Differences in autonomic nervous system activity between long-acting injectable aripiprazole and oral aripiprazole in schizophrenia.

BACKGROUND: Distinct oral atypical antipsychotics have different effects on autonomic nervous system (ANS) activity. Among them, oral aripiprazole has been linked to dysfunction of the ANS in schizophrenia. Long-acting injectable aripiprazole is a major treatment option for schizophrenia, but the effect of the aripiprazole formulation on ANS activity remains unclear. In this study, we compared ANS activity between oral aripiprazole and aripiprazole once-monthly (AOM) in schizophrenia. METHODS: Of the 122 patients with schizophrenia who participated in this study, 72 received oral aripiprazole and 50 received AOM as monotherapy. We used power spectral analysis of heart rate variability to assess ANS activity. RESULTS: Patients who received oral aripiprazole showed significantly diminished sympathetic nervous activity compared with those who received AOM. Multiple regression analysis revealed that the aripiprazole formulation significantly influenced sympathetic nervous activity. CONCLUSION: Compared with oral aripiprazole, AOM appears to have fewer adverse effects, such as sympathetic nervous dysfunction.

Local and Transient Changes of Sleep Spindle Density During Series of Prefrontal Repetitive Transcranial Magnetic Stimulation in Patients With a Major Depressive Episode.

The neuromodulatory effects of brain stimulation therapies notably involving repetitive transcranial magnetic stimulation (rTMS) on nocturnal sleep, which is critically disturbed in major depression and other neuropsychiatric disorders, remain largely undetermined. We have previously reported in major depression patients that prefrontal rTMS sessions enhanced their slow wave activity (SWA) power, but not their sigma power which is related to sleep spindle activity, for electrodes located nearby the stimulation site. In the present study, we focused on measuring the spindle density to investigate cumulative effects of prefrontal rTMS sessions on the sleep spindle activity. Fourteen male inpatients diagnosed with medication-resistant unipolar or bipolar depression were recruited and subjected to 10 daily rTMS sessions targeting the left dorsolateral prefrontal cortex (DLPFC). All-night polysomnography (PSG) data was acquired at four time points: Adaptation, Baseline, Post-1 (follow-up after the fifth rTMS session), and Post-2 (follow-up after the tenth rTMS session). Clinical and cognitive evaluations were longitudinally performed at Baseline, Post-1, and Post-2 time points to explore associations with the spindle density changes. The PSG data from 12 of 14 patients was analyzed to identify sleep spindles across the sleep stages II-IV at four electrode sites: F3 (frontal spindle near the stimulation site), F4 (contralateral homologous frontal region), P3 (parietal spindle in the hemisphere ipsilateral to the stimulation site), and P4 (contralateral parietal region). Statistical analysis by two-way ANOVA revealed that spindle density at F3 increased at Post-1 but decreased at Post-2 time points. Moreover, the local and transient increase of spindle density at F3 was associated with the previously reported SWA power increase at F3, possibly reflecting a shared mechanism of thalamocortical synchronization locally enhanced by diurnal prefrontal rTMS sessions. Clinical and cognitive correlations were not observed in this dataset. These findings suggest that diurnal rTMS sessions transiently modulate nocturnal sleep spindle activity at the stimulation site, although clinical and cognitive effects of the local changes warrant further investigation.

The association of genetic polymorphisms in CYP1A2, UGT1A4, and ABCB1 with autonomic nervous system dysfunction in schizophrenia patients treated with olanzapine.

BACKGROUND: Use of the antipsychotic drug olanzapine by patients with schizophrenia is associated with autonomic nervous system (ANS) dysfunction. It is presumed that there are interindividual differences in ANS dysfunction that correspond to pharmacogenetics. In this study, we investigated whether genetic polymorphisms in ABCB1, CYP1A2, and UGT1A4 are associated with this observed ANS dysfunction. METHODS: A total of 91 schizophrenia patients treated with olanzapine monotherapy participated in this study. A power spectral analysis of heart rate variability was used to assess ANS activity. The TaqMan system was used to genotype seven single nucleotide polymorphisms (SNPs) in CYP1A2 (rs2069514 and rs762551), UGT1A4 (rs2011425), and ABCB1 (rs1045642, rs1128503, rs2032582, rs2235048). RESULTS: Sympathetic nervous activity was significantly higher in individuals with the UGT1A4 rs2011425 G allele than in those with the UGT1A4 rs2011425 non-G allele (sympathetic activity, p = .001). Furthermore, sympathetic nervous activity was also significantly associated with UGT1A4 rs2011425 genotype as revealed by multiple regression analysis (sympathetic activity, p = .008). CONCLUSIONS: We suggest that the UGT1A4 rs2011425 polymorphism affects olanzapine tolerability because it is associated with the observed side effects of olanzapine in schizophrenia patients, namely sympathetic dysfunction.

