Uncoupling of ATP-Mediated Calcium Signaling and Dysregulated Interleukin-6 Secretion in Dendritic Cells by Nanomolar Thimerosal

Dendritic cells (DCs), a rare cell type widely distributed in the soma, are potent antigen-presenting cells that initiate primary immune responses. DCs rely on intracellular redox state and calcium (Ca(2+)) signals for proper development and function, but the relationship between these two signaling systems is unclear. Thimerosal (THI) is a mercurial used to preserve vaccines and consumer products, and is used experimentally to induce Ca(2+) release from microsomal stores. We tested adenosine triphosphate (ATP)-mediated Ca(2+) responses of DCs transiently exposed to nanomolar THI. Transcriptional and immunocytochemical analyses show that murine myeloid immature DCs (IDCs) and mature DCs (MDCs) express inositol 1,4,5-trisphosphate receptor (IP(3)R) and ryanodine receptor (RyR) Ca(2+) channels, known targets of THI. IDCs express the RyR1 isoform in a punctate distribution that is densest near plasma membranes and within dendritic processes, whereas IP(3)Rs are more generally distributed. RyR1 positively and negatively regulates purinergic signaling because ryanodine (Ry) blockade a) recruited 80% more ATP responders, b) shortened ATP-mediated Ca(2+) transients > 2-fold, and c) produced a delayed and persistent rise (≥ 2-fold) in baseline Ca(2+). THI (100 nM, 5 min) recruited more ATP responders, shortened the ATP-mediated Ca(2+) transient (≥ 1.4-fold), and produced a delayed rise (≥ 3-fold) in the Ca(2+) baseline, mimicking Ry. THI and Ry, in combination, produced additive effects leading to uncoupling of IP(3)R and RyR1 signals. THI altered ATP-mediated interleukin-6 secretion, initially enhancing the rate of cytokine secretion but suppressing cytokine secretion overall in DCs. DCs are exquisitely sensitive to THI, with one mechanism involving the uncoupling of positive and negative regulation of Ca(2+) signals contributed by RyR1

Tertiary Survey Performance in a Regional Trauma Hospital Without a Dedicated Trauma Service

Background: Initial management of trauma patients is focused on identifying life- and limb-threatening injuries and may lead to missed injuries. A tertiary survey can minimise the number and effect of missed injuries and involves a physical re-examination and review of all investigations within 24 h of admission. There is little information on current practice of tertiary survey performance in hospitals without a dedicated trauma service. We aimed to determine the rate of tertiary survey performance and the detail of documentation as well as the baseline rate of missed injuries. Methods: We performed a retrospective, descriptive study of all multitrauma patients who presented to an Australian level II regional trauma centre without a dedicated trauma service between May 2008 and February 2009. A medical records review was conducted to determine tertiary survey performance and missed injury rate. Results: Of 252 included trauma patients, 20% (n = 51) had a tertiary survey performed. A total of nine missed injuries were detected in eight patients (3.2%). Of the multiple components of the tertiary survey, most were poorly documented. Documentation was more comprehensive in the subgroup of patients who did have a formal tertiary survey. Conclusions: Tertiary survey performance was poor, as indicated by low documentation rates. The baseline missed injury rate was comparable to previous that of retrospective studies, although in this study an underestimation of true missed injury rates is likely. Implementing a formal, institutional tertiary survey may lead to improved tertiary survey performance and documentation and therefore improved trauma care in hospitals without a dedicated trauma service

Pediatric screen exposure and school related headache disability

BACKGROUND AND OBJECTIVES: Prolonged screen exposure is often cited as a trigger for pediatric headache. We present initial findings evaluating the association between adolescent screen use type, duration, and school disability. METHODS: New patients aged 12-17 years presenting to a headache clinic were screened and surveyed regarding headache characteristics, behavioral habits, school attendance, and screen utilization. RESULTS: 99 adolescents (29 M, 70 F) with average age 14.8 years and average headache frequency of 17 days per month completed the survey. Patients missed an average of five full days and three partial days of school due to headaches over the 90 days prior to survey completion.No statistically significant correlation was found between type or duration of screen exposure and monthly headache frequency, school attendance, or school functioning. A small positive association was seen between increasing duration of computer use, total hours screen use, and school absenteeism. While most adolescents reported prolonged screen use (58.6%) and luminosity (64.6%) worsened headaches, no statistical difference was seen in average number of headache days per month. CONCLUSIONS: Average monthly headache frequency in an adolescent population was not significantly correlated with type or duration of screen exposure. Further studies are needed to elucidate how screen utilization impacts school related headache disability

Clinical symptoms of CTE and other neurodegenerative conditions.

<p>Clinical symptoms of CTE and other neurodegenerative conditions.</p

A prospective evaluation of missed injuries in trauma patients, before and after formalising the trauma tertiary survey

Objective: This study prospectively evaluated in-hospital and postdischarge missed injury rates in admitted trauma patients, before and after the formalisation of a trauma tertiary survey (TTS) procedure. Methods: Prospective before-and-after cohort study. TTS were formalised in a single regional level II trauma hospital in November 2009. All multitrauma patients admitted between March–October 2009 (preformalisation of TTS) and December 2009–September 2010 (post-) were assessed for missed injury, classified into three types: Type I, in-hospital, (injury missed at initial assessment, detected within 24 h); Type II, in-hospital (detected in hospital after 24 h, missed at initial assessment and by TTS); Type III, postdischarge (detected after hospital discharge). Secondary outcome measures included TTS performance rates and functional outcomes at 1 and 6 months. Results” A total of 487 trauma patients were included (pre-: n = 235; post-: n = 252). In-hospital missed injury rate (Types I and II combined) was similar for both groups (3.8 vs. 4.8 %, P = 0.61), as were postdischarge missed injury rates (Type III) at 1 month (13.7 vs. 11.5 %, P = 0.43), and 6 months (3.8 vs. 3.3 %, P = 0.84) after discharge. TTS performance was substantially higher in the post-group (27 vs. 42 %, P 15 %. Some of these injuries were clinically relevant. Although TTS performance was significantly improved by formalising the process (from 27 to 42 %), this did not decrease missed injury rates

Clinical symptoms of CTE and other neurodegenerative conditions.

<p>Clinical symptoms of CTE and other neurodegenerative conditions.</p

History of substance (ab)use by primary TBI exposure groups.

<p>History of substance (ab)use by primary TBI exposure groups.</p