A critical evaluation of copper metabolism in indian wilson’s disease children with special reference to their phenotypes and relatives

Wilson’s disease is an autosomal recessive disorder of copper accumulation in various organs, with most common clinical manifestations such as hepatic, neurological, and renal dysfunctions. Serum copper and ceruloplasmin in Wilson’s disease were significantly lower as compared to normals, controls, and relatives of Wilson’s disease patients, whereas marked hypercupriuria (145 ± 7 μg/24 h) was observed in Wilson’s children only. A good correlation (r = 0.92) was found between non-ceruloplasmin-bound copper and 24-h urinary copper excretion in Wilson’s disease patients. Further, copper studies among the different phenotypes of Wilson’s disease revealed substantially low serum ceruloplasmin and a marked hypercupriuria in Wilson’s disease children associated with renal tubular acidosis as compared to the patients with either hepatological or neurological manifestations. Serum ceruloplasmin levels in 14 patients of Wilson’s disease were between 14 and 20 mg/dL. These patients of Wilson’s disease were confirmed by measuring liver biopsy copper, which was about nine times higher than normal hepatic copper content. During the family screening by copper studies, four asymptomatic siblings were diagnosed for Wilson’s disease. These subjects were then started on D-penicillamine therapy because presymptomatic treatment prevents progression of the disease complications.     

Asperger’s Syndrome,Subjectivity and the Senses

Situated at the intersection of anthropological work on illness narratives and research on the anthropology of autism, this paper is a close reading of an autobiographical narrative recounted by Peter, a young man diagnosed with Asperger’s Syndrome, a type of autism spectrum disorder (ASD). Responding to Solomon’s (2010a:252) call for phenomenologically grounded accounts of “the subjective, sensory, and perceptual experiences of autism … based on personal narratives and practices of being and self-awareness,” this paper calls into question key assumptions in the clinical and popular literature about ASD relating to theory of mind, empathy, capacity for metaphorical thinking, and ASD as a life-long condition.     

Selenium and its relationship with selenoprotein P and glutathione peroxidase in children and adolescents with Hashimoto’s thyroiditis and hypothyroidism

The essential trace element selenium (Se) is required for thyroid hormone synthesis and metabolism. Selenoproteins contain selenocysteine and are responsible for biological functions of selenium. Glutathione peroxidase (GPx) is one of the major selenoproteins which protects the thyroid cells from oxidative damage. Selenoprotein P (SePP) is considered as the plasma selenium transporter to tissues. The aim of this study was to evaluate serum Se and SePP levels, and GPx activity in erythrocytes of children and adolescents with treated Hashimoto’s thyroiditis, hypothyroidism, and normal subjects.Blood samples were collected from 32 patients with Hashimoto’s thyroiditis, 20 with hypothyroidism, and 25 matched normal subjects. All the patients were under treatment with levothyroxine and at the time of analysis all of the thyroid function tests were normal. GPx enzyme activity was measured by spectrophotometry at 340 nm. Serum selenium levels were measured by high-resolution continuum source graphite furnace atomic absorption. SePP, TPOAb (anti-thyroid peroxidase antibody), and TgAb (anti-thyroglobulin antibody) were determined by ELISA kits. T₄, T₃, T₃ uptake and TSH were also measured.Neither GPx activity nor SePP levels were significantly different in patients with Hashimoto’s thyroiditis or hypothyroidism compared to normal subjects. Although GPx and SePP were both lower in patients with hypothyroidism compared to those with Hashimoto’s thyroiditis and normal subjects but the difference was not significant. Serum Se levels also did not differ significantly in patients and normal subjects. We did not find any correlation between GPx or SePP with TPOAb or TgAb but SePP was significantly correlated with Se.Results show that in patients with Hashimoto’s thyroiditis or hypothyroidism who have been under treatment with levothyroxine and have normal thyroid function tests, the GPx, SePP and Se levels are not significantly different.     

Pedometer-determined physical activity levels of healthy children and children with Down’s syndrome

Purpose: Children with Down’s syndrome (DS) are considered sedentary and less engaged in recommended physical activity (PA) levels. This study compared the PA levels between children with DS and healthy children in Saudi Arabia.

Methods: The study included 85 children divided into two groups. The DS group comprised 37 children with DS aged 8–12?years recruited from the Down Syndrome Charitable Association and Al-Nahda Schools for DS. The healthy group comprised 41 healthy children aged 8–12?years recruited from regular schools in the same region. PA levels were measured over 7?days using a pedometer.

