Carbon quantum dots: An environmentally friendly and valued approach to sludge disposal.

Sewage sludge, produced daily and inherent to urban development, presents problems of disposal that are still challenging today. Its disposal still offers palliative solutions, where the final destination is generally in landfills or, restrictively, to use in agriculture. The synthesis of carbon quantum dots (CQDs) from sewage sludge is a better alternative to use the stock of organic material present in the sludge. The present work aims to produce Carbon quantum dots (CQDs) using principles of green chemistry and to use an alternative raw material intrinsic stock of carbon present in sewage sludge, making its final disposal more sustainable. The material obtained has a core structure mainly composed of sp2 carbon and nitrogen. The surface functional groups containing sulfur, nitrogen, and oxygen of CQDs were investigated using FTIR and TG/DSC coupled FTIR techniques. The CQDs showed a luminescence decay time equivalent to fluorescent compounds and with satisfying quantum yield since no passive/oxidizing agent or material purification process was used. The photoluminescence spectroscopy analysis showed that the CDQs excitation λmax was at 360 nm and caused a λmax emission at 437 nm (CQDsa) and 430 nm (CQDsb). The CQDs obtained showed sizes of 9.69 ± 2.64 nm (CQDsa) and 10.92 ± 2.69 nm (CQDsb). In vitro experiments demonstrated the uptake of CQDs by the endothelial cell line EAhy 926 and their nontoxicity. However, the production of CQDs can be used for the sustainable disposal of sewage sludge.

Cellulose nanofibers production using a set of recombinant enzymes.

Cellulose nanofibers (CNF) are renewable and biodegradable nanomaterials with attractive barrier, mechanical and surface properties. In this work, three different recombinant enzymes: an endoglucanase, a xylanase and a lytic polysaccharide monooxygenase, were combined to enhance cellulose fibrillation and to produce CNF from sugarcane bagasse (SCB). Prior to the enzymatic catalysis, SCB was chemically pretreated by sodium chlorite and KOH, while defibrillation was accomplished via sonication. We obtained much longer (µm scale length) and more thermostable (resisting up to 260 °C) CNFs as compared to the CNFs prepared by TEMPO-mediated oxidation. Our results showed that a cooperative action of the set of hydrolytic and oxidative enzymes can be used as a "green" treatment prior to the sonication step to produce nanofibrillated cellulose with advanced properties.

New glycemic metrics and traditional clinical and laboratory profiles of children and adolescents with type 1 diabetes mellitus in an outpatient follow-up.

INTRODUCTION: This study evaluated the demographic, clinical, and laboratory data - including traditional (as glycated hemoglobin, HbA1c) and new glycemic metrics (as time in range, TiR) - and the complications present in children and adolescents (CA) in outpatient follow-up, as well as their possible associations. METHODS: This retrospective observational study's data were compiled from the CA's medical records with T1DM (n = 78) being followed up at the Pediatric Endocrinology Service of the Federal University of Uberlândia. RESULTS: The average participants' age was 10.2 years (1-16), most of them (55%) being male, with a diagnosis time of 4.5 years (1-13), and a body mass index of 18 kg/m2. The group had HbA1c levels of 9.6% and an estimated average glycemia of 229.5 ± 103 mg/dL. TiR was 25% (7-54%); the short- (CV%) and medium-term (ΔHbA1c) glycemic variability was 45.7% and 1.5%, respectively. Approximately 10% had diabetes ketoacidosis in the last year of follow-up, about 6% had chronic complications, such as nephropathy or retinopathy, and 20% had some other associated autoimmune disease. 49% of the participants reported regular physical activity. CONCLUSION: The high values of HbA1c and glycemic variability amplitude, short TiR, and the early presence of chronic complications reveal that the treatment did not reach its goal in this population. Better education of patients and their families about the disease and greater adherence to intensive insulin treatment can optimize the control of diabetes in pediatric patients.

Mating-type locus rearrangements and shifts in thallism states in Citrus-associated Phyllosticta species.

