The phase of plasticity-induced neurochemical changes of high-frequency repetitive transcranial magnetic stimulation are different from visual perceptual learning.

Numerous studies have found that repetitive transcranial magnetic stimulation (rTMS) modulates plasticity. rTMS has often been used to change neural networks underlying learning, often under the assumption that the mechanism of rTMS-induced plasticity should be highly similar to that associated with learning. The presence of visual perceptual learning (VPL) reveals the plasticity of early visual systems, which is formed through multiple phases. Hence, we tested how high-frequency (HF) rTMS and VPL modulate the effect of visual plasticity by investigating neurometabolic changes in early visual areas. We employed an excitatory-to-inhibitory (E/I) ratio, which refers to glutamate concentration divided by GABA+ concentration, as an index of the degree of plasticity. We compared neurotransmitter concentration changes after applying HF rTMS to the visual cortex with those after training in a visual task, in otherwise identical procedures. Both the time courses of the E/I ratios and neurotransmitter contributions to the E/I ratio significantly differed between HF rTMS and training conditions. The peak E/I ratio occurred 3.5 h after HF rTMS with decreased GABA+, whereas the peak E/I ratio occurred 0.5 h after visual training with increased glutamate. Furthermore, HF rTMS temporally decreased the thresholds for detecting phosphene and perceiving low-contrast stimuli, indicating increased visual plasticity. These results suggest that plasticity in early visual areas induced by HF rTMS is not as involved in the early phase of development of VPL that occurs during and immediately after training.

Baseline Cerebro-Cerebellar Functional Connectivity in Afferent and Efferent Pathways Reveal Dissociable Improvements in Visuomotor Learning.

Visuomotor coordination is a complex process involving several brain regions, primarily the cerebellum and motor cortex. Studies have shown inconsistent resting-state functional magnetic resonance imaging (rsfMRI) results in the cerebellar cortex and dentate nucleus of the cerebro-cerebellar connections. Echoing anatomical pathways, these two different cerebellar regions are differentially responsible for afferent and efferent cerebro-cerebellar functional connections. The aim of this study was to measure the baseline resting-state functional connectivity of different cerebellar afferent and efferent pathways and to investigate their relationship to visuomotor learning abilities. We used different cerebellar repetitive transcranial magnetic stimulation (rTMS) frequencies before a pursuit rotor task to influence visuomotor performance. Thirty-eight right-handed participants were included and randomly assigned to three different rTMS frequency groups (1 Hz, 10 Hz and sham) and underwent baseline rsfMRI and pursuit rotor task assessments. We report that greater baseline functional connectivity in the afferent cerebro-cerebellar pathways was associated with greater accuracy improvements. Interestingly, lower baseline functional connectivity in the efferent dentato-thalamo-cortical pathways was associated with greater stability in visuomotor performance, possibly associated with the inhibitory role of the dentate nucleus and caused a reduction in the efferent functional connectivity. The functional dissociation of the cerebellar cortex and dentate nucleus and their connections, suggests that distinct mechanisms in the cerebellum regarding visuomotor learning, which should be investigated in future research.

Frequency-Dependent Effects of Cerebellar Repetitive Transcranial Magnetic Stimulation on Visuomotor Accuracy.

The cerebellum plays a critical role in acquiring visuomotor skills. Visuomotor task mastery requires improving both visuomotor accuracy and stability; however, the cerebellum's contribution to these processes remains unclear. We hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the cerebellum exerts frequency-dependent modulatory effects on both accuracy and stability in subjects performing a visuomotor coordination task (i.e., pursuit rotor task). We recruited 43 healthy volunteers and randomly assigned them to the high-frequency (HF), low-frequency (LF), and sham rTMS groups. We calculated changes in performance of the pursuit rotor task at the highest rotation speed and the minimum distance from target as indices of accuracy. We also calculated the intertrial variability (standard deviations) of time on target and distance from target as indices of stability. Visuomotor accuracy was significantly enhanced in the HF group and disrupted in the LF group compared to the sham group, indicating frequency-dependent effects of rTMS. In contrast, both HF and LF rTMS demonstrated no significant change in visuomotor stability. Surprisingly, our findings demonstrated that the accuracy and stability of visuomotor performance may be differentially influenced by cerebellar rTMS. This suggests that visuomotor accuracy and stability have different underlying neural mechanisms and revealed the possibility of training strategies based on cerebellar neuromodulation.