Life cycle assessment and life cycle costs for pre-disaster waste management systems.

This study develops a method of environmental and economic evaluation of an integrated disaster waste management system that considers the spatial scale of removal, transport, and treatment of disaster waste. A case study was conducted on combustibles, which is a type of disaster waste derived from dwellings, in Mie Prefecture, Japan. First, we calculated the quantity and the spatial distribution of disaster waste derived from dwellings and tsunami debris produced as a result of a large-scale earthquake. The quantity of disaster waste was estimated as 7,178,000t with functioning flood-preventing facilities and 11,956,000t without functioning flood prevention facilities. Ensuring resilience in the face of earthquakes and tsunamis by renovating flood-preventing facilities is extremely important in decreasing the production of wastes, especially in coastal regions. Next, the transportation network for transporting combustibles in disaster waste to temporary storage sites, incineration plants, and landfill was constructed using an optimization model. The results showed that if flood-preventing facilities do not function properly, the installation of temporary incineration facilities becomes essential. Life-cycle emissions of CO2, SOx, NOx, and PM and the costs of removal, storage, and treatment of combustibles were calculated as 258,000t, 618t, 1705t, 7.9t, and 246millionUSD, respectively, in the case of functioning flood-preventing facilities. If flood-preventing facilities do not function, the quantity of environmentally unfriendly emissions and the costs increase. This result suggested the significance of renovation in order to maintain the conditions of flood-preventing facilities to decrease the environmental burden and costs as well as keep the production of disaster waste at a minimum.

Lateralized hippocampal volume increase following high-frequency left prefrontal repetitive transcranial magnetic stimulation in patients with major depression.

AIM: Repetitive transcranial magnetic stimulation (rTMS) has been applied as a treatment for patients with treatment-resistant depression in recent years, and a large body of evidence has demonstrated its therapeutic efficacy through stimulating neuronal plasticity. The aim of this study was to investigate structural alterations in the hippocampus (HIPP) and amygdala (AM) following conventional rTMS in patients with depression. METHODS: Twenty-eight patients with depression underwent 10 daily 20-Hz left prefrontal rTMS over 2 weeks. The left dorsolateral prefrontal cortex (DLPFC) was identified using magnetic resonance imaging-guided neuronavigation prior to stimulation. Magnetic resonance imaging scans were obtained at baseline and after the completion of rTMS sessions. The therapeutic effects of rTMS were evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D17 ), and the volumes of the HIPP and AM were measured by a manual tracing method. RESULTS: Statistical analyses revealed a significant volume increase in the left HIPP (+3.4%) after rTMS but no significant volume change in the AM. No correlation was found between the left HIPP volume increase and clinical improvement, as measured by the HAM-D17 . CONCLUSION: The present study demonstrated that conventional left prefrontal rTMS increases the HIPP volume in the stimulated side, indicating a remote neuroplastic effect through the cingulum bundle.

Demonstration of short-term plasticity in the dorsolateral prefrontal cortex with theta burst stimulation: A TMS-EEG study.

