TD Group Research Articles

Effects of topical 0.8% piroxicam and 50+ sunscreen filters on actinic keratosis in hypertensive patients treated with or without photosensitizing diuretic drugs: an observational cohort study

BackgroundPhotosensitizing diuretics use (especially thiazide compounds) is associated with a significantly higher risk of squamous cell carcinoma (SCC). Actinic keratosis (AK) is a precursor of SCC.Study aimTo evaluate in a prospective cohort study the efficacy of topical piroxicam 0.8% and sunscreen 50+ (ACTX) in the treatment of AK in hypertensive subjects with or without TD treatment.Subjects and methodsA total of 119 hypertensive subjects with multiple AK (39 under chronic TD treatment; and 80 treated with other non-TD, non-photosensitizing antihypertensive drugs) were enrolled after their informed consent in a 6-month observational cohort study. All the subjects were treated with ACTX twice daily. The primary endpoint was the evolution of AK lesions at baseline, after 3 and 6 months. The secondary endpoint was the clearance of AK target lesions and field of cancerization by dermoscopic evaluation using a score evaluating erythema, scaling, pigmentation, and follicular plugs (ESPFP score; ranging from 0 to 20). An investigator, unaware of the type of antihypertensive treatments (TD or non-TD), performed all the clinical and dermoscopy evaluations.ResultsAt baseline, AK mean (SD) lesion number in TD group was 14.1(4) and 14.6(4) in the non-TD group. ESPFP mean (SD) score at baseline was 5.8(1.2) in both groups. A significant reduction of AK lesions in comparison with baseline was observed in both groups. A statistically significant greater reduction was observed in TD in comparison with the non-TD group (−54% vs −32%). ESPFP score was reduced in a higher proportion in the TD group in comparison with the non-TD group (−60% vs −37%, respectively). ACTX treatment was very well tolerated.ConclusionIn hypertensive subjects with multiple AK, the topical use of ACTX is associated with a significant reduction of lesions count with an improvement in the field cancerization. The clinical efficacy is more pronounced in subjects under thiazide diuretics treatment.

Maternal metabolic profile predicts high or low risk of an autism pregnancy outcome

BackgroundCurrently there is no test for pregnant mothers that can predict the probability of having a child that will be diagnosed with autism spectrum disorder (ASD). Recent estimates indicate that if a mother has previously had a child with ASD, the risk of having a second child with ASD is ∼18.7% (High Risk) whereas the risk of ASD in the general population is ∼1.7% (Low Risk). MethodsIn this study, metabolites of the folate-dependent transmethylation and transsulfuration biochemical pathways of pregnant mothers were measured to determine whether or not the risk of having a child with autism could be predicted by her metabolic profile. Pregnant mothers who have had a child with autism before were separated into two groups based on the diagnosis of their child whether the child had autism (ASD) or not (TD). Then these mothers were compared to a group of control mothers who have not had a child with autism before. A total of 107 mothers were in the High Risk category and 25 mothers in the Low Risk category. The High Risk category was further separated into 29 mothers in the ASD group and 78 mothers in the TD group. ResultsThe metabolic results indicated that among High Risk mothers, it was not possible to predict an autism pregnancy outcome. However, the metabolic profile was able to predict with approximately 90% sensitivity and specificity whether a mother fell into the High Risk group (18.7% risk) or Low Risk group (1.7% risk). ConclusionsBased upon these measurements it is not possible to determine during a pregnancy if a child will be diagnosed with ASD by age 3. However, differences in the folate-dependent transmethylation and transsulfuration metabolites are indicative of the risk level (High Risk of 18.7% vs. Low Risk of 1.7%) of the mother for having a child with ASD.

Deficits in auditory sensory discrimination among children with attention-deficit/hyperactivity disorder.

