Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex

The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation-guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10-s 5-Hz TMS pulses, with 50-s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF-MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief (p<0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 (p<0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.     

Hyaluronan reversed proteoglycan synthesis inhibited by mechanical stress: possible involvement of antioxidant effect

Introduction  

Abnormal mechanical stress loaded on the cartilage leads to the osteoarthritis (OA). Although intraarticular hyaluronan (HA) injection is an effective treatment for OA, the underlying mechanism has not been made clear.     

Experimental evaluation of relapse-risks in operated zygoma fractures

Objectives

Prevention of relapse, or postoperative dislocation, of the fixed zygoma is necessary to achieve optimal results in the treatment of zygoma fractures. Assuming that the occurrence of intensified stresses on mastication at the screw–bone interface (SBI) constitutes the essential cause of the relapse, we evaluated the stresses for three different fixation methods—fixation at the frontal process (FP), inferior orbital rim (IOR), and zygomatico-maxillary buttress (ZMB).

Methods

We used 10 computer-aided design (CAD) models simulating zygoma fractures in the experiment. For each CAD model, we fixed the fractured zygoma with four screws and one mini-plate at the FP, IOR, or ZMB. After applying a 5.5 kg force simulating mastication, we calculated the intensity and distribution patterns of the stresses occurring at the SBIs of the fixation screws using the finite element method. Thereby, we evaluated dynamic stability of the fixed zygoma for each of the three fixation methods.

Results

Greater stresses occur at the SBIs with IOR fixation than at those with FP and ZMB fixation. Although the stresses occurring at the SBIs on mastication demonstrated evenly distributed patterns with the FP and ZMB fixation, the stresses demonstrated concentration on one screw with the IOR fixation.

Conclusions

The fixed zygoma is more likely to cause relapse with the IOR fixation than with the FP or ZMB fixation. Hence, in performing zygoma fixation at the IOR, care should be taken to minimize the likelihood of postoperative relapse that is caused by skewed distribution of the stresses on the fixation screws.     

Development of demyelinating lesions in progressive multifocal leukoencephalopathy (PML): Comparison of magnetic resonance images and neuropathology of post‐mortem brain

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by opportunistic infection of JC polyomavirus (JCV). Today, increased attention has been focused on PML development in multiple sclerosis (MS) patients under disease‐modifying therapies (DMT). Although in the acquired immunodeficiency syndrome (AIDS) era, PML was thought to be a rapidly progressive disease with poor prognosis, drug‐associated PML is relatively slow in progress, and a favorable outcome may be expected with early diagnosis. However, early PML diagnosis on magnetic resonance imaging (MRI) is frequently difficult, and JCV DNA copy number in cerebrospinal fluid (CSF) is usually low. To facilitate early PML diagnosis on MRI, the pre‐mortem images were compared with neuropathology of the post‐mortem brain, and underlying pathology corresponding to the MRI findings was evaluated. As a result, PML lesions of the autopsied brain were divided into three parts, based on the disease extension patterns: (A) Progressive white matter lesion in the right frontoparietal lobe including the precentral gyrus. Huge demyelinated lesions were formed with fusions of numerous small lesions. (B) Central lesion including deep gray matters, such as the putamen and thalamus. The left thalamic lesion was contiguous with the pontine tegmentum. (C) Infratentorial lesion of brainstem and cerebellum. Demyelination in the pontine basilar region and in cerebellar white matter was contiguous via middle cerebellar peduncles (MCPs). In addition, (D) satellite lesions were scattered all over the brain. These observations indicate that PML lesions likely evolve with three steps in a tract‐dependent manner: (1) initiation; (2) extension/expansion of demyelinating lesions; and (3) fusion. Understanding of the PML disease evolution patterns would enable confident early diagnosis on MRI, which is essential for favorable prognosis with good functional outcome.     

A longitudinal study of socioeconomic status,family processes,and child adjustment from preschool until early elementary school: the role of social competence

Objective

Using a short-term longitudinal design, this study examined the concurrent and longitudinal relationships among familial socioeconomic status (SES; i.e., family income and maternal and paternal education levels), marital conflict (i.e., constructive and destructive marital conflict), parenting practices (i.e., positive and negative parenting practices), child social competence (i.e., social skills), and child behavioral adjustment (i.e., internalizing and externalizing problems) in a comprehensive model.

Methods

The sample included a total of 1604 preschoolers aged 5 years at Time 1 and first graders aged 6 years at Time 2 (51.5% male). Parents completed a self-reported questionnaire regarding their SES, marital conflict, parenting practices, and their children’s behavioral adjustment. Teachers also evaluated the children’s social competence.

Results

The path analysis results revealed that Time 1 family income and maternal and paternal education levels were respectively related to Time 1 social skills and Time 2 internalizing and externalizing problems, both directly and indirectly, through their influence on destructive and constructive marital conflict, as well as negative and positive parenting practices. Notably, after controlling for Time 1 behavioral problems as mediating mechanisms in the link between family factors (i.e., SES, marital conflict, and parenting practices) and behavioral adjustment, Time 1 social skills significantly and inversely influenced both the internalization and externalization of problems at Time 2.

Conclusions

The merit of examining SES, marital conflict, and parenting practices as multidimensional constructs is discussed in relation to an understanding of processes and pathways within families that affect child mental health functioning. The results suggest social competence, which is influenced by the multidimensional constructs of family factors, may prove protective in reducing the risk of child maladjustment, especially for children who are socioeconomically disadvantaged.

     

Interleukin-4 stimulates proliferation of endometriotic stromal cells

Several lines of evidence indicate that the Th2 immune response is associated with endometriosis. Although an increased concentration of interleukin (IL)-4, a typical Th2 cytokine, has been reported in endometriotic tissues, the implication of this for endometriosis has not been determined. To investigate a possible role of IL-4 in the development of endometriosis, we examined the presence of IL-4-producing cells in endometriotic tissues and the effect of IL-4 on proliferation of endometriotic stromal cells. Endometriotic stromal cells were isolated from endometriotic tissues obtained from women undergoing surgery for endometrioma. Immunohistochemistry of endometriotic tissues revealed that IL-4-positive cells were abundant in the stroma. The effect of IL-4 on proliferation of endometriotic stromal cells was studied using cell counting and BrdU incorporation assays. IL-4 (0.1 to 10 ng/ml) significantly increased cell number and BrdU incorporation in a dose-dependent manner, and the proliferative effect of IL-4 was inhibited by anti-IL-4 receptor antibody. IL-4-induced activation of mitogen-activated protein kinases in endometriotic stromal cells was examined by Western blotting. IL-4 induced phosphorylation of p38 mitogen-activated protein kinase, stress-activated protein kinase/c-Jun kinase, and p42/44 mitogen-activated protein kinase and inhibitors of these kinases suppressed IL-4-induced proliferation of endometriotic stromal cells. These findings suggest that proliferation of endometriotic stromal cells induced by locally produced IL-4 is involved in the development of endometriosis.