OBJECTIVES: To examine the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) on cortical reactivity in the dorsolateral prefrontal cortex. METHODS: 10 healthy participants were stimulated with either iTBS, cTBS or sham at F3 electrode. Single- and paired-pulse TMS and concurrent electroencephalography (EEG) were used to assess change in cortical reactivity and long-interval intracortical inhibition (LICI) via TMS-evoked potentials (TEPs) and TMS-evoked oscillations. RESULTS: Significant increases in N120 amplitudes (p<0.01) were observed following iTBS over prefrontal cortex. Changes in TMS-evoked theta oscillations and LICI of theta oscillations were also observed following iTBS (increase) and cTBS (decrease). Change in LICI of theta oscillations correlated with change in N120 amplitude following TBS (r=-0.670, p=0.001). CONCLUSIONS: This study provides preliminary evidence that TBS produces direct changes in cortical reactivity in the prefrontal cortex. Combining TBS with TMS-EEG may be a useful approach to optimise stimulation paradigms prior to the conduct of clinical trials. SIGNIFICANCE: TBS is able to modulate cortical reactivity and cortical inhibition in the prefrontal cortex.

Resting-state EEG gamma power and theta-gamma coupling enhancement following high-frequency left dorsolateral prefrontal rTMS in patients with depression.

OBJECTIVE: We aimed to investigate neuromodulatory effects of high-frequency left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) on resting-state electroencephalography (EEG) and their clinical and cognitive correlates in patients with depression. METHODS: Thirty-one patients diagnosed with depression included in the present study. Resting-state gamma power and theta-gamma coupling (TGC) were calculated before and after a course of rTMS. We explored the relationship among gamma power, TGC, and clinical/cognitive outcomes as measured with the Hamilton Rating Scale for Depression (HAM-D17), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST). RESULTS: Following rTMS, depressed patients demonstrated significant increases of resting gamma power at the F3 and F4 electrode sites and resting TGC at the C3 and T3 electrode sites. Furthermore, the increased gamma power at the F3 electrode site was significantly correlated with improved score on the HAM-D17 and BDI, while the increased TGC at the C3 electrode site was significantly correlated with reduced number of errors on the WCST. CONCLUSION: Thus, resting-state gamma power and TGC may represent potential biomarkers of depression associated with therapeutic effects of rTMS. SIGNIFICANCE: Resting-state EEG may provide potential biomarkers related to therapeutic effects of rTMS.

Environmental and economic evaluation of pre-disaster plans for disaster waste management: Case study of Minami-Ise, Japan.

Although it is important that disaster waste be demolished and removed as soon as possible after a natural disaster, it is also important that its treatment is environmentally friendly and economic. Local municipalities do not conduct environmental and economic feasibility studies of pre-disaster waste management; nevertheless, pre-disaster waste management is extremely important to promote treatment of waste after natural disasters. One of the reasons that they cannot conduct such evaluations is that the methods and inventory data required for the environmental and economic evaluation does not exist. In this study, we created the inventory data needed for evaluation and constructed evaluation methods using life cycle assessment (LCA) and life cycle cost (LCC) methodologies for future natural disasters. We selected the Japanese town of Minami-Ise for the related case study. Firstly, we estimated that the potential disaster waste generation derived from dwellings would be approximately 554,000t. Based on this result, the land area required for all the temporary storage sites for storing the disaster waste was approximately 55ha. Although the public domain and private land area in this case study is sufficient, several sites would be necessary to transport waste to other sites with enough space because local space is scarce. Next, we created inventory data of each process such as waste transportation, operation of the temporary storage sites, and waste treatment. We evaluated the environmental burden and cost for scenarios in which the disaster waste derived from specified kinds of home appliances (refrigerators, washing machines, air-conditioners and TV sets) was transported, stored and recycled. In the scenario, CO2, SOx, NOX and PM emissions and total cost were 142t, 7kg, 257kg, 38kg and 1772 thousand USD, respectively. We also focused on SOx emission as a regional pollution source because transportation and operation of the temporary storage sites generates air pollution. If the treatment of all waste were finished in 3years, the environmental standard would be satisfied by setting work duration to 4.8h/d.

Single Pulse Transcranial Magnetic Stimulation-Electroencephalogram Reveals No Electrophysiological Abnormality in Adults with High-Functioning Autism Spectrum Disorder.