Femtosecond control of phonon dynamics near a magnetic order critical point.

The spin-phonon interaction in spin density wave (SDW) systems often determines the free energy landscape that drives the evolution of the system. When a passing energy flux, such as photoexcitation, drives a crystalline system far from equilibrium, the resulting lattice displacement generates transient vibrational states. Manipulating intermediate vibrational states in the vicinity of the critical point, where the SDW order parameter changes dramatically, would then allow dynamical control over functional properties. Here we combine double photoexcitation with an X-ray free-electron laser (XFEL) probe to control and detect the lifetime and magnitude of the intermediate vibrational state near the critical point of the SDW in chromium. We apply Landau theory to identify the mechanism of control as a repeated partial quench and sub picosecond recovery of the SDW. Our results showcase the capabilities to influence and monitor quantum states by combining multiple optical photoexcitations with an XFEL probe. They open new avenues for manipulating and researching the behaviour of photoexcited states in charge and spin order systems near the critical point.

Synchrony Between Default-Mode and Sensorimotor Networks Facilitates Motor Function in Stroke Rehabilitation: A Pilot fMRI Study.

Stroke is the most common cause of complex disability in Taiwan. After stroke onset, persistent physical practice or exercise in the rehabilitation procedure reorganizes neural assembly for reducing motor deficits, known as neuroplasticity. Neuroimaging literature showed rehabilitative effects specific to the brain networks of the sensorimotor network (SMN) and default-mode network (DMN). However, whether between-network interactions facilitate the neuroplasticity after stroke rehabilitation remains a mystery. Therefore, we conducted the longitudinal assessment protocol of stroke rehabilitation, including three types of clinical evaluations and two types of functional magnetic resonance imaging (fMRI) techniques (resting state and grasp task). Twelve chronic stroke patients completed the rehabilitation protocol for at least 24 h and finished the three-time assessments: before, after rehabilitation, and 1 month after the cessation of rehabilitation. For comparison, age-matched normal controls (NC) underwent the same fMRI evaluation once without repeated measure. Increasing scores of the Fugl-Meyer assessment (FMA) and upper extremity performance test reflected the enhanced motor performances after the stroke rehabilitation process. Analysis of covariance (ANCOVA) results showed that the connections between posterior cingulate cortex (PCC) and iM1 were persistently enhanced in contrast to the pre-rehabilitation condition. The interactions between PCC and SMN were positively associated with motor performances. The enhanced cross-network connectivity facilitates the motor recovery after stroke rehabilitation, but the cross-network interaction was low before the rehabilitation process, similar to the level of NCs. Our findings suggested that cross-network connectivity plays a facilitatory role following the stroke rehabilitation, which can serve as a neurorehabilitative biomarker for future intervention evaluations.

The Immune Protection Induced by a Serine Protease Inhibitor From the Foodborne Parasite Trichinella spiralis.

