Pragmatic language interpretation after closed head injury: Relationship to executive functioning

Introduction: Closed head injury is associated with impairment in a range of executive skills, and with everyday difficulties in social interactions. Comprehension of pragmatic language plays an important role in social interactions. The present study was designed to examine performance on a task involving pragmatic judgement in people who had suffered closed head injury (CHI), and the relationship between this and any impairments in executive skills. Methods: Participants with CHI were compared to a matched healthy control group on a pragmatic inference task consisting of a series of brief vignettes. Participants made judgements about alternative responses in relation to social appropriateness/skill, and carried out several nonsocial executive tasks thought to play a role in pragmatic judgement. Results: The CHI group was poorer than the control group on the pragmatic measure, showing less discrimination than the control group between direct, literal interpretations and correct, indirect interpretations. They also performed more poorly on the nonsocial executive measures. Regression analysis showed an association between pragmatic performance and one of the executive tasks, a measure of inhibition. Conclusions: More work is needed to explore further the nature of any relationship between pragmatic judgement and executive skills.     

Does the Nature of Chondrolabral Injury Affect the Results of Open Surgery for Femoroacetabular Impingement?

BackgroundThe degree to which patient characteristics, clinical outcomes, and the nature, severity, and corresponding treatment of chondrolabral injury in femoroacetabular impingement (FAI) is associated with failure after surgery is incompletely understood.Questions/purposes(1) Are patient factors associated with failure (age, sex, body mass index, and preoperative modified Harris hip score [mHHS]) in the open surgical treatment of FAI? (2) Is the nature of chondrolabral injury associated with failure? (3) Are any specific chondrolabral injury treatment methods superior?MethodsBetween 2000 and 2008, 172 open surgical procedures in 167 patients were performed for the treatment of FAI by two surgeons at two separate academic medical centers. Ultimately, 142 patients were included in this retrospective study. Mean followup was 3 years (range, 1–12 years). Patient and clinical factors along with the nature, severity, and treatment of chondrolabral injuries were assessed for an association with failure, defined as conversion to THA or the inability to achieve the minimum clinically important difference of the mHHS. Thirty-two percent (45 of 142) of patients failed open surgical treatment of FAI.ResultsPatient factors associated with failure included age (odds ratio [OR], 1.04; p = 0.036) and preoperative mHHS (OR, 4.42; p = 0.033). Neither the nature of the labral lesion nor the severity of the chondral lesion demonstrated a relationship with failure (p > 0.05). Surgically, labral refixation was associated with a decrease in the risk of failure (OR, 0.31; p = 0.039).ConclusionsWe were unable to identify an increased risk of poor outcomes based on sex, body mass index, or severity of chondrolabral lesions. We did find an increased risk of poorer outcomes associated with age. Labral refixation was associated with a decrease in the risk of failure indicating that treatment methodology, rather than the nature of the chondrolabral injury, may be associated with clinical failure. Future studies will be needed to help determine optimal treatment strategies for chondrolabral injuries.

Level of Evidence

Level IV, therapeutic study.     

Profiling receptor tyrosine kinase activation by using Ab microarrays

Signal transduction in mammalian cells is mediated by complex networks of interacting proteins. Understanding these networks at a circuit level requires devices to measure the amounts and activities of multiple proteins in a rapid and accurate manner. Ab microarrays have previously been applied to the quantification of labeled recombinant proteins and proteins in serum. The development of methods to analyze intracellular signaling molecules on microarrays would make Ab arrays widely useful in systems biology. Here we describe the fabrication of multiplex Ab arrays sensitive to the amounts and modification states of signal transduction proteins in crude cell lysates and the integration of these arrays with 96-well microtiter plate technology to create microarrays in microplates. We apply the Ab arrays to monitoring the activation, uptake, and signaling of ErbB receptor tyrosine kinases in human tumor cell lines. Data obtained from multicolor ratiometric microarrays correlate well with data obtained by using traditional approaches, but the arrays are faster and simpler to use. The integration of microplate and microarray methods for crude cell lysates should make it possible to identify and analyze small molecule inhibitors of signal transduction processes with unprecedented speed and precision. We demonstrate the future potential of this approach by characterizing the action of the epidermal growth factor receptor inhibitor PD153035 on cells by using Ab arrays; direct scale-up to array-based screening in 96- and 384-well plates should allow small molecules to be identified with specific inhibitory profiles against a signaling network.     

