Stress, Microglial Activation, and Mental Disorders

Microglia play a major role in immune response in the brain. Recent progress in studies for microglia suggests that stress causes morphological alterations in microglia and affects microglial humoral release and phagocytosis. In this review, we present a molecular mechanism by which stress impacts microglia. Then, we describe current findings for the involvement of microglia in stress-related mental disorders including posttraumatic stress disorder (PTSD), depression, and pain enhancement. We focus on preclinical and clinical studies. Preclinical PTSD studies using animal models with fear memory dysregulation show neuroinflammation by microglia and altered microglial phagocytosis, two imaging studies and a postmortem study assessing neuroinflammation in PTSD patients show contradictory results. Imaging studies suggest neuroinflammation in depressed patients, postmortem studies show no microglial inflammatory changes in non-suicidal depressed patients. Although it has been established that microglia in the spinal cord play a pivotal role in chronic neuropathic pain, several preclinical studies suggest microglia also participate in stress-induced pain. A clinical study with induced microglia-like (iMG) cells and an imaging study indicate neuroinflammation by microglia in fibromyalgia patients. We believe that progress in interactive research between humans and animals elucidates the role of microglia in the pathophysiology of stress-related mental disorders

Prevalence of childhood obstructive sleep apnea syndrome and its role in daytime sleepiness

ObjectivesTo investigate childhood obstructive sleep apnea syndrome (OSAS) and its role in daytime sleepiness among school-age children.MethodsA questionnaire survey was conducted with 25,211 children aged 6–15 (mean, 10.39) years attending 148 elementary and 71 middle schools in 10 prefectures across Japan and their parents. Questions concerned 4 sleep habit items (bedtime, sleep onset latency, wake time after sleep onset, wake-up time) and 4 sleep disorder items (loud snoring, snorts/gasps, breathing pauses, seems very sleepy in the daytime). Total sleep time (TST) was calculated with sleep habits. Severe possible OSAS (p-OSAS) was defined as having loud snoring, snorts and gasps, or breathing pauses “frequently” (≥ 5 times per week), and mild p-OSAS was rated as having any of these “sometimes” (2–4 times per week). Severe daytime sleepiness was defined as seeming very sleepy “frequently” and mild daytime sleepiness as seeming very sleepy “sometimes”.ResultsMean prevalence of mild to severe p-OSAS and severe p-OSAS in children across all grade levels was 9.5% and 1.6%, respectively. p-OSAS was particularly prevalent in children at lower elementary levels, decreasing with advancing grade levels. Prevalence of mild and severe daytime sleepiness was 6.1% and 0.9%, respectively, among all children (7.0%). Prevalence of daytime sleepiness increased with advancing grade levels, particularly in middle-school level. Average TST was 8.4 ± 2.2 h in both elementary and middle-school levels, and decreased as grades advanced, particularly in middle-school levels. Multivariate logistic regression analysis showed that middle-school level, TST < 8 h, and p-OSAS were independent factors for daytime sleepiness. Strong correlations were found between severe daytime sleepiness and severe p-OSAS or TST < 6 h, and between daytime sleepiness and loud snoring or breathing pauses.Conclusionp-OSAS may be an independent factor influencing daytime sleepiness in school-age children. Loud snoring and breathing pauses could be clinical markers for children with severe daytime sleepiness

Risk factors for low adherence to methylphenidate treatment in pediatric patients with attention-deficit/hyperactivity disorder

Poor adherence is a major concern in the treatment of attention-deficit/hyperactivity disorder (ADHD). The objective of this study was to evaluate factors linked to early interruption of and low adherence to treatment with osmotic-release oral system methylphenidate hydrochloride (OROS-MPH) in pediatric patients with ADHD. A total of 1353 young people (age 6–17 years) with a diagnosis of ADHD who newly started OROS-MPH were extracted from the pharmacoepidemiological data of 3 million people in Japan. The cohort was retrospectively surveyed every month for 12 months. Ten possible risk factors were extracted from the data and analyzed by multivariable logistic regression. Sensitivity analysis was conducted to ensure the robustness of the analysis. The results revealed that treatment adherence was generally poor, with a tendency for discontinuation in the early stage. Multivariable logistic regression results showed that adherence is reduced by female sex, lower starting dose, and concomitant atomoxetine or hypnotics. These findings may help clinicians to predict the risk of poor adherence in the early stage of treatment and improve not only patients’ symptoms, but also their quality of life

Prevalence of childhood obstructive sleep apnea syndrome and its role in daytime sleepiness