Currently, eight Phyllosticta species are known to be associated with several Citrus hosts, incorporating diverse lifestyles: while some of them are endophytic (P. capitalensis and P. citribraziliensis), others are pathogenic (P. citriasiana, P. citricarpa, P. citrichinaensis and P. paracitricarpa). Sexual reproduction plays a key role in the interaction between these Phyllosticta species and their Citrus hosts, especially for the spread and persistence of the pathogenic species in the environment. Given this, differences in sexual reproduction strategies could be related to the differences in lifestyles. To evaluate this hypothesis, we characterized the mating-type loci of six Citrus-associated Phyllosticta species from whole genome assemblies. Mating-type genes in the Citrus-associated Phyllosticta species are highly variable in their sequence content, but the genomic locations and organization of the mating-type loci are conserved. Phyllosticta citriasiana, P. citribraziliensis, P. citricarpa and P. paracitricarpa are heterothallic, while P. capitalensis and P. citrichinaensis are homothallic. In addition, the P. citrichinaensis MAT1-2 idiomorph occurs in a separate location from the mating-type locus. Ancestral state reconstruction suggests that homothallism is the ancestral thallism state in Phyllosticta, with a shift to heterothallism in Phyllosticta species that are pathogenic to Citrus. Moreover, the homothallic strategies of P. capitalensis and P. citrichinaensis result from independent evolutionary events, as P. capitalensis locus likely represents the ancestral state, and P. citrichinaensis homothallism has risen through a reversion in a heterothallic ancestor and underwent remodelling events. As the pathogenic species P. citriasiana, P. citricarpa and P. paracitricarpa are heterothallic and incapable of selfing, disease management practices focused in preventing the occurrence of sexual reproduction could assist in the control of Citrus Black Spot and Citrus Tan Spot diseases. This study emphasizes the importance of studying Citrus-Phyllosticta interactions under evolutionary and genomic perspectives, as these approaches can provide valuable information about the association between Phyllosticta species and their hosts, and also serve as guidance for the improvement of disease management practices.

Hypnotizability-Related Effects of Pain Expectation on the Later Modulation of Cortical Connectivity.

This study examined hypnotizability-related modulation of the cortical network following expected and nonexpected nociceptive stimulation. The electroencephalogram (EEG) was recorded in 9 high (highs) and 8 low (lows) hypnotizable participants receiving nociceptive stimulation with (W1) and without (noW) a visual warning preceding the stimulation by 1 second. W1 and noW were compared to baseline conditions to assess the presence of any later effect and between each other to assess the effects of expectation. The studied EEG variables measured local and global features of the cortical connectivity. With respect to lows, highs exhibited scarce differences between experimental conditions. The hypnotizability-related differences in the later processing of nociceptive information could be relevant to the development of pain-related individual traits. Present findings suggest a lower impact of nociceptive stimulation in highs than in lows.

Microscopic analysis of colonization of Colletotrichum abscissum in citrus tissues.

Postbloom fruit drop (PFD), caused mainly by Colletotrichum abscissum, is one of the most severe citrus diseases and can causes up to 80% fruit loss in favorable climatic conditions. According to the literature, other Colletotrichum species colonize hosts using distinct strategies: intracellular hemibiotrophic or subcuticular intramural necrotrophic colonization. However, so far, for C. abscissum only the necrotrophic stage has been described and some aspects remain unclear in PFD disease cycle. To better understand the disease cycle, microscopy studies could be applied. However, even using eGFP strains (expressing green fluorescent protein), the results are unclear due to the autofluorescence of citrus leaves. To eliminate this problem and to study the interaction between C. abscissum-citrus we used a destaining and staining methodologies, and we observed that in leaves, even applying injury before inoculation, C. abscissum does not colonize adjacent tissues. Apparently, in the leaves the fungus only uses the nutrients exposed in the artificial lesions for growth, and then produces large amount of spores. However, in flowers, C. abscissum penetrated and colonized the tissues of the petals 12 h after inoculation. In the early stages of infection, we observed the development of primary biotrophic hyphae, suggesting this species as a hemibiotrophic fungus, with a short biotrophic phase during flower colonization followed by dominant necrotrophic colonization. In conclusion, the use of an eGFP strain of C. abscissum and a different methodology of destaining and staining allowed a better understanding of the morphology and mechanisms used by this citrus pathogen to colonize the host.

