After facing traumatic stress: Brain activation, cognition and stress coping in policemen

Introduction

Resilience can be defined as the capacity to recover following stress or trauma exposure by adopting healthy strategies for dealing with trauma and stress. Although the importance of stress resilience has been recognized, the underlying neurocognitive mediators have not yet been identified. Thus, the primary goal of this study was to investigate memory-related brain activity in traumatized policemen who attended a pre-traumatic general stress coping program.

Method

Ten traumatized male police officers were compared to demographically matched non-traumatized officers (n = 15) on associative memory by using a block design paradigm. Participants with either another psychiatric comorbidity or neurological disorder were excluded.During functional brain imaging (1.5-Tesla), face-profession pairs had to be encoded twice. For subsequent retrieval the faces were presented as cue stimuli for associating the category of the prior learned profession. Additionally, clinical pattern, stress coping style, and cognitive parameters were assessed.

Results

Less BOLD activation was found in the hippocampus, parahippocampal gyrus and fusiform gyrus in the trauma group when compared with the non-trauma group during encoding. This was accompanied by slower reaction times in the trauma group during retrieval. Further impairments were found in context memory and in the use of positive cognitive coping strategies.

Discussion

Support was provided for the presence of memory-related disturbances in brain activity associated with trauma even in a resilient population. The contribution of the changes in stress coping ability needs to be further examined in longitudinal studies.     

Effect of protein binding on the pharmacological activity of highly bound antibiotics

During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma protein binding values are applied in the analysis. The aim of this study was to evaluate this approach by experimentally measuring free, unbound concentrations for antibiotics with reportedly high protein binding and their corresponding antimicrobial activities in media containing commonly used protein supplements. Free, unbound ceftriaxone and ertapenem concentrations were determined in bacterial growth medium with and without bovine/human serum albumin, as well as adult bovine serum and human plasma using in vitro microdialysis. The corresponding antimicrobial activity was determined in MIC and time-kill curve experiments using Escherichia coli ATCC 25922 and Streptococcus pneumoniae ATCC 6303 as test strains. A semimechanistic maximum effect model was simultaneously fitted to the data and respective EC₅₀ (concentration at half-maximum effect) values compared. Protein binding differed significantly for ceftriaxone (P < 0.05) between human plasma (76.8 ± 11.0%) and commercially available bovine (20.2 ± 8.3%) or human serum albumin (56.9 ± 16.6%). Similar results were obtained for ertapenem (human plasma, 73.8 ± 11.6%; bovine serum albumin, 12.4 ± 4.8%; human serum albumin, 17.8 ± 11.5%). The MICs and EC₅₀s of both strains were significantly increased (P < 0.05) for ceftriaxone when comparing human and bovine serum albumin, whereas the EC₅₀s were not significantly different for ertapenem. Free, unbound antibiotic concentrations differed substantially between plasma and protein supplements and correlated well with antimicrobial efficacy. Therefore, free, active concentrations should be measured in the test system instead of correcting for literature protein binding values.     

Overexpression of CXCL16 and its receptor CXCR6/Bonzo promotes growth of human schwannomas

Chemokines and their receptors play a decisive role in tumor progression and metastasis. Here, we describe the expression of the CXCL16-CXCR6-system in human schwannomas of different localization and in malignant peripheral nerve sheath tumors. The transmembrane chemokine CXCL16 and its receptor CXCR6/Bonzo were overexpressed on the mRNA and protein levels in all tumor samples investigated as compared with normal peripheral or 8th cranial nerve tissues. Chromogenic immunostaining and confocal laser microscopy revealed that CXCL16 and CXCR6 were localized mainly on S-100 positive schwannoma cells. Cultured schwannoma cells responded to CXCL16-stimulation by phosphorylation of kinases p42/44 (Erk 2/1) that could be inhibited by the MEK1/2-inhibitor U0126 indicating an involvement of the mitogen-activated protein kinase signal transduction pathway. As a biological response, CXCL16 increased proliferation and induced migration of schwannomas. Hence, CXCL16 appears to be a novel growth factor for schwannomas of different localization.     

Intraoperative mapping of language functions: a longitudinal neurolinguistic analysis