Objectives To investigate childhood obstructive sleep apnea syndrome (OSAS) and its role in daytime sleepiness among school-age children. Methods A questionnaire survey was conducted with 25,211 children aged 6-15 (mean, 10.39) years attending 148 elementary and 71 middle schools in 10 prefectures across Japan and their parents. Questions concerned 4 sleep habit items (bedtime, sleep onset latency, wake time after sleep onset, wake-up time) and 4 sleep disorder items (loud snoring, snorts/gasps, breathing pauses, seems very sleepy in the daytime). Total sleep time (TST) was calculated with sleep habits. Severe possible OSAS (p-OSAS) was defined as having loud snoring, snorts and gasps, or breathing pauses frequently (>= 5 times per week), and mild p-OSAS was rated as having any of these sometimes (2-4 times per week). Severe daytime sleepiness was defined as seeming very sleepy frequently and mild daytime sleepiness as seeming very sleepy sometimes. Results Mean prevalence of mild to severe p-OSAS and severe p-OSAS in children across all grade levels was 9.5% and 1.6%, respectively. p-OSAS was particularly prevalent in children at lower elementary levels, decreasing with advancing grade levels. Prevalence of mild and severe daytime sleepiness was 6.1% and 0.9%, respectively, among all children (7.0%). Prevalence of daytime sleepiness increased with advancing grade levels, particularly in middle-school level. Average TST was 8.4 +/- 2.2 h in both elementary and middle-school levels, and decreased as grades advanced, particularly in middle-school levels. Multivariate logistic regression analysis showed that middle-school level, TST < 8 h, and p-OSAS were independent factors for daytime sleepiness. Strong correlations were found between severe daytime sleepiness and severe p-OSAS or TST < 6 h, and between daytime sleepiness and loud snoring or breathing pauses. Conclusion p-OSAS may be an independent factor influencing daytime sleepiness in school-age children. Loud snoring and breathing pauses could be clinical markers for children with severe daytime sleepiness

Effects of monthly intravenous ibandronate on bone mineral density and microstructure in patients with primary osteoporosis after teriparatide treatment: The MONUMENT study

Purpose: To investigate the effects of sequential therapy with monthly intravenous ibandronate on bone mineral density (BMD) and microstructure in patients with primary osteoporosis who received teriparatide treatment. Methods: Sixty-six patients with primary osteoporosis who had undergone teriparatide treatment for more than 12 months (mean 18.6 months) received sequential therapy with 1 mg/month intravenous ibandronate for 12 months. The patients were evaluated using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound, bone turnover markers, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6 and 12 months after beginning administration. Results: At 12 months after beginning sequential therapy,the bone resorption marker, tartrate-resistant acid phosphatase-5b, decreased by 39.5%, with 82.3% of the patients exhibiting levels within the normal limit. DXA revealed that the BMD of the lumbar spine increased by 3.2%, with 79.0% of the patients exhibiting a response, and 40.3% experiencing an increase in BMD over 5%. HR-pQCT revealed that the cortical thickness of the distal tibia was increased by 2.6%. The cortical area increased by 2.5%, and the buckling ratio (an index of cortical instability) decreased by 2.5%. Most parameters of the trabecular bone showed no significant changes. These changes in the cortical bone were observed in both the distal radius and tibia and appeared beginning 6 months after treatment initiation. Conclusions: Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment

Near-Field Scanning-Based Shielding Effectiveness Extraction for Board-Level Shielding Cans

The conventional definition of shielding effectiveness (SE) is well suited for calculations of far-field electromagnetic shielding. However, in the near field, SE calculations are not as straightforward. In radio-frequency interference (RFI) problems, the majority of field coupling occurs in the near field. Thus, a well-defined method for calculating the near-field SE is needed to estimate the suppression of RFI achieved by shielding cans. In this study, a method based on near-field scanning is developed to extract the SE of board-level shielding cans. The SE is defined by modeling the shielded noise source as equivalent dipole moments. The accuracy of the equivalent source is analyzed via the least-square error and correlation coefficient as confidence verification parameters. By applying the reciprocity theorem, the voltage coupled on a planar inverted F antenna from an unshielded and a shielded source is calculated. The coupled voltage from a shielded noise source serves as a reference to validate the effectiveness of the proposed method. Practical shielding cans were used to develop and validate the SE extraction method using full-wave 3D simulations and measurements

A New Reconstruction Method for a Source Above an Arbitrarily Shaped Ground Plane

Source reconstruction using equivalent dipole moments to replace the original noise source is widely used in radio frequency interference. The conventional reconstruction methods only work well in the cases of free space or with a large ground plane. In this article a new method is proposed for source reconstruction over an arbitrarily shaped ground plane. It uses the field below the ground plane to eliminate the arbitrary ground effect. Comparing to the method of solving surface integral equation, it is simple and does not need the ground geometric information. The new method is validated in the full-wave simulations

lmmunohistochemical reaction of myocardial fibers with actin antiserum in autopsy cases of myocardial infarction

The purpose of this study was to determine the immunoreactivity of myocardial actin filaments with actin antiserum and to examine the significance of its application to diseased human cardiac muscle. The actin was extracted and purified from chicken gizzards. Anti-actin rabbit serum was prepared and purified by affinity chromatography and defined by an immunoblotting test. Using the avidin-biotin-peroxidase complex (ABC) method, the actin antiserum was applied to paraffin sections prepared from hearts taken from routine autopsies of patients who had died of myocardial infarction. Reactivity was shown to be completely lost, not only in necrotized fibers, but also in non-specific degenerative fibers which could be identified by their eosinophilic cytoplasm with pyknotic nuclei, and clearly remaining and/or diminished cross-striations stained with hematoxylin-eosin. In contrast, hypertrophic myocardial fibers adjacent to granulation or scar tissue and those adjacent to infarcted foci exhibited a more intense reaction. These results indicated that the immunohistochemical reaction of actin filaments can be used for the easy detection of very mild degrees of degeneration of cardial muscle fibers, and for hypertrophic fibers adjacent to diseased foci. Studies of the immunoreactivity of actin protein suggestive of alteration at the molecular level might yield morphological clues regarding the nature of functional activity in the contraction of cardiac fibers