Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies

Reactive nitrogen species may play a mechanistic role in neurodegenerative diseases by posttranslationally altering normal brain proteins. In support of this hypothesis, we demonstrate that an anti-3-nitrotyrosine polyclonal antibody stains all of the major hallmark lesions of synucleinopathies including Lewy bodies, Lewy neurites and neuraxonal spheroids in dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and neurodegeneration with brain iron accumulation type 1, as well as glial and neuronal cytoplasmic inclusions in multiple system atrophy. This antibody predominantly recognized nitrated alpha-synuclein when compared to other in vitro nitrated constituents of these pathological lesions, such as neurofilament subunits and microtubules. Collectively, these findings imply that alpha-synuclein is nitrated in pathological lesions. The widespread presence of nitrated alpha-synuclein in diverse intracellular inclusions suggests that oxidation/nitration is involved in the onset and/or progression of neurodegenerative diseases.     

Exposure to herpes simplex virus,type 1 and reduced cognitive function

Herpes simplex virus, type 1 (HSV-1) causes cold sores, keratitis and rarely, fatal encephalitis. The infection is lifelong, with sensory ganglia serving as reservoirs of latent infection. Recently, exposure to HSV-1 has also been repeatedly associated with reduced cognitive function among healthy individuals without prior encephalitis. Though HSV-1 does not elevate risk for schizophrenia (SZ) per se, exposure is likewise associated with impaired cognitive functions among SZ patients. The range of cognitive changes observed in HSV-1 exposed persons has not been investigated systematically, nor is it known whether interaction between HSV-1 exposure and SZ related factors contributes to the impairment among SZ patients. Persons with or without schizophrenia/schizophreniform disorder (N = 298 total, DSM IV criteria) were assessed for HSV-1 exposure using serum HSV-1 antibody titers. The Penn Computerized Neurocognitive battery was used to assess eight cognitive domains with respect to accuracy and speed. There were no significant case–control differences in HSV-1 exposure. The SZ/schizophreniform disorder cases were significantly impaired in all cognitive domains compared with the controls. HSV-1 exposure was also associated with reduced cognitive function in the entire sample, but the magnitude of the effects and their patterns differed from the SZ related changes. Further, statistically significant interactions between HSV-1 exposure and SZ case status were not detected. HSV-1 exposure does not elevate risk for SZ, but it is associated with reduced function in specific cognitive domains regardless of SZ diagnostic status. An ‘epidiagnostic’ model for the association is proposed to explain the results.     

The Healthy Brains and Behavior Study: objectives,design, recruitment,and population coverage

Violence is increasingly viewed as a public health issue that may be ameliorated by health‐based interventions. The Healthy Brains and Behavior Study (HBBS) aims to identify environmental and biological risk factors for aggression in late childhood and to reduce aggression through psychological and nutritional treatments. Utilizing a cross‐disciplinary collaborative research approach, the HBBS has both human and animal components. The human component has two stages consisting of risk assessment followed by treatment. The risk assessment is based on 451 community‐residing children aged 11–12 years and their caregivers, during which genetic, brain imaging, neuroendocrine, psychophysiology, environment toxicology, neurocognitive, nutrition, psychological, social and demographic risk variables are collected. Children who met criteria (N = 219) for problematic aggressive behaviors were assigned to one of four treatment groups: cognitive‐behavior therapy (CBT) alone, nutritional supplements alone, both CBT and nutrition, or treatment‐as‐usual. Treatment duration was 12 weeks and all children whether in treatment or not were followed‐up at three, six, and 12 months. The animal component assessed the effects of dietary omega‐3 fatty acids on the development of aggression. This study contributes knowledge on how biological factors interact with social factors in shaping proactive and reactive aggression and assesses the efficacy of treatment approaches to reduce childhood aggression. Copyright © 2013 John Wiley & Sons, Ltd.     

Prevalence effect in a laboratory environment

PURPOSE: To measure observer performance at various levels of prevalence. MATERIALS AND METHODS: A multiobserver multiabnormality receiver operating characteristic (ROC) study to assess the effect of prevalence on observer performance was conducted. Fourteen observers, including eight faculty members, two fellows, and four residents, interpreted 1,632 posteroanterior chest images with five prevalence levels by using a nested study design. Performance comparisons were accomplished by using a multireader multicase approach to assess the effect of prevalence from 28% (69 of 249) to 2% (31 of 1,577) on diagnostic accuracy. The mean times required to review and report a case were analyzed and compared for different levels of prevalence and readers' experience. RESULTS: Area under the ROC curve demonstrated that, with the study experimental conditions, no significant effect could be measured as a function of prevalence (P >.05) for any abnormality, group of cases, or readers. There were no significant differences (P >.05) in the mean times required to review and report cases at different prevalence levels and with different groups of readers. CONCLUSION: The consistency in the results and the size of this study suggest that with laboratory conditions, if a prevalence effect exists, it is quite small in magnitude; hence, it will not likely alter conclusions derived from such studies.     