Structural analysis of the inactive state of the Escherichia coli DNA polymerase clamp-loader complex

Clamp-loader complexes are heteropentameric AAA+ ATPases that load sliding clamps onto DNA. The structure of the nucleotide-free Escherichia coli clamp loader had been determined previously and led to the proposal that the clamp-loader cycles between an inactive state, in which the ATPase domains form a closed ring, and an active state that opens up to form a "C" shape. The crystal structure was interpreted as being closer to the active state than the inactive state. The crystal structure of a nucleotide-bound eukaryotic clamp loader [replication factor C (RFC)] revealed a different and more tightly packed spiral organization of the ATPase domains, raising questions about the significance of the conformation seen earlier for the bacterial clamp loader. We describe crystal structures of the E. coli clamp-loader complex bound to the ATP analog ATPgammaS (at a resolution of 3.5 A) and ADP (at a resolution of 4.1 A). These structures are similar to that of the nucleotide-free clamp-loader complex. Only two of the three functional ATP-binding sites are occupied by ATPgammaS or ADP in these structures, and the bound nucleotides make no interfacial contacts in the complex. These results, along with data from isothermal titration calorimetry, molecular dynamics simulations, and comparison with the RFC structure, suggest that the more open form of the E. coli clamp loader described earlier and in the present work corresponds to a stable inactive state of the clamp loader in which the ATPase domains are prevented from engaging the clamp in the highly cooperative manner seen in the fully ATP-loaded RFC-clamp structure.     

Transseptal endocardial left ventricular pacing: an alternative technique for coronary sinus lead placement in cardiac resynchronization therapy.

BACKGROUND: Coronary sinus (CS) lead placement for transvenous left ventricular (LV) pacing in cardiac resynchronization therapy (CRT) has a failure rate at implant and short-term follow-up between 10% and 15%. OBJECTIVE: The purpose of this study was to assess the feasibility of transseptal endocardial LV pacing in patients in whom transvenous CS lead placement had failed. METHODS: An atrial transseptal LV lead placement was attempted in 10 patients (six females, age 69.4 +/- 9.6 years), in whom CS lead placement for CRT had failed. After transseptal puncture and septal dilatation from the femoral route, the left atrium was cannulated with a combination of catheters and guide wires from the left or right subclavian vein. After advancement of this guide catheter into the LV, a standard bipolar screw-in lead could be implanted in the posterolateral wall. All patients were maintained on anticoagulant therapy with warfarin after implant. RESULTS: An LV lead could be successfully implanted in nine of the 10 patients. The stimulation threshold was 0.78 +/- 0.24 V, and the R-wave amplitude was 14.2 +/- 9.7 mV. At 2 months' follow-up, the stimulation threshold was 1.48 +/- 0.35 V with a 0.064 +/- 0.027 ms pulse width. There was no phrenic nerve stimulation observed in any of the patients. There were no thromboembolic complications at follow-up. CONCLUSIONS: LV transseptal endocardial lead implantation from the pectoral area is a feasible approach in patients with a failed CS approach and in whom epicardial surgical lead placement is not an option. Longer follow-up is warranted to determine the risk of thromboembolic complications.     

Effects of Adult Romantic Attachment and Social Support on Resilience and Depression in Individuals with Spinal Cord Injuries

Background:

Spinal cord injury (SCI) can cause psychological consequences that negatively affect quality of life. It is increasingly recognized that factors such as resilience and social support may produce a buffering effect and are associated with improved health outcomes. However the influence of adult attachment style on an individual’s ability to utilize social support after SCI has not been examined.

Objective:

The purpose of this study was to examine relationships between adult romantic attachment perceived social support depression and resilience in individuals with SCI. In addition we evaluated potential mediating effects of social support and adult attachment on resilience and depression.

Methods:

Participants included 106 adults with SCI undergoing inpatient rehabilitation. Individuals completed measures of adult attachment (avoidance and anxiety) social support resilience and depression. Path analysis was performed to assess for presence of mediation effects.

Results:

When accounting for the smaller sample size support was found for the model (comparative fit index = .927 chi square = 7.86 P = .01 β = -0.25 standard error [SE] = -2.93 P < .05). The mediating effect of social support on the association between attachment avoidance and resilience was the only hypothesized mediating effect found to be significant (β = -0.25 SE = -2.93 P < .05).

Conclusion:

Results suggest that individuals with SCI with higher levels of attachment avoidance have lower perceived social support which relates to lower perceived resilience. Assessing attachment patterns during inpatient rehabilitation may allow therapists to intervene to provide greater support.