Results: The healthy group was more active than the DS group (p?p?p?Conclusions: The DS group had a high body mass index and physical inactivity compared with the second group. Obesity and physical inactivity among Saudi Arabian children with and without DS are major health concerns. Therefore, concerted efforts are needed to combat childhood obesity, promote PA, improve patient quality of life, and reduce the sedentary lifestyle among Saudi children and adolescents.     

Parental nonemployment in childhood and children’s health later in life

While the effects of joblessness on the health of the non-employed are well-documented, its long-term spillover consequences on the health of their relatives, especially children, remain poorly understood. This research explores the long-term associations of parental nonemployment spells experienced during early, mid and late childhood on children’s mental and physical health. The analysis exploits data drawn from the British Household Panel Survey (BHPS) and the UK Household Longitudinal Study (UKHLS), linking detailed parental socioeconomic information with their children between the years 1993 and 2013. This paper employs a Correlated Random Effects (CRE) probit model that allows accounting for unobserved heterogeneity as well as a non-linear Generalized Estimating Equations (GEE) random effects estimator accounting in addition for the dependency structure of the data. Results indicate that experiencing parental nonemployment during early and late childhood has a negative association on the children’s likelihood of suffering from long-standing illnesses later in life, while experiencing parental nonemployment during middle childhood negatively affects the young adult’s mental health. Moreover, experiencing parental nonemployment during late childhood increases the probability of both reporting poor or fair self-assessed health and the likelihood of consuming prescribed medicines in early adulthood. However, there seems to be a considerable effect heterogeneity by family socioeconomic status, parents’ gender, and frequencies of parental nonemployment spells. Current adulthood circumstances, such as level of educational attainment, job situation and household demographics, are used to explore the potential mechanisms affecting results. These findings may help policymakers shape appropriate responses to mitigate the psychological and physical burden derived from parental nonemployment, especially among already disadvantaged households.     

Sex differences in children’s investment in peers

It is hypothesized from within an evolutionary framework that females should be less invested in peer relations than males. Investment was operationalized as enjoyment in Study 1 and as preference for interaction in Study 2. In the first study, four- and six-year-old children’s enjoyment of peer interaction was observed in 26 groups of same-sex peers. Girls were rated as enjoying their interactions significantly less than boys. In the second study, six- and nine-year-old children were interviewed about the individuals with whom they spend time in their homes and neighborhoods and about the individuals who participate in their favorite activities. The proportion of individuals named by children who were peers was significantly lower for girls than boys both in children’s neighborhoods and in children’s favorite activities. Results strongly support the hypothesis that females and males have evolved differential preferences for interaction with peers.     

Functional Neuroanatomy and the Rationale for Using EEG Biofeedback for Clients with Asperger’s Syndrome

This paper reviews the symptoms of Asperger’s Syndrome (AS), a disorder along the autism continuum, and highlights research findings with an emphasis on brain differences. Existing theories concerning AS are described, including theory of mind (Hill and Frith in Phil Trans Royal Soc Lond, Bull 358:281–289, 2003), mirror neuron system (Ramachandran and Oberman in Sci Am 295(5):62–69, 2006), and Porges’ (Ann N Y Acad Sci 1008:31–47, 2003, The neurobiology of autism, Johns Hopkins University Press, Baltimore, 2004) polyvagal theory. (A second paper, Outcomes using EEG Biofeedback Training in Clients with Asperger’s Syndrome, summarizes clinical outcomes obtained with more than 150 clients.) Patterns seen with QEEG assessment are then presented. Single channel assessment at the vertex (CZ) reveals patterns similar to those found in Attention-Deficit/Hyperactivity Disorder. Using 19-channel data, significant differences (z-scores > 2) were found in the amplitude of both slow waves (excess theta and/or alpha) and fast waves (beta) at various locations. Differences from the norm were most often found in mirror neuron areas (frontal, temporal and temporal-parietal). There were also differences in coherence patterns, as compared to a normative database (Neuroguide). Low Resolution Electromagnetic Tomography Analysis (Pascual-Marqui et al. in Methods Find Exp Clin Pharmacol 24C:91–95, 2002) suggested the source of the abnormal activity was most often the anterior cingulate. Other areas involved included the amygdala, uncus, insula, hippocampal gyrus, parahippocampal gyrus, fusiform gyrus, and the orbito-frontal and/or ventromedial areas of the prefrontal cortex. Correspondence between symptoms and the functions of the areas found to have abnormalities is evident and those observations are used to develop a rationale for using EEG biofeedback, called neurofeedback (NFB), intervention. NFB training is targeted to improve symptoms that include difficulty reading and mirroring emotions, poor attention to the outside world, poor self-regulation skills, and anxiety. Porges’ polyvagal theory is used to emphasize the need to integrate NFB with biofeedback (BFB), particularly heart rate variability training. We term this emerging understanding the Systems Theory of Neural Synergy. The name underscores the fact that NFB and BFB influence dynamic circuits and emphasizes that, no matter where we enter the nervous system with an intervention, it will seek its own new balance and equilibrium.     

