Chronic changes in electrical excitability profoundly affect synaptic transmission throughout the lifetime of a neuron. We have previously explored persistent presynaptic silencing, a form of synaptic depression at glutamate synapses produced by ongoing neuronal activity and by strong depolarization. Here we investigate the involvement of the ubiquitin-proteasome system (UPS) in the modulation of presynaptic function. We found that proteasome inhibition prevented the induction of persistent presynaptic silencing. Specifically, application of the proteasome inhibitor MG-132 (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal) prevented decreases in the size of the readily releasable pool of vesicles and in the percentage of active synapses. Presynaptic silencing was accompanied by decreases in levels of the priming proteins Munc13-1 and Rim1. Importantly, overexpression of Rim1␣ prevented the induction of persistent presynaptic silencing. Furthermore, strong depolarization itself increased proteasome enzymatic activity measured in cell lysates. These results suggest that modulation of the UPS by electrical activity contributes to persistent presynaptic silencing by promoting the degradation of key presynaptic proteins.

Functional connectivity (fcMRI) was analyzed in individuals with spastic diplegia and age-matched controls. Pearson correlations (r-values) were computed between resting state spontaneous activity in selected seed regions (sROI) and each voxel throughout the brain. Seed ROI were centered on foci activated by tactile stimulation of the second fingertip in somatosensory and parietal dorsal attention regions. The group with diplegia showed significantly expanded networks for the somatomotor but not dorsal attention areas. These expanded networks overran nearly all topological representations in somatosensory and motor areas despite a sROI in a fingertip focus. A possible underlying cause for altered fcMRI in the group with dipegia, and generally sensorimotor deficits in spastic diplegia, is that prenatal third trimester white-matter injury leads to localized damage to subplate neurons. We hypothesize that intracortical connections become dominant in spastic diplegia through successful competition with diminished or absent thalamocortical inputs. Similar to the effects of subplate ablations on ocular dominance columns (Kanold and Shatz, Neuron 2006;51:627-638), a spike timing-dependent plasticity model is proposed to explain a shift towards intracortical inputs.

Background: The utility of dairy ingredients in the supplementary foods used in the treatment of childhood moderate acute malnutrition (MAM) remains unsettled. Objective: We evaluated the effectiveness of a peanut-based readyto-use supplementary food (RUSF) with soy protein compared with a novel RUSF containing dairy ingredients in the form of whey permeate and whey protein concentrate in the treatment of children with MAM. Design: We conducted a randomized, double-blind clinical effectiveness trial involving rural Malawian and Mozambican children 6-59 mo of age with MAM treated with either soy RUSF or a novel whey RUSF treatment of w75 kcal $ kg 21 $ d 21 for up to 12 wk. Results: The proportion of children that recovered from MAM was significantly higher in the group that received whey RUSF (960 of 1144; 83.9%) than in the group that received soy RUSF (874 of 1086; 80.5%; P , 0.04; risk difference 3.4%, 95% CI: 0.3%, 6.6%). Children who consumed whey RUSF also demonstrated better growth markers, with a higher mean midupper arm circumference (MUAC) at the time of discharge (P , 0.009), greater MUAC gain during the course of treatment (P , 0.003), higher mean weight-forheight z score at discharge (P , 0.008), and greater weight gain (P , 0.05). No significant differences were identified in length gain or time to recovery between the 2 groups. Conclusion: This study highlights the importance of milk protein in the treatment of MAM, because the use of a novel whey RUSF resulted in higher recovery rates and improved growth than did soy RUSF, although the whey RUSF supplement provided less total protein and energy than the soy RUSF. This study was registered at clinicaltrials.gov as NCT01790048.Am J Clin Nutr 2016;103:926-33.

Health care costs in the US have grown rapidly over the past several decades. As a result, there has been increasing interest in strategies to contain health care costs, without sacrificing the quality of medical care. While many factors contribute to rising costs, one major contributor to health care expenditure is diagnostic imaging. In this article, we address the growth of diagnostic imaging, the financial and clinical adverse effects of over-utilization, and discuss a variety of strategies to encourage appropriate use of diagnostic testing.

Hypertrophic olivary degeneration (HOD) is caused by disruption of the triangle of Guillain and Mollaret. We describe a child with a primitive neuroendocrine tumor who developed an expansile nonenhancing lesion in the olive after surgery and radiation therapy. Diffusion tensor imaging and tractography showed disruption of the central tegmental tract consistent with HOD. Subsequent transient enhancement of the olive was consistent with early radiation injury. Knowledge of coexisting complications such as HOD and radiation injury is essential for proper management.