Caregiver burden and family functioning in different neurological diseases.

Aim of this study is to examine caregiver burden and family functioning in different neurological conditions. Forty-two primary caregivers of patients with Amyotrophic Lateral Sclerosis (ALS), Alzheimer's Disease and other dementia (AD), Parkinson's Disease (PD), Acquired Brain Injuries (ABI) and Multiple Sclerosis (MS) were administered scales for the evaluation of caregiver burden (CBI) and family functioning (FACES IV). Caregiver burden was overall high, with caregivers of patients with ALS and ABI having exceeded the CBI cut-off score for possible burn-out. The average scores of caregivers of patients with AD or other dementia and PD were close to the cut-off score, whereas those of caregivers of patients with MS were significantly lower than the others. Family cohesion, family satisfaction and the quality of family communication were associated with reduced levels of caregiver burden, whereas disengagement was associated with a higher burden. The data from the present study confirm that caregiver burden is a relevant issue in the context of neurological diseases, especially for those causing higher degrees of impairment. Significant correlations with family functioning emerged as well, highlighting the importance of studying and treating caregiver burden within the context of family relations.

Scaffolds of bioactive glass-ceramic (Biosilicate®) and bone healing: A biological evaluation in an experimental model of tibial bone defect in rats.

This study aimed to investigate the in vivo tissue response of the Biosilicate® scaffolds in a model of tibial bone defect. Sixty male Wistar rats were distributed into bone defect control group (CG) and Biosilicate® scaffold group (BG).  Animals were euthanized 15, 30 and 45 days post-surgery. Stereomicroscopy, scanning electron microscopy, histopathological, immunohistochemistry and biomechanical analysis were used. Scaffolds had a total porosity of 44%, macroporosity of 15% with pore diameter of 230 µm. Higher amount of newly formed bone was observed on days 30 and 45 in BG. Immunohistochemistry analysis showed that the COX-2 expression was significantly higher on days 15 and 30 in BG compared with the CG. RUNX-2 immunoexpression was significantly higher in BG on days 15 and 45. No statistically significant difference was observed in RANKL immunoexpression in all experimental groups. BMP-9 immunoexpression was significantly upregulated in the BG on day 45. Biomechanical analysis showed a decrease in the biomechanical properties of the bone callus on days 30 and 45. The implantation of the Biosilicate® scaffolds was effective in stimulating newly bone formation and produced an increased immunoexpression of markers related to the bone repair.

Aerobic rehabilitation program for improving muscle function in Parkinson's disease.

BACKGROUND: Parkinson's Disease (PD) is characterized by progressive and disabling symptoms. An impaired oxidative metabolism efficiency was supposed to be involved in the systemic impairment. Rehabilitative treatment represents a valid tool in promoting skeletal muscle's adaptations, even if no solid studies on muscle metabolic features are still available. OBJECTIVE: To evaluate the efficiency of skeletal muscle oxidative metabolism in PD patients in comparison with age-matched controls and test the role of an intensive aerobic treatment on muscle oxidative metabolism and its clinical effects. METHODS: 60 PD patients and 32 age-matched healthy controls participated. Haematic lactate values were detected during and after a submaximal incremental exercise on treadmill. The number of steps completed during the exercise was recorded. From these patients 10 underwent to an intensive aerobic treatment on treadmill (4 sessions/week for 4 weeks). Haematic lactate values and functional scales were recorded before (T0) and after (T1) treatment. RESULTS: At rest no significant difference in hematic lactate values between PD and control subjects was found. Lactate blood levels were significantly higher (p < 0,001) after the aerobic exercise test in PD patients compared to controls. These values remained higher at any time during recovery period (p < 0,001). No significant relationship between lactate values and the number of completed steps was found. After the rehabilitation treatment haematic value of lactate showed a significant reduction (p < 0,05) at 0, 5 and 10 minutes of recovery period with a normalization of value at 30'. All functional scales showed an improvement trend at T1, in particular Berg Balance Scale and 6 Meter Walking Test showed a significant reduction (p < 0,001 and p < 0,05 respectively). CONCLUSION: Our data clearly show an impaired muscle oxidative efficiency in PD subjects. The intensive rehabilitation program on treadmill showed a beneficial effect on muscle oxidative metabolism, endurance and balance, confirming the focal role of rehabilitation in PD patients.