Serine protease inhibitors (SPI) are a superfamily of the proteins able to suppress serine protease activity, and may exert the major biological function in complement activation, inflammation, and fibrinolysis. A SPI was identified from Trichinella spiralis adult worms (AW) by immunoproteomics with early infection sera. The aim of this study was to investigate the protective immune elicited by TsSPI. The complete TsSPI cDNA sequence was cloned into pQE-80 L and then expressed in Escherichia coli BL21. The rTsSPI was purified and its antigenicity was determined by Western blotting analysis. By using anti-rTsSPI serum the native TsSPI was identified in somatic and ES proteins from muscle larvae (ML). The results of qPCR and immunofluorescence assay (IFA) revealed that the expression of the TsSPI gene was observed throughout all developmental stages of T. spiralis (ML, intestinal infective larvale, 3- and 6-days AW, and newborn larvae, NBL), located principally in cuticles, stichosome, and embryos of this parasitic nematode. Vaccination of mice with rTsSPI triggered high level of anti-TsSPI IgG response, and showed a 62.2 and 57.25% worm burden reduction in the recovery of intestinal AW at 6 days post-infection (dpi) and ML at 35 dpi, respectively. The TsSPI might be a novel potential target for anti-Trichinella vaccine.

A pinhole camera for ultrahigh-intensity laser plasma experiments.

A pinhole camera is an important instrument for the detection of radiation in laser plasmas. It can monitor the laser focus directly and assist in the analysis of the experimental data. However, conventional pinhole cameras are difficult to use when the target is irradiated by an ultrahigh-power laser because of the high background of hard X-ray emission generated in the laser/target region. Therefore, an improved pinhole camera has been developed that uses a grazing-incidence mirror that enables soft X-ray imaging while avoiding the effect of hard X-ray from hot dense plasmas.

[The protection of hydrogen-rich saline on a rat dry eye model induced by scopolamine hydrobromide].

Objective: To evaluate the effect of hydrogen-rich saline (HRS) on dry eye rats induced by subcutaneous injection of scopolamine hydrobromide. Methods: Experiment research. Thirty female Wistar rats at about six weeks old were randomly divided into the normal group, dry eye group, HRS eyedrops group, normal saline eyedrops group (NS), HRS intraperitoneal injection group and NS intraperitoneal injection group, with 5 rats in each group. The dry eye was induced by subcutaneous injection of scopolamine hydrobromide in the latter five groups. The clinical signs of dry eye such as tear volume (SⅠt), tear break-up time (BUT) and corneal epithelial fluorescein staining scores were evaluated on day 7, 14, 21 and 28. On the 28th day, ten eyes in each group were enucleated and processed for paraffin sections for HE, PAS and immunohistochemistry stainings. Analysis of variance was used to test the data, and independent samples t-test was used for comparison between the two groups. Two-way repeated measure ANOVA was used to compare the difference among groups at different time points, one-way ANOVA was used to test the comparisons of the clinical signs at one time, and LSD was used to for comparison between two groups. Results: Before and after the experiment of the day 7, 14, 21, 28, the values of SIt in HRS eyedrops group and HRS intraperitoneal injection group were respectively:(3.625±1.157),(3.313±0.704),(3.250±0.535),(3.313±0.372), (3.375±0.582)mm and (3.500±1.019), (2.893±0.656), (3.321±0.668), (3.179±0.575), (3.214±0.871)mm. The values of BUT were respectively: (2.750±0.707), (2.688±0.594), (2.813±0.753), (3.000±0.756), (2.750±0.707)s and (3.000±0.679), (2.321±0.464), (2.750±0.753), (3.214±0.699), (2.679±0.608)s. The values of fluorescein staining score were respectively: (6.250±0.707), (8.875±0.641), (8.750±0.707), (9.250±0.463), (8.250±1.282) and (6.000±0.679), (9.143±1.027), (8.857±0.770), (9.143±0.949), (8.500±0.760). The difference of SIt, BUT and fluorescein staining score between the groups was statistically significant on the 14th day(F=5.194, 3.894, 16.487, P<0.05), the values of SⅠt, BUT and fluorescein staining score of HRS eyedrops group showed significantly better than NS eyedrops group(P<0.05), HRS intraperitoneal injection group showed significantly better than NS intraperitoneal injection group(P<0.05), and there was no significant difference between HRS eyedrops group and HRS intraperitoneal injection group(P>0.05), which remained stable until the day 28. On the 28(th) day, HE, PAS and immunohistochemistry stainings showed the corneal and conjunctival epithelia became smooth and regular, the cell layer number decreased, the tissue hyperplasia and edema were lightened, and the size of goblet cells tended to be normal, and the squamous metaplasia and inflammation were relieved. In HRS eyedrops group and HRS intraperitoneal injection group. Conclusions: HRS eyedrops group and HRS intraperitoneal injection group can relieve the signs of dry eye, improve the pathological damage of cornea and conjunctiva, and protect the ocular surface of a rat dry eye model, which is better than NS groups from the 14(th) day. (Chin J Ophthalmol, 2017, 53: 363-372).

