ADHD and Challenging behaviour in People with Intellectual Disability: should we screen for ADHD?

PubMed

Perera, Bhathika; Courtenay, Ken

2017-09-01

People with Intellectual Disability (ID) have cognitive impairments that affect their level of functioning the causes of which are multiple and often unknown. Behavioural difficulties are common among people with ID. Attention Deficit Hyperactivity Disorder (ADHD) is recognised more among people with Intellectual Disability and could be a cause of problem behaviours. Screening and assessing for ADHD in people with ID is difficult because of the paucity of robust assessment tools and diagnostic criteria.

On the relationship between motor performance and executive functioning in children with intellectual disabilities.

PubMed

Hartman, E; Houwen, S; Scherder, E; Visscher, C

2010-05-01

It has been suggested that children with intellectual disabilities (ID) have motor problems and higher-order cognitive deficits. The aim of this study was to examine the motor skills and executive functions in school-age children with borderline and mild ID. The second aim was to investigate the relationship between the two performance domains. Sixty-one children aged between 7 and 12 years diagnosed with borderline ID (33 boys and 28 girls; 71 < IQ < 79) and 36 age peers with mild ID (24 boys and 12 girls; 54 < IQ < 70) were assessed. Their abilities were compared with those of 97 age- and gender-matched typically developing children. Qualitative motor skills, i.e. locomotor ability and object control, were evaluated with the Test of Gross Motor Development (TGMD-2). Executive functioning (EF), in terms of planning ability, strategic decision-making and problem solving, was gauged with the Tower of London (TOL) task. Compared with the reference group, the full ID cohort scored significantly lower on all assessments. For the locomotor skills, the children with mild ID scored significantly lower than the children with borderline ID, but for the object control skills and the TOL score, no significant differences between the two groups were found. Motor performance and EF correlated positively. At the most complex level, the TOL showed decision time to be a mediator between motor performance and EF: the children with the lower motor scores had significantly shorter decision times and lower EF scores. Analogously, the children with the lower object control scores had longer execution times and lower EF scores. The current results support the notion that besides being impaired in qualitative motor skills intellectually challenged children are also impaired in higher-order executive functions. The deficits in the two domains are interrelated, so early interventions boosting their motor and cognitive development are recommended.

Intellectual disability in young people in custody in New South Wales, Australia - prevalence and markers.

PubMed

Haysom, L; Indig, D; Moore, E; Gaskin, C

2014-11-01

Intellectual disability (ID) is known to be more common in incarcerated groups, especially incarcerated youth. Aboriginal young people have higher rates of ID, and make up half of all youth in juvenile custody in New South Wales (NSW), Australia. We aimed to describe the prevalence of possible ID and borderline intellectual functioning (BIF) in young people in NSW custody, and to describe the association between possible ID and Aboriginality after adjusting for the inequalities in social disadvantage. Baseline study of all youth in NSW Custodial Centres between August and October 2009, with 18-month follow-up. Using Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) and Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) cognitive assessments, possible ID was defined as Extremely Low Intellectual Quotient range (Full Scale Intellectual Quotient, FSIQ < 70), and possible BIF was defined as Borderline IQ range (FSIQ < 80). Risk factors for possible ID and BIF included age, gender, Aboriginality, socio-economic disadvantage, offending history and psychological disorders. N = 295 (65%) of all young people in NSW custody completed cognitive and psychological assessments (87% male, 50% Aboriginal, average age 17 years). Almost one half (45.8%) of young people had borderline or lower intellectual functioning (by IQ assessment), and 14% had an IQ in the extremely low range (FSIQ < 70), indicating a possible ID. Aboriginal participants were three times more likely than non-Aboriginal participants to have a possible ID, but after accounting for the excess disadvantage in the Aboriginal group, Aboriginality was no longer a marker of ID. Incarceration from a young age and psychosis were significantly associated with possible ID in Aboriginal participants, compared with Aboriginal participants first incarcerated at a later age, and Aboriginal participants without psychosis. The inequalities in criminal justice between Aboriginal and non-Aboriginal youth may exacerbate or contribute to the intellectual impairment of those incarcerated from a young age. Aboriginal young people with psychosis are also at high risk of cognitive impairments that might indicate a possible co-morbid ID, and these patients should be diverted at court into community assessment services, rather than incarcerated. These results highlight a need for better and earlier identification of young people (particularly Aboriginal youth) at risk of ID and other co-morbidities in the juvenile justice system. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

PubMed Central

Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa

2013-01-01

Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395

Incentive relativity in middle aged rats.

PubMed

Justel, N; Mustaca, A; Boccia, M; Ruetti, E

2014-01-24

Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Clinical outcomes of a specialised inpatient unit for adults with mild to severe intellectual disability and mental illness.

PubMed

Lunsky, Y; White, S E; Palucka, A M; Weiss, J; Bockus, S; Gofine, T

2010-01-01

Limitations of general psychiatric services have led to the development of specialised psychiatric programmes for patients with intellectual disability (ID) and mental health needs. Few studies have examined treatment outcomes of specialised inpatient units, and no studies have explored how the effects of intervention may differ for individuals at varying levels of cognitive ability. The present study examined clinical outcomes of inpatients with mild ID in contrast to inpatients with moderate to severe ID within the same service. Thirty-three patients (17 with mild ID and 16 with moderate to severe ID) discharged between 2006 and 2008 from a specialised inpatient unit in Canada for adults with ID and mental illness were studied. In addition to examining change in scores on clinical measures, outcomes with regard to length of stay, diagnostic change, residential change and re-admission to hospital were explored. Both groups demonstrated clinical improvement from admission to discharge. However, only patients with mild ID demonstrated improvements on the Global Assessment of Functioning. This study is one of the first to consider outcomes of higher and lower functioning individuals with ID on a specialised inpatient unit. Results suggest that outcomes may be different for these groups, and some clinical measures may be more sensitive to changes in patients with more severe disabilities.

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

PubMed Central

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke HM; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-01-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification. PMID:26757981

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila.

PubMed

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke Hm; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-08-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification.

[Concurrent validity of the HAWIK-IV and the Intelligence and Development Scales (IDS)].

PubMed

Hagmann-von Arx, Priska; Grob, Alexander; Petermann, Franz; Daseking, Monika

2012-01-01

The present study examined the concurrent validity of the Hamburg Wechsler Intelligenztest für Kinder - IV (HAWIK-IV; Petermann & Petermann, 2010) and the Intelligence and Development Scales (IDS; Grob, Meyer & Hagmann-von Arx, 2009). HAWIK-IV and IDS were administered in counterbalanced order to N = 172 children aged 6 to 11 years. The study presents the descriptive statistics, correlations, and an exploratory factor analysis of the data. There is a high correlation between HAWIK-IV Full Scale IQ and IDS intelligence score (r = .83). HAWIK-IV indices showed moderate to high correlations with the cognitive scales of the IDS (Cognition, Language, Mathematics). Low to absent correlations were found between HAWIK-IV indices and the noncognitive scales of the IDS (Social-Emotional Competence, Psychomotor, Achievement Motivation). The factor structure can be interpreted meaningfully and allows integration of the IDS cognitive, language, and mathematical subtests into the four HAWIK-IV indices. The results show that HAWIK-IV and IDS test results can be related to each other.

Visual local and global processing in low-functioning deaf individuals with and without autism spectrum disorder.

PubMed

Maljaars, J P W; Noens, I L J; Scholte, E M; Verpoorten, R A W; van Berckelaer-Onnes, I A

2011-01-01

The ComFor study has indicated that individuals with intellectual disability (ID) and autism spectrum disorder (ASD) show enhanced visual local processing compared with individuals with ID only. Items of the ComFor with meaningless materials provided the best discrimination between the two samples. These results can be explained by the weak central coherence account. The main focus of the present study is to examine whether enhanced visual perception is also present in low-functioning deaf individuals with and without ASD compared with individuals with ID, and to evaluate the underlying cognitive style in deaf and hearing individuals with ASD. Different sorting tasks (selected from the ComFor) were administered from four subsamples: (1) individuals with ID (n = 68); (2) individuals with ID and ASD (n = 72); (3) individuals with ID and deafness (n = 22); and (4) individuals with ID, ASD and deafness (n = 15). Differences in performance on sorting tasks with meaningful and meaningless materials between the four subgroups were analysed. Age and level of functioning were taken into account. Analyses of covariance revealed that results of deaf individuals with ID and ASD are in line with the results of hearing individuals with ID and ASD. Both groups showed enhanced visual perception, especially on meaningless sorting tasks, when compared with hearing individuals with ID, but not compared with deaf individuals with ID. In ASD either with or without deafness, enhanced visual perception for meaningless information can be understood within the framework of the central coherence theory, whereas in deafness, enhancement in visual perception might be due to a more generally enhanced visual perception as a result of auditory deprivation. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

Motherese in Interaction: At the Cross-Road of Emotion and Cognition? (A Systematic Review)

PubMed Central

Saint-Georges, Catherine; Chetouani, Mohamed; Cassel, Raquel; Apicella, Fabio; Mahdhaoui, Ammar; Muratori, Filippo; Laznik, Marie-Christine; Cohen, David

2013-01-01

Various aspects of motherese also known as infant-directed speech (IDS) have been studied for many years. As it is a widespread phenomenon, it is suspected to play some important roles in infant development. Therefore, our purpose was to provide an update of the evidence accumulated by reviewing all of the empirical or experimental studies that have been published since 1966 on IDS driving factors and impacts. Two databases were screened and 144 relevant studies were retained. General linguistic and prosodic characteristics of IDS were found in a variety of languages, and IDS was not restricted to mothers. IDS varied with factors associated with the caregiver (e.g., cultural, psychological and physiological) and the infant (e.g., reactivity and interactive feedback). IDS promoted infants’ affect, attention and language learning. Cognitive aspects of IDS have been widely studied whereas affective ones still need to be developed. However, during interactions, the following two observations were notable: (1) IDS prosody reflects emotional charges and meets infants’ preferences, and (2) mother-infant contingency and synchrony are crucial for IDS production and prolongation. Thus, IDS is part of an interactive loop that may play an important role in infants’ cognitive and social development. PMID:24205112

Intellectual Disability, Mild Cognitive Impairment, and Risk for Dementia

PubMed Central

Silverman, Wayne P.; Zigman, Warren B.; Krinsky-McHale, Sharon J.; Ryan, Robert; Schupf, Nicole

2013-01-01

People with intellectual disability (ID) are living longer than ever before, raising concerns about old-age associated disorders. Dementia is among the most serious of these disorders, and theories relating cognitive reserve to risk predict that older adults with ID should be particularly vulnerable. Previous estimates of relative risk for dementia associated with ID have been inconsistent, and the present analyses examined the possible influence of variation in diagnostic criteria on findings. As expected, relaxation in the stringency of case definition for adults with ID increased relative risk, underscoring the importance of developing valid criteria for defining mild cognitive impairment, early dementia, and distinguishing between the two in adults with ID. Once available, these standards will contribute to more effective evidence-based planning. PMID:24273589

Iron Deficiency with or without Anemia Impairs Prepulse Inhibition of the Startle Reflex

PubMed Central

Pisansky, Marc T.; Wickham, Robert J.; Su, Jianjun; Fretham, Stephanie; Yuan, Li-Lian; Sun, Mu; Gewirtz, Jonathan C.; Georgieff, Michael K.

2013-01-01

Iron deficiency (ID) during early life causes long-lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early-life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus-specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT-1). Our second model used a classic rat dietary-based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT-1 knockout model displayed reduced long-term potentiation (LTP) and elevated paired pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia. PMID:23733517

Prenatal iron deficiency and monoamine oxidase A (MAOA) polymorphisms: combined risk for later cognitive performance in rhesus monkeys.

PubMed

Golub, Mari; Hogrefe, Casey

2014-03-01

Monoamine oxidase A (MAOA) gene polymorphisms resulting in high and low transcription rates are associated with individual differences in reward efficacy and response inhibition. Iron deficiency (ID) is the most frequent single-nutrient deficiency worldwide, and prenatal ID has recently been shown to carry a risk for lower mental development scores in infants. In this study, a potential interaction of MAOA genotype and prenatal ID was studied in young male rhesus monkeys. Cognitive tasks, including problem solving, responsiveness to reward and attention, were used to characterize the potential interaction of these two fetal risks. ID was induced by feeding rhesus monkey dams an iron-deficient (10 ppm, ID) or an iron-sufficient (100 ppm, IS) diet during gestation (n = 10/group). Subgroups of the ID and IS diet offspring had low-MAOA or high-MAOA transcription rate polymorphisms. ID combined with low-MAOA genotype showed distinctive effects on reward preference and problem solving while ID in hi-MAOA juveniles modified response inhibition. Given the incidence of ID and MAOA polymorphisms in humans, this interaction could be a significant determinant of cognitive performance.

Vanillin improves scopolamine-induced memory impairment through restoration of ID1 expression in the mouse hippocampus

PubMed Central

Lee, Jae-Chul; Kim, In Hye; Cho, Jeong Hwi; Lee, Tae-Kyeong; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Bich Na; Yan, Bing Chun; Kim, Jong-Dai; Jeon, Yong Hwan; Lee, Young Joo; Won, Moo-Ho; Kang, Il Jun

2018-01-01

4-Hydroxy-3-methoxybenzaldehyde (vanillin), contained in a number of species of plant, has been reported to display beneficial effects against brain injuries. In the present study, the impact of vanillin on scopolamine-induced alterations in cognition and the expression of DNA binding protein inhibitor ID-1 (ID1), one of the inhibitors of DNA binding/differentiation proteins that regulate gene transcription, in the mouse hippocampus. Mice were treated with 1 mg/kg scopolamine with or without 40 mg/kg vanillin once daily for 4 weeks. Scopolamine-induced cognitive impairment was observed from 1 week and was deemed to be severe 4 weeks following the administration of scopolamine. However, treatment with vanillin in scopolamine-treated mice markedly attenuated cognitive impairment 4 weeks following treatment with scopolamine. ID1-immunoreactive cells were revealed in the hippocampus of vehicle-treated mice, and were hardly detected 4 weeks following treatment with scopolamine. However, treatment with vanillin in scopolamine-treated mice markedly restored ID1-immunoreactive cells and expression 4 weeks subsequent to treatment. The results of the present study suggested that vanillin may be beneficial for cognitive impairment, by preventing the reduction of ID1 expression which may be associated with cognitive impairment. PMID:29328430

Evaluation of Executive Functioning in People with Intellectual Disabilities

ERIC Educational Resources Information Center

Willner, P.; Bailey, R.; Parry, R.; Dymond, S.

2010-01-01

Background: Executive functioning (EF) is an important concept in cognitive psychology that has rarely been studied in people with intellectual disabilities (IDs). The aim of this study was to examine the validity of two test batteries and the structure of EF in this client group. Methods: We administered the children's version of the Behavioural…

A Comparative Neuropsychological Test Battery Differentiates Cognitive Signatures of Fragile X and Down Syndrome

ERIC Educational Resources Information Center

Kogan, C. S.; Boutet, I.; Cornish, K.; Graham, G. E.; Berry-Kravis, E.; Drouin, A.; Milgram, N. W.

2009-01-01

Background: Standardised neuropsychological and cognitive measures present some limitations in their applicability and generalisability to individuals with intellectual disability (ID). Alternative approaches to defining the cognitive signatures of various forms of ID are needed to advance our understanding of the profiles of strengths and…

Assessing the Effectiveness of the Cognitive Interview for Children with Severe Intellectual Disabilities

ERIC Educational Resources Information Center

Milne, Rebecca; Sharman, Stefanie J.; Powell, Martine B.; Mead, Sarah

2013-01-01

We examined whether the cognitive interview (CI) procedure increased event recall in children with severe intellectual disabilities (ID) compared with children with no ID. Forty-six children with and without ID watched a videotaped event; they were aged between eight and 11 years. The next day they were individually interviewed using the CI or a…

Face Preferences for Infant- and Adult-Directed Speakers in Infants of Depressed and Nondepressed Mothers: Association with Infant Cognitive Development.

PubMed

Kaplan, Peter S; Asherin, Ryan M; Vogeli, Jo M; Fekri, Shiva M; Scheyer, Kathryn E; Everhart, Kevin D

2018-01-01

Face preferences for speakers of infant-directed and adult-directed speech (IDS and ADS) were investigated in 4- to 13.5-month-old infants of depressed and non-depressed mothers. Following 1-min of exposure to an ID or AD speaker (order counterbalanced), infants had an immediate paired-comparison test with a still, silent image of the familiarized versus a novel face. In the test phase, ID face preference ratios were significantly lower in infants of depressed than non-depressed mothers. Infants' ID face preference ratios, but not AD face preference ratios, correlated with their percentile scores on the cognitive ( Cog ) scale of the Bayley Scales of Infant & Toddler Development (3 rd Edition; BSID III), assessed concurrently. Regression analyses revealed that infant ID face preferences significantly predicted infant Cog percentiles even after demographic risk factors and maternal depression had been controlled. Infants may use IDS to select social partners who are likely to support and facilitate cognitive development.

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

PubMed Central

Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

2016-01-01

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration. PMID:28066203

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment.

PubMed

Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

2016-01-01

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients ( p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) ( p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score ( p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups ( p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

A Novel Analog Reasoning Paradigm: New Insights in Intellectually Disabled Patients.

PubMed

Curie, Aurore; Brun, Amandine; Cheylus, Anne; Reboul, Anne; Nazir, Tatjana; Bussy, Gérald; Delange, Karine; Paulignan, Yves; Mercier, Sandra; David, Albert; Marignier, Stéphanie; Merle, Lydie; de Fréminville, Bénédicte; Prieur, Fabienne; Till, Michel; Mortemousque, Isabelle; Toutain, Annick; Bieth, Eric; Touraine, Renaud; Sanlaville, Damien; Chelly, Jamel; Kong, Jian; Ott, Daniel; Kassai, Behrouz; Hadjikhani, Nouchine; Gollub, Randy L; des Portes, Vincent

2016-01-01

Intellectual Disability (ID) is characterized by deficits in intellectual functions such as reasoning, problem-solving, planning, abstract thinking, judgment, and learning. As new avenues are emerging for treatment of genetically determined ID (such as Down's syndrome or Fragile X syndrome), it is necessary to identify objective reliable and sensitive outcome measures for use in clinical trials. We developed a novel visual analogical reasoning paradigm, inspired by the Progressive Raven's Matrices, but appropriate for Intellectually Disabled patients. This new paradigm assesses reasoning and inhibition abilities in ID patients. We performed behavioural analyses for this task (with a reaction time and error rate analysis, Study 1) in 96 healthy controls (adults and typically developed children older than 4) and 41 genetically determined ID patients (Fragile X syndrome, Down syndrome and ARX mutated patients). In order to establish and quantify the cognitive strategies used to solve the task, we also performed an eye-tracking analysis (Study 2). Down syndrome, ARX and Fragile X patients were significantly slower and made significantly more errors than chronological age-matched healthy controls. The effect of inhibition on error rate was greater than the matrix complexity effect in ID patients, opposite to findings in adult healthy controls. Interestingly, ID patients were more impaired by inhibition than mental age-matched healthy controls, but not by the matrix complexity. Eye-tracking analysis made it possible to identify the strategy used by the participants to solve the task. Adult healthy controls used a matrix-based strategy, whereas ID patients used a response-based strategy. Furthermore, etiologic-specific reasoning differences were evidenced between ID patients groups. We suggest that this paradigm, appropriate for ID patients and developmental populations as well as adult healthy controls, provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition, enabling testing for the effect of pharmacological or behavioural intervention in these specific populations.

Iron deficiency anemia and cognitive function in infancy.

PubMed

Carter, R Colin; Jacobson, Joseph L; Burden, Matthew J; Armony-Sivan, Rinat; Dodge, Neil C; Angelilli, Mary Lu; Lozoff, Betsy; Jacobson, Sandra W

2010-08-01

This study examined effects of iron deficiency anemia (IDA) on specific domains of infant cognitive function and the role of IDA-related socioemotional deficits in mediating and/or moderating these effects. Infants were recruited during routine 9-month visits to an inner-city clinic. IDA was defined as hemoglobin level <110 g/L with > or =2 abnormal iron deficiency indicators (mean corpuscular volume, red cell distribution width, zinc protoporphyrin, transferrin saturation, and ferritin). At 9 and 12 months, the Fagan Test of Infant Intelligence (FTII); A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale were administered. Analyses were adjusted for potential confounders, including age and sociodemographic variables. Twenty-eight infants met criteria for IDA, 28 had nonanemic iron deficiency (NA ID) and 21 had iron sufficiency (IS). There was a linear effect for object permanence at 9 months: infants with IDA were least likely to exhibit object permanence, IS most likely, and NA ID intermediate. Infants with IDA and those with hemoglobin level < or =105 g/L showed poorer recognition memory on the FTII than infants without IDA. The Behavior Rating Scale orientation/engagement measure partially mediated these effects. Stronger effects of IDA on these outcomes were seen in infants who scored more poorly on the socioemotional measures. These data indicate poorer object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months. These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function.

Cognitive behaviour therapy (CBT) for anxiety and depression in adults with mild intellectual disabilities (ID): a pilot randomised controlled trial.

PubMed

Hassiotis, Angela; Serfaty, Marc; Azam, Kiran; Strydom, Andre; Martin, Sue; Parkes, Charles; Blizard, Robert; King, Michael

2011-04-14

Several studies have showed that people with intellectual disabilities (ID) have suitable skills to undergo cognitive behavioural therapy (CBT). Case studies have reported successful use of cognitive behavioural therapy techniques (with adaptations) in people with ID. Modified cognitive behavioural therapy may be a feasible and effective approach for the treatment of depression, anxiety, and other mood disorders in ID. To date, two studies have reported group-based manaulised cognitive behavioural treatment programs for depression in people with mild ID. However, there is no individual manualised programme for anxiety or depression in people with intellectual disabilities. The aims of the study are to determine the feasibility of conducting a randomised controlled trial for CBT in people with ID. The data will inform the power calculation and other aspects of carrying out a definitive randomised controlled trial. Thirty participants with mild ID will be allocated randomly to either CBT or treatment as usual (TAU). The CBT group will receive up to 20 hourly individual CBT over a period of 4 months. TAU is the standard treatment which is available to any adult with an intellectual disability who is referred to the intellectual disability service (including care management, community support, medical, nursing or social support). Beck Youth Inventories (Beck Anxiety Inventory & Beck Depression Inventory) will be administered at baseline; end of treatment (4 months) and at six months to evaluate the changes in depression and anxiety. Client satisfaction, quality of life and the health economics will be secondary outcomes. The broad outcome of the study will be to produce clear guidance for therapists to apply an established psychological intervention and identify how and whether it works with people with intellectual disabilities. ISRCTN: ISRCTN38099525.

Cognitive behaviour therapy (CBT) for anxiety and depression in adults with mild intellectual disabilities (ID): a pilot randomised controlled trial

PubMed Central

2011-01-01

Background Several studies have showed that people with intellectual disabilities (ID) have suitable skills to undergo cognitive behavioural therapy (CBT). Case studies have reported successful use of cognitive behavioural therapy techniques (with adaptations) in people with ID. Modified cognitive behavioural therapy may be a feasible and effective approach for the treatment of depression, anxiety, and other mood disorders in ID. To date, two studies have reported group-based manaulised cognitive behavioural treatment programs for depression in people with mild ID. However, there is no individual manualised programme for anxiety or depression in people with intellectual disabilities. The aims of the study are to determine the feasibility of conducting a randomised controlled trial for CBT in people with ID. The data will inform the power calculation and other aspects of carrying out a definitive randomised controlled trial. Methods Thirty participants with mild ID will be allocated randomly to either CBT or treatment as usual (TAU). The CBT group will receive up to 20 hourly individual CBT over a period of 4 months. TAU is the standard treatment which is available to any adult with an intellectual disability who is referred to the intellectual disability service (including care management, community support, medical, nursing or social support). Beck Youth Inventories (Beck Anxiety Inventory & Beck Depression Inventory) will be administered at baseline; end of treatment (4 months) and at six months to evaluate the changes in depression and anxiety. Client satisfaction, quality of life and the health economics will be secondary outcomes. Discussion The broad outcome of the study will be to produce clear guidance for therapists to apply an established psychological intervention and identify how and whether it works with people with intellectual disabilities. Trial registration ISRCTN: ISRCTN38099525 PMID:21492437

Problem solving ability in children with intellectual disability as measured by the Raven's colored progressive matrices.

PubMed

Goharpey, Nahal; Crewther, David P; Crewther, Sheila G

2013-12-01

This study investigated the developmental trajectory of problem solving ability in children with intellectual disability (ID) of different etiologies (Down Syndrome, Idiopathic ID or low functioning Autism) as measured on the Raven's Colored Progressive Matrices test (RCPM). Children with typical development (TD) and children with ID were matched on total correct performance (i.e., non-verbal mental age) on the RCPM. RCPM total correct performance and the sophistication of error types were found to be associated with receptive vocabulary in all participants, suggesting that verbal ability plays a role in more sophisticated problem solving tasks. Children with ID made similar errors on the RCPM as younger children with TD as well as more positional error types. This result suggests that children with ID who are deficient in their cognitive processing resort to developmentally immature problem solving strategies when unable to determine the correct answer. Overall, the findings support the use of RCPM as a valid means of matching intellectual capacity of children with TD and ID. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rest but busy: Aberrant resting-state functional connectivity of triple network model in insomnia.

PubMed

Dong, Xiaojuan; Qin, Haixia; Wu, Taoyu; Hu, Hua; Liao, Keren; Cheng, Fei; Gao, Dong; Lei, Xu

2018-02-01

One classical hypothesis among many models to explain the etiology and maintenance of insomnia disorder (ID) is hyperarousal. Aberrant functional connectivity among resting-state large-scale brain networks may be the underlying neurological mechanisms of this hypothesis. The aim of current study was to investigate the functional network connectivity (FNC) among large-scale brain networks in patients with insomnia disorder (ID) during resting state. In the present study, the resting-state fMRI was used to evaluate whether patients with ID showed aberrant FNC among dorsal attention network (DAN), frontoparietal control network (FPC), anterior default mode network (aDMN), and posterior default mode network (pDMN) compared with healthy good sleepers (HGSs). The Pearson's correlation analysis was employed to explore whether the abnormal FNC observed in patients with ID was associated with sleep parameters, cognitive and emotional scores, and behavioral performance assessed by questionnaires and tasks. Patients with ID had worse subjective thought control ability measured by Thought Control Ability Questionnaire (TCAQ) and more negative affect than HGSs. Intriguingly, relative to HGSs, patients with ID showed a significant increase in FNC between DAN and FPC, but a significant decrease in FNC between aDMN and pDMN. Exploratory analysis in patients with ID revealed a significantly positive correlation between the DAN-FPC FNC and reaction time (RT) of psychomotor vigilance task (PVT). The current study demonstrated that even during the resting state, the task-activated and task-deactivated large-scale brain networks in insomniacs may still maintain a hyperarousal state, looking quite similar to the pattern in a task condition with external stimuli. Those results support the hyperarousal model of insomnia.

Thriving in Youth with Autism Spectrum Disorder and Intellectual Disability

ERIC Educational Resources Information Center

Weiss, Jonathan A.; Burnham Riosa, Priscilla

2015-01-01

Most research on mental health in individuals with autism spectrum disorder (ASD) and intellectual disability (ID) has focused on deficits. We examined individual (i.e., sociocommunicative skills, adaptive behavior, functional cognitive skills) and contextual (i.e., home, school, and community participation) correlates of thriving in 330 youth…

A Brief Assessment of Intelligence Decline in Schizophrenia As Represented by the Difference between Current and Premorbid Intellectual Quotient

PubMed Central

Ohi, Kazutaka; Sumiyoshi, Chika; Fujino, Haruo; Yasuda, Yuka; Yamamori, Hidenaga; Fujimoto, Michiko; Sumiyoshi, Tomiki; Hashimoto, Ryota

2017-01-01

Patients with schizophrenia elicit several clinical features, such as psychotic symptoms, cognitive impairment, and subtle decline of intelligence. The latter two features become evident around the onset of the illness, although they may exist even before the disease onset in a substantial proportion of cases. Here, we review the literature concerning intelligence decline (ID) during the progression of schizophrenia. ID can be estimated by comparing premorbid and current intellectual quotient (IQ) by means of the Adult Reading Test and Wechsler Adult Intelligence Scale (WAIS), respectively. For the purpose of brief assessment, we have recently developed the WAIS-Short Form, which consists of Similarities and Symbol Search and well reflects functional outcomes. According to the degree of ID, patients were classified into three distinct subgroups; deteriorated, preserved, and compromised groups. Patients who show deteriorated IQ (deteriorated group) elicit ID from a premorbid level (≥10-point difference between current and premorbid IQ), while patients who show preserved or compromised IQ do not show such decline (<10-point difference). Furthermore, the latter patients were divided into patients with preserved and compromised IQ based on an estimated premorbid IQ score >90 or below 90, respectively. We have recently shown the distribution of ID in a large cohort of schizophrenia patients. Consistent with previous studies, approximately 30% of schizophrenia patients had a decline of less than 10 points, i.e., normal intellectual performance. In contrast, approximately 70% of patients showed deterioration of IQ. These results indicate that there is a subgroup of schizophrenia patients who have mild or minimal intellectual deficits, following the onset of the disorder. Therefore, a careful assessment of ID is important in identifying appropriate interventions, including medications, cognitive remediation, and social/community services. PMID:29312019

Iron Deficiency Anemia and Cognitive Function in Infancy

PubMed Central

Carter, R. Colin; Jacobson, Joseph L.; Burden, Matthew J.; Armony-Sivan, Rinat; Dodge, Neil C.; Angelilli, Mary Lu; Lozoff, Betsy; Jacobson, Sandra W.

2011-01-01

OBJECTIVES This study examined effects of iron deficiency anemia (IDA) on specific domains of infant cognitive function and the role of IDA-related socioemotional deficits in mediating and/or moderating these effects. METHODS Infants were recruited during routine 9-month visits to an inner-city clinic. IDA was defined as hemoglobin level <110 g/L with ≥2 abnormal iron deficiency indicators (mean corpuscular volume, red cell distribution width, zinc protoporphyrin, transferrin saturation, and ferritin). At 9 and 12 months, the Fagan Test of Infant Intelligence (FTII); A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale were administered. Analyses were adjusted for potential confounders, including age and sociodemographic variables. RESULTS Twenty-eight infants met criteria for IDA, 28 had nonanemic iron deficiency (NA ID) and 21 had iron sufficiency (IS). There was a linear effect for object permanence at 9 months: infants with IDA were least likely to exhibit object permanence, IS most likely, and NA ID intermediate. Infants with IDA and those with hemoglobin level ≤105 g/L showed poorer recognition memory on the FTII than infants without IDA. The Behavior Rating Scale orientation/engagement measure partially mediated these effects. Stronger effects of IDA on these outcomes were seen in infants who scored more poorly on the socioemotional measures. CONCLUSIONS These data indicate poorer object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months. These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function. PMID:20660551

Intellectual, Adaptive, and Behavioral Functioning in Children with Urea Cycle Disorders

PubMed Central

Krivitzky, Lauren; Babikian, Talin; Lee, HyeSeung; Thomas, Nina Hattiangadi; Burk-Paull, Karen L.; Batshaw, Mark L.

2009-01-01

Inborn errors of urea synthesis lead to an accumulation of ammonia in blood and brain, and result in high rates of mortality and neurodevelopmental disability. The current study seeks to characterize the cognitive, adaptive, and emotional/behavioral functioning of children with Urea Cycle Disorders (UCDs). These domains were measured through testing and parent questionnaires in 92 children with UCDs (33 neonatal onset, 59 late onset). Results indicate that children who present with neonatal onset have poorer outcome than those who present later in childhood. Approximately half of the children with neonatal onset performed in the range of intellectual disability (ID), including a substantial number (~30%) who were severely impaired. In comparison, only a quarter of the late onset group were in the range of ID. There is also evidence that the UCD group has difficulties in aspects of emotional/behavioral and executive skills domains. In conclusion, children with UCDs present with a wide spectrum of cognitive outcomes. Children with neonatal onset disease have a much higher likelihood of having an intellectual disability, which becomes even more evident with increasing age. However, even children with late onset UCDs demonstrate evidence of neurocognitive and behavioral impairment, particularly in aspects of attention and executive functioning. PMID:19287347

GRASP1 regulates synaptic plasticity and learning through endosomal recycling of AMPA receptors

PubMed Central

Chiu, Shu-Ling; Diering, Graham Hugh; Ye, Bing; Takamiya, Kogo; Chen, Chih-Ming; Jiang, Yuwu; Niranjan, Tejasvi; Schwartz, Charles E.; Wang, Tao; Huganir, Richard L.

2017-01-01

Summary Learning depends on experience-dependent modification of synaptic efficacy and neuronal connectivity in the brain. We provide direct evidence for physiological roles of the recycling endosome protein GRASP1 in glutamatergic synapse function and animal behavior. Mice lacking GRASP1 showed abnormal excitatory synapse number, synaptic plasticity and hippocampal-dependent learning and memory due to a failure in learning-induced synaptic AMPAR incorporation. We identified two GRASP1 point mutations from intellectual disability (ID) patients that showed convergent disruptive effects on AMPAR recycling and glutamate uncaging-induced structural and functional plasticity. Wild-type GRASP1, but not ID mutants, rescues spine loss in hippocampal CA1 neurons of Grasp1 knockout mice. Together, these results demonstrate a requirement for normal recycling endosome function in AMPAR-dependent synaptic function and neuronal connectivity in vivo, and suggest a potential role for GRASP1 in the pathophysiology of human cognitive disorders. PMID:28285821

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability

PubMed Central

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-01-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1–3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal–parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID. PMID:27457812

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

PubMed

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-11-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

Cognitive Behavioral Therapy for Depressed Adults with Mild Intellectual Disability: A Pilot Study

PubMed Central

Hartley, Sigan L; Esbensen, Anna J; Shalev, Rebecca; Vincent, Lori B; Mihaila, Iulia; Bussanich, Paige

2015-01-01

Background There is a paucity of research on psychosocial treatments for depression in adults with intellectual disability (ID). In this pilot study, we explored the efficacy of a group CBT treatment that involved a caregiver component in adults with mild ID with a depressive disorder. Method Sixteen adults with mild ID and a depressive disorder participated in a 10-week group CBT treatment and 8 adults with mild ID with a depressive disorder served as a treatment as usual (TAU) control group. Adults with mild ID and caregivers completed measures of depressive symptoms, behavior problems, and social skills at pre-treatment, post-treatment, and a 3-month follow-up. Adults with mild ID also completed a series of tasks to measure their understanding of the principles of cognitive therapy pre- and post-treatment. Results The CBT group demonstrated significant decreases in depressive symptoms and behavior problems from pre-treatment to post-treatment and these effects were maintained at a 3-month follow-up. The CBT group demonstrated significant improvements in their ability to infer emotions and thoughts based on various situation-thought-emotion pairings from pre-treatment to post-treatment. Conclusions Findings indicate that adults with mild ID with a depressive disorder benefitted from a group CBT treatment with a caregiver component. Moreover, adults with mild ID appeared to benefit, at least in part, from the cognitive therapy components of the treatment, in addition to the behavior therapy components. PMID:26925187

Cognitive adverse events of topiramate in patients with epilepsy and intellectual disability.

PubMed

Brandt, Christian; Lahr, Denise; May, Theodor W

2015-04-01

Topiramate (TPM) is an effective antiepileptic drug (AED). A high proportion of patients, however, experiences cognitive adverse events (CAEs), especially in verbal fluency, memory spans, and working memory. To our knowledge, CAEs of TPM have not been studied systematically in patients with intellectual disability (ID). This may be due to the fact that many of those patients are not able to follow test instructions properly and that neuropsychological instruments are not validated for that group. Cognitive deterioration in patients with ID may thus easily be overlooked. Topiramate is in frequent use in persons with ID. We included 26 consecutive patients with epilepsy and ID in this observational study who had undergone neuropsychological examinations as part of clinical routine before and after the introduction of TPM into the therapeutic regimen (n=4) or before and after the withdrawal of TPM (n=22). Examinations under TPM showed reduced cognitive speed, reduced verbal memory, reduced verbal fluency, and reduced flexibility compared to examinations without TPM. Despite some limitations (especially small sample size, high interindividual variation of the results dependent on the degree of ID, effects of other - limited - changes in the therapeutic regimen), our study indicates that TPM in persons with epilepsy and ID may lead to CAEs comparable to those in persons with normal intelligence. Neuropsychological testing is mandatory in order not to miss CAEs that might severely impair quality of life. Copyright © 2015 Elsevier Inc. All rights reserved.

Mutations in two large pedigrees highlight the role of ZNF711 in X-linked intellectual disability.

PubMed

van der Werf, Ilse M; Van Dijck, Anke; Reyniers, Edwin; Helsmoortel, Céline; Kumar, Ajay Anand; Kalscheuer, Vera M; de Brouwer, Arjan Pm; Kleefstra, Tjitske; van Bokhoven, Hans; Mortier, Geert; Janssens, Sandra; Vandeweyer, Geert; Kooy, R Frank

2017-03-20

Intellectual disability (ID) affects approximately 1-2% of the general population and is characterized by impaired cognitive abilities. ID is both clinically as well as genetically heterogeneous, up to 2000 genes are estimated to be involved in the emergence of the disease with various clinical presentations. For many genes, only a few patients have been reported and causality of some genes has been questioned upon the discovery of apparent loss-of-function mutations in healthy controls. Description of additional patients strengthens the evidence for the involvement of a gene in the disease and can clarify the clinical phenotype associated with mutations in a particular gene. Here, we present two large four-generation families with a total of 11 males affected with ID caused by mutations in ZNF711, thereby expanding the total number of families with ID and a ZNF711 mutation to four. Patients with mutations in ZNF711 all present with mild to moderate ID and poor speech accompanied by additional features in some patients, including autistic features and mild facial dysmorphisms, suggesting that ZNF711 mutations cause non-syndromic ID. Copyright © 2016 Elsevier B.V. All rights reserved.

Frontal brain electrical activity (EEG) and heart rate in response to affective infant-directed (ID) speech in 9-month-old infants.

PubMed

Santesso, Diane L; Schmidt, Louis A; Trainor, Laurel J

2007-10-01

Many studies have shown that infants prefer infant-directed (ID) speech to adult-directed (AD) speech. ID speech functions to aid language learning, obtain and/or maintain an infant's attention, and create emotional communication between the infant and caregiver. We examined psychophysiological responses to ID speech that varied in affective content (i.e., love/comfort, surprise, fear) in a group of typically developing 9-month-old infants. Regional EEG and heart rate were collected continuously during stimulus presentation. We found the pattern of overall frontal EEG power was linearly related to affective intensity of the ID speech, such that EEG power was greatest in response to fear, than surprise than love/comfort; this linear pattern was specific to the frontal region. We also noted that heart rate decelerated to ID speech independent of affective content. As well, infants who were reported by their mothers as temperamentally distressed tended to exhibit greater relative right frontal EEG activity during baseline and in response to affective ID speech, consistent with previous work with visual stimuli and extending it to the auditory modality. Findings are discussed in terms of how increases in frontal EEG power in response to different affective intensity may reflect the cognitive aspects of emotional processing across sensory domains in infancy.

Needs among persons with human immunodeficiency virus and intellectual and developmental disabilities in community mental health care: a cross-sectional study.

PubMed

Durbin, A; Sirotich, F; Lunsky, Y; Roesslein, K; Durbin, J

2017-03-01

The experience of having human immunodeficiency virus (HIV) is often associated with co-occurring mental health issues. Community mental health services are an important source of support for persons with HIV living in the community. Persons with intellectual disability (ID) are vulnerable to HIV and may have unique support needs beyond those without ID receiving community care. This study compared support needs of men with HIV in community mental health programmes, with and without ID. The sample was composed of 138 HIV-positive men with and without ID receiving mental health case management from one community organisation in Ontario, Canada, on 31 March 2013. Staff-rated needs across 16 domains grouped into four clusters were measured using the Camberwell Assessment of Need: Basic needs (accommodation, food, public transportation, money and benefits); self-care/functional needs (looking after the home, self-care and daytime activities); health/safety needs (physical health, psychological distress, psychotic symptoms, safety to self and safety to others); and social needs (company, intimate relationships and sexual expression). Adjusted logistic regression models examined the association between ID and each need domain. One-quarter of the sample (n = 34/138, 24.6%) had co-occurring ID. Those with ID were more likely to have needs in the basic cluster [odds ratios: food 4.05 (1.14, 14.44), P:0.031; benefits 2.58 (1.05, 6.32), P:0.038)] and self-care/functional cluster [looking after the home (2.75 (1.17, 6.49), P:0.021); self-care (2.72 (1.18, 6.27), P:0.019)], but were less likely to have need for sexual expression: 0.35 (0.14,0.90), P:0.030) (social cluster). There were no differences in the domains in the health/safety cluster. Despite elevated cognitive needs in the basic and self-care/functional clusters for the ID group, limited other differences suggest that with moderate additional targeting, community mental health programmes for persons with HIV may be appropriate for men with ID. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Foundations of reading comprehension in children with intellectual disabilities.

PubMed

van Wingerden, Evelien; Segers, Eliane; van Balkom, Hans; Verhoeven, Ludo

2017-01-01

Knowledge about predictors for reading comprehension in children with intellectual disabilities (ID) is still fragmented. This study compared reading comprehension, word decoding, listening comprehension, and reading related linguistic and cognitive precursor measures in children with mild ID and typically developing controls. Moreover, it was explored how the precursors related to reading achievement. Children with mild ID and typical controls were assessed on reading comprehension, decoding, language comprehension, and linguistic (early literacy skills, vocabulary, grammar) and cognitive (rapid naming, phonological short-term memory, working memory, temporal processing, nonverbal reasoning) precursor measures. It was tested to what extent variations in reading comprehension could be explained from word decoding, listening comprehension and precursor measures. The ID group scored significantly below typical controls on all measures. Word decoding was at or above first grade level in half the ID group. Reading comprehension in the ID group was related to word decoding, listening comprehension, early literacy skills, and temporal processing. The reading comprehension profile of children with mild ID strongly resembles typical early readers. The simple view of reading pertains to children with mild ID, with additional influence of early literacy skills and temporal processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recognition of facial expressions of emotion by adults with intellectual disability: Is there evidence for the emotion specificity hypothesis?

PubMed

Scotland, Jennifer L; McKenzie, Karen; Cossar, Jill; Murray, Aja; Michie, Amanda

2016-01-01

This study aimed to evaluate the emotion recognition abilities of adults (n=23) with an intellectual disability (ID) compared with a control group of children (n=23) without ID matched for estimated cognitive ability. The study examined the impact of: task paradigm, stimulus type and preferred processing style (global/local) on accuracy. We found that, after controlling for estimated cognitive ability, the control group performed significantly better than the individuals with ID. This provides some support for the emotion specificity hypothesis. Having a more local processing style did not significantly mediate the relation between having ID and emotion recognition, but did significantly predict emotion recognition ability after controlling for group. This suggests that processing style is related to emotion recognition independently of having ID. The availability of contextual information improved emotion recognition for people with ID when compared with line drawing stimuli, and identifying a target emotion from a choice of two was relatively easier for individuals with ID, compared with the other task paradigms. The results of the study are considered in the context of current theories of emotion recognition deficits in individuals with ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive Behavioural Therapy from the Perspective of Clients with Mild Intellectual Disabilities: A Qualitative Investigation of Process Issues

ERIC Educational Resources Information Center

Pert, C.; Jahoda, A.; Stenfert Kroese, B.; Trower, P.; Dagnan, D.; Selkirk, M.

2013-01-01

Background: Clinicians working with clients who have mild intellectual disabilities (IDs) have shown growing enthusiasm for using a cognitive behavioural approach, amid increasing evidence of good treatment outcomes for this client group. However, very little is known about the views and experiences of clients with IDs who have undergone cognitive…

Reflecting on the efficacy of cognitive mapping for decision-making in intellectual disability care: a case study.

PubMed

Duryan, Meri; Nikolik, Dragan; van Merode, Godefridus; Curfs, Leopold M G

2015-01-01

The central aspect of this study is a set of reflections on the efficacy of soft operational research techniques in understanding the dynamics of a complex system such as intellectual disability (ID) care providers. Organizations providing services to ID patients are complex and have many interacting stakeholders with often different and competing interests. Understanding the causes for failures in complex systems is crucial for appreciating the multiple perspectives of the key stakeholders of the system. Knowing the factors that adversely affect delivery of a patient-centred care by ID provider organizations offers the potential for identifying more effective resource-allocation solutions. The authors suggest cognitive mapping as a starting point for system dynamics modelling of optimal resource-allocation projects in ID care. The application of the method is illustrated via a case study in one of the ID care providers in the Netherlands. The paper discusses some of the practical implications of applying problem-structuring methods that support gathering feedback from vulnerable service users and front-line workers. The authors concluded that cognitive mapping technique can assist the management of healthcare organizations in strategic decision-making. Copyright © 2013 John Wiley & Sons, Ltd.

The neuropsychology of the schizo-obsessive subtype of schizophrenia: a new analysis.

PubMed

Patel, D D; Laws, K R; Padhi, A; Farrow, J M; Mukhopadhaya, K; Krishnaiah, R; Fineberg, N A

2010-06-01

Interest in the neuro-cognitive profile of patients with schizophrenia and co-morbid obsessive compulsive disorder (schizo-OCD) is rising in response to reports of high co-morbidity rates. Whereas schizophrenia has been associated with global impairment in a wide range of neuro-cognitive domains, OCD is associated with specific deficits featuring impaired performance on tasks of motor and cognitive inhibition involving frontostriatal neuro-circuitry. We compared cognitive function using the CANTAB battery in patients with schizo-OCD (n=12) and a schizophrenia group without OCD symptoms (n=16). The groups were matched for IQ, gender, age, medication, and duration of illness. The schizo-OCD patients made significantly more errors on a task of attentional set-shifting (ID-ED set-shift task). By contrast, no significant differences emerged on the Stockings of Cambridge task, the Cambridge Gamble Task or the Affective Go/NoGo tasks. No correlation emerged between ID-ED performance and severity of schizophrenia, OCD or depressive symptoms, consistent with neurocognitive impairment holding trait rather than state-marker status. Schizo-obsessives also exhibited a trend toward more motor tics emphasizing a neurological contribution to the disorder.ConclusionOur findings reveal a more severe attentional set-shifting deficit and neurological abnormality that may be fundamental to the neuro-cognitive profile of schizo-OCD. The clinical implications of these impairments merit further exploration in larger studies.

Inquiry Learning in a Special Education Setting: Managing the Cognitive Loads of Intellectually Disabled Students

ERIC Educational Resources Information Center

Lee, Theodore T. H.; So, Winnie W. M.

2015-01-01

This study investigates the use of inquiry learning (IL) approach for intellectually disabled (ID) students. It draws on findings from the trial lessons of 6 classes of ID students in a project developing an adapted General Studies Curriculum for ID students at primary level. Data analysis focuses on examining how IL was employed for ID students.…

Feasibility and outcomes of the Berg Balance Scale in older adults with intellectual disabilities.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Evenhuis, Heleen M

2013-09-01

High incidence of falls and increased risk of fall-related injuries are seen in individuals with intellectual disabilities (ID). The Berg Balance Scale (BBS) is a reliable instrument for balance assessment in the population of (older) adults with ID. The aims of this study were to assess the balance capacities of a large group of older adults with ID with the BBS and look for gender and age effects, as well as reasons for drop-out on separate items, and to identify feasible subtests for subgroups in which the complete BBS is not feasible. The balance capacities of 1050 older clients with borderline to profound ID of three Dutch care-provider services (mean age 61.6 [sd=8.0]) were assessed with the BBS. The participants who completed all items of the BBS (n=508) were the functionally more able part of the study sample. Results showed that even this functionally more able part had poor balance capacities, with a mean BBS score of 47.2, 95% CI [46.3, 48.0], similar to adults in the general population aged around 20 years older. Balance capacities decreased with increasing age and females had poorer balance capacities than males. Difficulties understanding the task and physical limitations were most often the reasons for drop-out. Feasible subtests were identified for the subgroups with very low cognitive levels and wheelchair users. Low balance capacities of older adults with ID show the need for regular screening and the urge for fall prevention programs for individuals with ID. Copyright © 2013 Elsevier Ltd. All rights reserved.

Application of chromosomal microarrays in the evaluation of intellectual disability/global developmental delay patients - A study from a tertiary care genetic centre in India.

PubMed

Sharma, Pankaj; Gupta, Neerja; Chowdhury, Madhumita Roy; Sapra, Savita; Ghosh, Manju; Gulati, Sheffali; Kabra, Madhulika

2016-09-15

Intellectual disability (ID)/Global developmental delay (GDD) is a diverse group of disorders in terms of cognitive and non-cognitive functions and can occur with or without associated co-morbidities. It affects 1-3% of individuals globally and in at least 30-50% of cases the etiology remains unexplained. The widespread use of chromosomal microarray analysis (CMA) in a clinical setting has allowed the identification of submicroscopic copy number variations (CNVs), throughout the genome, associated with neurodevelopmental phenotypes including ID/GDD. In this study we investigated the utility of CMA in the detection of CNVs in 106 patients with unexplained ID/DD, dysmorphism with or without multiple congenital anomalies (MCA). CMA study was carried out using Agilent 8×60K chips and Illumina Human CytoSNP-12 chips. Pathogenic CNVs were found in 15 (14.2%) patients. In these patients, CNVs on single chromosome were detected in 10 patients while 5 patients showed co-occurrence CNVs on two chromosomes. The size of these CNVs ranged between 322kb to 13Mb. The yield of pathogenic CNVs was similar for both mild and severe ID/GDD cases. One patient described in this paper is considered to harbour a likely pathogenic CNV with deletion in 17q22 region. Only few cases have been described in literature for 17q22 deletion and patient reported here was found to have an atypical deletion in 17q22 region (Case 90). This study re-affirms the view point that CMA is a powerful diagnostic tool in the evaluation of idiopathic ID/GDD patients irrespective of the degree of severity. Identifying pathogenic CNVs helps in counseling and prenatal diagnosis if desired. Copyright © 2016 Elsevier B.V. All rights reserved.

The clinical outcomes of deep gray matter injury in children with cerebral palsy in relation with brain magnetic resonance imaging.

PubMed

Choi, Ja Young; Choi, Yoon Seong; Rha, Dong-Wook; Park, Eun Sook

2016-08-01

In the present study we investigated the nature and extent of clinical outcomes using various classifications and analyzed the relationship between brain magnetic resonance imaging (MRI) findings and the extent of clinical outcomes in children with cerebral palsy (CP) with deep gray matter injury. The deep gray matter injuries of 69 children were classified into hypoxic ischemic encephalopathy (HIE) and kernicterus patterns. HIE patterns were divided into four groups (I-IV) based on severity. Functional classification was investigated using the gross motor function classification system-expanded and revised, manual ability classification system, communication function classification system, and tests of cognitive function, and other associated problems. The severity of HIE pattern on brain MRI was strongly correlated with the severity of clinical outcomes in these various domains. Children with a kernicterus pattern showed a wide range of clinical outcomes in these areas. Children with severe HIE are at high risk of intellectual disability (ID) or epilepsy and children with a kernicterus pattern are at risk of hearing impairment and/or ID. Grading severity of HIE pattern on brain MRI is useful for predicting overall outcomes. The clinical outcomes of children with a kernicterus pattern range widely from mild to severe. Delineation of the clinical outcomes of children with deep gray matter injury, which are a common abnormal brain MRI finding in children with CP, is necessary. The present study provides clinical outcomes for various domains in children with deep gray matter injury on brain MRI. The deep gray matter injuries were divided into two major groups; HIE and kernicterus patterns. Our study showed that severity of HIE pattern on brain MRI was strongly associated with the severity of impairments in gross motor function, manual ability, communication function, and cognition. These findings suggest that severity of HIE pattern can be useful for predicting the severity of impairments. Conversely, children with a kernicterus pattern showed a wide range of clinical outcomes in various domains. Children with severe HIE pattern are at high risk of ID or epilepsy and children with kernicterus pattern are at risk of hearing impairment or ID. The strength of our study was the assessment of clinical outcomes after 3 years of age using standardized classification systems in various domains in children with deep gray matter injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Cultures of Contemporary Instructional Design Scholarship, Part One: Developments Based on Behavioral and Cognitive Science Foundations

ERIC Educational Resources Information Center

Willis, Jerry

2011-01-01

This is the first in a series of two articles examining the current status of instructional design (ID) scholarship and theory in four different cultures or traditions. In this article, the focus is on, first, ID models based on traditional behavioral theories of learning and, second, on models based on cognitive science and the learning sciences.…

Iron nutrition and premenopausal women: effects of poor iron status on physical and neuropsychological performance.

PubMed

McClung, James P; Murray-Kolb, Laura E

2013-01-01

Iron is a nutritionally essential trace element that functions through incorporation into proteins and enzymes, many of which contribute to physical and neuropsychological performance. Poor iron status, including iron deficiency (ID; diminished iron stores) and iron deficiency anemia (IDA; poor iron stores and diminished hemoglobin), affects billions of people worldwide. This review focuses on physical and neuropsychological outcomes associated with ID and IDA in premenopausal women, as the prevalence of ID and IDA is often greater in premenopausal women than other population demographics. Recent studies addressing the physiological effects of poor iron status on physical performance, including work productivity, voluntary activity, and athletic performance, are addressed. Similarly, the effects of iron status on neurological performance, including cognition, affect, and behavior, are summarized. Nutritional countermeasures for the prevention of poor iron status and the restoration of decrements in performance outcomes are described.

A Rubric for Extracting Idea Density from Oral Language Samples

PubMed Central

Chand, Vineeta; Baynes, Kathleen; Bonnici, Lisa M.; Farias, Sarah Tomaszewski

2012-01-01

While past research has demonstrated that low idea density (ID) scores from natural language samples correlate with late life risk for cognitive decline and Alzheimer’s disease pathology, there are no published rubrics for collecting and analyzing language samples for idea density to verify or extend these findings into new settings. This paper outlines the history of ID research and findings, discusses issues with past rubrics, and then presents an operationalized method for the systematic measurement of ID in language samples, with an extensive manual available as a supplement to this article (Analysis of Idea Density, AID). Finally, reliability statistics for this rubric in the context of dementia research on aging populations and verification that AID can replicate the significant association between ID and late life cognition are presented. PMID:23042498

Cognitive shifting and externalising problem behaviour in intellectual disability and autism spectrum disorder.

PubMed

Visser, E M; Berger, H J C; Van Schrojenstein Lantman-De Valk, H M J; Prins, J B; Teunisse, J P

2015-08-01

Behavioural problems are frequently reported in residential care for people with an intellectual disability (ID) in particular when they are additionally diagnosed with autism spectrum disorder (ASD). There are indications that impairment in cognitive shifting may be associated with problem behaviour. The objectives of this study were (1) to examine the relationship of cognitive shifting and severity of ASD symptoms with externalising problem behaviour in individuals with ID, with and without ASD, and (2) to examine whether a diagnosis based on shifting impairment is more predictive of externalising problem behaviour than an ASD diagnosis. Participants consisted of adolescents and young adults with mild ID, with and without ASD (n = 41). Pearson intercorrelations were computed to explore the relationship between shifting impairment and severity of ASD symptoms on the one hand and ratings of externalising problem behaviour on the other hand. t-Tests were performed to analyse differences in externalising problem behaviour. Unlike ASD symptom severity, shifting scores were found to be associated with externalising problem behaviour, but only if shifting was measured using rating scales and not when using neuropsychological tasks. Externalising problem behaviour scores significantly differed when groups were classified according to shifting impairment (impaired vs. non-impaired) but not when they were classified according to ID and ASD diagnoses. It is proposed to use a cognition-based approach when analysing problem behaviour, thus concentrating not so much on ID and ASD diagnosis and their corresponding symptoms, but rather placing the focus on cognitive symptoms. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

A Qualitative Investigation of Fifth- and Sixth-Grade Students' Attitudes towards Intellectual Disability

ERIC Educational Resources Information Center

Beaulieu-Bergeron, Rebecca; Morin, Diane

2016-01-01

Research suggests that attitudes of typically developing children towards intellectual disability (ID) play an important role in the social integration and acceptance of children with IDs. To date, however, few studies have investigated children's attitudes towards ID. The primary objective of this study was to examine the cognitive, affective,…

Exploring the Relations between In-Service Training, Prior Contacts and Teachers' Attitudes towards Persons with Intellectual Disability

ERIC Educational Resources Information Center

Sermier Dessemontet, Rachel; Morin, Diane; Crocker, Anne G.

2014-01-01

This study investigates the relations between teachers' attitudes towards persons with intellectual disability (ID), in-service training on ID, and prior contacts with persons with ID. A sample of Canadian elementary school teachers (N?=?118) completed the Attitudes Toward Intellectual Disability Questionnaire, which measures cognitive, affective…

Down syndrome: Cognitive and behavioral functioning across the lifespan.

PubMed

Grieco, Julie; Pulsifer, Margaret; Seligsohn, Karen; Skotko, Brian; Schwartz, Alison

2015-06-01

Individuals with Down syndrome (DS) commonly possess unique neurocognitive and neurobehavioral profiles that emerge within specific developmental periods. These profiles are distinct relative to others with similar intellectual disability (ID) and reflect underlying neuroanatomic findings, providing support for a distinctive phenotypic profile. This review updates what is known about the cognitive and behavioral phenotypes associated with DS across the lifespan. In early childhood, mild deviations from neurotypically developing trajectories emerge. By school-age, delays become pronounced. Nonverbal skills remain on trajectory for mental age, whereas verbal deficits emerge and persist. Nonverbal learning and memory are strengths relative to verbal skills. Expressive language is delayed relative to comprehension. Aspects of language skills continue to develop throughout adolescence, although language skills remain compromised in adulthood. Deficits in attention/executive functions are present in childhood and become more pronounced with age. Characteristic features associated with DS (cheerful, social nature) are personality assets. Children are at a lower risk for psychopathology compared to other children with ID; families report lower levels of stress and a more positive outlook. In youth, externalizing behaviors may be problematic, whereas a shift toward internalizing behaviors emerges with maturity. Changes in emotional/behavioral functioning in adulthood are typically associated with neurodegeneration and individuals with DS are higher risk for dementia of the Alzheimer's type. Individuals with DS possess many unique strengths and weaknesses that should be appreciated as they develop across the lifespan. Awareness of this profile by professionals and caregivers can promote early detection and support cognitive and behavioral development. © 2015 Wiley Periodicals, Inc.

Iron status of military personnel deployed to Afghanistan.

PubMed

Wilson, Candy; McClung, James P; Karl, J Philip; Brothers, Michael D

2011-12-01

Iron is a micronutrient necessary for energy metabolism and for oxygen transport and delivery. Depletion of iron stores (iron deficiency [ID]) may lead to iron deficiency anemia (IDA), which affects mood, cognitive function, and physical performance. Previous studies indicated that iron status may decline during military training. This study assessed the iron status and prevalence of ID and IDA in military personnel deployed to Bagram Air Base, Afghanistan (1492 m). Within the pool of 294 participants (149 male and 145 female), 2 males (1%) and 8 females (6%) presented with ID. Although IDA was not observed in males, 3 females (2%) met the criteria for IDA. Female sex (p = 0.05) and self-reported history of anemia (p < 0.05) were associated with diminished iron status. Amenorrhea was associated with higher ferritin (p < 0.05) and hemoglobin (p < 0.05) levels. Although ID and IDA did not affect a large portion of the deployed population assessed in this study, findings suggest that risk factors including female sex, history of anemia, and regular menstruation should be considered in the assessment of iron status in military personnel.

Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires.

PubMed

Fischer, Anja; Fischer, Marcus; Nicholls, Robert A; Lau, Stephanie; Poettgen, Jana; Patas, Kostas; Heesen, Christoph; Gold, Stefan M

2015-09-01

Multiple sclerosis and major depressive disorder frequently co-occur but depression often remains undiagnosed in this population. Self-rated depression questionnaires are a good option where clinician-based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self-report measures for depression in multiple sclerosis (MS). Moreover, head-to-head comparisons of common questionnaires are largely lacking. This could be particularly relevant for high-risk patients with depressive symptoms. Here, we compare the diagnostic accuracy of the Beck Depression Inventory (BDI) and 30-item version of the Inventory of Depressive Symptomatology Self-Rated (IDS-SR30) for major depressive disorder (MSS) against diagnosis by a structured clinical interview. Patients reporting depressive symptoms completed the BDI, the IDS-SR30 and underwent diagnostic assessment (Mini International Neuropsychiatric Interview, M.I.N.I.). Receiver-Operating Characteristic analyses were performed, providing error estimates and false-positive/negative rates of suggested thresholds. Data from n = 31 MS patients were available. BDI and IDS-SR30 total score were significantly correlated (r = 0.82). The IDS-SR30total score, cognitive subscore, and BDI showed excellent to good accuracy (area under the curve (AUC) 0.86, 0.91, and 0.85, respectively). Both the IDS-SR30 and the BDI are useful to quantify depressive symptoms showing good sensitivity and specificity. The IDS-SR30 cognitive subscale may be useful as a screening tool and to quantify affective/cognitive depressive symptomatology.

Apolipoprotein e4 Is Associated with More Rapid Decline in Odor Identification than in Odor Threshold or Dementia Rating Scale Scores

ERIC Educational Resources Information Center

Calhoun-Haney, R.; Murphy, C.

2005-01-01

Individuals with the apolipoprotein E e4 genetic risk factor for Alzheimer's disease (AD) show deficits in olfactory function. The purpose of the present study was to examine longitudinally odor identification (odor ID), odor threshold, picture identification, and global cognitive status in allele positive (e4+) and negative (e4-) persons.…

A structured physical activity and fitness programme for older adults with intellectual disabilities: results of a cluster-randomised clinical trial.

PubMed

van Schijndel-Speet, M; Evenhuis, H M; van Wijck, R; van Montfort, K C A G M; Echteld, M A

2017-01-01

The physical activity level of older adults with intellectual disabilities (ID) is extremely low, and their fitness levels are far beneath accepted norms for older people with normal intelligence and comparable with frail older people. A physical activity programme, including an education programme, was developed for older adults with ID using behaviour change techniques. The programme aimed at improving or maintaining adequate levels of physical activity (primary outcome measure) and motor fitness, cardio respiratory fitness, morphologic and metabolic fitness, activities of daily living, cognitive functioning and depressive symptoms (secondary outcome measures). The programme's efficacy was evaluated in a cluster-randomised clinical trial among people aged 43 years and over with mild-moderate levels of ID. Five day-activity centres were randomised to the participation group. In these centres, 81 older adults participated in groups of 8 to 10 in the programme, three times a week during 8 months. The programme was executed by physical activity instructors and staff of day-activity centres. Five other day-activity centres were randomised to the control group; 70 older adults in these centres received care as usual. The generalised linear model with mixed effects was used to test the programme's effectiveness. Significant effects were found on physical activity, muscle strength, systolic and diastolic blood pressure, serum cholesterol level and cognitive functioning, in favour of the programme's participants. No significant improvements were found on balance, serum glucose, weight, waist circumference, walking speed, mobility, depression or instrumental activities of daily living. The physical activity and fitness programme has established small but significant effects in this sample, but generalising the findings to other settings is difficult due to significant participant dropout. Implementation of evidence-based physical activity programmes among older adults with ID is recommended. Further research is needed to investigate the effectiveness of physical activity on daily life functioning and the development on chronic diseases in the long run. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Infant behavioral responses to infant-directed singing and other maternal interactions.

PubMed

de l'Etoile, Shannon K

2006-07-01

Seventy, 6-9-month-old infants were videotaped during six interactions: mother sings assigned song, "stranger" sings assigned song, mother sings song of choice, mother reads book, mother plays with toy, and mother and infant listen to recorded music. Infant-directed (ID) singing conditions elicited moderately positive cognitive behavior, low levels of positive physical behavior and minimal amounts of vocal behaviors, mostly negative. Across all conditions, cognitive scores remained positive at low to moderate levels. Physical responses were most positive during book and toy, most negative during recorded music, and differed by gender, especially during ID singing. Vocally, infants responded positively to toy, and 8-month-old infants vocalized more than younger infants, particularly during ID singing conditions. ID singing appears just as effective as book reading or toy play in sustaining infant attention and far more effective than listening to recorded music, while interactions involving objects may provide opportunity for shared attention.

Development and Psychometric Properties of an Assessment for Persons with Intellectual Disability--The InterRAI ID

ERIC Educational Resources Information Center

Martin, Lynn; Hirdes, John P.; Fries, Brant E.; Smith, Trevor F.

2007-01-01

This paper describes the development of the interRAI-Intellectual Disability (interRAI ID), a comprehensive instrument that assesses all key domains of interest to service providers relative to a person with an intellectual disability (ID). The authors report on the reliability and validity of embedded scales for cognition, self-care, aggression,…

Cognitive Behavioral Therapy for Depressed Adults with Mild Intellectual Disability: A Pilot Study

ERIC Educational Resources Information Center

Hartley, Sigan L.; Esbensen, Anna J.; Shalev, Rebecca; Vincent, Lori B.; Mihaila, Iulia; Bussanich, Paige

2015-01-01

There is a paucity of research on psychosocial treatments for depression in adults with intellectual disability (ID). In this pilot study, we explored the efficacy of a group CBT treatment that involved a caregiver component in adults with mild ID with a depressive disorder. Sixteen adults with mild ID and a depressive disorder participated in a…

Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires

PubMed Central

Fischer, Anja; Fischer, Marcus; Nicholls, Robert A; Lau, Stephanie; Poettgen, Jana; Patas, Kostas; Heesen, Christoph; Gold, Stefan M

2015-01-01

Objective Multiple sclerosis and major depressive disorder frequently co-occur but depression often remains undiagnosed in this population. Self-rated depression questionnaires are a good option where clinician-based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self-report measures for depression in multiple sclerosis (MS). Moreover, head-to-head comparisons of common questionnaires are largely lacking. This could be particularly relevant for high-risk patients with depressive symptoms. Here, we compare the diagnostic accuracy of the Beck Depression Inventory (BDI) and 30-item version of the Inventory of Depressive Symptomatology Self-Rated (IDS-SR30) for major depressive disorder (MSS) against diagnosis by a structured clinical interview. Methods Patients reporting depressive symptoms completed the BDI, the IDS-SR30 and underwent diagnostic assessment (Mini International Neuropsychiatric Interview, M.I.N.I.). Receiver-Operating Characteristic analyses were performed, providing error estimates and false-positive/negative rates of suggested thresholds. Results Data from n = 31 MS patients were available. BDI and IDS-SR30 total score were significantly correlated (r = 0.82). The IDS-SR30total score, cognitive subscore, and BDI showed excellent to good accuracy (area under the curve (AUC) 0.86, 0.91, and 0.85, respectively). Conclusion Both the IDS-SR30 and the BDI are useful to quantify depressive symptoms showing good sensitivity and specificity. The IDS-SR30 cognitive subscale may be useful as a screening tool and to quantify affective/cognitive depressive symptomatology. PMID:26445703

Executive functions and Prader-Willi syndrome: global deficit linked with intellectual level and syndrome-specific associations.

PubMed

Chevalère, Johann; Postal, Virginie; Jauregui, Joseba; Copet, Pierre; Laurier, Virginie; Thuilleaux, Denise

2015-05-01

The aim of this study was to support the growing evidence suggesting that Prader-Willi Syndrome (PWS) might present with an impairment of executive functions (EFs) and to investigate whether this impairment is specific to patients with PWS or due to their intellectual disability (ID). Six tasks were administered to assess EFs (inhibition, switching, updating, cognitive estimation, and planning) to 17 patients with PWS and 17 age-matched healthy individuals. Performance was significantly impaired in the PWS group on all EFs and after controlling for IQ level, intergroup differences remained only for switching and cognitive estimation. In conclusion, PWS seems to be associated with a global impairment of EFs that appears to be closely linked with intellectual impairment but also with the PWS itself.

Assessing theory of mind nonverbally in those with intellectual disability and ASD: the penny hiding game.

