Comparative efficacy of the Picture Exchange Communication System (PECS) versus a speech-generating device: Effects on requesting skills

An experimental, single-subject research study investigated the comparative efficacy of the Picture Exchange Communication System (PECS) versus a speech-generating device (SGD) in developing requesting skills for three elementary-age children with severe autism and little to no functional speech. Results demonstrated increases in requesting behavior for all participants across intervention phases with both augmentative and alternative communication (AAC) intervention strategies; however, difficulties were observed with picture discrimination. The Wilcoxon signed pair test did not reveal significant differences between PECS and the SGD for any participant. Findings suggest PECS and SGD are equally appropriate for developing initial requesting skills. Based on the current findings, successful implementation of either AAC strategy is achievable when appropriate instructional strategies are used.     

Age-related differences in the prevalence and correlates of anxiety in youth with autism spectrum disorders

Age-related differences in the prevalence and correlates of anxiety were cross-sectionally examined in 1316 children and adolescents with autism spectrum disorder (ASD) who presented for initial evaluation at 14 outpatient autism centers around the country and in Canada. The prevalence of clinical and subclinical anxiety as well as the correlates of anxiety were examined in three age groups of children: preschool, school age and adolescents. Findings showed that the prevalence of anxiety in each age group exceeded the prevalence of anxiety in the general population. Adolescents and school age children had the highest prevalence of clinical (40%) and subclinical anxiety (26%), respectively. Higher IQ and less ASD severity were each weakly correlated with more anxiety in preschool and school age children. Affective symptoms were strongly associated with anxiety in each age group. Age specific psychiatric comorbidities were also present. Anxiety was associated with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in the preschool group, ODD and somatic symptoms in the school age children, and ADHD symptoms in adolescents. These data underscore the need for prevention and treatment of anxiety as well as research examining the characteristics of anxiety in children with ASD using a developmental framework.     

Biosimilar DMARD in rheumatology: A general perspective with focus on India

Biologic disease modifying anti-rheumatic drugs (DMARD) have revolutionized the management of several rheumatic disorders, especially those with autoimmune inflammatory etiology. A decade of experience has further endorsed their efficacy and unraveled safety issues. Treat to target remission is the current mantra. Infections remain the single most important complication. However, the access to biologics has been severely restricted by their exorbitant cost. Several biologics will lose their patent in the imminent future. An exact replica of a protein molecule is difficult if not impossible. Molecules seemingly similar to biologics called biosimilars or ‘follow on biologics’ are likely to flood the markets world wide at a challenging and affordable price. However, the acceptability of biosimilars will be driven by several contentious issues connected with manufacture, standardization, extent of validation (compared to source innovator biologic), interchangeability (with biologic), regulatory issues, and other patient centric socioeconomic issues. India is likely to provide a fertile field for biosimilar drugs and patients stand to gain from an expanded access and newer treatment paradigms. The fierce competition between several pharmaceutical companies (Indian and multinationals) to gain supremacy will fuel better affordability, equity and access to medicine while upholding the science of quality drugs. The stage is now set for this next big revolution in therapeutics.     

Association of TM4SF4 with the Human Thiamine Transporter-2 in Intestinal Epithelial Cells

Background

The human thiamine transporter-2 (hTHTR-2) is involved in the intestinal absorption of thiamine. Recent studies with membrane transporters of other nutrients/substrates have shown that they have associated proteins that affect different aspects of their physiology and cell biology. Nothing is known about protein(s) that interact with hTHTR-2 in intestinal epithelial cells and influence its physiological function and/or its cell biology.

Aims

The aim of this study was to identify protein partner(s) that interact with hTHTR-2 in human intestinal cells and determine the physiological/biological consequence of that interaction.

Methods

The yeast split-ubiquitin two-hybrid approach was used to screen a human intestinal cDNA library. GST-pull-down and cellular co-localization approaches were used to confirm the interaction between hTHTR-2 and the associated protein(s). The effect of such an interaction on hTHTR-2 function was examined by ³H-thiamine uptake assays.

Results

Our screening results identified the human TransMembrane 4 SuperFamily 4 (TM4SF4) as a potential interactor with hTHTR-2. This interaction was confirmed by an in vitro GST-pull-down assay, and by live-cell confocal imaging of HuTu-80 cells co-expressing hTHTR-2–GFP and mCherry–TM4SF4 (the latter displayed a significant overlap of these two proteins in intracellular vesicles and at the cell membrane). Co-expression of hTHTR-2 with TM4SF4 in HuTu-80 cells led to a significant induction in thiamine uptake. In contrast, silencing TM4SF4 with gene-specific siRNA led to a significant decrease in thiamine uptake.

Conclusions

These results show for the first time that the accessory protein TM4SF4 interacts with hTHTR-2 and influences the physiological function of the thiamine transporter.