Delta Power Is Higher and More Symmetrical in Ischemic Stroke Patients with Cortical Involvement.

A brain injury resulting from unilateral stroke critically alters brain functionality and the complex balance within the cortical activity. Such modifications may critically depend on lesion location and cortical involvement. Indeed, recent findings pointed out the necessity of applying a stratification based on lesion location when investigating inter-hemispheric balance in stroke. Here, we tested whether cortical involvement could imply differences in band-specific activity and brain symmetry in post stroke patients with cortico-subcortical and subcortical strokes. We explored brain activity related to lesion location through EEG power analysis and quantitative Electroencephalography (qEEG) measures. Thirty stroke patients in the subacute phase and 10 neurologically intact age-matched right-handed subjects were enrolled. Stroke patients were equally subdivided in two groups based on lesion location: cortico-subcortical (CS, mean age ± SD: 72.21 ± 10.97 years; time since stroke ± SD: 31.14 ± 11.73 days) and subcortical (S, mean age ± SD: 68.92 ± 10.001 years; time since stroke ± SD: 26.93 ± 13.08 days) group. We assessed patients' neurological status by means of National Institutes of Health Stroke Scale (NIHSS). High density EEG at rest was recorded and power spectral analysis in Delta (1-4 Hz) and Alpha (8-14 Hz) bands was performed. qEEG metrics as pairwise derived Brain Symmetry Index (pdBSI) and Delta/Alpha Ratio (DAR) were computed and correlated with NIHSS score. S showed a lower Delta power in the Unaffected Hemisphere (UH) compared to Affected Hemisphere (AH; z = -1.98, p < 0.05) and a higher Alpha power compared to CS (z = -2.18, p < 0.05). pdBSI was negatively correlated with NIHSS (R = -0.59, p < 0.05). CS showed a higher value and symmetrical distribution of Delta band activity (z = -2.37, p < 0.05), confirmed also by a higher DAR value compared to S (z = -2.48, p < 0.05). Patients with cortico-subcortical and subcortical lesions show different brain symmetry in the subacute phase. Interestingly, in subcortical stroke patient brain activity is related with the clinical function. qEEG measures can be explicative of brain activity related to lesion location and they could allow precise definition of diagnostic-therapeutic algorithms in stroke patients.

A NEW HEALTH TECHNOLOGY ASSESSMENT SYSTEM FOR JAPAN? SIMULATING THE POTENTIAL IMPACT ON THE PRICE OF SIMEPREVIR.

OBJECTIVES: Japanese authorities have announced a plan to introduce a health technology assessment (HTA) system in 2016. This study assessed the potential impact of such a policy on the price of the antivirologic drug simeprevir. METHODS: Taking the antivirologic drug simeprevir as an example, we compared the current Japanese price with hypothetical prices that might result if a U.K. (cost-utility) or German (efficiency frontier) style HTA assessment was in place. RESULTS: The simeprevir unit price under the current Japanese pricing scheme is 13,122 Japanese yen (equivalent to 109.35 U.S. dollars as of April 2015). Depending on the selection of comparators and the pricing method, and assuming that HTA will be used as a basis for price setting, the estimated prices of simeprevir vary up to four times higher than under the current Japanese pricing scheme. CONCLUSIONS: Although the analysis is based on only one drug, it cannot be taken for granted that a new HTA system would reduce public healthcare expenditure in Japan.