PubMed

San José Cáceres, Antonia; Keren, Noa; Booth, Rhonda; Happé, Francesca

2014-10-01

Individuals with autism spectrum disorder (ASD) and low intellectual/language abilities are often omitted from experimental studies because of the challenges of testing these individuals. It is vital to develop appropriate and accessible tasks so that this significant part of the spectrum is not neglected. The theory of mind (ToM) has been extensively assessed in ASD, predominantly in relatively high-functioning individuals with reasonable language skills. This study aims to assess the ToM abilities of a sample of 132 participants with intellectual disability (ID) with and without ASD, matched in verbal mental age (VMA) and chronological age, using a naturalistic and nonverbal deception task: the Penny Hiding Game (PHG). The relationship between performance on the PHG and everyday adaptation was also studied. The PHG proved accessible to most participants, suggesting its suitability for use with individuals with low cognitive skills, attentional problems, and limited language. The ASD + ID group showed significantly more PHG errors, and fewer tricks, than the ID group. PHG performance correlated with Vineland adaptation scores for both groups. VMA was a major predictor of passing the task in both groups, and participants with ASD + ID required, on average, 2 years higher VMA than those with ID only, to achieve the same level of PHG success. VMA moderated the association between PHG performance and real-life social skills for the ASD + ID more than the ID group, suggesting that severely impaired individuals with ASD may rely on verbal ability to overcome their social difficulties, whereas individuals with ID alone may use more intuitive social understanding both in the PHG and everyday situations. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations

PubMed Central

Gardiner, Katheleen J

2015-01-01

Down syndrome (DS), also known as trisomy 21, is the most common genetic cause of intellectual disability (ID). Although ID can be mild, the average intelligence quotient is in the range of 40–50. All individuals with DS will also develop the neuropathology of Alzheimer’s disease (AD) by the age of 30–40 years, and approximately half will display an AD-like dementia by the age of 60 years. DS is caused by an extra copy of the long arm of human chromosome 21 (Hsa21) and the consequent elevated levels of expression, due to dosage, of trisomic genes. Despite a worldwide incidence of one in 700–1,000 live births, there are currently no pharmacological treatments available for ID or AD in DS. However, over the last several years, very promising results have been obtained with a mouse model of DS, the Ts65Dn. A diverse array of drugs has been shown to rescue, or partially rescue, DS-relevant deficits in learning and memory and abnormalities in cellular and electrophysiological features seen in the Ts65Dn. These results suggest that some level of amelioration or prevention of cognitive deficits in people with DS may be possible. Here, we review information from the preclinical evaluations in the Ts65Dn, how drugs were selected, how efficacy was judged, and how outcomes differ, or not, among studies. We also summarize the current state of human clinical trials for ID and AD in DS. Lastly, we describe the genetic limitations of the Ts65Dn as a model of DS, and in the preclinical testing of pharmacotherapeutics, and suggest additional targets to be considered for potential pharmacotherapies. PMID:25552901

A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family

PubMed Central

Sheereen, Atia; Alaamery, Manal; Bawazeer, Shahad; Al Yafee, Yusra; Massadeh, Salam; Eyaid, Wafaa

2017-01-01

Background Autosomal-recessive non-syndromic intellectual disability (ARNS-ID) is an aetiologically heterogeneous disorder. Although little is known about the function of human cereblon (CRBN), its relationship to mild cognitive deficits suggests that it is involved in the basic processes of human memory and learning. Objectives We aim to identify the genetic cause of intellectual disability and self-mutilation in a consanguineous Saudi family with five affected members. Methods Clinical whole-exome sequencing was performed on the proband patient, and Sanger sequencing was done to validate and confirm segregation in other family members. Results A missense variant (c. 1171T>C) in the CRBN gene was identified in five individuals with severe intellectual disability (ID) in a consanguineous Saudi family. The homozygous variant was co-segregating in the family with the phenotype of severe ID, seizures and self-mutilating behaviour. The missense mutation (p.C391R) reported here results in the replacement of a conserved cysteine residue by an arginine in the CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide) domain of CRBN, which contains a zinc-binding site. Conclusions These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to ARNS-ID and provide new insight into genotype–phenotype correlations between CRBN mutations and the aetiology of ARNS-ID. PMID:28143899

"Intellectual developmental disorders": reflections on the international consensus document for redefining "mental retardation-intellectual disability" in ICD-11.

PubMed

Bertelli, Marco O; Munir, Kerim; Harris, James; Salvador-Carulla, Luis

The debate as to whether intellectual disability (ID) should be conceptualized as a health condition or as a disability has intensified as the revision of World Health Organization's (WHO's) International Classification of Diseases (ICD) is being finalized. Defining ID as a health condition is central to retaining it in ICD, with significant implications for health policy and access to health services. The purpose of this paper is to include some reflections on the consensus document produced by the first WHO Working Group on the Classification of MR (WHO WG-MR) and on the process that was followed to realize it. The consensus report was the basis for the development of official recommendations sent to the WHO Advisory Group for ICD-11. A mixed qualitative approach was followed in a series of meetings leading to the final consensus report submitted to the WHO Advisory group. These recommendations combined prior expert knowledge with available evidence; a nominal approach was followed throughout with face-to-face conferences. The WG recommended a synonym set ("synset") ontological approach to the conceptualisation of this health condition underlying a clinical rationale for its diagnosis. It proposed replacing MR with Intellectual Developmental Disorders (IDD) in ICD-11, defined as "a group of developmental conditions characterized by a significant impairment of cognitive functions, which are associated with limitations of learning, adaptive behaviour and skills". The WG further advised that IDD be included under the parent category of neurodevelopmental disorders, that current distinctions (mild, moderate, severe and profound) be continued as severity qualifiers, and that problem behaviours removed from its core classification structure and instead described as associated features. Within the ID/IDD synset two different names combine distinct aspects under a single construct that describes its clinical as well as social, educational and policy utilities. The single construct incorporates IDD as a clinical meta-syndrome, and ID as its functioning and disability counterpart. IDD and ID are not synonymous or mirror concepts as they have different scientific, social and policy applications. New diagnostic criteria for IDD should be based on a developmental approach, which accounts for the complex causal factors known to impact the acquisition of specific cognitive abilities and adaptive behaviours. The paper focuses on a new clinical framework for the diagnosis of IDD that also includes and complements the existing social, educational and policy components inherent in ID.

“Intellectual developmental disorders”: reflections on the international consensus document for redefining “mental retardation-intellectual disability” in ICD-11

PubMed Central

Bertelli, Marco O.; Munir, Kerim; Harris, James; Salvador-Carulla, Luis

2016-01-01

Purpose The debate as to whether intellectual disability (ID) should be conceptualized as a health condition or as a disability has intensified as the revision of World Health Organization’s (WHO’s) International Classification of Diseases (ICD) is being finalized. Defining ID as a health condition is central to retaining it in ICD, with significant implications for health policy and access to health services. The purpose of this paper is to include some reflections on the consensus document produced by the first WHO Working Group on the Classification of MR (WHO WG-MR) and on the process that was followed to realize it. The consensus report was the basis for the development of official recommendations sent to the WHO Advisory Group for ICD-11. Design/methodology/approach A mixed qualitative approach was followed in a series of meetings leading to the final consensus report submitted to the WHO Advisory group. These recommendations combined prior expert knowledge with available evidence; a nominal approach was followed throughout with face-to-face conferences. Findings The WG recommended a synonym set (“synset”) ontological approach to the conceptualisation of this health condition underlying a clinical rationale for its diagnosis. It proposed replacing MR with Intellectual Developmental Disorders (IDD) in ICD-11, defined as “a group of developmental conditions characterized by a significant impairment of cognitive functions, which are associated with limitations of learning, adaptive behaviour and skills”. The WG further advised that IDD be included under the parent category of neurodevelopmental disorders, that current distinctions (mild, moderate, severe and profound) be continued as severity qualifiers, and that problem behaviours removed from its core classification structure and instead described as associated features. Originality/value Within the ID/IDD synset two different names combine distinct aspects under a single construct that describes its clinical as well as social, educational and policy utilities. The single construct incorporates IDD as a clinical meta-syndrome, and ID as its functioning and disability counterpart. IDD and ID are not synonymous or mirror concepts as they have different scientific, social and policy applications. New diagnostic criteria for IDD should be based on a developmental approach, which accounts for the complex causal factors known to impact the acquisition of specific cognitive abilities and adaptive behaviours. The paper focuses on a new clinical framework for the diagnosis of IDD that also includes and complements the existing social, educational and policy components inherent in ID. PMID:27066217

Intellectual Disabilities and Hearing Loss

ERIC Educational Resources Information Center

Herer, Gilbert R.

2012-01-01

Undetected/untreated hearing loss imposes significant limitations upon individuals with intellectual disabilities (ID). It can interfere with cognitive development, impede communicative and social interactions, and limit vocational aspirations. Over the past decade, the hearing of 9961 people with ID was evaluated at Special Olympics sports…

Benefits of extending and adjusting the level of difficulty on computerized cognitive training for children with intellectual disabilities.

PubMed

Ottersen, Jon; Grill, Katja M

2015-01-01

Training on working memory (WM) improves attention and WM in children with attention-deficit hyperactivity disorder and memory impairments. However, for children with intellectual disabilities (ID), the results have been less encouraging. In this preliminary study it was hypothesized that children with ID would benefit from an extended amount of training and that the level of difficulty during training would affect the outcome. We included 21 children with mild or moderate ID aged 8-13 years. They went through between 37 and 50 training sessions with an adaptive computerized program on WM and non-verbal reasoning (NVR). The children were divided into two subgroups with different difficulty levels during training. The transfer to untrained cognitive tests was compared to the results of 22 children with ID training only 25 sessions, and to a control group. We found that the training group with the extended training program improved significantly on a block design task measuring NVR and on a WM task compared to the control group. There was also a significantly larger improvement on block design relative to the training group with the shorter training time. The children that received easier training tasks also improved significantly more on a verbal WM task compared to children with more demanding tasks. In conclusion, these preliminary data suggest that children with ID might benefit from cognitive training with longer training periods and less demanding tasks, compared to children without disabilities.

Cognitive and linguistic predictors of reading comprehension in children with intellectual disabilities.

PubMed

van Wingerden, Evelien; Segers, Eliane; van Balkom, Hans; Verhoeven, Ludo

2014-11-01

A considerable number of children with intellectual disabilities (ID) are able to acquire basic word reading skills. However, not much is known about their achievements in more advanced reading comprehension skills. In the present study, a group of 49 children with ID and a control group of 21 typically developing children with word decoding skills in the normal ranges of first grade were compared in lower level (explicit meaning) and higher level (implicit meaning) reading comprehension abilities. Moreover, in the group of children with ID it was examined to what extent their levels of lower level and higher level reading comprehension could be predicted from their linguistic skills (word decoding, vocabulary, language comprehension) and cognitive skill (nonverbal reasoning). It was found that children with ID were weaker than typically developing children in higher level reading comprehension but not in lower level reading comprehension. Children with ID also performed below the control group on nonverbal reasoning and language comprehension. After controlling for nonverbal reasoning, linguistic skills predicted lower level reading comprehension but not higher level reading comprehension. It can be concluded that children with ID who have basic decoding skill do reasonably well on lower level reading comprehension but continue to have problems with higher level reading comprehension. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rehabilitation of traumatic brain injury in active duty military personnel and veterans: Defense and Veterans Brain Injury Center randomized controlled trial of two rehabilitation approaches.

PubMed

Vanderploeg, Rodney D; Schwab, Karen; Walker, William C; Fraser, Jamie A; Sigford, Barbara J; Date, Elaine S; Scott, Steven G; Curtiss, Glenn; Salazar, Andres M; Warden, Deborah L

2008-12-01

To determine the relative efficacy of 2 different acute traumatic brain injury (TBI) rehabilitation approaches: cognitive didactic versus functional-experiential, and secondarily to determine relative efficacy for different patient subpopulations. Randomized, controlled, intent-to-treat trial comparing 2 alternative TBI treatment approaches. Four Veterans Administration acute inpatient TBI rehabilitation programs. Adult veterans or active duty military service members (N=360) with moderate to severe TBI. One and a half to 2.5 hours of protocol-specific cognitive-didactic versus functional-experiential rehabilitation therapy integrated into interdisciplinary acute Commission for Accreditation of Rehabilitation Facilities-accredited inpatient TBI rehabilitation programs with another 2 to 2.5 hours daily of occupational and physical therapy. Duration of protocol treatment varied from 20 to 60 days depending on the clinical needs and progress of each participant. The 2 primary outcome measures were functional independence in living and return to work and/or school assessed by independent evaluators at 1-year follow-up. Secondary outcome measures consisted of the FIM, Disability Rating Scale score, and items from the Present State Exam, Apathy Evaluation Scale, and Neurobehavioral Rating Scale. The cognitive-didactic and functional-experiential treatments did not result in overall group differences in the broad 1-year primary outcomes. However, analysis of secondary outcomes found differentially better immediate posttreatment cognitive function (mean+/-SD cognitive FIM) in participants randomized to cognitive-didactic treatment (27.3+/-6.2) than to functional treatment (25.6+/-6.0, t332=2.56, P=.01). Exploratory subgroup analyses found that younger participants in the cognitive arm had a higher rate of returning to work or school than younger patients in the functional arm, whereas participants older than 30 years and those with more years of education in the functional arm had higher rates of independent living status at 1 year posttreatment than similar patients in the cognitive arm. Results from this large multicenter randomized controlled trial comparing cognitive-didactic and functional-experiential approaches to brain injury rehabilitation indicated improved but similar long-term global functional outcome. Participants in the cognitive treatment arm achieved better short-term functional cognitive performance than patients in the functional treatment arm. The current increase in war-related brain injuries provides added urgency for rigorous study of rehabilitation treatments. (http://ClinicalTrials.gov ID# NCT00540020.).

Functional abilities and cognitive decline in adult and aging intellectual disabilities. Psychometric validation of an Italian version of the Alzheimer's Functional Assessment Tool (AFAST): analysis of its clinical significance with linear statistics and artificial neural networks.

PubMed

De Vreese, L P; Gomiero, T; Uberti, M; De Bastiani, E; Weger, E; Mantesso, U; Marangoni, A

2015-04-01

(a) A psychometric validation of an Italian version of the Alzheimer's Functional Assessment Tool scale (AFAST-I), designed for informant-based assessment of the degree of impairment and of assistance required in seven basic daily activities in adult/elderly people with intellectual disabilities (ID) and (suspected) dementia; (b) a pilot analysis of its clinical significance with traditional statistical procedures and with an artificial neural network. AFAST-I was administered to the professional caregivers of 61 adults/seniors with ID with a mean age (± SD) of 53.4 (± 7.7) years (36% with Down syndrome). Internal consistency (Cronbach's α coefficient), inter/intra-rater reliabilities (intra-class coefficients, ICC) and concurrent, convergent and discriminant validity (Pearson's r coefficients) were computed. Clinical significance was probed by analysing the relationships among AFAST-I scores and the Sum of Cognitive Scores (SCS) and the Sum of Social Scores (SOS) of the Dementia Questionnaire for Persons with Intellectual Disabilities (DMR-I) after standardisation of their raw scores in equivalent scores (ES). An adaptive artificial system (AutoContractive Maps, AutoCM) was applied to all the variables recorded in the study sample, aimed at uncovering which variable occupies a central position and supports the entire network made up of the remaining variables interconnected among themselves with different weights. AFAST-I shows a high level of internal homogeneity with a Cronbach's α coefficient of 0.92. Inter-rater and intra-rater reliabilities were also excellent with ICC correlations of 0.96 and 0.93, respectively. The results of the analyses of the different AFAST-I validities all go in the expected direction: concurrent validity (r=-0.87 with ADL); convergent validity (r=0.63 with SCS; r=0.61 with SOS); discriminant validity (r=0.21 with the frequency of occurrence of dementia-related Behavioral Excesses of the Assessment for Adults with Developmental Disabilities, AADS-I). In our sample age and gender do not correlate with the scale and comparing the distribution of the AFAST-I and DMR-SCS and DMR-SOS expressed as ES, it appears that memory disorders and temporal and spatial disorientation (SCS) precede the loss of functional abilities, whereas changes in social behaviour (SOS) are less specific in detecting cognitive deterioration sufficient to provoke functional disability and vice versa. The results of AutoCM analysis reveal that the hub (core) of the entire network is represented by the functional domain 'personal/oral hygiene' in the entire study sample and 'use of toilet' in a subgroup of subjects who obtained an ES equal to 0 at DMR-SCS. These results confirm the reliability and validity of AFAST-I and emphasise the complexity of the relationship among functional status, cognitive functioning and behaviour also in adults/seniors with ID. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Cognitive Phenotype of Velocardiofacial Syndrome: A Review

ERIC Educational Resources Information Center

Furniss, Frederick; Biswas, Asit B.; Gumber, Rohit; Singh, Niraj

2011-01-01

The behavioural phenotype of velocardiofacial syndrome (VCFS), one of the most common human multiple anomaly syndromes, includes developmental disabilities, frequently including intellectual disability (ID) and high risk of diagnosis of psychotic disorders including schizophrenia. VCFS may offer a model of the relationship between ID and risk of…

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

PubMed

Massee, Laura A; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

2015-01-01

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered.

Biallelic missense variants in ZBTB11 can cause intellectual disability in human.

PubMed

Fattahi, Zohreh; Sheikh, Taimoor I; Musante, Luciana; Rasheed, Memoona; Taskiran, Ibrahim Ihsan; Harripaul, Ricardo; Hu, Hao; Kazeminasab, Somayeh; Alam, Muhammad Rizwan; Hosseini, Masoumeh; Larti, Farzaneh; Ghaderi, Zhila; Celik, Arzu; Ayub, Muhammad; Ansar, Muhammad; Haddadi, Mohammad; Wienker, Thomas F; Ropers, Hans Hilger; Kahrizi, Kimia; Vincent, John B; Najmabadi, H

2018-06-08

Exploring genes and pathways underlying Intellectual Disability (ID) provides insight into brain development and function, clarifying the complex puzzle of how cognition develops. As part of ongoing systematic studies to identify candidate ID genes, linkage analysis and next generation sequencing revealed ZBTB11, as a novel candidate ID gene. ZBTB11 encodes a less-studied transcription regulator and the two identified missense variants in this study may disrupt canonical Zn2+-binding residues of its C2H2 zinc finger domain, leading to possible altered DNA binding. Using HEK293T cells transfected with wild type and mutant GFP-ZBTB11 constructs, we found the ZBTB11 mutants being excluded from the nucleolus, where the wild-type recombinant protein is predominantly localized. Pathway analysis applied to ChIP-seq data deposited in the ENCODE database supports the localization of ZBTB11 in nucleoli, highlighting associated pathways such as rRNA synthesis, ribosomal assembly, RNA modification, stress sensing and provides a direct link between subcellular ZBTB11 location and its function. Furthermore, considering the report of prominent brain and spinal cord degeneration in a zebrafish Zbtb11 mutant, we investigated ZBTB11-ortholog knockdown in Drosophila melanogaster brain by targeting RNAi using the UAS/Gal4 system. The observed approximate reduction to a third of the mushroom body size - possibly through neuronal reduction or degeneration - may affect neuronal circuits in the brain that are required for adaptive behavior, specifying the role of this gene in nervous system. In conclusion, we report two ID families segregating ZBTB11 biallelic mutations disrupting Zn2+-binding motifs, and provide functional evidence linking ZBTB11 dysfunction to this phenotype.

Mother-Child Interaction and Resilience in Children with Early Developmental Risk

PubMed Central

Fenning, Rachel M.; Baker, Jason K.

2014-01-01

Although prenatal and genetic factors make strong contributions to the emergence of intellectual disability (ID), children's early environment may have the potential to alter developmental trajectories and to foster resilience in children with early risk. The present study examined mother-child interaction and the promotion of competence in 50 children with early developmental delays. Three related but distinct aspects of mother-child interaction were considered: maternal technical scaffolding, maternal positive-sensitivity, and mother-child dyadic pleasure. Children were classified as exhibiting undifferentiated delays at age three based upon performance on developmental assessments and the absence of known genetic syndromes. Mother-child interaction was assessed at age four through observational ratings of structured laboratory tasks and through naturalistic home observations. ID was identified at age five using the dual criteria of clinically significant delays in cognitive functioning and adaptive behavior. Maternal technical scaffolding and dyadic pleasure each uniquely predicted reduced likelihood of later ID, beyond the contributions of children's early developmental level and behavioral functioning. Follow-up analyses suggested that mother-child interaction was primarily important to resilience in the area of adaptive behavior, with scaffolding and dyadic pleasure differentially associated with particular sub-domains. Implications for theories of intellectual disability and for family-based early intervention and prevention efforts are discussed. PMID:22662771

Iron deficiency is a key determinant of health-related quality of life in patients with chronic heart failure regardless of anaemia status.

PubMed

Comín-Colet, Josep; Enjuanes, Cristina; González, Gina; Torrens, Ainhoa; Cladellas, Mercè; Meroño, Oona; Ribas, Nuria; Ruiz, Sonia; Gómez, Miquel; Verdú, José Maria; Bruguera, Jordi

2013-10-01

To evaluate the effect of iron deficiency (ID) and/or anaemia on health-related quality of life (HRQoL) in patients with chronic heart failure (CHF). We undertook a post-hoc analysis of a cohort of CHF patients in a single-centre study evaluating cognitive function. At recruitment, patients provided baseline information and completed the Minnesota Living with Heart Failure questionnaire (MLHFQ) for HRQoL (higher scores reflect worse HRQoL). At the same time, blood samples were taken for serological evaluation. ID was defined as serum ferritin levels <100 ng/mL or serum ferritin <800 ng/mL with transferrin saturation <20%. Anaemia was defined as haemoglobin ≤12 g/dL. A total of 552 CHF patients were eligible for inclusion, with an average age of 72 years and 40% in NYHA class III or IV. The MLHFQ overall summary scores were 41.0 ± 24.7 among those with ID, vs. 34.4 ± 26.4 for non-ID patients (P = 0.003), indicating worse HRQoL. When adjusted for other factors associated with HRQoL, ID was significantly associated with worse MLHFQ overall summary (P = 0.008) and physical dimension scores (P = 0.002), whereas anaemia was not (both P > 0.05). Increased levels of soluble transferrin receptor were also associated with impaired HRQoL (P ≤ 0.001). Adjusting for haemoglobin and C-reactive protein, ID was more pronounced in patients with anaemia compared with those without (P < 0.001). In patients with CHF, ID but not anaemia was associated with reduced HRQoL, mostly due to physical factors.

Parenting stress in mothers of children with an intellectual disability: the effects of parental cognitions in relation to child characteristics and family support.

PubMed

Hassall, R; Rose, J; McDonald, J

2005-06-01

Recent theories of stress and coping in parents of children with intellectual disabilities (ID) emphasize the importance of cognitive appraisals in influencing parents' levels of stress and their adaptations to difficulties presented by the children. This study investigated the relationships between parental cognitions, child characteristics, family support and parenting stress. The aspects of cognitions studied were: parenting self-esteem (including efficacy and satisfaction) and parental locus of control. The group studied consisted of 46 mothers of children with ID. The Vineland Adaptive Behavior Scales and Maladaptive Behavior Domain were administered by interview. Mothers also completed four questionnaires: the Family Support Scale, the Parenting Sense of Competence Scale, a shortened form of the Parental Locus of Control Scale and the Parenting Stress Index (Short Form). Data were analysed using Pearson's correlation coefficients, partial correlations and a regression analysis. The results indicated that most of the variance in parenting stress was explained by parental locus of control, parenting satisfaction and child behaviour difficulties. Whilst there was also a strong correlation between family support and parenting stress, this was mediated by parental locus of control. The results demonstrate the potential importance of parental cognitions in influencing parental stress levels. It is argued that these results have implications for clinical interventions for promoting parents' coping strategies in managing children with ID and behavioural difficulties.

Sex differences in performance over 7 years on the Wechsler Intelligence Scale for Children--Revised among adults with intellectual disability.

PubMed

Kittler, P; Krinsky-McHale, S J; Devenny, D A

2004-02-01

The aim of this study was to explore changes related to sex differences on the Wechsler Intelligence Scale for Children - Revised (WISC-R) subtest performance over a 7-year interval in middle-aged adults with intellectual disability (ID). Cognitive sex differences have been extensively studied in the general population, but there are few reports concerning individuals with ID. Sex differences are of current relevance to actively debated issues such as cognitive changes during menopause and risk for Alzheimer's disease. Given that hormonal effects on cognition have been observed in the general population, particularly in areas such as visuospatial processing, and individuals with Down's syndrome (DS) have been reported to be hormonally and reproductively atypical, we analysed our data to allow for the possibility of an aetiology-specific profile of sex differences for these adults. The WISC-R subtests were administered in a longitudinal study, as part of a more comprehensive test battery, at least twice within 7 years. Participants were 18 females with ID without DS [age at first test time (time 1): mean = 40.5; IQ: mean = 59.3], 10 males with ID without DS (age at time 1: mean = 42.4; IQ: mean = 59.4), 21 females with DS (age at time 1: mean = 37.9; IQ: mean = 51.6), and 21 males with DS (age at time 1: mean = 40.3; IQ: mean = 54.3). All participants were in the mild to moderate range of ID and were displaying no changes suggestive of early dementia. Females, regardless of aetiology of ID, exhibited a robust superiority on the coding subtest, which parallels the widely reported difference among adults in the general population. Additionally, there was a decline in overall performance during the 7-year study interval, particularly on the verbal subscale subtests, but there was no evidence of sex-differentiated decline. There were also marginal sex by aetiology interactions on the object assembly and block design subtests, suggesting that males with unspecified ID might perform better than their female peers, but among adults with DS, females might do better than males. This study supports the presence of cognitive sex differences in the population with ID as indicated by female superiority on the WISC-R coding subtest. Extending this observation to adults with ID has implications for explanations of female advantage on this task, which now have to account for its presence among individuals with a broader range of intellectual capabilities, more atypical developmental histories and more varied genotypes than previously considered. Trends towards sex by aetiology interactions on the two visuoconstructive subtests, while marginal, were sufficient to warrant continued consideration of the idea of a distinct profile of sex differences for adults with DS and to justify looking at the effects of sex separately within different aetiologies of ID.

Perceptual-motor coordination in persons with mild intellectual disability.

PubMed

Carmeli, Eli; Bar-Yossef, Tamar; Ariav, Claudette; Levy, Ran; Liebermann, Dario G

2008-01-01

There is limited experimental evidence to support the view that individuals with intellectual disabilities (ID) have a deficit in motor control. This work is a first attempt to evaluate their motor coordination. The study assessed the relationship between cognitive ability and sensorimotor integration. The clinical hypothesis is that adults with ID fall below non-ID adults in motor skills that involve hand-eye coordination. A group of 42 adults with ID (ID group) was compared to 48 age-matched typical adults (TA) using a mixed experimental design ('Task' as the within-subjects factor and 'Group' as the between-subjects factor). Participants performed the following tests twice: Box-and-Blocks, 25-Grooved-Pegboard, Stick Catching and overhead Beanbag-Throw. Pearson correlations and ANOVAs were used to test the hypothesis (p < or = 0.05). As expected, TA outperformed the ID group in all tests regardless of the hand used during for the assessment. However, TA individuals scored significantly better with one hand (i.e., the preferred and dominant hand) as opposed to persons with ID, who exhibited no hand preference. Test-retest correlations among the first and second assessment scores yielded moderate-strong coefficients, depending on the type of test (Box-and-Blocks = 0.92 and 0.96, 25-Grooved-Pegboard = 0.69 and 0.83, Stick-Catching = 0.88 and 0.94, Beanbag-Throw = 0.58 and 0.91 for ID and TA, respectively). Difficulties in the integration of perceptual information into motor action may result in inadequate solutions to daily motor problems. As it stems from our results, intellectual disability relates to inability to integrate visual inputs and hand movements. In people with mild ID such inability is observed using both hands (i.e., they show no hand preferences). Poor perceptual-motor coordination might have a functional significance in that it may lead to exclusion from vocational and recreational activities, and a decreasing competence of ADL. Assessing coordination in adults with ID may contribute to understanding the nature of the ID condition and may encourage an early rehabilitation.

The implications of having attention-deficit/hyperactivity disorder in male adolescents with intellectual disability.

PubMed

Carmeli, Eli; Klein, Neomy; Sohn, Mordechai

2007-01-01

Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. The purpose of this study was to demonstrate a correlation between social skills and ADHD among adolescents with intellectual disabilities (ID). The study concerns the specific cognitive and adaptive skills of adolescents dually diagnosed with mild intellectual disabilities and comorbid pathology as ADHD. Three age-and IQ-match groups (males, n = 12 in each group) were investigated. Group I--composed of adolescent diagnosed with mild ID, group II--adolescents diagnosed with ADHD, and group III--adolescents diagnosed with ID and ADHD. The instruments used in the study were Wechsler Intelligence Scale for Children (WISC, according to the chronological age of the subjects) and the short version of the Developmental Behavior Checklist (DBC). Results confirm that comorbidity is a factor differentiating. ADHD strongly increased the impairment of social skills, while behavioral disorders were less damaging in ID performance. The WISC and DBC instruments should be used with confidence in clinical and service settings, to allow a better assessment of co-occurrence morbidity in adolescents with ID. The interactions between intellectual disability and psychopathology behavior highlight the need to plan a more accurate diagnosis and appropriate rehabilitative intervention program, essential for improving the quality of life of the ID population.

A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family.

PubMed

Sheereen, Atia; Alaamery, Manal; Bawazeer, Shahad; Al Yafee, Yusra; Massadeh, Salam; Eyaid, Wafaa

2017-04-01

Autosomal-recessive non-syndromic intellectual disability (ARNS-ID) is an aetiologically heterogeneous disorder. Although little is known about the function of human cereblon (CRBN), its relationship to mild cognitive deficits suggests that it is involved in the basic processes of human memory and learning. We aim to identify the genetic cause of intellectual disability and self-mutilation in a consanguineous Saudi family with five affected members. Clinical whole-exome sequencing was performed on the proband patient, and Sanger sequencing was done to validate and confirm segregation in other family members. A missense variant (c. 1171T>C) in the CRBN gene was identified in five individuals with severe intellectual disability (ID) in a consanguineous Saudi family. The homozygous variant was co-segregating in the family with the phenotype of severe ID, seizures and self-mutilating behaviour. The missense mutation (p.C391R) reported here results in the replacement of a conserved cysteine residue by an arginine in the CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide) domain of CRBN, which contains a zinc-binding site. These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to ARNS-ID and provide new insight into genotype-phenotype correlations between CRBN mutations and the aetiology of ARNS-ID. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Intelligence involves risk-awareness and intellectual disability involves risk-unawareness: implications of a theory of common sense.

PubMed

Greenspan, Stephen; Switzky, Harvey N; Woods, George W

2011-12-01

Survival in the everyday world (in both social and practical functioning) depends on one's ability to recognise and avoid going down the worst possible path, especially when doing so places one at risk of death, injury, or social disaster. Most people possess "common sense" (the ability to recognise obvious risk) but some people lack that ability and thus are at high risk of engaging in "foolish" (i.e., risk-unaware) action. People who have a cognitive impairment are much less able to recognise and avoid risk, and this is what causes them to be seen as needing protection and support. In this paper, we argue that the answer to the question "What is intellectual disability (ID)?" is more likely to come from the question "What is unintelligent behavior?" than "What is intelligence?" The answer which comes from such a question is that "ID is a common sense deficit disorder characterised by unawareness of obvious social and practical risk." Several implications of this answer are explored for the field of intellectual disability. These implications are explored primarily for adults who may have ID, given that the inspiration for this paper came from the way existing ID definitions are applied or misapplied in the US adult criminal justice system.

Cytogenetic Studies of Rwandan Pediatric Patients Presenting with Global Developmental Delay, Intellectual Disability and/or Multiple Congenital Anomalies

PubMed Central

Uwineza, Annette; Hitayezu, Janvier; Jamar, Mauricette; Caberg, Jean-Hubert; Murorunkwere, Seraphine; Janvier, Ndinkabandi; Bours, Vincent

2016-01-01

Global developmental delay (GDD) is defined as a significant delay in two or more developmental domains: gross or fine motor, speech/language, cognitive, social/personal and activities of daily living. Many of these children will go on to be diagnosed with intellectual disability (ID), which is most commonly defined as having an IQ <75 in addition to impairment in adaptive functioning. Cytogenetic studies have been performed in 664 Rwandan pediatric patients presenting GDD/ID and/or multiple congenital abnormalities (MCA). Karyotype analysis was performed in all patients and revealed 260 chromosomal abnormalities. The most frequent chromosomal abnormality was Down syndrome and then Edward syndrome and Patau syndrome. Other identified chromosomal abnormalities included 47,XX,+del(9)(q11), 46,XY,del(13)(q34) and 46,XX,der(22)t(10;22)(p10;p10)mat. In conclusion, our results highlight the high frequency of cytogenetically detectable abnormalities in this series, with implications for the burden on the healthcare. This study demonstrates the importance of cytogenetic analysis in patients with GDD/ID and MCA. PMID:26507407

Fortified Iodine Milk Improves Iodine Status and Cognitive Abilities in Schoolchildren Aged 7-9 Years Living in a Rural Mountainous Area of Morocco.

PubMed

Zahrou, Fatima Ezzahra; Azlaf, Mehdi; El Menchawy, Imane; El Mzibri, Mohamed; El Kari, Khalid; El Hamdouchi, Asmaa; Mouzouni, Fatima-Zahra; Barkat, Amina; Aguenaou, Hassan

2016-01-01

Iodine is required for the production of the thyroid hormones essential for the growth and development of the brain. All forms of iodine deficiency (ID) affect the mental development of the child. Our study aims to assess the impact of ID on the intellectual development of Moroccan schoolchildren and to evaluate the effect of consumption of fortified milk on reducing ID. In a double-blind controlled trial conducted on schoolchildren, children were divided into two groups to receive fortified milk (30% of cover of RDI iodine) or nonfortified milk for 9 months. Urinary iodine was analyzed using the Sandell-Kolthoff reaction, a dynamic cognitive test using Raven's Standard Progressive Matrices to assess learning potential was performed at baseline and end line, and anthropometric assessment was done only at baseline. The study included schoolchildren who were severely iodine deficient. The prevalence of malnutrition was high in both groups; in this study, we found improvements in iodine status and in cognitive abilities among Moroccan schoolchildren. Our study showed that the consumption of fortified milk led to a clear improvement in iodine status and also appeared to have a favorable effect on the cognitive ability of Moroccan schoolchildren in a rural mountainous region.

Combining CBT and Behavior-Analytic Approaches to Target Severe Emotion Dysregulation in Verbal Youth with ASD and ID

ERIC Educational Resources Information Center

Parent, Veronique; Birtwell, Kirstin B.; Lambright, Nathan; DuBard, Melanie

2016-01-01

This article presents an individual intervention combining cognitive-behavioral and behavior-analytic approaches to target severe emotion dysregulation in verbal youth with autism spectrum disorder (ASD) concurrent with intellectual disability (ID). The article focuses on two specific individuals who received the treatment within a therapeutic…

Intellectual Disability and Developmental Risk: Promoting Intervention to Improve Child and Family Well-Being

ERIC Educational Resources Information Center

Crnic, Keith A.; Neece, Cameron L.; McIntyre, Laura Lee; Blacher, Jan; Baker, Bruce L.

2017-01-01

Initial intervention processes for children with intellectual disabilities (IDs) largely focused on direct efforts to impact core cognitive and academic deficits associated with the diagnosis. Recent research on risk processes in families of children with ID, however, has influenced new developmental system approaches to early intervention. Recent…

Differences in the intellectual profile of children with intellectual vs. learning disability.

PubMed

Cornoldi, Cesare; Giofrè, David; Orsini, Arturo; Pezzuti, Lina

2014-09-01

The WISC-IV was used to compare the intellectual profile of two groups of children, one with specific learning disorders (SLDs), the other with intellectual disabilities (ID), with a view to identifying which of the four main factor indexes and two additional indexes can distinguish between the groups. We collected information on WISC-IV scores for 267 children (Mage=10.61 [SD=2.51], range 6-16 years, females=99) with a diagnosis of either SLD or ID. Children with SLD performed better than those with ID in all measures. Only the SLD children, not the ID children, revealed significant differences in the four main factor indexes, and their scores for the additional General Ability Index (GAI) were higher than for the Cognitive Proficiency Index (CPI). Children with a diagnosis of SLD whose Full-Scale Intelligence Quotient (FSIQ) was <85 showed a similar pattern. Our findings confirm the hypothesis that children with SLD generally obtain high GAI scores, but have specific deficiencies relating to working memory and processing speed, whereas children with ID have a general intellectual impairment. These findings have important diagnostic and clinical implications and should be considered when making diagnostic decisions in borderline cognitive cases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Social perception in children with intellectual disabilities: the interpretation of benign and hostile intentions.

PubMed

Leffert, J S; Siperstein, G N; Widaman, K F

2010-02-01

A key aspect of social perception is the interpretation of others' intentions. Children with intellectual disabilities (IDs) have difficulty interpreting benign intentions when a negative event occurs. From a cognitive processing perspective, interpreting benign intentions can be challenging because it requires integration of conflicting information, as the social cues accompanying the negative event convey non-hostile intentions. The present study examined how children with ID process conflicting social information in a more diverse set of situational circumstances than was investigated previously, including situations involving hostile intentions. We hypothesised that when conflicting information in a social situation consists of mixed social cues that convey insincere benign intentions (a type of hostile intentions), children with ID would have difficulty arriving at an accurate interpretation, just as they do when a negative event is accompanied by cues that convey benign intentions. We also hypothesised that when a negative event is accompanied by cues that convey benign intentions, the presence of a highly salient negative event would pose added interpretation difficulty for these children. Methods Participants (58 children with ID and 189 children without ID in grades 2-6) viewed 13 videotaped vignettes. In each vignette, social cues that accompanied a negative event provided information about the intentions of the character that caused the event. After presenting each vignette, we asked the child questions designed to assess aspects of social perception, including his/her interpretation of intentions. Vignettes represented three types of situations that pose conflicting information: (1) a conflict between a negative event and social cues, which conveyed benign intentions (five items); (2) the presence of conflicting social cues that conveyed insincere benign intentions (four items); and (3) additional items designed to examine the effect of the salience of negative event and cues on accurate interpretation of benign intentions (four items). Teachers completed rating scales of social behaviour, enabling us to examine whether the ability to interpret intentions when conflicting information is present is related to children's social behaviour. Results Children with ID had lower interpretation accuracy than children without ID for all three social situations that presented conflicting information. Children with ID appeared to have particular difficulty interpreting benign intentions when a negative event (but not the social cue) was made salient. For children with ID, interpretation accuracy and teacher-rated social behaviour were related. Conclusions Results demonstrated that the presence of conflicting information poses cognitive processing challenges in a variety of social situations, making it difficult for children with ID to arrive at accurate interpretations. Children with ID were less likely than children without ID to interpret intentions accurately, not just when the social cues conveyed benign intentions, but also when mixed social cues conveyed hostile intentions. In addition, when social cues accompanying a negative event convey benign intentions, the relative salience of the negative event and the cues can affect interpretation accuracy for children with ID. Discussion focuses on implications for understanding the cognitive component of the social domain of adaptive behaviour, for explaining gullibility in children with ID and for instructional practices.

Dementia in intellectual disability: a review of diagnostic challenges.

PubMed

Nagdee, M

2011-07-01

The evaluation of dementia in individuals with intellectual disability (ID), which will guide subsequent intervention, care and management depends on the systematic review of a number of factors: (1) the individual historical context, obtained from multiple sources, (2) evaluation of the pre-existing cognitive, behavioural, psychiatric, medical and adaptive skill profile, (3) the constellation, and pattern of evolution, of presenting signs and symptoms, (4) results of focused investigations, and (5) refinement of the differential diagnosis. In patients with ID, standard clinical methods need to be supplemented by careful, longitudinal behavioural observations, and individually tailored assessment techniques. Co-morbidity, multiple biological, psychological and socioenvironmental factors, and complex interactions among events, are the reality for many ageing people with ID. Determining the various influences is often a formidable clinical task, but should be systematically carried out using medical, cognitive, behavioural, neuropsychiatric and psycho-social frameworks.

Mainstream health professionals' stigmatising attitudes towards people with intellectual disabilities: a systematic review.

PubMed

Pelleboer-Gunnink, H A; Van Oorsouw, W M W J; Van Weeghel, J; Embregts, P J C M

2017-05-01

Equal access to mainstream healthcare services for people with intellectual disabilities (ID) still requires attention. Although recent studies suggest that health professionals hold positive attitudes towards people with ID, stigmatising attitudes may influence their efforts to serve people with ID in community healthcare practice. To stimulate inclusion in mainstream healthcare services, this systematic review focussed on barriers in attitudes of mainstream health professionals towards people with ID. Five electronic databases were systematically searched and references in full text articles were checked for studies published in the English language between January 1994 and January 2016. A social-psychological triad of cognitive, affective and behavioural dimensions of stigmatising attitudes is used to structure and discuss the results. The literature search generated 2190 records with 30 studies that passed our exclusion criteria. Studies were mostly cross-sectional and of moderate quality. With respect to stigma, a lack of familiarity with and knowledge about people with ID was found. ID was considered as a stable condition not under personal control. Moreover, mainstream health professionals had either low or high expectations of the capabilities of people with ID. Professionals reported stress, lack of confidence, fear and anxiety, a tendency to treat people with ID differently and a lack of supporting autonomy. Stigmatising attitudes towards people with ID appeared to be present among mainstream health professionals. This might affect the ongoing challenges regarding inclusion in mainstream healthcare services. To facilitate inclusion in mainstream healthcare services, it is recommended to include contact and collaboration with experts-by-experience in education programs of health professionals. Future research should progress beyond descriptive accounts of stigma towards exploring relationships between cognitive, affective and behavioural dimensions as pointers for intervention. Finally, inclusion would benefit from an understanding of 'equal' treatment that means reasonable adjustments instead of undifferentiated treatment. © 2017 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of theScientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial

PubMed Central

Massee, Laura A.; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

2015-01-01

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered. PMID:26042037

Dementia and Mild Cognitive Impairment in Adults with Intellectual Disability: Issues of Diagnosis

ERIC Educational Resources Information Center

Krinsky-McHale, Sharon J.; Silverman, Wayne

2013-01-01

Individuals with intellectual disability (ID) are now living longer with the majority of individuals reaching middle and even "old age." As a consequence of this extended longevity they are vulnerable to the same age-associated health problems as elderly adults in the general population without ID. This includes dementia, a general term…

Including Adults with Intellectual Disabilities in Research: Scientists' Perceptions of Risks and Protections

ERIC Educational Resources Information Center

McDonald, Katherine E.; Kidney, Colleen A.; Nelms, Sandra L.; Parker, Michael R.; Kimmel, Ali; Keys, Christopher B.

2009-01-01

Social and cognitive characteristics of adults with intellectual disabilities (ID) place them at risk for inappropriate inclusion in or exclusion from research participation. As we grapple with how to include adults with ID in research in order to secure their right to contribute to scientific advancements and be positioned to derive benefit from…

Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task

PubMed Central

Janitzky, Kathrin; Lippert, Michael T.; Engelhorn, Achim; Tegtmeier, Jennifer; Goldschmidt, Jürgen; Heinze, Hans-Jochen; Ohl, Frank W.

2015-01-01

The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and essential for attention-dependent cognitive processes. In this study we used unilateral optogenetic silencing of the LC in an attentional set-shifting task (ASST) to evaluate the influence of the LC on prefrontal cortex-dependent functions in mice. We expressed the halorhodopsin eNpHR 3.0 to reversibly silence LC activity during task performance, and found that silencing selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired, suggesting an involvement of the medial prefrontal cortex (mPFC) and the orbitofrontal cortex. In contrast, those parts of the task that are less dependent on cognitive flexibility, i.e., compound discrimination (CD) and the intra-dimensional shifts (IDS) were not affected. Furthermore, attentional set formation was unaffected by LC silencing. Our results therefore suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks. PMID:26582980

Effects of digital Cognitive Behavioural Therapy for Insomnia on cognitive function: study protocol for a randomised controlled trial.

PubMed

Kyle, Simon D; Hurry, Madeleine E D; Emsley, Richard; Luik, Annemarie I; Omlin, Ximena; Spiegelhalder, Kai; Espie, Colin A; Sexton, Claire E

2017-06-17

The daytime effects of insomnia pose a significant burden to patients and drive treatment seeking. In addition to subjective deficits, meta-analytic data show that patients experience reliable objective impairments across several cognitive domains. While Cognitive Behavioural Therapy for Insomnia (CBT-I) is an effective and scalable treatment, we know little about its impact upon cognitive function. Trials of CBT-I have typically used proxy measures for cognitive functioning, such as fatigue or work performance scales, and no study has assessed self-reported impairment in cognitive function as a primary outcome. Moreover, only a small number of studies have assessed objective cognitive performance, pre-to-post CBT-I, with mixed results. This study specifically aims to (1) investigate the impact of CBT-I on cognitive functioning, assessed through both self-reported impairment and objective performance measures, and (2) examine whether change in sleep mediates this impact. We propose a randomised controlled trial of 404 community participants meeting criteria for Insomnia Disorder. In the DISCO trial (D efining the I mpact of improved S leep on CO gnitive function (DISCO)) participants will be randomised to digital automated CBT-I delivered by a web and/or mobile platform (in addition to treatment as usual (TAU)) or to a wait-list control (in addition to TAU). Online assessments will take place at 0 (baseline), 10 (post-treatment), and 24 (follow-up) weeks. At week 25, all participants allocated to the wait-list group will be offered digital CBT-I, at which point the controlled element of the trial will be complete. The primary outcome is self-reported cognitive impairment at post-treatment (10 weeks). Secondary outcomes include objective cognitive performance, insomnia severity, sleepiness, fatigue, and self-reported cognitive failures and emotional distress. All main analyses will be carried out on completion of follow-up assessments and will be based on the intention-to-treat principle. Further analyses will determine to what extent observed changes in self-reported cognitive impairment and objective cognitive performance are mediated by changes in sleep. The trial is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) based at Oxford University Hospitals NHS Trust and University of Oxford, and by the NIHR Oxford Health BRC. This study will be the first large-scale examination of the impact of digital CBT-I on self-reported cognitive impairment and objective cognitive performance. ISRCTN, ID: ISRCTN89237370 . Registered on 17 October 2016.

Genetics of recessive cognitive disorders.

PubMed

Musante, Luciana; Ropers, H Hilger

2014-01-01

Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elucidation has lagged behind. Here we review recent progress in this field, show that ARID is not rare even in outbred Western populations, and discuss the prospects for improving its diagnosis and prevention. Copyright © 2013 Elsevier Ltd. All rights reserved.

Can interpersonal contact help improve attitudes toward soldiers with intellectual disability? An Israeli study.

PubMed

Werner, S

2017-12-01

It has been argued that interpersonal contact is the best intervention for reducing negative attitudes and discrimination toward individuals with intellectual disabilities (ID). In Israel, the Equal in Uniform project makes it possible for individuals with ID to serve alongside soldiers without ID in ordinary military units in the Israeli Defense Forces. The project provided the opportunity to examine the effect of contact on the attitudes of soldiers without ID. Data analyses are based on data collected from 220 soldiers without ID via a self-administered questionnaire based on the Multidimensional Attitudes Scale. Of these, 138 were in contact with soldiers with ID as part of the project. A mediation model showed that the impact of contact with a soldier with ID on withdrawal behaviour was mediated by cognitive attributions and negative affect. Contact was directly associated with prosocial behaviour. Results support the importance of contact between soldiers with and without ID to bring about improved attitudes toward the former. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.

PubMed

Gleitz, Hélène Fe; Liao, Ai Yin; Cook, James R; Rowlston, Samuel F; Forte, Gabriella Ma; D'Souza, Zelpha; O'Leary, Claire; Holley, Rebecca J; Bigger, Brian W

2018-06-08

The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Visual perception and frontal lobe in intellectual disabilities: a study with evoked potentials and neuropsychology.

PubMed

Muñoz-Ruata, J; Caro-Martínez, E; Martínez Pérez, L; Borja, M

2010-12-01

Perception disorders are frequently observed in persons with intellectual disability (ID) and their influence on cognition has been discussed. The objective of this study is to clarify the mechanisms behind these alterations by analysing the visual event related potentials early component, the N1 wave, which is related to perception alterations in several pathologies. Additionally, the relationship between N1 and neuropsychological visual tests was studied with the aim to understand its functional significance in ID persons. A group of 69 subjects, with etiologically heterogeneous mild ID, performed an odd-ball task of active discrimination of geometric figures. N1a (frontal) and N1b (post-occipital) waves were obtained from the evoked potentials. They also performed several neuropsychological tests. Only component N1a, produced by the target stimulus, showed significant correlations with the visual integration, visual semantic association, visual analogical reasoning tests, Perceptual Reasoning Index (Wechsler Intelligence Scale for Children Fourth Edition) and intelligence quotient. The systematic correlations, produced by the target stimulus in perceptual abilities tasks, with the N1a (frontal) and not with N1b (posterior), suggest that the visual perception process involves frontal participation. These correlations support the idea that the N1a and N1b are not equivalent. The relationship between frontal functions and early stages of visual perception is revised and discussed, as well as the frontal contribution with the neuropsychological tests used. A possible relationship between the frontal activity dysfunction in ID and perceptive problems is suggested. Perceptive alteration observed in persons with ID could indeed be because of altered sensory areas, but also to a failure in the frontal participation of perceptive processes conceived as elaborations inside reverberant circuits of perception-action. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

Executive function in children with intellectual disability--the effects of sex, level and aetiology of intellectual disability.

PubMed

Memisevic, H; Sinanovic, O

2014-09-01

Executive function is very important in the children's overall development. The goal of this study was to assess the executive function in children with intellectual disability (ID) through the use of the Behavior Rating Inventory of Executive Function (BRIEF) teacher version. An additional goal was to examine the differences in executive function in relation to child's sex, level and aetiology of ID. The sample consisted of 90 children with ID attending two special education schools in Sarajevo, Bosnia and Herzegovina. There were 42 children with mild ID and 48 children with moderate ID. Of those, 54 were boys and 36 were girls. Children were classified into three etiological categories: 30 children with Down syndrome, 30 children with other genetic cause or organic brain injury and 30 children with unknown aetiology of ID. Special education teachers, who knew the children for at least 6 months filled the BRIEF. Children with ID had a significant deficit in executive function as measured by the BRIEF. There were no statistically significant differences in executive function in relation to the child's sex. Level of ID had a significant effect on executive function. In relation to the aetiology of ID, the only significant difference was on the Shift scale of the BRIEF. Knowing what executive function is most impaired in children with ID will help professionals design better intervention strategies. More attention needs to be given to the assessment of executive function and its subsequent intervention in the school settings. © 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Visual function of children with visual and other disabilities in Oman: A case series.

PubMed

Gogri, Urmi; Khandekar, Rajiv; Al Harby, Salah

2016-12-01

We assessed the visual functioning of the children with special needs in Oman between 2009 and 2012. We present the methods of assessing different visual functions, outcomes, and interventions carried out to improve their functioning. Optometrists assessed visual functions of children of "Day care centres" in Oman. Experts further assessed them and provided low vision care. Ocular movements, refractive corrections, near, distance, contrast color, motion, field of vision, and cognitive visual function test results were noted. Feedback to caregivers was given to improve visual functioning of these children. We grouped 321 participants, (196 [61.1%] boys, age range of 3-18 years) into 61; Down syndrome (DS), 72 with intellectual disabilities (IDs), 67; hearing impaired and 121 with other conditions. Refractive error and lag of accommodation were 26 (42.6%) and 14 (22.6%) among children with DS. Contrast sensitivity was impaired in 8 (12.7%) among hearing impaired children. Defective distant and near vision was in 162 (70%) and 104 (42%) of our cohort. Children with ID were most difficult to assess. Children in a group of other disabilities had a higher proportion of impaired visual functioning. They were given low vision aids (telescopes [22], filters [7], and magnifiers [3]) in large numbers compared to those in other groups. Visual functioning of children with other disabilities show great variation and difficult to group. The care, therefore, should be at individual level. All visual functions cannot be assessed at one time.

The Research on the Status, Rehabilitation, Education, Vocational Development, Social Integration and Support Services Related to Intellectual Disability in China

ERIC Educational Resources Information Center

Wu, Lihui; Qiu, Zhuoying; Wong, Daniel; Hernandez, Lucy Wong; Zhao, Qianlei

2010-01-01

Intellectual disability (ID) is a prevalent form of non-progressive cognitive impairment. The objectives of this articles are: to analyze the changes of ID in China, including its definition, prevalence, rehabilitation, education, vocational development, social life and support services; to review and to compare the issues of intellectual…

Improving Memory and Cognition in Individuals with Down Syndrome.

PubMed

Rafii, Michael S

2016-07-01

Down syndrome (DS), often due to trisomy 21, is the most common genetic cause of intellectual disability (ID). In addition, virtually all individuals with DS develop the neuropathology of Alzheimer's disease (AD) by the age of 40 years and almost 60 % will manifest symptoms of AD dementia by the age of 65 years. Currently, there are no pharmacological treatments available for ID in individuals with DS and only limited symptomatic treatments for AD dementia. Advances in our understanding in both the molecular basis of ID and the pathogenesis of AD have created opportunities to study potential therapeutic targets. Recent studies in animal models of DS continue to provide a rational basis for translating specific compounds into human clinical trials. However, target and compound selection are only initial steps in the drug development pathway. Other necessary considerations include appropriate study designs to assess efficacy in the DS population, as well as operational aspects specifically tailored to assess cognition in this population. We discuss recent progress in the development of compounds for both ID and AD in individuals with DS, as well as concepts for the design and conduct of clinical trials with such compounds.

A Consensus Network of Gene Regulatory Factors in the Human Frontal Lobe

PubMed Central

Berto, Stefano; Perdomo-Sabogal, Alvaro; Gerighausen, Daniel; Qin, Jing; Nowick, Katja

2016-01-01

Cognitive abilities, such as memory, learning, language, problem solving, and planning, involve the frontal lobe and other brain areas. Not much is known yet about the molecular basis of cognitive abilities, but it seems clear that cognitive abilities are determined by the interplay of many genes. One approach for analyzing the genetic networks involved in cognitive functions is to study the coexpression networks of genes with known importance for proper cognitive functions, such as genes that have been associated with cognitive disorders like intellectual disability (ID) or autism spectrum disorders (ASD). Because many of these genes are gene regulatory factors (GRFs) we aimed to provide insights into the gene regulatory networks active in the human frontal lobe. Using genome wide human frontal lobe expression data from 10 independent data sets, we first derived 10 individual coexpression networks for all GRFs including their potential target genes. We observed a high level of variability among these 10 independently derived networks, pointing out that relying on results from a single study can only provide limited biological insights. To instead focus on the most confident information from these 10 networks we developed a method for integrating such independently derived networks into a consensus network. This consensus network revealed robust GRF interactions that are conserved across the frontal lobes of different healthy human individuals. Within this network, we detected a strong central module that is enriched for 166 GRFs known to be involved in brain development and/or cognitive disorders. Interestingly, several hubs of the consensus network encode for GRFs that have not yet been associated with brain functions. Their central role in the network suggests them as excellent new candidates for playing an essential role in the regulatory network of the human frontal lobe, which should be investigated in future studies. PMID:27014338

Parenting Stress in Mothers of Children with an Intellectual Disability: The Effects of Parental Cognitions in Relation to Child Characteristics and Family Support

ERIC Educational Resources Information Center

Hassall, R.; Rose, J.; McDonald, J.

2005-01-01

Background: Recent theories of stress and coping in parents of children with intellectual disabilities (ID) emphasize the importance of cognitive appraisals in influencing parents' levels of stress and their adaptations to difficulties presented by the children. This study investigated the relationships between parental cognitions, child…

Validation of the attitudes toward intellectual disability: ATTID questionnaire.

PubMed

Morin, D; Crocker, A G; Beaulieu-Bergeron, R; Caron, J

2013-03-01

Individuals with an intellectual disability (ID) continue to experience major obstacles towards social, educational and vocational integration. Negative attitudes toward persons with ID has remained relevant over time and has led to discrimination and stigma. The present study describes the development of a new questionnaire for tapping into the general population's attitudes toward individuals with ID and addresses its psychometric properties. Adopting a multidimensional perspective, the Attitudes Toward Intellectual Disability Questionnaire (ATTID) was developed from a series of previously validated instruments and principles from the Montreal Declaration on Intellectual Disability (2004). The ATTID was administered by phone to 1605 randomly selected adult men and women, stratified by region in the Province of Quebec, Canada. The ATTID yielded a five-factor structure overlapping the tri-partite model of attitudes. The cognitive component was represented by two factors: knowledge of capacity and rights and knowledge of causes of ID. The affective component tapped into two factors: discomfort and sensitivity/compassion. Finally, the behavioural component emerged as a single factor. The ATTID had good internal consistency with Cronbach's alpha coefficients ranging from 0.59 to 0.89 for the five factors and of 0.92 for the overall questionnaire. Test-retest reliability yielded correlations from 0.62 to 0.83 for the five factors. The ATTID can be used to measure attitudes among different populations and allows comparisons over time within the same population as a function of various intervention strategies for de-stigmatising ID. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

Cytogenetic Studies of Rwandan Pediatric Patients Presenting with Global Developmental Delay, Intellectual Disability and/or Multiple Congenital Anomalies.

PubMed

Uwineza, Annette; Hitayezu, Janvier; Jamar, Mauricette; Caberg, Jean-Hubert; Murorunkwere, Seraphine; Janvier, Ndinkabandi; Bours, Vincent; Mutesa, Leon

2016-02-01

Global developmental delay (GDD) is defined as a significant delay in two or more developmental domains: gross or fine motor, speech/language, cognitive, social/personal and activities of daily living. Many of these children will go on to be diagnosed with intellectual disability (ID), which is most commonly defined as having an IQ <75 in addition to impairment in adaptive functioning. Cytogenetic studies have been performed in 664 Rwandan pediatric patients presenting GDD/ID and/or multiple congenital abnormalities (MCA). Karyotype analysis was performed in all patients and revealed 260 chromosomal abnormalities. The most frequent chromosomal abnormality was Down syndrome and then Edward syndrome and Patau syndrome. Other identified chromosomal abnormalities included 47,XX,+del(9)(q11), 46,XY,del(13)(q34) and 46,XX,der(22)t(10;22)(p10;p10)mat. In conclusion, our results highlight the high frequency of cytogenetically detectable abnormalities in this series, with implications for the burden on the healthcare. This study demonstrates the importance of cytogenetic analysis in patients with GDD/ID and MCA. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Does visual impairment lead to additional disability in adults with intellectual disabilities?

PubMed

Evenhuis, H M; Sjoukes, L; Koot, H M; Kooijman, A C

2009-01-01

This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based questionnaires, prior to expert assessment of visual function. With linear regression analysis the percentage of variance, explained by levels of visual function, was calculated for the total population and per ID level. A total of 107/269 participants were visually impaired or blind (WHO criteria). On top of the decrease by ID visual impairment significantly decreased daily living skills, communication & language, recognition/communication. Visual impairment did not cause more self-absorbed and withdrawn behaviour or anxiety. Peculiar looking habits correlated with visual impairment and not with ID. In the groups with moderate and severe ID this effect seems stronger than in the group with profound ID. Although ID alone impairs daily functioning, visual impairment diminishes the daily functioning even more. Timely detection and treatment or rehabilitation of visual impairment may positively influence daily functioning, language development, initiative and persistence, social skills, communication skills and insecure movement.

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial.

PubMed

Anderson-Hanley, Cay; Barcelos, Nicole M; Zimmerman, Earl A; Gillen, Robert W; Dunnam, Mina; Cohen, Brian D; Yerokhin, Vadim; Miller, Kenneth E; Hayes, David J; Arciero, Paul J; Maloney, Molly; Kramer, Arthur F

2018-01-01

Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d 's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI exercisers over 6 months. A larger RCT is needed to confirm these findings. Further innovation and clinical trial data are needed to develop accessible, yet engaging and effective interventions to combat cognitive decline for the growing MCI population. ClinicalTrials.gov ID: NCT02237560.

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial

PubMed Central

Anderson-Hanley, Cay; Barcelos, Nicole M.; Zimmerman, Earl A.; Gillen, Robert W.; Dunnam, Mina; Cohen, Brian D.; Yerokhin, Vadim; Miller, Kenneth E.; Hayes, David J.; Arciero, Paul J.; Maloney, Molly; Kramer, Arthur F.

2018-01-01

Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI exercisers over 6 months. A larger RCT is needed to confirm these findings. Further innovation and clinical trial data are needed to develop accessible, yet engaging and effective interventions to combat cognitive decline for the growing MCI population. ClinicalTrials.gov ID: NCT02237560 PMID:29780318

The Role of L2 Learner Goal Differences in Task-Generated Oral Production

ERIC Educational Resources Information Center

Ben Maad, Mohamed Ridha

2016-01-01

In light of the growing interest in the cognitive approach to task in second language (L2) research, comparatively little has been done to examine such effect over time and the role of individual differences (IDs). The present study was designed to verify some longitudinal evidence for the role of tasks in L2 production and whether IDs, in the…

Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS): Phase 2 Test and Evaluation Development Guide

DTIC Science & Technology

2014-11-01

location, based on the evidence provided in Datum ( OSINT , IMINT, and the BLUEBOOK). The targetSum and normalizationConstraint attributes indicate that the...34LessThanOrEqualTo" id="Pp" name="P(Attack | IMINT, OSINT )" type="AttackProbabilityReport_Pp"> <Datum locationId=ŕ-1" datumType=" OSINT ...AttackProbabilityProbe_Ppc targetSum=蔴.0" normalizationConstraint="LessThanOrEqualTo" id="Ppc" name="P(Attack | HUMINT, IMINT, OSINT )" type

Individual Difference Relations in Psychometric and Experimental Cognitive Tasks. Final Report. No. 163.

ERIC Educational Resources Information Center

Carroll, John B.

Fifty-five recent studies of individual differences (IDs) in elementary cognitive tasks (ECTs) are reviewed. Twenty-five data sets are examined, analyzed, or reanalyzed by factor analysis. The following promising dimensions are identified: basic perceptual processes, reaction and movement times, mental comparison and recognition tasks, retrieval…

Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family.

PubMed

Al-Amri, Ahmed; Saegh, Abeer Al; Al-Mamari, Watfa; El-Asrag, Mohammed E; Ivorra, Jose L; Cardno, Alastair G; Inglehearn, Chris F; Clapcote, Steven J; Ali, Manir

2016-07-01

Intellectual disability (ID) is the term used to describe a diverse group of neurological conditions with congenital or juvenile onset, characterized by an IQ score of less than 70 and difficulties associated with limitations in cognitive function and adaptive behavior. The condition can be inherited or caused by environmental factors. The genetic forms are heterogeneous, with mutations in over 500 known genes shown to cause the disorder. We report a consanguineous Omani family in which multiple individuals have ID and developmental delay together with some variably present features including short stature, microcephaly, moderate facial dysmorphism, and congenital malformations of the toes or hands. Homozygosity mapping combined with whole exome next generation sequencing identified a novel homozygous single base pair deletion in TUSC3, c.222delA, p.R74 fs. The mutation segregates with the disease phenotype in a recessive manner and is absent in 60,706 unrelated individuals from various disease-specific and population genetic studies. TUSC3 mutations have been previously identified as causing either syndromic or non-syndromic ID in patients from France, Italy, Iran and Pakistan. This paper supports the previous clinical descriptions of the condition caused by TUSC3 mutations and describes the seventh family with mutations in this gene, thus contributing to the genetic spectrum of mutations. This is the first report of a family from the Arabian peninsula with this form of ID. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Multicentre Italian Validation Study in Aging Adults with Down Syndrome and Other Forms of Intellectual Disabilities: Dementia Screening Questionnaire for Individuals with Intellectual Disabilities.

PubMed

Gomiero, Tiziano; Bertelli, Marco; Deb, Shoumitro; Weger, Elisabeth; Marangoni, Annachiara; De Bastiani, Elisa; Mantesso, Ulrico; De Vreese, Luc Pieter

2017-01-01

The USA National Task Group (NTG) guidelines advocate the use of an adapted version of Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) for dementia screening of individuals with Down syndrome (DS) and with other forms of ID (non-DS). In order to meet these guidelines, this study verifies the psychometric properties of an Italian version of the original DSQIID in a population composed of adults aged 40 years and over with DS and non-DS ID. Internal consistency, inter-rater and intra-rater reliabilities, structural validity, convergent validity and known group differences of DSQIID-I were assessed with 200 individuals with ID (mean of 55.2 years; range: 40-80 years) recruited from 15 different centers in Italy. Diagnosis of dementia was done according to IASSID diagnostic criteria and its degree of clinical certainty was defined according to Silverman et al.'s classification (2004). Cronbach's alpha for the DSQIID-I was 0.94. The ICCs for inter-rater and test-retest reliability were both 0.89. A Principal Component analysis revealed three domains, namely memory and confusion- related items, motor and functional disabilities, depression and apathy, which explained almost 40% of the overall variance. The total DSQIID-I score correlated significantly with DMR and differed significantly among those individuals (n = 34) with cognitive decline from those without (n = 166). Age, gender and severity of ID were unrelated to the DSQIID-I. The present study confirms the cross-cultural value of DSQIID which was proved to be a psychometrically valid and user-friendly observer-rated scale for dementia screening in adults with both DS and non-DS ID. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Experiences of High Intensity Therapists Delivering Cognitive Behavioural Therapy to People with Intellectual Disabilities

ERIC Educational Resources Information Center

Marwood, Hayley; Chinn, Deborah; Gannon, Kenneth; Scior, Katrina

2018-01-01

Background: People with intellectual disabilities (ID) should be able to access the Improving Access to Psychological Therapies (IAPT) programme, currently a main provider of mainstream mental health services in England. IAPT offer cognitive behavioural therapy (CBT) to individuals experiencing mental health problems, although its effectiveness…

Beyond Stimulus Deprivation: Iron Deficiency and Cognitive Deficits in Postinstitutionalized Children

ERIC Educational Resources Information Center

Doom, Jenalee R.; Gunnar, Megan R.; Georgieff, Michael K.; Kroupina, Maria G.; Frenn, Kristin; Fuglestad, Anita J.; Carlson, Stephanie M.

2014-01-01

Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on…

In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

2012-08-01

Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P < 0.05). Dopamine (DA) receptor D1 was upregulated in the hippocampus of Fe+DHA/EPA rats (fold-change = 1.25; P < 0.05) and there were significant Fe x DHA/EPA interactions on serotonin (5-HT) in the OB and on the DA metabolite dihydroxyphenylacetic acid in the FC and striatum. Working memory performance was impaired in ID+DHA/EPA rats compared with controls (P < 0.05). In the reference memory task, Fe+DHA/EPA improved learning behavior, but Fe or DHA/EPA alone did not. These findings suggest that feeding either Fe or DHA/EPA alone to adult rats with both ID and (n-3)FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.

Inhibition of muscle-specific gene expression by Id3: requirement of the C-terminal region of the protein for stable expression and function.

PubMed

Chen, B; Han, B H; Sun, X H; Lim, R W

1997-01-15

We have examined the role of an Id-like protein, Id3 (also known as HLH462), in the regulation of muscle-specific gene expression. Id proteins are believed to block expression of muscle-specific genes by preventing the dimerization between ubiquitous bHLH proteins (E proteins) and myogenic bHLH proteins such as MyoD. Consistent with its putative role as an inhibitor of differentiation, Id3 mRNA was detected in proliferating skeletal muscle cells, was further induced by basic fibroblast growth factor (bFGF) and was down-regulated in differentiated muscle cultures. Overexpression of Id3 efficiently inhibited the MyoD-mediated activation of the muscle-specific creatine kinase (MCK) reporter gene. Deletion analysis indicated that the C-terminal 15 amino acids of Id3 are critical for the full inhibitory activity while deleting up to 42 residues from the C-terminus of the related protein, Id2, did not affect its ability to inhibit the MCK reporter gene. Chimeric protein containing the N-terminal region of Id3 and the C-terminus of Id2 was also non-functional in transfected cells. In contrast, wild-type Id3, the C-terminal mutants, and the Id3/Id2 chimera could all interact with the E-protein E47in vitro. Additional studies indicated that truncation of the Id3 C-terminus might have adversely affected the expression level of the mutant proteins but the Id3/Id2 chimera was stably expressed. Taken together, our results revealed a more complex requirement for the expression and proper function of the Id family proteins than was hitherto expected.

Inhibition of muscle-specific gene expression by Id3: requirement of the C-terminal region of the protein for stable expression and function.

PubMed Central

Chen, B; Han, B H; Sun, X H; Lim, R W

1997-01-01

We have examined the role of an Id-like protein, Id3 (also known as HLH462), in the regulation of muscle-specific gene expression. Id proteins are believed to block expression of muscle-specific genes by preventing the dimerization between ubiquitous bHLH proteins (E proteins) and myogenic bHLH proteins such as MyoD. Consistent with its putative role as an inhibitor of differentiation, Id3 mRNA was detected in proliferating skeletal muscle cells, was further induced by basic fibroblast growth factor (bFGF) and was down-regulated in differentiated muscle cultures. Overexpression of Id3 efficiently inhibited the MyoD-mediated activation of the muscle-specific creatine kinase (MCK) reporter gene. Deletion analysis indicated that the C-terminal 15 amino acids of Id3 are critical for the full inhibitory activity while deleting up to 42 residues from the C-terminus of the related protein, Id2, did not affect its ability to inhibit the MCK reporter gene. Chimeric protein containing the N-terminal region of Id3 and the C-terminus of Id2 was also non-functional in transfected cells. In contrast, wild-type Id3, the C-terminal mutants, and the Id3/Id2 chimera could all interact with the E-protein E47in vitro. Additional studies indicated that truncation of the Id3 C-terminus might have adversely affected the expression level of the mutant proteins but the Id3/Id2 chimera was stably expressed. Taken together, our results revealed a more complex requirement for the expression and proper function of the Id family proteins than was hitherto expected. PMID:9016574

Xuefu zhuyu decoction improves cognitive impairment in experimental traumatic brain injury via synaptic regulation

PubMed Central

Zhou, Jing; Liu, Tao; Cui, Hanjin; Fan, Rong; Zhang, Chunhu; Peng, Weijun; Yang, Ali; Zhu, Lin; Wang, Yang; Tang, Tao

2017-01-01

An overarching consequence of traumatic brain injury (TBI) is the cognitive impairment. It may hinder individual performance of daily tasks and determine people's subjective well-being. The damage to synaptic plasticity, one of the key mechanisms of cognitive dysfunction, becomes the potential therapeutic strategy of TBI. In this study, we aimed to investigate whether Xuefu Zhuyu Decoction (XFZYD), a traditional Chinese medicine, provided a synaptic regulation to improve cognitive disorder following TBI. Morris water maze and modified neurological severity scores were performed to assess the neurological and cognitive abilities. The PubChem Compound IDs of the major compounds of XFZYD were submitted into BATMAN-TCM, an online bioinformatics analysis tool, to predict the druggable targets related to synaptic function. Furthermore, we validated the prediction through immunohistochemical, RT-PCR and western blot analyses. We found that XFZYD enhanced neuroprotection, simultaneously improved learning and memory performances in controlled cortical impact rats. Bioinformatics analysis revealed that the improvements of XFZYD implied the Long-term potentiation relative proteins including NMDAR1, CaMKII and GAP-43. The further confirmation of molecular biological studies confirmed that XFZYD upregulated the mRNA and protein levels of NMDAR1, CaMKII and GAP-43. Pharmacological synaptic regulation of XFZYD could provide a novel therapeutic strategy for cognitive impairment following TBI. PMID:29069769

Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4.

PubMed

Wissmann, Ralph; Bildl, Wolfgang; Oliver, Dominik; Beyermann, Michael; Kalbitzer, Hans-Robert; Bentrop, Detlef; Fakler, Bernd

2003-05-02

Cumulative inactivation of voltage-gated (Kv) K(+) channels shapes the presynaptic action potential and determines timing and strength of synaptic transmission. Kv1.4 channels exhibit rapid "ball-and-chain"-type inactivation gating. Different from all other Kvalpha subunits, Kv1.4 harbors two inactivation domains at its N terminus. Here we report the solution structure and function of this "tandem inactivation domain" using NMR spectroscopy and patch clamp recordings. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, whereas ID2 (residues 40-50) is a 2.5-turn helix made up of small hydrophobic amino acids. Functional analysis suggests that only ID1 may work as a pore-occluding ball domain, whereas ID2 most likely acts as a "docking domain" that attaches ID1 to the cytoplasmic face of the channel. Deletion of ID2 slows inactivation considerably and largely impairs cumulative inactivation. Together, the concerted action of ID1 and ID2 may promote rapid inactivation of Kv1.4 that is crucial for the channel function in short term plasticity.

Collaborative Recurrent Neural Networks forDynamic Recommender Systems

DTIC Science & Technology

2016-11-22

formulation leads to an efficient and practical method. Furthermore, we demonstrate the versatility of our model by applying it to two different tasks: music ...form (user id, location id, check-in time). The LastFM9 dataset consists of sequences of songs played by a user’s music player collected by using a...Jeffrey L Elman. Finding structure in time. Cognitive science, 14(2), 1990. Alex Graves, Abdel-rahman Mohamed, and Geoffrey Hinton. Speech recognition

The Effectiveness of Modified Multi-Component Cognitive Strategy Instruction in Expository Text Comprehension of Students with Mild Intellectual Disabilities

ERIC Educational Resources Information Center

Bilgi, Arzu Doganay; Özmen, E. Rüya

2018-01-01

This study investigates the effectiveness of Modified Multi-Component Cognitive Strategy Instruction (MMCSI) on expository text comprehension skills of students with mild intellectual disability (ID). Three students participated from inclusion classes of three different secondary schools in Turkey. The study was conducted using a multiple probe…

Cognitive Behavioural Therapy: From Face to Face Interaction to a Broader Contextual Understanding of Change

ERIC Educational Resources Information Center

Jahoda, A.; Dagnan, D.; Kroese, B. Stenfert; Pert, C.; Trower, P.

2009-01-01

Cognitive behavioural therapy (CBT) is increasingly used to address the emotional and interpersonal problems of people with ID. There is a limited but promising evidence base supporting this activity. However, these individuals face real and continuing challenges in their lives that have implications for their self and interpersonal perceptions.…

Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features.

PubMed

Battaglia, Agatino; Doccini, Viola; Bernardini, Laura; Novelli, Antonio; Loddo, Sara; Capalbo, Anna; Filippi, Tiziana; Carey, John C

2013-11-01

Submicroscopic chromosomal rearrangements are the most common identifiable causes of intellectual disability and autism spectrum disorders associated with dysmorphic features. Chromosomal microarray (CMA) can detect copy number variants <1 Mb and identifies size and presence of known genes. The aim of this study was to demonstrate the usefulness of CMA, as a first-tier tool in detecting the etiology of unexplained intellectual disability/autism spectrum disorders (ID/ASDs) associated with dysmorphic features in a large cohort of pediatric patients. We studied 349 individuals; 223 males, 126 females, aged 5 months-19 years. Blood samples were analyzed with CMA at a resolution ranging from 1 Mb to 40 Kb. The imbalance was confirmed by FISH or qPCR. We considered copy number variants (CNVs) causative if the variant was responsible for a known syndrome, encompassed gene/s of known function, occurred de novo or, if inherited, the parent was variably affected, and/or the involved gene/s had been reported in association with ID/ASDs in dedicated databases. 91 CNVs were detected in 77 (22.06%) patients: 5 (6.49%) of those presenting with borderline cognitive impairment, 54 (70.13%) with a variable degree of DD/ID, and 18/77 (23.38%) with ID of variable degree and ASDs. 16/77 (20.8%) patients had two different rearrangements. Deletions exceeded duplications (58 versus 33); 45.05% (41/91) of the detected CNVs were de novo, 45.05% (41/91) inherited, and 9.9% (9/91) unknown. The CNVs caused the phenotype in 57/77 (74%) patients; 12/57 (21.05%) had ASDs/ID, and 45/57 (78.95%) had DD/ID. Our study provides further evidence of the high diagnostic yield of CMA for genetic testing in children with unexplained ID/ASDs who had dysmorphic features. We confirm the value of CMA as the first-tier tool in the assessment of those conditions in the pediatric setting. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H.; Morton, Derrick J.

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, wemore » examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. - Highlights: • ID4 expression induces AR expression in PC3 cells, which generally lack AR. • ID4 expression increased apoptosis and decreased cell proliferation and invasion. • Overexpression of ID4 reduces tumor growth of subcutaneous xenografts in vivo. • ID4 induces p21 and FKBP51 expression- co-factors of AR tumor suppressor activity.« less

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells.

PubMed

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H; Morton, Derrick J; Patel, Divya; Joshi, Jugal; Upadhyay, Sunil; Chaudhary, Jaideep

2016-09-09

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, we examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparing the effects of treatment with sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women: a randomized controlled clinical trial

PubMed Central

Omidi, Abdollah; Ahmadvand, Afshin; Najarzadegan, Mohammad Reza; Mehrzad, Fateme

2016-01-01

Background Sexual dysfunction in women is prevalent and common in women after menopause. Many attempts to treat patients with sexual dysfunction by cognitive-behavioral therapy (CBT) methods. But to the best of our knowledge, there has been no study that compared these two methods. Objective The aim of this study was to assess and compare the effects of sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women. Methods In this randomized, controlled, clinical trial, 86 women with arousal and orgasm dysfunction were surveyed. The patients were divided into two groups, i.e., sildenafil and CBT groups. The patients in the sildenafil group were treated by 50 mg of oral sildenafil one hour before intercourse, and the other group had weekly sessions of CBT for eight weeks. Sexual dysfunctions were evaluated by the Female Sexual Function Index (FSFI), a sexual satisfaction questionnaire, and the Enrich marital satisfaction scale. Results The mean age of the participants was 33.14 ± 7.34 years. The mean scores for female sexual function index, sexual satisfaction, and the Enrich marital satisfaction scale were increased in both groups during treatment (p < 0.001). It was found that cognitive-behavioral therapy compared to treatment with sildenafil increased all subscales, except arousal, orgasm, and lubrication. Conclusion Cognitive-behavioral therapy is more effective than treatment with sildenafil for improving female sexual function. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2014070318338N1. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:27382439

DriveID: safety innovation through individuation.

PubMed

Sawyer, Ben; Teo, Grace; Mouloua, Mustapha

2012-01-01

The driving task is highly complex and places considerable perceptual, physical and cognitive demands on the driver. As driving is fundamentally an information processing activity, distracted or impaired drivers have diminished safety margins compared with non- distracted drivers (Hancock and Parasuraman, 1992; TRB 1998 a & b). This competition for sensory and decision making capacities can lead to failures that cost lives. Some groups, teens and elderly drivers for example, have patterns of systematically poor perceptual, physical and cognitive performance while driving. Although there are technologies developed to aid these different drivers, these systems are often misused and underutilized. The DriveID project aims to design and develop a passive, automated face identification system capable of robustly identifying the driver of the vehicle, retrieve a stored profile, and intelligently prescribing specific accident prevention systems and driving environment customizations.

Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease.

PubMed

Strupp, Barbara J; Powers, Brian E; Velazquez, Ramon; Ash, Jessica A; Kelley, Christy M; Alldred, Melissa J; Strawderman, Myla; Caudill, Marie A; Mufson, Elliott J; Ginsberg, Stephen D

2016-01-01

Although Down syndrome (DS) can be diagnosed prenatally, currently there are no effective treatments to lessen the intellectual disability (ID) which is a hallmark of this disorder. Furthermore, starting as early as the third decade of life, DS individuals exhibit the neuropathological hallmarks of Alzheimer's disease (AD) with subsequent dementia, adding substantial emotional and financial burden to their families and society at large. A potential therapeutic strategy emerging from the study of trisomic mouse models of DS is to supplement the maternal diet with additional choline during pregnancy and lactation. Studies demonstrate that maternal choline supplementation (MCS) markedly improves spatial cognition and attentional function, as well as normalizes adult hippocampal neurogenesis and offers protection to basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model of DS. These effects on neurogenesis and BFCNs correlate significantly with spatial cognition, suggesting functional relationships. In this review, we highlight some of these provocative findings, which suggest that supplementing the maternal diet with additional choline may serve as an effective and safe prenatal strategy for improving cognitive, affective, and neural functioning in DS. In light of growing evidence that all pregnancies would benefit from increased maternal choline intake, this type of recommendation could be given to all pregnant women, thereby providing a very early intervention for individuals with DS, and include babies born to mothers unaware that they are carrying a fetus with DS.

Maternal choline supplementation: A potential prenatal treatment for Down syndrome and Alzheimer’s disease

PubMed Central

Strupp, Barbara J.; Powers, Brian E.; Velazquez, Ramon; Ash, Jessica A.; Kelley, Christy M.; Alldred, Melissa J.; Strawderman, Myla; Caudill, Marie A.; Mufson, Elliott J.; Ginsberg, Stephen D.

2016-01-01

Although Down syndrome (DS) can be diagnosed prenatally, currently there are no effective treatments to lessen the intellectual disability (ID) which is a hallmark of this disorder. Furthermore, starting as early as the third decade of life, DS individuals exhibit the neuropathological hallmarks of Alzheimer’s disease (AD) with subsequent dementia, adding substantial emotional and financial burden to their families and society at large. A potential therapeutic strategy emerging from the study of trisomic mouse models of DS is to supplement the maternal diet with additional choline during pregnancy and lactation. Studies demonstrate that maternal choline supplementation (MCS) markedly improves spatial cognition and attentional function, as well as normalizes adult hippocampal neurogenesis and offers protection to basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model of DS. These effects on neurogenesis and BFCNs correlate significantly with spatial cognition, suggesting functional relationships. In this review, we highlight some of these provocative findings, which suggest that supplementing the maternal diet with additional choline may serve as an effective and safe prenatal strategy for improving cognitive, affective, and neural functioning in DS. In light of growing evidence that all pregnancies would benefit from increased maternal choline intake, this type of recommendation could be given to all pregnant women, thereby providing a very early intervention for DS fetuses, and include babies born to mothers unaware that they are carrying a DS fetus. PMID:26391046

Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability.

PubMed

Musante, Luciana; Püttmann, Lucia; Kahrizi, Kimia; Garshasbi, Masoud; Hu, Hao; Stehr, Henning; Lipkowitz, Bettina; Otto, Sabine; Jensen, Lars R; Tzschach, Andreas; Jamali, Payman; Wienker, Thomas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas W

2017-06-01

Intellectual disability (ID) is the hallmark of an extremely heterogeneous group of disorders that comprises a wide variety of syndromic and non-syndromic phenotypes. Here, we report on mutations in two aminoacyl-tRNA synthetases that are associated with ID in two unrelated Iranian families. In the first family, we identified a homozygous missense mutation (c.514G>A, p.Asp172Asn) in the cytoplasmic seryl-tRNA synthetase (SARS) gene. The mutation affects the enzymatic core domain of the protein and impairs its enzymatic activity, probably leading to reduced cytoplasmic tRNA Ser concentrations. The mutant protein was predicted to be unstable, which could be substantiated by investigating ectopic mutant SARS in transfected HEK293T cells. In the second family, we found a compound heterozygous genotype of the mitochondrial tryptophanyl-tRNA synthetase (WARS2) gene, comprising a nonsense mutation (c.325delA, p.Ser109Alafs*15), which very likely entails nonsense-mediated mRNA decay and a missense mutation (c.37T>G, p.Trp13Gly). The latter affects the mitochondrial localization signal of WARS2, causing protein mislocalization. Including AIMP1, which we have recently implicated in the etiology of ID, three genes with a role in tRNA-aminoacylation are now associated with this condition. We therefore suggest that the functional integrity of tRNAs in general is an important factor in the development and maintenance of human cognitive functions. © 2017 Wiley Periodicals, Inc.

Treatment of chronically depressed patients: A multisite randomized controlled trial testing the effectiveness of 'Cognitive Behavioral Analysis System of Psychotherapy' (CBASP) for chronic depressions versus usual secondary care

PubMed Central

Wiersma, Jenneke E; van Schaik, Digna JF; van Oppen, Patricia; McCullough, James P; Schoevers, Robert A; Dekker, Jack J; Blom, Marc BJ; Maas, Kristel; Smit, Johannes H; Penninx, Brenda WJH; Beekman, Aartjan TF

2008-01-01

Background 'Cognitive Behavioral Analysis System of Psychotherapy' (CBASP) is a form of psychotherapy specifically developed for patients with chronic depression. In a study in the U.S., remarkable favorable effects of CBASP have been demonstrated. However, no other studies have as yet replicated these findings and CBASP has not been tested outside the United States. This protocol describes a randomized controlled trial on the effectiveness of CBASP in the Netherlands. Methods/Design The purpose of the present paper is to report the study protocol of a multisite randomized controlled trial testing the effectiveness of 'Cognitive Behavioral Analysis System of Psychotherapy' (CBASP) for chronic depression in the Netherlands. In this study, CBASP in combination with medication, will be tested versus usual secondary care in combination with medication. The aim is to recruit 160 patients from three mental health care organizations. Depressive symptoms will be assessed at baseline, after 8 weeks, 16 weeks, 32 weeks and 52 weeks, using the 28-item Inventory for Depressive Symptomatology (IDS). Effect modification by co morbid anxiety, alcohol consumption, general and social functioning and working alliance will be tested. GEE analyses of covariance, controlling for baseline value and center will be used to estimate the overall treatment effectiveness (difference in IDS score) at post-treatment and follow up. The primary analysis will be by 'intention to treat' using double sided tests. An economic analysis will compare the two groups in terms of mean costs and cost-effectiveness from a societal perspective. Discussion The study will provide an answer to the question whether the favorable effects of CBASP can be replicated outside the US. Trial Registration The Dutch Cochrane Center, NTR1090. PMID:18366729

Brief Symptom Inventory symptom profiles of outpatients with borderline intellectual functioning and major depressive disorder or posttraumatic stress disorder: Comparison with patients from regular mental health care and patients with Mild Intellectual Disabilities.

PubMed

Wieland, Jannelien; Zitman, Frans G

2016-01-01

In most countries, people with borderline intellectual functioning (BIF) are not considered a separate group in mental health care. There is little to no research on the impact of BIF on the presentation, nature and severity of mental health problems. The aim of the present exploratory study was to compare, in a naturalistic setting of patients referred to secondary care, symptom profiles of patients with BIF diagnosed with either major depressive disorder (MDD) or posttraumatic stress disorder (PTSD) to patients from regular mental health care (RMHC) and patients with Mild ID diagnosed with the same disorders. We used a cohort of adolescent and adult outpatients (aged 16-88) with or without BIF diagnosed with a primary diagnosis MDD or PTSD. Primary outcome was the nature and severity of psychopathological symptoms assessed at baseline using the Brief Symptom Inventory. All outcomes were adjusted for gender and age. Results showed that BIF patients with a primary diagnosis MDD reported less severe symptoms on BSI Total and the subscales Depression, Obsession-Compulsion and Psychoticism than patients from regular mental health care (RMHC). There were no statistically significant differences in reported symptom severity on BSI Total and the different BSI subscales between BIF patients with PTSD and either patients from RMHC or patients with Mild ID. Patients Mild ID, did report significantly less severe symptoms on the subscale Depression and on the subscale Psychoticism than patients from RMHC. Since there were no other published studies into symptom profiles in patients with BIF compared to either patients with higher or lower levels of cognitive functioning, the study was mainly exploratory in nature, providing direction for future research. Results indicate that symptom profiles did not widely differ, but that there might be some characteristics unique to patients BIF separating them as a group from both patients from RMHC and patients with Mild ID. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive Biases in Individuals with Mild to Borderline Intellectual Disability and Alcohol Use-Related Problems

ERIC Educational Resources Information Center

van Duijvenbode, Neomi; Didden, Robert; Voogd, Hubert; Korzilius, Hubert P. L. M.; Engels, Rutger C. M. E.

2012-01-01

The primary aim of the present pilot study was to examine cognitive biases in individuals with mild to borderline ID and alcohol use-related problems. Participants (N = 57) performed the approach avoidance task, picture rating task and visual dot probe task, which was combined with eye-tracking methodology. They were admitted to a forensic setting…

The Multimedia-Based Learning System Improved Cognitive Skills and Motivation of Disabled Children with a Very High Rate

ERIC Educational Resources Information Center

Saad, Sawsan; Dandashi, Amal; Aljaam, Jihad M.; Saleh, Moataz

2015-01-01

A multimedia-based learning system to teach children with intellectual disabilities (ID) the basic living and science concepts is proposed. The tutorials' development is pedagogically based on Mayer's Cognitive Theory of Multimedia Learning combined with Skinner's Operant Conditioning Model. Two types of tutorials are proposed. In the first type;…

The Need for Credible Evidence: Comments on "On Some Recent Claims for the Efficacy of Cognitive Therapy for People with Intellectual Disabilities"

ERIC Educational Resources Information Center

Emerson, Eric

2006-01-01

Sturmey (2005) argues that the evidence base underlying approaches to intervention based on applied behavioural analysis (ABA) are significantly stronger than that underlying approaches to intervention based on cognitive therapy. He concludes that "the ethical imperative of beneficence requires that people, including people with ID, receive known…

SNP ID-info: SNP ID searching and visualization platform.

PubMed

Yang, Cheng-Hong; Chuang, Li-Yeh; Cheng, Yu-Huei; Wen, Cheng-Hao; Chang, Phei-Lang; Chang, Hsueh-Wei

2008-09-01

Many association studies provide the relationship between single nucleotide polymorphisms (SNPs), diseases and cancers, without giving a SNP ID, however. Here, we developed the SNP ID-info freeware to provide the SNP IDs within inputting genetic and physical information of genomes. The program provides an "SNP-ePCR" function to generate the full-sequence using primers and template inputs. In "SNPosition," sequence from SNP-ePCR or direct input is fed to match the SNP IDs from SNP fasta-sequence. In "SNP search" and "SNP fasta" function, information of SNPs within the cytogenetic band, contig position, and keyword input are acceptable. Finally, the SNP ID neighboring environment for inputs is completely visualized in the order of contig position and marked with SNP and flanking hits. The SNP identification problems inherent in NCBI SNP BLAST are also avoided. In conclusion, the SNP ID-info provides a visualized SNP ID environment for multiple inputs and assists systematic SNP association studies. The server and user manual are available at http://bio.kuas.edu.tw/snpid-info.

Tailored cognitive-behavioural therapy and exercise training improves the physical fitness of patients with fibromyalgia.

PubMed

van Koulil, S; van Lankveld, W; Kraaimaat, F W; van Helmond, T; Vedder, A; van Hoorn, H; Donders, A R T; Wirken, L; Cats, H; van Riel, P L C M; Evers, A W M

2011-12-01

Patients with fibromyalgia have diminished levels of physical fitness, which may lead to functional disability and exacerbating complaints. Multidisciplinary treatment comprising cognitive-behavioural therapy (CBT) and exercise training has been shown to be effective in improving physical fitness. However, due to the high drop-out rates and large variability in patients' functioning, it was proposed that a tailored treatment approach might yield more promising treatment outcomes. High-risk fibromyalgia patients were randomly assigned to a waiting list control group (WLC) or a treatment condition (TC), with the treatment consisting of 16 twice-weekly sessions of CBT and exercise training tailored to the patient's cognitive-behavioural pattern. Physical fitness was assessed with two physical tests before and 3 months after treatment and at corresponding intervals in the WLC. Treatment effects were evaluated using linear mixed models. The level of physical fitness had improved significantly in the TC compared with the WLC. Attrition rates were low, effect sizes large and reliable change indices indicated a clinically relevant improvement among the TC. A tailored multidisciplinary treatment approach for fibromyalgia consisting of CBT and exercise training is well tolerated, yields clinically relevant changes, and appears a promising approach to improve patients' physical fitness. ClinicalTrials.gov ID NCT00268606.

The validity and reliability of the Functional Strength Measurement (FSM) in children with intellectual disabilities.

PubMed

Aertssen, W F M; Steenbergen, B; Smits-Engelsman, B C M

2018-06-07

There is lack of valid and reliable field-based tests for assessing functional strength in young children with mild intellectual disabilities (IDs). The aim of this study was to investigate the test-retest reliability and construct validity of the Functional Strength Measurement in children with ID (FSM-ID). Fifty-two children with mild ID (40 boys and 12 girls, mean age 8.48 years, SD = 1.48) were tested with the FSM. Test-retest reliability (n = 32) was examined by a two-way interclass correlation coefficient for agreement (ICC 2.1A). Standard error of measurement and smallest detectable change were calculated. Construct validity was determined by calculating correlations between the FSM-ID and handheld dynamometry (HHD) (convergent validity), FSM-ID, FSM-ID and subtest strength of the Bruininks-Oseretsky test of motor proficiency - second edition (BOT-2) (convergent validity) and the FSM-ID and balance subtest of the BOT-2 (discriminant validity). Test-retest reliability ICC ranged 0.89-0.98. Correlation between the items of the FSM-ID and HHD ranged 0.39-0.79 and between FSM-ID and BOT-2 (strength items) 0.41-0.80. Correlation between items of the FSM-ID and BOT-2 (balance items) ranged 0.41-0.70. The FSM-ID showed good test-retest reliability and good convergent validity with the HHD and BOT-2 subtest strength. The correlations assessing discriminant validity were higher than expected. Poor levels of postural control and core stability in children with mild IDs may be the underlying factor of those higher correlations. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Breaking bad habits by improving executive function in individuals with obesity.

PubMed

Allom, Vanessa; Mullan, Barbara; Smith, Evelyn; Hay, Phillipa; Raman, Jayanthi

2018-04-16

Two primary factors that contribute to obesity are unhealthy eating and sedentary behavior. These behaviors are particularly difficult to change in the long-term because they are often enacted habitually. Cognitive Remediation Therapy has been modified and applied to the treatment of obesity (CRT-O) with preliminary results of a randomized controlled trial demonstrating significant weight loss and improvements in executive function. The objective of this study was to conduct a secondary data analysis of the CRT-O trial to evaluate whether CRT-O reduces unhealthy habits that contribute to obesity via improvements in executive function. Eighty participants with obesity were randomized to CRT-O or control. Measures of executive function (Wisconsin Card Sort Task and Trail Making Task) and unhealthy eating and sedentary behavior habits were administered at baseline, post-intervention and at 3 month follow-up. Participants receiving CRT-O demonstrated improvements in both measures of executive function and reductions in both unhealthy habit outcomes compared to control. Mediation analyses revealed that change in one element of executive function performance (Wisconsin Card Sort Task perseverance errors) mediated the effect of CRT-O on changes in both habit outcomes. These results suggest that the effectiveness of CRT-O may result from the disruption of unhealthy habits made possible by improvements in executive function. In particular, it appears that cognitive flexibility, as measured by the Wisconsin Card Sort task, is a key mechanism in this process. Improving cognitive flexibility may enable individuals to capitalise on interruptions in unhealthy habits by adjusting their behavior in line with their weight loss goals rather than persisting with an unhealthy choice. The RCT was registered with the Australian New Zealand Registry of Clinical Trials (trial id: ACTRN12613000537752 ).

Acute Effects of Modafinil on Brain Resting State Networks in Young Healthy Subjects

PubMed Central

Pieramico, Valentina; Ferretti, Antonio; Macchia, Antonella; Tommasi, Marco; Saggino, Aristide; Ciavardelli, Domenico; Manna, Antonietta; Navarra, Riccardo; Cieri, Filippo; Stuppia, Liborio; Tartaro, Armando; Sensi, Stefano L.

2013-01-01

Background There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects. Methodology A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven’s Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306. Principal Findings Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed. Conclusions and Significance Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects. Trial Registration ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306. PMID:23935959

Acute effects of modafinil on brain resting state networks in young healthy subjects.

PubMed

Esposito, Roberto; Cilli, Franco; Pieramico, Valentina; Ferretti, Antonio; Macchia, Antonella; Tommasi, Marco; Saggino, Aristide; Ciavardelli, Domenico; Manna, Antonietta; Navarra, Riccardo; Cieri, Filippo; Stuppia, Liborio; Tartaro, Armando; Sensi, Stefano L

2013-01-01

There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects. A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven's Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306. Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed. Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects. ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306.

Stanford-Binet & WAIS IQ Differences and Their Implications for Adults with Intellectual Disability (aka Mental Retardation).

PubMed

Silverman, Wayne; Miezejeski, Charles; Ryan, Robert; Zigman, Warren; Krinsky-McHale, Sharon; Urv, Tiina

2010-03-01

Stanford-Binet and Wechsler Adult Intelligence Scale (WAIS) IQs were compared for a group of 74 adults with intellectual disability (ID). In every case, WAIS Full Scale IQ was higher than the Stanford-Binet Composite IQ, with a mean difference of 16.7 points. These differences did not appear to be due to the lower minimum possible score for the Stanford-Binet. Additional comparisons with other measures suggested that the WAIS might systematically underestimate severity of intellectual impairment. Implications of these findings are discussed regarding determination of disability status, estimating prevalence of ID, assessing dementia and aging-related cognitive declines, and diagnosis of ID in forensic cases involving a possible death penalty.

Stanford-Binet & WAIS IQ Differences and Their Implications for Adults with Intellectual Disability (aka Mental Retardation)

PubMed Central

Silverman, Wayne; Miezejeski, Charles; Ryan, Robert; Zigman, Warren; Krinsky-McHale, Sharon; Urv, Tiina

2010-01-01

Stanford-Binet and Wechsler Adult Intelligence Scale (WAIS) IQs were compared for a group of 74 adults with intellectual disability (ID). In every case, WAIS Full Scale IQ was higher than the Stanford-Binet Composite IQ, with a mean difference of 16.7 points. These differences did not appear to be due to the lower minimum possible score for the Stanford-Binet. Additional comparisons with other measures suggested that the WAIS might systematically underestimate severity of intellectual impairment. Implications of these findings are discussed regarding determination of disability status, estimating prevalence of ID, assessing dementia and aging-related cognitive declines, and diagnosis of ID in forensic cases involving a possible death penalty. PMID:20401180

The cognitive profile of myotonic dystrophy type 1: A systematic review and meta-analysis.

PubMed

Okkersen, Kees; Buskes, Melanie; Groenewoud, Johannes; Kessels, Roy P C; Knoop, Hans; van Engelen, Baziel; Raaphorst, Joost

2017-10-01

To examine the cognitive profile of patients with myotonic dystrophy type 1 (DM1) on the basis of a systematic review and meta-analysis of the literature. Embase, Medline and PsycInfo were searched for studies reporting ≥1 neuropsychological test in both DM1 patients and healthy controls. Search, data extraction and risk of bias analysis were independently performed by two authors to minimize error. Neuropsychological tests were categorized into 12 cognitive domains and effect sizes (Hedges' g) were calculated for each domain and for tests administered in ≥5 studies. DM1 participants demonstrated a significantly worse performance compared to controls in all cognitive domains. Effect sizes ranged from -.33 (small) for verbal memory to -1.01 (large) for visuospatial perception. Except for the domains global cognition, intelligence and social cognition, wide confidence intervals (CIs) were associated with moderate to marked statistical heterogeneity that necessitates careful interpretation of results. Out of the individual tests, the Rey-Osterrieth complex figure-copy (both non-verbal memory and visuoconstruction) showed consistent impairment with acceptable heterogeneity. In DM1 patients, cognitive deficits may include a variable combination of global cognitive impairment with involvement across different domains, including social cognition, memory and visuospatial functioning. Although DM1 is a heterogeneous disorder, our study shows that meta-analysis is feasible, contributes to the understanding of brain involvement and may direct bedside testing. The protocol for this study has been registered in PROSPERO (International prospective register of systematic reviews) under ID: 42016037415. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cross-cultural adaptation, reliability, and validation of the Korean version of the identification functional ankle instability (IdFAI).

PubMed

Ko, Jupil; Rosen, Adam B; Brown, Cathleen N

2017-09-12

To cross-culturally adapt the Identification Functional Ankle Instability for use with Korean-speaking participants. The English version of the IdFAI was cross-culturally adapted into Korean based on the guidelines. The psychometric properties in the Korean version of the IdFAI were measured for test-retest reliability, internal consistency, criterion-related validity, discriminative validity, and measurement error 181 native Korean-speakers. Intra-class correlation coefficients (ICC 2,1 ) between the English and Korean versions of the IdFAI for test-retest reliability was 0.98 (standard error of measurement = 1.41). The Cronbach's alpha coefficient was 0.89 for the Korean versions of IdFAI. The Korean versions of the IdFAI had a strong correlation with the SF-36 (r s  = -0.69, p < .001) and the Korean version of the Cumberland Ankle Instability Tool (r s  = -0.65, p < .001). The cutoff score of >10 was the optimal cutoff score to distinguish between the group memberships. The minimally detectable change of the Korean versions of the IdFAI score was 3.91. The Korean versions of the IdFAI have shown to be an excellent, reliable, and valid instrument. The Korean versions of the IdFAI can be utilized to assess the presence of Chronic Ankle Instability by researchers and clinicians working among Korean-speaking populations. Implications for rehabilitation The high recurrence rate of sprains may result into Chronic Ankle Instability (CAI). The Identification of Functional Ankle Instability Tool (IdFAI) has been validated and recommended to identify patients with Chronic Ankle Instability (CAI). The Korean version of the Identification of Functional Ankle Instability Tool (IdFAI) may be also recommend to researchers and clinicians for assessing the presence of Chronic Ankle Instability (CAI) in Korean-speaking population.

The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability.

PubMed

Dijkhuizen, Annemarie; Hilgenkamp, Thessa I M; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

2016-01-01

The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and physical capacities. However, until recently, the impact of the significantly prevalent visual impairments on the performance of activities of daily living has not yet been revealed within this group. The purpose of this prospective cross-sectional study was to investigate the impact of visual impairment on the performance of activities of daily living for persons with a severe/profound intellectual disability. The Barthel Index (BI) and Comfortable Walking Speed (CWS) were used to measure the ability of performing activities of daily living (ADL) in 240 persons with severe/profound ID and having Gross Motor Functioning Classification System (GMFCS) levels I, II or III; this included 120 persons with visual impairment. The impact of visual impairment on ADL was analyzed with linear regression. The results of the study demonstrated that visual impairment slightly affects the ability of performing activities of daily living (BI) for persons experiencing a severe/profound intellectual disability. GMFCS Levels II or III, profound ID level, and visual impairment each have the effect of lowering BI scores. GMFCS Levels II or III, and profound ID level each have the effect of increasing CWS scores, which indicates a lower walking speed. A main effect of visual impairment is present on CWS, but our results do show a substantive interaction effect between GMFCS level III and visual impairment on Comfortable Walking Speed in persons with a severe/profound intellectual disability. Visual impairment has a slight effect on ability to perform ADL in persons experiencing severe/profound ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2

PubMed Central

Micheli, Laura; Ceccarelli, Manuela; Gioia, Roberta; D’Andrea, Giorgio; Farioli-Vecchioli, Stefano; Costanzi, Marco; Saraulli, Daniele; Cestari, Vincenzo; Tirone, Felice

2017-01-01

Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine), the other cognitive (the Morris water maze (MWM) training). Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate. PMID:28740463

Delayed Latency of Postural Muscles of Individuals with Intellectual Disabilities.

PubMed

Tolentino-Castro, J Walter; Mühlbeier, Andreas; Mochizuki, Luis; Wagner, Heiko

2018-01-01

Individuals with intellectual disabilities (ID) (50 < IQ < 79) show impaired motor and postural control, these impairments are highly related to falls and injuries. Recent studies demonstrated these impairments are related with fine and gross motor development, which are more strongly associated with cognition, and consequently language for individuals with ID than for without ID. Despite these studies, little is known about the structure and functioning of this population's spinal cord, which is highly involved in postural control. The aim of our study was to assess the latency of the reflex responses in postural muscles after unexpected lateral external perturbations, in individuals with intellectual disabilities compared to typically developed participants. We assessed 16 participants with intellectual disabilities, 9 males and 7 females (aged 24.06 ± 8.66 years) and 20 typical developed participants (CG), 11 females, 9 males, (aged 21.20±1.96 years). While the participants were in an upright standing position electromyography was used to collect data from M. obliquus externus abdominis (OE) muscles, which were activated by unpredictable perturbations applied by a servomotor on a hand-held grip, following the lateral external perturbation to the trunk. The intellectual disabilities group presented contralateral OE muscles latency of 85.71±27.24 ms, and CG group presented 68.62±10.25 ms, no differences was found. Ipsilateral OE muscles latency also did not differs between the groups, ID group showed 96.60±30.20 ms and CG group showed 95.57±33.53 ms. Our study furthers the knowledge about the muscular activity of individuals with intellectual disabilities. The present experimental results may suggest unique spinal cord processing of individuals with intellectual disabilities when they are faced with unexpected lateral external perturbations.

Comparison of parental estimate of developmental age with measured IQ in children with neurodevelopmental disorders.

PubMed

Chandler, S; Howlin, P; Simonoff, E; Kennedy, J; Baird, G

2016-07-01

Formal IQ tests are an important part of the diagnostic and needs-based assessment process for children with neurodevelopmental disorders. However, resources for such assessments are not always available. It has been suggested that parental estimates of their child's developmental age could serve as a proxy IQ when formal measures are unavailable. Parental estimates of their child's developmental age were converted to a developmental quotient (DQ) in 197 children with Autism Spectrum Disorder (ASD) aged 4-9 years, and 108 children with ADHD and intellectual disability (ADHD + ID) aged 7-15 years. Formal IQ assessments were then conducted. Parents completed the Social Communication Questionnaire ((SCQ), a measure of autism symptomatology) and a demographic questionnaire. In the ASD sample, 58% of parent estimates were within 15 points (i.e. one standard deviation) of the child's measured IQ score. Lower measured IQ and lower SCQ total score predicted higher parental accuracy. In the ADHD + ID sample, 74% of parental estimates were within 15 points of measured IQ. In this group, higher child IQ predicted greater parental accuracy. Parents in the ADHD + ID group were more likely to overestimate children's ability level than parents in the ASD group. In this study, the majority of parents of children with ADHD and ID were able to estimate their child's intellectual ability level with some accuracy. Parents of children with ASD were less accurate, but this may be because these parents were focussing more on children's level of adaptive functioning, which is known to be typically lower than cognitive ability in ASD. © 2016 John Wiley & Sons Ltd.

Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and phenotypic spectrum.

PubMed

Smogavec, Mateja; Cleall, Alison; Hoyer, Juliane; Lederer, Damien; Nassogne, Marie-Cécile; Palmer, Elizabeth E; Deprez, Marie; Benoit, Valérie; Maystadt, Isabelle; Noakes, Charlotte; Leal, Alejandro; Shaw, Marie; Gecz, Jozef; Raymond, Lucy; Reis, André; Shears, Deborah; Brockmann, Knut; Zweier, Christiane

2016-12-01

Heterozygous copy number variants (CNVs) or sequence variants in the contactin-associated protein 2 gene CNTNAP2 have been discussed as risk factors for a wide spectrum of neurodevelopmental and neuropsychiatric disorders. Bi-allelic aberrations in this gene are causative for an autosomal-recessive disorder with epilepsy, severe intellectual disability (ID) and cortical dysplasia (CDFES). As the number of reported individuals is still limited, we aimed at a further characterisation of the full mutational and clinical spectrum. Targeted sequencing, chromosomal microarray analysis or multigene panel sequencing was performed in individuals with severe ID and epilepsy. We identified homozygous mutations, compound heterozygous CNVs or CNVs and mutations in CNTNAP2 in eight individuals from six unrelated families. All aberrations were inherited from healthy, heterozygous parents and are predicted to be deleterious for protein function. Epilepsy occurred in all affected individuals with onset in the first 3.5 years of life. Further common aspects were ID (severe in 6/8), regression of speech development (5/8) and behavioural anomalies (7/8). Interestingly, cognitive impairment in one of two affected brothers was, in comparison, relatively mild with good speech and simple writing abilities. Cortical dysplasia that was previously reported in CDFES was not present in MRIs of six individuals and only suspected in one. By identifying novel homozygous or compound heterozygous, deleterious CNVs and mutations in eight individuals from six unrelated families with moderate-to-severe ID, early onset epilepsy and behavioural anomalies, we considerably broaden the mutational and clinical spectrum associated with bi-allelic aberrations in CNTNAP2. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cognitive and Psychosocial Factors in the Long-Term Development of Implicit and Explicit Second Language Knowledge in Adult Learners of Spanish at Increasing Proficiency

ERIC Educational Resources Information Center

Serafini, Ellen Johnson

2013-01-01

This study examined the second language (L2) development of adult learners of Spanish at three levels of proficiency during and after a semester of instruction. A fundamental goal was to identify cognitive and psychosocial individual differences (IDs) that can explain between-learner variation over time in order to expand our understanding of the…

A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults.

PubMed

Lewis, John E; Melillo, Angelica B; Tiozzo, Eduard; Chen, Lawrence; Leonard, Susanna; Howell, Mark; Diaz, Janelle; Gonzalez, Kathy; Woolger, Judi M; Konefal, Janet; Paterson, Elaine; Barnes, David

2014-02-04

Declining cognitive function is relatively common and increasingly prevalent. Studies have shown that different nutrients (e.g., Ginkgo biloba and vitamin E) appear to be effective at improving memory and concentration, while less is known about their effect on immunity. This study investigated the effect of Ginkgo Synergy(®) plus Choline (n = 33) and OPC Synergy(®) plus Catalyn(®) (n = 31) versus placebo (n = 33) in a 6-month, randomized, double-blind trial on cognitive and immune functioning among English-speaking, non-smoking, healthy older adults. The Stroop Color and Word Test, Trail Making Test A and B, Controlled Oral Word Association, Hopkins Verbal Learning, Mini-Mental State Exam, and Digit Symbol were administered at baseline and 3 and 6 months follow-up to assess cognitive functioning. Cytokines and growth factors were measured at baseline and 6 months to assess inflammation and immune functioning. Data were analyzed with linear mixed modeling. No serious adverse events were noted in this study. According to time on the Trail Making Test-B, the Ginkgo Synergy(®) plus Choline arm showed improvement from baseline to 3 months follow-up (mean difference = 24.2; SE = 6.4; 95% CI: 8.6, 39.7; p = 0.01). On the Controlled Oral Word Association Trial-S, the scores significantly increased for the Ginkgo Synergy(®) plus Choline arm from baseline to 6 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 3.9; p < 0.05) and for the OPC Synergy(®) plus Catalyn(®) arm from baseline to 3 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 4.0; p < 0.05). Epidermal growth factor significantly decreased from baseline to 6 months follow-up for the Ginkgo Synergy(®) plus Choline arm (mean difference = 120.7; SE = 28.4; 95% CI: 62.6, 178.8; p < 0.001). Our study showed isolated and modest effects of a Ginkgo biloba plus choline-based formula on cognitive and immune functioning among healthy older adults with no history of significant cognitive deficits. Our trial was registered with clinicaltrials.gov (ID: NCT01672359). This study was supported by a grant from Standard Process, Inc.

Factors influencing the mammography utilization among Taiwanese women with intellectual disabilities, a nationwide population-based study.

PubMed

Lai, Hsien-Tang; Kung, Pei-Tseng; Tsai, Wen-Chen

2014-12-01

Women with intellectual disabilities (ID) have cognitive impairment and communication difficulties; for both caregivers and clinical personnel, discovering the early symptoms of breast cancer among women with ID is challenging. The mammography utilization rate of women with ID was significantly lower than that of women in the general population. This study employed a 2008 database of people with disabilities in Taiwan as a research target and analyzed the mammography utilization rate of women with ID aged 50–69 years. In addition, relevant factors influencing mammography utilization among women with ID were also investigated. A total of 4370 participants were recruited and the majority were illiterate or had elementary-level educations (82.27%). The majority of the participants had ID that was more severe than mild (83.80%). The mammography utilization rate of women with ID was 4.32%, which was significantly lower than that of women in the general population (12%). The mammography utilization rate among women with ID who were married, had higher education levels, and had been diagnosed with cancer, diabetes, or mild ID was significantly higher. However, the mammography utilization rate among women with ID, who had elementary-level educations or were illiterate, was only 4.03%. The utilization rate among women with profound ID was only 2.65%. Women with ID who had undergone pap smears or had utilized adult preventive health services demonstrated a significantly higher mammography utilization rate. This study identified that education level, a diagnosis of diabetes, and the application of pap smears or adult preventive health services were primary factors that influenced the mammography utilization rate among women with ID. This study also observed that in Taiwan, the mammography utilization rate of women with ID was lower than that of pap smears and adult preventive health services, and was only half of that of people with disabilities. An unequal situation existed in regard to the acceptance of breast cancer screening among women with ID, and a different form of strategic planning must be adopted in public health policy. Because ID differs from other disabilities and most women with ID are illiterate, tailored courses are required to train primary caregivers and clinical personnel in providing knowledge and services. The objectives are to diagnose breast cancer at an early stage to decrease the risk of mortality and ensure their rights to health.

DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment.

PubMed

Petzoldt, Astrid G; Coutelis, Jean-Baptiste; Géminard, Charles; Spéder, Pauline; Suzanne, Magali; Cerezo, Delphine; Noselli, Stéphane

2012-05-01

In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.

Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina

PubMed Central

2012-01-01

Background Midkine is a small heparin binding growth factor expressed in numerous tissues during development. The unique midkine gene in mammals has two paralogs in zebrafish: midkine-a (mdka) and midkine-b (mdkb). In the zebrafish retina, during both larval development and adult photoreceptor regeneration, mdka is expressed in retinal stem and progenitor cells and functions as a molecular component of the retina’s stem cell niche. In this study, loss-of-function and conditional overexpression were used to investigate the function of Mdka in the retina of the embryonic zebrafish. Results The results show that during early retinal development Mdka functions to regulate cell cycle kinetics. Following targeted knockdown of Mdka synthesis, retinal progenitors cycle more slowly, and this results in microphthalmia, a diminished rate of cell cycle exit and a temporal delay of cell cycle exit and neuronal differentiation. In contrast, Mdka overexpression results in acceleration of the cell cycle and retinal overgrowth. Mdka gain-of-function, however, does not temporally advance cell cycle exit. Experiments to identify a potential Mdka signaling pathway show that Mdka functions upstream of the HLH regulatory protein, Id2a. Gene expression analysis shows Mdka regulates id2a expression, and co-injection of Mdka morpholinos and id2a mRNA rescues the Mdka loss-of-function phenotype. Conclusions These data show that in zebrafish, Mdka resides in a shared Id2a pathway to regulate cell cycle kinetics in retinal progenitors. This is the first study to demonstrate the function of Midkine during retinal development and adds Midkine to the list of growth factors that transcriptionally regulate Id proteins. PMID:23111152

Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina.

PubMed

Luo, Jing; Uribe, Rosa A; Hayton, Sarah; Calinescu, Anda-Alexandra; Gross, Jeffrey M; Hitchcock, Peter F

2012-10-30

Midkine is a small heparin binding growth factor expressed in numerous tissues during development. The unique midkine gene in mammals has two paralogs in zebrafish: midkine-a (mdka) and midkine-b (mdkb). In the zebrafish retina, during both larval development and adult photoreceptor regeneration, mdka is expressed in retinal stem and progenitor cells and functions as a molecular component of the retina's stem cell niche. In this study, loss-of-function and conditional overexpression were used to investigate the function of Mdka in the retina of the embryonic zebrafish. The results show that during early retinal development Mdka functions to regulate cell cycle kinetics. Following targeted knockdown of Mdka synthesis, retinal progenitors cycle more slowly, and this results in microphthalmia, a diminished rate of cell cycle exit and a temporal delay of cell cycle exit and neuronal differentiation. In contrast, Mdka overexpression results in acceleration of the cell cycle and retinal overgrowth. Mdka gain-of-function, however, does not temporally advance cell cycle exit. Experiments to identify a potential Mdka signaling pathway show that Mdka functions upstream of the HLH regulatory protein, Id2a. Gene expression analysis shows Mdka regulates id2a expression, and co-injection of Mdka morpholinos and id2a mRNA rescues the Mdka loss-of-function phenotype. These data show that in zebrafish, Mdka resides in a shared Id2a pathway to regulate cell cycle kinetics in retinal progenitors. This is the first study to demonstrate the function of Midkine during retinal development and adds Midkine to the list of growth factors that transcriptionally regulate Id proteins.

Vision Research Literature May Not Represent the Full Intellectual Range of Autism Spectrum Disorder

PubMed Central

Brown, Alyse C.; Chouinard, Philippe A.; Crewther, Sheila G.

2017-01-01

Sensory, in particular visual processing is recognized as often perturbed in individuals with Autism Spectrum Disorder (ASD). However, in terms of the literature pertaining to visual processing, individuals in the normal intelligence range (IQ = 90–110) and above, are more frequently represented in study samples than individuals who score below normal in the borderline intellectual disability (ID) (IQ = 71–85) to ID (IQ < 70) ranges. This raises concerns as to whether or not current research is generalizable to a disorder that is often co-morbid with ID. Thus, the aim of this review is to better understand to what extent the current ASD visual processing literature is representative of the entire ASD population as either diagnosed or recognized under DSM-5. Our recalculation of ASD prevalence figures, using the criteria of DSM-5, indicates approximately 40% of the ASD population are likely to be ID although searching of the visual processing literature in ASD up to July 2016 showed that only 20% of papers included the ASD with-ID population. In the published literature, the mean IQ sampled was found to be 104, with about 80% of studies sampling from the 96–115 of the IQ range, highlighting the marked under-representation of the ID and borderline ID sections of the ASD population. We conclude that current understanding of visual processing and perception in ASD is not based on the mean IQ profile of the DSM-5 defined ASD population that now appears to lie within the borderline ID to ID range. Give the importance of the role of vision for the social and cognitive processing in ASD, we recommend accurately representing ASD via greater inclusion of individuals with IQ below 80, in future ASD research. PMID:28261072

Intrinsic disorder in scaffold proteins: Getting more from less

PubMed Central

Cortese, Marc S.; Uversky, Vladimir N.; Dunker, A. Keith

2008-01-01

Regulation, recognition and cell signaling involve the coordinated actions of many players. Signaling scaffolds, with their ability to bring together proteins belonging to common and/or interlinked pathways, play crucial roles in orchestrating numerous events by coordinating specific interactions among signaling proteins. This review examines the roles of intrinsic disorder (ID) in signaling scaffold protein function. Several well-characterized scaffold proteins with structurally and functionally characterized ID regions are used here to illustrate the importance of ID for scaffolding function. These examples include scaffolds that are mostly disordered, only partially disordered or those in which the ID resides in a scaffold partner. Specific scaffolds discussed include RNase, voltage-activated potassium channels, axin, BRCA1, GSK-3β, p53, Ste5, titin, Fus3, BRCA1, Titin, MAP2, D-AKAP2 and AKAP250. Among the mechanisms discussed are: molecular recognition features, fly-casting, ease of encounter complex formation, structural isolation of partners, modulation of interactions between bound partners, masking of intramolecular interaction sites, maximized interaction surface per residue, toleration of high evolutionary rates, binding site overlap, allosteric modification, palindromic binding, reduced constraints for alternative splicing, efficient regulation via posttranslational modification, efficient regulation via rapid degradation, protection of normally solvent-exposed sites, enhancing the plasticity of interaction and molecular crowding. We conclude that ID can enhance scaffold function by a diverse array of mechanisms. In other words, scaffold proteins utilize several ID-facilitated mechanisms to enhance function, and by doing so, get more functionality from less structure. PMID:18619997

Promoting Road Safety for Preadolescent Boys with Mild Intellectual Disabilities: The Effect of Cognitive Style and the Role of Attention in the Identification of Safe and Dangerous Road-Crossing Sites

ERIC Educational Resources Information Center

Anastasia, Alevriadou

2010-01-01

An important pedestrian skill that young people with intellectual disabilities (ID) (mental retardation) find difficult is the ability to find a safe place to cross the road. Safe pedestrian behaviour relies on cognitive skills, including the ability to focus attention on the traffic environment and ignore irrelevant stimuli. Individuals with ID…

Effectiveness of cognitive behavioural therapy (CBT) programmes for anxiety or depression in adults with intellectual disabilities: A review of the literature.

PubMed

Unwin, Gemma; Tsimopoulou, Ioanna; Kroese, Biza Stenfert; Azmi, Sabiha

2016-01-01

Relatively little is known about the application of cognitive behavioural therapy (CBT) to people with intellectual disabilities (ID). This review sought to synthesise available evidence on the effectiveness of CBT for anxiety or depression to assess the current level of evidence and make recommendations for future research. A comprehensive systematic literature search was conducted to identify qualitative and quantitative studies. Robust criteria were applied to select papers that were relevant to the review. Included papers were subject to quality appraisal. Eleven out of the 223 studies considered met our inclusion criteria and were included in the review in which CBT was used with participants with ID and anxiety (n=3), depression (n=4) or a mixed clinical presentation (n=4). There remains a paucity of evidence of effectiveness, however, the studies indicate that CBT is feasible and well-tolerated and may be effective in reducing symptoms of depression among adults with mild ID. Qualitative data reflect a positive perception of CBT amongst clients and carers. Further research is required to investigate the components of CBT, suitability for CBT, and requisite skills for CBT, which uses valid, sensitive and more holistic outcome measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke.

PubMed

Malueka, Rusdy Ghazali; Dwianingsih, Ery Kus; Sutarni, Sri; Bawono, Rheza Gandi; Bayuangga, Halwan Fuad; Gofir, Abdul; Setyopranoto, Ismail

2017-12-29

Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = -0.232, p = 0.024). This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

[Iron deficiency in infants and toddlers: impact on health and preventive strategies].

PubMed

Moráis López, A; Dalmau Serra, J

2011-06-01

Infants and toddlers represent a risk population for iron deficiency (ID), due to their relatively high requirements, which are frequently associated with a poor intake of iron-rich foods. A possible association between ID and impaired cognitive and psychomotor development has been described, and it has been suggested that some of these effects can be irreversible. For this reason, prevention of ID has become a subject of much concern. To promote an adequate dietetic iron intake is the most important approach for the prevention of ID. Exclusive breast-feeding provides adequate amounts of iron during the first 4-6 months of life, and iron-fortified formula should be used when an alternative is necessary. Fortified cereals and foods containing haem iron, such as meat, should be introduced early in complementary feeding. In toddlers, iron requirements can be satisfied with a daily consumption of at least one serving of iron-containing foods, along with enhancers of iron absorption. When daily requirements are not properly met by food intake, and in some high-risk populations, screening for ID and iron supplementation should be considered. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Crystallized and fluid intelligence of university students with intellectual disability who are fully integrated versus those who studied in adapted enrichment courses

PubMed Central

Verkuilen, Jay; Shnitzer-Meirovich, Shlomit; Altman, Carmit

2018-01-01

Background Inclusion of people with intellectual disability (ID) in higher postsecondary academic education is on the rise. However, there are no scientific criteria for determining the eligibility for full inclusion of students with ID in university courses. This study focuses on two models of academic inclusion for students with ID: (a) separate adapted enrichment model: students with ID study in separate enrichment courses adapted to their level; (b) full inclusion model: students with ID are included in undergraduate courses, receive academic credits and are expected to accumulate the amount of credits for a B.A. Aim (a) To examine whether crystallized and fluid intelligence and cognitive tests can serve as screening tests for determining the appropriate placement of students with ID for the adapted enrichment model versus the full inclusion model. (b) To examine the attitudes towards the program of students with ID in the inclusion model. Method/Procedure The sample included 31 adults with ID: students with ID who were fully included (N = 10) and students with ID who participated in the adapted enrichment model (N = 21). Crystallized and fluid intelligence were examined (WAIS-III, Wechsler, 1997) and Hebrew abstract verbal tests (Glanz, 1989). Semi-structured interviews were conducted in order to examine the attitudes of students in the inclusion model towards the program. Outcomes and results The ANOVAs indicate that the most prominent difference between the groups was in vocabulary, knowledge and working memory. ROC analysis, a fundamental tool for diagnostic test evaluation, was used to determine the students’ eligibility for appropriate placement in the two models. Seven tests distinguished between the groups in terms of sensitivity and specificity. The interviews were analyzed according to three phases. Conclusions/Implications The results indicate that students with ID are able to participate in undergraduate courses and achieve academic goals. The general IQ and idioms test seem to be best determiners for appropriate placement of students with ID to one of the two models. The included students with ID are motivated and self-determined in continuing in the program. PMID:29684024

Crystallized and fluid intelligence of university students with intellectual disability who are fully integrated versus those who studied in adapted enrichment courses.

PubMed

Lifshitz, Hefziba; Verkuilen, Jay; Shnitzer-Meirovich, Shlomit; Altman, Carmit

2018-01-01

Inclusion of people with intellectual disability (ID) in higher postsecondary academic education is on the rise. However, there are no scientific criteria for determining the eligibility for full inclusion of students with ID in university courses. This study focuses on two models of academic inclusion for students with ID: (a) separate adapted enrichment model: students with ID study in separate enrichment courses adapted to their level; (b) full inclusion model: students with ID are included in undergraduate courses, receive academic credits and are expected to accumulate the amount of credits for a B.A. (a) To examine whether crystallized and fluid intelligence and cognitive tests can serve as screening tests for determining the appropriate placement of students with ID for the adapted enrichment model versus the full inclusion model. (b) To examine the attitudes towards the program of students with ID in the inclusion model. The sample included 31 adults with ID: students with ID who were fully included (N = 10) and students with ID who participated in the adapted enrichment model (N = 21). Crystallized and fluid intelligence were examined (WAIS-III, Wechsler, 1997) and Hebrew abstract verbal tests (Glanz, 1989). Semi-structured interviews were conducted in order to examine the attitudes of students in the inclusion model towards the program. The ANOVAs indicate that the most prominent difference between the groups was in vocabulary, knowledge and working memory. ROC analysis, a fundamental tool for diagnostic test evaluation, was used to determine the students' eligibility for appropriate placement in the two models. Seven tests distinguished between the groups in terms of sensitivity and specificity. The interviews were analyzed according to three phases. The results indicate that students with ID are able to participate in undergraduate courses and achieve academic goals. The general IQ and idioms test seem to be best determiners for appropriate placement of students with ID to one of the two models. The included students with ID are motivated and self-determined in continuing in the program.

Id4 functions downstream of Bmp signaling to restrict TCF function in endocardial cells during atrioventricular valve development.

PubMed

Ahuja, Suchit; Dogra, Deepika; Stainier, Didier Y R; Reischauer, Sven

2016-04-01

The atrioventricular canal (AVC) connects the atrial and ventricular chambers of the heart and its formation is critical for the development of the cardiac valves, chamber septation and formation of the cardiac conduction system. Consequently, problems in AVC formation can lead to congenital defects ranging from cardiac arrhythmia to incomplete cardiac septation. While our knowledge about early heart tube formation is relatively comprehensive, much remains to be investigated about the genes that regulate AVC formation. Here we identify a new role for the basic helix-loop-helix factor Id4 in zebrafish AVC valve development and function. id4 is first expressed in the AVC endocardium and later becomes more highly expressed in the atrial chamber. TALEN induced inactivation of id4 causes retrograde blood flow at the AV canal under heat induced stress conditions, indicating defects in AV valve function. At the molecular level, we found that id4 inactivation causes misexpression of several genes important for AVC and AV valve formation including bmp4 and spp1. We further show that id4 appears to control the number of endocardial cells that contribute to the AV valves by regulating Wnt signaling in the developing AVC endocardium. Copyright © 2016 Elsevier Inc. All rights reserved.

[Cognitive functions, their development and modern diagnostic methods].

PubMed

Klasik, Adam; Janas-Kozik, Małgorzata; Krupka-Matuszczyk, Irena; Augustyniak, Ewa

2006-01-01

Cognitive psychology is an interdisciplinary field whose main aim is to study the thinking mechanisms of humans leading to cognizance. Therefore the concept of human cognitive processes envelopes the knowledge related to the mechanisms which determine the way humans acquire information from the environment and utilize their knowledge and experience. There are three basic processes which need to be distinguished when discussing human perception development: acquiring sensations, perceptiveness and attention. Acquiring sensations means the experience arising from the stimulation of a single sense organ, i.e. detection and differentiation of sensory information. Perceptiveness stands for the interpretation of sensations and may include recognition and identification of sensory information. The attention process relates to the selectivity of perception. Mental processes of the higher order used in cognition, thanks to which humans tend to try to understand the world and adapt to it, doubtlessly include the processes of memory, reasoning, learning and problem solving. There is a great difference in the human cognitive functioning at different stages of one's life (from infancy to adulthood). The difference is both quantitative and qualitative. There are three main approaches to the human cognitive functioning development: Jean Piaget's approach, information processing approach and psychometric approach. Piaget's ideas continue to form the groundwork of child cognitive psychology. Piaget identified four developmental stages of child cognition: 1. Sensorimotor stage (birth - 2 years old); 2. Preoperational stage (ages 2-7); 3. Concrete operations (ages 7-11; 4. Formal operations (11 and more). The supporters of the information processing approach use a computer metaphor to present the human cognitive processes functioning model. The three important mechanisms involved are: coding, automation and strategy designing and they all often co-operate together. This theory has provided a theory. The psychometric approach concentrates on studying the differences in intelligence. The aim of this approach is to test intelligence by means of standardized tests (e.g. WISC-R, WAIS-R) used to show the individual differences among humans. Human cognitive functions determine individuals' adaptation capabilities and disturbances in this area indicate a number of psychopathological changes and are a symptom enabling to differentiate or diagnose one with a disorder. That is why the psychological assessment of cognitive functions is an important part of patients' diagnosis. Contemporary neuropsychological studies are to a great extent based computer tests. The use of computer methods has a number of measurement-related advantages. It allows for standardized testing environment, increasing therefore its reliability and standardizes the patient assessment process. Special attention should be paid to the neuropsychological tests included in the Vienna Test System (Cognitron, SIGNAL, RT, VIGIL, DAUF), which are used to assess the operational memory span, learning processes, reaction time, attention selective function, attention continuity as well as attention interference resistance. It also seems justified to present the CPT id test (Continuous Performance Test) as well as Free Recall. CPT is a diagnostic tool used to assess the attention selective function, attention continuity of attention, attention interference resistance as well as attention alertness. The Free Recall test is used in the memory processes diagnostics to assess patients' operational memory as well as the information organization degree in operational memory. The above mentioned neuropsychological tests are tools used in clinical assessment of cognitive function disorders.

Providing male rats deficient in iron and n-3 fatty acids with iron and alpha-linolenic acid alone affects brain serotonin and cognition differently from combined provision.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Zimmermann, Michael B

2014-06-13

We recently showed that a combined deficiency of iron (ID) and n-3 fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n-3 FAD alone. Providing these double-deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double-deficiency. Iron is a co-factor of the enzymes responsible for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double-deficient rats than ALA alone. In this study we examined whether providing double-deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double-deficiency. Using a 2 × 2 design, male rats with concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n-3 FAD diet for 5 weeks (postnatal day 56-91). Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age-matched controls. In the hippocampus, we found a significant Fe × ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe + ALA group. In the brain, we found significant antagonistic Fe × ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age-matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. These results indicate that providing either iron or ALA alone to double-deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on the conversion of ALA to EPA and DHA.

Providing male rats deficient in iron and n-3 fatty acids with iron and alpha-linolenic acid alone affects brain serotonin and cognition differently from combined provision

PubMed Central

2014-01-01

Background We recently showed that a combined deficiency of iron (ID) and n-3 fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n-3 FAD alone. Providing these double-deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double-deficiency. Iron is a co-factor of the enzymes responsible for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double-deficient rats than ALA alone. Methods In this study we examined whether providing double-deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double-deficiency. Using a 2 × 2 design, male rats with concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n-3 FAD diet for 5 weeks (postnatal day 56–91). Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age-matched controls. Results In the hippocampus, we found a significant Fe × ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe + ALA group. In the brain, we found significant antagonistic Fe × ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age-matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. Conclusion These results indicate that providing either iron or ALA alone to double-deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on the conversion of ALA to EPA and DHA. PMID:24928171

Large-scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe.

PubMed

Necci, Marco; Piovesan, Damiano; Tosatto, Silvio C E

2016-12-01

Intrinsic disorder (ID) in proteins has been extensively described for the last decade; a large-scale classification of ID in proteins is mostly missing. Here, we provide an extensive analysis of ID in the protein universe on the UniProt database derived from sequence-based predictions in MobiDB. Almost half the sequences contain an ID region of at least five residues. About 9% of proteins have a long ID region of over 20 residues which are more abundant in Eukaryotic organisms and most frequently cover less than 20% of the sequence. A small subset of about 67,000 (out of over 80 million) proteins is fully disordered and mostly found in Viruses. Most proteins have only one ID, with short ID evenly distributed along the sequence and long ID overrepresented in the center. The charged residue composition of Das and Pappu was used to classify ID proteins by structural propensities and corresponding functional enrichment. Swollen Coils seem to be used mainly as structural components and in biosynthesis in both Prokaryotes and Eukaryotes. In Bacteria, they are confined in the nucleoid and in Viruses provide DNA binding function. Coils & Hairpins seem to be specialized in ribosome binding and methylation activities. Globules & Tadpoles bind antigens in Eukaryotes but are involved in killing other organisms and cytolysis in Bacteria. The Undefined class is used by Bacteria to bind toxic substances and mediate transport and movement between and within organisms in Viruses. Fully disordered proteins behave similarly, but are enriched for glycine residues and extracellular structures. © 2016 The Protein Society.

Large‐scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe

PubMed Central

Necci, Marco; Piovesan, Damiano

2016-01-01

Abstract Intrinsic disorder (ID) in proteins has been extensively described for the last decade; a large‐scale classification of ID in proteins is mostly missing. Here, we provide an extensive analysis of ID in the protein universe on the UniProt database derived from sequence‐based predictions in MobiDB. Almost half the sequences contain an ID region of at least five residues. About 9% of proteins have a long ID region of over 20 residues which are more abundant in Eukaryotic organisms and most frequently cover less than 20% of the sequence. A small subset of about 67,000 (out of over 80 million) proteins is fully disordered and mostly found in Viruses. Most proteins have only one ID, with short ID evenly distributed along the sequence and long ID overrepresented in the center. The charged residue composition of Das and Pappu was used to classify ID proteins by structural propensities and corresponding functional enrichment. Swollen Coils seem to be used mainly as structural components and in biosynthesis in both Prokaryotes and Eukaryotes. In Bacteria, they are confined in the nucleoid and in Viruses provide DNA binding function. Coils & Hairpins seem to be specialized in ribosome binding and methylation activities. Globules & Tadpoles bind antigens in Eukaryotes but are involved in killing other organisms and cytolysis in Bacteria. The Undefined class is used by Bacteria to bind toxic substances and mediate transport and movement between and within organisms in Viruses. Fully disordered proteins behave similarly, but are enriched for glycine residues and extracellular structures. PMID:27636733

Adaptation and validation of the Tower of London test of planning and problem solving in people with intellectual disabilities.

PubMed

Masson, J D; Dagnan, D; Evans, J

2010-05-01

There is a need for validated, standardised tools for the assessment of executive functions in adults with intellectual disabilities (ID). This study examines the validity of a test of planning and problem solving (Tower of London) with adults with ID. Participants completed an adapted version of the Tower of London (ToL) while day-centre staff completed adaptive function (Adaptive Behaviour Scale - Residential and Community: Second Edition, modified version) and dysexecutive function (DEX-Independent Rater) questionnaires for each participant. Correlation analyses of test and questionnaire variables were undertaken. The adapted ToL has a robust structure and shows significant associations with independent living skills, challenging behaviour and behaviours related to dysexecutive function. The adapted ToL is a valid test for use with people with ID. However, there is also a need to develop other ecologically valid tools based on everyday planning tasks undertaken by people with ID.

Frontal Brain Electrical Activity (EEG) and Heart Rate in Response to Affective Infant-Directed (ID) Speech in 9-Month-Old Infants

ERIC Educational Resources Information Center

Santesso, Diane L.; Schmidt, Louis A.; Trainor, Laurel J.

2007-01-01

Many studies have shown that infants prefer infant-directed (ID) speech to adult-directed (AD) speech. ID speech functions to aid language learning, obtain and/or maintain an infant's attention, and create emotional communication between the infant and caregiver. We examined psychophysiological responses to ID speech that varied in affective…

Functional properties of behaviour problems depending on level of intellectual disability.

PubMed

Medeiros, K; Rojahn, J; Moore, L L; van Ingen, D J

2014-02-01

Behaviour problems are common among individuals with intellectual disabilities (ID) especially in those with more severe forms. The determination of the functional profile of a targeted behaviour has important implications for the design of customised behavioural interventions. We investigated the relationship between the level of ID and the functional profile of aggression, stereotypy and self-injurious behaviour (SIB) using the Questions about Behavioural Function (QABF). Two staff members at two time points completed the QABF for each of 115 adults with varying levels of ID participating in a day training and habilitation programme. Our results suggest that there is a differential relationship between the functions of behaviour problems and level of ID. While SIB is more often seen by raters to be maintained by escape of social demands and by attaining access to tangible items with the decline of the intellectual level, aggressive and stereotypic behaviours were identified more often as serving multiple functions equally across functioning level. © 2013 The Authors. Journal of Intellectual Disability Research © 2013 John Wiley & Sons Ltd, MENCAP & IASSIDD.

Executive Functioning in Individuals with Intellectual Disabilities and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Roelofs, R. L.; Visser, E. M.; Berger, H. J. C.; Prins, J. B.; Van Schrojenstein Lantman-De Valk, H. M. J.; Teunisse, J. P.

2015-01-01

Background: Executive functioning (EF) is important for adequate behavioural functioning and crucial for explaining symptoms of autism spectrum disorders (ASD) in individuals with normal intelligence, but is scarcely studied in individuals with ASD and intellectual disabilities (ID). We therefore study EF in an ID population by comparing…

PROspective MEmory Training to improve HEart failUre Self-care (PROMETHEUS): study protocol for a randomised controlled trial.

PubMed

Cameron, Jan; Rendell, Peter G; Ski, Chantal F; Kure, Christina E; McLennan, Skye N; Rose, Nathan S; Prior, David L; Thompson, David R

2015-04-29

Cognitive impairment is seen in up to three quarters of heart failure (HF) patients and has a significant negative impact on patients' health outcomes. Prospective memory, which is defined as memory to carry out future intentions, is important for functional independence in older adults and involves application of multiple cognitive processes that are often impaired in HF patients. The objective of this study is to examine the effects of prospective memory training on patients' engagement in HF self-care and health outcomes, carer strain and quality of life. The proposed study is a randomised, controlled trial in which 200 patients diagnosed with HF, and their carers will be recruited from 3 major hospitals across Melbourne. Eligible patients with HF will be randomised to receive either: 1) The Virtual Week Training Program - a computerised prospective memory (PM) training program (intervention) or 2) non-adaptive computer-based word puzzles (active control). HF patients' baseline cognitive function will be compared to a healthy control group (n = 60) living independently in the community. Patients will undergo a comprehensive assessment of PM, neuropsychological functioning, self-care, physical, and emotional functioning. Assessments will take place at baseline, 4 weeks and 12 months following intervention. Carers will complete measures assessing quality of life, strain, perceived control in the management of the patients' HF symptoms, and ratings of the patients' level of engagement in HF self-care behaviours. If the Virtual Week Training Program is effective in improving: 1) prospective memory; 2) self-care behaviours, and 3) wellbeing in HF patients, this study will enhance our understanding of impaired cognitive processes in HF and potentially is a mechanism to reduce healthcare costs. Australian New Zealand Clinical Trials Registry #366376; 27 May 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366376&isClinicalTrial=False .

CNS-directed gene therapy for the treatment of neurologic and somatic mucopolysaccharidosis type II (Hunter syndrome).

PubMed

Motas, Sandra; Haurigot, Virginia; Garcia, Miguel; Marcó, Sara; Ribera, Albert; Roca, Carles; Sánchez, Xavier; Sánchez, Víctor; Molas, Maria; Bertolin, Joan; Maggioni, Luca; León, Xavier; Ruberte, Jesús; Bosch, Fatima

2016-06-16

Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disease characterized by severe neurologic and somatic disease caused by deficiency of iduronate-2-sulfatase (IDS), an enzyme that catabolizes the glycosaminoglycans heparan and dermatan sulphate. Intravenous enzyme replacement therapy (ERT) currently constitutes the only approved therapeutic option for MPSII. However, the inability of recombinant IDS to efficiently cross the blood-brain barrier (BBB) limits ERT efficacy in treating neurological symptoms. Here, we report a gene therapy approach for MPSII through direct delivery of vectors to the CNS. Through a minimally invasive procedure, we administered adeno-associated virus vectors encoding IDS (AAV9- Ids ) to the cerebrospinal fluid of MPSII mice with already established disease. Treated mice showed a significant increase in IDS activity throughout the encephalon, with full resolution of lysosomal storage lesions, reversal of lysosomal dysfunction, normalization of brain transcriptomic signature, and disappearance of neuroinflammation. Moreover, our vector also transduced the liver, providing a peripheral source of therapeutic protein that corrected storage pathology in visceral organs, with evidence of cross-correction of nontransduced organs by circulating enzyme. Importantly, AAV9- Ids -treated MPSII mice showed normalization of behavioral deficits and considerably prolonged survival. These results provide a strong proof of concept for the clinical translation of our approach for the treatment of Hunter syndrome patients with cognitive impairment.

CNS-directed gene therapy for the treatment of neurologic and somatic mucopolysaccharidosis type II (Hunter syndrome)

PubMed Central

Motas, Sandra; Haurigot, Virginia; Garcia, Miguel; Marcó, Sara; Ribera, Albert; Roca, Carles; Sánchez, Víctor; Molas, Maria; Bertolin, Joan; Maggioni, Luca; León, Xavier; Ruberte, Jesús; Bosch, Fatima

2016-01-01

Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disease characterized by severe neurologic and somatic disease caused by deficiency of iduronate-2-sulfatase (IDS), an enzyme that catabolizes the glycosaminoglycans heparan and dermatan sulphate. Intravenous enzyme replacement therapy (ERT) currently constitutes the only approved therapeutic option for MPSII. However, the inability of recombinant IDS to efficiently cross the blood-brain barrier (BBB) limits ERT efficacy in treating neurological symptoms. Here, we report a gene therapy approach for MPSII through direct delivery of vectors to the CNS. Through a minimally invasive procedure, we administered adeno-associated virus vectors encoding IDS (AAV9-Ids) to the cerebrospinal fluid of MPSII mice with already established disease. Treated mice showed a significant increase in IDS activity throughout the encephalon, with full resolution of lysosomal storage lesions, reversal of lysosomal dysfunction, normalization of brain transcriptomic signature, and disappearance of neuroinflammation. Moreover, our vector also transduced the liver, providing a peripheral source of therapeutic protein that corrected storage pathology in visceral organs, with evidence of cross-correction of nontransduced organs by circulating enzyme. Importantly, AAV9-Ids-treated MPSII mice showed normalization of behavioral deficits and considerably prolonged survival. These results provide a strong proof of concept for the clinical translation of our approach for the treatment of Hunter syndrome patients with cognitive impairment. PMID:27699273

Conscious Sedation Procedures Using Intravenous Midazolam for Dental Care in Patients with Different Cognitive Profiles: A Prospective Study of Effectiveness and Safety

PubMed Central

Collado, Valérie; Faulks, Denise; Nicolas, Emmanuel; Hennequin, Martine

2013-01-01

The use of midazolam for dental care in patients with intellectual disability is poorly documented. This study aimed to evaluate the effectiveness and safety of conscious sedation procedures using intravenous midazolam in adults and children with intellectual disability (ID) compared to dentally anxious patients (DA). Ninety-eight patients with ID and 44 patients with DA programmed for intravenous midazolam participated in the study over 187 and 133 sessions, respectively. Evaluation criteria were success of dental treatment, cooperation level (modified Venham scale), and occurrence of adverse effects. The mean intravenous dose administered was 8.8±4.9 mg and 9.8±4.1 mg in ID and DA sessions respectively (t-test, NS). 50% N2O/O2 was administered during cannulation in 51% of ID sessions and 61% of DA sessions (NS, Fisher exact test). Oral or rectal midazolam premedication was administered for cannulation in 31% of ID sessions and 3% of DA sessions (p<0,001, Fisher exact test). Dental treatment was successful in 9 out of 10 sessions for both groups. Minor adverse effects occurred in 16.6% and 6.8% of ID and DA sessions respectively (p = 0.01, Fisher exact test). Patients with ID were more often very disturbed during cannulation (25.4% ID vs. 3.9% DA sessions) and were less often relaxed after induction (58.9% ID vs. 90.3% DA) and during dental treatment (39.5% ID vs. 59.7% DA) (p<0.001, Fisher exact test) than patients with DA. When midazolam sedation was repeated, cooperation improved for both groups. Conscious sedation procedures using intravenous midazolam, with or without premedication and/or inhalation sedation (50% N2O/O2), were shown to be safe and effective in patients with intellectual disability when administered by dentists. PMID:23940729

Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function.

PubMed

Willemsen, Marjolein H; Ba, Wei; Wissink-Lindhout, Willemijn M; de Brouwer, Arjan P M; Haas, Stefan A; Bienek, Melanie; Hu, Hao; Vissers, Lisenka E L M; van Bokhoven, Hans; Kalscheuer, Vera; Nadif Kasri, Nael; Kleefstra, Tjitske

2014-07-01

Kinesin superfamily (KIF) genes encode motor proteins that have fundamental roles in brain functioning, development, survival and plasticity by regulating the transport of cargo along microtubules within axons, dendrites and synapses. Mouse knockout studies support these important functions in the nervous system. The role of KIF genes in intellectual disability (ID) has so far received limited attention, although previous studies have suggested that many ID genes impinge on synaptic function. By applying next-generation sequencing (NGS) in ID patients, we identified likely pathogenic mutations in KIF4A and KIF5C. To further confirm the pathogenicity of these mutations, we performed functional studies at the level of synaptic function in primary rat hippocampal neurons. Four males from a single family with a disruptive mutation in the X-linked KIF4A (c.1489-8_1490delins10; p.?- exon skipping) showed mild to moderate ID and epilepsy. A female patient with a de novo missense mutation in KIF5C (c.11465A>C; p.(Glu237Lys)) presented with severe ID, epilepsy, microcephaly and cortical malformation. Knock-down of Kif4a in rat primary hippocampal neurons altered the balance between excitatory and inhibitory synaptic transmission, whereas the mutation in Kif5c affected its protein function at excitatory synapses. Our results suggest that mutations in KIF4A and KIF5C cause ID by tipping the balance between excitatory and inhibitory synaptic excitability. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Case-finding for cognitive impairment among people with Type 2 diabetes in primary care using the Test Your Memory and Self-Administered Gerocognitive Examination questionnaires: the Cog-ID study.

PubMed

Koekkoek, P S; Janssen, J; Kooistra, M; Biesbroek, J M; Groeneveld, O; van den Berg, E; Kappelle, L J; Biessels, G J; Rutten, G E H M

2016-06-01

To evaluate two cognitive tests for case-finding for cognitive impairment in older patients with Type 2 diabetes. Of 1243 invited patients with Type 2 diabetes, aged ≥70 years, 228 participated in a prospective cohort study. Exclusion criteria were: diagnosis of dementia; previous investigation at a memory clinic; and inability to write or read. Patients first filled out two self-administered cognitive tests (Test Your Memory and Self-Administered Gerocognitive Examination). Secondly, a general practitioner, blinded to Test Your Memory and Self-Administered Gerocognitive Examination scores, performed a structured evaluation using the Mini-Mental State Examination. Subsequently, patients suspected of cognitive impairment (on either the cognitive tests or general practitioner evaluation) and a random sample of 30% of patients not suspected of cognitive impairment were evaluated at a memory clinic. Diagnostic accuracy and area under the curve were determined for the Test Your Memory, Self-Administered Gerocognitive Examination and general practitioner evaluation compared with a memory clinic evaluation to detect cognitive impairment (mild cognitive impairment or dementia). A total of 44 participants were diagnosed with cognitive impairment. The Test Your Memory and Self-Administered Gerocognitive Examination questionnaires had negative predictive values of 81 and 85%, respectively. Positive predictive values were 39 and 40%, respectively. The general practitioner evaluation had a negative predictive value of 83% and positive predictive value of 64%. The area under the curve was ~0.70 for all tests. Both the tests evaluated in the present study can easily be used in case-finding strategies for cognitive impairment in patients with Type 2 diabetes in primary care. The Self-Administered Gerocognitive Examination had the best diagnostic accuracy and therefore we would have a slight preference for this test. Applying the Self-Administered Gerocognitive Examination would considerably reduce the number of patients in whom the general practitioner needs to evaluate cognitive functioning to tailor diabetes treatment. © 2015 Diabetes UK.

IRON DEFICIENCY AND INFANT MOTOR DEVELOPMENT

PubMed Central

Shafir, Tal; Angulo-Barroso, Rosa; Jing, Yuezhou; Lu Angelilli, Mary; Jacobson, Sandra W.; Lozoff, Betsy

2011-01-01

Background Iron deficiency (ID) during early development impairs myelination and basal ganglia function in animal models. Aims To examine the effects of iron deficiency anemia (IDA) and iron deficiency (ID) without anemia on infant motor skills that are likely related to myelination and basal ganglia function. Study design Observational study. Subjects Full-term inner-city African-American 9- to 10-month-old infants who were free of acute or chronic health problems with iron status indicators ranging from IDA to iron sufficiency (n = 106). Criteria for final iron status classification were met by 77 of these infants: 28 IDA, 28 non-anemic iron-deficient (NA ID), and 21 iron-sufficient (IS). Outcome measures Gross motor developmental milestones, Peabody Developmental Motor Scale, Infant Neurological International Battery (INFANIB), motor quality factor of the Bayley Behavioral Rating Scale, and a sequential/bi-manual coordination toy retrieval task. General linear model analyses tested for linear effects of iron status group and thresholds for effects. Results There were linear effects of iron status on developmental milestones, Peabody gross motor (suggestive trend), INFANIB standing item, motor quality, and toy retrieval. The threshold for effects was ID with or without anemia for developmental milestones, INFANIB standing item, and motor quality and IDA for toy retrieval. Conclusions Using a comprehensive and sensitive assessment of motor development, this study found poorer motor function in ID infants with and without anemia. Poorer motor function among non-anemic ID infants is particularly concerning, since ID without anemia is not detected by common screening procedures and is more widespread than IDA. PMID:18272298

A randomised active-controlled trial to examine the effects of an online mindfulness intervention on executive control, critical thinking and key thinking dispositions in a university student sample.

PubMed

Noone, Chris; Hogan, Michael J

2018-04-05

Arguments for including mindfulness instruction in higher education have included claims about the benefits of mindfulness practice for critical thinking. While there is theoretical support for this claim, empirical support is limited. The aim of this study was to test this claim by investigating the effects of an online mindfulness intervention on executive function, critical thinking skills and associated thinking dispositions. Participants recruited from a university were randomly allocated, following screening, to either a mindfulness meditation group or a sham meditation group. Both the researchers and the participants were blind to group allocation. The intervention content for both groups was delivered through the Headspace online application, an application which provides guided meditations to users. Both groups were requested to complete 30 guided mindfulness meditation sessions across a 6 week period. Primary outcome measures assessed mindfulness, executive functioning, critical thinking, actively open-minded thinking and need for cognition. Secondary outcome measures assessed wellbeing, positive and negative affect, and real-world outcomes. In a series of full-information maximum likelihood analyses, significant increases in mindfulness dispositions and critical thinking scores were observed in both the mindfulness meditation and sham meditation groups. However, no significant effects of group allocation were observed for either primary or secondary measures. Furthermore, mediation analyses testing the indirect effect of group allocation through executive functioning performance did not reveal a significant result and moderation analyses showed that the effect of the intervention did not depend on baseline levels of the key thinking dispositions, actively open-minded thinking and need for cognition. No evidence was found to suggest that engaging in guided mindfulness practice for 6 weeks using the online intervention method applied in this study improves critical thinking performance. While further research is warranted, claims regarding the benefits of mindfulness practice for critical thinking should be tempered in the meantime. The study was initially registered in the AEA Social Science Registry before the recruitment was initiated (RCT ID: AEARCTR-0000756; 14/11/2015) and retrospectively registered in the ISRCTN registry ( RCT ID: ISRCTN16588423 ) in line with requirements for publishing the study protocol.

Mindfulness-based cognitive therapy for adults with intellectual disabilities: an evaluation of the effectiveness of mindfulness in reducing symptoms of depression and anxiety.

PubMed

Idusohan-Moizer, H; Sawicka, A; Dendle, J; Albany, M

2015-02-01

Mindfulness-based interventions have been shown to be effective in the treatment of a range of health and psychological disorders in adults and young people without intellectual disabilities (ID). Clinical studies are emerging reporting on the efficacy of mindfulness-based interventions as a stand-alone treatment for common clinical disorders in adults with ID. This paper aims to evaluate the efficacy of an innovative structured mindfulness-based cognitive therapy (MBCT) group programme adapted for adults with ID with a diagnosis of either recurrent depression, anxiety or both clinical conditions and a history of deliberate self-harm behaviour. Two groups ran consecutively consisting of a total of fifteen participants and seven carers. All participants were recorded as having either a borderline, mild, or moderate ID. The group programme ran over a period of 9 weeks with a follow-up session at 6 weeks post group intervention. Outcome measures included the Hospital Anxiety and Depression Scale and two sub-scales from the Self-Compassion Scale administered at baseline, post therapy and at 6-week follow-up. The evaluation showed that participants reported an improvement in their experience of depression, anxiety, self-compassion and compassion for others. The most significant impact was in the reduced levels of anxiety reported. Improvements across all outcomes were maintained at 6-week follow-up. The results of the evaluation suggest that people with intellectual disabilities benefit from a structured MBCT group intervention and the results are maintained at 6-week follow-up. © 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Alternative Instructional Design Paradigms: What's Worth Discussing and What Isn't.

ERIC Educational Resources Information Center

Willis, Jerry

1998-01-01

Examines the paradigm debate over established (behavioral and cognitive) and alternative (constructivist) models of instructional design (ID). Discusses instructional strategies and principles, new terms versus new meaning, "straw man" and personalized arguments, expert-determined goals, research-based versus "brand-X" models,…

Effects of extending the one-more-than technique with the support of a mobile purchasing assistance system.

PubMed

Hsu, Guo-Liang; Tang, Jung-Chang; Hwang, Wu-Yuin

2014-08-01

The one-more-than technique is an effective strategy for individuals with intellectual disabilities (ID) to use when making purchases. However, the heavy cognitive demands of money counting skills potentially limit how individuals with ID shop. This study employed a multiple-probe design across participants and settings, via the assistance of a mobile purchasing assistance system (MPAS), to assess the effectiveness of the one-more-than technique on independent purchases for items with prices beyond the participants' money counting skills. Results indicated that the techniques with the MPAS could effectively convert participants' initial money counting problems into useful advantages for successfully promoting the independent purchasing skills of three secondary school students with ID. Also noteworthy is the fact that mobile technologies could be a permanent prompt for those with ID to make purchases in their daily lives. The treatment effects could be maintained for eight weeks and generalized across three community settings. Implications for practice and future studies are provided. Copyright © 2014 Elsevier Ltd. All rights reserved.

Attachment quality of children with ID and its link to maternal sensitivity and structuring.

PubMed

Feniger-Schaal, Rinat; Joels, Tirtsa

2018-05-01

Attachment theory produced a fertile field of research and clinical application. Although the topic of attachment of children with intellectual disability (ID) has received increasing research attention over the past 15 years, the empirical evidence is still limited. We applied theoretical and empirical knowledge of parenting typically developing children to examine the mother-child relationship in the ID population. The aim was to examine maternal sensitivity and structuring and its association with children's attachment classification and their disability. Forty preschool children (mean age 47.25, range 26-75 months) with non-specific ID and their mothers participated in the study. The mean developmental age was 25.92 months (SD = 10.89), The DQ mean score was 55.45 (SD = 17.28). We assessed children's quality of attachment using the SSP and maternal interactive behavior using the Emotional Availability Scales. Forty percent of children showed secure attachment, and 32.5% showed disorganized attachment. Attachment classifications correlated significantly with maternal sensitivity and maternal structuring but not with the child's cognitive disability. The results point to the importance of maternal interactive behavior for children with ID. Clinical implication may consider interventions aiming to enhance maternal sensitivity and structuring to improve children's quality of attachment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Patterns of Performance on the Modified Cued Recall Test in Spanish Adults With Down Syndrome With and Without Dementia.

PubMed

Benejam, Bessy; Fortea, Juan; Molina-López, Rafael; Videla, Sebastià

2015-11-01

The assessment of memory decline in people with intellectual disability (ID) is more difficult than in the general population, due to a lack of appropriate instruments and to preexisting cognitive impairment. The aim of this study was to describe performance of healthy adults with Down syndrome (healthy-DS; prospectively cohort) on a Spanish version of the modified Cued Recall Test (mCRT). We also recruited retrospectively a cohort of DS subjects with Dementia of the Alzheimer's Type (DS-DAT). Healthy-DS obtained higher scores on free recall and total score than DS-DAT. Age was the main factor associated with decreasing mCRT scores. The mCRT was useful in DS subjects with ID at the upper end of the spectrum or ID in the middle range of the spectrum, and discriminated well between DS subjects with and without DAT.

Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth

PubMed Central

Morton, Derrick; Sharma, Pankaj; Gorantla, Yamini; Joshi, Jugal; Nagappan, Perri; Pallaniappan, Ravi; Chaudhary, Jaideep

2016-01-01

ID4, a helix loop helix transcriptional regulator has emerged as a tumor suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate cancer whereas ectopic expression in prostate cancer cell lines blocks cancer phenotype. To directly investigate the anti-tumor property, full length human recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased apoptosis, decreased proliferation and colony formation. Intratumoral delivery of PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The study supports the feasibility of using nano-carrier encapsulated ID4 protein as a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways for example epigenetic re-programming, integration of multiple AR co-regulators or signaling pathways resulting in tumor suppressor activity of ID4. PMID:27487149

The Effects of Mindfulness on Persons with Mild Cognitive Impairment: Protocol for a Mixed-Methods Longitudinal Study.

PubMed

Wong, Wee Ping; Hassed, Craig; Chambers, Richard; Coles, Jan

2016-01-01

Mild cognitive impairment (MCI) not only negatively impacts upon a person's life, but it is also seen as an intermediate stage on the progression to Alzheimer's Disease (AD), and therefore warrants early intervention. However, there is currently no effective pharmacological treatment approved for MCI. There is a paucity of evidence that non-pharmacological interventions such as cognitive training could result in improvements in the daily activities functioning of persons with MCI. Growing evidence has shown that mindfulness meditation increases gray matter volume and concentration in brain regions such as the hippocampus and prefrontal cortex, strengthens brain functional connectivity, and enhances psychological well-being which could be beneficial to counteract the memory and cognitive decline of MCI. We aim to quantitatively investigate whether mindfulness practice can improve the cognitive function, psychological health, mindfulness and functional abilities in activities of daily living of the MCI participants over time; the relationship between the amount of mindfulness practice and degree of improvement in these health outcomes; and the differential effects and interactions of both formal and informal mindfulness practices. We will also qualitatively address the issues about the MCI participants' and familiar support persons' engagement with the program, the nature of group interactions, their program experience, their perceived effects and expectations of mindfulness practice, and the challenges encountered in practicing mindfulness. Our study is one of the first mixed-methods longitudinal studies with a 1-year follow-up using a pre- and post-intervention design. It involves the MCI participants and their familiar support person in a customized 8-week group-based mindfulness training program. The outcome measures will use the Montreal Cognitive Assessment, Depression Anxiety Stress Scales, Freiburg Mindfulness Inventory and Bayer Activities of Daily Living Scale. The qualitative methods will include participant observation during the program and semi-structured interviews at post-intervention and 1-year follow-up. This customized MCI group mindfulness training program presents as a promising and feasible non-pharmacological therapeutic intervention option for MCI and a possible preventive strategy for Alzheimer's disease. This study has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366695) and allocated the ACTRN12614000820606.

Psychometric Comparison of the Motivation Assessment Scale (MAS) and the Questions about Behavioral Function (QABF)

ERIC Educational Resources Information Center

Koritsas, S.; Iacono, T.

2013-01-01

Background: The Motivation Assessment Scale (MAS) and the Questions About Behavioral Function (QABF) are frequently used to assess the learned function of challenging behaviour in people with intellectual disability (ID). The aim was to explore and compare the psychometric properties of the MAS and the QABF. Method: Seventy adults with ID and…

Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs.

PubMed

Stinson, Julie; Inoue, Toshiaki; Yates, Paula; Clancy, Anne; Norton, John D; Sharrocks, Andrew D

2003-08-15

DNA binding by the ternary complex factor (TCF) subfamily of ETS-domain transcription factors is tightly regulated by intramolecular and intermolecular interactions. The helix-loop-helix (HLH)-containing Id proteins are trans-acting negative regulators of DNA binding by the TCFs. In the TCF, SAP-2/Net/ERP, intramolecular inhibition of DNA binding is promoted by the cis-acting NID region that also contains an HLH-like motif. The NID also acts as a transcriptional repression domain. Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP-1 and how Cdk-mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs. We demonstrate that the NID region of SAP-1 is an autoinhibitory motif that acts to inhibit DNA binding and also functions as a transcription repression domain. This region can be functionally replaced by fusion of Id proteins to SAP-1, whereby the Id moiety then acts to repress DNA binding in cis. Phosphorylation of the Ids by cyclin-Cdk complexes results in reduction in protein-protein interactions between the Ids and TCFs and relief of their DNA-binding inhibitory activity. In revealing distinct mechanisms through which HLH motifs modulate the activity of TCFs, our results therefore provide further insight into the role of HLH motifs in regulating TCF function and how the inhibitory properties of the trans-acting Id HLH proteins are themselves regulated by phosphorylation.

The Relationship Between Challenging Behaviour, Cognitions and Stress in Mothers of Individuals with Intellectual Disabilities.

PubMed

Rose, John; Nelson, Lisa; Hardiman, Rebecca

2016-11-01

Cognitions are starting to receive more prominence as important when examining a number of factors including the topography of challenging behaviour. This study examined the relationships between maternal stress, challenging behaviour (aggressive and self-injurious behaviours) and parental cognitions and specifically whether maternal cognitions mediated the effect of challenging behaviour on parenting stress. 46 mothers of children and young adults with ID completed questionnaires regarding their child's challenging behaviour, maternal cognitions and stress. Significant correlations were found between challenging behaviour and maternal stress. The overall mediation models for aggression and self-injurious behaviour were significant. The Challenging Behaviour Perception Questionnaire: Consequences client subscale was the only independent significant mediator for both behaviours. Cognitions do play an important part in mediating the relationship between challenging behaviour and stress. Further research is needed to examine the similarities and differences between the mediation models for aggression and self-injurious behaviour.

Cardiovascular Pharmacogenomics and Cognitive Function in Patients with Schizophrenia.

PubMed

Ward, Kristen M; Kraal, A Zarina; Flowers, Stephanie A; Ellingrod, Vicki L

2017-09-01

The authors sought to examine the impact of multiple risk alleles for cognitive dysfunction and cardiovascular disease risk on cognitive function and to determine if these relationships varied by cognitive reserve (CR) or concomitant medication use in patients with schizophrenia. They conducted a cross-sectional study in ambulatory mental health centers. A total of 122 adults with a schizophrenia spectrum diagnosis who were maintained on a stable antipsychotic regimen for at least 6 months before study enrollment were included. Patients were divided into three CR groups based on years of formal education: no high school completion or equivalent (low-education group [18 patients]), completion of high school or equivalent (moderate-education group [36 patients], or any degree of post-high school education (high-education group [68 patients]). The following pharmacogenomic variants were genotyped for each patient: AGT M268T (rs699), ACE insertion/deletion (or ACE I/D, rs1799752), and APOE ε2, ε3, and ε4 (rs429358 and rs7412). Risk allele carrier status (identified per gene as AGT M268 T carriers, ACE D carriers, and APOE ε4 carriers) was not significantly different among CR groups. The Brief Assessment of Cognition in Schizophrenia (BACS) scale was used to assess cognitive function. The mean ± SD patient age was 43.9 ± 11.6 years. Cardiovascular risk factors such as hypertension and hyperlipidemia diagnoses, and use of antihypertensive and lipid-lowering agents, did not significantly differ among CR groups. Mixed modeling revealed that risk allele carrier status was significantly associated with lower verbal memory scores for ACE D and APOE ε4 carriers, but AGT T carrier status was significantly associated with higher verbal memory scores (p=0.0188, p=0.0055, and p=0.0058, respectively). These results were only significant in the low-education group. In addition, medication-gene interactions were not significant predictors of BACS scores. ACE D and APOE ε4 carrier status, independent of medication use, was associated with lower verbal memory scores in patients with schizophrenia who had relatively lower CR, as identified by formal education. These results suggest that increasing CR may be protective against cognitive impairment that may be worsened by select cardiovascular risk alleles in patients with schizophrenia. © 2017 Pharmacotherapy Publications, Inc.

Social Perception in Children with Intellectual Disabilities: The Interpretation of Benign and Hostile Intentions

ERIC Educational Resources Information Center

Leffert, J. S.; Siperstein, G. N.; Widaman, K. F.

2010-01-01

Background: A key aspect of social perception is the interpretation of others' intentions. Children with intellectual disabilities (IDs) have difficulty interpreting benign intentions when a negative event occurs. From a cognitive processing perspective, interpreting benign intentions can be challenging because it requires integration of…

Predicting Expressive Vocabulary Acquisition in Children with Intellectual Disabilities: A 2-Year Longitudinal Study

ERIC Educational Resources Information Center

Vandereet, Joke; Maes, Bea; Lembrechts, Dirk; Zink, Inge

2010-01-01

Purpose: This study's objectives were to describe expressive vocabulary acquisition in children with intellectual disabilities (ID) and to examine specific pre- and early linguistic behaviors used to request and comment, chronological age, cognitive skills, and vocabulary comprehension as predictors of expressive vocabulary. Method: This study…

Atypical Sleep Architecture and Altered EEG Spectra in Williams Syndrome

ERIC Educational Resources Information Center

Gombos, F.; Bodizs, R.; Kovacs, I.

2011-01-01

Background: Williams syndrome (WS) is a neurodevelopmental genetic disorder characterised by physical abnormalities and a distinctive cognitive profile with intellectual disabilities (IDs) and learning difficulties. Methods: In our study, nine adolescents and young adults with WS and 9 age- and sex-matched typically developing (TD) participants…

Exploring the complexity of intellectual disability in fetal alcohol spectrum disorders.

PubMed

Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M

2014-01-01

Brain development in mammals is long lasting. It begins early during embryonic growth and is finalized in early adulthood. This progression represents a delicate choreography of molecular, cellular, and physiological processes initiated and directed by the fetal genotype in close interaction with environment. Not surprisingly, most aberrations in brain functioning including intellectual disability (ID) are attributed to either gene(s), or environment or the interaction of the two. The ensuing complexity has made the assessment of this choreography, ever challenging. A model to assess this complexity has used a mouse model (C57BL/6J or B6) that is subjected to prenatal alcohol exposure. The resulting pups show learning and memory deficits similar to patients with fetal alcohol spectrum disorder (FASD), which is associated with life-long changes in gene expression. Interestingly, this change in gene expression underlies epigenetic processes including DNA methylation and miRNAs. This paradigm is applicable to ethanol exposure at different developmental times (binge at trimesters 1, 2, and 3 as well as continuous preference drinking (70%) of 10% alcohol by B6 females during pregnancy). The exposure leads to life-long changes in neural epigenetic marks, gene expression, and a variety of defects in neurodevelopment and CNS function. We argue that this cascade may be reversed postnatally via drugs, chemicals, and environment including maternal care. Such conclusions are supported by two sets of results. First, antipsychotic drugs that are used to treat ID including psychosis function via changes in DNA methylation, a major epigenetic mark. Second, post-natal environment may improve (with enriched environments) or worsen (with negative and maternal separation stress) the cognitive ability of pups that were prenatally exposed to ethanol as well as their matched controls. In this review, we will discuss operational epigenetic mechanisms involved in the development of intellectual ability/disability in response to alcohol during prenatal or post-natal development. In doing so, we will explore the potential of epigenetic manipulation in the treatment of FASD and related disorders implicated in ID.

Exploring the Complexity of Intellectual Disability in Fetal Alcohol Spectrum Disorders

PubMed Central

Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M.

2014-01-01

Brain development in mammals is long lasting. It begins early during embryonic growth and is finalized in early adulthood. This progression represents a delicate choreography of molecular, cellular, and physiological processes initiated and directed by the fetal genotype in close interaction with environment. Not surprisingly, most aberrations in brain functioning including intellectual disability (ID) are attributed to either gene(s), or environment or the interaction of the two. The ensuing complexity has made the assessment of this choreography, ever challenging. A model to assess this complexity has used a mouse model (C57BL/6J or B6) that is subjected to prenatal alcohol exposure. The resulting pups show learning and memory deficits similar to patients with fetal alcohol spectrum disorder (FASD), which is associated with life-long changes in gene expression. Interestingly, this change in gene expression underlies epigenetic processes including DNA methylation and miRNAs. This paradigm is applicable to ethanol exposure at different developmental times (binge at trimesters 1, 2, and 3 as well as continuous preference drinking (70%) of 10% alcohol by B6 females during pregnancy). The exposure leads to life-long changes in neural epigenetic marks, gene expression, and a variety of defects in neurodevelopment and CNS function. We argue that this cascade may be reversed postnatally via drugs, chemicals, and environment including maternal care. Such conclusions are supported by two sets of results. First, antipsychotic drugs that are used to treat ID including psychosis function via changes in DNA methylation, a major epigenetic mark. Second, post-natal environment may improve (with enriched environments) or worsen (with negative and maternal separation stress) the cognitive ability of pups that were prenatally exposed to ethanol as well as their matched controls. In this review, we will discuss operational epigenetic mechanisms involved in the development of intellectual ability/disability in response to alcohol during prenatal or post-natal development. In doing so, we will explore the potential of epigenetic manipulation in the treatment of FASD and related disorders implicated in ID. PMID:25207264

The research on the status, rehabilitation, education, vocational development, social integration and support services related to intellectual disability in China.

PubMed

Wu, Lihui; Qiu, Zhuoying; Wong, Daniel; Hernandez, Lucy Wong; Zhao, Qianlei

2010-01-01

Intellectual disability (ID) is a prevalent form of non-progressive cognitive impairment. The objectives of this articles are: to analyze the changes of ID in China, including its definition, prevalence, rehabilitation, education, vocational development, social life and support services; to review and to compare the issues of intellectual disability in China with the international literatures and research studies and to provide useful updated information and reference data for scholars and researchers who study intellectual disability. Analyzed the data obtained from two national sample surveys on disability with respect to intellectual disability in China. The estimated prevalence of individuals with intellectual disabilities in China was 7.5‰ in 2006 nationally which was lower than the previous results obtained in the 1987 national survey. The fourth level of ID showed a downward trend, while the proportion among the population aged 60 and over with ID tended to increase. The 2006 national survey indicated that the prevalence of ID in rural areas was higher than that in urban areas. This finding was consistent with the national survey conducted in 1987. As indicated by the 2006 national survey, 29.4% cases had no known causes for the ID, the proportion tended to decrease as compared with the first survey. However, when compared to the 1987 report, the proportion of senile dementia among older people as indicated by the 2006 report was higher than before. During the past years, the prevention of ID and the quality of life of individuals with ID have improved due to the enactment and implementation of a series of national laws and regulations, however, there is more that needs to be done in the areas of education, vocational development, social integration and support services for individuals with ID in order to improve the quality of life of individuals with ID in China. The findings of this study are consistent with the research findings presented in the international literatures. ID is the conditions that deserve further study and deserve the attention of policy makers and rehabilitation professionals in China. Furthermore, with the ageing of population in China and its impact to the social security system, the in-depth study of ID and its implications has become more pertinent in China in the future. Copyright © 2010 Elsevier Ltd. All rights reserved.

XSIM Final Report: Modelling the Past and Future of Identity Management for Scientific Collaborations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cowles, Robert; Jackson, Craig; Welch, Von

The eXtreme Science Identity Management (XSIM1) research project: collected and analyzed real world data on virtual organization (VO) identity management (IdM) representing the last 15+ years of collaborative DOE science; constructed a descriptive VO IdM model based on that data; used the model and existing trends to project the direction for IdM in the 2020 timeframe; and provided guidance to scientific collaborations and resource providers that are implementing or seeking to improve IdM functionality. XSIM conducted over 20 semi­structured interviews of representatives from scientific collaborations and resource providers, both in the US and Europe; the interviewees supported diverse set ofmore » scientific collaborations and disciplines. We developed a definition of “trust,” a key concept in IdM, to understand how varying trust models affect where IdM functions are performed. The model identifies how key IdM data elements are utilized in collaborative scientific workflows, and it has the flexibility to describe past, present and future trust relationships and IdM implementations. During the funding period, we gave more than two dozen presentations to socialize our work, encourage feedback, and improve the model; we also published four refereed papers. Additionally, we developed, presented, and received favorable feedback on three white papers providing practical advice to collaborations and/or resource providers.« less

Psychiatric Disorders in Outpatients With Borderline Intellectual Functioning: Comparison With Both Outpatients From Regular Mental Health Care and Outpatients With Mild Intellectual Disabilities

PubMed Central

Wieland, Jannelien; Haan, Sara Kapitein-de; Zitman, Frans G

2014-01-01

Objective: In the Netherlands, patients with borderline intellectual functioning are eligible for specialized mental health care. This offers the unique possibility to examine the mix of psychiatric disorders in patients who, in other countries, are treated in regular outpatient mental health care clinics. Our study sought to examine the rates of all main Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis I psychiatric diagnoses in outpatients with borderline intellectual functioning of 2 specialized regional psychiatric outpatient departments and to compare these with rates of the same disorders in outpatients from regular mental health care (RMHC) and outpatients with mild intellectual disabilities (IDs). Method: Our study was a cross-sectional, anonymized medical chart review. All participants were patients from the Dutch regional mental health care provider Rivierduinen. Diagnoses of patients with borderline intellectual functioning (borderline intellectual functioning group; n = 235) were compared with diagnoses of patients from RMHC (RMHC group; n = 1026) and patients with mild ID (mild ID group; n = 152). Results: Compared with the RMHC group, psychotic and major depressive disorders were less common in the borderline intellectual functioning group, while posttraumatic stress disorder and V codes were more common. Compared with the mild ID group, psychotic disorders were significantly less common. Conclusion: Mental health problems in people with borderline intellectual functioning may not be well addressed in general psychiatry, or by standard psychiatry for patients with ID. Specific attention to this group in clinical practice and research may be warranted lest they fall between 2 stools. PMID:25007114

Psychiatric disorders in outpatients with borderline intellectual functioning: comparison with both outpatients from regular mental health care and outpatients with mild intellectual disabilities.

PubMed

Wieland, Jannelien; Kapitein-de Haan, Sara; Zitman, Frans G

2014-04-01

In the Netherlands, patients with borderline intellectual functioning are eligible for specialized mental health care. This offers the unique possibility to examine the mix of psychiatric disorders in patients who, in other countries, are treated in regular outpatient mental health care clinics. Our study sought to examine the rates of all main Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis I psychiatric diagnoses in outpatients with borderline intellectual functioning of 2 specialized regional psychiatric outpatient departments and to compare these with rates of the same disorders in outpatients from regular mental health care (RMHC) and outpatients with mild intellectual disabilities (IDs). Our study was a cross-sectional, anonymized medical chart review. All participants were patients from the Dutch regional mental health care provider Rivierduinen. Diagnoses of patients with borderline intellectual functioning (borderline intellectual functioning group; n = 235) were compared with diagnoses of patients from RMHC (RMHC group; n = 1026) and patients with mild ID (mild ID group; n = 152). Compared with the RMHC group, psychotic and major depressive disorders were less common in the borderline intellectual functioning group, while posttraumatic stress disorder and V codes were more common. Compared with the mild ID group, psychotic disorders were significantly less common. Mental health problems in people with borderline intellectual functioning may not be well addressed in general psychiatry, or by standard psychiatry for patients with ID. Specific attention to this group in clinical practice and research may be warranted lest they fall between 2 stools.

Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Yang, Guoyan; Wang, Yuyi; Tian, Jinzhou; Liu, Jian-Ping

2013-01-01

Background Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease. Methods We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249) Results 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A. Conclusions Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials. PMID:24086396

Motor competency and social communication skills in preschool children with autism spectrum disorder.

PubMed

Craig, Francesco; Lorenzo, Alessandro; Lucarelli, Elisabetta; Russo, Luigi; Fanizza, Isabella; Trabacca, Antonio

2018-06-01

This study aimed to investigate the association between motor competency and social communication in children with Autism Spectrum Disorder (ASD) compared with children with Intellectual Disabilities (ID) and typically developing (TD) children. Motor competency, ASD symptoms, and nonverbal Intelligent Quotient (IQ) were investigated through the following tests: Movement Assessment Battery for Children, second edition (MABC-2), Social Communication Questionnaire (SCQ), Autism Classification System of Functioning: Social Communication (ACSF:SC) and Leiter International Performances Scale Revised (Leiter-R). The ASD + ID and ID groups had lower MABC-2-manual dexterity mean scores, MABC-2-aiming and catching mean scores, MABC-2-static and dynamic balance mean scores and MABC-2-TTS compared with the TD group (P < 0.05). In addition, the ASD + ID group had lower MABC-2-aiming and catching mean scores compared with the ID group. In the ASD + ID group, we found a significant negative correlation (P < 0.001) between MABC-2-aiming and catching scores with SCQ scores, nonverbal IQ and ACSF:SC levels. Our findings provide new insight into the common neuropsychological mechanisms underlying social communication and motor deficits in ASD. Multiple deficits in motor functioning may be present in ASD and ID, however deficits involving the ability to integrate motor and social cues are somewhat specific to ASD. Autism Res 2018, 11: 893-902. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. This study highlighted the specificity of motor impairment in ASD comparing performances on a frequently used measure of motor impairment between clinical groups (ASD + ID and ID) and a non-clinical group. While previous research has suggested that multiple deficits in motor functioning may be present in ASD, our findings suggest that deficits in tasks involving the ability to integrate visual and motor cues (aiming and catching task) are somewhat specific to ASD. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

A puzzle form of a non-verbal intelligence test gives significantly higher performance measures in children with severe intellectual disability

PubMed Central

Bello, Katrina D; Goharpey, Nahal; Crewther, Sheila G; Crewther, David P

2008-01-01

Background Assessment of 'potential intellectual ability' of children with severe intellectual disability (ID) is limited, as current tests designed for normal children do not maintain their interest. Thus a manual puzzle version of the Raven's Coloured Progressive Matrices (RCPM) was devised to appeal to the attentional and sensory preferences and language limitations of children with ID. It was hypothesized that performance on the book and manual puzzle forms would not differ for typically developing children but that children with ID would perform better on the puzzle form. Methods The first study assessed the validity of this puzzle form of the RCPM for 76 typically developing children in a test-retest crossover design, with a 3 week interval between tests. A second study tested performance and completion rate for the puzzle form compared to the book form in a sample of 164 children with ID. Results In the first study, no significant difference was found between performance on the puzzle and book forms in typically developing children, irrespective of the order of completion. The second study demonstrated a significantly higher performance and completion rate for the puzzle form compared to the book form in the ID population. Conclusion Similar performance on book and puzzle forms of the RCPM by typically developing children suggests that both forms measure the same construct. These findings suggest that the puzzle form does not require greater cognitive ability but demands sensory-motor attention and limits distraction in children with severe ID. Thus, we suggest the puzzle form of the RCPM is a more reliable measure of the non-verbal mentation of children with severe ID than the book form. PMID:18671882

A puzzle form of a non-verbal intelligence test gives significantly higher performance measures in children with severe intellectual disability.

PubMed

Bello, Katrina D; Goharpey, Nahal; Crewther, Sheila G; Crewther, David P

2008-08-01

Assessment of 'potential intellectual ability' of children with severe intellectual disability (ID) is limited, as current tests designed for normal children do not maintain their interest. Thus a manual puzzle version of the Raven's Coloured Progressive Matrices (RCPM) was devised to appeal to the attentional and sensory preferences and language limitations of children with ID. It was hypothesized that performance on the book and manual puzzle forms would not differ for typically developing children but that children with ID would perform better on the puzzle form. The first study assessed the validity of this puzzle form of the RCPM for 76 typically developing children in a test-retest crossover design, with a 3 week interval between tests. A second study tested performance and completion rate for the puzzle form compared to the book form in a sample of 164 children with ID. In the first study, no significant difference was found between performance on the puzzle and book forms in typically developing children, irrespective of the order of completion. The second study demonstrated a significantly higher performance and completion rate for the puzzle form compared to the book form in the ID population. Similar performance on book and puzzle forms of the RCPM by typically developing children suggests that both forms measure the same construct. These findings suggest that the puzzle form does not require greater cognitive ability but demands sensory-motor attention and limits distraction in children with severe ID. Thus, we suggest the puzzle form of the RCPM is a more reliable measure of the non-verbal mentation of children with severe ID than the book form.

Iron deficiency is associated with food insecurity in pregnant females in the United States: National Health and Nutrition Examination Survey 1999-2010.

PubMed

Park, Clara Y; Eicher-Miller, Heather A

2014-12-01

Food-insecure pregnant females may be at greater risk of iron deficiency (ID) because nutrition needs increase and more resources are needed to secure food during pregnancy. This may result in a higher risk of infant low birth weight and possibly cognitive impairment in the neonate. The relationships of food insecurity and poverty income ratio (PIR) with iron intake and ID among pregnant females in the United States were investigated using National Health and Nutrition Examination Survey 1999-2010 data (n=1,045). Food security status was classified using the US Food Security Survey Module. One 24-hour dietary recall and a 30-day supplement recall were used to assess iron intake. Ferritin, soluble transferrin receptor, or total body iron classified ID. Difference of supplement intake prevalence, difference in mean iron intake, and association of ID and food security status or PIR were assessed using χ(2) analysis, Student t test, and logistic regression analysis (adjusted for age, race, survey year, PIR/food security status, education, parity, trimester, smoking, C-reactive protein level, and health insurance coverage), respectively. Mean dietary iron intake was similar among groups. Mean supplemental and total iron intake were lower, whereas odds of ID, classified by ferritin status, were 2.90 times higher for food-insecure pregnant females compared with food-secure pregnant females. Other indicators of ID were not associated with food security status. PIR was not associated with iron intake or ID. Food insecurity status may be a better indicator compared with income status to identify populations at whom to direct interventions aimed at improving access and education regarding iron-rich foods and supplements. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Vagus Nerve Stimulation in children: A focus on intellectual disability.

PubMed

Sourbron, Jo; Klinkenberg, Sylvia; Kessels, Alfons; Schelhaas, Helenius Jurgen; Lagae, Lieven; Majoie, Marian

2017-05-01

Vagus Nerve Stimulation (VNS) can be an efficacious add-on treatment in patients with drug-resistant epilepsy, who are not eligible for surgery. Evidence of VNS efficacy in children with intellectual disability (ID) is scarce. The purpose of this study was to review all available VNS data in the pediatric population (≤18 years old) and focus on the subpopulation with ID since appropriate treatment of these children is often challenging and complex. Cochrane, EMBASE, PubMed and MEDLINE were used to collect all research associated to VNS and ID (or synonyms) leading to a total of 37 studies. Seven studies showed the results of patients with ID and those without separately; thereby only these studies were included in the VNS meta-analysis. Our meta-analysis showed that VNS was less effective in pediatric epilepsy patients with ID compared to those without ID (Mantel-Haenszel meta-analysis; p = 0.028, OR 0.18 (CI 95% 0.039-0.84)). However, there were no prospective controlled studies. Numerous studies reported quality of life (QoL) improvements in this subpopulation. The most common adverse events were transient and well tolerated. Side effects on cognition and behavior were not reported. These results might be a reason to consider VNS early on in the treatment of this subgroup. The significantly greater amount of retrospective studies, differences in follow-up (FU), lack of control data, heterogeneous series and limited number of patients could have biased the outcome measurements. Hence, current data do not exclude VNS for children with drug-resistant epilepsy and ID but should be interpreted with caution. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The "id" knows more than the "ego" admits: neuropsychoanalytic and primal consciousness perspectives on the interface between affective and cognitive neuroscience.

PubMed

Solms, Mark; Panksepp, Jaak

2012-04-17

It is commonly believed that consciousness is a higher brain function. Here we consider the likelihood, based on abundant neuroevolutionary data that lower brain affective phenomenal experiences provide the "energy" for the developmental construction of higher forms of cognitive consciousness. This view is concordant with many of the theoretical formulations of Sigmund Freud. In this reconceptualization, all of consciousness may be dependent on the original evolution of affective phenomenal experiences that coded survival values. These subcortical energies provided a foundation that could be used for the epigenetic construction of perceptual and other higher forms of consciousness. From this perspective, perceptual experiences were initially affective at the primary-process brainstem level, but capable of being elaborated by secondary learning and memory processes into tertiary-cognitive forms of consciousness. Within this view, although all individual neural activities are unconscious, perhaps along with secondary-process learning and memory mechanisms, the primal sub-neocortical networks of emotions and other primal affects may have served as the sentient scaffolding for the construction of resolved perceptual and higher mental activities within the neocortex. The data supporting this neuro-psycho-evolutionary vision of the emergence of mind is discussed in relation to classical psychoanalytical models.

Delirium After Mechanical Ventilation in Intensive Care Units: The Cognitive and Psychosocial Assessment (CAPA) Study Protocol.

PubMed

Bulic, Daniella; Bennett, Michael; Rodgers, Helen; Nourse, Mary; Rubie, Patrick; Looi, Jeffrey Cl; Van Haren, Frank

2017-02-28

In the intensive care unit (ICU), critical illness delirium occurs in the context of multiple comorbidities, multi-organ failure, and invasive management techniques, such as mechanical ventilation, sedation, and lack of sleep. Delirium is characterized by an acute confusional state defined by fluctuating mental status, inattention, and either disorganized thinking or an altered level of consciousness. The long-term cognitive and psychosocial function of patients that experience delirium in the ICU is of crucial interest because preliminary data suggest a strong association between ICU-related delirium and long-term cognitive impairment. The aim of this study is to explore the relationship between delirium in the ICU and adverse outcomes by following mechanically ventilated patients for one year following their discharge from the ICU and collecting data on their long-term cognition and psychosocial function. This study will be conducted by enrolling patients in two tertiary ICUs in Australia. We aim to recruit 200 patients who have been mechanically ventilated for more than 24 hours. Data will be collected at the following three time points: (1) at discharge where they will be administered the Mini-Mental State Examination (MMSE); (2) at 6 months after discharge from the ICU discharge where the Impact of Events Scale Revised (IES-R) and the Telephone Inventory for Cognitive Status (TICS) tests will be administered; and (3) at 12 months after discharge from the ICU where the patients will be administered the TICS and IES-R tests, as well as the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE). The IQCODE will be administered to their "person responsible" or the significant other of the patient. Long-term cognition and psychosocial function will be the primary outcome of this study. Mortality will also be investigated as a secondary outcome. Active enrollment will take place until the end of September 2016 and data collection will conclude at the end of September 2017. The analysis and results are expected to be available by March 2018. Delirium during mechanical ventilation has been linked to longer ICU and hospital stays, higher financial burdens, increased risks of long-term cognitive impairment (ie, dementia), poor functional outcomes and quality of life, and decreased survival. However, delirium during mechanical ventilation in the ICU is not well understood. This study will advance our knowledge of the comprehensive, long-term effects of delirium on cognitive and psychosocial function. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616001116415; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371216 (Archived by WebCite at http://www.webcitation.org/ 6nfDkGTcW). ©Daniella Bulic, Michael Bennett, Helen Rodgers, Mary Nourse, Patrick Rubie, Jeffrey CL Looi, Frank Van Haren. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 28.02.2017.

Absolute and functional iron deficiency in professional athletes during training and recovery.

PubMed

Reinke, Simon; Taylor, William R; Duda, Georg N; von Haehling, Stephan; Reinke, Petra; Volk, Hans-Dieter; Anker, Stefan D; Doehner, Wolfram

2012-04-19

Iron deficiency (ID) is one of the most important metabolic dysfunctions. Athletic performance depends on oxygen transport and mitochondrial efficiency, thus on optimal iron balance. We hypothesised that physical extremes result in ID in elite athletes and that the short recovery period may be insufficient to allow a lasting replenishment of iron reserves. Iron metabolism was examined in 20 elite rowing athletes and 10 professional soccer players at the end of a competitive season, after recuperation and during pre-season training. Absolute ID values were defined as ferritin <30 μg/L, functional ID as ferritin 30-99 μg/L or 100-299 μg/L+transferrin saturation <20%. At the end of season, 27% of all athletes had absolute ID and 70% showed functional ID. Absolute iron depletion was not generally restored after recuperation and observed at all time points in 14% of the athletes. Although athletes with initially low ferritin levels showed a slight increase during recuperation (p<0.09), these increases remained within borderline levels. Furthermore, 10% showed borderline haemoglobin levels, suggestive of mild anaemia, as defined by the World Health Organisation. A significant proportion of professional athletes have ID, independent of the training mode. Although recuperation seems to allow a certain recovery of iron storage, particularly in athletes with initially low ferritin levels, this retrieval was insufficient to fully normalise reduced iron levels. Therefore, iron status should be carefully monitored during the various training and competitive periods in elite athletes. An adequate iron supplementation may be needed to maintain balanced iron stores. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study

PubMed Central

Chamberlain, Samuel R.; Odlaug, Brian L.; Potenza, Marc N.; Kim, Suck Won

2012-01-01

Rationale Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl d-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. Objective This study sought to examine the safety and efficacy of Memantine in PG. Methods Twenty-nine subjects (18 females) with DSM-IV PG were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra-dimensional (ID/ED) set shift task (assessing cognitive flexibility). Results Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8±4.3 at baseline to 8.9±7.1 at study endpoint (p<0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p<0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p=0.037) at study endpoint. The mean effective dose of memantine was 23.4±8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. Conclusions These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design. PMID:20721537

Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study.

PubMed

Grant, Jon E; Chamberlain, Samuel R; Odlaug, Brian L; Potenza, Marc N; Kim, Suck Won

2010-12-01

Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. This study sought to examine the safety and efficacy of Memantine in PG. Twenty-nine subjects (18 females) with DSM-IV PG were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra-dimensional (ID/ED) set shift task (assessing cognitive flexibility). Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8 ± 4.3 at baseline to 8.9 ± 7.1 at study endpoint (p < 0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p < 0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p = 0.037) at study endpoint. The mean effective dose of memantine was 23.4 ± 8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

Sleep and Daytime Functioning: A Short-Term Longitudinal Study of Three Preschool-Age Comparison Groups

ERIC Educational Resources Information Center

Anders, Thomas; Iosif, Ana-Maria; Schwichtenberg, A. J.; Tang, Karen; Goodlin-Jones, Beth

2012-01-01

This study examined sleep, sleepiness, and daytime performance in 68 children with autism, 57 children with intellectual disability (ID), and 69 typically developing preschool children. Children in the autism and ID groups had poorer daytime performance and behaviors than the typically developing children. Children in the ID group also were…

Parents' Perceptions of the Supports Received for Their Children's Problem Behaviors

ERIC Educational Resources Information Center

Schofield, Dean Alexander

2012-01-01

Individuals with significant intellectual disabilities (ID) are more likely to engage in problem behaviors than are people with milder disabilities or with no disability. It is widely considered that behavior problems serve a communicative function for individuals with severe ID and limited communication skills. Among people with significant ID,…

Characteristics associated with willingness to participate in a randomized controlled behavioral clinical trial using home-based personal computers and a webcam.

PubMed

Dodge, Hiroko H; Katsumata, Yuriko; Zhu, Jian; Mattek, Nora; Bowman, Molly; Gregor, Mattie; Wild, Katherine; Kaye, Jeffrey A

2014-12-23

Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam and the internet would have a positive effect on cognitive function among older adults with normal cognition or mild cognitive impairment. To examine the selectivity of samples, we conducted a mass mail-in survey distribution among community-dwelling older adults, assessing factors associated with a willingness to participate in the trial. Two thousand mail-in surveys were distributed to retirement communities in order to collect data on demographics, the nature and frequency of social activities, personal computer use and additional health-related variables, and interest in the prevention study. We also asked for their contact information if they were interested in being contacted as potential participants in the trial. Of 1,102 surveys returned (55.1% response rate), 983 surveys had complete data for all the variables of interest. Among them, 309 showed interest in the study and provided their contact information (operationally defined as the committed with interest group), 74 provided contact information without interest in the study (committed without interest group), 66 showed interest, but provided no contact information (interest only group), and 534 showed no interest and provided no contact information (no interest group). Compared with the no interest group, the committed with interest group were more likely to be personal computer users (odds ratio (OR) = 2.78), physically active (OR = 1.03) and had higher levels of loneliness (OR = 1.16). Increasing potential participants' familiarity with a personal computer and the internet before trial recruitment could increase participation rates and improve the generalizability of future studies of this type. The trial was registered on 29 March 2012 at ClinicalTirals.gov (ID number NCT01571427).

Dental care among young adults with intellectual disability

PubMed Central

Kancherla, Vijaya; Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn

2015-01-01

Dental care among young adults with intellectual disability (ID) is poorly documented and largely unmet. By using population-based data from the Metropolitan Atlanta Developmental Disabilities Follow-Up Study, we assessed factors associated with at least one or two dental visits per year among young adults with and without ID. Significantly fewer young adults with ID (45%) visited a dentist at least once per year, compared with those without ID (58%). ID severity and the presence of co-occurring developmental disabilities predicted dental care use. Sociodemographics, daily functioning, societal participation, dental services, and dental health factors were examined as predictors of dental care frequency. Our findings can help focus efforts toward improving the frequency of dental care visits among young adults with ID. PMID:23501584

Affective learning in adults with intellectual disability: an experiment using evaluative conditioning.

PubMed

Blanchette, I; Treillet, V; Davies, S R

2016-03-01

Evaluative conditioning is a form of affective learning in which initially neutral stimuli acquire an affective value through association with negative or positive stimuli. Recent research shows an important role for cognitive resources in this type of learning. This form of affective learning has rarely been studied in intellectual disability (ID). We examined evaluative conditioning in 16 adults with mild to moderate ID compared to age- and gender-matched control participants. Neutral shapes and symbols were repeatedly paired with positive, neutral or negative unconditioned stimuli (faces or International Affective Picture System images). There was also an extinction phase. There was significant acquisition of conditioning in both groups. Stimuli paired with positive images were evaluated more positively, and stimuli paired with negative images were evaluated more negatively. Post-extinction ratings however show that these novel affective associations were not maintained by individuals with ID as much as by individuals in the control group. We conclude that ID modulates some aspects of affective learning but not necessarily initial preference acquisition. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Identity-level representations affect unfamiliar face matching performance in sequential but not simultaneous tasks.

PubMed

Menon, Nadia; White, David; Kemp, Richard I

2015-01-01

According to cognitive and neurological models of the face-processing system, faces are represented at two levels of abstraction. First, image-based pictorial representations code a particular instance of a face and include information that is unrelated to identity-such as lighting, pose, and expression. Second, at a more abstract level, identity-specific representations combine information from various encounters with a single face. Here we tested whether identity-level representations mediate unfamiliar face matching performance. Across three experiments we manipulated identity attributions to pairs of target images and measured the effect on subsequent identification decisions. Participants were instructed that target images were either two photos of the same person (1ID condition) or photos of two different people (2ID condition). This manipulation consistently affected performance in sequential matching: 1ID instructions improved accuracy on "match" trials and caused participants to adopt a more liberal response bias than the 2ID condition. However, this manipulation did not affect performance in simultaneous matching. We conclude that identity-level representations, generated in working memory, influence the amount of variation tolerated between images, when making identity judgements in sequential face matching.

Marginal Iodine Deficiency Affects Dendritic Spine Development by Disturbing the Function of Rac1 Signaling Pathway on Cytoskeleton.

PubMed

Min, Hui; Dong, Jing; Wang, Yi; Wang, Yuan; Yu, Ye; Shan, Zhongyan; Xi, Qi; Teng, Weiping; Chen, Jie

2017-01-01

Iodine deficiency (ID)-induced thyroid hormone (TH) insufficient during development leads to impairments of brain function, such as learning and memory. Marginal ID has been defined as subtle insufficiency of TH, characterized as low thyroxine (T 4 ) levels, whether marginal ID potentially had adverse effects on the development of hippocampus and the underlying mechanisms remain unclear. Thus, in the present study, we established Wistar rat models with ID diet during pregnancy and lactation. The effects of marginal ID on long-term potentiation (LTP) were investigated in the hippocampal CA1 region. To study the development of dendritic spines in pyramidal cells, Golgi-Cox staining was conducted on postnatal day (PN) 7, PN14, PN21, and PN28. The activation of Rac1 signaling pathway, which is essential for dendritic spine development by regulating actin cytoskeleton, was also investigated. Our results showed that marginal ID slightly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Besides, the density of dendritic spines during the critical period of rat postnatal development was mildly decreased, and we found no significant change of spine morphology in marginal ID group. We also observed decreased activation of the Rac1 signaling pathway in pups subjected to maternal marginal ID. Our study may support the hypothesis that decreased T 4 induced by marginal ID results in slight impairments of LTP and leads to mild damage of dendritic spine development, which may be due to abnormal regulation of Rac1 signaling pathway on cytoskeleton.

Carbohydrate degrading polypeptide and uses thereof

DOEpatents

Sagt, Cornelis Maria Jacobus; Schooneveld-Bergmans, Margot Elisabeth Francoise; Roubos, Johannes Andries; Los, Alrik Pieter

2015-10-20

The invention relates to a polypeptide having carbohydrate material degrading activity which comprises the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 4, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional protein and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

The role of community nurses and residential staff in supporting women with intellectual disability to access breast screening services.

PubMed

Taggart, L; Truesdale-Kennedy, M; McIlfatrick, S

2011-01-01

Women with intellectual disability (ID) are surviving to the age group at greatest risk of developing breast cancer (50-69 years). These women are more likely to experience a greater number of risk factors placing them at an advanced threat of developing breast cancer. However, as a result of cognitive deficits and communication difficulties these women are dependent upon staff to support them to attend the breast screening clinics. The aim of this paper was to examine how community nurses and residential staff support women with ID to access breast screening services. Six focus groups were held with community nurses and residential staff who work in the field of ID in one region of the UK. The focus groups were tape recorded and the transcriptions were subjected to a thematic content analysis. Although many of the participants recognised the risk factors and signs/symptoms of breast cancer, there was still a deficit of knowledge. Both positive and negative experiences of women with ID attending for breast screening were reported; however, greater discussion focused on the latter. The participants identified 'a lack of health educational material' and also negative 'emotions, attitudes and physical barriers' as inhibiting factors for attendance. This paper highlights the need for developing a health promotion programme for women with ID focusing on breast awareness and information on screening, and also healthier lifestyles. Breast awareness via visual checks was identified for women with ID who refused to attend the breast clinics; however, issues of informed 'consent' and 'vulnerability' were raised for staff and also family carers having to undertake these checks. Development of user-friendly health educational literature using 'pictures, symbols, signs' and simplified words should be accessible to all ID staff, healthcare staff, and also women with ID. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

Pathways from Birth Weight to ADHD Symptoms through Fluid Reasoning in Youth with or without Intellectual Disability.

PubMed

Morgan, Julia E; Lee, Steve S; Loo, Sandra K; Yuhan, Joshua W; Baker, Bruce L

2018-05-01

Although individual differences in fluid reasoning reliably mediate predictions of attention-deficit/hyperactivity disorder (ADHD) symptoms from birth weight in youth with typical cognitive development (TD), it is unknown if this indirect effect operates similarly in the development of ADHD symptoms secondary to intellectual disability (ID). Thus, we evaluated mediation by fluid reasoning in a longitudinal sample of 163 youth (45% female) with (n = 52) or without (n = 111) ID who were followed prospectively from age 5 to age 13. At age 9, youth completed the Arithmetic subtest of the Wechsler Intelligence Scale for Children, a measure of fluid reasoning. At ages 9 and 13, mothers and teachers separately rated youth ADHD symptoms and mothers completed a diagnostic interview. Mediation was tested via path analysis with bootstrapped confidence intervals, and moderated mediation estimated whether indirect effects differed between ID and TD youth or based on youth IQ. Controlling for demographic factors and age 9 ADHD symptoms, age 9 Arithmetic mediated birth weight and multi-method/informant age 13 ADHD symptoms, such that birth weight positively predicted Arithmetic, which negatively predicted ADHD symptoms. Neither ID status nor IQ moderated the observed indirect effect through Arithmetic, suggesting that it was similar for ID and TD youth as well as across the range of youth IQs. These findings support previous evidence that fluid reasoning, as measured by Arithmetic, may causally mediate birth weight and ADHD symptoms, and suggest that this pathway operates similarly with respect to the development of ADHD symptoms in youth with ID.

20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition

PubMed Central

Piton, Amélie; Poquet, Hélène; Redin, Claire; Masurel, Alice; Lauer, Julia; Muller, Jean; Thevenon, Julien; Herenger, Yvan; Chancenotte, Sophie; Bonnet, Marlène; Pinoit, Jean-Michel; Huet, Frédéric; Thauvin-Robinet, Christel; Jaeger, Anne-Sophie; Le Gras, Stéphanie; Jost, Bernard; Gérard, Bénédicte; Peoc'h, Katell; Launay, Jean-Marie; Faivre, Laurence; Mandel, Jean-Louis

2014-01-01

Intellectual disability (ID) is characterized by an extraordinary genetic heterogeneity, with >250 genes that have been implicated in monogenic forms of ID. Because this complexity precluded systematic testing for mutations and because clinical features are often non-specific, for some of these genes only few cases or families have been unambiguously documented. It is the case of the X-linked gene encoding monoamine oxidase A (MAOA), for which only one nonsense mutation has been identified in Brunner syndrome, characterized in a single family by mild non-dysmorphic ID and impulsive, violent and aggressive behaviors. We have performed targeted high-throughput sequencing of 220 genes, including MAOA, in patients with undiagnosed ID. We identified a c.797_798delinsTT (p.C266F) missense mutation in MAOA in a boy with autism spectrum disorder, attention deficit and autoaggressive behavior. Two maternal uncles carry the mutation and have severe ID, with a history of maltreatment in early childhood. This novel missense mutation decreases MAOA enzymatic activity, leading to abnormal levels of urinary monoamines. The identification of this new point mutation confirms, for the first time since 1993, the monogenic implication of the MAOA gene in ID of various degrees, autism and behavioral disturbances. The variable expressivity of the mutation observed in male patients of this family may involve gene–environment interactions, and the identification of a perturbation in monoamine metabolism should be taken into account when prescribing psychoactive drugs in such patients. PMID:24169519

20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition.

PubMed

Piton, Amélie; Poquet, Hélène; Redin, Claire; Masurel, Alice; Lauer, Julia; Muller, Jean; Thevenon, Julien; Herenger, Yvan; Chancenotte, Sophie; Bonnet, Marlène; Pinoit, Jean-Michel; Huet, Frédéric; Thauvin-Robinet, Christel; Jaeger, Anne-Sophie; Le Gras, Stéphanie; Jost, Bernard; Gérard, Bénédicte; Peoc'h, Katell; Launay, Jean-Marie; Faivre, Laurence; Mandel, Jean-Louis

2014-06-01

Intellectual disability (ID) is characterized by an extraordinary genetic heterogeneity, with >250 genes that have been implicated in monogenic forms of ID. Because this complexity precluded systematic testing for mutations and because clinical features are often non-specific, for some of these genes only few cases or families have been unambiguously documented. It is the case of the X-linked gene encoding monoamine oxidase A (MAOA), for which only one nonsense mutation has been identified in Brunner syndrome, characterized in a single family by mild non-dysmorphic ID and impulsive, violent and aggressive behaviors. We have performed targeted high-throughput sequencing of 220 genes, including MAOA, in patients with undiagnosed ID. We identified a c.797_798delinsTT (p.C266F) missense mutation in MAOA in a boy with autism spectrum disorder, attention deficit and autoaggressive behavior. Two maternal uncles carry the mutation and have severe ID, with a history of maltreatment in early childhood. This novel missense mutation decreases MAOA enzymatic activity, leading to abnormal levels of urinary monoamines. The identification of this new point mutation confirms, for the first time since 1993, the monogenic implication of the MAOA gene in ID of various degrees, autism and behavioral disturbances. The variable expressivity of the mutation observed in male patients of this family may involve gene-environment interactions, and the identification of a perturbation in monoamine metabolism should be taken into account when prescribing psychoactive drugs in such patients.

Id-1 promotes osteosarcoma cell growth and inhibits cell apoptosis via PI3K/AKT signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Liang; Liao, Qi; Tang, Qiang

2016-02-12

Accumulating evidence reveals that Id-1 is upregulated and functions as a potential tumor promoter in several human cancer types. However, the role of Id-1 in osteosarcoma (OS) is unknown. In present study, we found that Id-1 expression was elevated in OS tissues than adjacent normal bone tissues. More importantly, we demonstrated that overexpression of Id-1 is significantly correlated with tumor progression and poor survival in OS patients. Furthermore, increased expression of Id-1 was observed in OS cell lines and ectopic expression of Id-1 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas knockdown of Id-1 suppressed OS cellsmore » growth. Moreover, our experimental data revealed that Id-1 promotes cell proliferation by facilitating cell cycle progression and inhibits cell apoptosis. Mechanistically, the effects of Id-1 in OS cells is at least partly through activation of PI3K/Akt signaling pathway. Therefore, we identified a tumorigenic role of Id-1 in OS and suggested a potential therapeutic target for OS patients. - Highlights: • Id-1 expression is positively correlated in OS patients with poor prognosis. • Overexpression of Id-1 promotes OS cell growth in vitro and in vivo. • Id-1induces cell cycle progression and inhibits cell apoptosis. • PI3K/Akt signaling pathway contributed to the oncogenic effects of Id-1 in OS cells.« less

Advanced Infantry Training: An Empirical Analysis Of (0341) Mortarman Success While Attending Advanced Mortarman Course

DTIC Science & Technology

2017-12-01

13 Table 2. TFDW File Descriptions ... evaluation FO Forward Observer FY Fiscal year GT General technical HLZ Helicopter landing zone ID Identification ITB Infantry Training...survive during AMCs most difficult training phases, to include FDC and advanced FDC evaluations . These events require a heightened degree of cognitive

Understanding of Facial Expressions of Emotion by Children with Intellectual Disabilities of Differing Aetiology

ERIC Educational Resources Information Center

Wishart, J. G.; Cebula, K. R.; Willis, D. S.; Pitcairn, T. K.

2007-01-01

Background: Interpreting emotional expressions is a socio-cognitive skill central to interpersonal interaction. Poor emotion recognition has been reported in autism but is less well understood in other kinds of intellectual disabilities (ID), with procedural differences making comparisons across studies and syndromes difficult. This study aimed to…

Numeracy Abilities of Children in Grades 4 to 6 with Mild Intellectual Disability in Singapore

ERIC Educational Resources Information Center

Cheong, Janice M. Y.; Walker, Zachary M.; Rosenblatt, Kara

2017-01-01

Mathematics is an important aspect of daily life. Basic numeracy skills are needed to accomplish everyday tasks. However, research regarding the relationship between cognitive ability, mental age, and basic numeracy skills for children with intellectual disability (ID) is scarce. This research study investigated the correlation between…

The Impact of Social Cognitive and Personality Factors on Teachers' Reported Inclusive Behaviour

ERIC Educational Resources Information Center

Wilson, Claire; Woolfson, Lisa Marks; Durkin, Kevin; Elliott, Mark A.

2016-01-01

Background: Inclusive education of children with intellectual disabilities (ID) is intended to maximize their educational experience within the mainstream school setting. While policy mandates inclusion, it is classroom teachers' behaviours that determine its success. Aims: This study provided a novel application of the theory of planned behaviour…

Theory of Mind "Emotion", Developmental Characteristics and Social Understanding in Children and Adolescents with Intellectual Disabilities

ERIC Educational Resources Information Center

Thirion-Marissiaux, Anne-Francoise; Nader-Grosbois, Nathalie

2008-01-01

Patterns of development of ToM-emotion abilities in intellectually disabled (ID) children and typically developing (TD) children matched on their developmental age were investigated. The links between cognition, language, social understanding and ToM-emotion abilities were examined. EDEI-R (Perron-Borelli, M. (1996). "Echelles Differentielles…

Theory of Mind "Beliefs", Developmental Characteristics and Social Understanding in Children and Adolescents with Intellectual Disabilities

ERIC Educational Resources Information Center

Thirion-Marissiaux, Anne-Francoise; Nader-Grosbois, Nathalie

2008-01-01

Patterns of development of ToM belief abilities in intellectually disabled (ID) children and typically developing (TD) children matched on their developmental age were investigated. The links between cognition, language, social understanding and ToM belief abilities were examined. EDEI-R [Perron-Borelli M. (1996). "Echelles Differentielles…

Cancer Prevention and Health Promotion for People with Intellectual Disabilities: An Exploratory Study of Staff Knowledge

ERIC Educational Resources Information Center

Hanna, L. M.; Taggart, L.; Cousins, W.

2011-01-01

Background: As people with intellectual disabilities (ID) are living longer, their chances of developing cancer also increases. However, recognising the early signs and symptoms of cancer in a population with cognitive impairment and communication difficulties poses difficulties for both family carers and professional care staff. Engagement in…

Effects of Dog-Assisted Therapy on Communication and Basic Social Skills of Adults With Intellectual Disabilities: A Pilot Study.

PubMed

Scorzato, Ivano; Zaninotto, Leonardo; Romano, Michela; Menardi, Chiara; Cavedon, Lino; Pegoraro, Alessandra; Socche, Laura; Zanetti, Piera; Coppiello, Deborah

2017-06-01

Thirty-nine adults with severe to profound intellectual disability (ID) were randomly assigned to either an experimental group (n = 21) or a control group (n = 18). Assessment was blinded and included selected items from the International Classification of Functioning, Disability and Health (ICF), the Behavioral Assessment Battery (BAB), and the Learning Accomplishment Profile (LAP). The experimental group, who attended a dog-assisted treatment intervention over a 20-week period, showed significant improvements in several cognitive domains, including attention to movement (BAB-AM), visuomotor coordination (BAB-VM), exploratory play (BAB-EP), and motor imitation (BAB-CO-MI), as well as in some social skills, as measured by LAP items. Effects were specific to the intervention and independent of age or basic level of disability.

Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype.

PubMed

DeBrosse, Suzanne D; Okajima, Kazuki; Zhang, Shulin; Nakouzi, Ghunwa; Schmotzer, Christine L; Lusk-Kopp, Marilyn; Frohnapfel, Mary Beth; Grahame, George; Kerr, Douglas S

2012-11-01

Pyruvate dehydrogenase complex (PDC) deficiency is a relatively common mitochondrial disorder that primarily presents with neurological manifestations and lactic acidemia. We analyzed the clinical outcomes and neurological features of 59 consented symptomatic subjects (27 M, 32 F), who were confirmed to have PDC deficiency with defined mutations in one of the genes of PDC (PDHA1, n = 53; PDHB, n = 4; DLAT, n = 2), including 47 different mutations, of which 22 were novel, and for whom clinical records and/or structured interviews were obtained. 39% of these subjects (23/59) have died. Of these, 91% (21/23) died before age 4 years, 61% (14/23) before 1 year, and 43% (10/23) before 3 months. 56% of males died compared with 25% of females. Causes of death included severe lactic acidosis, respiratory failure, and infection. In subjects surviving past 6 months, a broad range of intellectual outcomes was observed. Of 42 subjects whose intellectual abilities were professionally evaluated, 19% had normal or borderline intellectual ability (CQ/IQ ≥ 70), 10% had mild intellectual disability (ID) (CQ/IQ 55-69), 17% had moderate ID (CQ/IQ 40-54), 24% had severe ID (CQ/IQ 25-39) and 33% had profound ID (CQ/IQ<25). Assessment by parents was comparable. Of 10 subjects who reached age 12 years, 9 had had professional IQ assessments, and only 4 had IQs ≥ 70 (only 2 of these 4 had assessments after age 12 years). The average outcome for females was severe-to-profound ID, whereas that of males was mild-to-moderate ID. Of subjects for whom specific neurological data were available, the majority had hypotonia (89%), and hypertonia or mixed hyper-/hypotonia (49%) were common. Seizures (57%), microcephaly (49%), and structural brain abnormalities including ventriculomegaly (67%) and agenesis, dysgenesis, or hypoplasia of the corpus callosum (55%) were common. Leigh syndrome was found in only 35%. Structural brain abnormalities were more common in females, and Leigh syndrome was more common in males. In a subgroup of 16 ambulatory subjects >3.5 years in whom balance was evaluated, ataxia was found in 13. Peripheral neuropathy was documented in 2 cases but not objectively evaluated in most subjects. Outcomes of this population with genetically confirmed PDC deficiency are heterogeneous and not distinctive. Correlations between specific genotypes and outcomes were not established. Although more females survive, related to the prevalence of X-linked PDHA1 mutations, symptomatic surviving females are generally more severely impaired cognitively and have a different pattern of neurological impairment compared to males. Neonatal or infant onset of symptoms was associated with poor outcomes. Males with PDHA1 mutations and low fibroblast PDC activity were less likely to survive beyond infancy. Recurrence rate in siblings of subjects with PDHA1 mutation was less than 5%. Paradoxically, in this retrospective review, potential factors considered possibly relevant to development, such as in vitro PDC activity, specific mutations, use of ketogenic diets, supplements, or medications, were generally not confirmed to be significantly correlated with objective outcomes of survival or neuro-cognitive function. Therefore, the basis of variability of these outcomes remains largely undetermined. Copyright © 2012 Elsevier Inc. All rights reserved.

R&D100: IC ID

ScienceCinema

Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

2018-06-25

Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder.

PubMed

Chaudhry, A; Noor, A; Degagne, B; Baker, K; Bok, L A; Brady, A F; Chitayat, D; Chung, B H; Cytrynbaum, C; Dyment, D; Filges, I; Helm, B; Hutchison, H T; Jeng, L J B; Laumonnier, F; Marshall, C R; Menzel, M; Parkash, S; Parker, M J; Raymond, L F; Rideout, A L; Roberts, W; Rupps, R; Schanze, I; Schrander-Stumpel, C T R M; Speevak, M D; Stavropoulos, D J; Stevens, S J C; Thomas, E R A; Toutain, A; Vergano, S; Weksberg, R; Scherer, S W; Vincent, J B; Carter, M T

2015-09-01

Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Timing, duration, and severity of iron deficiency in early development and motor outcomes at 9 months

PubMed Central

Santos, Denise CC; Angulo-Barroso, Rosa M; Li, Ming; Bian, Yang; Sturza, Julie; Richards, Blair; Lozoff, Betsy

2017-01-01

BACKGROUND/OBJECTIVES Poorer motor development is reported in infants with iron deficiency (ID). The role of timing, duration and severity is unclear. We assessed relations between ID timing, duration, and severity and gross motor scores, neurological integrity, and motor behavior quality at 9 months. METHODS Iron status was determined at birth and 9 months in otherwise healthy term Chinese infants. The 9-month motor evaluation included the Peabody Developmental Motor Scale (PDMS-2), Infant Neurological International Battery (INFANIB), and motor quality factor. Motor outcomes were analyzed by ID timing (fetal-neonatal, infancy), duration, and severity. For severity, we also considered maternal iron status. RESULTS Data were available for 1194 infants. Iron status was classified as fetal-neonatal and infancy ID (n=253), fetal-neonatal ID (n=256), infancy ID (n=288), and not ID (n=397). Compared with not ID, infants with fetal-neonatal or infancy ID had lower locomotion scores (effect size ds=0.19, 0.18) and those with ID in both periods (longer duration) had lower locomotion and overall PDMS-2 gross motor scores (ds=0.20, 0.18); ID groups did not differ. More severe ID in late pregnancy was associated with lower INFANIB Vestibular function (p=0.01), and total score (p=0.03). More severe ID in infancy was associated with lower scores for locomotion (p=0.03), overall gross motor (p=0.05). CONCLUSIONS Fetal-neonatal and/or infancy ID was associated with lower overall gross motor development and locomotion test scores at 9 months. Associations with ID severity varied by ID timing: more severe ID in late pregnancy, poorer neurological integrity; more severe ID in infancy, poorer gross motor development. PMID:29235557

Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms.

PubMed

Larizza, L; Finelli, P

2018-04-19

Advances in genomic analyses based on next-generation sequencing and integrated omics approaches, have accelerated in an unprecedented way the discovery of causative genes of developmental delay (DD) and intellectual disability (ID) disorders. Chromatin dysregulation has been recognized as common pathomechanism of mendelian DD/ID syndromes due to mutation in genes encoding chromatin regulators referred as transcriptomopathies or epigenetic disorders. Common to these syndromes are the wide phenotypic breadth and the recognition of groups of distinct syndromes with shared signs besides cognitive impairment, likely mirroring common molecular mechanisms. Disruption of chromatin-associated transcription machinery accounts for the phenotypic overlap of Cornelia de Lange with KBG and with syndromes of the epigenetic machinery. The genes responsible for Smith-Magenis-related disorders act in interconnected networks and the molecular signature of histone acetylation disorders joins Rubinstein-Taybi-related syndromes. Deciphering pathway interconnection of clinically similar ID syndromes may enhance search of common targets useful for developing new therapeutics. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling.

PubMed

Snijders Blok, Lot; Madsen, Erik; Juusola, Jane; Gilissen, Christian; Baralle, Diana; Reijnders, Margot R F; Venselaar, Hanka; Helsmoortel, Céline; Cho, Megan T; Hoischen, Alexander; Vissers, Lisenka E L M; Koemans, Tom S; Wissink-Lindhout, Willemijn; Eichler, Evan E; Romano, Corrado; Van Esch, Hilde; Stumpel, Connie; Vreeburg, Maaike; Smeets, Eric; Oberndorff, Karin; van Bon, Bregje W M; Shaw, Marie; Gecz, Jozef; Haan, Eric; Bienek, Melanie; Jensen, Corinna; Loeys, Bart L; Van Dijck, Anke; Innes, A Micheil; Racher, Hilary; Vermeer, Sascha; Di Donato, Nataliya; Rump, Andreas; Tatton-Brown, Katrina; Parker, Michael J; Henderson, Alex; Lynch, Sally A; Fryer, Alan; Ross, Alison; Vasudevan, Pradeep; Kini, Usha; Newbury-Ecob, Ruth; Chandler, Kate; Male, Alison; Dijkstra, Sybe; Schieving, Jolanda; Giltay, Jacques; van Gassen, Koen L I; Schuurs-Hoeijmakers, Janneke; Tan, Perciliz L; Pediaditakis, Igor; Haas, Stefan A; Retterer, Kyle; Reed, Patrick; Monaghan, Kristin G; Haverfield, Eden; Natowicz, Marvin; Myers, Angela; Kruer, Michael C; Stein, Quinn; Strauss, Kevin A; Brigatti, Karlla W; Keating, Katherine; Burton, Barbara K; Kim, Katherine H; Charrow, Joel; Norman, Jennifer; Foster-Barber, Audrey; Kline, Antonie D; Kimball, Amy; Zackai, Elaine; Harr, Margaret; Fox, Joyce; McLaughlin, Julie; Lindstrom, Kristin; Haude, Katrina M; van Roozendaal, Kees; Brunner, Han; Chung, Wendy K; Kooy, R Frank; Pfundt, Rolph; Kalscheuer, Vera; Mehta, Sarju G; Katsanis, Nicholas; Kleefstra, Tjitske

2015-08-06

Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Based on our findings, mutations in DDX3X are one of the more common causes of ID, accounting for 1%-3% of unexplained ID in females. Although no de novo DDX3X mutations were identified in males, we present three families with segregating missense mutations in DDX3X, suggestive of an X-linked recessive inheritance pattern. In these families, all males with the DDX3X variant had ID, whereas carrier females were unaffected. To explore the pathogenic mechanisms accounting for the differences in disease transmission and phenotype between affected females and affected males with DDX3X missense variants, we used canonical Wnt defects in zebrafish as a surrogate measure of DDX3X function in vivo. We demonstrate a consistent loss-of-function effect of all tested de novo mutations on the Wnt pathway, and we further show a differential effect by gender. The differential activity possibly reflects a dose-dependent effect of DDX3X expression in the context of functional mosaic females versus one-copy males, which reflects the complex biological nature of DDX3X mutations. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Impaired Object Recognition but Normal Social Behavior and Ultrasonic Communication in Cofilin1 Mutant Mice

PubMed Central

Sungur, A. Özge; Stemmler, Lea; Wöhr, Markus; Rust, Marco B.

2018-01-01

Autism spectrum disorder (ASD), schizophrenia (SCZ) and intellectual disability (ID) show a remarkable overlap in symptoms, including impairments in cognition, social behavior and communication. Human genetic studies revealed an enrichment of mutations in actin-related genes for these disorders, and some of the strongest candidate genes control actin dynamics. These findings led to the hypotheses: (i) that ASD, SCZ and ID share common disease mechanisms; and (ii) that, at least in a subgroup of affected individuals, defects in the actin cytoskeleton cause or contribute to their pathologies. Cofilin1 emerged as a key regulator of actin dynamics and we previously demonstrated its critical role for synaptic plasticity and associative learning. Notably, recent studies revealed an over-activation of cofilin1 in mutant mice displaying ASD- or SCZ-like behavioral phenotypes, suggesting that dysregulated cofilin1-dependent actin dynamics contribute to their behavioral abnormalities, such as deficits in social behavior. These findings let us hypothesize: (i) that, apart from cognitive impairments, cofilin1 mutants display additional behavioral deficits with relevance to ASD or SCZ; and (ii) that our cofilin1 mutants represent a valuable tool to study the underlying disease mechanisms. To test our hypotheses, we compared social behavior and ultrasonic communication of juvenile mutants to control littermates, and we did not obtain evidence for impaired direct reciprocal social interaction, social approach or social memory. Moreover, concomitant emission of ultrasonic vocalizations was not affected and time-locked to social activity, supporting the notion that ultrasonic vocalizations serve a pro-social communicative function as social contact calls maintaining social proximity. Finally, cofilin1 mutants did not display abnormal repetitive behaviors. Instead, they performed weaker in novel object recognition, thereby demonstrating that cofilin1 is relevant not only for associative learning, but also for “non-matching-to-sample” learning. Here we report the absence of an ASD- or a SCZ-like phenotype in cofilin1 mutants, and we conclude that cofilin1 is relevant specifically for non-social cognition. PMID:29515378

Visual-Motor Integration in Children With Mild Intellectual Disability: A Meta-Analysis.

PubMed

Memisevic, Haris; Djordjevic, Mirjana

2018-01-01

Visual-motor integration (VMI) skills, defined as the coordination of fine motor and visual perceptual abilities, are a very good indicator of a child's overall level of functioning. Research has clearly established that children with intellectual disability (ID) have deficits in VMI skills. This article presents a meta-analytic review of 10 research studies involving 652 children with mild ID for which a VMI skills assessment was also available. We measured the standardized mean difference (Hedges' g) between scores on VMI tests of these children with mild ID and either typically developing children's VMI test scores in these studies or normative mean values on VMI tests used by the studies. While mild ID is defined in part by intelligence scores that are two to three standard deviations below those of typically developing children, the standardized mean difference of VMI differences between typically developing children and children with mild ID in this meta-analysis was 1.75 (95% CI [1.11, 2.38]). Thus, the intellectual and adaptive skill deficits of children with mild ID may be greater (perhaps especially due to their abstract and conceptual reasoning deficits) than their relative VMI deficits. We discuss the possible meaning of this relative VMI strength among children with mild ID and suggest that their stronger VMI skills may be a target for intensive academic interventions as a means of attenuating problems in adaptive functioning.

Clinical context and mechanism of functional tricuspid regurgitation in patients with and without pulmonary hypertension.

PubMed

Topilsky, Yan; Khanna, Amber; Le Tourneau, Thierry; Park, Soon; Michelena, Hector; Suri, Rakesh; Mahoney, Douglas W; Enriquez-Sarano, Maurice

2012-05-01

Functional tricuspid regurgitation (FTR) with structurally normal valve is of poorly defined mechanisms. Prevalence and clinical context of idiopathic FTR (Id-FTR) (without overt TR cause) are unknown. To investigate prevalence, clinical context, and mechanisms specific to FTR types, Id-FTR versus pulmonary hypertension-related (PHTN-FTR, systolic pulmonary pressure ≥50 mm Hg), we analyzed 1161 patients with prospectively quantified TR. Id-FTR (prevalence 12%) was associated with aging and atrial fibrillation. For mechanistic purposes, we measured valvular and right ventricular (RV) remodeling in 141 Id-FTR matched to 140 PHTN-FTR and to 99 controls with trivial TR for age, sex, atrial fibrillation, and ejection fraction. PHTN-FTR and Id-FTR were also matched for TR effective-regurgitant-orifice (ERO). Id-FTR valvular alterations (versus controls) were largest annular area (3.53±0.6 versus 2.74±0.4 cm(2), P<0.0001) and lowest valvular/annular coverage ratio (1.06±0.1 versus 1.45±0.2, P<0.0001) but normal valve tenting height. PHTN-FTR had mild annular enlargement but excessive valve tenting height (0.8±0.3 versus 0.35±0.1 cm, P<0.0001). Valvular changes were linked to specific RV changes, largest basal dilatation, and normal length (RV conical deformation) in Id-FTR versus longest RV with elliptical/spherical deformation in PHTN-FTR. With increasing FTR severity (ERO ≥40 mm(2)), changes specific to each FTR type were accentuated, and RV function (index of myocardial performance) was consistently reduced. Id-FTR is frequent, linked to aging and atrial fibrillation, can be severe, and is of unique mechanism. In Id-FTR, excess annular and RV-basal enlargement exhausts valvular/annular coverage reserve, and RV conical deformation does not cause notable valvular tenting. Conversely, PHTN-FTR is determined by valvular tethering with tenting linked to RV elongation and elliptical/spherical deformation. These specific FTR-mechanisms may be important in considering surgical correction in FTR.

Biofortification of riboflavin and folate in idli batter, based on fermented cereal and pulse, by Lactococcus lactis N8 and Saccharomyces boulardii SAA655.

PubMed

Chandrasekar Rajendran, S C; Chamlagain, B; Kariluoto, S; Piironen, V; Saris, P E J

2017-06-01

Lactococcus lactis N8 and Saccharomyces boulardii SAA655 were investigated for their ability to synthesize B-vitamins (riboflavin and folate) and their functional role as microbial starters in idli fermentation. In this study, ultra-high performance liquid chromatography and microbiological assay were used to determine the total riboflavin and folate content respectively. Increased levels of folate were evident in both L. lactis N8 and S. boulardii SAA655 cultivated medium. Enhanced riboflavin levels were found only in S. boulardii SAA655 grown medium, whereas decreased riboflavin level was found in L. lactis N8 cultivated medium. To evaluate the functional role of microbial starter strains, L. lactis N8 and S. boulardii SAA655 were incorporated individually and in combination into idli batter, composed of wet grounded rice and black gram. For the experiments, naturally fermented idli batter was considered as control. The results indicated that natural idli fermentation did not enhance the riboflavin level and depleted folate levels by half. In comparison with control, L. lactis N8 and S. boulardii SAA655 incorporated idli batter (individually and in combination) increased riboflavin and folate levels by 40-90%. Apart from compensating the folate loss caused by natural fermentation, S. boulardii SAA655 fermented idli batter individually and in combination with L. lactis N8 also showed the highest leavening character. Moreover, the microbial starter incorporation did not significantly influence the pH of idli batter. Incorporation of L. lactis N8 and S. boulardii SAA655 can evidently enhance the functional and technological characteristics of idli batter. UN General Assembly declared 2016 the International Year of pulses emphasizing the importance of legumes as staple food. Furthermore, this is the first experimental report of in situ biofortifcation of riboflavin and folate using microbes in pulse based fermented staple food. The current study suggests possible avenues for research towards an economical strategy to reduce B-vitamin deficiency among the consuming population. © 2017 The Society for Applied Microbiology.

Initial value problem of space dynamics in universal Stumpff anomaly

NASA Astrophysics Data System (ADS)

Sharaf, M. A.; Dwidar, H. R.

2018-05-01

In this paper, the initial value problem of space dynamics in universal Stumpff anomaly ψ is set up and developed in analytical and computational approach. For the analytical expansions, the linear independence of the functions U_{j} (ψ;σ); {j=0,1,2,3} are proved. The differential and recurrence equations satisfied by them and their relations with the elementary functions are given. The universal Kepler equation and its validations for different conic orbits are established together with the Lagrangian coefficients. Efficient representations of these functions are developed in terms of the continued fractions. For the computational developments we consider the following items: 1. Top-down algorithm for continued fraction evaluation. 2. One-point iteration formulae. 3. Determination of the coefficients of Kepler's equation. 4. Derivatives of Kepler's equation of any integer order. 5. Determination of the initial guess for the solution of the universal Kepler equation. Finally we give summary on the computational design for the initial value problem of space dynamics in universal Stumpff anomaly. This design based on the solution of the universal Kepler's equation by an iterative schemes of quadratic up to any desired order ℓ.

Parental social support, coping strategies, resilience factors, stress, anxiety and depression levels in parents of children with MPS III (Sanfilippo syndrome) or children with intellectual disabilities (ID).

PubMed

Grant, Sheena; Cross, Elaine; Wraith, James Edmond; Jones, Simon; Mahon, Louise; Lomax, Michelle; Bigger, Brian; Hare, Dougal

2013-03-01

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of four enzymes involved in the catabolism of the glycosaminoglycan heparan sulphate. It is a degenerative disorder, with a progressive decline in children's intellectual and physical functioning. There is currently no cure for the disorder. To date there is a paucity of research on how this disorder impacts parents psychological functioning. Specifically, research in the area has failed to employ adequate control groups to assess if the impact of this disorder on parents psychological functioning differs from parenting a child with intellectual disability (ID). The current study examined child behaviour and parental psychological functioning in 23 parents of children with MPS III and 23 parents of children with ID. Parents completed postal questionnaires about their child's behaviour and abilities and their own psychological functioning. Parents of children with MPS III reported fewer behavioural difficulties as their child aged, more severe level of intellectual disability, and similar levels of perceived social support, coping techniques, stress, anxiety and depression levels as parents of children with ID. Both groups of parents scored above the clinical cut off for anxiety and depression. Parents of children with MPS III rated themselves as significantly less future-orientated and goal directed than parents of children with ID. Services should develop support packages for parents of children with MPS III that incorporate an understanding of the unique stressors and current-difficulty approach of this population. Future research should examine gender differences between parental psychological functioning, using mixed qualitative and quantitative approaches, and utilise matched developmental level and typically developing control groups.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Long; Shi, Songting; Zhang, Juan

Highlights: Black-Right-Pointing-Pointer Expression of Id3 but not Id1 is induced by Wnt3a stimulation in C2C12 cells. Black-Right-Pointing-Pointer Wnt3a induces Id3 expression via canonical Wnt/{beta}-catenin pathway. Black-Right-Pointing-Pointer Wnt3a-induced Id3 expression does not depend on BMP signaling activation. Black-Right-Pointing-Pointer Induction of Id3 expression is critical determinant in Wnt3a-induced cell proliferation and differentiation. -- Abstract: Canonical Wnt signaling plays important roles in regulating cell proliferation and differentiation. In this study, we report that inhibitor of differentiation (Id)3 is a Wnt-inducible gene in mouse C2C12 myoblasts. Wnt3a induced Id3 expression in a {beta}-catenin-dependent manner. Bone morphogenetic protein (BMP) also potently induced Id3 expression. However,more » Wnt-induced Id3 expression occurred independent of the BMP/Smad pathway. Functional studies showed that Id3 depletion in C2C12 cells impaired Wnt3a-induced cell proliferation and alkaline phosphatase activity, an early marker of osteoblast cells. Id3 depletion elevated myogenin induction during myogenic differentiation and partially impaired Wnt3a suppressed myogenin expression in C2C12 cells. These results suggest that Id3 is an important Wnt/{beta}-catenin induced gene in myoblast cell fate determination.« less

A Pilot Study of a Test for Visual Recognition Memory in Adults with Moderate to Severe Intellectual Disability

ERIC Educational Resources Information Center

Pyo, Geunyeong; Ala, Tom; Kyrouac, Gregory A.; Verhulst, Steven J.

2010-01-01

Objective assessment of memory functioning is an important part of evaluation for Dementia of Alzheimer Type (DAT). The revised Picture Recognition Memory Test (r-PRMT) is a test for visual recognition memory to assess memory functioning of persons with intellectual disabilities (ID), specifically targeting moderate to severe ID. A pilot study was…

A matter of life and death: knowledge about the body and concept of death in adults with intellectual disabilities.

PubMed

McEvoy, J; Treacy, B; Quigley, J

2017-01-01

An increased awareness of how people with intellectual disabilities (ID) understand death and dying is necessary in supporting life-long learning, post-bereavement support and planning end-of-life care. Previous research suggests that adults with ID have a limited or 'patchy' understanding of the basic biological components of death. However, the relationship between biological understanding of how the body works and conceptualisation of death remains unexplored in this population. Thirty adults with ID were interviewed to assess their knowledge of human body function and their understanding of the concept of death. Using pictures, participants were asked if they recognised certain organs, asked to explain the function of various body parts and what would happen if certain body parts were missing or did not work. Participants who referred to 'life' or 'not dying' as the goal of body function were categorised as 'Life Theorisers'. In addition, participants were asked about the causes of death, whether all things die and the status of the body after death. The results support previous studies suggesting that understanding of death in adults with ID varies from partial to full comprehension and is associated with level of ID. Also, death comprehension was positively correlated with total body interview scores and 'Life Theorisers' who understood that body parts maintain life and who spontaneously appealed to 'vitalistic' concepts when reasoning about the human body were also more sophisticated in their understanding of death. The study highlights the relationship between knowledge about the goal of human body functioning and death comprehension in adults with ID. The potential that learning to adopt a 'vitalistic' approach to human functioning may have on the acquisition of a greater understanding of death and dying, understanding illness and supporting end-of-life planning is discussed. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Mental Illness and Intellectual Disability in Magistrates Courts in New South Wales, Australia

ERIC Educational Resources Information Center

Vanny, K. A.; Levy, M. H.; Greenberg, D. M.; Hayes, S. C.

2009-01-01

Background: Little is known about the prevalence of intellectual disability (ID) and/or cognitive impairment (CI) among accused persons in the Magistrates (Local) Courts, the personal, health and mental health characteristics of this cohort, and their service provision needs in the community. The study aimed to determine the prevalence of dual…

Perceptions of Death and Management of Grief in People with Intellectual Disability

ERIC Educational Resources Information Center

Meeusen-van de Kerkhof, Rianne; van Bommel, Hanneke; van de Wouw, Werner; Maaskant, Marian

2006-01-01

The authors examine the way in which people with intellectual disability (ID) handle death and mourning, and note that the way in which death and bereavement are being experienced depends--among other things--upon the intellectual and socio-emotional age of the individual. The authors used the theories formulated by Piaget (cognitive development),…

Evaluation of Cognitively Accessible Software to Increase Independent Access to Cellphone Technology for People with Intellectual Disability

ERIC Educational Resources Information Center

Stock, S. E.; Davies, D. K.; Wehmeyer, M. L.; Palmer, S. B.

2008-01-01

Background: There are over two billion telephones in use worldwide. Yet, for millions of Americans with intellectual disabilities (ID), access to the benefits of cellphone technology is limited because of deficits in literacy, numerical comprehension, the proliferation of features and shrinking size of cellphone hardware and user interfaces.…

Investigating the Relationship between Observed Mood and Emotions in People with Severe and Profound Intellectual Disabilities

ERIC Educational Resources Information Center

Vos, P.; De Cock, P.; Petry, K.; Van Den Noortgate, W.; Maes, B.

2013-01-01

Background: The measurement of subjective well-being in people with severe and profound intellectual disabilities (ID) is a difficult challenge. As they cannot self-report about their life satisfaction, because of severe communicative and cognitive limitations, behavioural observations of their emotions and moods are important in the measurement…

New Model of Mapping Difficulties in Solving Analogical Problems among Adolescents and Adults with Intellectual Disability

ERIC Educational Resources Information Center

Lifshitz, Hefziba; Weiss, Itzhak; Tzuriel, David; Tzemach, Moran

2011-01-01

The main goal of the study was to map the difficulties and cognitive processes among adolescents (aged 13-21, N = 30) and adults (aged 25-66, N = 30) with mild and moderate intellectual disability (ID) when solving analogical problems. The participants were administered the "Conceptual and Perceptual Analogical Modifiability" test. A…

Visual Perception and Frontal Lobe in Intellectual Disabilities: A Study with Evoked Potentials and Neuropsychology

ERIC Educational Resources Information Center

Munoz-Ruata, J.; Caro-Martinez, E.; Perez, L. Martinez; Borja, M.

2010-01-01

Background: Perception disorders are frequently observed in persons with intellectual disability (ID) and their influence on cognition has been discussed. The objective of this study is to clarify the mechanisms behind these alterations by analysing the visual event related potentials early component, the N1 wave, which is related to perception…

Inflammation and Oxidative Stress as Biomarkers of Premature Aging in Persons with Intellectual Disability

ERIC Educational Resources Information Center

Carmeli, Eli; Imam, Bita; Bachar, Asad; Merrick, Joav

2012-01-01

The decline in cognitive ability and physical performance in older adults with intellectual disabilities (ID) is accompanied by less participation in social activities and a sedentary lifestyle; however the pathogenesis is not clear yet. It was recently suggested that chronic disease, adverse drug reactions, and aging create a cascade of events…

Do PDAs Enhance the Organization and Memory Skills of Students with Cognitive Disabilities?

ERIC Educational Resources Information Center

Gillette, Yvonne; Depompei, Roberta

2008-01-01

The project studied the on-time behavior of 35 students with intellectual disabilities (ID) or traumatic brain injury (TBI) under three conditions--times and tasks list, paper planner, and two different personal data assistants (PDAs). Students participated for two 4-week periods, receiving one morning reminder during Period 1 and no reminders…

Writing abilities in intellectual disabilities: a comparison between Down and Williams syndrome.

PubMed

Varuzza, Cristiana; De Rose, Paola; Vicari, Stefano; Menghini, Deny

2015-02-01

Writing is a complex task that requires the integration of multiple cognitive, linguistic, and motor abilities. Until now, only a few studies investigated writing abilities in individuals with Intellectual Disability (ID). The aim of the present exploratory study was to provide knowledge on the organization of writing in two populations with ID, Down syndrome (DS) and Williams syndrome (WS), trying to disentangle different components of the process. A battery tapping diverse writing demands as low-level transcription skills as well as high-level writing skills was proposed to 13 individuals with WS, 12 individuals with DS and 11 mental-age-matched typically developing (TD) children. Results showed that the two groups with genetic syndromes did not differ from TD in writing a list of objects placed in bedroom, in the number of errors in the text composition, in a text copying task and in kind of errors made. However, in a word dictation task, individuals with DS made more errors than individuals with WS and TD children. In a pseudoword dictation task, both individuals with DS and WS showed more errors than TD children. Our results showed good abilities in individuals with ID in different aspects of writing, involving not only low-level transcription skills but also high-level composition skills. Contrary to the pessimistic view, considering individuals with ID vulnerable for failure, our results indicate that the presence of ID does not prevent the achievement of writing skills. Copyright © 2014 Elsevier Ltd. All rights reserved.

Physical fitness is predictive for a decline in daily functioning in older adults with intellectual disabilities: results of the HA-ID study.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Schoufour, Josje D; Evenhuis, Heleen M

2014-10-01

A high incidence of limitations in daily functioning is seen in older adults with intellectual disabilities (ID), along with poor physical fitness levels. The aim of this study was to assess the predictive value of physical fitness for daily functioning after 3 years, in 602 older adults with borderline to profound ID (≥ 50 years). At baseline, physical fitness levels and daily functioning (operationalized as basic activities of daily living [ADL] and mobility) were assessed. After 3 years, the measurements of daily functioning were repeated. At follow-up, 12.6% of the participants were completely independent in ADL and 48.5% had no mobility limitations. More than half of the participants (54.8%) declined in their ability to perform ADL and 37.5% declined in their mobility. Manual dexterity, visual reaction time, balance, comfortable and fast gait speed, muscular endurance, and cardiorespiratory fitness were significant predictors for a decline in ADL. For a decline in mobility, manual dexterity, balance, comfortable and fast walking speed, grip strength, muscular endurance, and cardiorespiratory fitness were all significant predictors. This proves the predictive validity of these physical fitness tests for daily functioning and stresses the importance of using physical fitness tests and implementing physical fitness enhancing programs in the care for older adults with ID. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polypeptide having or assisting in carbohydrate material degrading activity and uses thereof

DOEpatents

Schooneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; Los, Alrik Pieter

2016-02-16

The invention relates to a polypeptide which comprises the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 76% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 76% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having beta-glucosidase activity and uses thereof

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoonneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; De Jong, Rene Marcel

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well asmore » the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.« less

Polypeptide having swollenin activity and uses thereof

DOEpatents

Schoonneveld-Bergmans, Margot Elizabeth Francoise; Heijne, Wilbert Herman Marie; Vlasie, Monica D; Damveld, Robbertus Antonius

2015-11-04

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having beta-glucosidase activity and uses thereof

DOEpatents

Schooneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; De Jong, Rene Marcel; Damveld, Robbertus Antonius

2015-09-01

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 70% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 70% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having cellobiohydrolase activity and uses thereof

DOEpatents

Sagt, Cornelis Maria Jacobus; Schooneveld-Bergmans, Margot Elisabeth Francoise; Roubos, Johannes Andries; Los, Alrik Pieter

2015-09-15

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 93% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 93% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having acetyl xylan esterase activity and uses thereof

DOEpatents

Schoonneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; Los, Alrik Pieter

2015-10-20

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having carbohydrate degrading activity and uses thereof

DOEpatents

Schooneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; Vlasie, Monica Diana; Damveld, Robbertus Antonius

2015-08-18

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

The impacts of maternal iron deficiency and being overweight during pregnancy on neurodevelopment of the offspring.

PubMed

Berglund, Staffan K; Torres-Espínola, Francisco J; García-Valdés, Luz; Segura, Mª Teresa; Martínez-Zaldívar, Cristina; Padilla, Carmen; Rueda, Ricardo; Pérez García, Miguel; McArdle, Harry J; Campoy, Cristina

2017-10-01

Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI≥25 kg/m2) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113·3 (sd 9·9) v. 117·1 (sd 9·2), P=0·039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114·0 (sd 9·7) v. 121·5 (sd 10·9), P=0·039) and lower receptive, expressive and composite (99·5 (sd 8·6) v. 107·6 (sd 8·3), P=0·004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12·3 (sd 2·0) v. 13·0 (sd 2·1), P=0·037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.

Physical fitness is predictive for a decline in the ability to perform instrumental activities of daily living in older adults with intellectual disabilities: Results of the HA-ID study.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Schoufour, Josje D; Evenhuis, Heleen M

2015-01-01

The ability to perform instrumental activities of daily living (IADL) is important for one's level of independence. A high incidence of limitations in IADL is seen in older adults with intellectual disabilities (ID), which is an important determinant for the amount of support one needs. The aim of this study was to assess the predictive value of physical fitness for the ability to perform IADL, over a 3-year follow-up period, in 601 older adults with ID. At baseline, an extensive physical fitness assessment was performed. In addition, professional caregivers completed the Lawton IADL scale, both at baseline and at follow-up. The average ability to perform IADL declined significantly over the 3-year follow-up period. A decline in the ability to perform IADL was seen in 44.3% of the participants. The percentage of participants being completely independent in IADL declined from 2.7% to 1.3%. Manual dexterity, balance, comfortable and fast gait speed, muscular endurance, and cardiorespiratory fitness were significant predictors for a decline in IADL after correcting for baseline IADL and personal characteristics (age, gender, level of ID, and Down syndrome). This can be interpreted as representing the predictive validity of the physical tests for a decline in IADL. This study shows that even though older adults with ID experience dependency on others due to cognitive limitations, physical fitness also is an important aspect for IADL, which stresses the importance of using physical fitness tests and physical fitness enhancing programs in the care for older adults with ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of how people with intellectual disabilities organize information using computerized guidance.

PubMed

Lussier-Desrochers, Dany; Sauzéon, Hélène; Consel, Charles; Roux, Jeannie; Balland, Émilie; Godin-Tremblay, Valérie; N'Kaoua, Bernard; Lachapelle, Yves

2017-04-01

Access to residential settings for people with intellectual disabilities (ID) contributes to their social participation, but presents particular challenges. Assistive technologies can help people perform activities of daily living. However, the majority of the computerized solutions offered use guidance modes with a fixed, unchanging sequencing that leaves little room for self-determination to emerge. The objective of the project was to develop a flexible guidance mode and to test it with participants, to describe their information organization methods. This research used a descriptive exploratory design and conducted a comparison between five participants with ID and five participants with no ID. The results showed a difference in the information organization methods for both categories of participants. The people with ID used more diversified organization methods (categorical, schematic, action-directed) than the neurotypical participants (visual, action-directed). These organization methods varied depending on the people, but also on the characteristics of the requested task. Furthermore, several people with ID presented difficulties when switching from virtual to real mode. These results demonstrate the importance of developing flexible guidance modes adapted to the users' cognitive strategies, to maximize their benefits. Studies using experimental designs will have to be conducted to determine the impacts of more-flexible guidance modes Implications for rehabilitation Intervention approaches favouring, self-determination, decision making, action analysis and results anticipation must be promoted with people with intellectual disabilities. Fixed and rigid technological guidance mode, like those currently favoured in interventions, is appropriate for only some people's profiles or may depend on the nature of the task. It seems that people with ID use a wide spectrum of organization strategies and that adapting guidance modes to all these strategies is relevant.

Contralateral Associated Movements Correlate with Poorer Inhibitory Control, Attention and Visual Perception in Preschool Children.

PubMed

Kakebeeke, Tanja H; Messerli-Bürgy, Nadine; Meyer, Andrea H; Zysset, Annina E; Stülb, Kerstin; Leeger-Aschmann, Claudia S; Schmutz, Einat A; Arhab, Amar; Puder, Jardena J; Kriemler, Susi; Munsch, Simone; Jenni, Oskar G

2017-10-01

Contralateral associated movements (CAMs) frequently occur in complex motor tasks. We investigated whether and to what extent CAMs are associated with inhibitory control among preschool children in the Swiss Preschoolers' Health Study. Participants were 476 healthy, typically developing children (mean age = 3.88 years; 251 boys) evaluated on two consecutive afternoons. The children performed the Zurich Neuromotor Assessment, the statue subtest of the Neuropsychological Assessment for Children (NEPSY), and cognitive tests of the Intelligence and Development Scales-Preschool (IDS-P). CAMs were associated with poor inhibitory control on the statue test and poor selective attention and visual perception on the IDS-P. We attributed these findings to preschoolers' general immaturity of the central nervous system.

Array-CGH in children with mild intellectual disability: a population-based study.

PubMed

Coutton, Charles; Dieterich, Klaus; Satre, Véronique; Vieville, Gaëlle; Amblard, Florence; David, Marie; Cans, Christine; Jouk, Pierre-Simon; Devillard, Francoise

2015-01-01

Intellectual disability (ID) is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of ID originate from chromosomal imbalances. During the last years, array-CGH has successfully contributed to improve the diagnostic detection rate of genetic abnormalities in patients with ID. Most array-CGH studies focused on patients with moderate or severe intellectual disability. Studies on genetic etiology in children with mild intellectual disability (ID) are very rare. We performed array-CGH analysis in 66 children with mild intellectual disability assessed in a population-based study and for whom no genetic etiology was identified. We found one or more copy number variations (CNVs) in 20 out of 66 (~30 %) patients with a mild ID. In eight of them (~12 %), the CNVs were certainly responsible for the phenotype and in six they were potentially pathogenic for ID. Altogether, array-CGH helped to determine the etiology of ID in 14 patients (~21 %). Our results underscore the clinical relevance of array-CGH to investigate the etiology of isolated idiopathic mild ID in patients or associated with even subtle dysmorphic features or congenital malformations.

Is Higher Consumption of Animal Flesh Foods Associated with Better Iron Status among Adults in Developed Countries? A Systematic Review

PubMed Central

Jackson, Jacklyn; Williams, Rebecca; McEvoy, Mark; MacDonald-Wicks, Lesley; Patterson, Amanda

2016-01-01

Iron deficiency (ID) is the most prevalent nutrient deficiency within the developed world. This is of concern as ID has been shown to affect immunity, thermoregulation, work performance and cognition. Animal flesh foods provide the richest and most bioavailable source of dietary (haem) iron, however, it is unclear whether low animal flesh diets contribute to ID. This systematic review aimed to investigate whether a higher consumption of animal flesh foods is associated with better iron status in adults. CINAHL, Cochrane, EMBASE and MEDLINE were searched for published studies that included adults (≥18 years) from developed countries and measured flesh intakes in relation to iron status indices. Eight experimental and 41 observational studies met the inclusion criteria. Generally, studies varied in population and study designs and results were conflicting. Of the seven high quality studies, five showed a positive association between animal flesh intake (85–300 g/day) and iron status. However, the optimum quantity or frequency of flesh intake required to maintain or achieve a healthy iron status remains unclear. Results show a promising relationship between animal flesh intake and iron status, however, additional longitudinal and experimental studies are required to confirm this relationship and determine optimal intakes to reduce ID development. PMID:26891320

The helix-loop-helix protein id1 controls stem cell proliferation during regenerative neurogenesis in the adult zebrafish telencephalon.

PubMed

Rodriguez Viales, Rebecca; Diotel, Nicolas; Ferg, Marco; Armant, Olivier; Eich, Julia; Alunni, Alessandro; März, Martin; Bally-Cuif, Laure; Rastegar, Sepand; Strähle, Uwe

2015-03-01

The teleost brain has the remarkable ability to generate new neurons and to repair injuries during adult life stages. Maintaining life-long neurogenesis requires careful management of neural stem cell pools. In a genome-wide expression screen for transcription regulators, the id1 gene, encoding a negative regulator of E-proteins, was found to be upregulated in response to injury. id1 expression was mapped to quiescent type I neural stem cells in the adult telencephalic stem cell niche. Gain and loss of id1 function in vivo demonstrated that Id1 promotes stem cell quiescence. The increased id1 expression observed in neural stem cells in response to injury appeared independent of inflammatory signals, suggesting multiple antagonistic pathways in the regulation of reactive neurogenesis. Together, we propose that Id1 acts to maintain the neural stem cell pool by counteracting neurogenesis-promoting signals. © 2014 AlphaMed Press.

Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Tao; Tsui, Benjamin M. W.; Li, Xin

Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method inmore » pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio =1 ± 0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method. Conclusions: The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of {sup 11}C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.« less

Navy Information Dominance Corps: Human Capital Strategy 2012-2017

DTIC Science & Technology

2012-01-01

Information Dominance (ID) is the operational advantage gained from fully integrating information functions, capabilities, resources and people to...and information domains. The human component of ID is the Information Dominance Corps (IDC) and it has three core functions in this mission. First, it...processes, delivery of a Corps-wide learning continuum, and cultivation of an identifiable, inclusive Information Dominance culture and ethos. This

Health Status and ADL Functioning of Older Persons with Intellectual Disability: Community Residence versus Residential Care Centers

ERIC Educational Resources Information Center

Lifshitz, Hefziba; Merrick, Joav; Morad, Mohammed

2008-01-01

The objective of the study was to study differences in aging phenomena among adults with intellectual disability (ID), who live in community residence versus their peers in residential care centers and to determine the contribution of health status, age, gender, etiology and level of ID to the decline in ADL function with age. Our study was based…

Improving diabetes care for people with intellectual disabilities: a qualitative study exploring the perceptions and experiences of professionals in diabetes and intellectual disability services.

PubMed

Brown, M; Taggart, L; Karatzias, T; Truesdale, M; Walley, R; Northway, R; Macrae, S; Carey, M; Davies, M

2017-05-01

Globally, diabetes is increasing with concerns about the impact on outcomes, including premature death and the costs associated with managing the condition. Research indicates that adults with intellectual disabilities (ID) are two to three times more likely to develop diabetes; however, there has been limited focus on diabetes service utilisation in this population. The aim of this study is to explore the perceptions and experiences of diabetes and ID practitioners. A series of 1:1 semi-structured interviews were undertaken in one Scottish health service area. In total, 29 qualitative interviews were conducted: 10 with diabetes practitioners from primary and secondary care, 14 from ID services and 5 from community care services regarding diabetes service provision for this population. Thematic content analysis was undertaken to identify the themes and subthemes. Three main themes were identified: (1) enabling access to services to meet diabetes-related care needs of people with ID; (2) communication and service improvements between staff, patients and across services; and (3) providing person-centred diabetes care and developing adapted resources to increase patient self-care. The findings of this study have important international implications in how diabetes practitioners plan and deliver services for people with ID and other vulnerable groups with limited cognitive ability and communication skills and difficulties in self-management. The findings highlight that access to diabetes education and adapted resources is needed, and if 'reasonable adjustments' are made to service provision and practice, people with ID can benefit from improved healthcare. Developing joint clinics to share knowledge and resources between diabetes and ID practitioners may improve service delivery and continuity of care, and thereby diminish the costs of not providing quality care. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Emotional Development in Adults with Autism and Intellectual Disabilities: A Retrospective, Clinical Analysis

PubMed Central

Sappok, Tanja; Budczies, Jan; Bölte, Sven; Dziobek, Isabel; Dosen, Anton; Diefenbacher, Albert

2013-01-01

Individuals with intellectual disability (ID) are at risk for additional autism spectrum disorders (ASD). A large amount of research reveals deficits in emotion-related processes that are relevant to social cognition in ASD. However, studies on the structure and level of emotional development (ED) assessing emotional maturity according to the normative trajectory in typically developing children are scares. The level of ED can be evaluated by the ‘Scheme of Appraisal of Emotional Development’ (SAED), a semi-structured interview with a close caregiver. The SAED assesses the level of emotional developmental based on a five stage system in 10 domains, for example, ‘interaction with peers’ or ‘object permanence’, which are conducive to the overall emotional developmental level. This study examined the ED as measured by the SAED in 289 adults (mean age: 36 years) with ID with and without additional ASD. A lower level in ED was observed in ASD/ID combined that corresponded to the ED of typically developing children aged 1.5–3 years versus an ED with a corresponding age of 3–7 years in ID individuals without ASD. Moreover, distinct strengths in ‘object permanence’, and weaknesses in ‘interaction’, ‘verbal communication’, ‘experience of self’, ‘affect differentiation’, ‘anxiety’, and ‘handling of material objects’ led to a characteristic pattern of ED in ASD. SAED domains with highest discriminative power between ID individuals with and without ASD (5/10) were used to predict ASD group membership. The classification using a selection of SAED domains revealed a sensitivity of 77.5% and a specificity of 76.4%. ASD risk increased 2.7-fold with every SAED level. The recognition of delayed and uneven pattern of ED contributes to our understanding of the emotion-related impairments in adults with ID and ASD these individuals. Assessment of intra-individual ED could add value to the standard diagnostic procedures in ID, a population at risk for underdiagnosed ASD. PMID:24066092

Emotional development in adults with autism and intellectual disabilities: a retrospective, clinical analysis.

PubMed

Sappok, Tanja; Budczies, Jan; Bölte, Sven; Dziobek, Isabel; Dosen, Anton; Diefenbacher, Albert

2013-01-01

Individuals with intellectual disability (ID) are at risk for additional autism spectrum disorders (ASD). A large amount of research reveals deficits in emotion-related processes that are relevant to social cognition in ASD. However, studies on the structure and level of emotional development (ED) assessing emotional maturity according to the normative trajectory in typically developing children are scares. The level of ED can be evaluated by the 'Scheme of Appraisal of Emotional Development' (SAED), a semi-structured interview with a close caregiver. The SAED assesses the level of emotional developmental based on a five stage system in 10 domains, for example, 'interaction with peers' or 'object permanence', which are conducive to the overall emotional developmental level. This study examined the ED as measured by the SAED in 289 adults (mean age: 36 years) with ID with and without additional ASD. A lower level in ED was observed in ASD/ID combined that corresponded to the ED of typically developing children aged 1.5-3 years versus an ED with a corresponding age of 3-7 years in ID individuals without ASD. Moreover, distinct strengths in 'object permanence', and weaknesses in 'interaction', 'verbal communication', 'experience of self', 'affect differentiation', 'anxiety', and 'handling of material objects' led to a characteristic pattern of ED in ASD. SAED domains with highest discriminative power between ID individuals with and without ASD (5/10) were used to predict ASD group membership. The classification using a selection of SAED domains revealed a sensitivity of 77.5% and a specificity of 76.4%. ASD risk increased 2.7-fold with every SAED level. The recognition of delayed and uneven pattern of ED contributes to our understanding of the emotion-related impairments in adults with ID and ASD these individuals. Assessment of intra-individual ED could add value to the standard diagnostic procedures in ID, a population at risk for underdiagnosed ASD.

Specific needs of families of young adults with profound intellectual disability during and after transition to adulthood: What are we missing?

PubMed

Gauthier-Boudreault, Camille; Gallagher, Frances; Couture, Mélanie

2017-07-01

At the age of 21, the trajectory of services offered to youth with profound intellectual disability (ID) change significantly since access to specialised services is more limited. Despite the desire of parents to avoid any impact on their child, several factors can influence the course of this transition. However, there is little research on facilitators and obstacles to the transition to adulthood, and impacts on people with a profound ID. It is therefore difficult to provide solutions that meet their specific needs. The study aimed to document the needs of parents and young adults with profound ID during and after the transition to adulthood by exploring their transitioning experience and factors that influenced it. Using a descriptive qualitative design, two individual semi-structured interviews were conducted with fourteen (14) parents of young adults aged between 18 and 26 with a profound ID. At this point, many material, informative, cognitive and emotional needs of young adults and their parents are not met. Obstacles, mainly organisational, persist and result in a particularly difficult transition to adulthood experience. By knowing the specific needs of these families, it is possible to develop and implement solutions tailored to their reality. WHAT THE PAPERS ADDS?: The transition to adulthood is a critical period for families with young adults with an intellectual disability (ID), a reality observed internationally. Current literature on all levels of ID suggests some barriers to transition that lead to negative impacts on both parents and young adults with ID. However, presently, very little research exists on the reality of families of young adults with profound ID and factors influencing transition to adult life. Most of studies target people with mild to moderate ID. Considering the significant disabilities of people with profound ID, it is possible to imagine that their experience of transition will be even more difficult and they will present specific needs. The lack of understanding of these needs makes it difficult to introduce solutions tailored to their reality. The results of this current study suggest that many needs of young adults with profound ID and their parents are not met despite existent transition planning services. Transition to adulthood seems particularly difficult for these families who face many challenges. Parents in this study proposed different obstacles during transition to adulthood that could be improved for creation of future solutions adapted to their reality. Copyright © 2017. Published by Elsevier Ltd.

Deletion 2q37 syndrome: Cognitive-behavioral trajectories and autistic features related to breakpoint and deletion size.

PubMed

Fisch, Gene S; Falk, Rena E; Carey, John C; Imitola, Jaime; Sederberg, Maria; Caravalho, Karen S; South, Sarah

2016-09-01

Subtelomeric deletions have been reported in ∼2.5% of individuals with developmental disabilities. Subtelomeric deletion 2q37 has been detected in many individuals diagnosed with intellectual disabilities (ID) and autism spectrum disorders (ASD). Previously, genotype-phenotype correspondences were examined for their relationship to breakpoints 37.1, 37.2, or 37.3. Our purpose was to ascertain whether there were phenotypic differences at these breakpoints, elucidate the cognitive-behavioral phenotype in del2q37, and examine the genotype-phenotype association in the deletion with respect to cognitive-behavioral profiles and ASD. We administered a comprehensive cognitive-behavioral battery to nine children diagnosed with del 2q37, ages 3.9-17.75 years. ID for five tested with the Stanford-Binet (4th Edition) (SBFE) ranged from severe to mild [IQ Range: 36-59]. Adaptive behavior scores from the Vineland Adaptive Behavior Scale (VABS) were much below adequate levels (DQ Range: floor value ["19"] to 55). Autism scores from the Child Autism Rating Scale (CARS) ranged from 22 [non-autistic] to 56 [extremely autistic]; 5/8 [63%] children received scores on the autism spectrum. Participants with the largest deletions, 10.1 and 9.5 Mb, attained the highest IQ and DQ scores while those with the smallest deletions, 7.9 and 6.6 Mb, made the lowest IQ and DQ scores. No association between deletion breakpoint and phenotype were found. Assessment of the various deleted regions suggested histone deacetylase 4 gene (HDAC4) was a likely candidate gene for ASD in our sample. However, two earlier reports found no association between HDAC4 haploinsufficiency and ASD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Problematic Alcohol Use and Mild Intellectual Disability: Standardization of Pictorial Stimuli for an Alcohol Cue Reactivity Task

ERIC Educational Resources Information Center

van Duijvenbode, Neomi; Didden, Robert; Bloemsaat, Gijs; Engels, Rutger C. M. E.

2012-01-01

The present study focused on the first step in developing a cue reactivity task for studying cognitive biases in individuals with mild to borderline intellectual disability (ID) and alcohol use-related problems: the standardization of pictorial stimuli. Participants (N = 40), both with and without a history of alcohol use-related problems and…

The Relationship between Challenging Behaviour, Burnout and Cognitive Variables in Staff Working with People Who Have Intellectual Disabilities

ERIC Educational Resources Information Center

Mills, S.; Rose, J.

2011-01-01

Background: There is evidence to suggest a relationship between the way in which staff perceive challenging behaviour and burnout in staff working with people with intellectual disabilities (ID) and challenging behaviour. However, the evidence of a direct link is equivocal and it is possible that a number of different variables mediate this…

Cognitive Task Analysis of Experts in Designing Multimedia Learning Object Guideline (M-LOG)

ERIC Educational Resources Information Center

Razak, Rafiza Abdul; Palanisamy, Punithavathy

2013-01-01

The purpose of this study was to design and develop a set of guidelines for multimedia learning objects to inform instructional designers (IDs) about the procedures involved in the process of content analysis. This study was motivated by the absence of standardized procedures in the beginning phase of the multimedia learning object design which is…

A systematic literature review of the physical and psychosocial correlates of Special Olympics participation among individuals with intellectual disability.

PubMed

Tint, A; Thomson, K; Weiss, J A

2017-04-01

Special Olympics (SO) is commonly cited to play an important role in the lives of individuals with intellectual disabilities (ID). The purpose of the current review was to (a) synthesise key findings regarding the physical, psychological/emotional, social and/or intellectual/cognitive correlates of SO participation for individuals with ID and (b) highlight limitations in the extant research as well as directions for future research. A systematic review of electronic databases was undertaken. A total of 46 articles were confirmed to meet study criteria. Quality assessments of included studies were conducted using checklists from the Scottish Intercollegiate Guidelines Network methodology checklists (SIGN 50; SIGN 2008). There was a larger amount of support for physical, psychological/emotional and social outcomes as compared with cognitive/intellectual outcomes; however, many studies were confounded by measurement difficulties, sampling procedures and a lack of replicable methods, which hinder generalisation of results. This review highlights the need for a continued critical focus on SO programme evaluation research with more rigorous and replicable methods. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Managing Weight: What Do People with an Intellectual Disability Want from Mobile Technology?

PubMed

Smyth, Phil; McDowell, Claire; Leslie, Julian C; Leader, Geraldine; Donnelly, Mark; Simpson, Elizabeth; Skelly, Laura

2017-01-01

Obesity is a significant health challenge. People with Intellectual Disability (ID) are particularly vulnerable to developing obesity. Mobile technology has been developed to support the management of weight and obesity in the form of apps, although not with people with an ID in mind. As a result existing off-the-shelf weight management apps currently available may not be functional in supporting weight reduction within this population. This paper presents the results of consultations with people with ID regarding weight management, comfort with mobile technology and desired characteristics in apps designed for people with ID that target weight management.

Reduction of errors during practice facilitates fundamental movement skill learning in children with intellectual disabilities.

PubMed

Capio, C M; Poolton, J M; Sit, C H P; Eguia, K F; Masters, R S W

2013-04-01

Children with intellectual disabilities (ID) have been found to have inferior motor proficiencies in fundamental movement skills (FMS). This study examined the effects of training the FMS of overhand throwing by manipulating the amount of practice errors. Participants included 39 children with ID aged 4-11 years who were allocated into either an error-reduced (ER) training programme or a more typical programme in which errors were frequent (error-strewn, ES). Throwing movement form, throwing accuracy, and throwing frequency during free play were evaluated. The ER programme improved movement form, and increased throwing activity during free play to a greater extent than the ES programme. Furthermore, ER learners were found to be capable of engaging in a secondary cognitive task while manifesting robust throwing accuracy performance. The findings support the use of movement skills training programmes that constrain practice errors in children with ID, suggesting that such approach results in improved performance and heightened movement engagement in free play. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

ACE I/D and ACTN3 R/X polymorphisms as potential factors in modulating exercise-related phenotypes in older women in response to a muscle power training stimuli.

PubMed

Pereira, Ana; Costa, Aldo M; Izquierdo, Mikel; Silva, António J; Bastos, Estela; Marques, Mário C

2013-10-01

Genetic variation of the human ACE I/D and ACTN3 R577X polymorphisms subsequent to 12 weeks of high-speed power training on maximal strength (1RM) of the arm and leg muscles, muscle power performance (counter-movement jump), and functional capacity (sit-to-stand test) was examined in older Caucasian women [n = 139; mean age 65.5 (8.2) years; 67.0 (10.0) kg and 1.57 (0.06) m]. Chelex 100 was used for DNA extraction, and genotype was determined by PCR-RFLP methods. Muscular strength, power, and functional testing were conducted at baseline (T1) and after 12 weeks (T2) of high-speed power training. At baseline, the ACE I/D and ACTN3 R/X polymorphisms were not associated with muscle function or muscularity phenotypes in older Caucasian women. After the 12-week high-speed training program, subjects significantly increased their muscular and functional capacity performance (p < 0.05). For both polymorphisms, significant genotype-training interaction (p < 0.05) was found in all muscular performance indices, except for 1RM leg extension in the ACE I/D (p = 0.187). Analyses of the combined effects between genotypes showed significant differences in all parameters (p < 0.05) in response to high-speed power training between the power (ACTN3 RR + RX & ACE DD) versus "non-power" muscularity-oriented genotypes (ACTN3 XX & ACE II + ID)]. Our data suggest that the ACE and ACTN3 genotypes (single or combined) exert a significant influence in the muscle phenotypes of older Caucasian women in response to high-speed power training. Thus, the ACE I/D and ACTN3 R/X polymorphisms are likely factors in modulating exercise-related phenotypes in older women, particularly in response to a resistance training stimuli.

Effects of acupuncture and computer-assisted cognitive training for post-stroke attention deficits: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; McCaskey, Michael A; Yang, Shanli; Ye, Haicheng; Tao, Jing; Jiang, Cai; Schuster-Amft, Corina; Balzer, Christian; Ettlin, Thierry; Schupp, Wilfried; Kulke, Hartwig; Chen, Lidian

2015-12-02

A majority of stroke survivors present with cognitive impairments. Attention disturbance, which leads to impaired concentration and overall reduced cognitive functions, is strongly associated with stroke. The clinical efficacy of acupuncture with Baihui (GV20) and Shenting (GV24) as well as computer-assisted cognitive training in stroke and post-stroke cognitive impairment have both been demonstrated in previous studies. To date, no systematic comparison of these exists and the potential beneficial effects of a combined application are yet to be examined. The main objective of this pilot study is to evaluate the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The second objective is to test the effects of a combined cognitive intervention that incorporates computer-assisted cognitive training and acupuncture (ACoTrain). An international multicentre, single-blinded, randomised controlled pilot trial will be conducted. In a 1:1:1 ratio, 60 inpatients with post-stroke cognitive dysfunction will be randomly allocated into either the acupuncture group, the computer-assisted cognitive training group, or the ACoTrain group in addition to their individual rehabilitation programme. The intervention period of this pilot trial will last 4 weeks (30 minutes per day, 5 days per week, Monday to Friday). The primary outcome is the test battery for attentional performance. The secondary outcomes include the Trail Making Test, Test des Deux Barrages, National Institute of Health Stroke Scale, and Modified Barthel Index for assessment of daily life competence, and the EuroQol Questionnaire for health-related quality of life. This trial mainly focuses on evaluating the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The results of this pilot trial are expected to provide new insights on how Eastern and Western medicine can complement one another and improve the treatment of cognitive impairments in early stroke rehabilitation. Including patients with different cultural backgrounds allows a more generalisable interpretation of the results but also poses risks of performance bias. Using standardised and well-described assessments, validated for each region, is pivotal to allow pooling of the data. Clinical Trails.gov ID: NCT02324959 (8 December 2014).

A Qualitative Analysis of Imitation Performances of Preschoolers With Down Syndrome.

PubMed

Vanvuchelen, Marleen

2016-05-01

A number of studies suggest that imitation is a characteristic strength in children with Down Syndrome (DS). The present study aims to discover whether imitation performances are qualitatively phenotypical in DS. Eight preschoolers with DS were matched on chronological, mental, language and imitation age with 8 preschoolers with intellectual disability of undifferentiated etiology (ID-UND). Imitation performances on the Preschool Imitation and Praxis Scale were videotaped for blind scoring on 30 possible errors. Children with DS made fewer production errors (synkinesias, OR 0.3 [0.1-0.7]), but more conceptual errors (substitution, OR 2.5 [1.6-3.9]) compared to children with ID-UND. This finding is in line with the view of a cognitive phenotype in DS, which is characterized by preserved visuospatial and impaired language abilities.

The Atypical Cadherin Dachsous Controls Left-Right Asymmetry in Drosophila.

PubMed

González-Morales, Nicanor; Géminard, Charles; Lebreton, Gaëlle; Cerezo, Delphine; Coutelis, Jean-Baptiste; Noselli, Stéphane

2015-06-22

Left-right (LR) asymmetry is essential for organ development and function in metazoans, but how initial LR cue is relayed to tissues still remains unclear. Here, we propose a mechanism by which the Drosophila LR determinant Myosin ID (MyoID) transfers LR information to neighboring cells through the planar cell polarity (PCP) atypical cadherin Dachsous (Ds). Molecular interaction between MyoID and Ds in a specific LR organizer controls dextral cell polarity of adjoining hindgut progenitors and is required for organ looping in adults. Loss of Ds blocks hindgut tissue polarization and looping, indicating that Ds is a crucial factor for both LR cue transmission and asymmetric morphogenesis. We further show that the Ds/Fat and Frizzled PCP pathways are required for the spreading of LR asymmetry throughout the hindgut progenitor tissue. These results identify a direct functional coupling between the LR determinant MyoID and PCP, essential for non-autonomous propagation of early LR asymmetry. Copyright © 2015 Elsevier Inc. All rights reserved.

Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus.

PubMed

Tran, Phu V; Kennedy, Bruce C; Lien, Yu-Chin; Simmons, Rebecca A; Georgieff, Michael K

2015-02-15

Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency. Copyright © 2015 the American Physiological Society.

Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus

PubMed Central

Kennedy, Bruce C.; Lien, Yu-Chin; Simmons, Rebecca A.; Georgieff, Michael K.

2014-01-01

Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency. PMID:25519736

Variable expressivity of a likely pathogenic variant in KCNQ2 in a three-generation pedigree presenting with intellectual disability with childhood onset seizures.

PubMed

Hewson, Stacy; Puka, Klajdi; Mercimek-Mahmutoglu, Saadet

2017-08-01

KCNQ2 has been reported as a frequent cause of autosomal dominant benign familial neonatal seizures. De novo likely pathogenic variants in KCNQ2 have been described in neonatal or early infantile onset epileptic encephalopathy patients. Here, we report a three-generation family with six affected patients with a novel likely pathogenic variant (c.628C>T; p.Arg210Cys) in KCNQ2. Four family members, three adults and a child, presented with a childhood seizure onset with variability in the severity of seizures and response to treatment, intellectual disability (ID) as well as behavioral problems. The two youngest affected patients had a variable degree of global developmental delay with no seizures at their current age. This three-generation family with six affected members expands the phenotypic spectrum of KCNQ2 associated encephalopathy to KCNQ2 associated ID and or childhood onset epileptic encephalopathy. We think that KCNQ2 associated epileptic encephalopathy should be included in the differential diagnosis of childhood onset epilepsy and early onset global developmental delay, cognitive dysfunction, or ID. Furthermore, whole exome sequencing in families with ID and history of autosomal dominant inheritance pattern with or without seizures, may further broaden the phenotypic spectrum of KCNQ2 associated epileptic encephalopathy or encephalopathy. © 2017 Wiley Periodicals, Inc.

The Role of Community Nurses and Residential Staff in Supporting Women with Intellectual Disability to Access Breast Screening Services

ERIC Educational Resources Information Center

Taggart, L.; Truesdale-Kennedy, M.; McIlfatrick, S.

2011-01-01

Background: Women with intellectual disability (ID) are surviving to the age group at greatest risk of developing breast cancer (50-69 years). These women are more likely to experience a greater number of risk factors placing them at an advanced threat of developing breast cancer. However, as a result of cognitive deficits and communication…

Sex Differences in Performance over 7 Years on the Wechsler Intelligence Scale for Children Revised among Adults with Intellectual Disability

ERIC Educational Resources Information Center

Kittler, P.; Krinsky-McHale, S. J.; Devenny, D. A.

2004-01-01

The aim of this study was to explore changes related to sex differences on the Wechsler Intelligence Scale for Children Revised (WISC-R) subtest performance over a 7-year interval in middle-aged adults with intellectual disability (ID). Cognitive sex differences have been extensively studied in the general population, but there are few reports…

The Impact of Staff Initiated Referral and Intervention Protocols on Symptoms of Depression in People with Mild Intellectual Disability

ERIC Educational Resources Information Center

McGillivray, Jane A.; Kershaw, Mavis M.

2013-01-01

It has been estimated that people with ID experience the same and possibly higher levels of depression than the general population. Referral to a General Medical Practitioner (GP) for primary care is recommended practice for people with depression and cognitive behavioural (CB) therapy is now an accepted evidence based intervention. A growing body…

Impact of Dementia-Derived Nonpharmacological Intervention Procedures on Cognition and Behavior in Older Adults with Intellectual Disabilities: A 3-Year Follow-Up Study

ERIC Educational Resources Information Center

De Vreese, Luc P.; Mantesso, Ulrico; De Bastiani, Elisa; Weger, Elisabeth; Marangoni, Annachiara C.; Gomiero, Tiziano

2012-01-01

Dementia appears at a higher rate among some adults with intellectual disabilities (ID) and this potentially poses a greater risk of nursing home admission. Yet, to date, there is no evidence on the efficacy of general dementia-derived environment-, personnel-, and patient-oriented intervention strategies in delaying onset of dementia or in…

Mindfulness-Based Cognitive Therapy for Adults with Intellectual Disabilities: An Evaluation of the Effectiveness of Mindfulness in Reducing Symptoms of Depression and Anxiety

ERIC Educational Resources Information Center

Idusohan-Moizer, H.; Sawicka, A.; Dendle, J.; Albany, M.

2015-01-01

Background: Mindfulness-based interventions have been shown to be effective in the treatment of a range of health and psychological disorders in adults and young people without intellectual disabilities (ID). Clinical studies are emerging reporting on the efficacy of mindfulness-based interventions as a stand-alone treatment for common clinical…

An Expert Instructor's Use of Social Congruence, Cognitive Congruence, and Expertise in an Online Case-Based Instructional Design Course

ERIC Educational Resources Information Center

Watson, Sunnie Lee; Koehler, Adrie A.; Ertmer, Peggy; Kim, WooRi; Rico, Rudy

2018-01-01

Promoting and sustaining effective discussion--that which contributes to learning--is a skill that eludes many instructors (Darling-Hammond, 2008; Ge, Yamashiro, & Lee, 2000). This study explored the role and strategies of an expert instructor in an online advanced instructional design (ID) course that utilized a case-based learning (CBL)…

Iron assessment to protect the developing brain.

PubMed

Georgieff, Michael K

2017-12-01

Iron deficiency (ID) before the age of 3 y can lead to long-term neurological deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin concentrations followed by iron treatment. Furthermore, pre- or nonanemic ID alters neurobehavioral function and is 3 times more common than IDA in toddlers. Given the global prevalence of ID and the enormous societal cost of developmental disabilities across the life span, better methods are needed to detect the risk of inadequate concentrations of iron for brain development (i.e., brain tissue ID) before dysfunction occurs and to monitor its amelioration after diagnosis and treatment. The current screening and treatment strategy for IDA fails to achieve this goal for 3 reasons. First, anemia is the final state in iron depletion. Thus, the developing brain is already iron deficient when IDA is diagnosed owing to the prioritization of available iron to red blood cells over all other tissues during negative iron balance in development. Second, brain ID, independently of IDA, is responsible for long-term neurological deficits. Thus, starting iron treatment after the onset of IDA is less effective than prevention. Multiple studies in humans and animal models show that post hoc treatment strategies do not reliably prevent ID-induced neurological deficits. Third, most currently used indexes of ID are population statistical cutoffs for either hematologic or iron status but are not bioindicators of brain ID and brain dysfunction in children. Furthermore, their relation to brain iron status is not known. To protect the developing brain, there is a need to generate serum measures that index brain dysfunction in the preanemic stage of ID, assess the ability of standard iron indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of early iron treatment in preventing ID-induced brain dysfunction. © 2017 American Society for Nutrition.

ID2 collaborates with ID3 to suppress iNKT and innate-like tumors1

PubMed Central

Li, Jia; Roy, Sumedha; Kim, Young-Mi; Li, Shibo; Zhang, Baojun; Love, Cassandra; Reddy, Anupama; Rajagopalan, Deepthi; Dave, Sandeep; Diehl, Anna Mae; Zhuang, Yuan

2017-01-01

Inhibitor of DNA binding (ID) proteins, including ID1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins has been associated with a broad spectrum of tumors, recent studies have identified that ID3 plays a tumor suppressor role in the development of Burkitt’s lymphoma in humans and Hepatosplenic T cell lymphomas in mice. Here, we report rapid lymphoma development in Id2/Id3 double knockout (L-DKO) mice caused by unchecked expansion of either invariant Natural Killer T (iNKT) cells, or a unique subset of innate-like, CD1d-independent T cells. These populations started expansion in neonatal mice and, upon malignant transformation, caused fatality at age between 3–11 months. The malignant cells also gave rise to lymphomas upon transfer to Rag-deficient and wild-type hosts, reaffirming their inherent tumorigenic potential. Microarray analysis revealed a significantly modified program in these neonatal iNKT cells that ultimately led to their malignant transformation. The lymphoma cells demonstrated chromosome instability, along with upregulation of several different signaling pathways, including the cytokine-cytokine receptor interaction pathway, which can promote their expansion and migration. Dysregulation of genes with reported driver mutations and the NF-kB pathway were found to be shared between L-DKO lymphomas and human NKT tumors. Our work identifies a distinct premalignant state and multiple tumoriogenic pathways caused by loss function of ID2 and ID3. Thus, conditional deletion of Id2 and Id3 in developing T cells establishes a unique animal model for iNKT and relevant innate-like lymphomas. PMID:28258199

Intellectual disabilities, neuronal posttranscriptional RNA metabolism, and RNA-binding proteins: three actors for a complex scenario.