[Effectiveness of clinical pathway for treatment of advanced schistosomiasis hepatic fibrosis].

Objective To assess the effectiveness of the clinical pathway for the treatment of advanced schistosomiasis hepatic fibrosis. Methods The duration of hospital stay, gross hospitalization expense, individual-paid expense, interior diameter of portal vein, levels of four serum hepatic fibrosis-related parameters (PIIIP, CIV, HA, and LN), and activities of ALT, AST and γ-GT were assessed and compared between the advanced schistosomiasis patients receiving the clinical pathway and ones receiving non-clinical pathway. Results There were 142 advanced schistosomiasis patients with hepatic fibrosis receiving the clinical pathway of anti-hepatic fibrosis. Compared with the patients receiving non-clinical pathway, the gross hospitalization expenses reduced by 11.2% (t = 6.310, P < 0.05), and the individual-paid expenses reduced by 16.1% (t = 4.326, P < 0.05). The mean HA level was twice higher than the normal range, with a positive rising from 70.4% to 83.1%, and the abnormal rates of CIV and γ-GT were 64.1% and 28.9% respectively. Conclusions The clinical pathway can drastically reduce the treatment expenses in advanced schistosomiasis patients with hepatic fibrosis. However, the patients have a trend towards the persistent disease progression. Therefore, the researches of more effective therapeutic methods for advanced schistosomiasis hepatic fibrosis are urgently needed.

Sensitivity enhancement of task-evoked fMRI using ensemble empirical mode decomposition.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is widely used to investigate dynamic brain functions in neurological and psychological issues; however, high noise level limits its applicability for intensive and sophisticated investigations in the field of neuroscience. NEW METHOD: To deal with both issue (low sensitivity and dynamic signal), we used ensemble empirical mode decomposition (EEMD), an adaptive data-driven analysis method for nonstationary and nonlinear features, to filter task-irrelevant noise from raw fMRI signals. Using both simulations and representative fMRI data, we optimized the analytic parameters and identified non-meaningful intrinsic mode functions (IMFs) to remove noise. RESULTS: We revealed the following advantages of EEMD in fMRI analysis: (1) EEMD achieved high detectability for task engagement; (2) the functional sensitivity was markedly enhanced by removing task-irrelevant artifacts based on EEMD. COMPARISON WITH EXISTING METHOD(S): Compared with other noise-removal methods (e.g., band-pass filtering and independent component analysis), the EEMD-based artifact-removal method exhibited better spatial specificity and superior Gaussianity of the resulting t-score distribution. CONCLUSIONS: We found that EEMD method was efficient to enhance the functional sensitivity of evoked fMRI. The same strategy would be applicable to resting-state fMRI signal in the general purpose.

Regrowth of the adenoids after adenoidectomy down to the pharyngobasilar fascial surface.

