Neurofeedback training in children with ADHD: 6-month follow-up of a randomised controlled trial

Neurofeedback (NF) could help to improve attentional and self-management capabilities in children with attention-deficit/hyperactivity disorder (ADHD). In a randomised controlled trial, NF training was found to be superior to a computerised attention skills training (AST) (Gevensleben et al. in J Child Psychol Psychiatry 50(7):780–789, 2009). In the present paper, treatment effects at 6-month follow-up were studied. 94 children with ADHD, aged 8–12 years, completed either 36 sessions of NF training (n = 59) or a computerised AST (n = 35). Pre-training, post-training and follow-up assessment encompassed several behaviour rating scales (e.g., the German ADHD rating scale, FBB-HKS) completed by parents. Follow-up information was analysed in 61 children (ca. 65%) on a per-protocol basis. 17 children (of 33 dropouts) had started a medication after the end of the training or early in the follow-up period. Improvements in the NF group (n = 38) at follow-up were superior to those of the control group (n = 23) and comparable to the effects at the end of the training. For the FBB-HKS total score (primary outcome measure), a medium effect size of 0.71 was obtained at follow-up. A reduction of at least 25% in the primary outcome measure (responder criterion) was observed in 50% of the children in the NF group. In conclusion, behavioural improvements induced by NF training in children with ADHD were maintained at a 6-month follow-up. Though treatment effects appear to be limited, the results confirm the notion that NF is a clinically efficacious module in the treatment of children with ADHD.     

Concanavalin A Derivatives with Altered Biological Activities

Chemical derivatization of tetrameric concanavalin A (Con A) with succinic anhydride or acetic anhydride converts the protein to a dimeric molecule without altering its carbohydrate-binding specificity. At low concentrations, the dose-response curves for the mitogenic stimulation of mouse spleen cells by native Con A and succinyl-Con A are similar. Above lectin concentrations of 10 mug/ml, however, the response to Con A is diminished, while that for succinyl-Con A does not decrease until much higher doses are reached. We have attributed this difference mainly to the higher rate of cell death induced by the native Con A molecule. Con A also shows a greater capacity than succinyl-Con A to agglutinate sheep erythrocytes and to inhibit cap formation by immunoglobulin receptors on spleen cells. Moreover, at low concentrations, Con A induced its glycoprotein receptors to form caps, but succinyl-Con A did not induce cap formation. Addition of antibodies directed against Con A to succinyl-Con A bound on cells restored the properties of agglutination, inhibition of immunoglobulin receptor cap formation, and induction of cap formation by Con A receptors. Similar results have been obtained for acetyl-Con A. These data suggest that the altered biological activities of succinyl-Con A and acetyl-Con A are attributable to their reduced valence.     

A Physiological Mechanism for Hebb''s Postulate of Learning

Hebb's postulate of learning envisages that activation or inactivation of extant synaptic contacts in plastic neural networks depends on the synchronous impulse activity of pre- and postsynaptic nerve cells. The physiological mechanism proposed here for this process posits that at synapses acting according to Hebb's postulate, the receptors for the neurotransmitter are eliminated from the postsynaptic membrane by the transient reversals of the sign of membrane polarization that occur during action potential impulses in the postsynaptic cell. But, since the release of neurotransmitter drives the membrane potential of the synaptic zone towards a level about half-way between the negative-inside resting potential and the positive-inside action potential, it would follow that the membrane patches surrounding the receptors of a synapse whose activity has contributed to setting off the postsynaptic impulse would be spared the full extent of the noxious polarity reversal. This mechanism can account for a neurophysiologically documented example of the operation of Hebb's postulate, namely the plasticity of the connections between fourth- and fifth-order neurons in the visual cortex of cats.     

Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol)

Cardiovascular and peripheral adaptations to an aerobic conditioning program were studied in 30 hypertensive adults taking either placebo, beta 1-selective beta-adrenergic blocker (metoprolol) or beta 1-nonselective beta-adrenergic blocker (propranolol). The placebo group increased aerobic capacity (VO2max) 24% (p less than 0.002), largely explained by an increased peripheral arteriovenous (AV) oxygen difference with minimal changes in cardiac size and function. Resting blood pressure and total systemic resistance also decreased. The group taking a beta 1-selective beta blocker increased VO2max 8% (p less than 0.05), reduced resting blood pressure but had no significant change of AV oxygen difference or cardiac size or function. The group taking the beta 1-nonselective beta blocker propranolol had no increase in VO2max, no decrease in resting blood pressure and no cardiovascular or peripheral adaptations to the exercise program. Thus, beta 1-selective and beta 1-nonselective beta blockers attenuate conditioning in hypertensive patients to differing degrees, in each case by blocking peripheral mechanisms of conditioning.     

