Antibodies to microfilarial sheath in bancroftian filariasis--prevalence and characterization

Antibodies directed towards the sheaths of microfilariae have been implicated in the elimination of circulating microfilariae, both in experimental and human filariasis. In the present study antisheath antibodies have been detected in human sera by indirect immunoperoxidase assay (IPA) using fixed Wuchereria bancrofti microfilariae as antigen. One hundred and eighteen sera collected from an area endemic for Bancroftian filariasis were tested. While 80% of sera from microfilariae carriers had no demonstrable antisheath antibodies, more than 80% of amicrofilaraemic samples (chronic filariasis cases and endemic normals) had antisheath antibodies. The antibody activity was found in IgG, IgM and also IgE isotypes. IgG subclass typing with monospecific antisera revealed significantly higher antisheath activity in IgG2 in comparison with other IgG subclasses. The determinants on sheathed microfilariae reacting with antisheath antibodies were found to be thermostable (100 degrees C for 30 minutes), resistant to protease treatment and significantly sensitive to sodium periodate treatment, indicating the possible role of carbohydrate moieties in eliciting protective antisheath antibodies in Bancroftian filariasis.     

2011 CCNP Young Investigator Award paper: Inhibition of the cortex using transcranial magnetic stimulation in psychiatric populations: current and future directions

Several lines of evidence suggest that deficits in γ-aminobutyric acid (GABA) inhibitory neurotransmission are implicated in the pathophysiology of schizophrenia, bipolar disorder, major depressive disorder and obsessive–compulsive disorder. Cortical inhibition refers to a neurophysiological process, whereby GABA inhibitory interneurons selectively attenuate pyramidal neurons. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to measure cortical inhibition, excitability and plasticity in the cortex. These measures were traditionally specific to the motor cortex, which is an important limitation when nonmotor neurophysiological processes are of primary interest. Recently, TMS has been combined with electroencephalography (EEG) to derive such measurements directly from the cortex. This review focuses on neurophysiological studies related to inhibitory and excitatory TMS paradigms, linking dysfunctional GABAergic neurotransmission to disease states. We review evidence that suggests cortical inhibition deficits among psychiatric populations and demonstrate how each disorder has a specific neurophysiological response to treatment. We conclude by discussing the future directions of TMS combined with EEG, demonstrating the potential to identify biological markers of neuropsychiatric disorders.     

Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

Background

We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response.

Transitivity performance,relational hierarchy knowledge and awareness: Results of an instructional framing manipulation

The transitive inference (TI) paradigm has been widely used to examine the role of the hippocampus in generalization. Here we consider a surprising feature of experimental findings in this task: the relatively poor transitivity performance and levels of hierarchy knowledge achieved by adult human subjects. We focused on the influence of the task instructions on participants' subsequent performance—a single‐word framing manipulation which either specified the relation between items as transitive (i.e., OLD‐FRAME: choose which item is “older”) or left it ambiguous (i.e., NO‐FRAME: choose which item is “correct”). We show a marked but highly specific effect of manipulating prior knowledge through instruction: transitivity performance and levels of relational hierarchy knowledge were enhanced, but premise performance unchanged. Further, we show that hierarchy recall accuracy, but not conventional awareness scores, was a significant predictor of inferential performance across the entire group of participants. The current study has four main implications: first, our findings establish the importance of the task instructions, and prior knowledge, in the TI paradigm—suggesting that they influence the size of the overall hypothesis space (e.g., to favor a linear hierarchical structure over other possibilities in the OLD‐FRAME). Second, the dissociable effects of the instructional frame on premise and inference performance provide evidence for the operation of distinct underlying mechanisms (i.e., an associative mechanism vs. relational hierarchy knowledge). Third, our findings suggest that a detailed measurement of hierarchy recall accuracy may be a more sensitive index of relational hierarchy knowledge, than conventional awareness score—and should be used in future studies investigating links between awareness and inferential performance. Finally, our study motivates an experimental setting that ensures robust hierarchy learning across participants—therefore facilitating study of the neural mechanisms underlying the learning and representation of linear hierarchies. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Biomimetic Approach to Perforation Repair Using Dental Pulp Stem Cells and Dentin Matrix Protein 1

Introduction

Dentin regeneration could be an ideal treatment option to restore tissue function. This study was conducted to evaluate the ability of dental pulp stem cells (DPSCs) and dentin matrix protein 1 (DMP1) impregnated within a collagen scaffold to regenerate dentin.

Methods

Simulated perforations were created in 18 dentin wafers made from freshly extracted human molars. Six groups were established. They were (1) empty wafers, (2) mineral trioxide aggregate, (3) collagen scaffold, (4) scaffold with DMP1, (5) scaffold with DPSCs, and (6) scaffold with DPSCs and DMP1. One sample was placed subcutaneously in each mouse with three mice in each group. After 12 weeks, the samples were subjected to radiographic, histological, and immunohistochemical evaluations.

Results

DPSCs impregnated within a collagen scaffold differentiated into odontoblast-like cells forming a highly cellular, vascular, and mineralized matrix in the presence of DMP1.

Conclusions

A triad consisting of DPSCs, DMP1, and a collagen scaffold promotes dentin regeneration in a simulated perforation repair model.     

