Blended learning(BL)has been widely adopted to improve students’academic achievements in higher education.However,its success relies mainly on student engagement,which plays an essential role in active learning and p...Blended learning(BL)has been widely adopted to improve students’academic achievements in higher education.However,its success relies mainly on student engagement,which plays an essential role in active learning and provides a rich understanding of students’experiences.The study utilized three self-designed scales-the Teacher Support Scale,Student Engagement Scale,and Student Learning Experience Scale-to gauge and examine the impact and relationship between perceived teacher support,student behavioral engagement,and the intermediary role of learning experiences.A cohort of 899 college students undertaking the obligatory College English course through BL modes across five Chinese universities actively participated by completing a comprehensive questionnaire.The results showed significant correlations between perceived teacher support,learning experience,and behavioral engagement.Perceived teacher support significantly predicted students’behavioral engagement,with socio-affective support exerting the most substantial predictive effects.All predictive effects were partially mediated by learning experience(learning mode,online resources,overall LMS-based learning,interaction with their instructor and peers,and learning outcome).The influence of perceived teacher support on behavioral engagement differed between students who reported the most positive(vs.negative)learning experiences.Suggestions for further research are offered for consideration.展开更多
BACKGROUND Previous research suggests that parents raising a child with autism experience higher levels of psychological distress than parents of typically developing children and parents of children with other develo...BACKGROUND Previous research suggests that parents raising a child with autism experience higher levels of psychological distress than parents of typically developing children and parents of children with other developmental disorders. Little is known, however, about the intersection between the effects of socioeconomic status(SES) on the wellbeing and sense of parental competency of parents of preschoolers with autism and how it relates to child symptom severity.AIM To examine the relationship between their child's symptom severity, SES, as measured by neighbourhood advantage and occupational status, on the psychological wellbeing and perceived parenting competence among parents of preschoolers with autism.METHODS Parents of 117 preschool-aged children with a diagnosis of autism spectrum disorder(ASD), 107 mothers and 54 fathers, completed questionnaires about their child's symptoms of ASD and functioning, their own perceptions of their wellbeing and parental competence on entry to an early intervention program in Sydney, Australia. Parents also provided demographic information pertaining to their occupation, level of education attained and address(postcode). All children were also assessed for their severity of symptoms using the Autism Diagnostic Observation Schedule. The Australian Socioeconomic Index of occupationalstatus as a measure of familial SES and the Index of Relative Socio-economic Advantage and Disadvantage as a measure of neighbourhood advantage were used to examine the impact of SES on parental sense of competence and wellbeing.RESULTS Compared to normative populations, both mothers and fathers in our sample reported significantly higher levels of parenting sense of efficacy but lower levels of interest in the parenting role. Mothers also displayed higher levels of satisfaction. Both mothers and fathers displayed higher levels of depression than normative populations with mothers also reporting greater levels of stress and anxiety. Child symptom severity was associated with maternal parenting competency with these relationships amplified among mothers with higher familial SES and who lived in areas of greater neighbourhood advantage.Increased adaptive functioning was associated with better maternal wellbeing,particularly among mothers who lived in areas of greater neighbourhood advantage. Contrastingly, paternal parenting competence was generally not influenced by child adaptive functioning or symptom severity, although for those in higher familial SES brackets, children's symptom severity and maladaptive symptoms were negatively related to paternal sense of parenting efficacy. There was a trend towards moderate relationships between lower familial SES and greater depression, stress and anxiety among fathers, but no relationship with their child's ASD symptom severity or functioning.CONCLUSION SES differentially impacts wellbeing and sense of parenting competence and its relationship to the impact of child symptoms for mothers and fathers of preschoolers with autism.展开更多
Alzheimer's disease(AD) is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by...Alzheimer's disease(AD) is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by amyloid-β(Aβ) peptide and phosphorylated tau; which is accompanied by progressive impairment of memory. Diverse signaling pathways are linked to AD, and among these the Wnt signaling pathway is becoming increasingly relevant, since it plays essential roles in the adult brain. Initially, Wnt signaling activation was proposed as a neuroprotective mechanism against Aβ toxicity. Later, it was reported that it participates in tau phosphorylation and processes of learning and memory. Interestingly, in the last years we demonstrated that Wnt signaling is fundamental in amyloid precursor protein(APP) processing and that Wnt dysfunction results in Aβ production and aggregation in vitro. Recent in vivo studies reported that loss of canonical Wnt signaling exacerbates amyloid deposition in a transgenic(Tg) mouse model of AD. Finally, we showed that inhibition of Wnt signaling in a Tg mouse previously at the appearance of AD signs, resulted in memory loss, tau phosphorylation and Aβ formation and aggregation; indicating that Wnt dysfunction accelerated the onset of AD. More importantly, Wnt signaling loss promoted cognitive impairment, tau phosphorylation and Aβ1–42 production in the hippocampus of wild-type(WT) mice, contributing to the development of an Alzheimer's-like neurophatology. Therefore, in this review we highlight the importance of Wnt/β-catenin signaling dysfunction in the onset of AD and propose that the loss of canonical Wnt signaling is a triggering factor of AD.展开更多
Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s d...Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid metabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxidative stress. Within cells, the endoplasmic reticulum (ER) appears to be particularly susceptible to such metabolic disruption. Sirtuin 1?(Sirt1) and leptin have received attention recently as they are central regulatory factors for the body’s metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings concerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on metabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.展开更多
This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with n...This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged -〉 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions: anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only (partial coefficient = 0.453, P = 0.045), after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.661, P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.573, P = 0.004) in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.展开更多
Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s ...Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s disease.Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity,the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies.We have previously established and validated budding yeast,Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ.Using colony counting based methods,oligomeric Aβ42 was shown to induce dose-dependent cell death in yeast.We have adapted this method for high throughput screening by developing an absorbance-based growth assay.We further validated the assay with treatments previously shown to protect oligomer Aβ42 induced cell death in mammalian and yeast cells.This assay offers a platform for studying underlying mechanisms of oligomer Aβ42 induced cell death using gene deletion/overexpression libraries and developing novel agents that alleviate Aβ42 induced cell death.展开更多
The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be i...The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be involved in cell suicide in various organ diseases with the importance of accelerated aging that requires early intervention with drug therapy to prevent diseases such as non alcoholic fatty liver disease (NAFLD) that has increased in children and reached to approx. 40% of the global population. Obesity is induced by various diets and lifestyle factors such as stress, anxiety and depression which are important to consider with the global increase in obesity and are possibly linked to the rise in individuals with brain disorders that involve neurodegeneration. Xenobiotics such as the endocrine disruptor chemicals that have increased in the environment in various developed countries lead to various chronic endocrine diseases as populations divert towards unhealthy diets and lifestyles with induction of NAFLD and obesity. The amount and nature of food intake that improves and increases liver lipid and xenobiotic metabolism in obese individuals have become important to decrease the risk for increased adiposity in man. High fibre or protein diets that contain leucine may improve liver glucose, lipid and xenobiotic metabolism and require further investigation with xenobiotics such as endocrine disruptors involved in appetite dysregulation and metabolic disorders in developed countries. The use of anti-obese drugs that reduce food intake and improve hypercholesterolemia and cardiovascular disease has been assessed in obesity with drug therapy closely involved either in the prevention or induction of NAFLD and obesity in man.展开更多
AIM To identify factors that promote a positive start to school for children with autism spectrum disorder(ASD).METHODS Web of Science,MEDLINE,Scopus,and Psych INFO searches were conducted to identify literature publi...AIM To identify factors that promote a positive start to school for children with autism spectrum disorder(ASD).METHODS Web of Science,MEDLINE,Scopus,and Psych INFO searches were conducted to identify literature published after 1991 and relevant to school transition processes in children with ASD.Twenty studies were deemed eligible for inclusion.These studies evaluated a range of factors including school readiness,parent and teacher perspectives on transition practices,characteristics of children with ASD that are associated with successful transition to school and the impact of school based intervention programs.RESULTS A review of these studies showed that children with ASD are less school ready emotionally than their peers and those children with ASD appear to have more externalising behaviours and self-regulation difficulties that affect their school engagement and their relationships with their teachers.There was a paucity of research looking at interventions targeting school readiness.However,school-based behavioural interventions appear to improve cognitive,language and daily living skills,but have less impact on socialisation and peer inclusion.CONCLUSION Children with ASD face more challenges transitioning to school,particularly with social interaction.Further development and implementation of specific schoolbased interventions is needed in order to assist children with autism to maximise their success in starting school.展开更多
In the current global epidemic for Non Alcoholic Fatty Liver Disease (NAFLD), diabetes and neuro-degenerative diseases such as Alzheimer’s disease there has been a major interest in magnesium therapy to delay the sev...In the current global epidemic for Non Alcoholic Fatty Liver Disease (NAFLD), diabetes and neuro-degenerative diseases such as Alzheimer’s disease there has been a major interest in magnesium therapy to delay the severity of NAFLD, Type 3 diabetes and neurodegeneration in the developing and developed world. The objective of magnesium therapy is to activate the anti-aging gene Sirtuin 1 (Sirt1) to prevent cardiovascular disease, NAFLD and diabetes. Reduced consumption of nutrients such as fatty acids, glucose, cholesterol and increased magnesium consumption is closely linked to reduced bacterial lipopolysaccharides (LPS) and activation of Sirt1 relevant to active nuclear and mitochondria interactions with the prevention of myocardial infarction and Type 3 diabetes. Magnesium deficiency and its effects on Sirt1 regulation have become important with magnesium deficiency associated with appetite dysregulation, senescence, glucose/nitric oxide dyshomeostasis, increased ceramide and toxic amyloid beta formation. Magnesium therapy activates the peripheral sink amyloid beta clearance pathway with the reversal of cell senescence associated with various chronic diseases such as cardiovascular disease, Type 3 diabetes and Alzheimer’s disease.展开更多