Distal femur fractures of the elderly--different treatment options in a biomechanical comparison

Background

Fractures of the distal femur, especially in the elderly patient, are an unsolved problem in orthopaedic and trauma surgery. Poor bone stock quality caused by osteoporosis often results in bad implant anchorage in the distal part with a high risk of secondary failures such as cutout. This study investigates the biomechanical characteristics of four implants with different distal locking options under quasi-static torsional and cyclic axial loading. Therefore, an osteoporotic bone model simulating severe osteoporotic conditions was used.

Methods

Four different implants (T2 intramedullary nail, supracondylar nail (SCN), distal femoral nail (DFN) and the AxSOS angular stable plate) with different distal locking options were instrumented using an osteoporotic bone model. Five specimens per implant and per loading type (torsional and axial) were used. Mechanical testing was performed under physiologic loading conditions. First, a torsional test was performed in internal and external rotation (10 Nm), with a new specimen; a stepwise cyclic axial loading was conducted until failure of the construct.

Findings

For torsional loading, the lowest range of motion (ROM) and neutral zone (NZ) was found for the AxSOS plate construct. The SCN and T2 constructs showed similar results, and the highest ROM and NZ were found for the constructs treated with the DFN. Axial stiffness was highest for SCN constructs and in the same range for DFN and T2. The lowest stiffness showed in the AxSOS plate constructs with 47% of SCN stiffness. Under cyclic axial loading, the SCN constructs showed the highest number of cycles to failure, followed by AxSOS (70%), DFN (69%) and T2 (48%).

Interpretation

In conclusion of this biomechanical study, we can clinically suggest that, if, in general, torsional stability is required (e.g., for bedridden patients) the AxSOS plate will be sufficient. By contrast, the findings of this study support the fact that the SCN should be considered for mobile patients where early postoperative mobilisation for rehabilitation is desired.     

Compartment-specific expression and function of the chemokine IP-10/CXCL10 in a model of renal endothelial microvascular injury

The recruitment of inflammatory cells into renal tissue, mainly T cells and monocytes, is a typical feature of various renal diseases such as glomerulonephritis, thrombotic angiopathies, allograft rejection, and vasculitis. T cells predominantly infiltrate the tubulointerstitium, whereas monocytes are present in the tubulointerstitial and glomerular compartment. Because chemokines play a pivotal role in leukocyte trafficking under inflammatory conditions, this study investigated whether a differential expression of chemokines contributes to the precise coordination of leukocyte subtype trafficking in a rat model of renal microvascular endothelial injury. Renal microvascular endothelial injury was induced in rats by selective renal artery perfusion with an anti-endothelial antibody. Induction of the disease led to severe glomerular and tubulointerstitial endothelial injury with subsequent upregulation of chemokines followed by inflammatory cell recruitment. Among the analyzed chemokine mRNA, IP-10/CXCL10 (119-fold), acting via CXCR3 on activated T cells, and MCP-1/CCL2 (65-fold), acting via CCR2 on monocytes, were by far the most strongly upregulated chemokines. In situ hybridization revealed that IP-10/CXCL10 mRNA was selectively expressed by endothelial cells in the tubulointerstitial area, co-localizing with infiltrating T cells. Despite extensive damage of glomerular vasculature, no IP-10/CXCL10 expression by glomerular endothelial cells was detected. MCP-1/CCL2 mRNA in contrast was detectable in the glomerulus and the tubulointerstitium. Treatment with a neutralizing anti-IP-10/CXCL10 antibody significantly reduced the number of infiltrating tubulointerstitial T cells without affecting monocyte migration and led to an improved renal function. Our study demonstrates a role of IP-10/CXCL10 on T cell recruitment in a rat model of renal endothelial microvascular injury. Furthermore, a differential chemokine expression profile by endothelial cells in different renal compartments was found. These findings are consistent with the hypothesis that functional heterogeneity of endothelial cells from different vascular sites exists and provide an insight into the molecular mechanisms that may mediate compartment-specific T cell and monocyte recruitment in inflammatory renal disease.     