Interactive computer-aided diagnosis of breast masses: computerized selection of visually similar image sets from a reference library

RATIONALE AND OBJECTIVES: The clinical utility of interactive computer-aided diagnosis (ICAD) systems depends on clinical relevance and visual similarity between the queried breast lesions and the ICAD-selected reference regions. The objective of this study is to develop and test a new ICAD scheme that aims improve visual similarity of ICAD-selected reference regions. MATERIALS AND METHODS: A large and diverse reference library involving 3,000 regions of interests was established. For each queried breast mass lesion by the observer, the ICAD scheme segments the lesion, classifies its boundary spiculation level, and computes 14 image features representing the segmented lesion and its surrounding tissue background. A conditioned k-nearest neighbor algorithm is applied to select a set of the 25 most "similar" lesions from the reference library. After computing the mutual information between the queried lesion and each of these initially selected 25 lesions, the scheme displays the six reference lesions with the highest mutual information scores. To evaluate the automated selection process of the six "visually similar" lesions to the queried lesion, we conducted a two-alternative forced-choice observer preference study using 85 queried mass lesions. Two sets of reference lesions selected by one new automated ICAD scheme and the other previously reported scheme using a subjective rating method were randomly displayed on the left and right side of the queried lesion. Nine observers were asked to decide for each of the 85 queried lesions which one of the two reference sets was "more visually similar" to the queried lesion. RESULTS: In classification of mass boundary spiculation levels, the overall agreement rate between the automated scheme and an observer is 58.8% (Kappa = 0.31). In observer preference study, the nine observers preferred on average the reference lesion sets selected by the automated scheme as being more visually similar than the set selected by the subjective rating approach in 53.2% of the queried lesions. The results were not significantly different for the two methods (P = .128). CONCLUSIONS: This study suggests that using the new automated ICAD scheme, the interobserver variability related issues can thus be avoided. Furthermore, the new scheme maintains the similar performance level as the previous scheme using the subjective rating method that can select reference sets that are significantly more visually similar (P < .05) than when using traditional ICAD schemes in which the mass boundary spiculation levels are not accurately detected and quantified.     

Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

Pediatric patients with achondroplasia: CT evaluation of the craniocervical junction

Twenty-six patients (4 months to 6 years old) with achondroplasia complicated by sleep apnea and/or other neurologic manifestations underwent plain computed tomography (CT) of the craniocervical junction; six also underwent CT myelography. For objectification, multiplanar reconstruction was used to complement axial plane measurements by providing coronal and sagittal measurements; multiplanar reconstruction also improved perception of the longitudinal relationships between the brain stem and subarachnoid space. A narrow subarachnoid space was found in all 26 patients; marked cord compression was present in nine, six of whom underwent CT myelography. These six had marked focal obliteration of the subarachnoid space on both plain CT and CT myelography. Since the subarachnoid space immediately above and below the craniocervical junction is normally capacious, when marked constriction was present, no additional information could have been gained from CT myelography. Thus, plain CT was shown to be sufficient for surgical planning (suboccipital decompression) in nine patients with cord compression due to achondroplasia.     

Evaluation of the role of L-arginine on spermatological parameters,seminal plasma nitric oxide levels and arginase enzyme activities in rams

The purpose of this study is to investigate the effects of L-arginine on spermatological parameters, seminal plasma nitric oxide levels and arginase enzyme activities. Fertile rams that are 2–3 years old and weighing 50–60 kg were used as material. The semen was collected by artificial vagina at 1st, 4th, 24th, 48th, 72nd, 96th and 120th hours for the control group before L-arginine administration. For treatment groups, L-arginine was administered intraperitoneally at a dose of 5 mg kg⁻¹ bw⁻¹ and semen was collected at the time point described for the control group. Spermatological characteristics of semen samples (semen volume, pH, sperm motility, concentration and abnormal sperm rate), seminal plasma nitric oxide levels and arginase enzyme activities were determined. Increased seminal plasma nitric oxide level (p < .01), seminal plasma arginase activity (p < .01), semen volume (p < .05), semen mass activity (p < .05), sperm motility (p < .05) and concentration (p < .01) and decreased abnormal sperm rate (p < .05 and p < .01) were observed by L-arginine administration. In conclusion, it may be concluded that L-arginine application in rams during the breeding season may have positive effects on rams' reproductive performance.     

Myocardial infarct size quantification by MR imaging early after coronary artery occlusion in dogs

The feasibility of using magnetic resonance (MR) imaging to estimate myocardial infarct size was explored in an in vitro model using only the inherent differences in contrast between infarcted and noninfarcted myocardium. Eight dogs underwent coronary occlusion; their hearts were removed 6 hours later. Estimates of T2 for normal and infarcted myocardium were derived from MR images. Infarct size was quantified anatomically using triphenyltetrazolium-chloride (TTC) staining and compared with MR estimates. The T2 values derived from the images clearly discriminated between infarcted (126 +/- 22 msec) and normal myocardium (88 +/- 10 msec, P less than .05), providing images with good contrast between normal and infarcted myocardium. Comparable differences in T2 values were also noted from spectrometric determinations. Estimates of infarct size by MR imaging compared well with TTC estimates (r = 0.98) over a wide range of infarct sizes from 3% to 29% of the left ventricular mass. These results suggest the potential for in vivo quantification of infarct size based on the inherent contrast difference between infarcted and normal myocardium.