OBJECTIVES: This study aimed to explore adenoid regrowth after transoral power-assisted adenoidectomy down to the pharyngobasilar fascial surface. METHODS: Transoral adenoidectomy down to the pharyngobasilar fascia surface was performed on 39 patients under endoscopic guidance, using a power-assisted system. The operation time, amount of blood loss and iatrogenic injury, presence of complications, and success and regrowth rates were recorded to assess the feasibility, safety and effectiveness of our surgical technique. RESULTS: In this adenoidectomy procedure, the pharyngobasilar fascia was left intact. The estimated blood loss was 5-50 ml (mean 15 ml), and the success rate was 97.3 per cent. Early complications occurred in 2.3 per cent of patients, while no long-term complications occurred in the cohort. No regrowth was found in the follow-up assessments, which were performed for 18-36 months after surgery. CONCLUSION: Adenoid regrowth was rare after adenoidectomy down to the pharyngobasilar fascial surface. The pharyngobasilar fascia can therefore be considered a surgical boundary for adenoidectomy.

Maturation and spawning induction in Hawaiian opihi Cellana spp. by hormone GnRH.

Gonadotropin releasing hormone (GnRH) is a neuropeptide hormone whic plays an important role in control of the reproduction among vertebrates and some work is showing that it is active in invertebrate species. We matured and spawned the Hawaiian opihi Cellana spp. by using salmon GnRH analogue. In the first experiment on maturation, twelve adult opihi (3.18+/-0.23cm, shell length) were injected weekly with salmon GnRHa at dose of 250ng.g-1 body weight (BW) for a 6-week period. Gonad development was assessed using gonadosomatic index (GSI) and histological techniques. GSI incorporated with histological analysis showed that the gonads reached full maturation after 4 weeks. GSI increased significantly (31%) in comparison to the control group of saline solution injection did not produce any maturity in opihi. For the spawning trial, eight ripe opihi were administered a single injection at dose of 1000ng.g-1 BW. The results showed that an average of 33% of the animal spawned in 4-6h after hormone injection. Fertilized eggs developed through embryo and to the com plete larval stage of veligers. Our preliminary findings in this study provide a new aspect of hormone controlling reproduction of opihi, which could be applied in opihi aquaculture.

Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians.

The efficacy of insulin in stimulating whole-body glucose disposal (insulin sensitivity) was quantified using direct methodology in thirty lacto-ovo vegetarians and in thirty meat-eaters. All subjects were adult, lean (BMI <23 kg/m2), healthy and glucose tolerant. Lacto-ovo vegetarians were more insulin sensitive than meat-eaters, with a steady-state plasma glucose (mmol/l) of 4.1 (95 % CI 3.5, 5.0) v. 6.9 (95 % CI 5.2, 7.5; respectively. In addition, lacto-ovo vegetarians had lower body Fe stores, as indicated by a serum ferritin concentration (microg/l) of 35 (95 % CI 21, 49) compared with 72 (95 % CI 45, 100) for meat-eaters To test whether or not Fe status might modulate insulin sensitivity, body Fe was lowered by phlebotomy in six male meat-eaters to levels similar to that seen in vegetarians, with a resultant approximately 40 % enhancement of insulin-mediated glucose disposal Our results demonstrate that lacto-ovo vegetarians are more insulin sensitive and have lower Fe stores than meat-eaters. In addition, it seems that reduced insulin sensitivity in meat-eaters is amenable to improvement by reducing body Fe. The latter finding is in agreement with results from animal studies where, no matter how induced, Fe depletion consistently enhanced glucose disposal.

Insulin resistance as a predictor of age-related diseases.

The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.

Antioxidant activity of tocopherols, tocotrienols, and gamma-oryzanol components from rice bran against cholesterol oxidation accelerated by 2,2'-azobis(2-methylpropionamidine) dihydrochloride.

