Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities. CSF and serum samples of 15 SCI and ten healthy participants were included in the study. The neurological assessments were scored on admission and at discharge from the hospital using the American Spinal Injury Association Impairment Score (AIS) grades. The CSF and serum concentrations of SBDP150, S100B, GFAP, NF-L, UCHL-1, Tau, and IL-6 were significantly higher in SCI patients when compared with the control group. The CSF GBDP 38/44K, UCHL-L1, S100B, GFAP, and Tau levels were significantly higher in the AIS A patients. This study demonstrated a strong correlation between biomarker levels in the diagnosis and injury severity of SCI but no association with short-term outcomes. Future prospective controlled studies need to be done to support the results of this study.

Combined GFAP, NFL, Tau, and UCH-L1 panel increases prediction of outcomes in neonatal encephalopathy.

BACKGROUND: Neuroprognostication in neonates with neonatal encephalopathy (NE) may be enhanced by early serial measurement of a panel of four brain-specific biomarkers. METHODS: To evaluate serum biomarkers, 40 NE samples and 37 healthy neonates from a biorepository were analyzed. Blood samples were collected at 0-6, 12, 24, 48, and 96 h of life. MRI provided a short-term measure of injury. Long-term outcomes included death or a Bayley III score at 17-24 months of age. RESULTS: Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), and Tau peaked at 0-6 h of life, while neurofilament light chain (NFL) peaked at 96 h of life. These four marker concentrations at 96 h of life differentiated moderate/severe from none/mild brain injury by MRI, while GFAP and Tau showed early discrimination. For long-term outcomes, GFAP, NFL, Tau, and UCH-L1 could differentiate a poor outcome vs good outcome as early as 0-6 h of life, depending on the Bayley domain, and a combination of the four markers enhanced the sensitivity and specificity. Machine learning trajectory analyses identified upward trajectory patients with a high concordance to poor outcomes. CONCLUSION: GFAP, NFL, Tau, and UCH-L1 may be of neuroprognostic significance after NE. IMPACT: Serial measurements of GFAP, NFL, Tau, and UCH-L1 show promise in aiding the bedside clinician in making treatment decisions in neonatal encephalopathy. The panel of four neuroproteins increased the ability to predict neurodevelopmental outcomes. The study utilized a trajectory analysis that enabled predictive modeling. A panel approach provides the bedside clinician with objective data to individualize care. This study provides the foundation to develop a point of care device in the future.

Characterization of Calpain and Caspase-6-Generated Glial Fibrillary Acidic Protein Breakdown Products Following Traumatic Brain Injury and Astroglial Cell Injury.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites at A-56*A-61 and (ii) major C-terminal cleavage sites at T-383*Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78/R-79 and D-225/A-226, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.

Automated, miniaturized, and scalable screening of healthcare workers, first responders, and students for SARS-CoV-2 in San Diego County

BackgroundSuccessful containment strategies for SARS-CoV-2, the causative virus of the COVID-19 pandemic, have involved widespread population testing that identifies infections early and enables rapid contact tracing. In this study, we developed a rapid and inexpensive RT- qPCR testing pipeline for population-level SARS-CoV-2 detection, and used this pipeline to establish a clinical laboratory dedicated to COVID-19 testing at the University of California San Diego (UCSD) with a processing capacity of 6,000 samples per day and next-day result turnaround times. Methods and findingsUsing this pipeline, we screened 6,786 healthcare workers and first responders, and 21,220 students, faculty, and staff from UCSD. Additionally, we screened 6,031 preschool-grade 12 students and staff from public and private schools across San Diego County that remained fully or partially open for in-person teaching during the pandemic. Between April 17, 2020 and February 5, 2021, participants provided 161,582 nasal swabs that were tested for the presence of SARS-CoV-2. Overall, 752 positive tests were obtained, yielding a test positivity rate of 0.47%. While the presence of symptoms was significantly correlated with higher viral load, most of the COVID-19 positive participants who participated in symptom surveys were asymptomatic at the time of testing. The positivity rate among preschool-grade 12 schools that remained open for in-person teaching was similar to the positivity rate at UCSD and lower than that of San Diego County, with the children in private schools being less likely to test positive than the adults at these schools. ConclusionsMost schools across the United States have been closed for in-person learning for much of the 2020-2021 school year, and their safe reopening is a national priority. However, as there are no vaccines against SARS-CoV-2 currently available to the majority of school-aged children, the traditional strategies of mandatory masking, physical distancing, and repeated viral testing of students and staff remain key components of risk mitigation in these settings. The data presented here suggest that the safety measures and repeated testing actions taken by participating healthcare and educational facilities were effective in preventing outbreaks, and that a similar combination of risk-mitigation strategies and repeated testing may be successfully adopted by other healthcare and educational systems.

A survey of general surgery clerkships in Australian and New Zealand medical schools.

BACKGROUND: Surgical clerkships facilitate development of knowledge and competency, but their structure and content vary. Establishment of new medical schools and raising student numbers are new challenges to the provision of standardized surgical teaching across Australasian medical schools. A survey was conducted to investigate how Australian and New Zealand medical schools structure their general surgery clerkships. METHODS: Between April and August 2009, a 30-item web-based survey was electronically sent to academic and administrative staff members of 22 Australian and New Zealand medical schools. RESULTS: Eighteen surveys were returned by 16 medical schools, summarizing 20 clerkships. Ten schools utilize five or more different clinical teaching sites for general surgery clerkships and these include urban and rural hospitals from both public and private health sectors. Student teaching and assessment methods are similar between clerkships and standardized across clinical sites during 10 and 16 of the clerkships, respectively. Only eight of the surveyed clerkships use centralized assessments to evaluate student learning outcomes across different clinical sites. Four clerkships do not routinely use direct observational student assessments. CONCLUSIONS: Australian and New Zealand medical schools commonly assign students to multiple diverse clinical sites during general surgery clerkships and they vary in their approaches to standardizing curriculum delivery and student assessment across these sites. Differences in student learning are likely to exist and deficiencies in clinical ability may go undetected. This should be a focus for future improvement.