Assessment and management of over-activity and sleep disorder in mucopolysaccharidoses

There is a growing awareness, based on both research and clinical studies, that abnormal sleep and circadian functioning are associated with the various forms of mucopolysaccharidoses (MPS), with sleep respiratory problems seemingly common in many forms of MPS. In the case of MPS III, there is evidence of syndrome-specific sleep disturbance related to an abnormal and possibly unique circadian rhythm. The presence of such patterns of sleep and activity has detrimental consequences for both the person with MPS and also invariably for her/his family and carers. On the basis of current evidence, routine assessment of sleep functioning is clearly warranted for all children with MPS III together with appropriate medical and behavioral interventions as required

The ‘I Wonder’ Curriculum: An Enquiry-Based Approach to History in Junior Infants

The aim of this self-study action research project was to enhance my teaching of the Myself strand of the Junior Infant History curriculum so that lessons reflected the lives of the children I teach. The research was conducted in a multi-grade Junior/Senior Infant class in an urban DEIS school. In line with the principles of self-study action research, my values were articulated and used to highlight times when my values and practice were in tension. To address this tension, an intervention was designed to ensure History lessons were child-centred, democratic and inclusive. This was achieved through use of a dialogic teaching method, I-wonder questions and sharing of historical evidence to encourage children to ask questions about their own lives and the lives of their families. Families became involved when these questions were sent home in children’s History Portfolios. Further involvement from families occurred when they were invited into school to work on an art-based Family Tree Project. A qualitative approach was taken to data collection as this method allowed for a range of voices to be included in my research, including the voice of children, parents/grandparents, colleagues and academics. Data was collected using questionnaires, interviews, work samples, photographs and a teacher reflective journal. The ethical implications were considered and addressed prior to commencing research. A reflexive thematic analysis approach was taken to data analysis resulting in the emergence of four findings. The findings revealed the central place of parents/grandparents sharing details of the children’s histories to help children meet the objectives of the History curriculum. Furthermore, the research found that teacher-sharing of stories, photographs and artefacts from their own history awakens the children’s curiosity and acts as a stimulus for historical enquiry. The remaining findings were that children’s ability to act agentically during History lessons is impacted by adult perceptions of agency and children’s ability to formulate questions about their lives. Illustrations have been used in Chapter One to show the research journey and changes to my mindset when teaching History as a result. These images have been included with kind permission from the illustrator, David Mahon. The self-study research approach has had an impact on the way I teach the Myself strand of the History curriculum. My planning in the future will include participation from parents/grandparents and use of historical evidence. Lessons will be child-led, based on children’s questions, so that the objectives of the History curriculum are tailored to each child in my class

Assessment of sleep in children with mucopolysaccharidosis Type III

Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III), yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7–10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep diary. Actigraphic data revealed that children with MPS III had significantly longer sleep onset latencies and greater daytime sleep compared to controls, but night-time sleep duration did not differ between groups. In the MPS III group, sleep efficiency declined, and sleep onset latency increased, with age. Questionnaire responses showed that MPS III patients had significantly more sleep difficulties in all domains compared to controls. Melatonin concentrations showed an alteration in the circadian system in MPS III, which suggests that treatment for sleep problems should attempt to synchronise the sleep-wake cycle to a more regular pattern. Actigraphy was tolerated by children and this monitoring device can be recommended as a measure of treatment success in research and clinical practice

Deposition of SnS Thin Films from Sn(II) Thioamidate Precursors

Two thioamide pro-ligands, R¹N­(H)­C­(S)­R² (R¹ = <i>t</i>-Bu, R² = i-Pr and R¹ = i-Pr, R² = i-Pr), were synthesized by treatment of the corresponding amides with Lawesson’s reagent. Reactions of [Sn­{N­(SiMe₃)₂}₂] with two molar equivalents of each thioamide pro-ligand yielded the tin­(II) thioamidate species, bis­(2-methyl-<i>N</i>-(1-methylethyl)-propanethioamide)­tin­(II) and Bis­[<i>N</i>-(1,1-dimethylethyl)-2-methylpropanethioamide]­tin­(II). Both of the new tin compounds have been characterized by ¹H, ¹³C­{¹H}, and ¹¹⁹Sn NMR spectroscopy and elemental analysis. In addition, the solid-state structure of bis­(2-methyl-<i>N</i>-(1-methylethyl)-propanethioamide)­tin­(II) has been determined through a single crystal X-ray diffraction analysis and shown to display a monomeric constitution in which the tin­(II) center occupies a distorted <i>pseudo</i> square pyramidal geometry defined by the N₂S₂ donors and the stereochemically active lone pair. Both tin­(II) derivatives have been assessed for their potential as single source precursors to SnS by TGA and by NMR spectroscopic analysis of the volatile organic products produced during their thermolysis. Both compounds have been utilized in the growth of thin films by aerosol-assisted chemical vapor deposition (AACVD). These latter studies provided film growth at temperatures as low as 200 °C. The films have been analyzed by PXRD, Raman spectroscopy, XPS, AFM, and SEM and are shown to comprise primarily the orthorhombic (Herzenbergite) phase of SnS, which is contaminated by only low levels of residual carbon (<5 at %). Although further films deposited onto Mo-coated substrates produced only limited photocurrents when illuminated, these results demonstrate the potential of such simple thioamidate derivatives to act as single source precursors to useful metal sulfide thin film materials

Measuring endogenous changes in serotonergic neurotransmission with [11C]Cimbi-36 positron emission tomography in humans

Abstract Developing positron emission tomography (PET) radioligands for the detection of endogenous serotonin release will enable the investigation of serotonergic deficits in many neuropsychiatric disorders. The present study investigates how acute challenges that aim to increase or decrease cerebral serotonin levels affect binding of the serotonin 2A receptor (5-HT2AR) agonist radioligand [11C]Cimbi-36. In a randomized, double-blind, placebo-controlled, three-arm design, 23 healthy volunteers were PET scanned twice with [11C]Cimbi-36: at baseline and following double-blind assignment to one of three interventions (1) infusion of the selective serotonin reuptake inhibitor (SSRI) citalopram preceded by oral dosing of the 5-HT1AR antagonist pindolol, (n = 8) (2) acute tryptophan depletion (ATD) (n = 7) and (3) placebo (n = 8). Two-sample t-tests revealed no significant group differences in percent change of neocortical [11C]Cimbi-36 binding from baseline to intervention between placebo and citalopram/pindolol (p = 0.4) or between placebo and ATD (p = 0.5). Notably, there was a significantly larger within-group variation in 5-HT2AR binding after intervention with citalopram/pindolol, as compared with placebo (p = 0.007). These findings suggest that neither ATD nor a combination of citalopram and pindolol elicit acute unidirectional changes in serotonin levels sufficient to be detected with [11C]Cimbi-36 PET in neocortex. We suggest that the large interindividual variation in 5-HT2AR binding after citalopram/pindolol reflects that after an acute SSRI intervention, individuals respond substantially different in terms of their brain serotonin levels. Our observation has a potential impact for the understanding of patient responses to SSRI

Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression

Background - Bipolar disorder is frequently misdiagnosed as major depressive disorder, delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation might therefore help discriminate bipolar from major depressive disorder. Methods - Thirty-one depressed individuals—15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, ages 18–55 years, matched for age, age of illness onset, illness duration, and depression severity—and 16 age- and gender-matched healthy control subjects performed two event-related paradigms: labeling the emotional intensity of happy and sad faces, respectively. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC). Results - During classification of happy faces, we found profound and asymmetrical differences in EC between the OMPFC and amygdala. Left-sided differences involved top-down connections and discriminated between depressed and control subjects. Furthermore, greater medication load was associated with an amelioration of this abnormal top-down EC. Conversely, on the right side the abnormality was in bottom-up EC that was specific to bipolar disorder. These effects replicated when we considered only female subjects. Conclusions - Abnormal, left-sided, top-down OMPFC–amygdala and right-sided, bottom-up, amygdala–OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression

A Functional Role for Modality-Specific Perceptual Systems in Conceptual Representations

Theories of embodied cognition suggest that conceptual processing relies on the same neural resources that are utilized for perception and action. Evidence for these perceptual simulations comes from neuroimaging and behavioural research, such as demonstrations of somatotopic motor cortex activations following the presentation of action-related words, or facilitation of grasp responses following presentation of object names. However, the interpretation of such effects has been called into question by suggestions that neural activation in modality-specific sensorimotor regions may be epiphenomenal, and merely the result of spreading activations from “disembodied”, abstracted, symbolic representations. Here, we present two studies that focus on the perceptual modalities of touch and proprioception. We show that in a timed object-comparison task, concurrent tactile or proprioceptive stimulation to the hands facilitates conceptual processing relative to control stimulation. This facilitation occurs only for small, manipulable objects, where tactile and proprioceptive information form part of the multimodal perceptual experience of interacting with such objects, but facilitation is not observed for large, nonmanipulable objects where such perceptual information is uninformative. Importantly, these facilitation effects are independent of motor and action planning, and indicate that modality-specific perceptual information plays a functionally constitutive role in our mental representations of objects, which supports embodied assumptions that concepts are grounded in the same neural systems that govern perception and action