Objective: In this pilot study, given the prevalence of hypertension and panic disorder as described in the literature, we proposed to fill the gaps in the literature on the possible utility of SSRI medication as an a...Objective: In this pilot study, given the prevalence of hypertension and panic disorder as described in the literature, we proposed to fill the gaps in the literature on the possible utility of SSRI medication as an adjunct treatment in individuals with panic disorder and hypertension. Methods: We planned to only recruit patients with panic disorder who fit the criteria independently for treatment with SSRI;i.e. treatment would be given based on clinical need and currently accepted Pharmaceutical Benefits Scheme (PBS) criteria. Thereafter, we would monitor their BP at baseline, 14 days and 28 days to determine if there has been an effect on the individual’s BP. Results: Based on the observation above, there may be a trend of a reduction in systolic and diastolic BP after the commencement of sertraline. Conclusion: In order to confirm this observation, a larger sample size is required in the future. This pilot study proposed to meet the objectives as listed below;however due to difficulty with recruitment, only 2 out of 4 participants will be discussed in the analysis.展开更多
BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-p...BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia.METHODS Study 1 reviewed articles obtained from PubMed,PsycINFO,Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders.Study 2 examined language deficits and activities of daily living in 20 PWA(median age:58,range:28-65 years;13 men)with the Western Aphasia Battery-Revised and the Barthel Index,respectively.Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales,including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale.In addition,an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves.This observational study is based on the baseline assessment of an intervention clinical trial(EudraCT:2017-002858-36;ClinicalTrials.gov identifier:NCT04134416).RESULTS The literature review revealed a broad spectrum of NPS in PWA,including depression,anxiety,apathy,agitation/aggression,eating and sleep disorders,psychosis,and hypomania/mania.These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA.Study 2 showed that the 20 participants had mild-to-moderate aphasia severity and were functionally independent.A wide range of comorbid NPS was found in the post-stroke aphasic population(median number of NPS:5,range:1-8).The majority of PWA(75%)had depressive symptoms,followed by agitation/aggression(70%),irritability(70%),anxiety(65%)and appetite/eating symptoms(65%).Half of them also presented symptoms of apathy,whereas euphoria and psychotic symptoms were rare(5%).Domain-specific scales revealed that 45%of participants had apathy and 30%were diagnosed with depression and anxiety.CONCLUSION Concurrent NPS are frequent in the chronic period of post-stroke aphasia.Therefore,further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.展开更多
This pilot study examined the psychometric properties and clinical utility of a brief neuropsychological instrument (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The test-retest reliabil...This pilot study examined the psychometric properties and clinical utility of a brief neuropsychological instrument (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The test-retest reliability, practice effects and convergent validity of RBANS were examined in participants without objective cognitive impairment. The tests were administered at two time points at approximately a two weeks’ interval, with 30 cognitively intact participants with a mean age of 63.3 ± 5.8 years. Adequate test-retest reliabilities were found for RBANS subtests, index and total scale scores with significant gain scores in immediate memory and visuospatial function. The RBANS showed good convergent validity and the RBANS supplemented with executive and language measures (Colour Trails Test and 30-item modified Boston Naming Test, respectively) demonstrated excellent convergent validity with a formal neuropsychological battery. This pilot study has provided the preliminary evidence of reliability and convergent validity of the RBANS. Additionally, it also provides insight on the practice effects so that clinicians may assess significant changes in RBANS subtests and domain indexes for clinical practice.展开更多
AIM To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism.METHODS Twenty-one participants transitioning from an early intervention pro...AIM To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism.METHODS Twenty-one participants transitioning from an early intervention program were assessed at two time points; at the end of their preschool placement and approximately 5 mo later following their transition to school. Child characteristics were assessed using the Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scales, Social Communication Questionnaire and the Repetitive Behaviour Scale. Transition outcomes were assessed using Teacher Rating Scale of School Adjustment and the Social Skills Improvement System Rating Scales to provide an understanding of each child's school adjustment. The relationship between child characteristics and school outcomes was evaluated. RESULTS Cognitive ability and adaptive behaviour were shown to be associated with successful transition to school outcomes including participation in the classroom and being comfortable with the classroom teacher. These factors were also associated with social skills in the classroom including assertiveness and engagement. CONCLUSION Supporting children on the spectrum in the domains of adaptive behaviour and cognitive ability, including language skills, is important for a successful transition to school. Providing the appropriate support within structured transition programs will assist children on the spectrum with this important transition, allowing them to maximise their learning and behavioural potential.展开更多
In Australia, perinatal depression affects 15% - 20% of pregnant women. Depression does not go away on its own, getting help at early stages shown to be effective in treating antenatal depression. Aim of this study is...In Australia, perinatal depression affects 15% - 20% of pregnant women. Depression does not go away on its own, getting help at early stages shown to be effective in treating antenatal depression. Aim of this study is to assess and describe the screening of women through the antenatal clinic and measure the outcome of services provided (such as counselling, social assistance) for those at risk of depression, in a general hospital setting in an ethnically diverse part of Sydney, Australia. Data from 193 women were obtained through accessing the psychosocial and screening assessments completed at the antenatal clinic between 2007 and 2008. Data regarding patients’ psychosocial characteristics, referrals and interventions were also gathered from hospital records. Data revealed that 60.4% of women screened scored ≥10 on the Edinburgh Postnatal Depression Scale (EDPS) which is indicative of significant depressive symptomatology. Of these women, 39.4% went on to receive a formal diagnosis. Women who indicated that they had planned their pregnancies (47.2%) were significantly less likely to report having major worries and stressors over the last 12 months (p < 0.05) in comparison to those who indicated that their pregnancies were unplanned. Data showed while screening methods are effective, regrettably a high proportion of women, despite presenting with “at risk” symptomatology levels, do not engage in intervention programs. Further research is required to explore the barriers in accessing both screening and intervention services (particularly in a culturally diverse area such as this), and how services can improve processes and patient participation.展开更多
Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with com...Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).展开更多
The understanding of cholesterol and its pathogenesis to Alzheimer’s disease (AD) pathogenic process is important for the possible prevention of AD. High fibre diets that contain phytosterols have been shown to lower...The understanding of cholesterol and its pathogenesis to Alzheimer’s disease (AD) pathogenic process is important for the possible prevention of AD. High fibre diets that contain phytosterols have been shown to lower LDL and increase HDL cholesterol and are implicated in membrane cholesterol and amyloid beta (Aβ) homeostasis. The convergence of diet and AD may be related to the effects of phytosterols since plasma cholesterol is closely linked and regulated by phytosterols. Dietary fibre modifications that are low in fat and glucose reduce the risk for AD by not only effecting cell membranes and nutrient sensing G coupled receptors but also by regulating number of nuclear receptors such as histone deacetylases (HDAC) and peroxisome proliferator activated receptors (PPAR) that control glucose, fatty acids and cholesterol and have significant effects on the brain cholesterol homeostasis and amyloidosis. The peripheral sink Aβ hypothesis indicates that the peripheral clearance of Aβ and its regulation by dietary phytosterols is of substantial interest since it may delay hypercholesterolemia and the early onset of amyloid plaque development. Liver disease has been of central importance with aging and programmed cell death pathways. Nutritional therapy has emerged as a novel approach to control appetite and the role of nutrigenomics as an early nutritional therapy may assist genes to delay liver and brain diseases such as Parkinson’s disease (PD) and Huntington’s disease (HD) that are associated with aging. The understanding of phytosterols and the role of these lipids in drug therapy such as cholesterol lowering drugs may provide molecular mechanisms that are involved in the regulation of cell Aβ clearance and metabolism. High fibre diets also contain various fatty acids such as the short chain fatty acids (SCFA) and the understanding of synergistic effects of SCFA and phytosterols in glucose regulation and cholesterol homeostasisis important to our understanding of diet, lifestyle and drugs in relation to peripheral amyloidosis and gene expression that play an early role in the development of AD.展开更多
Immune-mediated activation of tryptophan(TRYP) catabolism via the kynurenine pathway(KP) is a consistent finding in all inflammatory disorders.Several studies by our group and others have examined the neurotoxic p...Immune-mediated activation of tryptophan(TRYP) catabolism via the kynurenine pathway(KP) is a consistent finding in all inflammatory disorders.Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites,including quinolinic acid(QUIN) in neuroinflammatory neurological disorders,including Alzheimer's disease(AD),multiple sclerosis,amylotropic lateral sclerosis(ALS),and AIDS related dementia complex(ADC).Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response.Under physiological conditions,QUIN is metabolized to the essential pyridine nucleotide,nicotinamide adenine dinucleotide(NAD+),which represents an important metabolic cofactor and electron transporter.NAD+ also serves as a substrate for the DNA ‘nick sensor' and putative nuclear repair enzyme,poly(ADP-ribose) polymerase(PARP).Free radical initiated DNA damage,PARP activation and NAD+ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.展开更多
基金Zhejiang Provincial Philosophy and Social Sciences Planning Project from Zhejiang Office of Philosophy and Social Science(21NDJC092YB)Zhejiang Provincial Educational Science Plan Project(2021SCG166)。
文摘Blended learning(BL)has been widely adopted to improve students’academic achievements in higher education.However,its success relies mainly on student engagement,which plays an essential role in active learning and provides a rich understanding of students’experiences.The study utilized three self-designed scales-the Teacher Support Scale,Student Engagement Scale,and Student Learning Experience Scale-to gauge and examine the impact and relationship between perceived teacher support,student behavioral engagement,and the intermediary role of learning experiences.A cohort of 899 college students undertaking the obligatory College English course through BL modes across five Chinese universities actively participated by completing a comprehensive questionnaire.The results showed significant correlations between perceived teacher support,learning experience,and behavioral engagement.Perceived teacher support significantly predicted students’behavioral engagement,with socio-affective support exerting the most substantial predictive effects.All predictive effects were partially mediated by learning experience(learning mode,online resources,overall LMS-based learning,interaction with their instructor and peers,and learning outcome).The influence of perceived teacher support on behavioral engagement differed between students who reported the most positive(vs.negative)learning experiences.Suggestions for further research are offered for consideration.