Research into children with attention-deficit/hyperactivity disorder (ADHD) has focused on complex cognitive dysfunction, but less attention has been paid to sensory perception processes underlying the symptoms of ADHD. Based on signal detection theory, the present study compared the sensory discrimination ability and decision bias of children with and without ADHD. It also investigated the differences between ADHD with predominantly inattentive (ADHDi) and combined presentations (ADHDc). The sample of 75 children and adolescents with ADHD (24 ADHDi, 51 ADHDc) (16 females and 59 males) and 22 typical developing controls (TD) (8 females and 14 males) completed an auditory signal detection task. Participants were asked to detect signals against levels of transient background noise (35, 45, 55, and 65dB). The results showed that with the increase of noise levels, both the ADHD and TD groups demonstrated decreased sensory discrimination. Although both groups successfully detected signal against noise levels from 35 to 55dB, the ADHD group showed lower discrimination ability than that of the TD group. For decision bias, no group difference was found. Further comparisons regarding the predominant symptom presentation of ADHD sub-groups showed no differences. Current research has suggested that the deficit in ADHD people's signal detection performance can be attributed to sensory discrimination rather than decision bias. We suggest that background noise should be taken into account when using auditory stimuli to investigate cognitive functions in people with ADHD.

The effects of different GSK-3β inhibitors and dose-response relationship in severe acute pancreatitis associated kidney injury in rats

Objective To observe the dose-response relationship of the GSK-3β inhibitor TDZD-8 in severe acute pancreatitis (SAP) associated kidney injury in rats. In order to identify the most effective class of GSK-3β inhibitor and its effective and reasonable safe dose in SAP associated kidney injury model in rats by comparing three kinds of frequently-used GSK-3β inhibitor TDZD-8, lithium chloride (LiCL), SB216763 in this model. Methods Totally 96 SPF male Wistar rats were randomly(random number) divided into 8 groups (n=12): sham operation group (SO group), severe acute pancreatitis group (SAP group), TDZD-8 pretreatment groups (TD group, marked TD1, TD2, TD3 and TD4 group, respectively) at different dosage (0.25, 0.5, 1.0 and 2.0 mg/kg), LiCL pretreatment groups (L group, 40 mg/kg), and SB216763 pretreatment group (SB group, 1 mg/kg). SAP model was induced by retrograde infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats in each group were sacrificed at 12 h after operation. Then the mortality, quantity of ascites, serum AMY, Cr, BUN and ALT were recorded, and the pathological changes of pancreatic tissues and kidney tissues were observed. Results Compared with the SO group, the levels of ascites, serum AMY, Cr, BUN, ALT and pancreatic and renal pathologic score in the SAP group were all significantly increased (P 0.05), but the levels of AMY, Cr, BUN, ALT, pancreatic and renal pathologic score were significantly reduced in the TD3 group than those in the L and SB groups (P 0.05), while p-GSK-3β ser9 protein expression in the SAP group was lower than that in the SO group (P<0.05), and p-GSK-3β ser9 protein expression in the TD3, L and SB groups were stronger than that in the SAP group. Among them, p-GSK-3β ser9 protein expression was highest in the TD3 group, followed by the L group, finally the SB group, and the differences were statistically significant (P<0.05). Conclusions Among the three different GSK-3β inhibitors, TDZD-8 is the most effective GSK-3β inhibitor for SAP associated with kidney injury in rats. The GSK-3β inhibitor TDZD-8 1 mg/kg administered intravenously is safe, effective and optimal dosage for attenuating the severity of severe acute pancreatitis associated with kidney injury. Key words: Severe acute pancreatitis; Kidney injury; Glycogen synthase kinase-3β inhibitor; TDZD-8; Dose-response relationship

