Role of NMDA receptors in adult primate cortical somatosensory plasticity

We have previously shown that most of the reorganization that typically follows median nerve transection in adult squirrel monkeys is dependent on normally functioning N-methyl-D-aspartate (NMDA) receptors. Here, we have evaluated two additional hypotheses: (1) is the immediate "unmasking" found after median nerve transection NMDA receptor-dependent? and (2) are NMDA receptors necessary for both the initiation and maintenance of the second phase of reorganizational changes, or only the former? To address these issues, we implanted osmotic minipumps subcutaneously to deliver an NMDA receptor antagonist (3-((+/-)-2- carboxypiperazin-4-yl)propyl-1-phosphonic acid, CPP) systemically either before examining the immediate effects of median nerve transection, or after reorganization had presumably occurred. For the first set of experiments, NMDA receptor blockade was initiated either 1 or 4 weeks prior to multi-unit mapping in area 3b followed by transection of the median nerve and remapping of the cortex. In the second set of experiments, median nerve transection was followed 4 weeks later by either 1 or 4 weeks of NMDA receptor blockade prior to terminal mapping. We report that the immediate unmasking of new receptive fields after acute nerve injury is not prevented by NMDA receptor blockade; nor are completely reorganized cortical maps dependent upon NMDA receptors for their maintenance. We conclude that the immediate changes in cortical topography are not due to an NMDA receptor-dependent mechanism, but more likely due to release from tonic inhibition. Furthermore, the later phase of reorganization, as for some forms of hippocampal long-term potentiation (LTP), is dependent on normally functioning NMDA receptors for its initiation, but not for its maintenance.     

The floating knee in the pediatric patient. Nonoperative versus operative stabilization

The results of nonoperative and operative or rigid stabilization of ipsilateral femur and tibia fractures in children and adolescents were evaluated. Twenty-nine consecutive patients with open physes (30 affected extremities) were reviewed. Their mean followup was 8.6 years (range, 1.1-18.6 years). The nonoperative group consisted of 16 patients and 16 extremities treated by skeletal traction of the femoral fracture, closed reduction and splinting or casting of the tibia fractures, and eventual immobilization in a hip spica cast. The operative group, was comprised of 13 patients and 14 extremities in which one or both fractures were treated by open reduction and internal fixation, intramedullary fixation, or external fixation. Despite higher modified injury severity scores and skeletal injury scores, the patients who were treated operatively had a significantly reduced hospital stay, 20.1 days versus 34.9 days, respectively; decreased time to unsupported weightbearing, 16.8 weeks compared with 22.3 weeks, respectively; and fewer complications. Operative stabilization of the femur had a significant effect on decreasing the length of hospital stay and the time to unassisted weightbearing. The patients also were analyzed according to their age at the time of injury: 9 years of age or younger and 10 years of age and older. The younger children who were treated nonoperatively had an increased rate of lower extremity length discrepancy, angular malunion, and need for a secondary surgical procedure as compared with younger children who were treated operatively with rigid fixation. Based on the results of the current study, operative stabilization of at least the femur fracture and, preferably, both fractures in the treatment of a child with a floating knee is recommended, even for younger children.     

Recent Chemical Exposures and Blood Volatile Organic Compound Levels in a Large Population-Based Sample

Little is known about factors that influence blood levels of volatile organic compounds in nonoccupationally exposed populations. The authors examined the possible relationship between recent self-reported chemical exposures and elevated blood volatile organic compound levels among 982 adult participants in the Third National Health and Nutrition Examination Survey. A strong dose-response effect was indicated (p < .001) for increasing lifetime pack-years of cigarettes smoked for elevated levels of toluene, styrene, and benzene. A positive dose-response effect was indicated for daily alcohol consumption with respect to elevated blood levels of 2-butanone and acetone. For volatile organic compounds typically found in 10-75% of the population, the establishment of a link with specific environmental exposures is relatively easy because there is less effect of confounding in this group. Some volatile organic compounds, however, are seen in less than 10% of the general population; finding these compounds at any level may warrant a search for a particular exposure.     

