The Pupillary Light Reflex as a Biomarker of Concussion.

The size of our pupils changes continuously in response to variations in ambient light levels, a process known as the pupillary light reflex (PLR). The PLR is not a simple reflex as its function is modulated by cognitive brain function and any long-term changes in brain function secondary to injury should cause a change in the parameters of the PLR. We performed a retrospective clinical review of the PLR of our patients using the BrightLamp Reflex iPhone app. The PLR variables of latency, maximum pupil diameter (MaxPD), minimum pupil diameter (MinPD), maximum constriction velocity (MCV), and the 75% recovery time (75% PRT) were associated with significant differences between subjects who had suffered a concussion and those that had not. There were also significant differences in PLR metrics over the life span and between genders and those subjects with and without symptoms. The differences in PLR metrics are modulated not only by concussion history but also by gender and whether or not the person has symptoms associated with a head injury. A concussive injury to the brain is associated with changes in the PLR that persist over the life span, representing biomarkers that might be used in clinical diagnosis, treatment, and decision making

Brain Vital Signs in Elite Ice Hockey: Towards Characterizing Objective and Specific Neurophysiological Reference Values for Concussion Management.

Background: Prior concussion studies have shown that objective neurophysiological measures are sensitive to detecting concussive and subconcussive impairments in youth ice-hockey. These studies monitored brain vital signs at rink-side using a within-subjects design to demonstrate significant changes from pre-season baseline scans. However, practical clinical implementation must overcome inherent challenges related to any dependence on a baseline. This requires establishing the start of normative reference data sets. Methods: The current study collected specific reference data for N = 58 elite, youth, male ice-hockey players and compared these with a general reference dataset from N = 135 of males and females across the lifespan. The elite hockey players were recruited to a select training camp through CAA Hockey, a management agency for players drafted to leagues such as the National Hockey League (NHL). The statistical analysis included a test-retest comparison to establish reliability, and a multivariate analysis of covariance to evaluate differences in brain vital signs between groups with age as a covariate. Findings: Test-retest assessments for brain vital signs evoked potentials showed moderate-to-good reliability (Cronbach's Alpha > 0.7, Intraclass correlation coefficient > 0.5) in five out of six measures. The multivariate analysis of covariance showed no overall effect for group (p = 0.105), and a significant effect of age as a covariate was observed (p < 0.001). Adjusting for the effect of age, a significant difference was observed in the measure of N100 latency (p = 0.022) between elite hockey players and the heterogeneous control group. Interpretation: The findings support the concept that normative physiological data can be used in brain vital signs evaluation in athletes, and should additionally be stratified for age, skill level, and experience. These can be combined with general norms and/or individual baseline assessments where appropriate and/or possible. The current results allow for brain vital sign evaluation independent of baseline assessment, therefore enabling objective neurophysiological evaluation of concussion management and cognitive performance optimization in ice-hockey

Metabolomic and transcriptomic stress response of Escherichia coli

GC-MS-based analysis of the metabolic response of Escherichia coli exposed to four different stress conditions reveals reduction of energy expensive pathways.Time-resolved response of E. coli to changing environmental conditions is more specific on the metabolite as compared with the transcript level.Cease of growth during stress response as compared with stationary phase response invokes similar transcript but dissimilar metabolite responses.Condition-dependent associations between metabolites and transcripts are revealed applying co-clustering and canonical correlation analysis

Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer

BACKGROUND: YKL-40 has been implicated as a mediator of collagen synthesis and extracellular matrix re-modeling as well as mitogenesis. Elevated serum levels of YKL-40 have been associated with worse survival in a variety of malignancies including breast cancer. We wished to determine if immunohistochemically detected expression had prognostic implications in breast cancer. METHODS: A prospectively collected database of breast cancer patients treated at the University Hospital of Newark was used for analysis. Immunohistochemistry was performed on archived tumor tissue from 109 patients for whom full clinical information and follow up was available. RESULTS: YKL-40 expression was noted in 37 patients (34%). YKL-40 immunoreactivity significantly correlated with larger tumor size, poorer tumor differentiation, and a greater likelihood of being estrogen and/or progesterone receptor negative. No significant correlation was demonstrated between YKL-40 status and nodal stage. At a mean follow up of 3.2 years, disease-free survival was significantly worse in the subset of patients whose tumors demonstrated YKL-40 expression compared to the non-expressors. In multivariate analysis, YKL-40 status was independent of T-stage and N-stage in predicting disease recurrence. CONCLUSION: Immunoreactivity for YKL-40 was a significant predictor of breast cancer relapse in this subset of patients. This was independent of T or N-stage and suggests that tumor immunohistochemistry for this protein may be a valuable prognostic marker in breast cancer

Prevention and Mitigation of Acute Radiation Syndrome in Mice by Synthetic Lipopeptide Agonists of Toll-Like Receptor 2 (TLR2)

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios

Identification of Antifungal Compounds Active against Candida albicans Using an Improved High-Throughput Caenorhabditis elegans Assay

Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans–C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe