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Background: ALS is a progressive neurodegenerative disease without a cure and limited treatment options. Edaravone, a free radical scavenger, was shown to slow disease progression in a select group of patients with ALS over 6 months; however, the effect on survival was not investigated in randomized trials. The objective of this study is to describe real-world survival effectiveness over a longer timeframe. Methods: This retrospective cohort study included patients with ALS across Canada with symptom onset up to three years. Those with a minimum 6-month edaravone exposure between 2017 and 2022 were enrolled in the interventional arm, and those without formed the control arm. The primary outcome of tracheostomy-free survival was compared between the two groups, accounting for age, sex, ALS-disease progression rate, disease duration, pulmonary vital capacity, bulbar ALS-onset, and presence of frontotemporal dementia or C9ORF72 mutation using inverse propensity treatment weights. Results: 182 patients with mean ± SD age 60±11 years were enrolled in the edaravone arm and 860 in the control arm (mean ± SD age 63±12 years). Mean ± SD time from onset to edaravone initiation was 18±10 months. Tracheostomy-free survival will be calculated. Conclusions: This study will provide evidence for edaravone effectiveness on tracheostomy-free survival in patients with ALS.
Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total and pathogenic IgG autoantibody levels through FcRn blockade. ADAPT was a phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT could enroll in ADAPT+ (open-label extension). Methods: Efgartigimod (10 mg/kg intravenous) was administered in cycles of 4 weekly infusions, with subsequent cycles initiated based on clinical evaluation. ADAPT+ evaluated long-term safety and tolerability of efgartigimod in patients with gMG. Efficacy was assessed utilizing MG-ADL and QMG scores. Results: Of 167 patients from ADAPT, 151 (90%) entered ADAPT+, and 145 received ≥1 cycle as of January 2022. Over 217.55 patient-years of follow-up (mean duration per patient, 548 days), incidence of adverse events did not increase with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. All AChR-Ab+ patients (n=111) demonstrated consistent improvements (mean change [SE], week 3 of cycle 1) in MG-ADL (-5.0 [0.33]; up to 14 cycles) and QMG (-4.7 [0.41]; up to 7 cycles) scores during each cycle. Conclusions: These ADAPT+ analyses suggest long-term efgartigimod treatment is well tolerated and efficacious. Additional final data cut analyses will be presented at CNSF 2023.
This study aimed to explore the utility of the eosinophil percentage in peripheral blood for guiding post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps.
Forty-four patients with chronic rhinosinusitis with nasal polyps underwent functional endoscopic sinus surgery and were randomly divided into two groups. Patients in the standard treatment group used oral and nasal spray glucocorticoids. In the biomarker treatment group, patients with peripheral blood eosinophil percentage values less than 3.05 per cent did not receive glucocorticoid treatment, whereas patients with values 3.05 per cent or above were part of the standard treatment group. Visual Analogue Scale, Sino-Nasal Outcome Test-22 scores, endoscopic Lund–Kennedy scores, eosinophils, interleukin-5 and eosinophil cationic protein in peripheral blood, and nasal secretions were measured.
After functional endoscopic sinus surgery, the Visual Analogue Scale, Sino-Nasal Outcome Test-22 and Lund–Kennedy scores were significantly reduced in both groups; there were no significant differences in those indicators between the groups during the three follow-up visits.
Peripheral blood eosinophil percentage offers a potential biomarker to guide post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps.
The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses’ Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.
l-theanine is a unique nonproteinogenic amino acid found in tea, and has recently received considerable attention because of its various biological activities. However, there is no available research report on the use of l-theanine as a feed additive in ducks. This study was conducted to investigate the potential benefits and appropriate dosages of l-theanine on the growth performance, immune function, serum biochemical parameters, and jejunum morphology and antioxidant capacity of ducks. A total of 600 1-day-old Chaohu ducks were randomly allocated into five dietary treatment groups supplemented with 0 (control group), 300, 600, 900 and 1500 mg/kg of l-theanine. Each group included five replicates of 24 birds each. Body weight at day 28 was increased (P<0.05) by l-theanine. From days 15 to 28, l-theanine elevated cumulative BW gain (BWG) and cumulative feed intake (FI), and decreased feed to gain ratio. From days 1 to 28, l-theanine elevated (P<0.05) cumulative BWG and cumulative FI. l-theanine elevated (P<0.05) the relative weight of bursa of Fabricus (day 14), thymus (day 14), spleen (day 28) and liver (day 28). On day 28, l-theanine decreased (P<0.05) serum glucose, uric acid, triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, insulin, interleukin-2 (IL-2) and IL-6 contents, and elevated (P<0.05) serum total protein, globulin (GLB), immune globulin A (IgA) and IgG contents, but only serum insulin, interferon-γ, tumor necrosis factor-α and IL-6 contents was decreased (P<0.05) and serum GLB and IgM content was elevated (P<0.05) by l-theanine on day 14. On day 14, l-theanine decreased (P<0.05) jejunum crypt depth, and elevated (P<0.05) jejunum villus height, villus height to crypt depth ratio (V/C), goblet cell number and total superoxide dismutase (T-SOD) activity. On day 28, l-theanine decreased (P<0.05) jejunum malondialdehyde content, and elevated (P<0.05) jejunum villus height, V/C, goblet cell number, and T-SOD, catalase and glutathione peroxidase activities. l-theanine levels caused quadratic effect on the growth performance, relative organ weight, serum parameters, jejunum morphology and antioxidant capacity. In conclusion, l-theanine can be used as a promising feed additive for ducks, and its optimal supplementation level was 600 to 900 mg/kg based on the current experimental condition.
The neuropsychological origins of negative syndrome of schizophrenia remain elusive. Evidence from behavioural studies, which utilised emotion-inducing pictures to elicit motivated behaviour generally reported that that schizophrenia patients experienced similar affective experience as healthy individuals but failed to translate emotional salience to motivated behaviour, a phenomenon called emotion–behaviour decoupling. However, a few studies have examined emotion–behaviour decoupling in non-psychotic high-risk populations, who are relatively unaffected by medication effects.
In this study, we examined the nature and extent of emotion–behaviour decoupling in in three independent samples (65 schizophrenia patients v. 63 controls; 40 unaffected relatives v. 45 controls; and 32 individuals with social anhedonia v. 32 controls). We administered an experimental task to examine their affective experience and its coupling with behaviour, using emotion-inducing slides, and allowed participants to alter stimulus exposure using button-pressing to seek pleasure or avoid aversion.
Schizophrenia patients reported similar affective experiences as their controls, while their unaffected relatives and individuals with high levels of social anhedonia exhibited attenuated affective experiences, in particular in the arousal aspect. Compared with their respective control groups, all of the three groups showed emotion–behaviour decoupling.
Our findings support that both genetically and behaviourally high-risk groups exhibit emotion–behaviour decoupling. The familial association apparently supports its role as a putative trait marker for schizophrenia.
Numerical simulations are used to investigate the hydrodynamic benefits of body–fin and fin–fin interactions in a fish model in carangiform swimming. The geometry and kinematics of the model are reconstructed in three-dimensions from high-speed videos of a live fish, Crevalle Jack (Caranx hippos), during steady swimming. The simulations employ an immersed-boundary-method-based incompressible Navier–Stokes flow solver that allows us to quantitatively characterize the propulsive performance of the fish median fins (the dorsal and the anal fins) and the caudal fin using three-dimensional full body simulations. This includes a detailed analysis of associated performance enhancement mechanisms and their connection to the vortex dynamics. Comparisons are made using three different models containing different combinations of the fish body and fins to provide insights into the force production. The results indicate that the fish produces high performance propulsion by utilizing complex interactions among the fins and the body. By connecting the vortex dynamics and surface force distribution, it is found that the leading-edge vortices produced by the caudal fin are associated with most of the thrust production in this fish model. These vortices could be strengthened by the vorticity capture from the vortices generated by the posterior body during undulatory motion. Meanwhile, the pressure difference between the two sides of posterior body resulting from the posterior body vortices (PBVs) helps with the alleviation of the body drag. The appearance of the median fins in the posterior region further strengthens the PBVs and caudal-fin wake capture mechanism. This work provides new physical insights into how body–fin and fin–fin interactions enhance thrust production in swimming fishes, and emphasizes that movements of both the body and fins contribute to overall swimming performance in fish locomotion.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
Patients with schizophrenia have intact ability to experience emotion, but empirical evidence suggests that they fail to translate emotional salience into effortful behaviour. Previous research in patients with chronic schizophrenia suggests that working memory is important in integrating emotion and behaviour. This study aimed to examine avolition and anhedonia in patients with first-episode schizophrenia and clarify the role of working memory in emotion–behaviour coupling.
