Examination of the Construct Validity of Impact™ Computerized Test,Traditional, and Experimental Neuropsychological Measures

Although computerized neuropsychological screening is becoming a standard for sports concussion identification and management, convergent validity studies are limited. Such studies are important for several reasons: reference to established measures is needed to establish validity; examination of the computerized battery relative to a more traditional comprehensive battery will help understand the strengths and limitations of the computer battery; and such an examination will help inform the output of the computerized battery. We compared scores on the ImPACT? battery to a comprehensive battery of traditional neuropsychological measures and several experimental measures used in the assessment of sports-related concussion in 54 healthy male athletes. Convergent validity was demonstrated for four of the five ImPACT? domain scores. Two cognitive domains often compromised as a result of mild TBI were not directly identified by the ImPACT? battery: sustained attention and auditory working memory. Affective symptoms correlated with performance on measures of attention and working memory. In this healthy sample the correlations between the domains covered by ImPACT? and the neuropsychological battery supports ImPACT? as a useful screening tool for assessing many of the cognitive factors related to mTBI. However, the data suggest other sources of data need to be considered when identifying and managing concussions.     

How distracting is distracting pain?

The study was to determine the effect of preexisting pain on the perception of a painful stimulus. We conducted a cross-section study at an urban ED using convenience sampling. Adult patients who had a 20-g IV catheter placed as part of their ED care were eligible for the study. Patients were excluded for the following reasons: more than one IV attempt, altered mental status, visual impairment, intoxication, or a physical abnormality at the IV site. Patients were asked to indicate on a 10-cm visual analog scale (VAS) the amount of pain they had at baseline immediately before IV placement. They were then asked to indicate on a separate VAS the amount of pain caused by the IV placement. Correlation between baseline pain and pain of the IV was assessed using Pearson's rho. One hundred patients were enrolled in the study. The pain of IV placement did not differ significantly by gender, race, who placed the IV, or the location of the IV. The correlation between baseline pain and pain of the IV placement was poor (rho =.14, confidence interval:-.06-.33). The response to a standardized painful stimulus among ED patients does not correlate highly with the severity of preexisting pain.     

The Sequential Relation Between Changes in Catastrophizing and Changes in Posttraumatic Stress Disorder Symptom Severity

Catastrophizing has been discussed as a cognitive precursor to the emergence of posttraumatic stress disorder (PTSD) symptoms following the experience of stressful events. Implicit in cognitive models of PTSD is that treatment-related reductions in catastrophizing should yield reductions in PTSD symptoms. The tenability of this prediction has yet to be tested. The present study investigated the sequential relation between changes in a specific form of catastrophizing—symptom catastrophizing—and changes in PTSD symptom severity in a sample of 73 work-disabled individuals enrolled in a 10-week behavioral activation intervention. Measures of symptom catastrophizing and PTSD symptom severity were completed at pre-, mid-, and posttreatment assessment points. Cross-sectional analyses of pretreatment data revealed that symptom catastrophizing accounted for significant variance in PTSD symptom severity, β = .40, p < .001, sr = .28 (medium effect size), even when controlling for known correlates of symptom catastrophizing, such as pain and depression. Significant reductions in symptom catastrophizing and PTSD symptoms were observed during treatment, with large effect sizes, ds = 1.42 and 0.94, respectively, ps < .001. Cross-lagged analyses revealed that early change in symptom catastrophizing predicted later change in PTSD symptoms; early changes in PTSD symptom severity did not predict later change in symptom catastrophizing. These findings are consistent with the conceptual models that posit a causal relation between catastrophizing and PTSD symptom severity. The clinical implications of the findings are discussed.     

Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP‐8 activity from 2 to 6 weeks post‐injury, with peak increases in activity occurring at 4 weeks post‐injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96 h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP‐8 activity in situ. Our findings suggest that inhibition of MMP‐8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:500–506, 2014.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody

Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.