Emotional Expressivity in Toddlers With Autism Spectrum Disorder

There is a prevailing notion that children with autism spectrum disorder (ASD) exhibit intense negative and attenuated positive emotions, although the empirical evidence regarding their emotional expressiveness (EE) is limited. Given the importance of emotions in shaping social and cognitive development, we examined intensity and valence of EE and links between EE and autism severity and parent-reported temperament in ASD. Toddlers (aged 21.2 months) with ASD (n= 43), developmental delay (DD, n= 16), and typical development (TD, n= 40) underwent standardized probes designed to induce anger, joy, and fear. Intensity of EE through facial and vocal channels were coded offline. Autism severity and temperament were quantified using the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Early Childhood Behavior Questionnaire (ECBQ). The ASD group exhibited less intense fear compared to both the DD and TD groups, more intense anger than DD but not TD, with no differences in joy intensity. All groups showed similar levels of incongruous negative EE. Intensity of fear and anger were not associated with severity of autism symptoms, but lower intensity of joy was related to greater autism severity. Expressed fear and joy were associated with temperament. The study provides no support for a negative emotionality bias in ASD. Instead, toddlers with ASD display a muted response to threat and an accentuated response to goal blockage, whereas the ability to express positive emotions appears intact. Negative emotionality and social disability dimensions are independent. The study demonstrates the complexity of EE in ASD and motivates investigations into underlying mechanisms as well as its role in shaping complex phenotypes of affected children.

Receptive Language Skills in Slovak-Speaking Children With Intellectual Disability: Understanding Words, Sentences, and Stories.

The study aims to describe receptive language skills in children with intellectual disability (ID) and to contribute to the debate on deviant versus delayed language development. This is the 1st study of receptive skills in children with ID who speak a Slavic language, providing insight into how language development is affected by disability and also language typology. Twenty-eight Slovak-speaking children participated in the study (14 children with ID and 14 typically developing [TD] children matched on nonverbal reasoning abilities). The children were assessed by receptive language tasks targeting words, sentences, and stories, and the groups were compared quantitatively and qualitatively. The groups showed similar language profiles, with a better understanding of words, followed by sentences, with the poorest comprehension for stories. Nouns were comprehended better than verbs; sentence constructions also showed a qualitatively similar picture, although some dissimilarities emerged. Verb comprehension was strongly related to sentence comprehension in both groups and related to story comprehension in the TD group only. The findings appear to support the view that receptive language skills follow the same developmental route in children with ID as seen in younger TD children, suggesting that language development is a robust process and does not seem to be differentially affected by ID even when delayed.

Icariin: a Potential Compound for the Recovery of Tibial Dyschondroplasia Affected Chicken Via Up-Regulating BMP-2 Expression

BackgroundTibial dyschondroplasia (TD) is a skeletal disease of fast growing chicken and other avian species. It is characterized by an avascular and non-mineralized growth plate, which leads to a deformed tibial bone and lameness. Unfortunately, this disease is not only responsible for causing huge economic losses but also raises animal welfare concerns. Icariin is a flavonoid, which is isolated from Epimedium pubescens herb, and it has been used to cure different diseases including bone fractures and osteoporosis.ResultsWe designed this experiment to use icariin for the treatment of TD affect chickens; for this purpose, a total of 180 chicks were equally divided into three groups: control, TD and icariin. All the three groups were offered ad libitum same normal standard diet with an addition of thiram (50 mg/kg) from 3rd day to 7th day in TD and icariin group in order to induce TD in chickens. After the induction of TD, the chickens in icariin groups were fed standard diet with an addition of icariin at the rate of 10 mg/kg in drinking water to check the therapeutic effect of this flavonoid on TD. Our results showed that the icariin helped in restoring the TD lesion into a normal structure with significantly (P < 0.05) up-regulating the bone morphogenetic protein-2 (BMP-2) expression in the tibial growth plates (GP).ConclusionsIcariin increased the vascular area in the growth plate and decreased the average TD score. In conclusion, this study shows that icariin is a potential compound for the recovery of TD affected chickens via up-regulating the BMP-2 expression without posing a threat of ingestion of toxic veterinary drug residues to human beings upon the consumption of treated chickens.