基金part of the Child and Family Outcomes Study at the KU Marcia Burgess Autism Specific Early Learning and Care Centre, funded by the Australian Government with the University of New South Wales as a research partner
文摘BACKGROUND Previous research suggests that parents raising a child with autism experience higher levels of psychological distress than parents of typically developing children and parents of children with other developmental disorders. Little is known, however, about the intersection between the effects of socioeconomic status(SES) on the wellbeing and sense of parental competency of parents of preschoolers with autism and how it relates to child symptom severity.AIM To examine the relationship between their child's symptom severity, SES, as measured by neighbourhood advantage and occupational status, on the psychological wellbeing and perceived parenting competence among parents of preschoolers with autism.METHODS Parents of 117 preschool-aged children with a diagnosis of autism spectrum disorder(ASD), 107 mothers and 54 fathers, completed questionnaires about their child's symptoms of ASD and functioning, their own perceptions of their wellbeing and parental competence on entry to an early intervention program in Sydney, Australia. Parents also provided demographic information pertaining to their occupation, level of education attained and address(postcode). All children were also assessed for their severity of symptoms using the Autism Diagnostic Observation Schedule. The Australian Socioeconomic Index of occupationalstatus as a measure of familial SES and the Index of Relative Socio-economic Advantage and Disadvantage as a measure of neighbourhood advantage were used to examine the impact of SES on parental sense of competence and wellbeing.RESULTS Compared to normative populations, both mothers and fathers in our sample reported significantly higher levels of parenting sense of efficacy but lower levels of interest in the parenting role. Mothers also displayed higher levels of satisfaction. Both mothers and fathers displayed higher levels of depression than normative populations with mothers also reporting greater levels of stress and anxiety. Child symptom severity was associated with maternal parenting competency with these relationships amplified among mothers with higher familial SES and who lived in areas of greater neighbourhood advantage.Increased adaptive functioning was associated with better maternal wellbeing,particularly among mothers who lived in areas of greater neighbourhood advantage. Contrastingly, paternal parenting competence was generally not influenced by child adaptive functioning or symptom severity, although for those in higher familial SES brackets, children's symptom severity and maladaptive symptoms were negatively related to paternal sense of parenting efficacy. There was a trend towards moderate relationships between lower familial SES and greater depression, stress and anxiety among fathers, but no relationship with their child's ASD symptom severity or functioning.CONCLUSION SES differentially impacts wellbeing and sense of parenting competence and its relationship to the impact of child symptoms for mothers and fathers of preschoolers with autism.
基金supported by grants PFB (Basal Financing Program) 12/2007 from the Basal Centre for Excellence in Science and Technology and FONDECYT,No.1120156(to NCI)a pre-doctoral fellowship from the National Commission of Science and Technology of Chile(CONICYT)(to CTR)
文摘Alzheimer's disease(AD) is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by amyloid-β(Aβ) peptide and phosphorylated tau; which is accompanied by progressive impairment of memory. Diverse signaling pathways are linked to AD, and among these the Wnt signaling pathway is becoming increasingly relevant, since it plays essential roles in the adult brain. Initially, Wnt signaling activation was proposed as a neuroprotective mechanism against Aβ toxicity. Later, it was reported that it participates in tau phosphorylation and processes of learning and memory. Interestingly, in the last years we demonstrated that Wnt signaling is fundamental in amyloid precursor protein(APP) processing and that Wnt dysfunction results in Aβ production and aggregation in vitro. Recent in vivo studies reported that loss of canonical Wnt signaling exacerbates amyloid deposition in a transgenic(Tg) mouse model of AD. Finally, we showed that inhibition of Wnt signaling in a Tg mouse previously at the appearance of AD signs, resulted in memory loss, tau phosphorylation and Aβ formation and aggregation; indicating that Wnt dysfunction accelerated the onset of AD. More importantly, Wnt signaling loss promoted cognitive impairment, tau phosphorylation and Aβ1–42 production in the hippocampus of wild-type(WT) mice, contributing to the development of an Alzheimer's-like neurophatology. Therefore, in this review we highlight the importance of Wnt/β-catenin signaling dysfunction in the onset of AD and propose that the loss of canonical Wnt signaling is a triggering factor of AD.
文摘Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid metabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxidative stress. Within cells, the endoplasmic reticulum (ER) appears to be particularly susceptible to such metabolic disruption. Sirtuin 1?(Sirt1) and leptin have received attention recently as they are central regulatory factors for the body’s metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings concerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on metabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.
基金supported by the Research Grants Council of the Hong Kong SAR,No. 452906
文摘This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged -〉 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions: anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only (partial coefficient = 0.453, P = 0.045), after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.661, P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.573, P = 0.004) in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.
