Harnessing Repetitive Behaviours to Engage Attention and Learning in a Novel Therapy for Autism: An Exploratory Analysis

Rigorous, quantitative examination of therapeutic techniques anecdotally reported to have been successful in people with autism who lack communicative speech will help guide basic science toward a more complete characterisation of the cognitive profile in this underserved subpopulation, and show the extent to which theories and results developed with the high-functioning subpopulation may apply. This study examines a novel therapy, the “Rapid Prompting Method” (RPM). RPM is a parent-developed communicative and educational therapy for persons with autism who do not speak or who have difficulty using speech communicatively. The technique aims to develop a means of interactive learning by pointing amongst multiple-choice options presented at different locations in space, with the aid of sensory “prompts” which evoke a response without cueing any specific response option. The prompts are meant to draw and to maintain attention to the communicative task – making the communicative and educational content coincident with the most physically salient, attention-capturing stimulus – and to extinguish the sensory–motor preoccupations with which the prompts compete. Video-recorded RPM sessions with nine autistic children ages 8–14 years who lacked functional communicative speech were coded for behaviours of interest. An analysis controlled for age indicates that exposure to the claimed therapy appears to support a decrease in repetitive behaviours and an increase in the number of multiple-choice response options without any decrease in successful responding. Direct gaze is not related to successful responding, suggesting that direct gaze might not be any advantage for this population and need not in all cases be a precondition to communication therapies

Skin cancer precursor immunotherapy for squamous cell carcinoma prevention

BACKGROUND: Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma (SCC). However, the long-term effectiveness of calcipotriol plus 5-FU treatment for SCC prevention is unknown. METHODS: We performed a blinded prospective cohort study on participants of a randomized double-blind clinical trial in which a 4-day course of topical calcipotriol plus 5-FU combination was compared to Vaseline plus 5-FU (control) for AK treatment. SCC and basal cell carcinoma (BCC) incidences were assessed at 1, 2, and 3 years after trial. Tissues were analyzed for calcipotriol plus 5-FU-induced T cell immunity in the skin. RESULTS: Calcipotriol plus 5-FU-induced tissue-resident memory T (Trm) cell formation in face and scalp skin associated with significantly higher erythema scores compared with control (P \u3c 0.01). Importantly, more participants in the test cohort remained SCC-free over the more than 1,500-day follow-up period (P = 0.0765), and significantly fewer developed SCC on the treated face and scalp within 3 years (2 of 30 [7%] versus 11 of 40 [28%] in control group, hazard ratio 0.215 [95% CI: 0.048-0.972], P = 0.032). Accordingly, significantly more epidermal Trm cells persisted in the calcipotriol plus 5-FU-treated face and scalp skin compared with control (P = 0.0028). There was no significant difference in BCC incidence between the treatment groups. CONCLUSION: A short course of calcipotriol plus 5-FU treatment on the face and scalp is associated with induction of robust T cell immunity and Trm formation against AKs and significantly lowers the risk of SCC development within 3 years of treatment. FUNDING: This research was supported by internal academic funds and by grants from the Burroughs Wellcome Fund, Sidney Kimmel Foundation, Cancer Research Institute, and NIH

The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders

MicroRNA profiling of the bovine alveolar macrophage response to Mycobacterium bovis infection suggests pathogen survival is enhanced by microRNA regulation of endocytosis and lysosome trafficking

peer-reviewedMycobacterium bovis, the causative agent of bovine tuberculosis, a major problem for global agriculture, spreads via an airborne route and is taken up by alveolar macrophages (AM) in the lung. Here, we describe the first next-generation sequencing (RNA-seq) approach to temporally profile miRNA expression in primary bovine AMs post-infection with M. bovis. One, six, and forty miRNAs were identified as significantly differentially expressed at 2, 24 and 48 h post-infection, respectively. The differential expression of three miRNAs (bta-miR-142-5p, bta-miR-146a, and bta-miR-423-3p) was confirmed by RT-qPCR. Pathway analysis of the predicted mRNA targets of differentially expressed miRNAs suggests that these miRNAs preferentially target several pathways that are functionally relevant for mycobacterial pathogenesis, including endocytosis and lysosome trafficking, IL-1 signalling and the TGF-β pathway. Over-expression studies using a bovine macrophage cell-line (Bomac) reveal the targeting of two key genes in the innate immune response to M. bovis, IL-1 receptor-associated kinase 1 (IRAK1) and TGF-β receptor 2 (TGFBR2), by miR-146. Taken together, our study suggests that miRNAs play a key role in tuning the complex interplay between M. bovis survival strategies and the host immune response

Pennsylvania Folklife Vol. 25, Folk Festival Supplement

• Quilts, Quilts, Quilts • America\u27s Heritage is Endowed with Contributions of the Pennsylvania Dutch • The Hospitality Tent: H is for Help - That\u27s What it\u27s all About • Pottery: A Folk Art Expressing the Most in Simplest Terms • It Never Rains on our Parade - On the Fourth of July • Vegetable Dyeing at the Kutztown Folk Festival • Festival Focus • Folk Festival Program • Festival Foods: The Original Touch of the Dutch • Ursinus College Studies at the Festival • Behind the Scenes of We Like Our Country, But We Love Our God • Reverse Glass Tinsel Painting • Tin, Tole and Independencehttps://digitalcommons.ursinus.edu/pafolklifemag/1069/thumbnail.jp