A meta-analysis of cortical inhibition and excitability using transcranial magnetic stimulation in psychiatric disorders

ObjectiveTo evaluate transcranial magnetic stimulation (TMS) measures of inhibition and excitation in obsessive–compulsive disorder (OCD), major depressive disorder (MDD) and schizophrenia (SCZ).MethodsParadigms included: short-interval cortical inhibition (SICI), cortical silent period (CSP), resting motor threshold, intracortical facilitation, and motor evoked potential amplitude. A literature search was performed using PubMed, Ovid Medline, Embase Psychiatry and PsycINFO 1990 through April 2012.ResultsA significant Hedge’s g was found for decreased SICI (g = 0.572, 95% confidence interval [0.179, 0.966], p = 0.004), enhanced intracortical facilitation (g = 0.446, 95% confidence interval [0.042, 0.849], p = 0.030) and decreased CSP (g = ?0.466, 95% confidence interval [?0.881, ?0.052], p = 0.027) within the OCD population. For MDD, significant effect sizes were demonstrated for decreased SICI (g = 0.641, 95% confidence interval [0.384, 0.898], p = 0.000) and shortened CSP (g = ?1.232, 95% confidence interval [?1.530, ?0.933], p = 0.000). In SCZ, a significant Hedge’s g was shown for decreased SICI (g = 0.476, 95% confidence interval [0.331, 0.620], p = 0.000).ConclusionInhibitory deficits are a ubiquitous finding across OCD, MDD, SCZ and enhancement of intracortical facilitation is specific to OCD.SignificanceProvides a clear platform from which diagnostic procedures can be developed.     

Improvement in intraoperative transcranial electrical motor-evoked potentials in tethered cord surgery: an analysis of 45 cases

Background

Improvement of transcranial electrical motor-evoked potentials (TeMEPs) following untethering during tethered cord surgery (TCS) and its clinical significance have not been analyzed in the literature.

Methods

Forty-five consecutive cases of tethered cord were operated on with multimodality intraoperative neurophysiological monitoring (IONM) between February 2005 and January 2012. Intraoperative TeMEP change was classified as improvement, worsening or no change. Motor, sensory, bladder and bowel symptoms and signs were evaluated preoperatively, in the first week post-surgery and at the last follow-up (maximum of 2 years).

Results

Patient age ranged from 5 to 44 years (mean, 16?±?10 years), with 30 children. Intraoperative MEPs improved in 23 (51 %), remained the same in 21 (46.7 %) and worsened in 1 (2 %) patient. Motor improvement occurred in 7 patients and clinical improvement in 17 patients in the immediate postoperative period. Postoperative neurological worsening occurred in one patient (2.2 %). Improved and stable MEPs correlated with the motor (p?=?0.002) and clinical improvement (p?=?0.02) in the immediate postoperative period. Follow-up was available in 35 patients (77.7 %), ranging from 5 to 24 months (median, 21 months; mean, 17.7?±?6.8 months). There was late clinical improvement in 73.5 % of the patients in whom the intraoperative MEP had remained the same or improved. However, there was no statistically significant correlation between MEP change and long-term outcome.

Conclusions

Intraoperative MEP improvement occurs in about 50 % of the patients following successful untethering. This finding probably provides support to the ischemic theory of tethered cord syndrome.     

TDP-43 in ubiquitinated inclusions in the inferior olives in frontotemporal lobar degeneration and in other neurodegenerative diseases: a degenerative process distinct from normal ageing

Ubiquitin immunoreactive (UBQ-ir) inclusions were present to variable extents in the inferior olivary nucleus (ION) in 37/48 (77%) patients with frontotemporal lobar degeneration (FTLD), in 10/11 (91%) patients with motor neurone disease (MND), in 5/5 (100%) patients with Alzheimer’s disease (AD), 5/7 (71%) patients with dementia with Lewy bodies, 13/19 (68%) patients with Parkinson’s disease, 11/11(100%) patients with Progressive Supranuclear Palsy, 2/6 (33%) patients with Multisystem Atrophy, 1/3 (33%) patients with Huntington’s disease and in 14/14 (100%) normal elderly control subjects. In FTLD, UBQ-ir inclusions were present in 26/32 (81%) patients with FTLD-U, in 10/15 (67%) patients with tauopathy, and in the single patient with Dementia Lacking Distinctive Histology. In 13 FTLD-U patients, and in a single AD and in 2 MND patients, the UBQ-ir inclusions had a rounded, spicular or skein-type appearance, and these were also TDP-43 immunoreactive (TDP-43-ir). In all other affected patients in all diagnostic groups, and in control subjects, the UBQ-ir neuronal cytoplasmic inclusions (NCI) were of a conglomerated type, resembling a cluster of large granules or globules, but were never TDP-43-ir. In 3 of the 13 FTLD-U patients with spicular NCI, conglomerated NCI were also present but in separate cells. Double-labelling immunohistochemistry, and confocal microscopy, for UBQ and TDP-43 confirmed that only the spicular UBQ-ir inclusions in patients with FTLD-U, AD and MND contained TDP-43, though in these patients there were occasional TDP-43 immunoreactive inclusions that were not UBQ-ir. Nuclear TDP-43 immunoreactivity was absent in ION in FTLD-U, AD or MND when TDP-43 cytoplasmic inclusions were present, but remained in neurones with UBQ-ir, TDP-43 negative inclusions. The target protein within the UBQ-ir, TDP-43-negative inclusions remains unknown, but present studies indicate that this is not tau, neurofilament or internexin proteins. These TDP-43 negative, UBQ-ir inclusions appear to be more related to ageing than neurodegeneration, and are without apparent diagnostic significance. The pathophysiological mechanism leading to their formation, and any consequences their presence may have on nerve cell function, remain unknown.     

Mechanisms of fatigue in normal intercostal muscle and muscle from patients with myasthenia gravis

Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility. © 1993 John Wiley & Sons, Inc.