Efficacy of a combined therapeutic approach in the management of Pisa Syndrome.

BACKGROUND: Pisa syndrome (PS) represents an important source of disability in Parkinson's disease (PD). Currently no consensus has been reached on its definition or diagnostic criteria, and therapeutic approaches are unspecific and often futile. Recently the role of abdominal muscles, and in particular of the external oblique (EO), in the pathogenesis of PS was hypothesized. OBJECTIVES: To evaluate the role of EO and propose a combined therapeutic approach in the management of PS. METHODS: Ten PD patients with PS underwent a combined protocol based on repeated lidocaine injection in EO and rehabilitation program. RESULTS: Our data confirm the primary role of EO muscles in PS pathogenesis and showed an improvement in truncal flexion and balance with a positive impact on patients' quality of life after treatment. CONCLUSIONS: These data highlight the need for accurate characterization of PS focusing on the role of abdominal muscles and the need for a specific rehabilitation protocol for PS management.

Defective chromatic and achromatic visual pathways in developmental dyslexia: Cues for an integrated intervention programme.

PURPOSE: As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. METHODS: Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. RESULTS: Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. CONCLUSION: These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

Neurophysiological Characterization of Subacute Stroke Patients: A Longitudinal Study.

Various degrees of neural reorganization may occur in affected and unaffected hemispheres in the early phase after stroke and several months later. Recent literature suggests to apply a stratification based on lesion location and to consider patients with cortico-subcortical and subcortical strokes separately: different lesion location may also influence therapeutic response. In this study we used a longitudinal approach to perform TMS assessment (Motor Evoked Potentials, MEP, and Silent Period, SP) and clinical evaluations (Barthel Index, Fugl-Meyer Assessment for upper limb motor function and Wolf Motor Function Test) in 10 cortical-subcortical and 10 subcortical ischemic stroke patients. Evaluations were performed in a window between 10 and 45 days (t0) and at 3 months after the acute event (t1). Our main finding is that 3 months after the acute event patients affected by subcortical stroke presented a reduction in contralateral SP duration in the unaffected hemisphere; this trend is related to clinical improvement of upper limb motor function. In conclusion, SP proved to be a valid parameter to characterize cortical reorganization patterns in stroke survivors and provided useful information about motor recovery within 3 months in subcortical patients.

Treatment outcomes with hypofractionated high-dose radiation therapy for prostate cancer.

AIM: To report the treatment results of a retrospective cohort of prostate cancer patients treated with Hypo-RT with a high equivalent biological effective dose (BED). BACKGROUND: Hypofractionated radiotherapy (Hypo-RT) has gained popularity and interest in the treatment of prostate cancer. However, there are few experiences with adequate follow-up reporting treatment results using high equivalent dose with Hypo-RT. MATERIALS AND METHODS: We assigned 149 men with low-, intermediate- and high-risk prostate cancer to receive Hypo-RT with a total dose of 69 Gy/23 fractions. Late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified RTOG criteria. Biochemical no evidence of disease (bNED) was defined as the nadir prostate-specific antigen level plus 2 ng/mL. RESULTS: The median follow-up was 53 months. For the entire cohort, the 5-year bNED rate was 94.6%, and for low-, intermediate- and high-risk patients the 5-year bNED was 100%, 96.4%, and 86% (p = 0.007), respectively. The 5-year overall survival rate was 92%. Only 1 patient died from the disease at 48 months after treatment, giving a 5-year cancer-specific survival of 98%. The worst grade ≥2 rate GI and GU toxicity was 13.4% and 14%, respectively. No grade >3 toxicity was observed. The presence of grade ≥2 GI and GU toxicity at the last follow-up was only 1.3% and 3%, respectively. CONCLUSIONS: Hypo-RT (69 Gy/23 fractions) with a high equivalent BED produces excellent rates of biochemical control for low, intermediate and high-risk prostate cancer. The long term GU and GI toxicity rates were considered low and acceptable.