Behavioral Own-Body-Transformations in Children and Adolescents With Typical Development, Autism Spectrum Disorder, and Developmental Coordination Disorder

Background: In motor imitation, taking a partner's perspective often involves a mental body transformation from an embodied, ego-centered viewpoint to a disembodied, hetero-centered viewpoint. Impairments of both own-body-transformation (OBT) and abnormalities in visual-spatial processing have been reported in patients with neurodevelopmental disorders including autism spectrum disorder (ASD). In the context of a visual-motor interactive task, studying OBT impairments while disentangling the contribution of visual-spatial impairments associated with motor coordination problems has not been investigated.Methods: 85 children and adolescents (39 controls with typical development, TD; 29 patients with ASD; 17 patients with developmental coordination disorder, DCD), aged 6–19 years, participated in a behavioral paradigm in which participants interacted with a virtual tightrope walker (TW) standing and moving with him. The protocol enables to distinguish ego-centered and hetero-centered perspectives.Results: We show that (1) OBT was possible but difficult for children with neurodevelopmental disorders, as well as for TD children, when the task required the participant to perform a mental rotation in order to adopt a hetero-centered perspective. (2) Using multivariate models, hetero-centered perspective score was significantly associated with age, TW orientation, latency, and diagnosis. ASD and TD groups' performances were close and significantly correlated with age. However, it was not the case for DCD, since this group was specifically handicapped by visual-spatial impairments. (3) ASD and DCD did not perform similarly: motor performance as shown by movement amplitude was better in DCD than ASD. ASD motor response was more ambiguous and hardly readable.Conclusion: Changing perspective in a spatial environment is possible for patients with ASD although delayed compared with TD children. In patients with DCD, their visual-spatial impairments negatively modulated their performances in the experiment.

Immunogenicity and safety of a second booster dose of an acellular pertussis vaccine combined with reduced antigen content diphtheria-tetanus toxoids 10 years after a first booster in adolescence: An open, phase III, non-randomized, multi-center study

ABSTRACTPertussis is a highly contagious disease, for which periodic peaks in incidence and an increasing number of outbreaks have been observed over the last decades. The reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine (Tdap) can be used to boost individuals aged ≥10 years, vaccinated in infancy with a diphtheria-tetanus-acellular pertussis vaccine (DTaP), to reduce pertussis morbidity and maintain protection against diphtheria and tetanus throughout adolescence and adulthood. This phase III, open-label, non-randomized, multicenter follow-up study (NCT01738477) enrolled 19–30-year-old participants from the United States who had received booster vaccination 10 years earlier with either Tdap (Tdap group) or Td (Td group). In total, 128 (Tdap group) and 37 (Td group) participants received Tdap vaccination. After administration of Tdap, all participants were seroprotected (antibody concentrations ≥0.1 international units [IU]/ml) against diphtheria and tetanus. Immune responses to a second Tdap dose in the Tdap group were shown to be non-inferior to responses elicited by a first Tdap dose in the Td group for diphtheria and tetanus and to a 3-dose DTaP vaccination during infancy for pertussis antigens (primary objectives). Post-booster vaccination, all participants in both groups had antibody concentrations above assay cut-offs and antibody geometric mean concentrations increased by 3.8–15.5-fold compared to pre-booster levels for all antigens. The incidence of adverse events was similar in the Td (80.6%) and Tdap (85.6%) groups (no serious adverse events reported). A Tdap dose administered after previous Td or Tdap vaccination was shown to be immunogenic and well-tolerated in young adults, supporting repeated vaccination with Tdap at 10-year intervals.

New Methods for the Fabrication of Composites for Supercapacitor Electrodes with High Active Mass Loading

ABSTRACTMnO2-multiwalled carbon nanotube (MWCNT) supercapacitor electrodes with active mass loading of 30-45 mg cm-2 were prepared. In method 1, MnO2 and MWCNT were dispersed using 3,4-dihydroxybenzaldehyde (DHB) and toluidine blue (TD), respectively. The Schiff base formation between amino group of TD and aldehyde group of DHB facilitated improved mixing of MnO2 and MWCNT. In method 2, gallocyanine (GC) was used as a co-dispersant for MnO2 and MWCNT. The catecholate type bonding of DHB and GC allowed for adsorption of the dispersant molecules on MnO2 nanoparticles. The electrodes, prepared by method 1 showed higher capacitance, compared to the electrode, prepared by method 2. The highest capacitance of 7.8 F cm-2 (173 F g-1, 139 F cm-3) was obtained at a scan rate of 2 mV s-1 and active mass loading of 45 mg cm-2.

