Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca²⁺ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.     

A novel retroviral mutagenesis screen identifies prognostic genes in RUNX1 mediated myeloid leukemogenesis

Using a novel retroviral shuttle vector approach we identified genes that collaborate with a patient derived RUNX1 (AML1) mutant. RUNX1 mutations occurs in 40% of myelodysplastic syndromes (MDS). MDS are a group of hematopoietic stem cell disorders that are characterized by dysplasia that often progress to acute myeloid leukemia (AML). Our goal was to identify genes dysregulated by vector-mediated genotoxicity that may collaborate with the RUNX1 mutant (D171N). D171N expressing cells have a survival and engraftment disadvantage and require additional genetic lesions to survive and persist. By dysregulating genes near the integrated vector provirus, the shuttle vector can promote transformation of D171N cells and tag the nearby genes that collaborate with D171N. In our approach, a gammaretroviral shuttle vector that expresses D171N is used to transduce CD105⁺, Sca-1⁺ mouse bone marrow. Mutagenized cells are expanded in liquid culture and vector integration sites from surviving cells are then identified using a retroviral shuttle vector approach. We repeatedly recovered integrated vector proviruses near genes (Itpkb, Ccdc12, and Nbeal2). To assess the prognostic significance of the genes identified we examined differential expression, overall survival, and relapse free survival of AML patients with alteration in the genes identified using The Cancer Genome Atlas (TCGA) AML data set. We found that ITPKB functions as an independent factor for poor prognoses and RUNX1 mutations in conjunction with ITPKB, CCDC12, and NBEAL2 have prognostic potential in AML.     

Computer-assisted capnogram analysis

Characteristic abnormal carbon dioxide waveforms from patients with mechanically ventilated lungs are observed when, for example, valves are incompetent, the airway is obstructed, the breathing circuit becomes disconnected, or a patient overrides mechanical ventilation with spontaneous breaths. Automated observation of the carbon dioxide waveform provides a uniform, concise, and consistent interpretation of the capnogram. This article describes a computer algorithm for analyzing and classifying capnograms as normal or as belonging to one of the categories above. The algorithm also generates a diagnostic message when the capnogram deviates from a learned norm for at least three consecutive waveforms (and thus reduces the influence of artifacts). Clinical experience shows reliable waveform recognition by the algorithm.Supported in part by a grant from Datascope Corporation.The authors thank David A. Paulus, MD, and Jeffrey M. Feldman, MD, for their assistance and advice.     

Peripheral neuropathy as initial manifestation of primary systemic vasculitides

Peripheral neuropathies are well-known complications of primary systemic vasculitides. In rare cases, peripheral neuropathies are among the first symptoms of these diseases. In this prospective study, 89 consecutive adult patients with newly diagnosed primary systemic vasculitis were screened, of whom 22 patients (25 %, 12 men, ten women, mean age, 59 years, range, 26–82 years) suffered from peripheral neuropathy due to systemic vasculitis at initial presentation. Peripheral neuropathy was most frequent in newly diagnosed patients with eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome, 12 out of 20 patients, 60 %) and polyarteritis nodosa (three out of six patients, 50 %), and less common in patients with granulomatosis with polyangiitis (six out of 47 patients, 13 %) and microscopic polyangiitis (one out of 16 patients, 6 %). Multiplex mononeuropathy was more frequent (n = 13, 59 %) than symmetric polyneuropathy (n = 9, 41 %). The nerves commonly affected were the peroneal nerve, followed by the sural, posterior tibial, and median nerves. Treatment options were chosen according to current guidelines of the national neurological and rheumatologic societies, with initial corticosteroid monotherapy for patients with a mild disease form and a combination of corticosteroids and intravenously pulsed cyclophosphamide for patients with a more extended organ involvement. During follow-up (mean, 34 months, range, 12–112 months), new neurological complications were rare (9 %): One patient suffered from a cerebral infarct while another patient sustained epileptic seizures. Two patients (9 %) died from sepsis (after 60 months) or severe gastrointestinal bleeding (after 13 months). The degree of neurological disability measured by the functional disability score (described by Prineas) improved in 20 of 22 patients after 12 months of therapy.     

A personalized systems medicine approach to refractory rumination

Rationale, aims and objectives As with many functional disorders, rumination syndrome poses a great dilemma when approached via standard of care. This case report illustrates how rumination syndrome may be effectively approached using the systems medicine. Method The patient's treatment involved two distinctively different treatment cycles. Initially she was treated in an academic tertiary inpatient and outpatient multidisciplinary program with a primary symptom‐based focus with little improvement. She subsequently sought care at a systems‐based integrative medicine clinic within an academic family medicine centre, which identified the inciting events, diagnosed the current pathology and developed a stepwise treatment plan. Results The patient is now rumination free. Conclusion Chronic or refractory diseases, especially when regarded as ‘functional’ may be approached by a systems medicine methodology, which allows physicians to fine‐tune the vast amount of specific pieces of knowledge to achieve an integrated approach to managing the whole person.     

Does habitual body avoidance and checking behavior influence the decrease of negative emotions during body exposure in eating disorders?

Abstract

The aim of the present study was to assess whether habitual body avoidance and body-checking behavior influences the decrease of negative emotions during body exposure. Twenty-one eating-disordered female participants completed the Body Image Avoidance Questionnaire and the Body Checking Questionnaire. On another day, a 40-min body exposure session was conducted under standardized conditions. Every 10 min, negative emotions were assessed. It was shown that the extent of decrease in negative emotions during the body exposure session could be predicted by a lower degree of body checking. Results indicate that habitual checking behavior seems to negatively influence the effect of body exposure. Therefore, an adaptation of body exposure to patients with a higher degree of body-checking behavior might be promising.     

Spatial Resolution of an Eye Containing a Grouped Retina: Ganglion Cell Morphology and Tectal Physiology in the Weakly Electric Fish Gnathonemus petersii

The retina of the weakly electric fish Gnathonemus petersii is a so‐called grouped retina where photoreceptors are bundled. These bundles are regarded as functional units and this type of retinal specialization is uniquely found in teleosts. To understand how this anatomical organization influences visual information processing we investigated the morphology and distribution of retinal ganglion cells (GCs) and the response properties of retinal afferents terminating in the major retinorecipient area, the optic tectum. GCs were classified based on their dendritic morphology (dendritic field diameters <90–100 μm: narrow‐field GCs; 110–280 μm: widefield GCs; >280 μm: giant GCs). Within these classes subtypes were distinguished based on the ramification patterns of the dendrites in the sublaminae of the inner plexiform layer. Properties of presumed optic nerve terminals were investigated in the optic tectum using extracellular recordings. Physiological classes could be observed based on their response to visual stimuli (on; off; on‐off, and fast units). Receptive field sizes and spatiotemporal properties were classified and the topographical representation of the visual space was mapped in the tectum. Gratings of low spatial frequencies were best responded to and followed up to high temporal frequencies (>30 Hz). Most of the recorded units were directionally selective. No evidence of distorted topographies in the tectum was found, i.e., no overrepresentation of the retina was seen in the tectum opticum. The grouped retina of G. petersii seems to be optimized for the detection of large, fast objects in an environment of low optical quality. J. Comp. Neurol. 521:4075–4093, 2013. © 2013 Wiley Periodicals, Inc.