Extensive Functional Evaluations to Monitor Aerobic Training in Becker Muscular Dystrophy: A Case Report.

Low-intensity aerobic training seems to have positive effects on muscle strength, endurance and fatigue in Becker Muscular Dystrophy (BMD) patients. We describe the case of a 33-year old BMD man, who performed a four-week aerobic training. Extensive functional evaluations were executed to monitor the efficacy of the rehabilitative treatment. Results evidenced an increased force exertion and an improvement in muscle contraction during sustained exercise. An improvement of walk velocity, together with agility, endurance capacity and oxygen consumption during exercise was observed. Moreover, an enhanced metabolic efficiency was evidenced, as shown by reduced lactate blood levels after training. Interestingly, CK showed higher levels after the training protocol, revealing possible muscle damage. In conclusion, aerobic training may represent an effective method improving exercise performance, functional status and metabolic efficiency. Anyway, a careful functional assessment should be taken into account as a useful approach in the management of the disease's rehabilitative treatment.

Whole brain radiotherapy and stereotactic radiosurgery for patients with recursive partitioning analysis I and lesions <5 cm(3): A matched pair analysis.

OBJECTIVE: The intention of this study is to compare whole brain radiotherapy and stereotactic radiosurgery (WBRT + SRS) with WBRT in patients with 1-4 brain metastases to find a subgroup of patients that have a great benefit with aggressive treatment. MATERIALS AND METHODS: Between December 2002 and December 2013, 60 patients with 1-4 brain metastases were treated by WBRT + SRS. In this period, 60 patients treated with WBRT were matched with patients treated with WBRT + SRS. RESULTS: The median survival for the entire cohort was 8.3 months. In the univariate analysis, WBRT + SRS (0.031), the presence of extracranial disease (P = 0.02), Karnofsky performance score <70 (P = 0.0001), and age >65 (P = 0.001) years were significant factors for survival. In the entire cohort, the median survival for recursive partitioning analysis (RPA) classes I, II, and III was 11, 7, and 3 months, respectively (P = 0.0001). In a stratified analysis, only RPA class I achieved statistical significance for 1-year survival between the groups (WBRT + SRS = 51% and WBRT = 23%, P = 0.03). Cox regression analysis revealed WBRT + SRS, age >65 years, and extracranial disease as independent prognostic factors. In the univariate analysis, lesion volume ≤5 cm 3 (P = 0.002) and WBRT + SRS (P = 0.003) were the significant factors associated with better brain control. CONCLUSION: WBRT plus SRS was an independent prognostic factor for survival. However, the combined treatment appears to be justified only in patients with RPA I and lesion volume ≤5 cm 3, independently of the number of lesions.

Blink reflex in subjects with different hypnotizability: New findings for an old debate.

Hypnotizability is associated with attentional characteristics whose neurophysiological bases are still under debate. Aim of the study was the assessment of possible hypnotizability-related differences in blink reflex (BR) which has a nociceptive component, is sensitive to attentional-emotional traits and states and is modulated by the brain dopamine content. In 10 high (highs) and 10 low hypnotizable participants (lows) BR was induced by electrical nociceptive stimulation of the right supraorbital nerve in the absence (noW) and in the presence of a visual cue preceding the electrical stimulation by 0.1ms (W01) and by 1ms (W1). The studied variables were: the amplitude of BR components (R1, R2, R3), the amplitude of the quick change (TO) of heart rate ("turbulence") induced by stimulation and its recovery slope (TS), the role of the Behavioral Inhibition/Activation System (BIS/BAS) in the variability BR and cardiac turbulence. Repeated measures ANOVA did not show any significant difference between highs and lows in blink reflex. TO indicated stimulation related HR increase in highs and decrease in lows, TS was larger in highs. BIS and BAS accounted for the warning effects on the BR amplitude and modulated the hypnotizability and warning effects on TO and TS. Findings do not support dopamine based hypnotizability-related attentional abilities. In contrast, they indicate that hypnotizability modulates the short-lasting cardiac response to electrical nociceptive stimulation.