Understanding Disorder Within Variation: Production of English Grammatical Forms by English Language Learners.

This study examines English performance on a set of 11 grammatical forms in Spanish-English bilingual, school-age children in order to understand how item difficulty of grammatical constructions helps correctly classify language impairment (LI) from expected variability in second language acquisition when taking into account linguistic experience and exposure. Three hundred seventy-eight children's scores on the Bilingual English-Spanish Assessment-Middle Extension (Peña, Bedore, Gutiérrez-Clellen, Iglesias, & Goldstein, 2008) morphosyntax cloze task were analyzed by bilingual experience groups (high Spanish experience, balanced English-Spanish experience, high English experience, ability (typically developing [TD] vs. LI), and grammatical form. Classification accuracy was calculated for the forms that best differentiated TD and LI groups. Children with LI scored lower than TD children across all bilingual experience groups. There were differences by grammatical form across bilingual experience and ability groups. Children from high English experience and balanced English-Spanish experience groups could be accurately classified on the basis of all the English grammatical forms tested except for prepositions. For bilinguals with high Spanish experience, it was possible to rule out LI on the basis of grammatical production but not rule in LI. It is possible to accurately identify LI in English language learners once they use English 40% of the time or more. However, for children with high Spanish experience, more information about development and patterns of impairment is needed to positively identify LI.

T15. LONGITUDINAL ASSOCIATIONS BETWEEN CHILDHOOD SALIVARY CORTISOL LEVELS AND PRODROMAL SYMPTOMS IN LATE ADOLESCENCE: FINDINGS FROM A HIGH-RISK COHORT

BackgroundIndividuals with established psychosis are characterised by a distinct pattern of hypothalamic-pituitary-adrenal (HPA) axis dysfunctions which include both elevated daytime cortisol levels and a blunted cortisol awakening response (CAR). Whilst these patterns of dysfunction have also been observed among those at elevated risk for the disorder, longitudinal studies are scarce. As such, the relevance of these HPA axis abnormalities for the progression of psychopathology in high-risk populations is unknown. Utilising data from a well-characterised, longitudinal cohort of youth at elevated risk for schizophrenia and their typically-developing peers (The Child Health and Development Study), we aimed to investigate the extent to which HPA axis function determined in childhood is a significant predictor of putative prodromal status and psychopathology in late adolescence/early adulthood.MethodsThe sample comprised high-risk individuals who presented either multiple antecedents of schizophrenia (developmental delays, psychopathology, and psychotic-like experiences: ASz=21) or a family history of illness (FHx=13), and typically-developing youth with neither antecedents nor a family history (TD=36). Participants were recruited at age 9–12 years using a community screening method and assessed biennially throughout adolescence. At the age 11–14 years assessment phase, participants collected salivary cortisol samples in their home environment which were used to determine diurnal cortisol secretion and the CAR. At the age 17–21 years assessment phase, participants completed measures of prodromal symptoms (Prodromal Questionnaire: PQ), depression (Quick Inventory of Depressive Symptomatology questionnaire: QIDS), and anxiety (Social Interaction Anxiety Scale: SIAS). Established PQ thresholds were used to identify participants who met probable prodromal status. Logistic and linear regression analyses were used to examine the extent to which salivary cortisol measures at age 11–14 years predicted probable prodromal status and continuous psychopathology measures at 17–21 years, respectively.ResultsRelative to the TD group, ASz youth were characterised by higher depression (B=0.24, p=0.05) and disorganised symptoms (B=0.36, p=0.007) at 17–21 years whilst FHx youth obtained higher scores on the PQ general symptoms scale (B=0.24, p=0.048). Analyses performed in the total sample indicated that the CAR was negatively associated with depression symptoms (B=-0.28, p=0.006) and PQ negative symptoms (B=-0.30, p=0.004) at age 17–21 years. Positive associations were observed between diurnal cortisol and positive (B=0.41, p=0.02), disorganised (B=0.30, p=0.04), and general (B=0.29, p=0.03) PQ symptoms. Diurnal cortisol levels were also significantly associated with probable prodromal status at follow-up (OR=1.04, p=0.04). No significant interactions were observed between group status and salivary cortisol levels in any model. After adjustment for potential confounders (age, follow-up time, sex, BMI, and pubertal status), the CAR continued to show significant associations with both depression (p=0.006) and PQ negative symptoms (p=0.007) whilst only a statistical trend was observed for the relationship between diurnal cortisol levels and positive symptoms (p=0.055).DiscussionThe current study is the first to examine the extent to which HPA axis function can predict development of prodromal symptoms in a high-risk cohort. Our finding that more abnormal HPA axis function (i.e., a decreased CAR and higher diurnal cortisol) at age 11–14 years is associated with both prodromal and depression symptoms at age 17–21 has important implications for aetiological theories and for clinical practice.