基金supported by the National Health and Medical Research Council-Australian Research Council dementia research development fellowship(APP1107109)to PB
文摘Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s disease.Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity,the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies.We have previously established and validated budding yeast,Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ.Using colony counting based methods,oligomeric Aβ42 was shown to induce dose-dependent cell death in yeast.We have adapted this method for high throughput screening by developing an absorbance-based growth assay.We further validated the assay with treatments previously shown to protect oligomer Aβ42 induced cell death in mammalian and yeast cells.This assay offers a platform for studying underlying mechanisms of oligomer Aβ42 induced cell death using gene deletion/overexpression libraries and developing novel agents that alleviate Aβ42 induced cell death.
文摘The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be involved in cell suicide in various organ diseases with the importance of accelerated aging that requires early intervention with drug therapy to prevent diseases such as non alcoholic fatty liver disease (NAFLD) that has increased in children and reached to approx. 40% of the global population. Obesity is induced by various diets and lifestyle factors such as stress, anxiety and depression which are important to consider with the global increase in obesity and are possibly linked to the rise in individuals with brain disorders that involve neurodegeneration. Xenobiotics such as the endocrine disruptor chemicals that have increased in the environment in various developed countries lead to various chronic endocrine diseases as populations divert towards unhealthy diets and lifestyles with induction of NAFLD and obesity. The amount and nature of food intake that improves and increases liver lipid and xenobiotic metabolism in obese individuals have become important to decrease the risk for increased adiposity in man. High fibre or protein diets that contain leucine may improve liver glucose, lipid and xenobiotic metabolism and require further investigation with xenobiotics such as endocrine disruptors involved in appetite dysregulation and metabolic disorders in developed countries. The use of anti-obese drugs that reduce food intake and improve hypercholesterolemia and cardiovascular disease has been assessed in obesity with drug therapy closely involved either in the prevention or induction of NAFLD and obesity in man.
基金the financial support of the Cooperative Research Centre for Living with Autism (Autism CRC),established and supported under the Australian Government’s Cooperative Research Centres Program as well as funding from the Commonwealth Department of Social Services
文摘AIM To identify factors that promote a positive start to school for children with autism spectrum disorder(ASD).METHODS Web of Science,MEDLINE,Scopus,and Psych INFO searches were conducted to identify literature published after 1991 and relevant to school transition processes in children with ASD.Twenty studies were deemed eligible for inclusion.These studies evaluated a range of factors including school readiness,parent and teacher perspectives on transition practices,characteristics of children with ASD that are associated with successful transition to school and the impact of school based intervention programs.RESULTS A review of these studies showed that children with ASD are less school ready emotionally than their peers and those children with ASD appear to have more externalising behaviours and self-regulation difficulties that affect their school engagement and their relationships with their teachers.There was a paucity of research looking at interventions targeting school readiness.However,school-based behavioural interventions appear to improve cognitive,language and daily living skills,but have less impact on socialisation and peer inclusion.CONCLUSION Children with ASD face more challenges transitioning to school,particularly with social interaction.Further development and implementation of specific schoolbased interventions is needed in order to assist children with autism to maximise their success in starting school.
文摘In the current global epidemic for Non Alcoholic Fatty Liver Disease (NAFLD), diabetes and neuro-degenerative diseases such as Alzheimer’s disease there has been a major interest in magnesium therapy to delay the severity of NAFLD, Type 3 diabetes and neurodegeneration in the developing and developed world. The objective of magnesium therapy is to activate the anti-aging gene Sirtuin 1 (Sirt1) to prevent cardiovascular disease, NAFLD and diabetes. Reduced consumption of nutrients such as fatty acids, glucose, cholesterol and increased magnesium consumption is closely linked to reduced bacterial lipopolysaccharides (LPS) and activation of Sirt1 relevant to active nuclear and mitochondria interactions with the prevention of myocardial infarction and Type 3 diabetes. Magnesium deficiency and its effects on Sirt1 regulation have become important with magnesium deficiency associated with appetite dysregulation, senescence, glucose/nitric oxide dyshomeostasis, increased ceramide and toxic amyloid beta formation. Magnesium therapy activates the peripheral sink amyloid beta clearance pathway with the reversal of cell senescence associated with various chronic diseases such as cardiovascular disease, Type 3 diabetes and Alzheimer’s disease.
文摘Objective: In this pilot study, given the prevalence of hypertension and panic disorder as described in the literature, we proposed to fill the gaps in the literature on the possible utility of SSRI medication as an adjunct treatment in individuals with panic disorder and hypertension. Methods: We planned to only recruit patients with panic disorder who fit the criteria independently for treatment with SSRI;i.e. treatment would be given based on clinical need and currently accepted Pharmaceutical Benefits Scheme (PBS) criteria. Thereafter, we would monitor their BP at baseline, 14 days and 28 days to determine if there has been an effect on the individual’s BP. Results: Based on the observation above, there may be a trend of a reduction in systolic and diastolic BP after the commencement of sertraline. Conclusion: In order to confirm this observation, a larger sample size is required in the future. This pilot study proposed to meet the objectives as listed below;however due to difficulty with recruitment, only 2 out of 4 participants will be discussed in the analysis.