PubMed

Bardoni, Barbara; Abekhoukh, Sabiha; Zongaro, Samantha; Melko, Mireille

2012-01-01

Intellectual disability (ID) is the most frequent cause of serious handicap in children and young adults and interests 2-3% of worldwide population, representing a serious problem from the medical, social, and economic points of view. The causes are very heterogeneous. Genes involved in ID have various functions altering different pathways important in neuronal function. Regulation of mRNA metabolism is particularly important in neurons for synaptic structure and function. Here, we review ID due to alteration of mRNA metabolism. Functional absence of some RNA-binding proteins--namely, FMRP, FMR2P, PQBP1, UFP3B, VCX-A--causes different forms of ID. These proteins are involved in different steps of RNA metabolism and, even if a detailed analysis of their RNA targets has been performed so far only for FMRP, it appears clear that they modulate some aspects (translation, stability, transport, and sublocalization) of a subset of RNAs coding for proteins, whose function must be relevant for neurons. Two other proteins, DYRK1A and CDKL5, involved in Down syndrome and Rett syndrome, respectively, have been shown to have an impact on splicing efficiency of specific mRNAs. Both proteins are kinases and their effect is indirect. Interestingly, both are localized in nuclear speckles, the nuclear domains where splicing factors are assembled, stocked, and recycled and influence their biogenesis and/or their organization. Copyright © 2012 Elsevier B.V. All rights reserved.

The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual Disability in Two Azeri Families

PubMed Central

Kahrizi, Kimia; Musante, Luciana; Fattahi, Zohreh; Hosseini, Masoumeh; Maqsoud, Fariba; Farajollahi, Reza; Wienker, Thomas F.; Ropers, H. Hilger; Najmabadi, Hossein

2015-01-01

Cognitive impairment or intellectual disability (ID) is a widespread neurodevelopmental disorder characterized by low IQ (below 70). ID is genetically heterogeneous and is estimated to affect 1–3% of the world’s population. In affected children from consanguineous families, autosomal recessive inheritance is common, and identifying the underlying genetic cause is an important issue in clinical genetics. In the framework of a larger project, aimed at identifying candidate genes for autosomal recessive intellectual disorder (ARID), we recently carried out single nucleotide polymorphism-based genome-wide linkage analysis in several families from Ardabil province in Iran. The identification of homozygosity-by-descent loci in these families, in combination with whole exome sequencing, led us to identify possible causative homozygous changes in two families. In the first family, a missense variant was found in GRM1 gene, while in the second family, a frameshift alteration was identified in TRMT1, both of which were found to co-segregate with the disease. GRM1, a known causal gene for autosomal recessive spinocerebellar ataxia (SCAR13, MIM#614831), encodes the metabotropic glutamate receptor1 (mGluR1). This gene plays an important role in synaptic plasticity and cerebellar development. Conversely, the TRMT1 gene encodes a tRNA methyltransferase that dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl methionine as the methyl group donor. We recently presented TRMT1 as a candidate gene for ARID in a consanguineous Iranian family (Najmabadi et al., 2011). We believe that this second Iranian family with a biallelic loss-of-function mutation in TRMT1 gene supports the idea that this gene likely has function in development of the disorder. PMID:26308914

The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual Disability in Two Azeri Families.

PubMed

Davarniya, Behzad; Hu, Hao; Kahrizi, Kimia; Musante, Luciana; Fattahi, Zohreh; Hosseini, Masoumeh; Maqsoud, Fariba; Farajollahi, Reza; Wienker, Thomas F; Ropers, H Hilger; Najmabadi, Hossein

2015-01-01

Cognitive impairment or intellectual disability (ID) is a widespread neurodevelopmental disorder characterized by low IQ (below 70). ID is genetically heterogeneous and is estimated to affect 1-3% of the world's population. In affected children from consanguineous families, autosomal recessive inheritance is common, and identifying the underlying genetic cause is an important issue in clinical genetics. In the framework of a larger project, aimed at identifying candidate genes for autosomal recessive intellectual disorder (ARID), we recently carried out single nucleotide polymorphism-based genome-wide linkage analysis in several families from Ardabil province in Iran. The identification of homozygosity-by-descent loci in these families, in combination with whole exome sequencing, led us to identify possible causative homozygous changes in two families. In the first family, a missense variant was found in GRM1 gene, while in the second family, a frameshift alteration was identified in TRMT1, both of which were found to co-segregate with the disease. GRM1, a known causal gene for autosomal recessive spinocerebellar ataxia (SCAR13, MIM#614831), encodes the metabotropic glutamate receptor1 (mGluR1). This gene plays an important role in synaptic plasticity and cerebellar development. Conversely, the TRMT1 gene encodes a tRNA methyltransferase that dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl methionine as the methyl group donor. We recently presented TRMT1 as a candidate gene for ARID in a consanguineous Iranian family (Najmabadi et al., 2011). We believe that this second Iranian family with a biallelic loss-of-function mutation in TRMT1 gene supports the idea that this gene likely has function in development of the disorder.

Id1 expression promotes peripheral CD4{sup +} T cell proliferation and survival upon TCR activation without co-stimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Chen; Jin, Rong; Wang, Hong-Cheng

2013-06-21

Highlights: •Id1 expression enables naïve T cell proliferation without anti-CD28 co-stimulation. •Id1 expression facilitates T cells survival when stimulated with anti-CD3. •Elevation of IL-2 production by Id1 contributes increased proliferation and survival. •Id1 potentiates NF-κB activation by anti-CD3 stimulation. -- Abstract: Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïvemore » CD4{sup +} cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.« less

Operational Art and the Sustainment Warfighting Function

DTIC Science & Technology

2011-12-01

Infantry Division (ID) a continuous sustainment line of operation. The leap- frogging of Forward Logisitics Bases provided 3rd Infantry Division (ID...victims. A C-17 Globemaster III departed North Carolina and delivered 14,000 Meals Ready-to- Eat , or MREs, and 14,000 quarts of water in a 7-hour round

Intellectual disability and homelessness.

PubMed

Mercier, C; Picard, S

2011-04-01

The association between poverty and intellectual disability (ID) has been well documented. However, little is known about persons with ID who face circumstances of extreme poverty, such as homelessness. This paper describes the situation of persons with ID who were or are homeless in Montreal and are currently receiving services from a team dedicated to homeless persons. (1) To describe the characteristics, history and current situation of these persons; and (2) to report within-group differences as a function of gender and current residential status. The data were collected from files using an anonymous chart summary. Descriptive statistics on the whole sample (n = 68) and inferential statistics on cross-tabulations by gender and residential status were performed. Persons with ID exhibited several related problems. Some of these persons, primarily women, experienced relatively short periods of homelessness and their situations stabilised once they were identified and followed up. Other persons with ID experienced chronic homelessness that appeared to parallel the number and severity of their other problems. When compared with a previous epidemiological study of the homeless in Montreal, the population of homeless persons with ID differed from the overall homeless population in a number of respects. The results suggest prevention and intervention targets. The need for epidemiological research appears particularly clear in light of the fact that below-average intellectual functioning has been identified as a risk factor for homelessness and a predisposing factor for vulnerability among street people. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Iron supplementation until 6 months protects marginally low-birth-weight infants from iron deficiency during their first year of life.

PubMed

Berglund, Staffan K; Westrup, Björn; Domellöf, Magnus

2015-03-01

Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000-2500 g) infants, of iron supplements given until 6 months of life. In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg · kg(-1) · day(-1) of iron supplements from 6 weeks to 6 months of age. At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.006). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Iron supplements with 2 mg · kg(-1) · day(-1) until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.

Glutamatergic synapses in neurodevelopmental disorders.

PubMed

Moretto, Edoardo; Murru, Luca; Martano, Giuseppe; Sassone, Jenny; Passafaro, Maria

2018-06-08

Neurodevelopmental disorders (NDDs) are a group of diseases whose symptoms arise during childhood or adolescence and that impact several higher cognitive functions such as learning, sociability and mood. Accruing evidence suggests that a shared pathogenic mechanism underlying these diseases is the dysfunction of glutamatergic synapses. We summarize present knowledge on autism spectrum disorders (ASD), intellectual disability (ID), Down syndrome (DS), Rett syndrome (RS) and attention-deficit hyperactivity disorder (ADHD), highlighting the involvement of glutamatergic synapses and receptors in these disorders. The most commonly shared defects involve α-amino-3-hydroxy-5-methyl- 4-isoxazole propionic acid receptors (AMPARs), N-methyl-d-aspartate receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), whose functions are strongly linked to synaptic plasticity, affecting both cell-autonomous features as well as circuit formation. Moreover, the major scaffolding proteins and, thus, the general structure of the synapse are often deregulated in neurodevelopmental disorders, which is not surprising considering their crucial role in the regulation of glutamate receptor positioning and functioning. This convergence of defects supports the definition of neurodevelopmental disorders as a continuum of pathological manifestations, suggesting that glutamatergic synapses could be a therapeutic target to ameliorate patient symptomatology. Copyright © 2017. Published by Elsevier Inc.

Genetic influence on exercise-induced changes in physical function among mobility-limited older adults

PubMed Central

Hsu, Fang-Chi; Brinkley, Tina E.; Carter, Christy S.; Church, Timothy S.; Dodson, John A.; Goodpaster, Bret H.; McDermott, Mary M.; Nicklas, Barbara J.; Yank, Veronica; Johnson, Julie A.; Pahor, Marco

2014-01-01

To date, physical exercise is the only intervention consistently demonstrated to attenuate age-related declines in physical function. However, variability exists in seniors' responsiveness to training. One potential source of variability is the insertion (I allele) or deletion (D allele) of a 287 bp fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. This polymorphism is known to influence a variety of physiological adaptions to exercise. However, evidence is inconclusive regarding the influence of this polymorphism on older adults' functional responses to exercise. This study aimed to evaluate the association of ACE I/D genotypes with changes in physical function among Caucasian older adults (n = 283) following 12 mo of either structured, multimodal physical activity or health education. Measures of physical function included usual-paced gait speed and performance on the Short Physical Performance Battery (SPPB). After checking Hardy-Weinberg equilibrium, we used using linear regression to evaluate the genotype*treatment interaction for each outcome. Covariates included clinic site, body mass index, age, sex, baseline score, comorbidity, and use of angiotensin receptor blockers or ACE inhibitors. Genotype frequencies [II (19.4%), ID (42.4%), DD (38.2%)] were in Hardy-Weinberg equilibrium (P > 0.05). The genotype*treatment interaction was statistically significant for both gait speed (P = 0.002) and SPPB (P = 0.020). Exercise improved gait speed by 0.06 ± 0.01 m/sec and SPPB score by 0.72 ± 0.16 points among those with at least one D allele (ID/DD carriers), but function was not improved among II carriers. Thus, ACE I/D genotype appears to play a role in modulating functional responses to exercise training in seniors. PMID:24423970

Synaptic dysfunction and intellectual disability.

PubMed

Valnegri, Pamela; Sala, Carlo; Passafaro, Maria

2012-01-01

Intellectual disability (ID) is a common and highly heterogeneous paediatric disorder with a very severe social impact. Intellectual disability can be caused by environmental and/or genetic factors. Although in the last two decades a number of genes have been discovered whose mutations cause mental retardation, we are still far from identifying the impact of these mutations on brain functions. Many of the genes mutated in ID code for several proteins with a variety of functions: chromatin remodelling, pre-/post-synaptic activity, and intracellular trafficking. The prevailing hypothesis suggests that the ID phenotype could emerge from abnormal cellular processing leading to pre- and/or post-synaptic dysfunction. In this chapter, we focus on the role of small GTPases and adhesion molecules, and we discuss the mechanisms through which they lead to synaptic network dysfunction.

Home literacy environment of pre-school children with intellectual disabilities.

PubMed

van der Schuit, M; Peeters, M; Segers, E; van Balkom, H; Verhoeven, L

2009-12-01

For pre-school children, the home literacy environment (HLE) plays an important role in the development of language and literacy skills. As there is little known about the HLE of children with intellectual disabilities (ID), the aim of the present study was to investigate the HLE of children with ID in comparison with children without disabilities. Parent questionnaires concerning aspects of the HLE were used to investigate differences between 48 children with ID, 107 children without disabilities of the same chronological age and 36 children without disabilities of the same mental age (MA). Furthermore, for the children with ID, correlations were computed between aspects of the HLE and children's non-verbal intelligence, speech intelligibility, language and early literacy skills. From the results of the multivariate analyses of variance it could be concluded that the HLE of children with ID differed from that of children in the chronological age group on almost all aspects. When compared with children in the MA group, differences in the HLE remained. However, differences mainly concerned child-initiated activities and not parent-initiated activities. Correlation analyses showed that children's activities with literacy materials were positively related with MA, productive syntax and vocabulary age, and book orientation skills. Also, children's involvement during storybook reading was related with their MA, receptive language age, productive syntax and vocabulary age, book orientation and rapid naming of pictures. The amount of literacy materials parents provided was related to a higher productive syntax age and level of book orientation of the children. Parent play activities were also positively related to children's speech intelligibility. The cognitive disabilities of the children were the main cause of the differences found in the HLE between children with ID and children without disabilities. Parents also adapt their level to the developmental level of their child, which may not always be the most stimulating for the children.

Prevalence and Correlates of Elopement in a Nationally Representative Sample of Children with Developmental Disabilities in the United States.

PubMed

Kiely, Bridget; Migdal, Talia R; Vettam, Sujit; Adesman, Andrew

2016-01-01

Despite increased awareness and concern about children with developmental disabilities wandering away from adult supervision, there is a paucity of research about elopement. This is the first study to examine and report the prevalence and correlates of elopement in a nationally representative sample of school-age children in the United States with an autism spectrum disorder (ASD) and/or cognitive impairment. Data were obtained from the CDC's "Pathways" Survey, a follow-up telephone survey of the parents of 4,032 children with a developmental condition. 3,518 children that had ASD, intellectual disability (ID), and/or developmental delay (DD) at the time of survey administration were included for analysis. Children were divided into three condition groups: ASD-only; ID/DD-only; ASD+ID/DD. Logistic regression analyses were used to compare the prevalence of elopement and rates of preventive measure use (barriers and/or electronic devices) across condition groups, and to examine the clinical and demographic correlates of elopement. T-tests were also performed to compare scores on the Children's Social Behavior Questionnaire (CSBQ) between wanderers and non-wanderers. Overall, 26.7% of children had reportedly eloped within the previous year, most commonly from public places. Children with ASD-only and ASD+ID/DD were more likely to have eloped than those with ID/DD-only. Across all groups, wanderers scored higher than non-wanderers on five out of six CSBQ subscales; they were more likely not to realize when there is danger, to have difficulty distinguishing between strangers and familiar people, to show sudden mood changes, to over-react to everything/everyone, to get angry quickly, to get lost easily, and to panic in new situations or if change occurs. Even after controlling for elopement history, parents of children in the ASD+ID/DD group were more likely than those in the other condition groups to report using physical or electronic measures to prevent wandering.

High-throughput sequencing technology to reveal the composition and function of cecal microbiota in Dagu chicken.

PubMed

Xu, Yunhe; Yang, Huixin; Zhang, Lili; Su, Yuhong; Shi, Donghui; Xiao, Haidi; Tian, Yumin

2016-11-04

The chicken gut microbiota is an important and complicated ecosystem for the host. They play an important role in converting food into nutrient and energy. The coding capacity of microbiome vastly surpasses that of the host's genome, encoding biochemical pathways that the host has not developed. An optimal gut microbiota can increase agricultural productivity. This study aims to explore the composition and function of cecal microbiota in Dagu chicken under two feeding modes, free-range (outdoor, OD) and cage (indoor, ID) raising. Cecal samples were collected from 24 chickens across 4 groups (12-w OD, 12-w ID, 18-w OD, and 18-w ID). We performed high-throughput sequencing of the 16S rRNA genes V4 hypervariable regions to characterize the cecal microbiota of Dagu chicken and compare the difference of cecal microbiota between free-range and cage raising chickens. It was found that 34 special operational taxonomic units (OTUs) in OD groups and 4 special OTUs in ID groups. 24 phyla were shared by the 24 samples. Bacteroidetes was the most abundant phylum with the largest proportion, followed by Firmicutes and Proteobacteria. The OD groups showed a higher proportion of Bacteroidetes (>50 %) in cecum, but a lower Firmicutes/Bacteroidetes ratio in both 12-w old (0.42, 0.62) and 18-w old groups (0.37, 0.49) compared with the ID groups. Cecal microbiota in the OD groups have higher abundance of functions involved in amino acids and glycan metabolic pathway. The composition and function of cecal microbiota in Dagu chicken under two feeding modes, free-range and cage raising are different. The cage raising mode showed a lower proportion of Bacteroidetes in cecum, but a higher Firmicutes/Bacteroidetes ratio compared with free-range mode. Cecal microbiota in free-range mode have higher abundance of functions involved in amino acids and glycan metabolic pathway.

Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.

PubMed

Redin, Claire; Gérard, Bénédicte; Lauer, Julia; Herenger, Yvan; Muller, Jean; Quartier, Angélique; Masurel-Paulet, Alice; Willems, Marjolaine; Lesca, Gaétan; El-Chehadeh, Salima; Le Gras, Stéphanie; Vicaire, Serge; Philipps, Muriel; Dumas, Michaël; Geoffroy, Véronique; Feger, Claire; Haumesser, Nicolas; Alembik, Yves; Barth, Magalie; Bonneau, Dominique; Colin, Estelle; Dollfus, Hélène; Doray, Bérénice; Delrue, Marie-Ange; Drouin-Garraud, Valérie; Flori, Elisabeth; Fradin, Mélanie; Francannet, Christine; Goldenberg, Alice; Lumbroso, Serge; Mathieu-Dramard, Michèle; Martin-Coignard, Dominique; Lacombe, Didier; Morin, Gilles; Polge, Anne; Sukno, Sylvie; Thauvin-Robinet, Christel; Thevenon, Julien; Doco-Fenzy, Martine; Genevieve, David; Sarda, Pierre; Edery, Patrick; Isidor, Bertrand; Jost, Bernard; Olivier-Faivre, Laurence; Mandel, Jean-Louis; Piton, Amélie

2014-11-01

Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation. We report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern. We analysed 106 patients with ID of unknown aetiology following array-CGH analysis and other genetic investigations. Ninety per cent of these patients were males, and 75% sporadic cases. We identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1). We also detected four possibly causative mutations (eg, in NLGN3) requiring further investigations. We present detailed reasoning for assigning causality for each mutation, and associated patients' clinical information. Some genes were hit more than once in our cohort, suggesting they correspond to more frequent ID-associated conditions (KDM5C, MECP2, DYRK1A, TCF4). We highlight some unexpected genotype to phenotype correlations, with causative mutations being identified in genes associated to defined syndromes in patients deviating from the classic phenotype (DMD, TCF4, MECP2). We also bring additional supportive (HCFC1, MED13L) or unsupportive (SHROOM4, SRPX2) evidences for the implication of previous candidate genes or mutations in cognitive disorders. With a diagnostic yield of 25% targeted sequencing appears relevant as a first intention test for the diagnosis of ID, but importantly will also contribute to a better understanding regarding the specific contribution of the many genes implicated in ID and autism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing

PubMed Central

Redin, Claire; Gérard, Bénédicte; Lauer, Julia; Herenger, Yvan; Muller, Jean; Quartier, Angélique; Masurel-Paulet, Alice; Willems, Marjolaine; Lesca, Gaétan; El-Chehadeh, Salima; Le Gras, Stéphanie; Vicaire, Serge; Philipps, Muriel; Dumas, Michaël; Geoffroy, Véronique; Feger, Claire; Haumesser, Nicolas; Alembik, Yves; Barth, Magalie; Bonneau, Dominique; Colin, Estelle; Dollfus, Hélène; Doray, Bérénice; Delrue, Marie-Ange; Drouin-Garraud, Valérie; Flori, Elisabeth; Fradin, Mélanie; Francannet, Christine; Goldenberg, Alice; Lumbroso, Serge; Mathieu-Dramard, Michèle; Martin-Coignard, Dominique; Lacombe, Didier; Morin, Gilles; Polge, Anne; Sukno, Sylvie; Thauvin-Robinet, Christel; Thevenon, Julien; Doco-Fenzy, Martine; Genevieve, David; Sarda, Pierre; Edery, Patrick; Isidor, Bertrand; Jost, Bernard; Olivier-Faivre, Laurence; Mandel, Jean-Louis; Piton, Amélie

2014-01-01

Background Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation. Methods We report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern. We analysed 106 patients with ID of unknown aetiology following array-CGH analysis and other genetic investigations. Ninety per cent of these patients were males, and 75% sporadic cases. Results We identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1). We also detected four possibly causative mutations (eg, in NLGN3) requiring further investigations. We present detailed reasoning for assigning causality for each mutation, and associated patients’ clinical information. Some genes were hit more than once in our cohort, suggesting they correspond to more frequent ID-associated conditions (KDM5C, MECP2, DYRK1A, TCF4). We highlight some unexpected genotype to phenotype correlations, with causative mutations being identified in genes associated to defined syndromes in patients deviating from the classic phenotype (DMD, TCF4, MECP2). We also bring additional supportive (HCFC1, MED13L) or unsupportive (SHROOM4, SRPX2) evidences for the implication of previous candidate genes or mutations in cognitive disorders. Conclusions With a diagnostic yield of 25% targeted sequencing appears relevant as a first intention test for the diagnosis of ID, but importantly will also contribute to a better understanding regarding the specific contribution of the many genes implicated in ID and autism. PMID:25167861

Does cognitive behavioral therapy alter mental defeat and cognitive flexibility in patients with panic disorder?

PubMed

Nagata, Shinobu; Seki, Yoichi; Shibuya, Takayuki; Yokoo, Mizue; Murata, Tomokazu; Hiramatsu, Yoichi; Yamada, Fuminori; Ibuki, Hanae; Minamitani, Noriko; Yoshinaga, Naoki; Kusunoki, Muga; Inada, Yasushi; Kawasoe, Nobuko; Adachi, Soichiro; Oshiro, Keiko; Matsuzawa, Daisuke; Hirano, Yoshiyuki; Yoshimura, Kensuke; Nakazato, Michiko; Iyo, Masaomi; Nakagawa, Akiko; Shimizu, Eiji

2018-01-12

Mental defeat and cognitive flexibility have been studied as explanatory factors for depression and posttraumatic stress disorder. This study examined mental defeat and cognitive flexibility scores in patients with panic disorder (PD) before and after cognitive behavioral therapy (CBT), and compared them to those of a gender- and age-matched healthy control group. Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the control group (n = 35) received no treatment. Patients completed the Mental Defeat Scale and the Cognitive Flexibility Scale before the intervention, following eight CBT sessions, and following 16 CBT sessions, while the control group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental Defeat and Cognitive Flexibility Scale scores were significantly higher on the Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of the control group participants were. In addition, the average Mental Defeat Scale scores of the patients decreased significantly, from 22.2 to 12.4, while their average Cognitive Flexibility Scale scores increased significantly, from 42.8 to 49.5. These results suggest that CBT can reduce mental defeat and increase cognitive flexibility in patients with PD Trial registration The study was registered retrospectively in the national UMIN Clinical Trials Registry on June 10, 2016 (registration ID: UMIN000022693).

Mental health needs and availability of mental health care for children and adolescents with intellectual disability in Berlin.

PubMed

Soltau, B; Biedermann, J; Hennicke, K; Fydrich, T

2015-11-01

The increased risk of mental health problems in children and adolescents with intellectual disability (ID) has been reported in several studies. However, almost no research has been conducted on parents' experiences with the general mental health system. We have investigated the prevalence of emotional and behavioural problems in children with ID as well as the availability and quality of mental health care from the parents' point of view. Teachers of specialised schools for ID in Berlin were asked to complete the Teacher's Report Form (TRF) of the Child Behavior Checklist. Information was collected for 1226 children and adolescents aged 6-18 years with mild to profound ID (response 70.5%). The availability and quality of mental health care was assessed by a questionnaire given to parents who had already been seeking help for their children. A total of 330 parents completed the questionnaires (response 62.0%). In addition to univariate analysis, we conducted multiple logistic regressions regarding the psychopathology reported by teachers (TRF-syndrome scales) and difficulties concerning mental health care reported by parents for a paired sample of 308 children. Overall, 52.4% of the children and adolescents with ID had a total problem score on the TRF in the deviant range (47.1% when eliminating four items reflecting cognitive deficits). Compared with the general population normative sample of children, this is a three-time higher prevalence. The most striking problems were thought problems (schizoid and obsessive-compulsive), aggressive behaviour, attention problems and social problems. Parents whose children had more severe behavioural or emotional dysfunction reported more difficulties with the mental health system. From the parents' point of view, mental health professionals frequently did not feel responsible or were not sufficiently skilled for the treatment of children with ID. As a consequence, 96% of all parents were longing for specialised in- and outpatient services. This study confirms the findings from other studies regarding the high rate of co-occurrence of ID and mental health problems in youths. Results indicate that both are strongly requested by parents: specialised in- and outpatient services, as well as more professional general services and equitable treatment for all children, with and without ID. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

The Contributions of Memory and Vocabulary to Non-Verbal Ability Scores in Adolescents with Intellectual Disability

PubMed Central

Mungkhetklang, Chantanee; Bavin, Edith L.; Crewther, Sheila G.; Goharpey, Nahal; Parsons, Carl

2016-01-01

It is usually assumed that performance on non-verbal intelligence tests reflects visual cognitive processing and that aspects of working memory (WM) will be involved. However, the unique contribution of memory to non-verbal scores is not clear, nor is the unique contribution of vocabulary. Thus, we aimed to investigate these contributions. Non-verbal test scores for 17 individuals with intellectual disability (ID) and 39 children with typical development (TD) of similar mental age were compared to determine the unique contribution of visual and verbal short-term memory (STM) and WM and the additional variance contributed by vocabulary scores. No significant group differences were found in the non-verbal test scores or receptive vocabulary scores, but there was a significant difference in expressive vocabulary. Regression analyses indicate that for the TD group STM and WM (both visual and verbal) contributed similar variance to the non-verbal scores. For the ID group, visual STM and verbal WM contributed most of the variance to the non-verbal test scores. The addition of vocabulary scores to the model contributed greater variance for both groups. More unique variance was contributed by vocabulary than memory for the TD group, whereas for the ID group memory contributed more than vocabulary. Visual and auditory memory and vocabulary contributed significantly to solving visual non-verbal problems for both the TD group and the ID group. However, for each group, there were different weightings of these variables. Our findings indicate that for individuals with TD, vocabulary is the major factor in solving non-verbal problems, not memory, whereas for adolescents with ID, visual STM, and verbal WM are more influential than vocabulary, suggesting different pathways to achieve solutions to non-verbal problems. PMID:28082922

The impact of staff initiated referral and intervention protocols on symptoms of depression in people with mild intellectual disability.

PubMed

McGillivray, Jane A; Kershaw, Mavis M

2013-02-01

It has been estimated that people with ID experience the same and possibly higher levels of depression than the general population. Referral to a General Medical Practitioner (GP) for primary care is recommended practice for people with depression and cognitive behavioural (CB) therapy is now an accepted evidence based intervention. A growing body of literature indicates that people with ID and depression may benefit from CB strategies. The aim of the current study was to compare (i) CB group intervention strategies with referral to a GP; (ii) CB group intervention strategies only; and (iii) referral to a GP only on symptoms of depression among people with mild ID. Staff from six participating agencies received training in (a) how to identify and screen individuals with mild ID for depressive symptoms and risk factors for depression, and (b) supportive referral of identified individuals to GPs for mental health services. In addition, staff from four of the agencies undertook (c) training on how to deliver group CB intervention strategies. Eighty-two participants were allocated to one of the three intervention groups. Depressive symptoms and negative automatic thoughts were assessed prior to the intervention, at the conclusion of the intervention, and at eight months follow-up. Compared to GP referral alone, those participants who received CB strategies both with and without GP referral displayed significant reductions in depressive symptoms. The use of CB strategies only also resulted in a significant reduction in frequency of negative automatic thoughts. The findings of this study support routine screening of individuals with mild ID for depression and the delivery of group CB intervention programmes by trained staff within community-based disability agencies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Iron deficiency in a tertiary gastroenterology center in Romania: prevalence and significancy.

PubMed

Preda, Carmen Monica; Proca, Doina; Sandra, Irina; Horeanga, Boroka Claudia; Fulger, Larisa Elena; Manuc, Teodora; Bancila, Ion; Balas, Oana Elena; Manuc, Mircea; Diculescu, Mircea; Baicus, Cristian; Tieranu, Cristian; Constantinescu, Ileana

2018-01-01

Introduction: Iron deficiency has been known to cause significant functional impairment, lower quality of life and higher morbidity and mortality. The aim of this study was to estimate the prevalence and significance of iron deficiency in our patients and medical staff. Material and methods: We performed a prospective cross-sectional study: In July 2016, 383 persons were screened for the presence of iron deficiency (ID): 325 patients and 58 people from the medical staff. Transferrin saturation (TSAT), serum ferritin (SF) and complete blood count were performed. Absolute ID was diagnosed if SF <100 ng/ml and TSAT <20%. Relative ID was defined by SF >100 ng/ml and TSAT <20%. Results: The group of medical staff was younger and had a greater proportion of women. The prevalence of absolute ID was 22.5% in patients and 43.1% in medical staff; relative ID was present in 15% of patients and 1.7% of medical staff. Among patients, the absolute ID was significantly correlated with the female sex (p=0.002) and pre-menopausal status (p=0.01) but did not correlate with diagnosis, age, BMI, nonsteroidal anti-inflammatory drug (NSAID), aspirin or acenocoumarol consumption. The relative ID is associated with advanced age (p=0.03) and diagnosis of cancer and liver cirrhosis (p=0.01). Conclusions: Absolute ID had a high prevalence among patients (22.5%), but there was even a bigger issue among the medical staff (43.1%). Absolute ID was correlated with female sex and pre-menopausal status. Relative ID was related to advanced age, cancer and liver cirrhosis. Abbreviations: serum ferritine- SF, transferrin saturation coefficient- TSAT, iron deficiency- ID, inflammatory bowel diseases- IBD, quality of life- QoL, GI- gastrointestinal.

Iron deficiency in a tertiary gastroenterology center in Romania: prevalence and significancy

PubMed Central

Preda, Carmen Monica; Proca, Doina; Sandra, Irina; Horeanga, Boroka Claudia; Fulger, Larisa Elena; Manuc, Teodora; Bancila, Ion; Balas, Oana Elena; Manuc, Mircea; Diculescu, Mircea; Baicus, Cristian; Tieranu, Cristian; Constantinescu, Ileana

2018-01-01

Introduction:Iron deficiency has been known to cause significant functional impairment, lower quality of life and higher morbidity and mortality. The aim of this study was to estimate the prevalence and significance of iron deficiency in our patients and medical staff. Material and methods:We performed a prospective cross-sectional study: In July 2016, 383 persons were screened for the presence of iron deficiency (ID): 325 patients and 58 people from the medical staff. Transferrin saturation (TSAT), serum ferritin (SF) and complete blood count were performed. Absolute ID was diagnosed if SF <100 ng/ml and TSAT <20%. Relative ID was defined by SF >100 ng/ml and TSAT <20%. Results:The group of medical staff was younger and had a greater proportion of women. The prevalence of absolute ID was 22.5% in patients and 43.1% in medical staff; relative ID was present in 15% of patients and 1.7% of medical staff. Among patients, the absolute ID was significantly correlated with the female sex (p=0.002) and pre-menopausal status (p=0.01) but did not correlate with diagnosis, age, BMI, nonsteroidal anti-inflammatory drug (NSAID), aspirin or acenocoumarol consumption. The relative ID is associated with advanced age (p=0.03) and diagnosis of cancer and liver cirrhosis (p=0.01). Conclusions:Absolute ID had a high prevalence among patients (22.5%), but there was even a bigger issue among the medical staff (43.1%). Absolute ID was correlated with female sex and pre-menopausal status. Relative ID was related to advanced age, cancer and liver cirrhosis. Abbreviations: serum ferritine- SF, transferrin saturation coefficient- TSAT, iron deficiency- ID, inflammatory bowel diseases- IBD, quality of life- QoL, GI- gastrointestinal PMID:29696062

POWERS forID: Personalized Online Weight and Exercise Response System for Individuals with Intellectual Disability: study protocol for a randomized controlled trial.

PubMed

Neumeier, William H; Guerra, Nichole; Thirumalai, Mohanraj; Geer, Betty; Ervin, David; Rimmer, James H

2017-10-23

Intellectual disability (ID) is characterized by limitations in intellectual functioning and adaptive behavior. Adults with ID exhibit higher rates of obesity and poorer health status compared to the general population. Continuity of care and barriers to health-related activities may contribute to the poorer health status observed in this population. To address this problem, a tailored weight management online health information and communication technology platform, known as POWERS forID , was developed and is being tested to determine if this delivery mechanism can improve weight maintenance/weight loss in adults with ID. Obese adults with mild-to-moderate ID (n = 70) are randomized to the POWERS forID intervention or control group for a 24-week trial. Each group undergoes an assessment that includes body weight, waist circumference, and percent body fat at baseline and at weeks 6, 12, and 24. Physical activity barriers, healthy eating barriers, food frequency, and psychosocial wellbeing are measured at baseline and at weeks 12 and 24. Blood lipids are assessed at baseline and 24 weeks. Participants randomized to POWERS forID receive access to the POWERS forID website and calls from a health coach (weekly during weeks 1-12, biweekly during weeks 13-24). The health coach employs motivational interviewing techniques adapted for individuals with ID to promote behavior change. Participants randomized to the control group receive standard clinical weight-loss care. Differences in weight, waist circumference, blood lipids, percent body fat, and psychosocial self-report will be assessed. Barriers and facilitators of implementation as well as perception of study outcomes will be conducted via qualitative analysis. POWERS forID is a novel information and communication technology platform designed to address health needs for adults with ID. This article describes the development and components of POWERS forID . The overall aim is to assess usability and feasibility of POWERS forID for promoting weight loss for obese adults with ID over the course of a 24-week randomized control trial. Clinicaltrials.gov, NCT03139760 . Registered on XXX.

The co-occurrence of mental disorders in children and adolescents with intellectual disability/intellectual developmental disorder

PubMed Central

Munir, Kerim M.

2016-01-01

Purpose of review The study summarizes supportive epidemiological data regarding the true co-occurrence (comorbidity) and course of mental disorders in children with intellectual disability/intellectual developmental disorders (ID/IDD) across the lifespan. Recent findings Published studies involving representative populations of children and adolescents with ID/IDD have demonstrated a three to four-fold increase in prevalence of co-occurring mental disorders. The effect of age, sex, and severity (mild, moderate, severe, and profound) and socioeconomic status on prevalence is currently not clearly understood. To date there are no prevalence estimates of co-occurring mental disorders in youth identified using the new DSM-5 (and proposed ICD-11) definition of ID/IDD using measures of intellectual functions and deficits in adaptive functioning with various severity levels defined on the basis of adaptive functioning, and not intellectual quotient scores. Summary The true relationship between two forms of morbidity remains complex and causal relationships that may be true for one disorder may not apply to another. The new conceptualization of ID/IDD offers a developmentally better informed psychobiological approach that can help distinguish co-occurrence of mental disorders within the neurodevelopmental section with onset during the developmental period as well as the later onset of other mental disorders. PMID:26779862

The co-occurrence of mental disorders in children and adolescents with intellectual disability/intellectual developmental disorder.

PubMed

Munir, Kerim M

2016-03-01

The study summarizes supportive epidemiological data regarding the true co-occurrence (comorbidity) and course of mental disorders in children with intellectual disability/intellectual developmental disorders (ID/IDD) across the lifespan. Published studies involving representative populations of children and adolescents with ID/IDD have demonstrated a three to four-fold increase in prevalence of co-occurring mental disorders. The effect of age, sex, and severity (mild, moderate, severe, and profound) and socioeconomic status on prevalence is currently not clearly understood. To date there are no prevalence estimates of co-occurring mental disorders in youth identified using the new DSM-5 (and proposed ICD-11) definition of ID/IDD using measures of intellectual functions and deficits in adaptive functioning with various severity levels defined on the basis of adaptive functioning, and not intellectual quotient scores. The true relationship between two forms of morbidity remains complex and causal relationships that may be true for one disorder may not apply to another. The new conceptualization of ID/IDD offers a developmentally better informed psychobiological approach that can help distinguish co-occurrence of mental disorders within the neurodevelopmental section with onset during the developmental period as well as the later onset of other mental disorders.

The Influence of Anger-Arousal Level on Attribution of Hostile Intent and Problem Solving Capability in an Individual with a Mild Intellectual Disability and a History of Difficulties with Aggression

ERIC Educational Resources Information Center

MacMahon, Kenneth M. A.; Jahoda, Andrew; Espie, Colin A.; Broomfield, Niall M.

2006-01-01

Background: Recent studies have suggested that cognitive biases may play an important mediating role in aggressive outbursts from people with mild intellectual disabilities (IDs). Essentially, some individuals may frequently perceive other people as acting towards them in a hostile fashion. This biased perception may develop through repeated…

Holographic calculation for large interval Rényi entropy at high temperature

NASA Astrophysics Data System (ADS)

Chen, Bin; Wu, Jie-qiang

2015-11-01

In this paper, we study the holographic Rényi entropy of a large interval on a circle at high temperature for the two-dimensional conformal field theory (CFT) dual to pure AdS3 gravity. In the field theory, the Rényi entropy is encoded in the CFT partition function on n -sheeted torus connected with each other by a large branch cut. As proposed by Chen and Wu [Large interval limit of Rényi entropy at high temperature, arXiv:1412.0763], the effective way to read the entropy in the large interval limit is to insert a complete set of state bases of the twist sector at the branch cut. Then the calculation transforms into an expansion of four-point functions in the twist sector with respect to e-2/π T R n . By using the operator product expansion of the twist operators at the branch points, we read the first few terms of the Rényi entropy, including the leading and next-to-leading contributions in the large central charge limit. Moreover, we show that the leading contribution is actually captured by the twist vacuum module. In this case by the Ward identity the four-point functions can be derived from the correlation function of four twist operators, which is related to double interval entanglement entropy. Holographically, we apply the recipe in [T. Faulkner, The entanglement Rényi entropies of disjoint intervals in AdS/CFT, arXiv:1303.7221] and [T. Barrella et al., Holographic entanglement beyond classical gravity, J. High Energy Phys. 09 (2013) 109] to compute the classical Rényi entropy and its one-loop quantum correction, after imposing a new set of monodromy conditions. The holographic classical result matches exactly with the leading contribution in the field theory up to e-4 π T R and l6, while the holographical one-loop contribution is in exact agreement with next-to-leading results in field theory up to e-6/π T R n and l4 as well.

ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism.

PubMed

Contini, Mauro; Compagnino, Elisa; Cattadori, Gaia; Magrì, Damiano; Camera, Marina; Apostolo, Anna; Farina, Stefania; Palermo, Pietro; Gertow, Karl; Tremoli, Elena; Fiorentini, Cesare; Agostoni, Piergiuseppe

2016-04-01

The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor's protection of the lungs in HF during acute fluid overload. 100 HF patients (left ventricular ejection fraction ≤40 %) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500 cc saline. ACE I/D genotype prevalence was: DD = 28, ID =55 and II = 17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco -2.3 ± 1.3 vs. -0.8 ± 1.9 and -0.6 ± 1 mL/mmHg/min, p < 0.0001 and p < 0.01; Dm -7 ± 5 vs. -3.2 ± 7.4 and -1.3 ± 5 mL/mmHg/min, p < 0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8 ± 1.9 vs. -0.8 ± 2.3, p = 0.01). ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors.

Decreased serum hepcidin, inflammation, and improved functional iron status six-months post-restrictive bariatric surgery.

USDA-ARS?s Scientific Manuscript database

Excess adiposity is associated with low-grade inflammation and decreased iron status. Iron depletion (ID) in obesity is thought to be mediated by an inflammation-induced increase in the body’s main regulator of iron homeostasis, hepcidin. Elevated hepcidin can result in ID as it prevents the release...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

Executive Functions and Adaptive Behaviour in Autism Spectrum Disorders with and without Intellectual Disability

PubMed Central

Panerai, Simonetta; Tasca, Domenica; Ferri, Raffaele; Genitori D'Arrigo, Valentina; Elia, Maurizio

2014-01-01

Executive functions (EF) in autism spectrum disorders (ASD) have been often investigated, although results seem to be rather inconsistent. The first aim of this study was to detect which EF components are common to the ASD continuum (from high- to low-functioning ASD) and identify a possible EF profile for ASD people. Planning, mental flexibility, inhibition of response, generativity, and ecologic EF were investigated. This study was extended not only to high-functioning ASD, but also to ASD with intellectual disability (ID). The second aim was to find EF aspects correlating with adaptive skills in ASD. A total of 61 children participated in the study (27 ASD with and without ID and 34 controls). Results highlight an executive profile characterised by impaired flexibility and deficient planning; these deficits are associated with decreased adaptive ability, particularly socialization, and a deficient shifting in ecologic conditions. These features are present in all ASD subgroups with and without ID; for this reason, they might be assumed as being specific features in ASD. PMID:24829905

Familiarity and recollection in Williams syndrome.

PubMed

Costanzo, Floriana; Vicari, Stefano; Carlesimo, Giovanni A

2013-01-01

Interest is being shown in a componential analysis of performance on declarative memory tasks that distinguishes two different kinds of access to stored memories, recollection and familiarity. From a developmental perspective, it has been hypothesized that recollection emerges later and shows more developmental changes than familiarity. Nevertheless, the contribution of recollection and familiarity to the recognition performance of individuals with intellectual disabilities (ID) has been rarely examined. The present study was aimed at investigating the qualitative profile of declarative long-term memory in a group of individuals with Williams syndrome (WS). We compared 13 individuals with WS and 13 mental-age-matched typically developing children in two different experimental paradigms to assess the contribution of familiarity and recollection to recognition performance. We adopted a modified version of the process dissociation procedure and a task dissociation procedure, both of which are suited to individuals with ID. Results of both experimental paradigms demonstrated reduced recollection and spared familiarity in the declarative memory performances of individuals with WS. These results provide direct evidence of a dissociation between recollection and familiarity in a neurodevelopmental disorder and are discussed in relation to alternative approaches for explaining abnormal cognition in individuals with ID. Copyright © 2011 Elsevier Ltd. All rights reserved.

Relaxation therapy and anxiety, self-esteem, and emotional regulation among adults with intellectual disabilities: A randomized controlled trial.

PubMed

Bouvet, Cyrille; Coulet, Aurélie

2016-09-01

This pilot study is a randomized controlled trial on the effects of relaxation on anxiety, self-esteem, and emotional regulation in adults with intellectual disabilities (ID) working in a center of supported employment in France. We studied 30 adults with mild or moderate ID who were split at random into a relaxation group (RG, 15 subjects), who completed 10 sessions of relaxation therapy, and a control group (CG, 15 subjects), who were on a waiting list. The method used is the pretest and posttest. Variables were assessed by the State-Trait Anxiety Inventory form Y scale, the Rosenberg Self-Esteem scale, and the Emotion Regulation Questionnaire. We found that in the RG, relaxation significantly reduced state anxiety, t(14, 15) = 17.8***, d = -0.72, and improved self-esteem, t(14, 15) = -7.7***, d = 1.03, and cognitive reappraisal, t(14, 15) = -6.3***, d = 1.3, while the CG showed no change for these variables. We conclude that relaxation seems to be an interesting therapeutic option for reducing anxiety in people with ID in a supported employment setting. © The Author(s) 2015.

Grief and its Complications in Individuals with Intellectual Disability

PubMed Central

Brickell, Claire; Munir, Kerim

2011-01-01

Bereavement and loss have significant impact on the lives of individuals with intellectual disability (ID). Although there is a growing impetus to define the symptoms of grief that predict long-term functional impairment, little is known about maladaptive grieving among individuals with ID. We examine the literature concerning the phenomenology of traumatic grief (TG) in the general population, along with what is known about the manifestations of grief in individuals with ID. We then apply modern theories of grief and grief resolution to individuals with ID in order to highlight potential areas of vulnerability in this population and to lay the groundwork for interventions that will facilitate their adaptation to loss. We provide a theoretical framework for the proposition that individuals (including children and adults) with ID are more susceptible to TG, based on an increased risk of secondary loss, barriers to communicating about the loss, and difficulty finding meaning in the loss. We conclude that individuals with ID should be considered as potential candidates for targeted bereavement interventions. Further research is required, however, in order to develop population-appropriate measurement scales for testing these hypotheses. PMID:18306095

Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures.

PubMed

Dai, Yu-Jie; Zhang, Xin; Yang, Yang; Nan, Hai-Yan; Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Bo; Zhang, Jin; Qiu, Zi-Yu; Gao, Yi; Cui, Guang-Bin; Chen, Bi-Liang; Wang, Wen

2018-03-14

The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

Physical function is weakly associated with angiotensin-converting enzyme gene I/D polymorphism in elderly Japanese subjects.

PubMed

Yoshihara, A; Tobina, T; Yamaga, T; Ayabe, M; Yoshitake, Y; Kimura, Y; Shimada, M; Nishimuta, M; Nakagawa, N; Ohashi, M; Hanada, N; Tanaka, H; Kiyonaga, A; Miyazaki, H

2009-01-01

The turning point in the deterioration of physical function seems to occur between the ages of 70 and 80 years. In particular, muscle strength may decline even more in subjects older than 75. A recent study found that the angiotensin-converting enzyme (ACE) genotype also affects physiological left ventricular hypertrophy. A very limited number of papers have examined genetic differences in resistance and endurance forms of a single sporting discipline. The purpose of this study was to evaluate the relationship between ACE genotype and physical function by controlling the known confounding factors including dental status. We selected 431 subjects who were aged 76 years and did not require special care for their daily activities. We conducted a medical examination, followed by 5 physical function tests, as follows: (1) maximum hand grip strength, (2) maximal isometric knee extensor strength, (3) maximal stepping rate for 10 s, (4) one-leg standing time with eyes open and (5) 10-meter maximum walking speed. Subjects were genotyped for the ACE intron 16 Alu insertion. In addition, serum concentrations of total cholesterol, total protein, IgA and IgG were measured at a commercial laboratory. The Eichner index was used as an indicator of occlusal condition. Multiple linear regression analysis was performed to evaluate the relationship between the ACE gene insertion/deletion (I/D) polymorphism and physical function considering confounding factors. The ACE gene I/D polymorphism was positively associated with hand grip strength and 10-meter maximum walking speed. Betas of hand grip strength were 0.09 for I/D (p = 0.022) and 0.12 for insertion/insertion (I/I; p = 0.004). Betas of 10-meter walking speed were -0.11 for I/D (p = 0.093) and -0.14 for I/I (p = 0.039). Dental status such as Eichner index class C was significantly associated with one-leg standing time with eyes open (beta -0.11; p = 0.028). This study suggests that there is a significant relationship between ACE genotype and physical function. In particular, subjects with the ACE deletion/deletion genotype were associated with upper extremities. Copyright 2009 S. Karger AG, Basel.

Drug burden index to define the burden of medicines in older adults with intellectual disabilities: An observational cross-sectional study.

PubMed

O'Connell, Juliette; Burke, Éilish; Mulryan, Niamh; O'Dwyer, Claire; Donegan, Clare; McCallion, Philip; McCarron, Mary; Henman, Martin C; O'Dwyer, Máire

2018-03-01

The drug burden index (DBI) is a dose-related measure of anticholinergic and sedative drug exposure. This cross-sectional study described DBI in older adults with intellectual disabilities (ID) and the most frequently reported therapeutic classes contributing to DBI and examined associations between higher DBI scores and potential adverse effects as well as physical function. This study analysed data from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a representative study on the ageing of people with ID in Ireland. Self- and objectively-reported data were collected on medication use and physical health, including health conditions. The Barthel index was the physical function measure. The study examined 677 individuals with ID, of whom 644 (95.1%) reported taking medication and 78.6% (n = 532) were exposed to medication with anticholinergic and/or sedative activity. 54.2% (n = 367) were exposed to high DBI score (≥1). Adjusted multivariate regression analysis revealed no significant association between DBI score and daytime dozing, constipation or falls. After adjusting for confounders (sex, age, level of ID, comorbidities, behaviours that challenge, history of falls), DBI was associated with significantly higher dependence in the Barthel index (P = 0.002). This is the first time DBI has been described in older adults with ID. Scores were much higher than those observed in the general population and higher scores were associated with higher dependence in Barthel index activities of daily living. © 2017 The British Pharmacological Society.

Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites.

PubMed

Elam, W Austin; Schrank, Travis P; Campagnolo, Andrew J; Hilser, Vincent J

2013-04-01

Intrinsically disordered (ID) proteins function in the absence of a unique stable structure and appear to challenge the classic structure-function paradigm. The extent to which ID proteins take advantage of subtle conformational biases to perform functions, and whether signals for such mechanism can be identified in proteome-wide studies is not well understood. Of particular interest is the polyproline II (PII) conformation, suggested to be highly populated in unfolded proteins. We experimentally determine a complete calorimetric propensity scale for the PII conformation. Projection of the scale into representative eukaryotic proteomes reveals significant PII bias in regions coding for ID proteins. Importantly, enrichment of PII in ID proteins, or protein segments, is also captured by other PII scales, indicating that this enrichment is robustly encoded and universally detectable regardless of the method of PII propensity determination. Gene ontology (GO) terms obtained using our PII scale and other scales demonstrate a consensus for molecular functions performed by high PII proteins across the proteome. Perhaps the most striking result of the GO analysis is conserved enrichment (P < 10(-8) ) of phosphorylation sites in high PII regions found by all PII scales. Subsequent conformational analysis reveals a phosphorylation-dependent modulation of PII, suggestive of a conserved "tunability" within these regions. In summary, the application of an experimentally determined polyproline II (PII) propensity scale to proteome-wide sequence analysis and gene ontology reveals an enrichment of PII bias near disordered phosphorylation sites that is conserved throughout eukaryotes. Copyright © 2013 The Protein Society.

Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

2012-08-01

Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P < 0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P < 0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P < 0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P < 0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.

Infectious Disease Stigmas: Maladaptive in Modern Society

PubMed Central

Smith, Rachel A.; Hughes, David

2014-01-01

At multiple times in human history people have asked if there are good stigmas. Is there some useful function stigmas serve in the context of our evolutionary history; is stigma adaptive? This essay discusses stigmas as a group-selection strategy and the human context in which stigmas likely appeared. The next section explores how human patterns have changed in modern society and the consequences for infectious disease (ID) stigmas in the modern age. The concluding section suggests that while social-living species may be particularly apt to create and communicate ID stigmas and enact ID-related stigmatization, such stigma-related processes no longer function to protect human communities. Stigmas do not increase the ability of modern societies to survive infectious diseases, but in fact may be important drivers of problematic disease dynamics and act as catalysts for failures in protecting public health. PMID:25477728

Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability.

PubMed

Frielink, N; Schuengel, C; Embregts, P

2017-07-01

According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic motivation for people with intellectual disability (ID) due to their cognitive limitations. The current study challenges this proposal by testing whether the four subtypes of extrinsic motivation can be differentiated among people with ID as well. The subtypes of extrinsic motivation were measured using two adapted versions of the Self-Regulation Questionnaire, one regarding exercise and one regarding support. In total, 186 adults with mild to borderline ID participated in the study. Results supported the distinction between the four subtypes of extrinsic motivation regarding both exercise and support. In addition, the correlation coefficients supported a quasi-simplex pattern of correlations among the subtypes, indicating that adjacent subtypes were more closely related than non-adjacent subtypes. Moreover, the study showed sufficient Cronbach's alphas and test-retest reliabilities for early stage research. Overall, the results of the current study provide initial evidence for the universality of the four subtypes of extrinsic motivation across populations with and without ID. © 2017 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.

A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1-42-injected mice.

PubMed

Jia, Tingting; Sun, Zhiguo; Lu, Ying; Gao, Jie; Zou, Hao; Xie, Fangyuan; Zhang, Guoqing; Xu, Hao; Sun, Duxin; Yu, Yuan; Zhong, Yanqiang

2016-01-01

Due to the impermeability of the blood-brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood-brain barrier permeability-surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P<0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β1-42-injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics.

Increased Training Intensity Induces Proper Membrane Localization of Actin Remodeling Proteins in the Hippocampus Preventing Cognitive Deficits: Implications for Fragile X Syndrome.

PubMed

Martinez, L A; Tejada-Simon, Maria Victoria

2018-06-01

Behavioral intervention therapy has proven beneficial in the treatment of autism and intellectual disabilities (ID), raising the possibility of certain changes in molecular mechanisms activated by these interventions that may promote learning. Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by autistic features and intellectual disability and can serve as a model to examine mechanisms that promote learning. FXS results from mutations in the fragile X mental retardation 1 gene (Fmr1) that prevents expression of the Fmr1 protein (FMRP), a messenger RNA (mRNA) translation regulator at synapses. Among many other functions, FMRP organizes a complex with the actin cytoskeleton-regulating small Rho GTPase Rac1. As in humans, Fmr1 KO mice lacking FMRP display autistic-like behaviors and deformities of actin-rich synaptic structures in addition to impaired hippocampal learning and synaptic plasticity. These features have been previously linked to proper function of actin remodeling proteins that includes Rac1. An important step in Rac1 activation and function is its translocation to the membrane, where it can influence synaptic actin cytoskeleton remodeling during hippocampus-dependent learning. Herein, we report that Fmr1 KO mouse hippocampus exhibits increased levels of membrane-bound Rac1, which may prevent proper learning-induced synaptic changes. We also determine that increasing training intensity during fear conditioning (FC) training restores contextual memory in Fmr1 KO mice and reduces membrane-bound Rac1 in Fmr1 KO hippocampus. Increased training intensity also results in normalized long-term potentiation in hippocampal slices taken from Fmr1 KO mice. These results point to interventional treatments providing new therapeutic options for FXS-related cognitive dysfunction.

Physical Fitness Profile in Adults with Intellectual Disabilities: Differences between Levels of Sport Practice

ERIC Educational Resources Information Center

Cuesta-Vargas, Antonio Ignacio; Paz-Lourido, Berta; Rodriguez, Alejandro

2011-01-01

Neuromuscular and aerobic capacity can be reduced in people with intellectual disabilities (ID). Previous studies suggest these individuals might be particularly susceptible to losing basic functions because of poor physical fitness. The aim of this study is to describe the physical fitness profile of adult athletes with ID and identify whether…

Schizophrenia-Spectrum Psychoses in People With and Without Intellectual Disability

ERIC Educational Resources Information Center

Bouras, N.; Martin, G.; Leese, M.; Vanstraelen, M.; Holt, G.; Thomas, C.; Hindler, C.; Boardman, J.

2004-01-01

Although there is an increased risk of schizophrenia-spectrum psychoses (SSP) in people with intellectual disability (ID), there is a paucity of research evidence into clinical presentation of the disorder in comparison with research into SSP in people without ID. Aims The aims of the study were to compare clinical, functional, and social factors…

The Diagnosis of Depression in People with Severe Limitations in Intellectual Functioning

ERIC Educational Resources Information Center

Scott, Haleigh; Havercamp, Susan M.

2015-01-01

People with intellectual disability (ID) were once considered immune to developing psychopathology, including affective disorders such as depression. Now research has shown that people with ID do suffer from depression, and the focus is on understanding how to best diagnose and provide treatment. Research has come a long way in adapting the…

FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end

PubMed Central

Sato, Koichi; Shimomuki, Mayo; Katsuki, Yoko; Takahashi, Daisuke; Kobayashi, Wataru; Ishiai, Masamichi; Miyoshi, Hiroyuki; Takata, Minoru; Kurumizaka, Hitoshi

2016-01-01

The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork. PMID:27694619

Inhibitor of differentiation 1 transcription factor promotes metabolic reprogramming in hepatocellular carcinoma cells

PubMed Central

Sharma, Bal Krishan; Kolhe, Ravindra; Black, Stephen M.; Keller, Jonathan R.; Mivechi, Nahid F.; Satyanarayana, Ande

2016-01-01

Reprograming of metabolism is one of the central hallmarks of cancer. The majority of cancer cells depend on high rates of glycolysis and glutaminolysis for their growth and survival. A number of oncogenes and tumor suppressors have been connected to the regulation of altered glucose and glutamine metabolism in cancer cells. For example, the oncogene c-Myc plays vital roles in cancer cell metabolic adaptation by directly regulating various genes that participate in aerobic glycolysis and glutaminolysis. Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays important roles in cell proliferation, differentiation, and cell fate determination. Overexpression of Id1 causes intestinal adenomas and thymic lymphomas in mice, suggesting that Id1 could function as an oncogene. Despite it being an oncogene, whether Id1 plays any prominent role in cancer cell metabolic reprograming is unknown. Here, we demonstrate that Id1 is strongly expressed in human and mouse liver tumors and in hepatocellular carcinoma (HCC) cell lines, whereas its expression is very low or undetectable in normal liver tissues. In HCC cells, Id1 expression is regulated by the MAPK/ERK pathway at the transcriptional level. Knockdown of Id1 suppressed aerobic glycolysis and glutaminolysis, suggesting that Id1 promotes a metabolic shift toward aerobic glycolysis. At the molecular level, Id1 mediates its metabolic effects by regulating the expression levels of c-Myc. Knockdown of Id1 resulted in down-regulation (∼75%) of c-Myc, whereas overexpression of Id1 strongly induced (3-fold) c-Myc levels. Interestingly, knockdown of c-Myc resulted in down-regulation (∼60%) of Id1, suggesting a positive feedback-loop regulatory mechanism between Id1 and c-Myc. Under anaerobic conditions, both Id1 and c-Myc are down-regulated (50–70%), and overexpression of oxygen-insensitive hypoxia-inducible factor 1α (Hif1α) or its downstream target Mxi1 resulted in a significant reduction of c-Myc and Id1 (∼70%), suggesting that Hif1α suppresses Id1 and c-Myc under anaerobic conditions via Mxi1. Together, our findings indicate a prominent novel role for Id1 in liver cancer cell metabolic adaptation.—Sharma, B. K., Kolhe, R., Black, S. M., Keller, J. R., Mivechi, N. F., Satyanarayana, A. Inhibitor of differentiation 1 transcription factor promotes metabolic reprogramming in hepatocellular carcinoma cells. PMID:26330493

Iron deficiency impairs developing hippocampal neuron gene expression, energy metabolism and dendrite complexity

PubMed Central

Bastian, Thomas W.; von Hohenberg, William C.; Mickelson, Daniel J.; Lanier, Lorene M.; Georgieff, Michael K.

2016-01-01

Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments, including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a similar degree of neuronal ID as seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e., BdnfVI, Camk2a, Vamp1, Psd95, Cfl1, Pfn1, Pfn2, and Gda) and mitochondrial function (i.e., Ucp2, Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons was reduced. By 18DIV, a partial recovery of dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism, is responsible for the effects of fetal/neonatal ID and IDA on hippocampal neuron dendritic and synaptic maturation. Impairments in these neurodevelopmental processes likely underlie the negative impact of early life ID and IDA on hippocampus-mediated learning and memory. PMID:27669335

Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

PubMed Central

Anthony, Bruno J.; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

2016-01-01

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social–emotional functioning. White and Black youth (n = 64; ages 6–17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation. PMID:26439481

Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

PubMed

Ratto, Allison B; Anthony, Bruno J; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

2016-03-01

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black youth (n = 64; ages 6-17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation.

Preliminary findings of serum creatinine and estimated glomerular filtration rate (eGFR) in adolescents with intellectual disabilities.

PubMed

Lin, Jin-Ding; Lin, Lan-Ping; Hsieh, Molly; Lin, Pei-Ying

2010-01-01

The present study aimed to describe the kidney function profile - serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents with ID who participated in annual health examinations as they enrolled into special education schools in Taiwan. We used serum samples to determine participants' creatinine profiles, and the Cockcroft-Gault formula to calculate the data of eGFR to present the chronic kidney disease. The results found 22% of the participants have abnormal serum creatinine value (creatinine>1.0mg/dl) and 59.6%, 36.4% and 4.0% at chronic kidney disease (CKD) stage 1, 2 and 3 cases accordingly based on the Cockcroft-Gault formula. No CKD stage 4 and 5 cases in this study. That is, there were 4% CKD cases (eGFR <60 mL/min/1.73 m(2); CKD stage 3, 4 and 5) in adolescents with ID in this study. The results also indicated that gender and BMI could significantly predict abnormal creatinine condition in multivariate logistic regression analysis. Those boys with ID were more likely to have abnormal creatinine value than girls with ID (OR=10.13, 95% CI=5.96-17.23). In term of BMI, those underweight adolescents with ID were less likely to have high creatinine value compared to normal weight group (OR=0.45, 95% CI=0.28-0.72). In summary, this study provides the preliminary information of creatinine and estimated GFR in people with ID; we suggest the public health policy should initiate appropriate management strategies to monitor kidney function and to improve treatment outcomes of chronic kidney disease for this vulnerable population. Copyright © 2010 Elsevier Ltd. All rights reserved.

Caregivers' reported functional limitations in activities of daily living among middle-aged adults with intellectual disabilities.

PubMed

Lin, Lan-Ping; Hsia, Yi-Chen; Hsu, Shang-Wei; Loh, Ching-Hui; Wu, Chia-Ling; Lin, Jin-Ding

2013-12-01

This study was conducted to describe the functioning of Activities of Daily Living (ADL) and to examine socio-economic effects on ADL functioning among adults with intellectual disabilities (ID) aged 45 years and older (N=480) in Taiwan. The Barthel Index (BI) was used to determine a baseline level of ADL functioning in the study participants. There are five categories of functional impairment using the following cut-off values in Taiwan: total dependence (BI score 0-20), severe (BI score 21-60), moderate (BI score 61-90), mild (BI score 91-99), and total independence (BI score 100) (Taiwan Department of Health, 2012). The results revealed that 2.3% of adults with ID were in total dependence, 11.9% were in severe dependence, 27.9% were in moderate dependence, 8.1% had a mild dependence, and 49.8% were totally independent. In the multiple linear regression model of the ADL score, we determined that educational level, comorbid Down's syndrome, and disability level are the variables able to significantly predict ADL score (R(2)=0.190) after controlling for the factors of age, marital status, and other comorbidity conditions. Those ID adults with a lower education level (primary vs. literate, β=4.780, p=0.031; intermediate vs. literate, β=6.642, p=0.030), with comorbid Down's syndrome (β=-7.135, p=0.063), and with a more severe disability condition (severe vs. mild, β=-7.650, p=0.007; profound vs. mild, β=-19.169, p<0.001) had significantly lower ADL scores. The present study highlights the need to support mobility in older adults with ID as much as possible to optimize independence in this group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Insomnia Disorder and Brain's Default-Mode Network.

PubMed

Marques, Daniel Ruivo; Gomes, Ana Allen; Caetano, Gina; Castelo-Branco, Miguel

2018-06-09

Insomnia disorder (ID) is a prevalent sleep disorder that significantly compromises the physical and mental health of individuals. This article reviews novel approaches in the study of brain networks and impaired function in ID through the application of modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI). The default-mode network (DMN) is presumed to be correlated with self-referential information processing, and it appears to be altered or unbalanced in insomnia. A growing body of evidence suggests the lack of deactivation of brain regions comprising the DMN when insomnia patients are at rest. Moreover, core areas of the DMN demonstrate greater activation in insomnia patients when compared to healthy controls in self-referential related tasks. Despite the few studies on the topic, underpinning the correlation between abnormal DMN activity and ID deserves further attention in the future. Implications for therapeutics are briefly outlined.

Defense system shortcuts and limits of scope.

PubMed

Rewald, E; Francischetti, M M

2000-10-01

Defense, as a key factor of life, shares the biological tendencies of simplicity and energy saving. We propose that, like the mind, defense tends to rely on shortcuts via immune memes. Also, response repetition may induce the formation of virtual 'modules' [toolkits] to simplify and perfect performance. Engaged modules may expand by proliferating or by capturing immune components from the 'dormant' and even perhaps from active ones. With regard to recovery and/or survival, complexity of the integrated defense system (IDS) (1) requires to be inside of what we call the 'functional window'. In contrast to the physiological and common disease repair, energy is squandered when IDS perceives real danger. Our concern is the uncertain transition to conditions that do not fit into the IDS routine and, even worse, that are outside the functional window where the system is lacking. Copyright 2000 Harcourt Publishers Ltd.

Social Skills Training for Adolescents With Intellectual Disabilities: A School-Based Evaluation.

PubMed

O'Handley, Roderick D; Ford, W Blake; Radley, Keith C; Helbig, Kate A; Wimberly, Joy K

2016-07-01

Individuals with intellectual disabilities (ID) often demonstrate impairments in social functioning, with deficits becoming more apparent during adolescence. This study evaluated the effects of the Superheroes Social Skills program, a program that combines behavioral skills training and video modeling to teach target social skills, on accurate demonstration of three target social skills in adolescents with ID. Skills taught in the present study include Expressing Wants and Needs, Conversation, and Turn Taking. Four adolescents with ID participated in a 3-week social skills intervention, with the intervention occurring twice per week. A multiple baseline across skills design was used to determine the effect of the intervention on social skill accuracy in both a training and generalization setting. All participants demonstrated substantial improvements in skill accuracy in both settings, with teacher ratings of social functioning further suggesting generalization of social skills to nontraining settings. © The Author(s) 2016.

Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma.

PubMed

Cook, Peter J; Thomas, Rozario; Kingsley, Philip J; Shimizu, Fumiko; Montrose, David C; Marnett, Lawrence J; Tabar, Viviane S; Dannenberg, Andrew J; Benezra, Robert

2016-10-01

In glioblastoma (GBM), Id1 serves as a functional marker for self-renewing cancer stem-like cells. We investigated the mechanism by which cyclooxygenase-2 (Cox-2)-derived prostaglandin E2 (PGE2) induces Id1 and increases GBM self-renewal and radiation resistance. Mouse and human GBM cells were stimulated with dimethyl-PGE2 (dmPGE2), a stabilized form of PGE2, to test for Id1 induction. To elucidate the signal transduction pathway governing the increase in Id1, a combination of short interfering RNA knockdown and small molecule inhibitors and activators of PGE2 signaling were used. Western blotting, quantitative real-time (qRT)-PCR, and chromatin immunoprecipitation assays were employed. Sphere formation and radiation resistance were measured in cultured primary cells. Immunohistochemical analyses were carried out to evaluate the Cox-2-Id1 axis in experimental GBM. In GBM cells, dmPGE2 stimulates the EP4 receptor leading to activation of ERK1/2 MAPK. This leads, in turn, to upregulation of the early growth response1 (Egr1) transcription factor and enhanced Id1 expression. Activation of this pathway increases self-renewal capacity and resistance to radiation-induced DNA damage, which are dependent on Id1. In GBM, Cox-2-derived PGE2 induces Id1 via EP4-dependent activation of MAPK signaling and the Egr1 transcription factor. PGE2-mediated induction of Id1 is required for optimal tumor cell self-renewal and radiation resistance. Collectively, these findings identify Id1 as a key mediator of PGE2-dependent modulation of radiation response and lend insight into the mechanisms underlying radiation resistance in GBM patients. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A 3D Faraday Shield for Interdigitated Dielectrometry Sensors and Its Effect on Capacitance

PubMed Central

Risos, Alex; Long, Nicholas; Hunze, Arvid; Gouws, Gideon

2016-01-01

Interdigitated dielectrometry sensors (IDS) are capacitive sensors investigated to precisely measure the relative permittivity (ϵr) of insulating liquids. Such liquids used in the power industry exhibit a change in ϵr as they degrade. The IDS ability to measure ϵr in-situ can potentially reduce maintenance, increase grid stability and improve safety. Noise from external electric field sources is a prominent issue with IDS. This paper investigates the novelty of applying a Faraday cage onto an IDS as a 3D shield to reduce this noise. This alters the spatially distributed electric field of an IDS affecting its sensing properties. Therefore, dependency of the sensor’s signal with the distance to a shield above the IDS electrodes has been investigated experimentally and theoretically via a Green’s function calculation and FEM. A criteria of the shield’s distance s = s0 has been defined as the distance which gives a capacitance for the IDS equal to 1 − e−2=86.5% of its unshielded value. Theoretical calculations using a simplified geometry gave a constant value for s0/λ = 1.65, where λ is the IDS wavelength. In the experiment, values for s0 were found to be lower than predicted as from theory and the ratio s0/λ variable. This was analyzed in detail and it was found to be resulting from the specific spatial structure of the IDS. A subsequent measurement of a common insulating liquid with a nearby noise source demonstrates a considerable reduction in the standard deviation of the relative permittivity from σunshielded=±9.5% to σshielded=±0.6%. The presented findings enhance our understanding of IDS in respect to the influence of a Faraday shield on the capacitance, parasitic capacitances of the IDS and external noise impact on the measurement of ϵr. PMID:28042868

A 3D Faraday Shield for Interdigitated Dielectrometry Sensors and Its Effect on Capacitance.