Are the components of social reciprocity transdiagnostic across pediatric neurodevelopmental disorders? Evidence for common and disorder-specific social impairments

Deficits in social communication are a core feature of autism spectrum disorder (ASD), yet significant social problems have been observed in youth with many neurodevelopmental disorders. In this preliminary investigation, we aimed to explore whether domains of social reciprocity (i.e., social communication, social cognition, social awareness, social motivation, and restricted and repetitive behaviors) represent transdiagnostic traits. These domains were compared across youth ages 7–17 with obsessive-compulsive disorder (OCD; N = 32), tic disorders (TD; N = 20), severe mood dysregulation (N = 33) and autism spectrum disorder (N = 35). While the ASD group was rated by parents as exhibiting the greatest social reciprocity deficits across domains, a high proportion of youth with severe mood dysregulation also exhibited pronounced deficits in social communication, cognition, and awareness. The ASD and severe mood dysregulation groups demonstrated comparable scores on the social awareness domain. In contrast, social motivation and restricted and repetitive behaviors did not appear to be transdiagnostic domains in severe mood dysregulation, OCD, or TD groups. The present work provides preliminary support that social awareness, and to a lesser extent social communication and cognition, may represent features of social reciprocity that are transdiagnostic across ASD and severe mood dysregulation.

Randomized Controlled Trial of the Safety and Immunogenicity of Revaccination With Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) in Adults 10 Years After a Previous Dose.

BackgroundReduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States.MethodsWe performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination.ResultsA solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no significant differences in the rates of injection-site reactions, systemic reactions, or serious adverse events between the vaccine groups. A robust antibody response to each pertussis antigen in the Tdap-vaccinated group was found; postvaccination-to-prevaccination geometric mean antibody concentration ratios were 8:1 (pertussis toxoid), 5.9 (filamentous hemagglutinin), 6.4 (pertactin), and 5.2 (fimbriae 2 and 3). Postvaccination geometric mean concentrations of tetanus antibody (4.20 and 4.74 IU/mL, respectively) and diphtheria antibody (10.1 and 12.6 IU/mL, respectively) were similar in the Tdap and Td groups, and the rates of seroprotection against tetanus and diphtheria were >99% in both groups.ConclusionsA second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults.

Socio-emotional adjustment of adolescents with cochlear implants: Loneliness, emotional autonomy, self-concept, and emotional experience at the hospital.