We recruited 72 participants with first-episode schizophrenia and 61 healthy controls, and used a validated emotion-inducing behavioural paradigm to measure participants' affective experiences and how experienced emotion coupled with behaviour. Participants were given the opportunity to expend effort to increase or decrease their exposure to emotion-inducing photographs. Participants with schizophrenia having poor working memory were compared with those with intact working memory in their liking and emotion–behaviour coupling.
Patients with first-episode schizophrenia experienced intact ‘in-the-moment’ emotion, but their emotion was less predictive of the effort expended, compared with controls. The emotion–behaviour coupling was significantly weaker in patients with schizophrenia with poor working memory than in those with intact working memory. However, compared with controls, patients with intact working also showed substantial emotion–behaviour decoupling.
Our findings provide strong evidence for emotion–behaviour decoupling in first-episode schizophrenia. Although working memory deficits contribute to defective translation of liking into effortful behaviour, schizophrenia alone affects emotion–behaviour coupling.
Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia.
Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17–21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect.
Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression.
Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.
Amyotrophic lateral sclerosis (ALS) is a devastating cause of progressive weakness, respiratory failure and death. To date there is no effective therapy to meaningfully extend survival but continuously emerging targets and putative treatments are studied in clinical trials. Canadian epidemiological data on ALS is scarce and the socioeconomic impact of ALS on Canadian society is unclear. The Canadian Neuromuscular Disease Registry (CNDR) is a national clinic-based registry of patients with neuromuscular diseases with the goal of facilitating the design and execution of clinical research.
We conducted a national stakeholder survey to assess interest for a Canadian ALS registry and an assessment of expected case ascertainment. A dataset derivation meeting was held to establish the registry medical dataset.
We report the results of the national stakeholder survey, case ascertainment assessment, and the derived dataset that have resulted in the current implementation of a Canadian registry of patients with ALS.
The development of this long sought-after resource is a significant step forward for the Canadian ALS patient and research communities that will result in more efficient clinical trial recruitment and advancements in our understanding of ALS in Canada.
To study the interactive influence of implanted nano platinum black electrodes (as compared with pure platinum electrodes) on rabbit orbicularis oculi muscle morphology and function.
The influence of the two types of electrode on the orbicularis oculi muscle was monitored in a rabbit model of facial paralysis. Biological electric current and exciting current were administered to biological tissue, and morphological and functional changes were identified. Changes in orbicularis oculi muscle contraction, electrode configuration and performance associated with long-term electrical stimulation were observed over 28 days of implantation.
The nano platinum black electrode was superior to the pure platinum electrode in the following aspects: morphology and functionality, electrical excitation function of the orbicularis oculi muscle (as assessed by electromyography), muscle contraction function and biological tissue changes. Furthermore, the nano platinum black electrode features had good stability.
Microelectrode surface modification with nano platinum black can effectively increase the microelectrode surface area and improve electrode performance, and is associated with good tissue compatibility.
The Chinese Spectral Radioheliograph (CSRH) is under construction in Mingantu station of NAOC in China. Now, CSRH-I which includes antenna, receiver and correlator in decimetric wave range has been established. This paper introduced calibration on CSRH and present some results of data processing.