OBJECTIVE: Neuroimaging and electrophysiological research have revealed a range of neural abnormalities in autism spectrum disorder (ASD), but a comprehensive understanding remains elusive. We utilized a novel methodology among individuals with ASD and matched controls, combining transcranial magnetic stimulation (TMS) with concurrent electroencephalogram (EEG) recording (TMS-EEG) to explore cortical function and connectivity in three sites implicated in the neuropathophysiology of ASD (dorsolateral prefrontal cortex, primary motor cortex, and temporoparietal junction). As there is evidence for neurobiological gender differences in ASD, we also examined the influence of biological sex. METHODS: TMS pulses were applied to each of the three sites (right lateralized) during 20-channel EEG recording. RESULTS: We did not identify any differences in the EEG response to TMS between ASD and control groups. This finding remained when data were stratified by sex. Nevertheless, traits and characteristics associated with ASD were correlated with the neurophysiological response to TMS. CONCLUSION: While TMS-EEG did not appear to clarify the neuropathophysiology of ASD, the relationships identified between the neurophysiological response to TMS and clinical characteristics warrant further investigation.

Enhancement of Working Memory and Task-Related Oscillatory Activity Following Intermittent Theta Burst Stimulation in Healthy Controls.

Noninvasive brain stimulation is increasingly being investigated for the enhancement of cognition, yet current approaches appear to be limited in their degree and duration of effects. The majority of studies to date have delivered stimulation in "standard" ways (i.e., anodal transcranial direct current stimulation or high-frequency transcranial magnetic stimulation). Specialized forms of stimulation, such as theta burst stimulation (TBS), which more closely mimic the brains natural firing patterns may have greater effects on cognitive performance. We report here the findings from the first-ever investigation into the persistent cognitive and electrophysiological effects of intermittent TBS (iTBS) delivered to the left dorsolateral prefrontal cortex. In 19 healthy controls, active iTBS significantly improved performance on an assessment of working memory when compared with sham stimulation across a period of 40 min post stimulation. The behavioral findings were accompanied by increases in task-related fronto-parietal theta sychronization and parietal gamma band power. These results have implications for the role of more specialized stimulation approaches in neuromodulation.

Potentiation of quantitative electroencephalograms following prefrontal repetitive transcranial magnetic stimulation in patients with major depression.

The long-lasting effects of repetitive transcranial magnetic stimulation (rTMS) on electroencephalogram (EEG) activity are not clear. We aimed to investigate the cumulative rTMS effects on EEG and clinical outcomes in patients with major depression. Twenty-five patients with medication-resistant depression underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex. We measured resting EEG and spectrum-power before and after the rTMS course. Clinical efficacy was evaluated with the Hamilton's Depression Rating Scale (HAM-D) and Wisconsin Card Sorting Test (WCST). In an ANOVA model, including all prefrontal electrodes, post hoc analyses revealed significant time effects on the theta (F1,24 = 7.89, P = 0.010; +43%), delta (F1,24 = 6.58, P = 0.017; +26%), and alpha (F1,24 = 4.64, P = 0.042; 31%) bands without site specificity. Clinical correlations were observed between F4 alpha power increases and improvements in HAM-D retardation, F3 alpha power increases and improvements of the absolute changes in perseveration and error number on the WCST, and C3 and C4 theta power increases and improvements of the percent change in perseveration and error number on the WCST following rTMS. Consecutive prefrontal rTMS could induce long-lasting EEG potentiations beyond the aftereffects, resulting in improved cognitive and depressive symptoms.

Localized potentiation of sleep slow-wave activity induced by prefrontal repetitive transcranial magnetic stimulation in patients with a major depressive episode.

BACKGROUND: The effects of repetitive transcranial magnetic stimulation (rTMS) on sleep structure in major depression are currently unknown. OBJECTIVE: To determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in major depression. METHODS: In this open-label pilot study, twelve male patients with relatively mild depression, who had been medication-resistant, underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline, Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session). Discrete Fourier Transform (DFT) band power analyses were performed to quantify delta and sigma band activities during Stages II-IV, and determine time courses of these activities between Baseline and Post-1 (first five sessions) and between Post-1 and Post-2 (last five sessions). RESULTS: Post-hoc tests based on a three-way ANOVA model indicated significant delta power increase at F3 (t11 = -2.762, P = 0.018) during the first five sessions; however, sigma power was unchanged. No significant band power changes were observed during the second half. Stages II-IV (percent total sleep time) increased significantly during the first half (t12 = -2.43, P = 0.033). No other significant changes in sleep parameters or clinical correlations were observed. CONCLUSIONS: The first five sessions of high frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3, possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This increased activity was not observed during the last half, possibly due to a homeostatic regulation mechanism intrinsic to SWA.