Hounsfield units as predictor for cage subsidence and loss of reduction: following posterior-anterior stabilization in thoracolumbar spine fractures

Study design

A retrospective, longitudinal cohort study.

Objective

The purpose of this study was to examine whether Hounsfield units (HUs), as an alternative bone mineral density measurement to dual-energy X-ray absorptiometry and quantitative computed tomography, which lead to additional radiation exposure for patients, has an effect on the maintenance of reduction in bisegmental Cobb angle (CA) and cage subsidence in patients who receive bisegmental spine stabilization after traumatic thoracolumbar spine fractures.

Methods

A total of 81 patients with a mean follow-up of 12 months were analyzed. CAs and cage subsidence were measured intraoperatively and at follow-up. HU was measured, and patients were subsequently assigned based on HU to three HU subgroups (group 1: HU?<?110 [poor bone quality (BQ)]; group 2: HU 180–110 [diminished BQ]; group 3: HU?>?180 [good BQ]).

Results

Following anterior stabilization, loss of reduction and cage subsidence differed between patients with poor and diminished BQ but not significantly, and both groups showed significantly more loss of reduction and cage subsidence than patients with good BQ.

Conclusion

BQ, estimated with HU, had significant effects on cage subsidence and loss of reduction. We recommend measuring HU before surgery and applying additional treatment strategies, such as polymethylmethacrylate augmentation of endplates or anterior plates, for patients with HU?<?180.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

Open image in new window

     

Intracranial Aneurysms Treated by Flow-Diverting Stents: Long-Term Follow-Up with Contrast-Enhanced Magnetic Resonance Angiography

Purpose

Long-term data on aneurysm treatment with flow-diverting stents are still sparse, and follow-up protocols differ widely between institutions. We present long-term results, with a focus on the usefulness of contrast-enhanced MR angiography (ceMRA).

Materials and Methods

Interventions and follow-up imaging of patients with aneurysms treated by flow-diverting stents (“Pipeline,” “Silk” and “FRED” models) without additional coiling were analyzed. All MRI scans included dedicated two-phase ceMRA. Aneurysm occlusion rates, size of the aneurysmal sac and complications were evaluated on MRI and digital subtraction angiography (DSA), where available. The ability of ceMRA to depict aneurysm occlusion and stent patency was graded on a three-point scale.

Results

Twenty-five patients with 102 MRI scans were included. The median duration of follow-up was 830 days. Aneurysm occlusion rates were 52% at 3 months (10 of 19 patients), 72% at 6 months (18/25) and 84% overall (21/25). Shrinkage of the aneurysmal sac was found in 19 patients (76%) and in 12 cases to <50% of the original size (48%). CeMRA assessability of aneurysmal occlusion was graded as good in all cases. When compared to DSA (18 cases), ceMRA had a sensitivity of 100% and specificity of 91% regarding aneurysm remnant detection. Assessability of the stent lumen varied and was limited in most cases.

Conclusions

Flow-diverter treatment achieves high occlusion rates and can cause major aneurysm shrinkage. CeMRA is highly valuable regarding imaging of the aneurysmal sac. There are limitations regarding the assessability of the stent lumen on ceMRA.

Level of Evidence

Level 4, Case Series.

     

Graded synaptic transmission at the Caenorhabditis elegans neuromuscular junction

Most neurotransmission is mediated by action potentials, whereas sensory neurons propagate electrical signals passively and release neurotransmitter in a graded manner. Here, we demonstrate that Caenorhabditis elegans neuromuscular junctions release neurotransmitter in a graded fashion. When motor neurons were depolarized by light-activation of channelrhodopsin-2, the evoked postsynaptic current scaled with the strength of the stimulation. When motor neurons were hyperpolarized by light-activation of halorhodopsin, tonic release of synaptic vesicles was decreased. These data suggest that both evoked and tonic neurotransmitter release is graded in response to membrane potential. Acetylcholine synapses are depressed by high-frequency stimulation, in part due to desensitization of the nicotine-sensitve ACR-16 receptor. By contrast, GABA synapses facilitate before becoming depressed. Graded transmission and plasticity confer a broad dynamic range to these synapses. Graded release precisely transmits stimulation intensity, even hyperpolarizing inputs. Synaptic plasticity alters the balance of excitatory and inhibitory inputs into the muscle in a use-dependent manner.