Recent studies have reported contrasting results in the socio-emotional adjustment of Italian adolescents with cochlear implants (CIs). The aim of the present study is to explore the relationship between the socio-emotional adjustment of adolescents with CIs, the quality of their hospital stay, and their age at CI activation. The participants were 29 adolescents with CIs (CI group) and 29 typically developing adolescents (TD group). The Emotional Autonomy Scale, the Loneliness and Aloneness Scale for Children and Adolescents, and the Multidimensional Self-Concept Scale were administered to each participant. The emotional experience reported during the hospital stay was considered for each participant in the CI group. The adolescents with CIs displayed significantly higher levels of loneliness and lower levels of aversion toward aloneness than the TD group participants. Adolescents who had received the CI in preschool displayed a higher level of physical self-concept than adolescents who had received it later. The adolescents' emotional experiences at the hospital were reported to be quite complex and related to their relationships with parents. In summary, the findings point to a specific type of fragility in socio-emotional adjustment-focused on loneliness/aloneness-rather than a general one.

Adaptive behavior in infants and toddlers with Down syndrome and fragile X syndrome.

Individuals with Down syndrome (DS) experience deficits across all domains of adaptive functioning, however little is known about the emergence and age-related changes of these impairments compared to other neurogenetic disorders with similar intellectual disability impairments, such as fragile X syndrome (FXS). Adaptive behavior is key for optimal functioning in these populations. Participants aged 5-45 months comprised three age-matched groups, DS (n = 64), FXS (n = 69), and typically developing controls (TD; n = 69). Adaptive behavior was measured on the Vineland Adaptive Behavior Scales-II. Regressions were used to examine adaptive behavior in a cross-sectional design across age. DS infants and toddlers evidenced deficits across all areas of adaptive behaviors compared to the age-matched TD group, with clear impairments present in the first year of life. Motor skills were the area of greatest weakness in children with DS with significant impairment evident at 12 months of age that remained low through 3 years. Compared to age-matched children with FXS, children with DS showed initially lower standard scores at 12 months of age, but slower declines in standard scores across age, resulting in less impaired functioning at 36 months. This is the first study to compare adaptive behavior in infants and toddlers with DS to FXS, and demonstrate the phenotypic specificity of adaptive profiles in this diagnostic group. These findings provide evidence that adaptive behavior should be a major target of intervention in children with FXS and DS, and that these differences are potentially driven by unique etiologies attributable to each disorder.

Resounding failure to replicate links between developmental language disorder and cerebral lateralisation.

BackgroundIt has been suggested that failure to establish cerebral lateralisation may be related to developmental language disorder (DLD). There has been weak support for any link with handedness, but more consistent reports of associations with functional brain lateralisation for language. The consistency of lateralisation across different functions may also be important. We aimed to replicate previous findings of an association between DLD and reduced laterality on a quantitative measure of hand preference (reaching across the midline) and on language laterality assessed using functional transcranial Doppler ultrasound (fTCD).MethodsFrom a sample of twin children aged from 6;0 to 11;11 years, we identified 107 cases of DLD and 156 typically-developing comparison cases for whom we had useable data from fTCD yielding a laterality index (LI) for language function during an animation description task. Handedness data were also available for these children.ResultsIndices of handedness and language laterality for this twin sample were similar to those previously reported for single-born children. There were no differences between the DLD and TD groups on measures of handedness or language lateralisation, or on a categorical measure of consistency of left hemisphere dominance. Contrary to prediction, there was a greater incidence of right lateralisation for language in the TD group (19.90%) than the DLD group (9.30%), confirming that atypical laterality is not inconsistent with typical language development. We also failed to replicate associations between language laterality and language test scores.Discussion and ConclusionsGiven the large sample studied here and the range of measures, we suggest that previous reports of atypical manual or language lateralisation in DLD may have been false positives.