Predictive association of copper metabolism proteins with Alzheimer’s disease and Parkinson’s disease: a preliminary perspective

Neurodegenerative diseases, Alzheimer’s disease (AD) and Parkinson’s disease (PD), constitute a major worldwide health problem. Several hypothesis have been put forth to elucidate the basis of onset and pathogenesis of AD and PD; however, till date, none of these seems to clearly elucidate the complex pathoetiology of these disorders. Notably, copper dyshomeostasis has been shown to underlie the pathophysiology of several neurodegenerative diseases including AD and PD. Numerous studies have concluded beyond doubt that imbalance in copper homeostatic mechanisms in conjunction with aging causes an acceleration in the copper toxicity elicited oxidative stress, which is detrimental to the central nervous system. Amyloid precursor protein and α-synuclein protein involved in AD and PD are copper binding proteins, respectively. In this review, we have discussed the possible association of copper metabolism proteins with AD and PD along with briefly outlining the expanding proportion of “copper interactome” in human biology. Using network biology, we found that copper metabolism proteins, superoxide dismutase 1 and ceruloplasmin may represent direct and indirect link with AD and PD, respectively.     

Hair-aluminum concentrations and children’s classroom behavior

The study investigated the relationship between children’s hair-Al concentrations and children’s behavioral performance in school. Hair-Al levels of 102 children drawn from a general school population were correlated with teachers’ ratings of the children on the Walker Problem Behavior Identification Checklist (WPBIC). Increasing hair-Al values correlated significantly with increased scores on the WPBIC total scale score. A continuing reexamination of Al exposure in the young is needed in order to determine the margin of safety regarding potentially toxic levels of Al.     

Effect of l-arginine on metabolism of polyamines in rat’s brain with extrahepatic cholestasis

Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of l-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with l-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with l-arginine. Increased plasma γ-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of l-arginine (P < 0.001). Cholestasis increased the brain’s putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of l-arginine in BDL rats prevents metabolic disorders of polyamines and establishs a neuroprotective role in the brain during cholestasis.     

Teachers’ civic socialization practices and children’s civic engagement

We examined the degree to which civic learning activities and civic discussion in the classroom were associated with children’s civic engagement in the upper elementary grades. We also explored the types of civic activities used by teachers during middle childhood. Survey data were collected from 359 ethnically and economically diverse 4th–6th grade students (M age?=?10.56, 56% female), their parents, and teachers (n?=?20) from six public schools in Southern California. The results of path analyses showed that teachers’ greater use of civic learning activities was associated with higher levels of social responsibility to people and civic values in students. However, general civic discussion was not associated with any indicators of children’s civic engagement. Additionally, teachers reported using numerous types of civic activities, thus showing the diversity in “civic learning” across classrooms. Practical implications for elementary civic education are discussed.     

The Study of Cognitive Characteristics in Asperger’s Disorder by Using a Modified Prisoner’s Dilemma Game with a Variable Payoff Matrix

Individuals with Asperger’s Disorder (ASP) have difficulties in social reciprocity and in providing appropriate cooperative behavior. The Prisoner’s Dilemma (PD) is a well-known model in game theory that illustrates the paradoxical disposition of interaction between two individuals with opposing interests, and may be a useful tool in the diagnosis of ASP in early childhood. In this study, we investigated the cognitive characteristics of ASP by using a modified PD game. The subjects were 29 individuals with ASP and 28 age- and IQ-matched controls. In the PD game, each of two players has two cards: card 1 represents cooperation and card 2 betrayal. The score each player obtains is decided according to a 2 x 2 payoff matrix and depends on the combination of their selections. The P-score (“P” for punishment) is defined as the score that is given when they both select betrayal. Comparing the two groups, the mean P-score at the end of the game and the mean total score were significantly higher in the ASP group, while the rate of selection of cooperative choice in both groups did not differ significantly. The classification of the shape of the graph according to fluctuation of the P-score revealed that in the ASP group only 2 cases (6.9%) showed continuous decrease of P-score compared to 8 control cases (28.6%) demonstrating similar results. However, the reasons were thought to be different: ASP subjects presumably selected card 2 because of a preference for the number itself, whereas control subjects preferentially chose this card to enhance their chance of winning the competition. It is often difficult to diagnose ASP in the young especially when they lack the distinctive clinical features of ASD in early childhood. Given the limited number of objective tools to evaluate the cognitive characteristics of ASP subjects, the PD game might be a useful diagnostic support tool for ASP.     