基金Supported by Ministerio de Economía,Industria y Competitividad,Instituto de Salud Carlos III,Madrid,Spain,No. PI16/01514
文摘BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia.METHODS Study 1 reviewed articles obtained from PubMed,PsycINFO,Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders.Study 2 examined language deficits and activities of daily living in 20 PWA(median age:58,range:28-65 years;13 men)with the Western Aphasia Battery-Revised and the Barthel Index,respectively.Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales,including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale.In addition,an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves.This observational study is based on the baseline assessment of an intervention clinical trial(EudraCT:2017-002858-36;ClinicalTrials.gov identifier:NCT04134416).RESULTS The literature review revealed a broad spectrum of NPS in PWA,including depression,anxiety,apathy,agitation/aggression,eating and sleep disorders,psychosis,and hypomania/mania.These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA.Study 2 showed that the 20 participants had mild-to-moderate aphasia severity and were functionally independent.A wide range of comorbid NPS was found in the post-stroke aphasic population(median number of NPS:5,range:1-8).The majority of PWA(75%)had depressive symptoms,followed by agitation/aggression(70%),irritability(70%),anxiety(65%)and appetite/eating symptoms(65%).Half of them also presented symptoms of apathy,whereas euphoria and psychotic symptoms were rare(5%).Domain-specific scales revealed that 45%of participants had apathy and 30%were diagnosed with depression and anxiety.CONCLUSION Concurrent NPS are frequent in the chronic period of post-stroke aphasia.Therefore,further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.
文摘This pilot study examined the psychometric properties and clinical utility of a brief neuropsychological instrument (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The test-retest reliability, practice effects and convergent validity of RBANS were examined in participants without objective cognitive impairment. The tests were administered at two time points at approximately a two weeks’ interval, with 30 cognitively intact participants with a mean age of 63.3 ± 5.8 years. Adequate test-retest reliabilities were found for RBANS subtests, index and total scale scores with significant gain scores in immediate memory and visuospatial function. The RBANS showed good convergent validity and the RBANS supplemented with executive and language measures (Colour Trails Test and 30-item modified Boston Naming Test, respectively) demonstrated excellent convergent validity with a formal neuropsychological battery. This pilot study has provided the preliminary evidence of reliability and convergent validity of the RBANS. Additionally, it also provides insight on the practice effects so that clinicians may assess significant changes in RBANS subtests and domain indexes for clinical practice.
基金Supported by Cooperative Research Centre for Living with Autism(Autism CRC)established and supported under the Australian Government's Cooperative Research Centres Program as well as funding from the Commonwealth Department of Social Services
文摘AIM To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism.METHODS Twenty-one participants transitioning from an early intervention program were assessed at two time points; at the end of their preschool placement and approximately 5 mo later following their transition to school. Child characteristics were assessed using the Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scales, Social Communication Questionnaire and the Repetitive Behaviour Scale. Transition outcomes were assessed using Teacher Rating Scale of School Adjustment and the Social Skills Improvement System Rating Scales to provide an understanding of each child's school adjustment. The relationship between child characteristics and school outcomes was evaluated. RESULTS Cognitive ability and adaptive behaviour were shown to be associated with successful transition to school outcomes including participation in the classroom and being comfortable with the classroom teacher. These factors were also associated with social skills in the classroom including assertiveness and engagement. CONCLUSION Supporting children on the spectrum in the domains of adaptive behaviour and cognitive ability, including language skills, is important for a successful transition to school. Providing the appropriate support within structured transition programs will assist children on the spectrum with this important transition, allowing them to maximise their learning and behavioural potential.
文摘In Australia, perinatal depression affects 15% - 20% of pregnant women. Depression does not go away on its own, getting help at early stages shown to be effective in treating antenatal depression. Aim of this study is to assess and describe the screening of women through the antenatal clinic and measure the outcome of services provided (such as counselling, social assistance) for those at risk of depression, in a general hospital setting in an ethnically diverse part of Sydney, Australia. Data from 193 women were obtained through accessing the psychosocial and screening assessments completed at the antenatal clinic between 2007 and 2008. Data regarding patients’ psychosocial characteristics, referrals and interventions were also gathered from hospital records. Data revealed that 60.4% of women screened scored ≥10 on the Edinburgh Postnatal Depression Scale (EDPS) which is indicative of significant depressive symptomatology. Of these women, 39.4% went on to receive a formal diagnosis. Women who indicated that they had planned their pregnancies (47.2%) were significantly less likely to report having major worries and stressors over the last 12 months (p < 0.05) in comparison to those who indicated that their pregnancies were unplanned. Data showed while screening methods are effective, regrettably a high proportion of women, despite presenting with “at risk” symptomatology levels, do not engage in intervention programs. Further research is required to explore the barriers in accessing both screening and intervention services (particularly in a culturally diverse area such as this), and how services can improve processes and patient participation.