Subskills associated with spelling ability in children with and without autism spectrum disorders

Background and aims Effective literacy instruction demands a clear understanding of the subskills that underpin children’s reading and writing abilities. Some previous research on reading has questioned whether the same subskills support literacy acquisition for typically developing children and children with autism spectrum disorders. This study examined the subskills associated with spelling ability in a group of 20 children with ASD aged 5–12 years (ASD group). A group of 20 typically developing children matched for age and word spelling accuracy (TD group) provided comparative data. Methods Participants completed standardised assessments of vocabulary, phonological awareness, letter knowledge and word spelling. Errors produced in response to the word spelling assessment were analysed for evidence of phonological awareness. In addition, all spelling attempts were analysed for evidence of phonological, orthographic, and morphological awareness, ‘linguistic awareness’, using the Computerised Spelling Sensitivity System. Results Correlation and regression analyses showed statistically significant relationships between phonological awareness and word spelling accuracy for children in the ASD and TD groups. Spelling errors produced by both groups contained evidence of phonological awareness. Analysis of all spelling attempts showed that the overall level of linguistic awareness encoded by children in the ASD and TD groups was not significantly different. Conclusions These findings provide evidence that phonological awareness and other subskills support spelling in children with autism spectrum disorders as they do in typically developing children. Implications The similar spelling profiles exhibited by children with autism spectrum disorders and their typically developing peers suggest that these populations may benefit from literacy instruction that targets the same underpinning subskills.

Exercise training and dietary restriction affect PINK1/Parkin and Bnip3/Nix-mediated cardiac mitophagy in mice.

The aim of this study was to investigate the effects of exercise training and dietary restriction on cardiac PINK1/Parkin and Bnip3/Nix pathways involved in mitophagy. C57BL/6 mice were assigned to control (C), exercise training (T), dietary restriction (D) and exercise training + dietary restriction (TD) groups. T group undertook 10 weeks of swimming training. D group was subjected to 40% food reduction. TD group undertook the combination of exercise training and food reduction. Suspectable mitophagy autophagosomes can be observed in T and D groups and more autophagosomes appeared in TD group. In T group, both PINK1 mRNA and protein levels increased significantly (p < 0.01) but Bnip3 and Nix expressions decreased significantly (p < 0.05). Dietary restriction resulted in elevation of Drp1 (p < 0.01) and reduction and Nix (p < 0.05) in D group. The load in TD group resulted in serious mitochondrial abnormalities and myofibrillar damages accompanied by increases in PINK1 and Drp1 levels (p < 0.01) and decreases in Bnip3 and Nix levels (p < 0.05). The increase in PINK1 expression (exercise protocol) or Drp1 expression (diet protocol) contributes to cardiac activation of mitophagy, whereas Bnip3 and Nix are not implicated in this activation.

Relationship Between Functional Level and Muscle Thickness in Young Children With Cerebral Palsy.

ObjectiveTo investigate the relationship between functional level and muscle thickness (MT) of the rectus femoris (RF) and the gastrocnemius (GCM) in young children with cerebral palsy (CP).MethodsThe study participants were comprised of 26 children (50 legs) with spastic CP, aged 3–6 years, and 25 age-matched children with typical development (TD, 50 legs). The MT of the RF, medial GCM, and lateral GCM was measured with ultrasound imaging. The functional level was evaluated using the Gross Motor Function Measurement-88 (GMFM-88), Gross Motor Function Classification System (GMFCS), and based on the mobility area of the Korean version of the Modified Barthel Index (K-MBI). The measurement of spasticity was evaluated with the Modified Ashworth Scale (MAS).ResultsWe note that the height, weight, body mass index, and MT of the RF, and the medial and lateral GCM were significantly higher in the TD group (p<0.05). There was a direct relationship between MT of the RF and medial GCM and the GMFM-88, GMFCS, and mobility scores of the K-MBI in individuals with early CP. In addition, we have noted that there was a direct relationship between MT of the lateral GCM and the GMFM-88 and GMFCS. Although there was a tendency toward lower MT with increasing MAS ratings in the knee and ankle, the correlation was not statistically significant.ConclusionIn young children with CP, MT of the RF and GCM was lower than in age-matched children with TD. Furthermore, it is noted with confidence that a significant positive correlation existed between MT and functional level as evaluated using the GMFM-88, GMFCS, and mobility area of K-MBI.