Supplementation with antioxidants and folinic acid for children with Down’s syndrome: randomised controlled trial

Objectives To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down’s syndrome.Design Randomised controlled trial with two by two factorial design.Setting Children living in the Midlands, Greater London, and the south west of England.Participants 156 infants aged under 7 months with trisomy 21.Intervention Daily oral supplementation with antioxidants (selenium 10 μg, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo.Main outcome measures Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months.Results Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval −2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, −1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results.Conclusions This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down’s syndrome.Trial registration Clinical trials {"type":"clinical-trial","attrs":{"text":"NCT00378456","term_id":"NCT00378456"}}NCT00378456.     

Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson’s Disease

Aims

Although subthalamic nucleus deep brain stimulation (STN-DBS) is effective in patients with advanced Parkinson’s disease (PD), its physiological mechanisms remain unclear. Because STN-DBS is effective in patients with PD whose motor symptoms are dramatically alleviated by L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, the higher preoperative catecholamine levels might be related to the better clinical outcome after surgery. We aimed to examine the correlation between the preoperative catecholamine levels and postoperative clinical outcome after subthalamic nucleus deep brain stimulation. The effectiveness of STN-DBS in the patient who responded well to dopaminergic medication suggest the causal link between the dopaminergic system and STN-DBS. We also examined how catecholamine levels were modulated after subthalamic stimulation.

Methods

In total 25 patients with PD were enrolled (Mean age 66.2 ± 6.7 years, mean disease duration 11.6 ± 3.7 years). Mean levodopa equivalent doses were 1032 ± 34.6 mg before surgery. Cerebrospinal fluid and plasma catecholamine levels were measured an hour after oral administration of antiparkinsonian drugs before surgery. The mean Unified Parkinson’s Disease Rating Scale scores (UPDRS) and the Parkinson’s disease Questionnaire-39 (PDQ-39) were obtained before and after surgery. Of the 25 patients, postoperative cerebrospinal fluid and plasma were collected an hour after oral administration of antiparkinsonian drugs during on stimulation at follow up in 11 patients.

Results

Mean levodopa equivalent doses significantly decreased after surgery with improvement in motor functions and quality of life. The preoperative catecholamine levels had basically negative correlations with postoperative motor scores and quality of life, suggesting that higher preoperative catecholamine levels were related to better outcome after STN-DBS. The preoperative plasma levels of L-DOPA had significantly negative correlations with postoperative UPDRS- III score in off phase three months after STN-DBS. The preoperative cerebrospinal fluid (CSF) 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxytryptamine (5-HT) levels had significantly negative correlations with postoperative UPDRS- III score in off phase one year after STN-DBS and the preoperative CSF homovanilic acid (HVA) levels had significant negative correlations with postoperative UPDRS- III score in on phase three months after STN-DBS. In PDQ-39 SI (summary index), preoperative plasma dopamine (DA) level had significantly negative correlations with postoperative PDQ-39 SI one year after STN-DBS suggesting that higher preoperative plasma DA level resulted in better quality of life (QOL) one year after STN-DBS. The stepwise multiple linear regression study revealed that higher preoperative plasma HVA levels had negative influence on the postoperative motor symptoms (i.e., increase in the score of UPDRS), whereas higher preoperative CSF L-DOPA levels had positive influence on the postoperative motor symptoms and QOL (decrease in the score of UPDRS and PDQ-39 SI) The catecholamine levels were not significantly reduced postoperatively in 11 patients despite the significant reduction in levodopa equivalent doses. Unexpectedly, CSF HVA levels significantly increased from 0.00089±0.0003 ng/μl to 0.002±0.0008 ng/μl after STN-DBS.

Conclusion

The preoperative catecholamine levels might affect the postoperative motor symptoms and quality of life. The catecholamine levels were not significantly reduced postoperatively despite the significant reduction in levodopa equivalent doses.