基金supported by grants from Edith Cowan Universitythe McCusker Alzheimer’s Research Foundationthe National Health and Medical Research Council
文摘Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).
基金supported by the Base to Clinical and Scientific Research Cooperation fund of Capital Medical University(15JL67)the High-tech personnel training grant from Beijing Health System(2015-3-104)the Beijing municipal education commission on science and technology plan projects(KM201610025021)
文摘The understanding of cholesterol and its pathogenesis to Alzheimer’s disease (AD) pathogenic process is important for the possible prevention of AD. High fibre diets that contain phytosterols have been shown to lower LDL and increase HDL cholesterol and are implicated in membrane cholesterol and amyloid beta (Aβ) homeostasis. The convergence of diet and AD may be related to the effects of phytosterols since plasma cholesterol is closely linked and regulated by phytosterols. Dietary fibre modifications that are low in fat and glucose reduce the risk for AD by not only effecting cell membranes and nutrient sensing G coupled receptors but also by regulating number of nuclear receptors such as histone deacetylases (HDAC) and peroxisome proliferator activated receptors (PPAR) that control glucose, fatty acids and cholesterol and have significant effects on the brain cholesterol homeostasis and amyloidosis. The peripheral sink Aβ hypothesis indicates that the peripheral clearance of Aβ and its regulation by dietary phytosterols is of substantial interest since it may delay hypercholesterolemia and the early onset of amyloid plaque development. Liver disease has been of central importance with aging and programmed cell death pathways. Nutritional therapy has emerged as a novel approach to control appetite and the role of nutrigenomics as an early nutritional therapy may assist genes to delay liver and brain diseases such as Parkinson’s disease (PD) and Huntington’s disease (HD) that are associated with aging. The understanding of phytosterols and the role of these lipids in drug therapy such as cholesterol lowering drugs may provide molecular mechanisms that are involved in the regulation of cell Aβ clearance and metabolism. High fibre diets also contain various fatty acids such as the short chain fatty acids (SCFA) and the understanding of synergistic effects of SCFA and phytosterols in glucose regulation and cholesterol homeostasisis important to our understanding of diet, lifestyle and drugs in relation to peripheral amyloidosis and gene expression that play an early role in the development of AD.
基金supported by the University of Macao(SRG2014-00019-FHSMYRG2015-00230-FHS+4 种基金MYRG2016-00005-FHS)the Affiliated Brain Hospital of Guangzhou Medical University(2016YFC0906302816713342014Y2-001052015BAI13B02)
文摘背景:迟发性运动障碍(TD)的临床特征是异常不自主运动。TD具有严重的不可逆的致残性和社会功能损害。目的 :此荟萃分析基于随机对照试验(RCTs)文献系统评估褪黑素对精神分裂症患者迟发性运动障碍的临床疗效和安全性。方法 :两位独立评估者从以下数据库对相关的临床随机对照试验(RCT)文献进行检索(万方数据、中国知网(CNKI)、中国生物医学文摘数据库和PubM ed、PsycI NFO、Embase、Cochrane Library数据库),检索时间截止于2017年6月8日。以TD症状严重程度为主要结局指标,采用Rev Man 5.3版本进行统计分析,对RCTs的质量评估采用Cochrane风险评估偏倚和Jadad量表来评估各种偏倚的风险性。采用GRADE(Grades of Recommendation,Assessment,Development,and Evaluation)系统推荐分级方法对meta-分析结果的整体证据质量水平进行分级评价。结果 :最终筛选确定4个RCTs(n=130)。3个RCTs采用双盲法,1个RCT单盲,根据Cochrane风险评估偏倚和Jadad量表显示3个RCTs的疗效评估指标的证据质量被评定为"高质量"。与对照组相比,根据不自主运动量表(AIMS)评定褪黑素可改善TD严重程度(4个RCTs,n=130,加权平均差值(WMD):-1.52(95%CI:-3.24,0.20),p=0.08;I2=0%),但尚没有达到显著差异。根据等级方法,改善TD症状的meta分析结果的整体证据质量被评为"低",而关于不良反应和认知损害方面则数据太少。结论 :荟萃分析表明,褪黑素或可改善精神分裂症TD症状。但仍有待今后更高质量和更大样本的RCTs验证。
基金NHMRC Postdoctoral Fellowship at the University of New South Wales
文摘Immune-mediated activation of tryptophan(TRYP) catabolism via the kynurenine pathway(KP) is a consistent finding in all inflammatory disorders.Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites,including quinolinic acid(QUIN) in neuroinflammatory neurological disorders,including Alzheimer's disease(AD),multiple sclerosis,amylotropic lateral sclerosis(ALS),and AIDS related dementia complex(ADC).Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response.Under physiological conditions,QUIN is metabolized to the essential pyridine nucleotide,nicotinamide adenine dinucleotide(NAD+),which represents an important metabolic cofactor and electron transporter.NAD+ also serves as a substrate for the DNA ‘nick sensor' and putative nuclear repair enzyme,poly(ADP-ribose) polymerase(PARP).Free radical initiated DNA damage,PARP activation and NAD+ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.