OBJECT: This prospective longitudinally designed study was conducted to evaluate language functions pre- and postoperatively in patients who underwent microsurgical treatment of tumors in close proximity to or within language areas and to detect those patients at risk for a postoperative aphasic disturbance. METHODS: Between 1991 and 2005, 153 awake craniotomies with subsequent cortical mapping of language functions were performed in 149 patients. Language functions were assessed using a standardized test battery. Risk factors were obtained from multivariate logistic regression models. RESULTS: Language mapping was able to be performed in all patients, and complete tumor resection was achieved in 48.4%. Within 21 days after surgery a new language deficit (aphasic disturbance) was observed in 41 (32%) of the 128 cases without preoperative deficits. There were a total of 60 cases involving postoperative aphasic disturbances, including cases both with and without preoperative disturbances. Risk factors for postoperative aphasic disturbance were preoperative aphasia (p<0.0002), intraoperative complications (p<0.02), language-positive sites within the tumor (p<0.001), and nonfrontal lesion location (p<0.001). In patients without a preoperative deficit, a normal (yet submaximal) naming performance was a powerful predictor for an early postoperative aphasic disturbance (p<0.0003). Seven months after treatment 10.9% of the 128 cases without preoperative aphasic disturbances continued to demonstrate new postoperative language disturbances. A total of 17.6% of all cases demonstrated new postoperative language disturbances after 7 months. Risk factors for persistent aphasic disturbance were increased age (>40 years, p<0.02) and preoperative aphasia (p<0.001). CONCLUSIONS: Every attempt should be undertaken to preserve language-relevant areas intraoperatively, even when they are located within the tumor. New postoperative deficits resolve in the majority of patients, which may be a result of cortical mapping as well as functional reorganization.     

Association of lipopolysaccharide-binding protein and coronary artery disease in men.

OBJECTIVES: In this study we tested the hypothesis that lipopolysaccharide-binding protein (LBP) might be able to be used as a biomarker for coronary artery disease (CAD). BACKGROUND: The mechanisms by which the innate immune recognition of pathogens could lead to atherosclerosis remain unclear. Lipopolysaccharide-binding protein is the first protein to encounter lipopolysaccharide and to deliver it to its cellular targets, toll-like receptors; therefore, its presence might be a reliable biomarker that indicates activation of innate immune responses. METHODS: A total of 247 men undergoing elective coronary angiography were studied, and the extent of coronary atherosclerosis was assessed by 2 established scores: "extent score" and "severity score." Levels of LBP, markers of inflammation, and traditional risk factors for CAD were assessed. RESULTS: Serum LBP concentration was significantly increased in 172 patients with angiographically confirmed CAD compared with 75 individuals without coronary atherosclerosis (20.6 +/- 8.7 pg/ml vs. 17.1 +/- 6.0 pg/ml, respectively; p = 0.002). Moreover in multivariable logistic regression analyses, adjusted for established cardiovascular risk factors and markers of systemic inflammation, LBP was a significant and independent predictor of prevalent CAD (p < 0.05 in all models). CONCLUSIONS: Lipopolysaccharide-binding protein might serve as a novel marker for CAD in men. The present results underlie the potential importance of innate immune mechanisms for CAD. Further studies are warranted to bolster the data and to identify pathogenetic links between innate immune system activation and atherosclerosis.     

Lung MRI at 1.5 and 3 Tesla: observer preference study and lesion contrast using five different pulse sequences

OBJECTIVES: To compare the image quality and lesion contrast of lung MRI using 5 different pulse sequences at 1.5 T and 3 T. MATERIALS AND METHODS: Lung MRI was performed at 1.5 T and 3 T using 5 pulse sequences which have been previously proposed for lung MRI: 3D volumetric interpolated breath-hold examination (VIBE), true fast imaging with steady-state precession (TrueFISP), half-Fourier single-shot turbo spin-echo (HASTE), short tau inversion recovery (STIR), T2-weighted turbo spin-echo (TSE). In addition to 4 healthy volunteers, 5 porcine lungs were examined in a dedicated chest phantom. Lung pathology (nodules and infiltrates) was simulated in the phantom by intrapulmonary and intrabronchial injections of agarose. CT was performed in the phantom for correlation. Image quality of the sequences was ranked in a side-by-side comparison by 3 blinded radiologists regarding the delineation of pulmonary and mediastinal anatomy, conspicuity of pulmonary nodules and infiltrates, and presence of artifacts. The contrast of nodules and infiltrates (CNODULES and CINFILTRATES) defined by the ratio of the signal intensities of the lesion and adjacent normal lung parenchyma was determined. RESULTS: There were no relevant differences regarding the preference for the individual sequences between both field strengths. TSE was the preferred sequence for the visualization of the mediastinum at both field strengths. For the visualization of lung parenchyma the observers preferred TrueFISP in volunteers and TSE in the phantom studies. At both field strengths VIBE achieved the best rating for the depiction of nodules, whereas HASTE was rated best for the delineation of infiltrates. TrueFISP had the fewest artifacts in volunteers, whereas STIR showed the fewest artifacts in the phantom. For all but the TrueFISP sequence the lesion contrast increased from 1.5 T to 3 T. At both field strengths VIBE showed the highest CNODULES (6.6 and 7.1) and HASTE the highest CINFILTRATES (6.1 and 6.3). CONCLUSION: The imaging characteristics of different pulse sequences used for lung MRI do not substantially differ between 1.5 T and 3 T. A higher lesion contrast can be expected at 3 T.