Editor's Choice: Toward high-throughput phenotyping: unbiased automated feature extraction and selection from knowledge sources

Objective Analysis of narrative (text) data from electronic health records (EHRs) can improve population-scale phenotyping for clinical and genetic research. Currently, selection of text features for phenotyping algorithms is slow and laborious, requiring extensive and iterative involvement by domain experts. This paper introduces a method to develop phenotyping algorithms in an unbiased manner by automatically extracting and selecting informative features, which can be comparable to expert-curated ones in classification accuracy.Materials and methods Comprehensive medical concepts were collected from publicly available knowledge sources in an automated, unbiased fashion. Natural language processing (NLP) revealed the occurrence patterns of these concepts in EHR narrative notes, which enabled selection of informative features for phenotype classification. When combined with additional codified features, a penalized logistic regression model was trained to classify the target phenotype.Results The authors applied our method to develop algorithms to identify patients with rheumatoid arthritis and coronary artery disease cases among those with rheumatoid arthritis from a large multi-institutional EHR. The area under the receiver operating characteristic curves (AUC) for classifying RA and CAD using models trained with automated features were 0.951 and 0.929, respectively, compared to the AUCs of 0.938 and 0.929 by models trained with expert-curated features.Discussion Models trained with NLP text features selected through an unbiased, automated procedure achieved comparable or slightly higher accuracy than those trained with expert-curated features. The majority of the selected model features were interpretable.Conclusion The proposed automated feature extraction method, generating highly accurate phenotyping algorithms with improved efficiency, is a significant step toward high-throughput phenotyping.     

Discordant intracellular and plasma D-2-hydroxyglutarate levels in a patient with IDH2 mutated angioimmunoblastic T-cell lymphoma

Objectives: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with mutations in genes encoding isocitrate dehydrogenase1 and 2 (IDH1 and IDH2). Mutant IDH generates the oncometabolite D-2-hydroxyglutarate (D-2HG). We report the first case of discordant intracellular and plasma D-2HG levels in a patient with IDH2 R172S mutated AITL. Methods: An 87-year-old woman was diagnosed with AITL in the groin lymph node by morphologic and immunophenotypic analyses, and molecular studies by DNA sequencing. D-2HG was measured in both tumoral tissue and in pre-treatment plasma by liquid chromatography-tandem mass spectrometry. Results: While D-2HG was markedly elevated in the tissue sample, its level in plasma was normal. We discuss this discordant D-2HG result within the context of previously reported discordant 2HG results in other IDH mutated tumors, and its implication for using circulating D-2HG as a biomarker of IDH mutation. In addition, this case also harbored mutations in RHOA, TET2, and TP53. The molecular pathogenesis is briefly discussed. Conclusion: While our case suggests that circulating D-2HG is not a reliable marker of IDH mutation in AITL, more cases need to be studied to arrive at a definite conclusion.     

Longitudinal Impact of a Randomized Clinical Trial to Improve Family Function,Reduce Maternal Stress and Improve Child Outcomes in Families of Children with ADHD

Objective Evaluate the efficacy of a 12 month nursing case-management intervention over a period of 18 months, 6 months after the end of intervention, for families of children attention deficit hyperactivity disorder (ADHD). Methods Mother and child dyads were enrolled to participate in a randomized controlled clinical trial. Children were 4–18 years old. Data were collected at baseline, 6, 12, and 18 months or 6 months after the termination of direct intervention. Longitudinal analyses, using generalized estimating equations, were conducted to assess change in study outcomes relating to family function, maternal stress, and child behavior over the 18 month period. Results Compared to control families, some family function outcomes were moderately improved in the intervention group. In particular, intervention families demonstrated substantial improvement in implementing family behavior controls (p value?=?0.038) and improvement in family satisfaction (not statistically significant p?=?0.062). Although there was improvement in the overall family function measure there was not a statistically significant difference between groups. Maternal stress and child behavior outcomes were not significantly different between control and intervention groups by the end of the intervention. Conclusions for Practice Addressing ADHD is complex and requires the assessment of comorbidities that might exacerbate negative behavior. Our findings support the latest American Academy of Pediatrics guidelines to use behavioral therapy as the first line of treatment in young children. Nursing case-management interventions that provide direct family education and improve family function, especially with respect to providing structure and behavior control, may complement and facilitate behavioral therapy for treatment of ADHD and improving child behavior.     

Combining Self-Affirmation and Implementation Intentions: Evidence of Detrimental Effects on Behavioral Outcomes

Background

There is limited evidence that self-affirmation manipulations can promote health behavior change.

Purpose

The purpose of this study was to explore whether the efficacy of a self-affirmation manipulation at promoting exercise could be enhanced by an implementation intention intervention.

Methods

Participants (Study 1?N?=?120, Study 2?N?=?116) were allocated to one of four conditions resulting from the two (self-affirmation manipulation: no affirmation, affirmation) by two (implementation intention manipulation: no implementation intention, implementation intention) experimental design. Exercise behavior was assessed 1 week post-intervention.

Results

Contrary to prediction, those participants receiving both manipulations were significantly less likely to increase the amount they exercised compared to those receiving only the self-affirmation manipulation.

Conclusion

Incorporating an implementation intention manipulation alongside a self-affirmation manipulation had a detrimental effect on exercise behavior; participants receiving both manipulations exercised significantly less in the week following the intervention.