PubMed

Risos, Alex; Long, Nicholas; Hunze, Arvid; Gouws, Gideon

2016-12-31

Interdigitated dielectrometry sensors (IDS) are capacitive sensors investigated to precisely measure the relative permittivity ( ϵ r ) of insulating liquids. Such liquids used in the power industry exhibit a change in ϵ r as they degrade. The IDS ability to measure ϵ r in-situ can potentially reduce maintenance, increase grid stability and improve safety. Noise from external electric field sources is a prominent issue with IDS. This paper investigates the novelty of applying a Faraday cage onto an IDS as a 3D shield to reduce this noise. This alters the spatially distributed electric field of an IDS affecting its sensing properties. Therefore, dependency of the sensor's signal with the distance to a shield above the IDS electrodes has been investigated experimentally and theoretically via a Green's function calculation and FEM. A criteria of the shield's distance s = s 0 has been defined as the distance which gives a capacitance for the IDS equal to 1 - e - 2 = 86.5 % of its unshielded value. Theoretical calculations using a simplified geometry gave a constant value for s 0 / λ = 1.65, where λ is the IDS wavelength. In the experiment, values for s 0 were found to be lower than predicted as from theory and the ratio s 0 / λ variable. This was analyzed in detail and it was found to be resulting from the specific spatial structure of the IDS. A subsequent measurement of a common insulating liquid with a nearby noise source demonstrates a considerable reduction in the standard deviation of the relative permittivity from σ unshielded = ± 9.5% to σ shielded = ± 0.6%. The presented findings enhance our understanding of IDS in respect to the influence of a Faraday shield on the capacitance, parasitic capacitances of the IDS and external noise impact on the measurement of ϵ r .

Alterations in CDH15 and KIRREL3 in Patients with Mild to Severe Intellectual Disability

PubMed Central

Bhalla, Kavita; Luo, Yue; Buchan, Tim; Beachem, Michael A.; Guzauskas, Gregory F.; Ladd, Sydney; Bratcher, Shelly J.; Schroer, Richard J.; Balsamo, Janne; DuPont, Barbara R.; Lilien, Jack; Srivastava, Anand K.

2008-01-01

Cell-adhesion molecules play critical roles in brain development, as well as maintaining synaptic structure, function, and plasticity. Here we have found the disruption of two genes encoding putative cell-adhesion molecules, CDH15 (cadherin superfamily) and KIRREL3 (immunoglobulin superfamily), by a chromosomal translocation t(11;16) in a female patient with intellectual disability (ID). We screened coding regions of these two genes in a cohort of patients with ID and controls and identified four nonsynonymous CDH15 variants and three nonsynonymous KIRREL3 variants that appear rare and unique to ID. These variations altered highly conserved residues and were absent in more than 600 unrelated patients with ID and 800 control individuals. Furthermore, in vivo expression studies showed that three of the CDH15 variations adversely altered its ability to mediate cell-cell adhesion. We also show that in neuronal cells, human KIRREL3 colocalizes and interacts with the synaptic scaffolding protein, CASK, recently implicated in X-linked brain malformation and ID. Taken together, our data suggest that alterations in CDH15 and KIRREL3, either alone or in combination with other factors, could play a role in phenotypic expression of ID in some patients. PMID:19012874

Improvement in Self-reported Quality of Life with Cognitive Therapy for Recurrent Major Depressive Disorder

PubMed Central

Jha, Manish Kumar; Minhajuddin, Abu; Thase, Michael E.; Jarrett, Robin B.

2014-01-01

Background Major Depressive Disorder is common, often recurrent and/or chronic. Theoretically, assessing quality of life (QoL) in addition to the current practice of assessing depressive symptoms has the potential to offer a more comprehensive evaluation of the effects of treatment interventions and course of illness. Methods Before and after acute-phase cognitive therapy (CT), 492 patients from Continuation Phase Cognitive Therapy Relapse Prevention trial (Jarrett et al., 2013, Jarrett and Thase, 2010) completed the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Inventory of Depressive Symptomatology Self-report (IDS-SR) & Beck Depression Inventory (BDI); clinicians completed Hamilton Rating Scale for Depression-17-items. Repeated measures analysis of variance evaluated the improvement in QoL before/after CT and measured the effect sizes. Change analyses to assess clinical significance (Hageman and Arrindell, 1999) were conducted. Results At the end of acute-phase CT, a repeated measure analysis of variance produced a statistically significant increase in Q-LES-Q scores with effect sizes of 0.48 - 1.3; 76.9 - 91.4% patients reported clinically significant improvement. Yet, only 11 - 38.2% QoL scores normalized. An analysis of covariance showed that change in depression severity (covariates=IDS-SR, BDI) completely accounted for the improvement in Q-LES-Q scores. Limitations There were only two time points of observation; clinically significant change analyses lacked matched normal controls; and generalizability is constrained by sampling characteristics. Conclusions: Quality of life improves significantly in patients with recurrent MDD after CT; however, this improvement is completely accounted for by change in depression severity. Normalization of QoL in all patients may require targeted, additional, and/or longer treatment. PMID:25082112

Improvement in self-reported quality of life with cognitive therapy for recurrent major depressive disorder.

PubMed

Jha, Manish Kumar; Minhajuddin, Abu; Thase, Michael E; Jarrett, Robin B

2014-01-01

Major depressive disorder (MDD) is common, often recurrent and/or chronic. Theoretically, assessing quality of life (QoL) in addition to the current practice of assessing depressive symptoms has the potential to offer a more comprehensive evaluation of the effects of treatment interventions and course of illness. Before and after acute-phase cognitive therapy (CT), 492 patients from Continuation Phase Cognitive Therapy Relapse Prevention trial (Jarrett et al., 2013; Jarrett and Thase, 2010) completed the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Inventory of Depressive Symptomatology Self-report (IDS-SR) and Beck Depression Inventory (BDI); clinicians completed Hamilton Rating Scale for Depression-17-items. Repeated measures analysis of variance evaluated the improvement in QoL before/after CT and measured the effect sizes. Change analyses to assess clinical significance (Hageman and Arrindell, 1999) were conducted. At the end of acute-phase CT, a repeated measure analysis of variance produced a statistically significant increase in Q-LES-Q scores with effect sizes of 0.48-1.3%; 76.9-91.4% patients reported clinically significant improvement. Yet, only 11-38.2% QoL scores normalized. An analysis of covariance showed that change in depression severity (covariates=IDS-SR, BDI) completely accounted for the improvement in Q-LES-Q scores. There were only two time points of observation; clinically significant change analyses lacked matched normal controls; and generalizability is constrained by sampling characteristics. Quality of life improves significantly in patients with recurrent MDD after CT; however, this improvement is completely accounted for by change in depression severity. Normalization of QoL in all patients may require targeted, additional, and/or longer treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Visual Local and Global Processing in Low-Functioning Deaf Individuals with and without Autism Spectrum Disorder

ERIC Educational Resources Information Center

Maljaars, J. P. W.; Noens, I. L. J.; Scholte, E. M.; Verpoorten, R. A. W.; van Berckelaer-Onnes, I. A.

2011-01-01

Background: The ComFor study has indicated that individuals with intellectual disability (ID) and autism spectrum disorder (ASD) show enhanced visual local processing compared with individuals with ID only. Items of the ComFor with meaningless materials provided the best discrimination between the two samples. These results can be explained by the…

Iron Deficiency Is a Determinant of Functional Capacity and Health-related Quality of Life 30 Days After an Acute Coronary Syndrome.

PubMed

Meroño, Oona; Cladellas, Mercè; Ribas-Barquet, Núria; Poveda, Paula; Recasens, Lluis; Bazán, Víctor; García-García, Cosme; Ivern, Consol; Enjuanes, Cristina; Orient, Salvador; Vila, Joan; Comín-Colet, Josep

2017-05-01

Iron deficiency (ID) is a prevalent condition in patients with ischemic heart disease and heart failure. Little is known about the impact of ID on exercise capacity and quality of life (QoL) in the recovery phase after an acute coronary syndrome (ACS). Iron status and its impact on exercise capacity and QoL were prospectively evaluated in 244 patients 30 days after the ACS. QoL was assessed by the standard EuroQoL-5 dimensions, EuroQoL visual analogue scale, and Heart-QoL questionnaires. Exercise capacity was analyzed by treadmill/6-minute walk tests. The effect of ID on cardiovascular mortality and readmission rate was also investigated. A total of 46% of the patients had ID. These patients had lower exercise times (366±162 vs 462±155seconds; P<.001), metabolic consumption rates (7.9±2.9 vs 9.3±2.6 METS; P=.003), and EuroQoL-5 dimensions (0.76±0.25 vs 0.84±0.16), visual analogue scale (66±16 vs 72±17), and Heart-QoL (1.9±0.6 vs 2.2±0.6) scores (P<.05). ID independently predicted lower exercise times (OR, 2.9; 95%CI, 1.1-7.6; P=.023) and worse QoL (OR, 1.9; 95%CI, 1.1-3.3; P<.001) but had no effect on cardiovascular morbidity or mortality. ID, a prevalent condition in ACS patients, results in a poorer mid-term functional recovery, as measured by exercise capacity and QoL. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy.

PubMed

Trembley, Michael A; Quijada, Pearl; Agullo-Pascual, Esperanza; Tylock, Kevin M; Colpan, Mert; Dirkx, Ronald A; Myers, Jason R; Mickelsen, Deanne M; de Mesy Bentley, Karen; Rothenberg, Eli; Moravec, Christine S; Alexis, Jeffrey D; Gregorio, Carol C; Dirksen, Robert T; Delmar, Mario; Small, Eric M

2018-05-01

Background -Hypertrophic cardiomyocyte (CM) growth and dysfunction accompanies various forms of heart disease. The mechanisms responsible for transcriptional changes that impact cardiac physiology and the transition to heart failure (HF) are not well understood. The intercalated disc (ID) is a specialized intercellular junction coupling CM electrical activity and force transmission, and is gaining attention as a mechanosensitive signaling hub and hotspot for causative mutations in cardiomyopathy. Methods -Transmission electron microscopy, confocal microscopy, and single-molecule localization microscopy (SMLM) were used to examine changes in ID structure and protein localization in the murine and human heart. We conducted detailed cardiac functional assessment and transcriptional profiling of mice lacking myocardin-related transcription factor-A (MRTF-A) and -B specifically in adult CMs to evaluate the role of mechanosensitive regulation of gene expression in load-induced ventricular remodeling. Results -We found that MRTFs localize to IDs in the healthy human heart and accumulate in the nucleus in heart failure (HF). Although mice lacking MRTFs in adult CMs display normal cardiac physiology at baseline, pressure overload leads to rapid HF characterized by sarcomere disarray, ID disintegration, chamber dilation and wall thinning, cardiac functional decline, and partially penetrant acute lethality. Transcriptional profiling reveals a program of actin cytoskeleton and CM adhesion genes driven by MRTFs during pressure overload. Indeed, conspicuous remodeling of gap junctions at IDs identified by SMLM may partially stem from a reduction in Mapre1 expression, which we show is a direct mechanosensitive MRTF target. Conclusions -Taken together, our study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates crosstalk between the actin and microtubule cytoskeleton and maintains ID integrity and CM homeostasis in heart disease.

Id2 Complexes with the SNAG Domain of Snai1 Inhibiting Snai1-Mediated Repression of Integrin β4

PubMed Central

Chang, Cheng; Yang, Xiaofang; Pursell, Bryan

2013-01-01

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as α6β4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits β4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress β4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the β4 promoter and constrains the repressive function of Snai1. Disruption of the complex by depleting Id2 resulted in Snai1-mediated β4 repression with a concomitant increase in H3K27Me3 modification on the β4 promoter. These findings establish a novel function for Id2 in regulating Snai1 that has significant implications for the regulation of epithelial gene expression. PMID:23878399

Effects of the natural flavonoid delphinidin on diabetic microangiopathy.

PubMed

Bertuglia, S; Malandrino, S; Colantuoni, A

1995-04-01

The purpose of the present study was to investigate the effects of the flavonoid delphinidin chloride (CAS 528-53-0, IdB 1056) on diabetic microangiopathy. Hamsters were injected with alloxan and cheek pouch microcirculation was observed by a fluorescent microscopy technique 90 days from alloxan. The increase in permeability, the number of adhering leukocytes to venular vessel wall and vasodilatory responses to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured. In diabetic group microvascular permeability and the number of sticking leukocytes to the venular endothelium were increased. Vasoconstriction by Ach was observed while the vasodilation by SNP was significantly attenuated in diabetic animals. These results are consistent for a decreased relaxation and suggest also an impairment in the smooth muscle cell function in diabetic arterioles. IdB 1056 exhibited an inhibitory effect on increased microvascular permeability and on leukocytes adhering to the venular vessels. Indeed, the treatment with IdB 1056 in diabetic hamsters pretreated or not with indometacin, a cyclooxygenase inhibitor, restored the relaxant responses to Ach and SNP. In conclusion, the effects of IdB 1056 observed in vivo at the microcirculatory level prevent the injury to endothelial cell function associated with diabetes and/or oxidative stress.

Inductive learning of thyroid functional states using the ID3 algorithm. The effect of poor examples on the learning result.

PubMed

Forsström, J

1992-01-01

The ID3 algorithm for inductive learning was tested using preclassified material for patients suspected to have a thyroid illness. Classification followed a rule-based expert system for the diagnosis of thyroid function. Thus, the knowledge to be learned was limited to the rules existing in the knowledge base of that expert system. The learning capability of the ID3 algorithm was tested with an unselected learning material (with some inherent missing data) and with a selected learning material (no missing data). The selected learning material was a subgroup which formed a part of the unselected learning material. When the number of learning cases was increased, the accuracy of the program improved. When the learning material was large enough, an increase in the learning material did not improve the results further. A better learning result was achieved with the selected learning material not including missing data as compared to unselected learning material. With this material we demonstrate a weakness in the ID3 algorithm: it can not find available information from good example cases if we add poor examples to the data.

DD angiotensin-converting enzyme gene polymorphism is associated with endothelial dysfunction in normal humans.

PubMed

Butler, R; Morris, A D; Burchell, B; Struthers, A D

1999-05-01

A polymorphism within the angiotensin-converting enzyme (ACE) gene may increase the risk of myocardial infarction in individuals previously thought to be at low cardiovascular risk. The mechanism through which it exerts this effect is unknown but may be due to increased angiotensin II-induced nitric oxide (NO) breakdown and/or reduced bradykinin-mediated NO release. We investigated whether endothelial function was different between different ACE genotypes. We performed a cross-sectional study comparing the endothelial function of the 3 genotypes (II: n=25; ID: n=31; DD: n=12). Mean+/-SD ages of the subjects were 24+/-4 (II), 25+/-6 (ID), and 25+/-6 (DD) years. We assessed the impact of the genotypes on endothelial function and found that the DD genotype was associated with a significant blunting in endothelial-dependent vasodilatation (forearm blood flow data are presented as mean+/-SD ratio of blood flow in response to 3 incrementally increasing doses of each vasoactive agent in the test arm to blood flow in the control arm; the comparison is between DD versus ID versus II; the P value is an expression of an overall difference by ANOVA, and the 95% CIs are of a pairwise comparison between genotypes): acetylcholine, 2.88+/-1.45 versus 3.81+/-1.93 versus 4.23+/-2.37 (P=0.002; 95% CI [II versus ID], -0.19 to 0.91; 95% CI [II versus DD], 0.36 to 1.80; 95% CI [ID versus DD], 0.02 to 1.42). There was also a significant difference with the endothelial-independent vasodilator sodium nitroprusside, with values of 2.11+/-1.00 versus 2.55+/-1.36 versus 2.75+/-1.18 (P<0.05; 95% CI [II versus ID], -0.15 to 0.51; 95% CI [II versus DD], 0.03 to 0.89; 95% CI [ID versus DD], -0.13 to 0.71), but not with verapamil. There was no effect of the ACE genotype on endothelial-dependent or -independent vasoconstrictors NG-monomethyl-L-arginine or norepinephrine. Investigating the effects of cigarette smoking on each genotype demonstrated that for II and DD genotypes, acetylcholine responses were further blunted if subjects smoked. These data demonstrate that the DD ACE genotype in a young population is associated with a blunting of stimulated endothelial NO and donated NO responses but not to non-NO vasodilators or vasoconstrictors.

A versus F: the effects of implicit letter priming on cognitive performance.

PubMed

Ciani, Keith D; Sheldon, Kennon M

2010-03-01

It has been proposed that motivational responses outside people's conscious awareness can be primed to affect academic performance. The current research focused on the relationship between primed evaluative letters (A and F), explicit and implicit achievement motivation, and cognitive performance. Given the evaluative connotation associated with letter grades, we wanted to know if exposure to the letter A before a task could improve performance, and exposure to the letter F could impair performance. If such effects are found, we suspected that they may be rooted in implicit approach versus avoidance motivation, and occur without participants' awareness. The current research was conducted at a large research university in the USA. Twenty-three undergraduates participated in Expt 1, 32 graduate students in Expt 2, and 76 undergraduates in Expt 3. Expts 1 and 2 were conducted in classroom settings, and Expt 3 in a laboratory. In Expt 1, participants were randomly assigned to either the A or F condition. The letter manipulation came in the form of an ostensible Test Bank ID code on the cover of an analogy test, which participants were prompted to view and write on each page of their test. Expt 2 followed a similar procedure but included the neutral letter J as a third condition to serve as a control. In Expt 3, participants' letter condition was presented in the form of an ostensible Subject ID code prior to an anagram test. Expts 1-3 demonstrated that exposure to the letter A enhances performance relative to the exposure to the letter F, whereas exposure to the letter F prior to an achievement task can impair performance. This effect was demonstrated using two different types of samples (undergraduate and graduate students), in two different experimental settings (classroom and laboratory), using two different types of achievement tasks (analogy and anagram), and using two different types of letter presentation (Test Bank ID and Subject ID). Results from the funnelled debriefing, self-report goals, and word-stem completion support our position that the effect of letter on academic performance takes place outside the conscious awareness of participants. Our findings suggest that students are vulnerable to evaluative letters presented before a task, and support years of research highlighting the significant role that nonconscious processes play in achievement settings.

Can integrating the Memory Support Intervention into cognitive therapy improve depression outcome? Study protocol for a randomized controlled trial.

PubMed

Harvey, Allison G; Dong, Lu; Lee, Jason Y; Gumport, Nicole B; Hollon, Steven D; Rabe-Hesketh, Sophia; Hein, Kerrie; Haman, Kirsten; McNamara, Mary E; Weaver, Claire; Martinez, Armando; Notsu, Haruka; Zieve, Garret; Armstrong, Courtney C

2017-11-14

The Memory Support Intervention was developed in response to evidence showing that: (1) patient memory for treatment is poor, (2) poor memory for treatment is associated with poorer adherence and poorer outcome, (3) the impact of memory impairment can be minimized by the use of memory support strategies and (4) improved memory for treatment improves outcome. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether the Memory Support Intervention improves illness course and functional outcomes. As a "platform" for the next step in investigating this approach, we focus on major depressive disorder (MDD) and cognitive therapy (CT). Adults with MDD (n = 178, including 20% for potential attrition) will be randomly allocated to CT + Memory Support or CT-as-usual and will be assessed at baseline, post treatment and at 6 and 12 months' follow-up (6FU and 12FU). We will compare the effects of CT + Memory Support vs. CT-as-usual to determine if the new intervention improves the course of illness and reduces functional impairment (aim 1). We will determine if patient memory for treatment mediates the relationship between treatment condition and outcome (aim 2). We will evaluate if previously reported poor treatment response subgroups moderate target engagement (aim 3). The Memory Support Intervention has been developed to be "transdiagnostic" (relevant to a broad range of mental disorders) and "pantreatment" (relevant to a broad range of types of treatment). This study protocol describes a "next step" in the treatment development process by testing the Memory Support Intervention for major depressive disorder (MDD) and cognitive therapy (CT). If the results are promising, future directions will test the applicability to other kinds of interventions and disorders and in other settings. ClinicalTrials.gov, ID: NCT01790919 . Registered on 6 October 2016.

Enhanced ID Pit Sizing Using Multivariate Regression Algorithm

NASA Astrophysics Data System (ADS)

Krzywosz, Kenji

2007-03-01

EPRI is funding a program to enhance and improve the reliability of inside diameter (ID) pit sizing for balance-of plant heat exchangers, such as condensers and component cooling water heat exchangers. More traditional approaches to ID pit sizing involve the use of frequency-specific amplitude or phase angles. The enhanced multivariate regression algorithm for ID pit depth sizing incorporates three simultaneous input parameters of frequency, amplitude, and phase angle. A set of calibration data sets consisting of machined pits of various rounded and elongated shapes and depths was acquired in the frequency range of 100 kHz to 1 MHz for stainless steel tubing having nominal wall thickness of 0.028 inch. To add noise to the acquired data set, each test sample was rotated and test data acquired at 3, 6, 9, and 12 o'clock positions. The ID pit depths were estimated using a second order and fourth order regression functions by relying on normalized amplitude and phase angle information from multiple frequencies. Due to unique damage morphology associated with the microbiologically-influenced ID pits, it was necessary to modify the elongated calibration standard-based algorithms by relying on the algorithm developed solely from the destructive sectioning results. This paper presents the use of transformed multivariate regression algorithm to estimate ID pit depths and compare the results with the traditional univariate phase angle analysis. Both estimates were then compared with the destructive sectioning results.

Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection.

PubMed

Pettis, Ronald J; Ginsberg, Barry; Hirsch, Laurence; Sutter, Diane; Keith, Steven; McVey, Elaine; Harvey, Noel G; Hompesch, Marcus; Nosek, Leszek; Kapitza, Christoph; Heinemann, Lutz

2011-04-01

This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) injection under euglycemic glucose clamp conditions. Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 microneedle lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1-3 followed by a repetitive ID 1.5-mm microneedle dose (Day 4) and an SC dose (Day 5). Microneedle ID delivery resulted in more rapid absorption of IL, with decreased time to maximum insulin concentration (ID vs. SC: 36.0-46.4 vs. 64.3 min, P < 0.05) and higher fractional availability at early postinjection times. ID produced more rapid effects on glucose uptake with shorter times to maximal and early half-maximal glucose infusion rates (GIRs) (ID vs. SC: time to maximum GIR, 106-112 vs. 130 min, P < 0.05; early half-maximal GIR, 29-35 vs. 42 min), increased early GIR area under the curve (AUC), and faster offset of insulin action (shorter time to late half-maximal GIR: 271-287 vs. 309 min). Relative total insulin bioavailability (AUC to 360 min and AUC to infinite measurement) did not significantly differ between administration routes. ID PK/PD parameters showed some variation as a function of needle length. Delivery of ID IL was generally well tolerated, although transient, localized wheal formation and redness were observed at injection sites. Microneedle ID insulin lispro delivery enables more rapid onset and offset of metabolic effect than SC therapy and is safe and well tolerated; further study for insulin therapy is warranted.

Evaluation of Intradermal and Subcutaneous Infusion Set Performance Under 24-Hour Basal and Bolus Conditions

PubMed Central

McVey, Elaine; Keith, Steven; Herr, Joshua K.; Sutter, Diane; Pettis, Ronald J.

2015-01-01

Background: This study sought to assess the function and delivery reliability of intradermal (ID) infusion sets used with commercial insulin pumps. Method: Healthy subjects (n = 43) were randomized to either ID or subcutaneous (SC) arms, and received basal/bolus placebo delivery for 24 hours. Subjects received 4 of 8 infusion set combinations (ID: microneedle design A or B, with 2 pump brands [Animas or MiniMed]; SC: Teflon Quickset or steel Rapid-D, Animas pump only, with or without overtaping) and were evaluated for pump occlusion alarms, fluid leakage, pain, and tissue tolerability. A novel algorithm was developed to determine flow consistency based on fluid pressure, and the duration and occurrence rate for periods of unalarmed but interrupted flow (“silent occlusions’”) were compared. Results: ID delivery was successfully maintained over the 24-hour infusion period. The number of silent occlusions was lower for ID microneedle cannula design B than A (P < .01) and lower for Rapid-D SC device compared to Quick-set (P = .03). There was no significant difference in the number of occlusion alarms between the ID and SC devices with the Animas pump. However, the pumps tested with ID devices had significantly different alarm rates (MiniMed 29.5%, Animas 0%, P < .001). Leakage and tissue tolerability were comparable across devices. Conclusion: The ID infusion set reliably delivered diluent for an extended 24-hour period in healthy subjects and was well tolerated. Silent occlusion flow interruptions could be detected in both ID and SC infusion sets using a proprietary algorithm. This algorithm is a promising method for quantitatively evaluating infusion set flow performance. PMID:26319228

Design of Distortion-Invariant Optical ID Tags for Remote Identification and Verification of Objects

NASA Astrophysics Data System (ADS)

Pérez-Cabré, Elisabet; Millán, María Sagrario; Javidi, Bahram

Optical identification (ID) tags [1] have a promising future in a number of applications such as the surveillance of vehicles in transportation, control of restricted areas for homeland security, item tracking on conveyor belts or other industrial environment, etc. More specifically, passive optical ID tag [1] was introduced as an optical code containing a signature (that is, a characteristic image or other relevant information of the object), which permits its real-time remote detection and identification. Since their introduction in the literature [1], some contributions have been proposed to increase their usefulness and robustness. To increase security and avoid counterfeiting, the signature was introduced in the optical code as an encrypted function [2-5] following the double-phase encryption technique [6]. Moreover, the design of the optical ID tag was done in such a way that tolerance to variations in scale and rotation was achieved [2-5]. To do that, the encrypted information was multiplexed and distributed in the optical code following an appropriate topology. Further studies were carried out to analyze the influence of different sources of noise. In some proposals [5, 7], the designed ID tag consists of two optical codes where the complex-valued encrypted signature was separately introduced in two real-valued functions according to its magnitude and phase distributions. This solution was introduced to overcome some difficulties in the readout of complex values in outdoors environments. Recently, the fully phase encryption technique [8] has been proposed to increase noise robustness of the authentication system.

Institutional care and iron deficiency increase ADHD symptomology and lower IQ 2.5-5 years post-adoption.

PubMed

Doom, Jenalee R; Georgieff, Michael K; Gunnar, Megan R

2015-05-01

Increased ADHD symptomology and lower IQ have been reported in internationally adopted (IA) children compared to non-adopted peers (Hostinar, Stellern, Schaefer, Carlson & Gunnar, 2012; Kreppner, O'Connor & Rutter, 2001). However, it is unclear whether these outcomes are due to institutional deprivation specifically or to co-occurring micronutrient deficiencies that disrupt brain development (Fuglestad, Rao & Georgieff, 2008b). In this study, IA children were compared to children raised in their biological families to examine differences in ADHD symptomology and IQ 2.5-5 years post-adoption and to assess the contributions of iron deficiency (ID) and duration of deprivation to these cognitive outcomes. ADHD symptoms (parent- and experimenter-reported) and IQ were evaluated in 88 IA (M = 62.1 months, SD = 2.4) and 35 non-adopted children (M = 61.4 months, SD = 1.6). IA children were assessed 29-64 months post-adoption (M = 41.9 months, SD = 10.2). ID was assessed during the initial post-adoption medical visit in 69 children, and children were classified into four groups by iron status, ranging from normal to ID anemia (most severe). IA children had greater ADHD symptomology, p < .01, and lower IQ, p = .001, than non-adopted children. Within the IA group, children with more severe ID at adoption had greater ADHD symptomology, r(69) = 0.40, p = .001, and lower IQ, r(68) = -0.28, p < .05. Duration of institutional care was positively correlated with ADHD symptoms, r(86) = .28, p < .01, but not IQ, r(85) = -.08, p = .52. Longitudinal results indicate improvement in IQ from 12 months post-adoption to age 5 for children with greater ID severity at adoption and longer duration of institutional care but no improvement in ADHD symptoms. These results signify continuing effects of early deprivation and ID on ADHD symptoms and IQ years after adoption. A video abstract of this article can be viewed at http://www.youtube.com/watch?v=vUFDAS3DD1c. © 2014 John Wiley & Sons Ltd.

Modernization of Defense Logistics Standard Systems. Establishing the Functional Baseline. Volume 2. Appendix H

DTIC Science & Technology

1991-09-01

and "DD" is the numeric value of the day (01-31). [61 Time ( TM ). The time type is symbolized by the representation " TM ." Format for this type is...VERSION ID M DT 06/06 M TM 04/04 M ID 01/01 M ID 05/05 ISA13 112 ISA14 113 ISA15 114 ISA16 115INTERCHANGE *ACKNOWLEDG. * S1TEST 14 * SUBELEMENT N CTRL...Max - 6 Date of the interchange. DLMS Usage: As above. 109 Interchange Time Type - TM Min - 4 Max - 4 Time of the interchange. DLMS Usage: As above

Evaluation of a group intervention for convicted arsonists with mild and borderline intellectual disabilities.

PubMed

Taylor, John L; Thorne, Ian; Robertson, Alison; Avery, Ginny

2002-01-01

The extent to which people with intellectual disabilities (ID) set fires is difficult to ascertain. However, services working with people with ID and offending or quasi-offending histories are increasing the amount of attention that they give to this difficult and perplexing issue. This is due to the real and perceived threat that it presents to society and the seriousness with which it viewed by the criminal justice system. Against this background there is very little available in the research literature concerning treatment interventions for fire-setting behaviour in this client group, and even less regarding their effectiveness. In the current study 14 men and women with mild and borderline ID, convictions for arson and detained in a hospital low secure service were offered and completed a broadly cognitive behavioural, approximately 40-session group-based intervention. The treatment was aimed primarily at reducing fire interest and attitudes associated with fire-setting behaviour. Participants were assessed pre- and post-treatment on a number of fire-specific, anger, self-esteem and depression measures. Following treatment, significant improvements were found in all areas assessed, excepting depression. Despite the limitations of the study design, the results provide encouragement and some guidance to practitioners who are required to develop interventions for this challenging, yet much neglected client group.

The impact of social cognitive and personality factors on teachers' reported inclusive behaviour.

PubMed

Wilson, Claire; Woolfson, Lisa Marks; Durkin, Kevin; Elliott, Mark A

2016-09-01

Inclusive education of children with intellectual disabilities (ID) is intended to maximize their educational experience within the mainstream school setting. While policy mandates inclusion, it is classroom teachers' behaviours that determine its success. This study provided a novel application of the theory of planned behaviour (TPB) in this setting. It examined the effect of TPB variables and personality on reported inclusive teaching behaviours for learners with ID. The sample comprised 145 primary school teachers (85% female) from mainstream schools across Scotland. Participants completed a TPB questionnaire assessing attitudes (instrumental and affective), subjective norms (injunctive and descriptive norms), perceptions of control (self-efficacy and controllability), and behavioural intentions towards using inclusive strategies. The Big Five Personality Index, measuring extraversion, conscientiousness, openness, neuroticism, and agreeableness, was also completed. Teaching practices were reported 2 weeks later. Instrumental attitudes, descriptive norm, self-efficacy, and neuroticism predicted teachers' intentions to use inclusive strategies. Further, conscientiousness had indirect effects on intentions through TPB variables. These intentions, however, did not predict reported behaviour expected by TPB. Instead, self-efficacy was the only significant predictor of reported behaviour. This study demonstrates the application of TPB to an educational setting and contributes to the understanding of teachers' reported use of inclusive strategies for children with ID. © 2016 The British Psychological Society.

Adaptation and Validation of the Tower of London Test of Planning and Problem Solving in People with Intellectual Disabilities

ERIC Educational Resources Information Center

Masson, J. D.; Dagnan, D.; Evans, J.

2010-01-01

Background: There is a need for validated, standardised tools for the assessment of executive functions in adults with intellectual disabilities (ID). This study examines the validity of a test of planning and problem solving (Tower of London) with adults with ID. Method: Participants completed an adapted version of the Tower of London (ToL) while…

Mediation between Staff and Elderly Persons with Intellectual Disability with Alzheimer Disease as a Means of Enhancing Their Daily Functioning

ERIC Educational Resources Information Center

Lifshitz, Hefziba; Klein, Pnina S.

2011-01-01

This study presents a new way of mediation between staff and elderly persons with intellectual disability (ID) and Alzheimer type dementia (AD), i.e., the MISC (Mediational Intervention for Sensitizing Caregivers (Klein, 1988, 2003) model. The MISC was adopted for interactions between staff and adults with ID and AD based on observations of…

Population-based cross-sectional study on insulin resistance and insulin-secretory capacity in Japanese school children.

PubMed

Nishimura, Rimei; Sano, Hironari; Onda, Yoshiko; Tsujino, Daisuke; Ando, Kiyotaka; Ebara, Futoshi; Matsudaira, Toru; Ishikawa, Shinichiro; Sakamoto, Takuya; Tajima, Naoko; Utsunomiya, Kazunori

2017-09-01

Little information is available regarding the status of insulin resistance (IR) and insulin deficiency (ID), as well as their relationship with obesity in children using the homeostasis model assessment (HOMA) in a population-based setting. The study included a total of 445 ninth-grade children participating in health check-up programs implemented in Tsunan Town, Niigata, Japan (boys/girls, 252/193 [participation rates: 98.1/95.5%]). HOMA of insulin resistance ≥2.5 was defined as IR, and HOMA of β-cell function <40 defined as ID. The medians (25-75th percentiles) of HOMA of insulin resistance, HOMA of β-cell function, Disposition Index and body mass index in boys were 1.2 (0.8-1.7), 64 (44-93), 52 (43-64) and 19.2 (18.0-20.7) kg/m 2 , respectively, vs 1.5 (1.0-2.0), 86 (63-120), 60 (50-74) and 20.4 (18.9-22.0) kg/m 2 , respectively, in girls. The HOMA of insulin resistance, HOMA of β-cell function and Disposition Index values were significantly higher in the girls (P = 0.002, P < 0.001 and P < 0.001, respectively). Those with IR accounted for a significantly higher proportion of girls than boys (15.5/8.7%; P = 0.027); those with obesity accounted for 9.9/10.7% (boys/girls); and those with IR and obesity accounted for 2.4/4.7%. Those with ID accounted for a significantly higher proportion of boys than girls (20.6/8.8%; P = 0.001), whereas those with ID and obesity accounted for a very small proportion of either group (0.4/0.5%). The presence of IR was higher among the girls. In contrast, ID was more frequent among the boys. The infrequent presence of ID among children might support the presence of non-obese type 2 diabetes adults in Japan. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Semantic Domains and Denotational Semantics

DTIC Science & Technology

1989-02-14

are continuous functions PL N -* PN FL :PN -PN such that IL 0 %FL = id and T1/L o IL -- id. Then the function RL (r,s) = TLo 4L represents the constant...would actually reduce the abstractness of denotations. The popularity of continuations seems to be partly due to the accompanying notational convenience...R.L ’ES.(~’ , r) s’)] ( rl (s))) (ext~ rl , _L R ,S’ E S). (g(r’, r2), ’]r( )) (S[Sile)(SIS1Je) S[ < S > =Ae E Env. fix(Ah R -, R. Ar E R. ext[As E S

Novel hits for acetylcholinesterase inhibition derived by docking-based screening on ZINC database.

PubMed

Doytchinova, Irini; Atanasova, Mariyana; Valkova, Iva; Stavrakov, Georgi; Philipova, Irena; Zhivkova, Zvetanka; Zheleva-Dimitrova, Dimitrina; Konstantinov, Spiro; Dimitrov, Ivan

2018-12-01

The inhibition of the enzyme acetylcholinesterase (AChE) increases the levels of the neurotransmitter acetylcholine and symptomatically improves the affected cognitive function. In the present study, we searched for novel AChE inhibitors by docking-based virtual screening of the standard lead-like set of ZINC database containing more than 6 million small molecules using GOLD software. The top 10 best-scored hits were tested in vitro for AChE affinity, neurotoxicity, GIT and BBB permeability. The main pharmacokinetic parameters like volume of distribution, free fraction in plasma, total clearance, and half-life were predicted by previously derived models. Nine of the compounds bind to the enzyme with affinities from 0.517 to 0.735 µM, eight of them are non-toxic. All hits permeate GIT and BBB and bind extensively to plasma proteins. Most of them are low-clearance compounds. In total, seven of the 10 hits are promising for further lead optimisation. These are structures with ZINC IDs: 00220177, 44455618, 66142300, 71804814, 72065926, 96007907, and 97159977.

Angiotensin-converting enzyme insertion/deletion polymorphism is associated with cerebral white matter changes in Alzheimer's disease.

PubMed

Chou, Ping-Song; Wu, Shyh-Jong; Kao, Yi-Hui; Chou, Mei-Chuan; Tai, Shu-Yu; Yang, Yuan-Han

2017-06-01

The presence of cerebral white matter changes (WMC) has been reported as an important predictor of the rapidity of cognitive decline in Alzheimer's disease (AD). The association between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and WMC in AD is yet to be elucidated. The present study aimed to examine the association between the ACE I/D polymorphism and WMC among AD patients in Taiwan. A total of 403 patients clinically diagnosed with AD were recruited in a cross-sectional study carried out in an area hospital in Kaohsiung, Taiwan. The ACE I/D polymorphism was genotyped, and cerebral white matter rating was carried out using the visual rating scale for age-related white matter changes. The I allele was associated with a significantly lower total age-related white matter changes scale score compared with the D allele (4.83 vs 5.93, P = 0.013). The total age-related white matter changes scale score was significantly lower for the I/I genotype than for the I/D (4.37 vs 5.87, P = 0.009) and I/D + D/D genotypes (4.37 vs 5.91, P = 0.006), with no differences observed between the I/I + I/D and the D/D genotypes (5.08 vs 6.09, P = 0.373), after adjustment for age and hypertension. A stratified analysis by sex demonstrated that the I/I genotype was associated with significant lower WMC than other genotypes in women, but not in men. The present study supports the hypothesis that the ACE I/D polymorphism is associated with the severity of WMC in patients with AD. Patients with AD who are homozygous for the I allele might be less likely to develop WMC, especially women. Geriatr Gerontol Int 2017; 17: 945-950. © 2016 Japan Geriatrics Society.

Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression.

PubMed

Helmreich, Isabella; Wagner, Stefanie; Mergl, Roland; Allgaier, Antje-Kathrin; Hautzinger, Martin; Henkel, Verena; Hegerl, Ulrich; Tadić, André

2012-06-01

In the efficacy evaluation of antidepressant treatments, the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the 'gold standard'. We previously had shown that the Inventory of Depressive Symptomatology (IDS) was more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et al. 2011). Furthermore, studies suggest that the unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo-verum differences. The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding the effect sizes, it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression (e.g. atypical symptoms, sleep disturbances), which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be carefully assessed in the decision for using unidimensional subscales.

Trust Management for Encounter-Based Routing in Delay Tolerant Networks

DTIC Science & Technology

2010-05-15

8217 4 O-i 0.5 E 1.6 a 90% M 300 i / fc -vfc 0.8:0.2 « 2 1 IDS 6OO5 Oil (0, 2] mis D WS p/DS 0.5% Eo [12,24] hrs I/;.• [160,320 480] min. Below we...34 IEEE Infocom, Barcelona , Spain, Apr. 2006, pp. 1-11. [3] J.H. Cho, A. Swami and I.R. Chen, "Modeling and Analysis of Trust Management for Cognitive

Intellectual Disability in Children Aged Less than Seven Years Born Moderately and Late Preterm Compared with Very Preterm and Term-Born Children--A Nationwide Birth Cohort Study

ERIC Educational Resources Information Center

Hirvonen, M.; Ojala, R.; Korhonen, P.; Haataja, P.; Eriksson, K.; Rantanen, K.; Gissler, M.; Luukkaala, T.; Tammela, O.

2017-01-01

Background: Prematurity has been shown to be associated with an increased risk of intellectual disability (ID). Method: The aim was to establish whether the prevalence of ID, defined as significant limitations in both intellectual (intelligence quotient below 70) and adaptive functioning among moderately preterm (MP; 32[superscript + 0]-33…

Dipicolinate salt of imidazole: Discovering its structure and properties using different experimental methodologies and quantum chemical investigations

NASA Astrophysics Data System (ADS)

Thirumurugan, R.; Anitha, K.

2018-03-01

A novel organic proton transfer complex of imidazolium dipicolinate (ID) has been synthesized and it was grown as single crystals using slow evaporation method. The molecular structure of synthesized compound and vibrational modes of its functional groups were confirmed by (1H and 13C) NMR, FTIR and FT-Raman spectroscopic studies, respectively. Single crystal X-ray diffraction (SCXRD) analysis confirmed the orthorhombic system with noncentrosymmetric (NCS), P212121, space group of grown ID crystal. UV-Vis-NIR spectral study confirmed its high optical transparency within the region of 285-1500 nm. Powder second harmonic generation (SHG) efficiency of ID crystal was confirmed and it was 6.8 times that of KDP crystal. TG-DTA and DSC analysis revealed the higher thermal stability of grown crystal as 249 °C. The dielectric response and mechanical behaviour of grown crystal were studied effectively. Density functional theory calculations were performed to probe the relationship between the structure and its properties including molecular optimization, Mulliken atomic charge distribution, frontier molecular orbital (FMOs) and molecular electrostatic potential map (MEP) analysis and first hyperpolarizability. All these experimental and computational results were discussed in this communication and it endorsed the ID compound as a potential NLO candidate could be employed in optoelectronics device applications in near future.

Iron isotopic composition of blood serum in anemia of chronic kidney disease.

PubMed

Anoshkina, Yulia; Costas-Rodríguez, Marta; Speeckaert, Marijn; Van Biesen, Wim; Delanghe, Joris; Vanhaecke, Frank

2017-05-24

Chronic kidney disease (CKD) is a general term for disorders that affect the structure and function of the kidneys. Iron deficiency (ID) and anemia occur in the vast majority of CKD patients, most of whom are elderly. However, establishing the cause of anemia in CKD, and therefore making an informed decision concerning the corresponding therapeutic treatment, is still a challenge. High-precision Fe isotopic analysis of blood serum samples of CKD patients with and without ID/anemia was performed via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose. Patients with CKD and/or iron disorders showed a heavier serum Fe isotopic composition than controls. Many clinical parameters used for the diagnosis and follow-up of anemia correlated significantly with the serum Fe isotopic composition. In contrast, no relation was observed between the serum Fe isotopic composition and the estimated glomerular filtration rate as a measure of kidney function. Among the CKD patients, the serum Fe isotopic composition was substantially heavier in the occurrence of ID anemia, while erythropoietin-related anemia did not exert this effect. The Fe isotopic composition can thus be useful for distinguishing these different types of anemias in CKD patients, i.e. ID anemia vs. erythropoietin-related anemia.

Prenatal Ethanol Exposure and Neocortical Development: A Transgenerational Model of FASD.

PubMed

Abbott, Charles W; Rohac, David J; Bottom, Riley T; Patadia, Sahil; Huffman, Kelly J

2017-07-06

Fetal Alcohol Spectrum Disorders, or FASD, represent a range of adverse developmental conditions caused by prenatal ethanol exposure (PrEE) from maternal consumption of alcohol. PrEE induces neurobiological damage in the developing brain leading to cognitive-perceptual and behavioral deficits in the offspring. Alcohol-mediated alterations to epigenetic function may underlie PrEE-related brain dysfunction, with these changes potentially carried across generations to unexposed offspring. To determine the transgenerational impact of PrEE on neocortical development, we generated a mouse model of FASD and identified numerous stable phenotypes transmitted via the male germline to the unexposed third generation. These include alterations in ectopic intraneocortical connectivity, upregulation of neocortical Rzrβ and Id2 expression accompanied by both promoter hypomethylation of these genes and decreased global DNA methylation levels. DNMT expression was also suppressed in newborn PrEE cortex, providing further insight into how ethanol perturbs DNA methylation leading to altered regulation of gene transcription. These PrEE-induced, transgenerational phenotypes may be responsible for cognitive, sensorimotor, and behavioral deficits seen in humans with FASD. Thus, understanding the possible epigenetic mechanisms by which these phenotypes are generated may reveal novel targets for therapeutic intervention of FASD and lead to advances in human health. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Performance norms for a rhesus monkey neuropsychological testing battery: acquisition and long-term performance.

PubMed

Weed, M R; Taffe, M A; Polis, I; Roberts, A C; Robbins, T W; Koob, G F; Bloom, F E; Gold, L H

1999-10-25

A computerized behavioral battery based upon human neuropsychological tests (CANTAB, CeNeS, Cambridge, UK) has been developed to assess cognitive behaviors of rhesus monkeys. Monkeys reliably performed multiple tasks, providing long-term assessment of changes in a number of behaviors for a given animal. The overall goal of the test battery is to characterize changes in cognitive behaviors following central nervous system (CNS) manipulations. The battery addresses memory (delayed non-matching to sample, DNMS; spatial working memory, using a self-ordered spatial search task, SOSS), attention (intra-/extra-dimensional shift, ID/ED), motivation (progressive-ratio, PR), reaction time (RT) and motor coordination (bimanual task). As with human neuropsychological batteries, different tasks are thought to involve different neural substrates, and therefore performance profiles should assess function in particular brain regions. Monkeys were tested in transport cages, and responding on a touch sensitive computer monitor was maintained by food reinforcement. Parametric manipulations of several tasks demonstrated the sensitivity of performance to increases in task difficulty. Furthermore, the factors influencing difficulty for rhesus monkeys were the same as those shown to affect human performance. Data from this study represent performance of a population of healthy normal monkeys that will be used for comparison in subsequent studies of performance following CNS manipulations such as infection with simian immunodeficiency virus (NeuroAIDS) or drug administration.

Knowledge, perceptions and preferences of elderly regarding protein-enriched functional food.

PubMed

van der Zanden, Lotte D T; van Kleef, Ellen; de Wijk, René A; van Trijp, Hans C M

2014-09-01

Promoting protein consumption in the elderly population may contribute to improving the quality of their later years in life. Our study aimed to explore knowledge, perceptions and preferences of elderly consumers regarding protein-enriched food. We conducted three focus groups with independently living (ID) elderly (N = 24, Mage = 67 years) and three with elderly living in a residential home (RH) (N = 18, Mage = 83 years). Both the ID and RH elderly were predominantly sceptical about functional food in general. Confusion, distrust and a perceived lack of personal relevance were main perceived barriers to purchasing and consuming these products, although a majority of the participants did report occasionally consuming at least one type of functional food. For the ID elderly, medical advice was an important facilitator that could overcome barriers to purchasing and consuming protein-enriched food, indicating the importance of personal relevance for this group. For the RH elderly, in contrast, sensory appeal of protein-enriched foods was a facilitator. Carrier preferences were similar for the two groups; the elderly preferred protein-enriched foods based on healthy products that they consumed frequently. Future studies should explore ways to deal with the confusion and distrust regarding functional food within the heterogeneous population of elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.

Health care needs of children with Down syndrome and impact of health system performance on children and their families.

PubMed

Phelps, Randall A; Pinter, Joseph D; Lollar, Donald J; Medlen, Joan Guthrie; Bethell, Christina D

2012-04-01

The functional, financial, and social impact on families of children with Down syndrome (DS) in the United States and the role of the US health care system in ameliorating these impacts have not been well characterized. We sought to describe the demographic characteristics and functional difficulties of these children and to determine whether children with DS, compared with children with "intellectual disability" (ID) generally, and compared with other "children and youth with special health care needs" (CYSHCN), are more or less likely to receive health care that meets quality standards related to care coordination and to have their health care service needs met. This study analyzed data from the 2005-2006 National Survey of Children with Special Health Care Needs (n = 40,723). Children and youth aged 0 to 17 years with special health care need (CYSHCN) who experience DS (n = 395) and/or IDs (n = 4252) were compared with each other and other CYSHCN on a range of functioning, family impact, and health care quality variables using bivariate and multivariate methods. Data were weighted to represent all CYSHCN in the United States. Compared with CYSHCN without DS, children with DS were significantly less likely to receive comprehensive care within a medical home (29.7% vs 47.3%; p < .001). Parents of children with DS were also significantly more likely to cut back or stop work due to their child's health needs (23.5% vs 55.1%; p < .001). Although overall system performance was poorer for children with DS compared with those with ID and no DS after adjustment for family income, prevalence on most aspects of quality of care and family impacts evaluated were similar for these 2 groups. In this study, the families of children with DS, and ID generally, are burdened disproportionately when compared with other CYSHCN, reflecting the combination of impairments intrinsic to DS and ID and impacts of suboptimal medical care coordination and social support.

Isotopic discrimination of stable isotopes of nitrogen (δ15N) and carbon (δ13C) in a host-specific holocephalan tapeworm.

PubMed

Navarro, J; Albo-Puigserver, M; Coll, M; Saez, R; Forero, M G; Kutcha, R

2014-09-01

During the past decade, parasites have been considered important components of their ecosystems since they can modify food-web structures and functioning. One constraint to the inclusion of parasites in food-web models is the scarcity of available information on their feeding habits and host-parasite relationships. The stable isotope approach is suggested as a useful methodology to determine the trophic position and feeding habits of parasites. However, the isotopic approach is limited by the lack of information on the isotopic discrimination (ID) values of parasites, which is pivotal to avoiding the biased interpretation of isotopic results. In the present study we aimed to provide the first ID values of δ(15)N and δ(13)C between the gyrocotylidean tapeworm Gyrocotyle urna and its definitive host, the holocephalan Chimaera monstrosa. We also test the effect of host body size (body length and body mass) and sex of the host on the ID values. Finally, we illustrate how the trophic relationships of the fish host C. monstrosa and the tapeworm G. urna could vary relative to ID values. Similar to other studies with parasites, the ID values of the parasite-host system were negative for both isotopic values of N (Δδ(15)N = - 3.33 ± 0.63‰) and C (Δδ(13)C = - 1.32 ± 0.65‰), independent of the sex and size of the host. By comparing the specific ID obtained here with ID from other studies, we illustrate the importance of using specific ID in parasite-host systems to avoid potential errors in the interpretation of the results when surrogate values from similar systems or organisms are used.

A comprehensive framework for functional diversity patterns of marine chromophytic phytoplankton using rbcL phylogeny

PubMed Central

Samanta, Brajogopal; Bhadury, Punyasloke

2016-01-01

Marine chromophytes are taxonomically diverse group of algae and contribute approximately half of the total oceanic primary production. To understand the global patterns of functional diversity of chromophytic phytoplankton, robust bioinformatics and statistical analyses including deep phylogeny based on 2476 form ID rbcL gene sequences representing seven ecologically significant oceanographic ecoregions were undertaken. In addition, 12 form ID rbcL clone libraries were generated and analyzed (148 sequences) from Sundarbans Biosphere Reserve representing the world’s largest mangrove ecosystem as part of this study. Global phylogenetic analyses recovered 11 major clades of chromophytic phytoplankton in varying proportions with several novel rbcL sequences in each of the seven targeted ecoregions. Majority of OTUs was found to be exclusive to each ecoregion, whereas some were shared by two or more ecoregions based on beta-diversity analysis. Present phylogenetic and bioinformatics analyses provide a strong statistical support for the hypothesis that different oceanographic regimes harbor distinct and coherent groups of chromophytic phytoplankton. It has been also shown as part of this study that varying natural selection pressure on form ID rbcL gene under different environmental conditions could lead to functional differences and overall fitness of chromophytic phytoplankton populations. PMID:26861415

[Effects of Square-Stepping Exercise inducing activation of the brain's cognitive function in community-dwelling older Japanese females--Focus on the baseline cognitive function level and age].

PubMed

Abe, Takumi; Tsuji, Taishi; Kitano, Naruki; Muraki, Toshiaki; Hotta, Kazushi; Okura, Tomohiro

2015-01-01

The purpose of this study was to investigate whether the degree of improvement in cognitive function achieved with an exercise intervention in community-dwelling older Japanese women is affected by the participant's baseline cognitive function and age. Eighty-eight women (mean age: 70.5±4.2 years) participated in a prevention program for long-term care. They completed the Square-Stepping Exercise (SSE) program once a week, 120 minutes/session, for 11 weeks. We assessed participants' cognitive function using 5 cognitive tests (5-Cog) before and after the intervention. We defined cognitive function as the 5-Cog total score and defined the change in cognitive function as the 5-cog post-score minus the pre-score. We divided participants into four groups based on age (≤69 years or ≥70 years) and baseline cognitive function level (above vs. below the median cognitive function level). We conducted two-way analysis of variance. All 4 groups improved significantly in cognitive function after the intervention. There were no baseline cognitive function level×age interactions and no significant main effects of age, although significant main effects of baseline cognitive function level (P=0.004, η(2)=0.09) were observed. Square-Stepping Exercise is an effective exercise for improving cognitive function. These results suggest that older adults with cognitive decline are more likely to improve their cognitive function with exercise than if they start the intervention with high cognitive function. Furthermore, during an exercise intervention, baseline cognitive function level may have more of an effect than a participant's age on the degree of cognitive improvement.

Molecular Characterization of Cryptosporidium spp. in Children from Mexico

PubMed Central

Valenzuela, Olivia; González-Díaz, Mariana; Garibay-Escobar, Adriana; Burgara-Estrella, Alexel; Cano, Manuel; Durazo, María; Bernal, Rosa M.; Hernandez, Jesús; Xiao, Lihua

2014-01-01

Cryptosporidiosis is a parasitic disease caused by Cryptosporidium spp. In immunocompetent individuals, it usually causes an acute and self-limited diarrhea; in infants, infection with Cryptosporidium spp. can cause malnutrition and growth retardation, and declined cognitive ability. In this study, we described for the first time the distribution of C. parvum and C. hominis subtypes in 12 children in Mexico by sequence characterization of the 60-kDa glycoprotein (GP60) gene of Cryptosporidium. Altogether, 7 subtypes belonging to 4 subtype families of C. hominis (Ia, Ib, Id and Ie) and 1 subtype family of C. parvum (IIa) were detected, including IaA14R3, IaA15R3, IbA10G2, IdA17, IeA11G3T3, IIaA15G2R1 and IIaA16G1R1. The frequency of the subtype families and subtypes in the samples analyzed in this study differed from what was observed in other countries. PMID:24755606

Molecular characterization of Cryptosporidium spp. in children from Mexico.

PubMed

Valenzuela, Olivia; González-Díaz, Mariana; Garibay-Escobar, Adriana; Burgara-Estrella, Alexel; Cano, Manuel; Durazo, María; Bernal, Rosa M; Hernandez, Jesús; Xiao, Lihua

2014-01-01

Cryptosporidiosis is a parasitic disease caused by Cryptosporidium spp. In immunocompetent individuals, it usually causes an acute and self-limited diarrhea; in infants, infection with Cryptosporidium spp. can cause malnutrition and growth retardation, and declined cognitive ability. In this study, we described for the first time the distribution of C. parvum and C. hominis subtypes in 12 children in Mexico by sequence characterization of the 60-kDa glycoprotein (GP60) gene of Cryptosporidium. Altogether, 7 subtypes belonging to 4 subtype families of C. hominis (Ia, Ib, Id and Ie) and 1 subtype family of C. parvum (IIa) were detected, including IaA14R3, IaA15R3, IbA10G2, IdA17, IeA11G3T3, IIaA15G2R1 and IIaA16G1R1. The frequency of the subtype families and subtypes in the samples analyzed in this study differed from what was observed in other countries.

Inpatient group therapeutic interventions for patients with intellectual disabilities.

PubMed

Reddy, Vilash

2015-03-01

Group therapy can be an effective mode of therapy, used on an inpatient unit, as it can allow patients to become allies in their journey to understand and overcome their mental health needs. The therapeutic principles discussed by Dr Irvin Yalom illustrate the significance and importance of group therapy, which was strongly incorporated into interactive behavior therapy (IBT) developed by Dr Daniel J Tomasulo. IBT is a type of group therapy, more action oriented, created to allow patients with intellectual disabilities (IDs) to better comprehend discussed topics, by designing and tailoring activities to meet their cognitive and linguistic capabilities. Additional details found in this article will illustrate the methods by which IBT is capable of meeting the needs of patients with ID. Such adjustments include shorter duration of activities to maximize concentration, proactive role-playing involving the synergistic effort of all members of the group, and limiting the authoritative role of the therapist in a group environment. © The Author(s) 2014.

The effectiveness of ICT-based neurocognitive and psychosocial rehabilitation programmes in people with mild dementia and mild cognitive impairment using GRADIOR and ehcoBUTLER: study protocol for a randomised controlled trial.

PubMed

Vanova, Martina; Irazoki, Eider; García-Casal, J Antonio; Martínez-Abad, Fernando; Botella, Cristina; Shiells, Kate R; Franco-Martín, Manuel A

2018-02-12

Cognitive rehabilitation is a highly individualised, non-pharmacological intervention for people with mild cognitive impairment (MCI) and dementia, which in recent years has also been developed for various IT platforms. In this study, we aim to evaluate the effectiveness of the cognitive rehabilitation software GRADIOR in a multi-centre, single-blinded randomised controlled trial with people with MCI and mild dementia. A total of 400 people with MCI and mild dementia will be randomly allocated to one of four groups. This trial will compare the cognitive rehabilitation treatment using the GRADIOR programme with a psychosocial stimulation intervention (PSS) using the ehcoBUTLER platform, with a combined treatment consisting of GRADIOR and ehcoBUTLER, and with a group receiving treatment as usual during a period of 1 year. The outcomes of this clinical trial will be to determine any relevant changes in cognition, mood, quality of life, activities of daily living and quality of patient-carer relationship after 4 months and 1 year of intervention in a cross-sectional group comparison. Participants will be followed-up for 1 year to investigate potential long-term effects of the conducted treatments. Current Controlled Trials ISRCTN, ID: 15742788 . Registered on 12 June 2017.

Safe Gene Therapy for Type 1 Diabetes

DTIC Science & Technology

2011-10-01

together with FoxP3+eGFP+ T- regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and progression will be monitored. As well, the ability...together with FoxP3+eGFP+ T- regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and progression will be monitored. As well, the ability of...10. In addition, we will continue to investigate their potential therapeutic function in halting the progression of islet-autoimmunity in prediabetic

Group Centric Networking: Addressing Information Sharing Requirements at the Tactical Edge

DTIC Science & Technology

2016-04-10

gateways are typically used to translate information from one network to another. The challenge with gateways is to understand what information...should be relayed from one network to another (with different message formats and technologies) and what platform should perform the gateway function such...information centric paradigm in that GCN does not specify what constitutes a group ID. Group IDs can be mapped to named data objects, content identifiers

Assessment of subjective and objective cognitive function in bipolar disorder: Correlations, predictors and the relation to psychosocial function.

PubMed

Demant, Kirsa M; Vinberg, Maj; Kessing, Lars V; Miskowiak, Kamilla W

2015-09-30

Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented cognitive complaints underwent assessment of objective and subjective cognitive function and psychosocial functioning as part of their participation in two clinical trials. We investigated the association between global and domain-specific objective and subjective cognitive function and between global cognitive function and psychosocial function. We also identified clinical variables that predicted objective and subjective cognitive function and psychosocial functioning. There was a correlation between global subjective and objective measures of cognitive dysfunction but not within the individual cognitive domains. However, the correlation was weak, suggesting that cognitive complaints are not an assay of cognition per se. Self-rated psychosocial difficulties were associated with subjective (but not objective) cognitive impairment and both subjective cognitive and psychosocial difficulties were predicted by depressive symptoms. Our findings indicate that adequate assessment of cognition in the clinical treatment of BD and in drug trials targeting cognition requires implementation of not only subjective measures but also of objective neuropsychological tests. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

TERENA eScience PKI

NASA Astrophysics Data System (ADS)

Sova, Milan

Several National Research and Education Networks associated in TERENA have joined their efforts to build a shared PKI able to serve potentially millions of users from their constituency. The TCS eScience Personal CA takes advantage of national identity federations to facilitate user identity vetting and enrollment procedures. The system uses identity management systems (IdMS) at participating institutions to perform the functions of registration authorities. The certificate enrollment application acts as a SAML Service Provider relying on information provided by IdMS performing as SAML Identity Providers (IdP). When applying for a personal certificate, users authenticate at their home IdP using credentials they normally use to access local services. The IdP controls the certificate issuance process by releasing SAML attributes specifying the user's eligibility for the service and the information to be included in the certificate such as the user's name and email address. The TCS eScience Personal CA is part of the TERENA Certificate Service that uses a commercial PKI provider. Outsourcing the actual CA machinery to a specialized company results in professional-level services such as CRL and OCSP management. The paper describes the legal, organizational and technical aspects of the TCS eScience PKI.

Enhancing visual search abilities of people with intellectual disabilities.

PubMed

Li-Tsang, Cecilia W P; Wong, Jackson K K

2009-01-01

This study aimed to evaluate the effects of cueing in visual search paradigm for people with and without intellectual disabilities (ID). A total of 36 subjects (18 persons with ID and 18 persons with normal intelligence) were recruited using convenient sampling method. A series of experiments were conducted to compare guided cue strategies using either motion contrast or additional cue to basic search task. Repeated measure ANOVA and post hoc multiple comparison tests were used to compare each cue strategy. Results showed that the use of guided strategies was able to capture focal attention in an autonomic manner in the ID group (Pillai's Trace=5.99, p<0.0001). Both guided cue and guided motion search tasks demonstrated functionally similar effects that confirmed the non-specific character of salience. These findings suggested that the visual search efficiency of people with ID was greatly improved if the target was made salient using cueing effect when the complexity of the display increased (i.e. set size increased). This study could have an important implication for the design of the visual searching format of any computerized programs developed for people with ID in learning new tasks.

Iron deficiency and iron-deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential.

PubMed

Black, Maureen M; Quigg, Anna M; Hurley, Kristen M; Pepper, Margery Reese

2011-11-01

This article examines the association of iron deficiency (ID) and iron deficiency anemia (IDA) with children's development and behavior, with the goal of providing recommendations to prevent the developmental loss associated with these conditions. Children's risk for ID and IDA is particularly high during the second 6 months of life when prenatal stores are depleted. Longitudinal studies from infancy through adolescence and early adulthood suggest that socioemotional development is uniquely vulnerable to ID and IDA, perhaps being associated with shared neural pathways, and the effects of early iron deficiencies may be irreversible. In addition to direct effects on brain function, ID and IDA may also affect child development indirectly through non-responsive mother-child interactions. Maternal ID is a global problem that may contribute to high rates of maternal depression and non-responsive caregiving. Intervention trials illustrate that children benefit from both nutritional intervention and early learning interventions that promote responsive mother-child interactions. Recommendations to reduce the developmental loss associated with ID and IDA are to reduce the incidence of these conditions by efforts to prevent premature birth, delay cord clamping, ensure adequate maternal iron status, provide iron-rich complementary foods, and ensure access to postnatal interventions that promote responsive mother-infant interaction patterns and early learning opportunities for infants. © 2011 International Life Sciences Institute.

Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in children and adolescents with intellectual disabilities.

PubMed

Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

2010-01-01

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3-21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value (R(2)=0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value (R(2)=0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

Staff attributions towards men with intellectual disability who have a history of sexual offending and challenging behaviour.

PubMed

MacKinlay, L; Langdon, P E

2009-09-01

Staff working within secure services for people with intellectual disabilities (ID) are likely to work with sexual offenders, but very little attention has been paid to how they think about this sexual offending behaviour. Forty-eight staff working within secure services for people with ID were recruited and completed the Attribution Style Questionnaire in relation to the sexual offending behaviour and challenging behaviour of men with mild ID. Attributions towards challenging behaviour and sexual offending were compared and relationships between level of ID and seriousness of the sexual offence were explored. The results indicated that staff attributed sexual offending as more external to the staff group than they did for challenging behaviour. Sexual offending behaviour was also seen as more stable, and less controllable by people with ID than was challenging behaviour. Sexual offending was also attributed as more uncontrollable by the staff group than challenging behaviour. There was a significant negative correlation between general intellectual functioning and several attributional dimensions regarding sexual offending, but not challenging behaviour. Sexual offending that was coded as more serious was attributed as universal and uncontrollable by the staff group. The differences between staff attributions regarding challenging behaviour and sexual offending potentially relate to the decision-making processes involved in deciding whether or not to involve criminal justice agencies when someone with ID commits a sexual offence. Further research within this area is warranted.

Cognitive Performance and Long-Term Social Functioning in Psychotic Disorder: A Three-Year Follow-Up Study

PubMed Central

Simons, Claudia J. P.; Bartels-Velthuis, Agna A.; Pijnenborg, Gerdina H. M.

2016-01-01

Objective Studies have linked cognitive functioning to everyday social functioning in psychotic disorders, but the nature of the relationships between cognition, social cognition, symptoms, and social functioning remains unestablished. Modelling the contributions of non-social and social cognitive ability in the prediction of social functioning may help in more clearly defining therapeutic targets to improve functioning. Method In a sample of 745 patients with a non-affective psychotic disorder, the associations between cognition and social cognition at baseline on the one hand, and self-reported social functioning three years later on the other, were analysed. First, case-control comparisons were conducted; associations were subsequently further explored in patients, investigating the potential mediating role of symptoms. Analyses were repeated in a subsample of 233 patients with recent-onset psychosis. Results Information processing speed and immediate verbal memory were stronger associated with social functioning in patients than in healthy controls. Most cognition variables significantly predicted social functioning at follow-up, whereas social cognition was not associated with social functioning. Symptoms were robustly associated with follow-up social functioning, with negative symptoms fully mediating most associations between cognition and follow-up social functioning. Illness duration did not moderate the strength of the association between cognitive functioning and follow-up social functioning. No associations were found between (social) cognition and follow-up social functioning in patients with recent-onset psychosis. Conclusions Although cognitive functioning is associated with later social functioning in psychotic disorder, its role in explaining social functioning outcome above negative symptoms appears only modest. In recent-onset psychosis, cognition may have a negligible role in predicting later social functioning. Moreover, social cognition tasks may not predict self-reported social functioning. PMID:27082629

Access to Medicare-funded annual comprehensive health assessments for rural people with intellectual disability.

PubMed

Burton, Heather; Walters, Lucie

2013-01-01

People with intellectual disability (ID) comprise 2-3% of the Australian population. They mostly rely on their GP for primary health care. In rural areas where there are issues with health workforce shortages, there is a risk that people with ID may not get timely access to primary care or may not be aware of the range of healthcare services available to support them. Internationally, research has shown that regular health assessments are beneficial for people with ID. Annual comprehensive health assessments (ACHAs) have been shown to result in increased detection of medical conditions and could assist in reducing the gap in mortality between people with ID and the broader population. In Australia, people with ID have been eligible to access ACHAs under Medicare since 2007. These provide for a regular review of the person's physical, psychological and social functioning. This study explored the extent to which rural people with ID were accessing these ACHAs, and factors which affected their access to ACHAs. In this qualitative study in-depth interviews were conducted with 18 participants including people with ID, carers/support workers and rural doctors. Interviews were then coded and analysed for themes. Seven themes were identified: (1) healthcare barriers in rural areas; (2) cohesion of rural communities; (3) the way rural doctors practice; (4) lack of knowledge/understanding; (5) venturing into new territory; (6) the role of the practice nurse; and (7) the health communication triangle. Despite the well-known problems of lack of services and distance to specialists in rural Australia, there are compensatory factors which were perceived as improving the wellbeing of people with ID, such as increased social cohesion and community connectedness. More education is needed to ensure that the rationale for ACHAs for people with ID is understood and that doctors feel confident to use them. The number of Medicare reforms implemented in a relatively short period presented change-management challenges for rural practices with rural workforce pressures. The role of the carer/support worker is crucial in the health assessment process and can improve the transfer of information about a client with ID between the disability and health sectors and within the health sector.

Knowledge that people with intellectual disabilities have of their inhaled asthma medications: messages for pharmacists.

PubMed

Davis, Sharon R; Durvasula, Seeta; Merhi, Diana; Young, Paul M; Traini, Daniela; Bosnic Anticevich, Sinthia Z

2016-02-01

Fifteen percent of Australians with intellectual disability (ID) are reported to have asthma. People with ID are at risk of poor health knowledge due to deficits in intellectual and adaptive functioning, but their medication knowledge has largely been ignored in research to date. To explore the level of understanding of asthma medication use of people with ID who self-administer their inhaled medications, in order to inform future educational support. Setting The research was conducted in NSW, Australia, at the participants' homes, the point of health care access, or the offices of relevant support organisations. In this qualitative study face-to-face interviews were conducted with people with ID using a semi-structured interview guide. The interviews were recorded, transcribed and thematically analysed. Main outcome Identification of barriers to asthma medication self-management by people with ID. Seventeen people with ID who self-administer their asthma medications were interviewed. Factors influencing their asthma medication knowledge and use included understanding of their illness and the need for medication; aspects of self-management and autonomy versus dependence. This sample of people with ID had a good understanding of the importance of using their inhaled asthma medications, as well as asthma triggers, and the difference between use of preventer and reliever medications. Both enablers and barriers to asthma medication self-management were identified in the domains of managing attacks, adherence, knowledge of side effects and sources of information on correct use of inhalers. The level of autonomy for medication use varied, with motivation to self-manage asthma influenced by the level of support that was practically available to individual participants. This research investigated aspects of asthma medication self-management of people with ID. Based on the barriers identified, pharmacists should promote use of spacers and written asthma action plans as well as counsel people with ID about how to recognise and minimise side effects of asthma medications. Specific strategies for pharmacists when educating people with ID and their caregivers include active listening to determine understanding of concepts, exercising care with language, and working with the person's known routines to maximise adherence with preventer medications.

Social support and intellectual disabilities: a comparison between social networks of adults with intellectual disability and those with physical disability.

PubMed

Lippold, T; Burns, J

2009-05-01

Social support has been identified as a major protective factor in preventing mental health problems and also as a major contributor to quality of life. People with intellectual disabilities (ID) have been identified as having limited social support structures. Interventions have been focused on promoting their social presence and integration. However, previous studies have shown that this does not always lead to the formation of social relationships. To date few studies have looked at how having an ID leads to impoverished social networks. This study aimed to do this by contrasting the social relationships of people with physical disabilities (PD) and people with ID. Two groups of participants were recruited; 30 people with mild ID and 17 people with PD. Social and functional support networks were assessed, in addition to life experiences. Between and within group differences were then explored statistically. Adults with ID had more restricted social networks than PD, despite being involved in more activities. Social support for adults with ID was mainly provided by family and carers and few relationships with non-disabled people were identified. In contrast adults with PD had larger social networks than had been reported in the mainstream literature and had a balance of relationships with disabled and non-disabled people. The results suggest that there are additional processes attached to having an ID, which lead to continued impoverished lifestyles. The findings also endorse other work that suggests being physically integrated and engaged in a wide range of activities does not guarantee good social and emotional support.

1H, 13C, and 15N resonance assignments for the protein coded by gene locus BB0938 of Bordetella bronchiseptica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossi, Paolo; Ramelot, Theresa A.; Xiao, Rong

2005-11-01

The product of gene locus BB0938 from Bordetella bronchiseptica (Swiss-Prot ID: Q7WNU7-BORBR; NESG target ID: BoR11; Wunderlich et al., 2004; Pfam ID: PF03476) is a 128-residue protein of unknown function. This broadly conserved protein family is found in eubacteria and eukaryotes. Using triple resonance NMR techniques, we have determined 98% of backbone and 94% of side chain 1H, 13C, and 15N resonance assignments. The chemical shift and 3J(HN?Ha) scalar coupling data reveal a b topology with a seven-residue helical insert, ??????????. BMRB deposit with accession number 6693. Reference: Wunderlich et al. (2004) Proteins, 56, 181?187.

1H, 13C, and 15N resonance assignments for Escherichia coli ytfP, a member of the broadly conserved UPF0131 protein domain family

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aramini, James M.; Swapna, G.V.T.; Huang, Yuanpeng

2005-11-01

Protein ytfP from Escherichia coli (Swiss-Prot ID: YTFP-ECOLI; NESG target ID: ER111; Wunderlich et al., 2004) is a 113-residue member of the UPF0131 protein family (Pfam ID: PF03674) of unknown function. This domain family is found in organisms from all three kingdoms, archaea, eubacteria and eukaryotes. Using triple resonance NMR techniques, we have determined 97% of backbone and 91% of side chain 1H, 13C, and 15N resonance assignments. The chemical shift and 3J(HN?Ha) scalar coupling data reveal a mixed a/b topology,????????. BMRB deposit with Accession No. 6448. Reference: Wunderlich et al. (2004) Proteins, 56, 181?187.

Prevalence of older people with intellectual disability in Sweden: a spatial epidemiological analysis.

PubMed

Ng, N; Sandberg, M; Ahlström, G

2015-12-01

The expected increase in longevity of individuals with intellectual disabilities (ID) in many countries of the world is a direct result of medical and social advances, which have also extended the longevity of the general population. It is important to assess the need for social services for people with ID across different administrative levels to ensure sufficient resources are allocated to where they are most needed. This study estimates the annual prevalence of older people with ID from 2004 to 2012 and in different counties and municipalities in Sweden, by sex and age group; identifies proxy indicators related to the care of older people with ID in different counties in 2012 in Sweden and analyses the spatial distribution and clustering of municipalities with a high prevalence of older people with ID. Individuals with ID were identified through the national register based on the Swedish Act concerning Support and Service for Persons with Certain Functional Impairments (the LSS act) and the national death register. This study focuses on older individuals aged 55+ during the period of 2004-2012. The estimated prevalence was calculated at the county and municipality level and plotted on a municipality-level map. Moran's I statistics was used to identify any spatial clustering of municipalities with a large number of individuals with ID. The prevalence of ID among older individuals aged 55+ in Sweden increased from 2004 to 2012. The prevalence was consistently higher among men, and the gender gap increased slightly in recent years. Age-specific prevalence estimates showed ID to be higher in younger age groups, and the gender gap decreased in older age groups. The prevalence was higher in northern counties in Sweden (over 500 individuals per 100 000 population aged 55+). Higher prevalence areas were clustered in northern municipalities, whereas municipalities with high prevalence of older individuals with ID in the middle and southern regions of Sweden demonstrated a more widespread distribution. The existence of clusters of counties with a high prevalence of older individuals with ID necessitates further assessment of how resources have been allocated to different counties and municipalities in Sweden. Investigations of the quality of social services provided to individuals with ID across different counties in Sweden are warranted. It is important to ensure that high quality supports are being provided to older individuals with ID in order to grant them the same right to healthy ageing as their counterparts living without ID throughout their life course. © 2015 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Endogenous sex hormones and cognitive function in the elderly.

PubMed

Boss, Lisa; Kang, Duck-Hee; Bergstrom, Nancy; Leasure, J Leigh

2015-08-01

Estrogen and testosterone may influence cognitive function in the older adult, but the relationship between sex hormones and cognitive function is complex. To examine associations of sex hormones and cognitive function among older adults ≥65 years old. Using a cross-sectional research design, data were collected once from 71 elderly (mean age 86.4 years). Global cognitive function and executive function were measured with standardized instruments, and saliva samples were collected for salivary estradiol and testosterone. Estradiol was significantly and positively correlated with global cognitive function in men only (r = 0.54, p < 0.05). Testosterone was not significantly correlated with global cognitive function or executive function in either gender. Associations between sex hormones and cognitive function were mostly non-significant. However, higher estradiol was significantly correlated with better global cognitive function in men, suggesting gender-specific differences. Along with sex hormones, other comorbidity may need to be assessed together in relation to cognitive function in the elderly. Accordingly, clinicians play an important role in educating and promoting beneficial actions to preserve cognitive function.

Perceptions of emotion expression and sibling-parent emotion communication in Latino and non-Latino white siblings of children with intellectual disabilities.

PubMed

Long, Kristin A; Lobato, Debra; Kao, Barbara; Plante, Wendy; Grullón, Edicta; Cheas, Lydia; Houck, Christopher; Seifer, Ronald

2013-06-01

Examine general emotion expression and sibling-parent emotion communication among Latino and non-Latino white (NLW) siblings of children with intellectual disabilities (ID) and matched comparisons. 200 siblings (ages 8-15 years) completed the newly developed Sibling-Parent Emotion Communication Scale and existing measures of general emotion expression and psychosocial functioning. Preliminary analyses evaluated scale psychometrics across ethnicity. Structure and internal consistency of the emotion expression and communication measures differed by respondent ethnicity. Latino siblings endorsed more general emotion expression problems and marginally lower sibling-parent emotion communication than NLW siblings. Siblings of children with ID reported marginally more general emotion expression problems than comparisons. Emotion expression problems and lower sibling-parent emotion communication predicted more internalizing and somatic symptoms and poorer personal adjustment, regardless of ID status. Siblings of children with ID endorsed poorer personal adjustment. Cultural differences in emotion expression and communication may increase Latino siblings' risk for emotional adjustment difficulties.

Trajectories of change in cognitive function in people with chronic obstructive pulmonary disease.

PubMed

Park, Soo Kyung

2018-04-01

To describe changes in cognitive function, as measured by the trail making test; to identify distinct patterns of change in cognitive function; and to examine predictors of change in cognitive function in people with severe chronic obstructive pulmonary disease. How cognitive function changes in people with chronic obstructive pulmonary disease and what factors influence those changes over time is not well known, despite the fact that it declines rapidly in this population and significantly impacts functional decline in healthy older adults. A secondary analysis and longitudinal study with a follow-up period of 3 years. A data set from the National Emphysema Treatment Trial provided participant data. Patients with severe chronic obstructive pulmonary disease (n = 307) were recruited at a clinical site. Several demographic and clinical measures were assessed at baseline. Trail making test scores were measured at baseline, 1, 2 and 3 years. Cognitive function was stable for 3 years in people with chronic obstructive pulmonary disease. However, four distinct patterns of change in cognitive function were identified. Age, education, 6-min walk distance and cognitive impairment scores at baseline on the trail making test Part B were significant predictors of worsening cognitive function and below-average cognitive function over 3 years. These findings suggest that increasing exercise capacity improves cognitive function and delays deterioration of cognitive function in people with COPD. Understanding the trajectories of change in cognitive function and predictors of change in cognitive function over 3 years may enable health care providers to identify patients at greatest risk of developing mental deterioration and those who might benefit from interventions to improve cognitive function. Health care providers should periodically assess and frequently screen people with COPD for cognitive function. © 2018 John Wiley & Sons Ltd.

Overexpression of an Isoprenyl Diphosphate Synthase in Spruce Leads to Unexpected Terpene Diversion Products That Function in Plant Defense1[W][OPEN

PubMed Central

Nagel, Raimund; Berasategui, Aileen; Paetz, Christian; Gershenzon, Jonathan; Schmidt, Axel

2014-01-01

Spruce (Picea spp.) and other conifers employ terpenoid-based oleoresin as part of their defense against herbivores and pathogens. The short-chain isoprenyl diphosphate synthases (IDS) are situated at critical branch points in terpene biosynthesis, producing the precursors of the different terpenoid classes. To determine the role of IDS and to create altered terpene phenotypes for assessing the defensive role of terpenoids, we overexpressed a bifunctional spruce IDS, a geranyl diphosphate and geranylgeranyl diphosphate synthase in white spruce (Picea glauca) saplings. While transcript level (350-fold), enzyme activity level (7-fold), and in planta geranyl diphosphate and geranylgeranyl diphosphate levels (4- to 8-fold) were significantly increased in the needles of transgenic plants, there was no increase in the major monoterpenes and diterpene acids of the resin and no change in primary isoprenoids, such as sterols, chlorophylls, and carotenoids. Instead, large amounts of geranylgeranyl fatty acid esters, known from various gymnosperm and angiosperm plant species, accumulated in needles and were shown to act defensively in reducing the performance of larvae of the nun moth (Lymantria monacha), a conifer pest in Eurasia. These results show the impact of overexpression of an IDS and the defensive role of an unexpected accumulation product of terpenoid biosynthesis with the potential for a broader function in plant protection. PMID:24346420

Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function.

PubMed

Wang, Yonggang; Zhang, Zhiguo; Guo, Weiying; Sun, Weixia; Miao, Xiao; Wu, Hao; Cong, Xianling; Wintergerst, Kupper A; Kong, Xiangbo; Cai, Lu

2014-07-01

Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the antioxidative system and is inducible by sulforaphane (SFN). To test whether SFN prevents diabetes-induced testicular cell death, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 mo to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 4-mo SFN treatment. IDS-T2DM induced significant increases in testicular cell death presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress. Diabetes also significantly increased testicular oxidative damage and inflammation. All of these diabetic effects were significantly prevented by SFN treatment with upregulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular cell death presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly downregulating testicular Nrf2 expression and function. SFN upregulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death. Copyright © 2014 the American Physiological Society.

The effect of transcranial direct current stimulation (tDCS) on locomotion and balance in patients with chronic stroke: study protocol for a randomised controlled trial.

PubMed

Geiger, M; Supiot, A; Zory, R; Aegerter, P; Pradon, D; Roche, N

2017-10-23

Following stroke, patients are often left with hemiparesis that reduces balance and gait capacity. A recent, non-invasive technique, transcranial direct current stimulation, can be used to modify cortical excitability when used in an anodal configuration. It also increases the excitability of spinal neuronal circuits involved in movement in healthy subjects. Many studies in patients with stroke have shown that this technique can improve motor, sensory and cognitive function. For example, anodal tDCS has been shown to improve motor performance of the lower limbs in patients with stroke, such as voluntary quadriceps strength, toe-pinch force and reaction time. Nevertheless, studies of motor function have been limited to simple tasks. Surprisingly, the effects of tDCS on the locomotion and balance of patients with chronic stroke have never been evaluated. In this study, we hypothesise that anodal tDCS will improve balance and gait parameters in patients with chronic stroke-related hemiparesis through its effects at cortical and spinal level. This is a prospective, randomised, placebo-controlled, double-blinded, single-centre, cross-over study over 36 months. Forty patients with chronic stroke will be included. Each patient will participate in three visits: an inclusion visit, and two visits during which they will all undergo either one 30-min session of transcranial direct current stimulation or one 30-min session of placebo stimulation in a randomised order. Evaluations will be carried out before, during and twice after stimulation. The primary outcome is the variability of the displacement of the centre of mass during gait and a static-balance task. Secondary outcomes include clinical and functional measures before and after stimulation. A three-dimensional gait analysis, and evaluation of static balance on a force platform will be also conducted before, during and after stimulation. These results should constitute a useful database to determine the aspects of complex motor function that are the most improved by transcranial direct current stimulation in patients with hemiparesis. It is the first essential step towards validating this technique as a treatment, coupled with task-oriented training. ClinicalTrials.gov, ID: NCT02134158 . First received on 18 December 2013; last updated on 14 September 2016. Other study ID numbers: P120135 / AOM12126, 2013-A00952-43.

Preliminary neurocognitive outcomes in Jeavons syndrome.

PubMed

Fournier-Goodnight, Ashley S; Gabriel, Marsha; Perry, M Scott

2015-11-01

Jeavons syndrome (JS, eyelid myoclonia with absences [EMA]) consists of a triad of symptoms including eyelid myoclonia that may be accompanied by absence seizures, eye closure-induced EEG paroxysms or seizures, and photosensitivity. The age of onset ranges between 2 and 14 years with symptoms peaking between 6 and 8 years of age. Though investigation of the clinical, EEG, and neurological features of JS has occurred, neurocognitive functioning has not been well-delineated despite suggestion that a subtype of the syndrome is characterized in part by cognitive impairment. The purpose of this study was to define neurocognitive functioning in a more detailed manner by examining global IQ and relevant neurocognitive domains (i.e., verbal and nonverbal reasoning, attention, executive functioning, memory) in pediatric patients. The sample (N=6, 4 females) ranged in age from 8 to 15 years (M=11, SD=2.82). All participants completed neuropsychological evaluations. Statistical analyses revealed performance that was below average on measures of global IQ, processing speed and rote, verbal learning coupled with average nonverbal reasoning, and sustained attention. There was also evidence of impaired higher-level verbal reasoning. While global IQ ranged from low average to borderline impaired, no participant could be accurately described as impaired or having intellectual disability (ID) given the consistently average performance noted on some higher-order tasks including nonverbal reasoning. Copyright © 2015 Elsevier Inc. All rights reserved.

Lower Limb Function in Elderly Korean Adults Is Related to Cognitive Function.

PubMed

Kim, A-Sol; Ko, Hae-Jin

2018-05-01

Patients with cognitive impairment have decreased lower limb function. Therefore, we aimed to investigate the relationship between lower limb function and cognitive disorders to determine whether lower limb function can be screened to identify cognitive decline. Using Korean National Health Insurance Service-National Sample Cohort database data, we assessed the cognitive and lower limb functioning of 66-year-olds who underwent national health screening between 2010 and 2014. Cognitive function was assessed via a questionnaire. Timed Up-and-Go (TUG) and one-leg-standing (OLS) tests were performed to evaluate lower limb function. Associations between cognitive and lower limb functions were analyzed, and optimal cut-off points for these tests to screen for cognitive decline, were determined. Cognitive function was significantly correlated with TUG interval ( r = 0.414, p < 0.001) and OLS duration ( r = −0.237, p < 0.001). Optimal cut-off points for screening cognitive disorders were >11 s and ≤12 s for TUG interval and OLS duration, respectively. Among 66-year-olds who underwent national health screening, a significant correlation between lower limb and cognitive function was demonstrated. The TUG and OLS tests are useful screening tools for cognitive disorders in elderly patients. A large-scale prospective cohort study should be conducted to investigate the causal relationship between cognitive and lower limb function.

De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.

PubMed

Tanaka, Akemi J; Cho, Megan T; Retterer, Kyle; Jones, Julie R; Nowak, Catherine; Douglas, Jessica; Jiang, Yong-Hui; McConkie-Rosell, Allyn; Schaefer, G Bradley; Kaylor, Julie; Rahman, Omar A; Telegrafi, Aida; Friedman, Bethany; Douglas, Ganka; Monaghan, Kristin G; Chung, Wendy K

2016-01-01

We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

The effects of lifelong cognitive lifestyle on executive function in older people with Parkinson's disease.

PubMed

Hindle, John V; Martin-Forbes, Pamela A; Martyr, Anthony; Bastable, Alexandra J M; Pye, Kirstie L; Mueller Gathercole, Virginia C; Thomas, Enlli M; Clare, Linda

2017-12-01

Active lifelong cognitive lifestyles increase cognitive reserve and have beneficial effects on global cognition, cognitive decline and dementia risk in Parkinson's disease (PD). Executive function is particularly impaired even in early PD, and this impacts on quality of life. The effects of lifelong cognitive lifestyle on executive function in PD have not been studied previously. This study examined the association between lifelong cognitive lifestyle, as a proxy measure of cognitive reserve, and executive function in people with PD. Sixty-nine people diagnosed with early PD without dementia were recruited as part of the Bilingualism as a protective factor in Age-related Neurodegenerative Conditions study. Participants completed a battery of tests of executive function. The Lifetime of Experiences Questionnaire was completed as a comprehensive assessment of lifelong cognitive lifestyle. Non-parametric correlations compared clinical measures with executive function scores. Cross-sectional analyses of covariance were performed comparing the performance of low and high cognitive reserve groups on executive function tests. Correlational analyses showed that better executive function scores were associated with younger age, higher levodopa dose and higher Lifetime of Experiences Questionnaire scores. Higher cognitive reserve was associated with better motor function, but high and low cognitive reserve groups did not differ in executive function. Cognitive reserve, although associated with global cognition, does not appear to be associated with executive function. This differential effect may reflect the specific cognitive profile of PD. The long-term effects of cognitive reserve on executive function in PD require further exploration. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The relationship between change in cognition and change in functional ability in schizophrenia during cognitive and psychosocial rehabilitation.

PubMed

Rispaud, Samuel G; Rose, Jennifer; Kurtz, Matthew M

2016-10-30

While a wealth of studies have evaluated cross-sectional links between cognition and functioning in schizophrenia, few have investigated the relationship between change in cognition and change in functioning in the context of treatment trials targeted at cognition. Identifying cognitive skills that, when improved, predict improvement in functioning will guide the development of more targeted rehabilitation for this population. The present study identifies the relationship between change in specific cognitive skills and change in functional ability during one year of cognitive rehabilitation. Ninety-six individuals with schizophrenia were assessed with a battery of cognitive measures and a measure of performance-based functioning before and after cognitive training consisting of either drill-and-practice cognitive remediation or computer skills training. Results revealed that while working and episodic memory, problem-solving, and processing speed skills all improved during the trial, only improved working memory and processing speed skills predicted improvement in functional ability. Secondary analyses revealed these relationships were driven by individuals who showed a moderate level (SD≥0.5) of cognitive improvement during the trial. These findings suggest that while a variety of cognitive skills may improve during training targeted at cognition, only improvements in a subset of cognitive functions may translate into functional gains. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long sleep duration is associated with lower cognitive function among middle-age adults - the Doetinchem Cohort Study.

PubMed

van Oostrom, Sandra H; Nooyens, Astrid C J; van Boxtel, Martin P J; Verschuren, W M Monique

2018-01-01

In older adults, both short and long sleep duration are associated with lower cognitive function, suggesting an inverted U-shaped association between sleep duration and cognitive outcomes. This study examined whether sleep duration is associated with (changes in) cognitive function in a middle-aged population. In the Doetinchem Cohort Study, the cognitive function of 2970 men and women aged 41-75 years at baseline (1995-2007) was examined 2-3 times, with 5-year time intervals. Global cognitive function and the domains memory, information processing speed, and cognitive flexibility were assessed. In multivariable linear regression models, (change in) self-reported sleep duration was studied in association with the level and change in cognitive function. In a subsample of the population (n = 2587), the association of sleep duration and feeling rested with cognitive function was studied. Sleep duration of 9 h and more was statistically significantly associated with lower global cognitive function (p < 0.01), memory (p = 0.02), and flexibility (p = 0.03), compared to a sleep duration of 7 or 8 h. Among adults feeling frequently not well rested, both short and long sleep duration were associated with a lower speed of cognitive function. An inverted U-shaped association between sleep duration and cognitive function was observed for speed, flexibility, and global cognitive function. Sleep duration was not associated with change in cognitive function. Middle-age adults with long sleep duration had a lower cognitive function. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A comparison of the social competence of children with moderate intellectual disability in inclusive versus segregated school settings.

PubMed

Hardiman, Sharon; Guerin, Suzanne; Fitzsimons, Elaine

2009-01-01

This is the first study to compare the social competence of children with moderate intellectual disability in inclusive versus segregated school settings in the Republic of Ireland. A convenience sample was recruited through two large ID services. The sample comprised 45 children across two groups: Group 1 (n=20; inclusive school) and Group 2 (n=25; segregated school). Parents and teachers completed the Strengths and Difficulties Questionnaire and the Adaptive Behaviour Scale-School: 2nd edition. A series of 2 x 2 ANOVAs were carried out on social competence scores using educational placement type (inclusive vs segregated school) and proxy rater (parent vs teacher) as the independent variables. Key findings indicated that children in inclusive schools did not differ significantly from children in segregated schools on the majority of proxy ratings of social competence. This supports the belief that children with intellectual disabilities can function well in different educational settings. Present findings highlight the importance of utilising the functional model of ID when selecting and designing school placements for children with moderate ID.

Language at Three Timescales: The Role of Real-Time Processes in Language Development and Evolution.

PubMed

McMurray, Bob

2016-04-01

Evolutionary developmental systems (evo-devo) theory stresses that selection pressures operate on entire developmental systems rather than just genes. This study extends this approach to language evolution, arguing that selection pressure may operate on two quasi-independent timescales. First, children clearly must acquire language successfully (as acknowledged in traditional evo-devo accounts) and evolution must equip them with the tools to do so. Second, while this is developing, they must also communicate with others in the moment using partially developed knowledge. These pressures may require different solutions, and their combination may underlie the evolution of complex mechanisms for language development and processing. I present two case studies to illustrate how the demands of both real-time communication and language acquisition may be subtly different (and interact). The first case study examines infant-directed speech (IDS). A recent view is that IDS underwent cultural to statistical learning mechanisms that infants use to acquire the speech categories of their language. However, recent data suggest is it may not have evolved to enhance development, but rather to serve a more real-time communicative function. The second case study examines the argument for seemingly specialized mechanisms for learning word meanings (e.g., fast-mapping). Both behavioral and computational work suggest that learning may be much slower and served by general-purpose mechanisms like associative learning. Fast-mapping, then, may be a real-time process meant to serve immediate communication, not learning, by augmenting incomplete vocabulary knowledge with constraints from the current context. Together, these studies suggest that evolutionary accounts consider selection pressure arising from both real-time communicative demands and from the need for accurate language development. Copyright © 2016 Cognitive Science Society, Inc.

Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency–Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus123

PubMed Central

Tran, Phu V; Kennedy, Bruce C; Pisansky, Marc T; Won, Kyoung-Jae; Gewirtz, Jonathan C; Simmons, Rebecca A; Georgieff, Michael K

2016-01-01

Background: Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. Objectives: We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offspring’s hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. Methods: Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. Results: Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. Conclusions: Fetal-neonatal iron deficiency reprograms molecular networks associated with the pathogenesis of neurologic and psychological disorders in adult rats. The positive response to prenatal choline represents a potential adjunctive therapeutic supplement to the high-risk group. PMID:26865644

Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency-Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus.

PubMed

Tran, Phu V; Kennedy, Bruce C; Pisansky, Marc T; Won, Kyoung-Jae; Gewirtz, Jonathan C; Simmons, Rebecca A; Georgieff, Michael K

2016-03-01

Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offspring's hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. Fetal-neonatal iron deficiency reprograms molecular networks associated with the pathogenesis of neurologic and psychological disorders in adult rats. The positive response to prenatal choline represents a potential adjunctive therapeutic supplement to the high-risk group. © 2016 American Society for Nutrition.

Parenting stress and child behaviour problems among parents with intellectual disabilities: the buffering role of resources.

PubMed

Meppelder, M; Hodes, M; Kef, S; Schuengel, C

2015-07-01

Parents with intellectual disabilities (ID) are at risk for high levels of parenting stress. The present study evaluated resources, including parental adaptive functioning, financial resources and access to a support network, as moderators of the association between child behaviour problems and parenting stress. A total of 134 parents with ID and their children (ages 1-7 years) were recruited from 10 Dutch care organisations. Questionnaires were administered to the parents to obtain information on parenting stress in the parent and child domain, financial resources and their support network. Teachers and care workers reported on child behaviour problems and parental adaptive functioning, respectively. Parents experienced more stress with regard to their children than towards their own functioning and situation. Parenting stress was less in parents who were not experiencing financial hardship. Child behaviour problems were associated with high child-related parenting stress, not parent-related parenting stress. Large support networks decreased the association between child behaviour problems and child-related parenting stress. Financial resources did not significantly moderate the association. Parenting stress among parents with ID is focused on problems with the child, especially when little social support is available. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

A comparison of family financial and employment impacts of fragile X syndrome, autism spectrum disorders, and intellectual disability.

PubMed

Ouyang, Lijing; Grosse, Scott D; Riley, Catharine; Bolen, Julie; Bishop, Ellen; Raspa, Melissa; Bailey, Donald B

2014-07-01

This study compares the family financial and employment impacts of having a child with fragile X syndrome (FXS), autism spectrum disorder (ASD), or intellectual disabilities (ID). Data from a 2011 national survey of families of children with FXS were matched with data from the National Survey of Children with Special Health Care Needs 2009-2010 to form four analytic groups: children with FXS (n=189), children with special health care needs with ASD only (n=185), ID only (n=177), or both ASD and ID (n=178). Comparable percentages of parents of children with FXS (60%) and parents of children with both ASD and ID (52%) reported that their families experienced a financial burden as a result of the condition, both of which were higher than the percentages of parents of children with ASD only (39%) or ID only (29%). Comparable percentages of parents of children with FXS (40%) and parents of children with both ASD and ID (46%) reported quitting employment because of the condition, both of which were higher than the percentages of parents of children with ID only (25%) or ASD only (25%). In multivariate analyses controlling for co-occurring conditions and functional difficulties and stratified by age, adjusted odds ratios for the FXS group aged 12-17 years were significantly elevated for financial burden (2.73, 95% CI 1.29-5.77), quitting employment (2.58, 95% CI 1.18-5.65) and reduced hours of work (4.34, 95% CI 2.08-9.06) relative to children with ASD only. Among children aged 5-11 years, the adjusted odds ratios for the FXS group were elevated but statistically insignificant for financial burden (1.63, 95% CI 0.85-3.14) and reducing hours of work (1.34, 95% CI 0.68-2.63) relative to children with ASD only. Regardless of condition, co-occurring anxiety or seizures, limits in thinking, reasoning, or learning ability, and more irritability were significantly associated with more caregiver financial and employment impacts. Proper management of anxiety or seizures and functional difficulties of children with FXS or other developmental disabilities may be important in alleviating adverse family caregiver impacts. Published by Elsevier Ltd.

The European Community Directive -- An Alternative Environmental Impact Assessment Procedure after Massey?

DTIC Science & Technology

1993-09-30

competitive conditions, thereby directly affecting the functioning of the common market .’l B. Environmental Impact Assessment 1. Background The Preamble to the...of the conmon market ." Treaty of Rome, supra note 120, art. 100. ’"EC Directive, supra note 22, Preamble. 14Id. art. 1.2. 16Id. 51 member states...dairy products. (d) Brewing and malting. (e) Confectionery and syrup manufacture. (f) Installations for the slaughter of animals. 86 0 0 (g

Correlating interleukin-12 stimulated interferon-γ production and the absence of ectodermal dysplasia and anhidrosis (EDA) in patients with mutations in NF-κB essential modulator (NEMO).

PubMed

Haverkamp, Margje H; Marciano, Beatriz E; Frucht, David M; Jain, Ashish; van de Vosse, Esther; Holland, Steven M

2014-05-01

Patients with hypomorphic mutations in Nuclear Factor-κB Essential Modulator (NEMO) are immunodeficient (ID) and most display ectodermal dysplasia and anhidrosis (EDA). We compared cytokine production by NEMO-ID patients with and without EDA. PBMCs of NEMO-ID patients, four with EDA carrying E315A, C417R, D311N and Q403X, and three without EDA carrying E315A, E311_L333del and R254G, were cultured with PHA, PHA plus IL-12p70, LPS, LPS plus IFN-γ, TNF and IL-1β. The production of various cytokines was measured in the supernatants. Fifty-nine healthy individuals served as controls. PBMCs of NEMO-ID patients without EDA produce subnormal amounts of IFN-γ after stimulation with PHA, but normal amounts of IFN-γ after PHA plus IL-12p70. In contrast, IFN-γ production by patients with EDA was low in both cases. Patients with EDA also generate lower PHA-stimulated IL-10 and IL-1β than controls, whereas the production of these cytokines by patients without EDA was normal. Responses of PBMCs in NEMO-ID patients with EDA to PHA with and without IL-12p70 appear less robust than in NEMO-ID patients without EDA. This possibly indicates a better preserved NEMO function in our patients without EDA.

Expanding the genetic heterogeneity of intellectual disability.

PubMed

Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M; Alkuraya, Hisham; Salih, Mustafa A; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S

2017-11-01

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

Speed-difficulty trade-off in speech: Chinese versus English

PubMed Central

Sun, Yao; Latash, Elizaveta M.; Mikaelian, Irina L.

2011-01-01

This study continues the investigation of the previously described speed-difficulty trade-off in picture description tasks. In particular, we tested a hypothesis that the Mandarin Chinese and American English are similar in showing logarithmic dependences between speech time and index of difficulty (ID), while they differ significantly in the amount of time needed to describe simple pictures, this difference increases for more complex pictures, and it is associated with a proportional difference in the number of syllables used. Subjects (eight Chinese speakers and eight English speakers) were tested in pairs. One subject (the Speaker) described simple pictures, while the other subject (the Performer) tried to reproduce the pictures based on the verbal description as quickly as possible with a set of objects. The Chinese speakers initiated speech production significantly faster than the English speakers. Speech time scaled linearly with ln(ID) in all subjects, but the regression coefficient was significantly higher in the English speakers as compared with the Chinese speakers. The number of errors was somewhat lower in the Chinese participants (not significantly). The Chinese pairs also showed a shorter delay between the initiation of speech and initiation of action by the Performer, shorter movement time by the Performer, and shorter overall performance time. The number of syllables scaled with ID, and the Chinese speakers used significantly smaller numbers of syllables. Speech rate was comparable between the two groups, about 3 syllables/s; it dropped for more complex pictures (higher ID). When asked to reproduce the same pictures without speaking, movement time scaled linearly with ln(ID); the Chinese performers were slower than the English performers. We conclude that natural languages show a speed-difficulty trade-off similar to Fitts’ law; the trade-offs in movement and speech production are likely to originate at a cognitive level. The time advantage of the Chinese participants originates not from similarity of the simple pictures and Chinese written characters and not from more sloppy performance. It is linked to using fewer syllables to transmit the same information. We suggest that natural languages may differ by informational density defined as the amount of information transmitted by a given number of syllables. PMID:21479658

Ozone-induced dissociation on a traveling wave high-resolution mass spectrometer for determination of double-bond position in lipids.

PubMed

Vu, Ngoc; Brown, Jeffery; Giles, Kevin; Zhang, Qibin

2017-09-15

The position of C=C within fatty acyl chains affects the biological function of lipids. Ozone-induced dissociation mass spectrometry (OzID-MS) has great potential in determination of lipid double-bond position, but has generally been implemented on low-resolution ion trap mass spectrometers. In addition, most of the OzID-MS experiments carried out so far were focused on the sodiated adducts of lipids; fragmentation of the most commonly observed protonated ions generated in LC/MS-based lipidomics workflow has been less explored. Ozone generated in line from an ozone generator was connected to the trap and transfer gas supply line of a Synapt G2 high-resolution mass spectrometer. Protonated ions of different phosphatidylcholines (PC) were generated by electrospray ionization through direct infusion. Different parameters, including traveling wave height and velocity, trap entrance and DC potential, were adjusted to maximize the OzID efficiency. sn-positional isomers and cis/trans isomers of lipids were compared for their reactivity with ozone. Traveling wave height and velocity were tuned to prolong the encounter time between lipid ions and ozone, and resulted in improved OzID efficiency, as did increasing trapping region DC and entrance potential. Under optimized settings, at least 1000 times enhancement in OzID efficiency was achieved compared to that under default settings for monounsaturated PC standards. Monounsaturated C=C in the sn-2 PC isomer reacted faster with ozone than the sn-1 isomer. Similarly, the C=C in trans PC reacted faster than in cis PC. This is the first implementation of OzID in the trap and transfer region of a traveling wave enabled high-resolution mass spectrometer. The OzID reaction efficiency is significantly improved by slowing down ions in the trap region for their prolonged interaction with ozone. This will facilitate application of high-resolution OzID-MS in lipidomics. Copyright © 2017 John Wiley & Sons, Ltd.

The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells.

PubMed

Dong, Hye-Jin; Jang, Gyu-Beom; Lee, Hwa-Yong; Park, Se-Ra; Kim, Ji-Young; Nam, Jeong-Seok; Hong, In-Sun

2016-03-11

Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44(+) subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression.

Iron deficiency and iron deficiency anaemia in women.

PubMed

Percy, Laura; Mansour, Diana; Fraser, Ian

2017-04-01

Iron deficiency (ID) is the most common micronutrient deficiency worldwide with >20% of women experiencing it during their reproductive lives. Hepcidin, a peptide hormone mostly produced by the liver, controls the absorption and regulation of iron. Understanding iron metabolism is pivotal in the successful management of ID and iron deficiency anaemia (IDA) using oral preparations, parenteral iron or blood transfusion. Oral preparations vary in their iron content and can result in gastrointestinal side effects. Parenteral iron is indicated when there are compliance/tolerance issues with oral iron, comorbidities which may affect absorption or ongoing iron losses that exceed absorptive capacity. It may also be the preferred option when rapid iron repletion is required to prevent physiological decompensation or given preoperatively for non-deferrable surgery. As gynaecologists, we focus on managing women's heavy menstrual bleeding (HMB) and assume that primary care clinicians are treating the associated ID/IDA. We now need to take the lead in diagnosing, managing and initiating treatment for ID/IDA and treating HMB simultaneously. This dual management will significantly improve their quality of life. In this chapter we will summarise the importance of iron in cellular functioning, describe how to diagnose ID/IDA and help clinicians choose between the available treatment options. Copyright © 2016. Published by Elsevier Ltd.

A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome.

PubMed

McCarron, M; McCallion, P; Reilly, E; Dunne, P; Carroll, R; Mulryan, N

2017-09-01

To examine dementia characteristics, age at onset and associated co-morbidities in persons with Down syndrome. A total of 77 people with Down syndrome aged 35 years and older were followed up from 1996 to 2015. The diagnosis of dementia was established using the modified ICD 10 Criteria and a combination of objective and informant-based tests. Cognitive tests included the Test for Severe Impairment and the Down Syndrome Mental Status Examination; adaptive behaviour was measured using the Daily Living Skills Questionnaire, and data from the Dementia Questionnaire for People with Intellectual Disabilities have been available since 2005. Over the 20-year period, 97.4% (75 of 77) persons developed dementia with a mean age of dementia diagnosis of 55 years (SD = 7.1, median = 56 years). Clinical dementia was associated with cognitive and function decline and seizure activity. Risk for dementia increased from 23% in those aged 50 years to 80% in those aged 65 years and above. There were no differences by level of ID. The previously reported high risk levels for dementia among people with Down syndrome were confirmed in this data as was the relationship with late onset epilepsy. The value of the instruments utilised in tracking decline and helping to confirm diagnosis is further highlighted. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

PubMed

Golan, Daniel; Doniger, Glen M; Wissemann, Karl; Zarif, Myassar; Bumstead, Barbara; Buhse, Marijean; Fafard, Lori; Lavi, Idit; Wilken, Jeffrey; Gudesblatt, Mark

2018-02-01

The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

The influence of ACE ID and ACTN3 R577X polymorphisms on lower-extremity function in older women in response to high-speed power training.

PubMed

Pereira, Ana; Costa, Aldo M; Leitão, José C; Monteiro, António M; Izquierdo, Mikel; Silva, António J; Bastos, Estela; Marques, Mário C

2013-12-06

We studied the influence of the ACE I/D and ACTN3 R577X polymorphisms (single or combined) on lower-extremity function in older women in response to high-speed power training. One hundred and thirty-nine healthy older Caucasian women participated in this study (age: 65.5 ± 8.2 years, body mass: 67.0 ± 10.0 kg and height: 1.57 ± 0.06 m). Walking speed (S10) performance and functional capacity assessed by the "get-up and go" (GUG) mobility test were measured at baseline (T1) and after a consecutive 12-week period of high-speed power training (40-75% of one repetition maximum in arm and leg extensor exercises; 3 sets 4-12 reps, and two power exercises for upper and lower extremity). Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR methods. Genotype distributions between groups were compared by Chi-Square test and the gains in physical performance were analyzed by two-way, repeated-measures ANOVA. There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes (P > 0.05). ACE I/D and ACTN3 polymorphisms showed a significant interaction genotype-training only in S10 (P = 0.012 and P = 0.044, respectively) and not in the GUG test (P = 0.311 and P = 0.477, respectively). Analyses of the combined effects between genotypes showed no other significant differences in all phenotypes (P < 0.05) at baseline. However, in response to high-speed power training, a significant interaction on walking speed (P = 0.048) was observed between the "power" (ACTN3 RR + RX & ACE DD) versus "non-power" muscularity-oriented genotypes (ACTN3 XX & ACE II + ID)]. Thus, ACE I/D and ACTN3 R577X polymorphisms are likely candidates in the modulation of exercise-related gait speed phenotype in older women but not a significant influence in mobility traits.

Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villard, E.; Soubrier, F.; Tiret, L.

1996-06-01

Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms couldmore » be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.« less

The role of cognitive impairment in psychosocial functioning in remitted depression.

PubMed

Knight, Mattew J; Air, Tracy; Baune, Bernhard T

2018-08-01

Cognitive dysfunction is a prevalent and disabling symptom of Major Depressive Disorder (MDD), and is often retained in the remitted stage of illness. Emerging evidence suggests that cognitive impairment may be associated with dysfunction in a number of psychosocial domains (e.g., workplace productivity, social relationships). The current study explored the relationship between cognition and psychosocial functioning in remitted MDD and in healthy controls. Data were obtained from 182 participants of the Cognitive Function and Mood Study (CoFaM-S), a cross-sectional study of cognition, mood, and social cognition in mood disorders. Participants' (Remitted MDD n = 72, Healthy n = 110) cognition was assessed with a battery of cognitive tests including the Repeatable Battery for the Assessment of Neuropsychological Function (RBANS) and other standard measures of cognition (e.g., The Tower of London task). Psychosocial functioning was clinically evaluated with the Functioning Assessment Short Test (FAST). The results indicated that executive functioning was the strongest independent predictor of functioning in remitted MDD patients, whereas various cognitive domains predicted psychosocial functioning in healthy individuals. Psychosocial functioning was measured with a clinical interview, and was therefore reliant on clinicians' judgement of impairment, as opposed to more objective measures of functioning. These findings suggest that executive cognition plays an important role in functional recovery in remitted depression, and may be a crucial target in adjunctive treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Gender differences influence the outcome of geriatric rehabilitation following hip fracture.

PubMed

Arinzon, Zeev; Shabat, Shay; Peisakh, Alexander; Gepstein, Reuven; Berner, Yitshal N

2010-01-01

Hip fracture represents the most dramatic expression of the disease, in terms of morbidity, medical cost and mortality. The incidence of hip fracture increases substantially with age. The purpose of this study was to evaluate the association between gender and geriatric rehabilitation outcome after traumatic hip fracture. Ninety-nine community-dwelling elderly patients (older than 65 years), 64 women and 35 men, who were admitted to geriatric rehabilitation after operated hip fracture were studied. We assessed the patients' clinical and demographic data, preoperative risk (ASA), type of fracture and orthopedic repair, pain intensity (VAS), cognitive (MMSE), mood (Zung IDS), and functional status (FIM) on admission and at the end of geriatric rehabilitation. Men had higher mean number of comorbid conditions at the time of the fracture. Men recovered more from depressed mood in comparison with women during the rehabilitation. Significant improvement in FIM motor subscore on discharge was found in both groups. The FIM motor subscore gain was higher in men (24.47) in comparison with women (19.22, p=0.036). Those differences were demonstrated in mean subscores of transfers (p=0.004), and locomotion (p=0.019). Women were more functionally dependent in locomotion, transfers and sphincter control. There were no differences between the groups by duration on rehabilitation stay. Recovery after hip fracture depends in large part on the pre-fracture health and functional ability of the patient. Gender differences in functional recovery may affect therapeutic and rehabilitative decision making. Functional recovery after traumatic hip fracture was better in men in comparison with women.

The influence of medical burden severity and cognition on functional competence in older community-dwelling individuals with schizophrenia.

PubMed

Tsoutsoulas, Christopher; Mulsant, Benoit H; Kalache, Sawsan M; Kumar, Sanjeev; Ghazala, Zaid; Voineskos, Aristotle N; Butters, Meryl A; Menon, Mahesh; Rajji, Tarek K

2016-02-01

Cognition predicts functional competence among individuals with schizophrenia across the lifespan. However, as these individuals age, increasing levels of medical burden may also contribute to functional deficits both directly and indirectly through cognition. Thus, we assessed the relationship among, cognition, medical burden, and functional competence in older individuals with schizophrenia. We analyzed data obtained from 60 community-dwelling participants with schizophrenia and 30 control participants aged 50 or above. Cognition was assessed using the MATRICS Consensus Cognitive Battery (MCCB), functional competence was assessed using the USCD Performance-Based Skills Assessment (UPSA), and medical burden was assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Group differences were assessed using independent samples t-tests or chi-square tests. Mediation analyses using bootstrapping techniques were used to assess whether cognition mediated the effects of medical burden on functional competence. Participants with schizophrenia had higher levels of medical burden, cognitive deficits, and functional impairments. In participants with schizophrenia, cognition, but not medical burden, predicted functional competence after adjusting for age, education, gender, clinical symptoms, and anticholinergic burden of medications. In control participants, cognition and medical burden both predicted functional competence after adjusting for age, education, and gender. Further, cognition was found to fully mediate the association between medical burden and functional competence in control participants. Cognition is a robust predictor of functional competence among older individuals with schizophrenia, regardless of medical burden. Cognitive deficits associated with schizophrenia may mask any further cognitive impairment associated with medical burden and its impact on function. Copyright © 2015 Elsevier B.V. All rights reserved.

Predicting cognitive function of the Malaysian elderly: a structural equation modelling approach.

PubMed

Foong, Hui Foh; Hamid, Tengku Aizan; Ibrahim, Rahimah; Haron, Sharifah Azizah; Shahar, Suzana

2018-01-01

The aim of this study was to identify the predictors of elderly's cognitive function based on biopsychosocial and cognitive reserve perspectives. The study included 2322 community-dwelling elderly in Malaysia, randomly selected through a multi-stage proportional cluster random sampling from Peninsular Malaysia. The elderly were surveyed on socio-demographic information, biomarkers, psychosocial status, disability, and cognitive function. A biopsychosocial model of cognitive function was developed to test variables' predictive power on cognitive function. Statistical analyses were performed using SPSS (version 15.0) in conjunction with Analysis of Moment Structures Graphics (AMOS 7.0). The estimated theoretical model fitted the data well. Psychosocial stress and metabolic syndrome (MetS) negatively predicted cognitive function and psychosocial stress appeared as a main predictor. Socio-demographic characteristics, except gender, also had significant effects on cognitive function. However, disability failed to predict cognitive function. Several factors together may predict cognitive function in the Malaysian elderly population, and the variance accounted for it is large enough to be considered substantial. Key factor associated with the elderly's cognitive function seems to be psychosocial well-being. Thus, psychosocial well-being should be included in the elderly assessment, apart from medical conditions, both in clinical and community setting.

Effects of childhood trauma exposure and cortisol levels on cognitive functioning among breast cancer survivors.

PubMed

Kamen, Charles; Scheiber, Caroline; Janelsins, Michelle; Jo, Booil; Shen, Hanyang; Palesh, Oxana

2017-10-01

Cognitive functioning difficultiesin breast cancer patients receiving chemotherapy are common, but not all women experience these impairments. Exposure to childhood trauma may impair cognitive functioning following chemotherapy, and these impairments may be mediated by dysregulation of hypothalamic-pituitary-adrenal (HPA) axis function and cortisol slope. This study evaluated the association between childhood trauma exposure, cortisol, and cognition in a sample of breast cancer survivors. 56 women completed measures of trauma exposure (the Traumatic Events Survey), salivary cortisol, and self-reported cognitive functioning (the Functional Assessment of Cancer Therapy - Cognitive). We examined correlations between childhood trauma exposure and cognitive functioning, then used linear regression to control for factors associated with cognition (age, education, time since chemotherapy, depression, anxiety, and insomnia), and the MacArthur approach to test whether cortisol levels mediated the relationship between trauma and cognitive functioning. 57.1% of the sample had experienced at least one traumatic event in childhood, with 19.6% of the sample witnessing a serious injury, 17.9% experiencing physical abuse, and 14.3% experiencing sexual abuse. Childhood trauma exposure and cognitive functioning were moderately associated (r=-0.29). This association remained even when controlling for other factors associated with cognition; the final model explained 47% of the variance in cognitive functioning. The association between childhood trauma and cognitive functioning was mediated by steeper cortisol slope (partial r=0.35, p=0.02). Childhood trauma exposure is associated with self-reported cognitive functioning among breast cancer survivors and is mediated by cortisol dysregulation. Trauma should be considered, among other factors, in programs aiming to address cognition in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

PubMed

Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

2015-01-01

The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

Unmet Health Services Needs Among US Children with Developmental Disabilities: Associations with Family Impact and Child Functioning.

PubMed

Lindly, Olivia J; Chavez, Alison E; Zuckerman, Katharine E

To determine associations of unmet needs for child or family health services with (1) adverse family financial and employment impacts and (2) child behavioral functioning problems among US children with autism spectrum disorder (ASD), developmental delay (DD), and/or intellectual disability (ID). This was a secondary analysis of parent-reported data from the 2009 to 2010 National Survey of Children with Special Health Care Needs linked to the 2011 Survey of Pathways to Diagnosis and Services. The study sample (n = 3,518) represented an estimated 1,803,112 US children aged 6 to 17 years with current ASD, DD, and/or ID (developmental disabilities). Dependent variables included adverse family financial and employment impacts, as well as child behavioral functioning problems. The independent variables of interest were unmet need for (1) child health services and (2) family health services. Multivariable logistic regression models were fit to examine associations. Unmet need for child and family health services, adverse family financial and employment impacts, and child behavioral functioning problems were prevalent among US children with developmental disabilities. Unmet needs were associated with an increased likelihood of adverse family employment and financial impacts. Unmet needs were associated with an increased likelihood of child behavioral functioning problems the following year; however, this association was not statistically significant. Unmet needs are associated with adverse impacts for children with developmental disabilities and their families. Increased access to and coordination of needed health services following ASD, DD, and/or ID diagnosis may improve outcomes for children with developmental disabilities and their families.

Five clinical tests to assess balance following ball exercises and treadmill training in adult persons with intellectual disability.

PubMed

Carmeli, Eli; Bar-Chad, Shmuel; Lotan, Meir; Merrick, Joav; Coleman, Raymond

2003-08-01

Incidence rates of falling increase progressively with aging. Preventing or delaying the onset of functional decline is a crucial important goal, because more individuals with intellectual disability (ID) are living well into their sixth and seventh decades. The question of whether walking and ball exercises can effect balance performance has never been reported. This pilot study was conducted to determine the effects of therapeutic training on improving balance capabilities in adults with mild ID. The study included 13 women and 4 men, aged 50-67 years (mean age 56.5 years) residing in a residential care center. Five clinical tests were used to determine the "real" picture of the locomotor function and balance before and after the training protocol. Baseline values were determined using 2 control groups of age-matched adults with and without ID. The tests included modified get-up-and-go, full turn, forward reach, sit-to-stand, and one-legged standing. Therapeutic training for 6 months included dynamic ball exercises and treadmill walking with a 2-3% positive inclination. Participants in the program showed little to no improvement in terms of their static and dynamic balance compared to their initial values. Thus, only 2 of the tests showed statistical significance. Lack of improvement was noted in both postural and balance control in adults with mild ID as a result of 6 months of intervention by means of ball exercise and treadmill training.

Cardiovascular disease biomarkers on cognitive function in older adults: Joint effects of cardiovascular disease biomarkers and cognitive function on mortality risk.

PubMed

Loprinzi, Paul D; Crush, Elizabeth; Joyner, Chelsea

2017-01-01

Previous research demonstrates an inverse association between age and cardiovascular disease (CVD) biomarkers with cognitive function; however, little is known about the combined associations of CVD risk factors and cognitive function with all-cause mortality in an older adult population, which was the purpose of this study. Data from the 1999-2002 NHANES were used (N=2,097; 60+yrs), with mortality follow-up through 2011. Evaluated individual biomarkers included mean arterial pressure (MAP), high-sensitivity C-reactive protein (CRP), HDL-C, total cholesterol (TC), A1C, and measured body mass index (BMI). Cognitive function was assessed using the Digit Symbol Substitution Test (DSST). Further, 4 groups were created based on CVD risk and cognitive function. Group 1: high cognitive function and low CVD risk; Group 2: high cognitive function and high CVD risk; Group 3: low cognitive function and low CVD risk; Group 4: low cognitive function and high CVD risk. An inverse relationship was observed where those with more CVD risk factors had a lower (worse) cognitive function score. Compared to those in Group 1, only those in Group 3 and 4 had an increase mortality risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular basis of pharmacotherapies for cognition in Down syndrome

PubMed Central

Gardiner, Katheleen J.

2009-01-01

Intellectual disability (ID) in Down syndrome (DS) ranges from low normal to severely impaired, and has a significant impact on the quality of life of the individuals affected and their families. Because the incidence of DS remains at approximately one in 700 live births and the life span is now >50 years, development of pharmacotherapies for cognitive deficits is an important goal. DS is due to an extra copy of human chromosome 21 and has often been considered too complex a genetic abnormality to be amenable to intervention. However, recent successes in rescuing learning/memory impairments in a mouse model of DS suggest that this negative outlook may not be justified. In this article, we first review the DS phenotype, chromosome 21 gene content and mouse models, and then discuss recent successes and remaining challenges in the identification of targets for and preclinical evaluation of potential therapeutics. PMID:19963286

Are Non-Intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

ERIC Educational Resources Information Center

Ratto, Allison B.; Anthony, Bruno J.; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

2016-01-01

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black…

Is cognitive adaptation training (CAT) compensatory, restorative, or both?

PubMed

Fredrick, Megan M; Mintz, Jim; Roberts, David L; Maples, Natalie J; Sarkar, Sonali; Li, Xueying; Velligan, Dawn I

2015-08-01

Cognitive adaptation training (CAT) is a psychosocial treatment incorporating environmental supports including signs, checklists to bypass the cognitive deficits of schizophrenia. Our objective was to examine the association between CAT, functional outcomes, and cognitive test performance (cognition). The two research questions were as follows: 1) Does cognition mediate the effect of CAT intervention on functional outcome? 2) Does CAT impact cognitive test performance? A total of 120 participants with schizophrenia were randomized to one of three treatments: 1) CAT (weekly for 9months; monthly thereafter), 2) generic environmental supports (given to participants on clinic visits to promote adaptive behavior), or 3) treatment as usual (TAU). Assessments of cognition and functional outcome were conducted at baseline, 9 and 24months. Mediation analyses and mixed effects regression were conducted. Mediation analyses revealed that during the initial 9months, the direct path from treatment group to functional outcome on the primary measure was positive and highly significant. CAT significantly improved functional outcome compared to the other treatments. However, paths involving cognition were negligible. There was no evidence that cognition mediated improvement in functional outcomes. At 24months, cognition improved more in CAT compared to other treatment groups. The test for cognition mediating improvement in functional outcomes was not significant at this time point. However, improvement in functional outcome led to better performance on cognitive testing. We concluded that improvement in cognition is not a necessary condition for improvement in functional outcome and that greater engagement in functional behavior has a positive impact on cognition. Copyright © 2015 Elsevier B.V. All rights reserved.

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2008-04-08

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2010-10-05

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

Perceptions of Emotion Expression and Sibling–Parent Emotion Communication in Latino and Non-Latino White Siblings of Children With Intellectual Disabilities

PubMed Central

Lobato, Debra; Kao, Barbara; Plante, Wendy; Grullón, Edicta; Cheas, Lydia; Houck, Christopher; Seifer, Ronald

2013-01-01

Objective Examine general emotion expression and sibling–parent emotion communication among Latino and non-Latino white (NLW) siblings of children with intellectual disabilities (ID) and matched comparisons. Methods 200 siblings (ages 8–15 years) completed the newly developed Sibling–Parent Emotion Communication Scale and existing measures of general emotion expression and psychosocial functioning. Preliminary analyses evaluated scale psychometrics across ethnicity. Results Structure and internal consistency of the emotion expression and communication measures differed by respondent ethnicity. Latino siblings endorsed more general emotion expression problems and marginally lower sibling–parent emotion communication than NLW siblings. Siblings of children with ID reported marginally more general emotion expression problems than comparisons. Emotion expression problems and lower sibling–parent emotion communication predicted more internalizing and somatic symptoms and poorer personal adjustment, regardless of ID status. Siblings of children with ID endorsed poorer personal adjustment. Conclusion Cultural differences in emotion expression and communication may increase Latino siblings’ risk for emotional adjustment difficulties. PMID:23459309

Decreased Openness to Experience Is Associated with Migraine-Type Headaches in Subjects with Lifetime Depression.

PubMed

Magyar, Mate; Gonda, Xenia; Pap, Dorottya; Edes, Andrea; Galambos, Attila; Baksa, Daniel; Kocsel, Natalia; Szabo, Edina; Bagdy, Gyorgy; Elliott, Rebecca; Kokonyei, Gyongyi; Juhasz, Gabriella

2017-01-01

Migraine and depression frequently occur as comorbid conditions, and it has been hypothesized that migraine with and without depression may have a different genetic background. A distinct personality trait constellation has been described in migraineurs. Less attention, however, was paid to personality differences in migraineurs with and without depression which may also shed light on differences in the neurobiological, background. The aim of our study was to investigate big five personality traits, headaches, and lifetime depression (DEP) in a large European general population sample. Relationship between DEP, Big Five Inventory personality traits, and headaches identified by the ID-Migraine Questionnaire were investigated in 3,026 individuals from Budapest and Manchester with multivariate and logistic regression analyses. Both DEP and migraine(ID) showed differences in personality traits. Neuroticism was an independent risk factor for both conditions while a significant interaction effect appeared between the two in the case of openness. Namely, subjects with migraine(ID) and without DEP scored higher on openness compared to those who had depression. While we confirmed previous results that high neuroticism is a risk factor for both depression and migraine, openness to experience was significantly lower in the co-occurrence of migraine and depression. Our results suggest that increased openness, possibly manifested in optimal or advantageous cognitive processing of pain experience in migraine may decrease the risk of co-occurrence of depression and migraine and thus may provide valuable insight for newer prevention and intervention approaches in the treatment of these conditions.

An RFID Based Smart Feeder for Hummingbirds.

PubMed

Ibarra, Vicente; Araya-Salas, Marcelo; Tang, Yu-ping; Park, Charlie; Hyde, Anthony; Wright, Timothy F; Tang, Wei

2015-12-16

We present an interdisciplinary effort to record feeding behaviors and control the diet of a hummingbird species (Phaethornis longirostris, the long-billed hermit or LBH) by developing a Radio Frequency Identification (RFID) based smart feeder. The system contains an RFID reader, a microcontroller, and a servo-controlled hummingbird feeder opener; the system is presented as a tool for studying the cognitive ability of the LBH species. When equipped with glass capsule RFID tags (which are mounted on the hummingbird), the smart feeder can provide specific diets for predetermined sets of hummingbirds at the discretion of biologists. This is done by reading the unique RFID tag on the hummingbirds and comparing the ID number with the pre-programmed ID numbers stored in the smart feeder. The smart feeder records the time and ID of each hummingbird visit. The system data is stored in a readily available SD card and is powered by two 9 V batteries. The detection range of the system is approximately 9-11 cm. Using this system, biologists can assign the wild hummingbirds to different experimental groups and monitor their diets to determine if they develop a preference to any of the available nectars. During field testing, the smart feeder system has demonstrated consistent detection (when compared to detections observed by video-recordings) of RFID tags on hummingbirds and provides pre-designed nectars varying water and sugar concentrations to target individuals. The smart feeder can be applied to other biological and environmental studies in the future.

An RFID Based Smart Feeder for Hummingbirds

PubMed Central

Ibarra, Vicente; Araya-Salas, Marcelo; Tang, Yu-ping; Park, Charlie; Hyde, Anthony; Wright, Timothy F.; Tang, Wei

2015-01-01

We present an interdisciplinary effort to record feeding behaviors and control the diet of a hummingbird species (Phaethornis longirostris, the long-billed hermit or LBH) by developing a Radio Frequency Identification (RFID) based smart feeder. The system contains an RFID reader, a microcontroller, and a servo-controlled hummingbird feeder opener; the system is presented as a tool for studying the cognitive ability of the LBH species. When equipped with glass capsule RFID tags (which are mounted on the hummingbird), the smart feeder can provide specific diets for predetermined sets of hummingbirds at the discretion of biologists. This is done by reading the unique RFID tag on the hummingbirds and comparing the ID number with the pre-programmed ID numbers stored in the smart feeder. The smart feeder records the time and ID of each hummingbird visit. The system data is stored in a readily available SD card and is powered by two 9 V batteries. The detection range of the system is approximately 9–11 cm. Using this system, biologists can assign the wild hummingbirds to different experimental groups and monitor their diets to determine if they develop a preference to any of the available nectars. During field testing, the smart feeder system has demonstrated consistent detection (when compared to detections observed by video-recordings) of RFID tags on hummingbirds and provides pre-designed nectars varying water and sugar concentrations to target individuals. The smart feeder can be applied to other biological and environmental studies in the future. PMID:26694402

Physical Activity and Cognitive Functioning of Children: A Systematic Review.

PubMed

Bidzan-Bluma, Ilona; Lipowska, Małgorzata

2018-04-19

Childhood is an important and sensitive period for cognitive development. There is limited published research regarding the relationship between sports and cognitive functions in children. We present studies that demonstrate the influence of physical activity on health, especially a positive correlation between sports and cognitive functions. The keywords “children, cognition, cognitive function, physical activity, and brain” were searched for using PsycInfo, Medline, and Google Scholar, with publication dates ranging from January 2000 to November 2017. Of the 617 results, 58 articles strictly connected to the main topics of physical activity and cognitive functioning were then reviewed. The areas of attention, thinking, language, learning, and memory were analyzed relative to sports and childhood. Results suggest that engaging in sports in late childhood positively influences cognitive and emotional functions. There is a paucity of publications that investigate the impact of sports on pre-adolescents’ cognitive functions, or explore which cognitive functions are developed by which sporting disciplines. Such knowledge would be useful in developing training programs for pre-adolescents, aimed at improving cognitive functions that may guide both researchers and practitioners relative to the wide range of benefits that result from physical activity.

Generation of dendritic cells from positively selected CD14+ monocytes for anti-tumor immunotherapy.

PubMed

Curti, Antonio; Isidori, Alessandro; Ferri, Elisa; Terragna, Carolina; Neyroz, Paolo; Cellini, Claudia; Ratta, Marina; Baccarani, Michele; Lemoli, Roberto M

2004-07-01

Peripheral blood CD14+ monocytes from multiple myeloma (MM) patients can be induced to differentiate into fully functional, mature, CD83+ dendritic cells (DCs) which are highly efficient in priming autologous T lymphocytes in response to the patient-specific tumor idiotype (Id). We have recently scaled up our manufacturing protocol for application in a phase I-II clinical trial of anti-Id vaccination with DCs in MM patients. Elegible patients received a series of by-monthly immunizations consisting of three subcutaneous and two intravenous injections of Id-keyhole limpet hemocyanin (KLH)-pulsed DCs (5 x -, 10 x -, 50 x 10(6) cells and 10 x -, 50 x 10(6) cells, respectively). To generate DCs, monocytes were labeled with clinical grade anti-CD14 conjugates and positively selected by immunomagnetic separation. Cells were then cultured, according to Good Manufacturing Practice guidelines, in FCS-free medium in cell culture bags, and differentiated to DCs with GM-CSF plus IL-4 followed by TNF-alpha or, more recently, by a cocktail of IL-1beta, IL-6, TNF-alpha and prostaglandin-E2. Before maturation, Mo-DCs were pulsed with the autologous Id as whole protein or Id (VDJ)-derived HLA class I restricted peptides. Ten MM patients, who had been treated with two courses of high-dose chemotherapy with peripheral blood stem cell support, entered into the clinical study. CD14+ monocytes were enriched from 16.1+/-5.7% to 95.5+/-3.2% (recovery 67.9+/-15%, viability > 97%). After cell culture, phenotypic analysis showed that 89.6+/-6.6% of the cells were mature DCs. We obtained 2.89+/-1 x 10(8) DCs/leukapheresis which represented 24.5+/-9% of the initial number of CD14+ cells. Notably, the cytokine cocktail induced a significantly higher percentage and yield (31+/-10.9 of initial CD14+ cells) of DCs than TNF-alpha alone, secretion of larger amounts of IL-12, potent stimulatory activity on allogeneic and autologous T cells. Storage in liquid nitrogen did not modify the phenotype or functional characteristics of pre-loaded DCs. The recovery of thawed, viable DCs, was 78+/-10%. Thus, positive selection of CD14+ monocytes allows the generation of a uniform population of mature pre-loaded DCs which can be cryopreserved with no effects on phenotype and function and are suitable for clinical trials. Based on these results, a DCs-based phase II trial of anti-Id vaccination with VDJ-derived HLA class I-restricted peptides and KLH is underway for lymphoma patients.

Relationship between cardiac autonomic function and cognitive function in Alzheimer's disease.

PubMed

Nonogaki, Zen; Umegaki, Hiroyuki; Makino, Taeko; Suzuki, Yusuke; Kuzuya, Masafumi

2017-01-01

Alzheimer's disease (AD) affects many central nervous structures and neurotransmitter systems. These changes affect not only cognitive function, but also cardiac autonomic function. However, the functional relationship between cardiac autonomic function and cognition in AD has not yet been investigated. The objective of the present study was to evaluate the association between cardiac autonomic function measured by heart rate variability and cognitive function in AD. A total of 78 AD patients were recruited for this study. Cardiac autonomic function was evaluated using heart rate variability analysis. Multiple linear regression analysis was used to model the association between heart rate variability and cognitive function (global cognitive function, memory, executive function and processing speed), after adjustment for covariates. Global cognitive function was negatively associated with sympathetic modulation (low-to-high frequency power ratio). Memory performance was positively associated with parasympathetic modulation (high frequency power) and negatively associated with sympathetic modulation (low-to-high frequency power ratio). These associations were independent of age, sex, educational years, diabetes, hypertension and cholinesterase inhibitor use. Cognitive function, especially in the areas of memory, is associated with cardiac autonomic function in AD. Specifically, lower cognitive performance was found to be associated with significantly higher cardiac sympathetic and lower parasympathetic function in AD. Geriatr Gerontol Int 2017; 17: 92-98. © 2015 Japan Geriatrics Society.

The Influence of Frontal Lobe Tumors and Surgical Treatment on Advanced Cognitive Functions.

PubMed

Fang, Shengyu; Wang, Yinyan; Jiang, Tao

2016-07-01

Brain cognitive functions affect patient quality of life. The frontal lobe plays a crucial role in advanced cognitive functions, including executive function, meta-cognition, decision-making, memory, emotion, and language. Therefore, frontal tumors can lead to serious cognitive impairments. Currently, neurosurgical treatment is the primary method to treat brain tumors; however, the effects of the surgical treatments are difficult to predict or control. The treatment may both resolve the effects of the tumor to improve cognitive function or cause permanent disabilities resulting from damage to healthy functional brain tissue. Previous studies have focused on the influence of frontal lesions and surgical treatments on patient cognitive function. Here, we review cognitive impairment caused by frontal lobe brain tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognition and Context: Rural-Urban Differences in Cognitive Aging Among Older Mexican Adults.

PubMed

Saenz, Joseph L; Downer, Brian; Garcia, Marc A; Wong, Rebeca

2017-04-01

To describe differences in cognitive functioning across rural and urban areas among older Mexican adults. We include respondents aged 50+ in the 2012 Mexican Health and Aging Study (MHAS). Cognitive functioning by domain is regressed as a function of community size. The role of educational attainment in explaining rural/urban differences in cognitive functioning is examined. Respondents residing in more rural areas performed worse across five cognitive domains. The majority, but not all, of the association between community size and cognitive functioning was explained by lower education in rural areas. Respondents residing in more rural areas were disadvantaged in terms of cognitive functioning compared with those residing in more urban areas. Poorer cognitive functioning in late life may be the result of historical educational disadvantage in rural areas or selection through migration from rural to urban regions for employment.

Social isolation and cognitive function in Appalachian older adults.

PubMed

DiNapoli, Elizabeth A; Wu, Bei; Scogin, Forrest

2014-03-01

Investigating the relation between social isolation and cognitive function will allow us to identify components to incorporate into cognitive interventions. Data were collected from 267 Appalachian older adults (M = 78.5, range 70-94 years). Overall cognitive functioning and specific cognitive domains were assessed from data of a self-assembled neuropsychological battery of frequently used tasks. Social isolation, social disconnectedness, and perceived isolation were measured from the Lubben Social Network scale-6. Results indicated a significant positive association between all predictor variables (e.g., social isolation, social disconnectedness, and perceived isolation) and outcome variables (e.g., overall cognitive function, memory, executive functioning, attention, and language abilities). Perceived isolation accounted for nearly double the amount of variance in overall cognitive functioning than social disconnectedness (10.2% vs. 5.7%). Findings suggest that social isolation is associated with poorer overall cognitive functioning and this remains true across varied cognitive domains. © The Author(s) 2012.

Synergistic effects of aerobic exercise and cognitive training on cognition, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline: study protocol for a randomized controlled trial.

PubMed

Yeh, Ting-Ting; Wu, Ching-Yi; Hsieh, Yu-Wei; Chang, Ku-Chou; Lee, Lin-Chien; Hung, Jen-Wen; Lin, Keh-Chung; Teng, Ching-Hung; Liao, Yi-Han

2017-08-31

Aerobic exercise and cognitive training have been effective in improving cognitive functions; however, whether the combination of these two can further enhance cognition and clinical outcomes in stroke survivors with cognitive decline remains unknown. This study aimed to determine the treatment effects of a sequential combination of aerobic exercise and cognitive training on cognitive function and clinical outcomes. Stroke survivors (n = 75) with cognitive decline will be recruited and randomly assigned to cognitive training, aerobic exercise, and sequential combination of aerobic exercise and cognitive training groups. All participants will receive training for 60 minutes per day, 3 days per week for 12 weeks. The aerobic exercise group will receive stationary bicycle training, the cognitive training group will receive cognitive-based training, and the sequential group will first receive 30 minutes of aerobic exercise, followed by 30 minutes of cognitive training. The outcome measures involve cognitive functions, physiological biomarkers, daily function and quality of life, physical functions, and social participation. Participants will be assessed before and immediately after the interventions, and 6 months after the interventions. Repeated measures of analysis of variance will be used to evaluate the changes in outcome measures at the three assessments. This trial aims to explore the benefits of innovative intervention approaches to improve the cognitive function, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline. The findings will provide evidence to advance post-stroke cognitive rehabilitation. ClinicalTrials.gov, NCT02550990 . Registered on 6 September 2015.

Redefining the MED13L syndrome

PubMed Central

Adegbola, Abidemi; Musante, Luciana; Callewaert, Bert; Maciel, Patricia; Hu, Hao; Isidor, Bertrand; Picker-Minh, Sylvie; Le Caignec, Cedric; Delle Chiaie, Barbara; Vanakker, Olivier; Menten, Björn; Dheedene, Annelies; Bockaert, Nele; Roelens, Filip; Decaestecker, Karin; Silva, João; Soares, Gabriela; Lopes, Fátima; Najmabadi, Hossein; Kahrizi, Kimia; Cox, Gerald F; Angus, Steven P; Staropoli, John F; Fischer, Ute; Suckow, Vanessa; Bartsch, Oliver; Chess, Andrew; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M; Kalscheuer, Vera M

2015-01-01

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits. PMID:25758992

Redefining the MED13L syndrome.

PubMed

Adegbola, Abidemi; Musante, Luciana; Callewaert, Bert; Maciel, Patricia; Hu, Hao; Isidor, Bertrand; Picker-Minh, Sylvie; Le Caignec, Cedric; Delle Chiaie, Barbara; Vanakker, Olivier; Menten, Björn; Dheedene, Annelies; Bockaert, Nele; Roelens, Filip; Decaestecker, Karin; Silva, João; Soares, Gabriela; Lopes, Fátima; Najmabadi, Hossein; Kahrizi, Kimia; Cox, Gerald F; Angus, Steven P; Staropoli, John F; Fischer, Ute; Suckow, Vanessa; Bartsch, Oliver; Chess, Andrew; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M; Kalscheuer, Vera M

2015-10-01

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.

Executive Function in Children with Intellectual Disability--The Effects of Sex, Level and Aetiology of Intellectual Disability

ERIC Educational Resources Information Center

Memisevic, H.; Sinanovic, O.

2014-01-01

Background: Executive function is very important in the children's overall development. The goal of this study was to assess the executive function in children with intellectual disability (ID) through the use of the Behavior Rating Inventory of Executive Function (BRIEF) teacher version. An additional goal was to examine the differences in…