Understanding genetic and environmental effects on white matter development in the first years of life is of great interest, as it provides insights into the etiology of neurodevelopmental disorders. In this study, the genetic and environmental effects on white matter were estimated using data from 173 neonatal twin subjects. Diffusion tensor imaging scans were acquired around 40 days after birth and were non-rigidly registered to a group-specific atlas and parcellated into 98 ROIs. A model of additive genetic, and common and specific environmental variance components was used to estimate overall and regional genetic and environmental contributions to diffusion parameters of fractional anisotropy, radial diffusivity, and axial diffusivity. Correlations between the regional heritability values and diffusion parameters were also examined. Results indicate that individual differences in overall white matter microstructure, represented by the average diffusion parameters over the whole brain, are heritable, and estimates are higher than found in studies in adults. Estimates of genetic and environmental variance components vary considerably across different white matter regions. Significant positive correlations between radial diffusivity heritability and radial diffusivity values are consistent with regional genetic variation being modulated by maturation status in the neonatal brain: the more mature the region is, the less genetic variation it shows. Common environmental effects are present in a few regions that tend to be characterized by low radial diffusivity. Results from the joint diffusion parameter analysis suggest that multivariate modeling approaches might be promising to better estimate maturation status and its relationship with genetic and environmental effects.
The current trends in stimulated Brillouin scattering and optical phase conjugation are overviewed. This report is formed by the selected papers presented in the “Fifth International Workshop on stimulated Brillouin scattering and phase conjugation 2010” in Japan. The nonlinear properties of phase conjugation based on stimulated Brillouin scattering and photo-refraction can compensate phase distortions in the high power laser systems, and they will also open up potentially novel laser technologies, e.g., phase stabilization, beam combination, pulse compression, ultrafast pulse shaping, and arbitrary waveform generation.
This study was conducted to determine the effects of soy isoflavones on changes in body and tissue weight and on insulin-like factor I (IGF-I) and peroxisome proliferator-activated receptor-γ (PPARγ) gene and protein expression in muscle and adipose tissues in Chinese Guangxi minipig, as a model for studying human nutrition. A total of 72 male Chinese Guangxi minipigs were fed basal diet (control, Con), low dose of soy isoflavones and high dose of soy isoflavones (HSI). The results showed that HSI increased the body weight (BW) gain and fat percentage of minipigs (P < 0.05). In addition, the serum concentrations of IGF-I and interleukin-6 were increased by high levels of soy isoflavones (P < 0.05). Furthermore, a diet containing soy isoflavones enhanced IGF-I mRNA expression levels in longissimus muscle, but decreased these levels in perirenal fat. However, the mRNA and protein expression levels of PPARγ in longissimus muscle and subcutaneous adipose tissue were both increased when compared with the Con. The data indicated that soy isoflavones regulated the BW gain and fat percentage of Chinese Guangxi minipigs, which also showed changes in IGF-I system and PPARγ. However, further research is required to clarify the causative relationship.
The effect of TiB2 on the densification behavior and properties of microwave-sintered AlN/TiB2 ceramic was investigated. The densification of the composite was significantly retarded in nitrogen atmosphere due to strong nitridation of TiB2 compared to sintering in argon atmosphere. The densities of the AlN/TiB2 composites containing different amounts of TiB2 all reached 99% of the theoretical density during 2 h of sintering at 1850 and 1900 °C. Microstructure analysis revealed that the TiB2 particles were dispersed in the AlN matrix while AlN grains retained its contiguity. This microstructure led to a composite with superior properties; thermal conductivity as high as 149 W/(m K) was achieved. The microwave sintered composites are harder and tougher than pure AlN. Microwave-sintered AlN/TiB2 composite is a promising material for structural applications in which high thermal conductivity and controlled dielectric loss are important.
Although advances have been made in the synthesis of raw carbon nanotube (CNT) materials, the lack of efficient processes for assembly and integration of CNTs into functional forms has hindered the development of CNT-based devices. Here we report a dielectrophorestic method to manipulate, align and assemble CNTs into one-dimensional nanostructures using an alternating-current electric field. Pre-formed CNTs dispersed in water are assembled into micro-electrodes and sub-micron diameter fibrils with variable lengths from 1 μm to over 1 cm. The CNTs within the fibril are bonded by van der Waals forces and are aligned along the fibril axis. This method affords fine control of the fibril length and is capable of parallel fabrication of multiple fibrils using the same material source. The short CNT fibrils can potentially be used as probes for scanning probe microscopes and the long ones as electrodes or conducting nanowires.