Properties of ultrasonic waves in bovine bone marrow.

We investigated the properties of ultrasonic waves in bovine bone marrow. Six bone marrow samples were obtained from different parts (proximal, middle and distal) of the shafts of two bovine femora without destruction. The measured frequency range was 3 to 10 MHz, and the temperature range was 15 to 40°C. Both wave velocity and attenuation coefficient in bone marrow always decreased as temperature increased. The velocity ranged from 1400 to 1610 m/s and attenuation coefficient ranged from 4 to 16 dB/cm. Wave velocities in bone marrow were similar to those in water, whereas the temperature dependences were different, and the wave attenuation coefficients were much higher than those in water. The dependence of velocity on temperature changed slightly around 23-24°C, where a transition from soft gel to oily liquid occurred. The transition temperature was confirmed by differential scanning calorimetry (DSC). Below this transition temperature, positive velocity dispersion was observed.

Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder.

AIMS: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder. METHODS: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3-D high-spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age- and gender-matched healthy controls. Optimized voxel-based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State-Trait Anxiety Inventory and Revised Neuroticism-Extraversion-Openness Personality Inventory scores. RESULTS: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior-medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait-Anxiety (beta = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait-Anxiety (beta = -0.394, F = 5.341, P = 0.032) and Neuroticism trait (beta = -0.492, F = 6.989, P = 0.017). CONCLUSIONS: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment.

Numerical and experimental study on the wave attenuation in bone--FDTD simulation of ultrasound propagation in cancellous bone.

In cancellous bone, longitudinal waves often separate into fast and slow waves depending on the alignment of bone trabeculae in the propagation path. This interesting phenomenon becomes an effective tool for the diagnosis of osteoporosis because wave propagation behavior depends on the bone structure. Since the fast wave mainly propagates in trabeculae, this wave is considered to reflect the structure of trabeculae. For a new diagnosis method using the information of this fast wave, therefore, it is necessary to understand the generation mechanism and propagation behavior precisely. In this study, the generation process of fast wave was examined by numerical simulations using elastic finite-difference time-domain (FDTD) method and experimental measurements. As simulation models, three-dimensional X-ray computer tomography (CT) data of actual bone samples were used. Simulation and experimental results showed that the attenuation of fast wave was always higher in the early state of propagation, and they gradually decreased as the wave propagated in bone. This phenomenon is supposed to come from the complicated propagating paths of fast waves in cancellous bone.

Supercritical carbon dioxide extraction of ubiquinones and menaquinones from activated sludge.

Supercritical CO2 (scCO2) extraction, with methanol as modifier, was applied to the determination of ubiquinones and menaquinones in activated sludge. Four ubiquinones and 12 menaquinones species were identified based on retention time and UV spectrum in 0.1g dried activated sludge. The optimum extraction conditions were at a pressure of 25 MPa, a temperature of 55 degrees C, and 10% (v/v) methanol for 15 min. At this condition, the concentrations of extracted ubiquinones and menaquinones were found to be 0.181 and 0.326 micromol/g-dry-cell, respectively. The results were comparable with those obtained by organic solvent extraction based on diversity and dissimilarity indices. Furthermore, the method was evaluated in term of repeatability, which resulted in an RSD of < or =10%. The experimental results have demonstrated the technique to be simple, fast, and with less consumption of organic solvents. This work shows the potential application of supercritical CO2 extraction to microbial community analysis using quinone profile.

Systematic characterization of Escherichia coli genes/ORFs affecting biofilm formation.

To understand the nature and function of bacterial biofilm and the process of its formation, we have performed systematic screening of a complete set of Escherichia coli genes/open reading frames (ORFs) to identify those that affect biofilm development upon over-expression. In contrast to the biofilm of strain AG1 used as a control, some of the genes/ORFs when over-expressed led to the formation of an abnormal biofilm such as thin, mat-like, filamentous or one easily detaching from various surfaces. Disruptants of selected genes were constructed in order to clarify their roles in the different stages of biofilm formation. Our results suggest that diverse metabolic pathways contribute to the development of biofilm.