have similar attitudes but significant differences in the extent of these attitudes towards the care of the alcohol-intoxicated patient.

Missed opportunities for earlier HIV diagnosis in an emergency department despite an HIV screening program.

In 2005 we implemented an emergency department HIV testing program that emphasized screening by nurses but also allowed for clinician diagnostic testing. We noted that clinicians often ordered tests that proved to be positive on patients who had been missed by screening, while others who tested positive had made previous visits when screening was available, but were not tested. The study objective was to quantify missed screening opportunities and assess the extent to which diagnostic testing contributes to the detection of HIV infection. Triage nurses were to offer screening to medically stable patients 12 years of age or older. Clinicians could order diagnostic testing in patients with signs and symptoms concerning for HIV. Nurses performed rapid HIV tests on oral fluid specimens. Charts of all patients testing positive between April 1, 2005 and November 31, 2006 were reviewed. The 2006 annual census was 75,000 visits with 47% of patients black, 32% Hispanic, 44% female, and 98% 12 years of age or older. Ninety-five patients tested HIV positive; 66 (69.5%) were diagnosed on their first visit but 29 (30.5%) made a total of 59 visits (range, 1-8) before testing positive. Patients were screening eligible during 54 (91.5%) of these 59 visits but screening was not offered during 34 (63.0%) of them, representing missed screening opportunities. On the day of diagnosis, 80 (84.2%) of the 95 patients were screening eligible but 20 (25.0%) of them were not offered screening, representing missed screening opportunities. Diagnostic testing identified HIV in 44 patients; 15 were screening ineligible, 20 were not offered screening, and 9 declined screening. Missed opportunities for earlier diagnosis occurred frequently despite an HIV screening program. Clinician diagnostic testing was an important adjunct to screening.

A HIV-1 minimal gag protein is superior to nucleocapsid at in vitro annealing and exhibits multimerization-induced inhibition of reverse transcription.

HIV-1 uses tRNA3Lys to prime reverse transcription of its viral RNA. In this process, the 3'-end of tRNA3Lys must be annealed to the primer binding site of HIV-1 genomic RNA, and the two molecules together form a complex structure. During annealing, the nucleocapsid (NC) protein enhances the unwinding of tertiary structures within both RNA molecules. Moreover, the packaging of tRNA3Lys occurs prior to viral budding at a time when NC is still part of the Pr55Gag polyprotein. In contrast, Pr55Gag is able to produce virus-like particles on its own. We have recently shown that an N-terminal extended form of NC (mGag), containing all of the minimal elements required for virus-like particle formation, possesses greater affinity for HIV-1 genomic RNA than does NC alone. We have now studied the tRNA3Lys-annealing properties of mGag in comparison to those of NC and report that the former is more efficient in this regard than the latter. We have also tested each of a mutant version of mGag, an extended form of mGag, and an almost full-length form of Gag, and showed that all of these possessed greater tRNA-annealing capacity than did the viral NC protein. Yet, surprisingly, multimerization of Gag-related proteins did not abrogate this annealing process but rather resulted in dramatically reduced levels of reverse transcriptase processivity. These results suggest that the initial stages of reverse transcription may be regulated by the multimerization of Pr55Gag polyprotein at times prior to the cleavage of NC.