The antioxidant activities of vitamin E (alpha-tocopherol, alpha-tocotrienol, gamma-tocopherol, and gamma-tocotrienol) and gamma-oryzanol components (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, and campesteryl ferulate) purified from rice bran were investigated in a cholesterol oxidation system accelerated by 2,2'-azobis(2-methylpropionamidine) dihydrochloride. All components exhibited significant antioxidant activity in the inhibition of cholesterol oxidation. The highest antioxidant activity was found for 24-methylenecycloartanyl ferulate, and all three gamma-oryzanol components had activities higher than that of any of the four vitamin E components. Because the quantity of gamma-oryzanol is up to 10 times higher than that of vitamin E in rice bran, gamma-oryzanol may be a more important antioxidant of rice bran in the reduction of cholesterol oxidation than vitamin E, which has been considered to be the major antioxidant in rice bran. The antioxidant function of these components against cholesterol oxidation may contribute to the potential hypocholesterolemic property of rice bran.

Hyperinsulinemia: the missing link among oxidative stress and age-related diseases?

Mounting evidence supports Harman's hypothesis that aging is caused by free radicals and oxidative stress. Although it is known that oxidant species are produced during metabolic reactions, it is largely unknown which factor(s), of physiological or pathophysiological significance, modulate their production in vivo. In this hypothesis paper, it is postulated that hyperinsulinemia may have such function and therefore promote aging, independently of elevations of glycemia. Hyperinsulinemia is secondary to impaired insulin stimulated glucose metabolism at the level of skeletal muscle (insulin resistance) and is seen in about one third of glucose tolerant humans following dietary carbohydrate intake. If other insulin-stimulated (or inhibited) pathways retain normal sensitivity to the hormone, hyperinsulinemia could, by its effects on antioxidative enzymes and on free radical generators, enhance oxidative stress. Other proaging effects of insulin involve the inhibition of proteasome and the stimulation of polyunsaturated fatty acid (PUFA) synthesis and of nitric oxide (NO). The hypothesis that hyperinsulinemia accelerates aging also offers a metabolic explanation for the life-prolonging effect of calorie restriction and of mutations decreasing the overall activity of insulin-like receptors in the nematode Caenorhabditis elegans.

Non-contiguous regions of Z-DNA in a DNA dodecamer.

The conformation of the self-complimentary DNA dodecamer d(br5CGbr5CGAATTbr5CGbr5CG) has been investigated in a variety of salt and solvent conditions by one and two-dimensional 1H NMR. In low salt aqueous solutions, the molecule forms a regular B-DNA structure similar to the unmodified dodecamer. However, in aqueous solution containing high salt concentration and methanol, the dodecamer adopts a structure in which the br5CGbr5CG ends of the molecule are in a Z-DNA like conformation and the AATT region is neither standard B-DNA nor Z-DNA. The implications of these results for the structure of junctions between B and Z-DNA and the sequence specificity of Z-DNA are discussed.

Amphoteric tetracycline-sensitive electrodes and their selectivities.

Electrodes that are sensitive to cationic and anionic species of tetracycline have been constructed. The cation-sensitive electrode responds to monoprotonated tetracycline over the pH range 1.9-3.2. The anion-sensitive electrode responds at pH 8.0-11.0 to the singly-charged tetracyclinate anion resulting from dissociation of the enolic group of the B ring. The electrode selectivities have been investigated.

Investigation of bilirubin removal by NK-110 resin hemoperfusion in jaundiced dogs.

A jaundiced dog model was made by common bile duct-inferior vena cava shunt with a silicon rubber tube. Blood bilirubin levels increased from 0.25 +/- 0.16 (SD) mg% to 15 +/- 1.4 (SD) mg%. These dog models were treated with a column containing 200 gm of macroreticular resin NK-110 which was linked between the femoral artery and vein. The rate of blood flow through the column was 200 ml/min. It was shown that total bilirubin reduced from 15 +/- 1.4 (SD) to 7.4 +/- 0.61 (SD), conjugated bilirubin decreased from 6.97 +/- 0.63 to 3.5 +/- 0.33 (SD) and unconjugated bilirubin from 7.8 +/- 2.1 to 4.2 +/- 0.4 (SD). There were no significant changes in protein, electrolyte, blood gases and acid base balance. Results show that NK-110 resin has good blood-compatible and adsorption properties.