Clinical and economic impact of rivaroxaban on the burden of atrial fibrillation: The case study of Japan.

OBJECTIVES: Atrial fibrillation (AF) affects an estimated 1.5 million individuals in Japan, increasing their stroke risk and imposing considerable costs on the Japanese healthcare system. To reduce stroke incidence, guidelines recommend using anticoagulants in moderate-to-high risk non-valvular AF (NVAF) patients; however, many patients receive no treatment, aspirin only, or remain poorly-controlled on vitamin K antagonists (VKAs) due to high VKA discontinuation rates and non-adherence to guidelines. A prevalence-based Markov model was developed to estimate the clinical and budgetary impact of treating these patients with Xarelto(TM) (rivaroxaban, Bayer AG) in Japan. METHODS: Population, baseline risk of events, and associated management costs were estimated using data from Japanese publications where available. Treatment efficacy and safety were derived from published data and the J-ROCKET AF trial. Drug and physician visit costs were based on data from the Ministry of Health, Labor, and Welfare, the J-ROCKET AF trial, and Japanese clinical guidelines. RESULTS: This model demonstrates that increased use of rivaroxaban in inadequately-managed NVAF patients could avoid 456 081 non-fatal ischemic strokes (IS) and 76 975 cardiovascular deaths over 10 years in Japan. This clinical benefit offsets the increased incidence of myocardial infarctions and anticoagulant-related bleeding. Decreased event costs could lead to a ¥188.4 billion decrease in net spending over the analysis time horizon. CONCLUSIONS: Introducing rivaroxaban may decrease the burden of NVAF in Japanese society. From a clinical perspective, the reduction in IS and embolic events outweighs the increased risk of anticoagulant-related bleeding; from an economic perspective, reduced event costs offset drug and physician visit costs, resulting in cost savings.

EEG Theta Dynamics within Frontal and Parietal Cortices for Error Processing during Reaching Movements in a Prism Adaptation Study Altering Visuo-Motor Predictive Planning.

Modulation of frontal midline theta (fmθ) is observed during error commission, but little is known about the role of theta oscillations in correcting motor behaviours. We investigate EEG activity of healthy partipants executing a reaching task under variable degrees of prism-induced visuo-motor distortion and visual occlusion of the initial arm trajectory. This task introduces directional errors of different magnitudes. The discrepancy between predicted and actual movement directions (i.e. the error), at the time when visual feedback (hand appearance) became available, elicits a signal that triggers on-line movement correction. Analysis were performed on 25 EEG channels. For each participant, the median value of the angular error of all reaching trials was used to partition the EEG epochs into high- and low-error conditions. We computed event-related spectral perturbations (ERSP) time-locked either to visual feedback or to the onset of movement correction. ERSP time-locked to the onset of visual feedback showed that fmθ increased in the high- but not in the low-error condition with an approximate time lag of 200 ms. Moreover, when single epochs were sorted by the degree of motor error, fmθ started to increase when a certain level of error was exceeded and, then, scaled with error magnitude. When ERSP were time-locked to the onset of movement correction, the fmθ increase anticipated this event with an approximate time lead of 50 ms. During successive trials, an error reduction was observed which was associated with indices of adaptations (i.e., aftereffects) suggesting the need to explore if theta oscillations may facilitate learning. To our knowledge this is the first study where the EEG signal recorded during reaching movements was time-locked to the onset of the error visual feedback. This allowed us to conclude that theta oscillations putatively generated by anterior cingulate cortex activation are implicated in error processing in semi-naturalistic motor behaviours.