Identifying Medication Management Smartphone App Features Suitable for Young Adults With Developmental Disabilities: Delphi Consensus Study

Background: Smartphone apps can be a tool to facilitate independent medication management among persons with developmental disabilities. At present, multiple medication management apps exist in the market, but only 1 has been specifically designed for persons with developmental disabilities. Before initiating further app development targeting this population, input from stakeholders including persons with developmental disabilities, caregivers, and professionals regarding the most preferred features should be obtained. Objective: The aim of this study was to identify medication management app features that are suitable to promote independence in the medication management process by young adults with developmental disabilities using a Delphi consensus method. Methods: A compilation of medication management app features was performed by searching the iTunes App Store, United States, in February 2016, using the following terms: adherence, medication, medication management, medication list, and medication reminder. After identifying features within the retrieved apps, a final list of 42 features grouped into 4 modules (medication list, medication reminder, medication administration record, and additional features) was included in a questionnaire for expert consensus rating. A total of 52 experts in developmental disabilities, including persons with developmental disabilities, caregivers, and professionals, were invited to participate in a 3-round Delphi technique. The purpose was to obtain consensus on features that are preferred and suitable to promote independence in the medication management process among persons with developmental disabilities. Consensus for the first, second, and third rounds was defined as ≥90%, ≥80%, and ≥75% agreement, respectively. Results: A total of 75 responses were received over the 3 Delphi rounds—30 in the first round, 24 in the second round, and 21 in the third round. At the end of the third round, cumulative consensus was achieved for 60% (12/20) items in the medication list module, 100% (3/3) in the medication reminder module, 67% (2/3) in the medication administration record module, and 63% (10/16) in the additional features module. In addition to the medication list, medication reminder, and medication administration record features, experts selected the following top 3 most important additional features: automatic refills through pharmacies; ability to share medication information from the app with providers; and ability to share medication information from the app with family, friends, and caregivers. The top 3 least important features included a link to an official drug information source, privacy settings and password protection, and prescription refill reminders. Conclusions: Although several mobile apps for medication management exist, few are specifically designed to support persons with developmental disabilities in the complex medication management process. Of the 42 different features assessed, 64% (27/42) achieved consensus for inclusion in a future medication management app. This study provides information on the features of a medication management app that are most important to persons with developmental disabilities, caregivers, and professionals

UMSAE Workshop/Trailer Redesign and E4 Facility Layout

The design project presented to our design team has three parts. The existing University of Manitoba Student Chapter of SAE International (UMSAE) workshop must be redesigned to improve the poor organization and work flow that is present. The UMSAE travel trailer must be redesigned, and a detailed universal loading scheme must be created to reduce trailer loading time and improve trailer organization when at competition. Finally, a building layout must be created for the Faculty of Engineering workspaces in the E4 building, a proposed addition to the existing EITC facility that will be shared with the Faculty of Architecture as an inclusive design center. This report presents the final recommended designs for each project section. The UMSAE workshop redesign uses a shelving system with colored totes to organize items and sort them between teams. The entire back room is used as a storage unit, which includes the installation of a sheet metal rack and chemical cabinets. Common tools are located on two color-coded shadow boards, which can be rolled to different locations depending on who requires them. Designated areas for team vehicles, tools, and storage are marked on the floor of the room to maintain workflow and travel lanes. Material disposal is defined with a simple flow chart and appropriate storage containers for each type of waste produced in the shop. The UMSAE trailer is redesigned with the addition of a shelving unit, hanging rack, tool chest, and folding workbench. The shelving unit is used as a place to store colored totes, which are organized into totes with objects common to all teams, and totes with team-specific objects. This improves loading speed and organization, as only the team-specific totes must be swapped out of the trailer. A set of hanging racks allows cords, ropes, and straps to be placed on the trailer walls. An integrated tool chest with a top work surface organizes tools effectively while providing a work surface for small assembly operations. If more work surface area is required, a folding table, attached to the trailer wall, can be extended beside the tool chest and to allow […]UMSA

The ARiBo tag: a reliable tool for affinity purification of RNAs under native conditions

Although RNA-based biological processes and therapeutics have gained increasing interest, purification of in vitro transcribed RNA generally relies on gel-based methods that are time-consuming, tedious and denature the RNA. Here, we present a reliable procedure for affinity batch purification of RNA, which exploits the high-affinity interaction between the boxB RNA and the N-peptide from bacteriophage λ. The RNA of interest is synthesized with an ARiBo tag, which consists of an activatable ribozyme (the glmS ribozyme) and the λBoxB RNA. This ARiBo-fusion RNA is initially captured on Glutathione-Sepharose resin via a GST/λN-fusion protein, and the RNA of interest is subsequently eluted by ribozyme self-cleavage using glucosamine-6-phosphate. Several GST/λN-fusion proteins and ARiBo tags were tested to optimize RNA yield and purity. The optimized procedure enables one to quickly obtain (3 h) highly pure RNA (>99%) under native conditions and with yields comparable to standard denaturing gel-based protocols. It is widely applicable to a variety of RNAs, including riboswitches, ribozymes and microRNAs. In addition, it can be easily adapted to a wide range of applications that require RNA purification and/or immobilization, including isolation of RNA-associated complexes from living cells and high-throughput applications

Importance of the NCp7-like domain in the recognition of pre-let-7g by the pluripotency factor Lin28

The pluripotency factor Lin28 is a highly conserved protein comprising a unique combination of RNA-binding motifs, an N-terminal cold-shock domain and a C-terminal region containing two retroviral-type CCHC zinc-binding domains. An important function of Lin28 is to inhibit the biogenesis of the let-7 family of microRNAs through a direct interaction with let-7 precursors. Here, we systematically characterize the determinants of the interaction between Lin28 and pre-let-7g by investigating the effect of protein and RNA mutations on in vitro binding. We determine that Lin28 binds with high affinity to the extended loop of pre-let-7g and that its C-terminal domain contributes predominantly to the affinity of this interaction. We uncover remarkable similarities between this C-terminal domain and the NCp7 protein of HIV-1, not only in terms of primary structure but also in their modes of RNA binding. This NCp7-like domain of Lin28 recognizes a G-rich bulge within pre-let-7g, which is adjacent to one of the Dicer cleavage sites. We hypothesize that the NCp7-like domain initiates RNA binding and partially unfolds the RNA. This partial unfolding would then enable multiple copies of Lin28 to bind the extended loop of pre-let-7g and protect the RNA from cleavage by the pre-microRNA processing enzyme Dicer

Structural and functional characterization of interactions involving the Tfb1 subunit of TFIIH and the NER factor Rad2

The general transcription factor IIH (TFIIH) plays crucial roles in transcription as part of the pre-initiation complex (PIC) and in DNA repair as part of the nucleotide excision repair (NER) machinery. During NER, TFIIH recruits the 3′-endonuclease Rad2 to damaged DNA. In this manuscript, we functionally and structurally characterized the interaction between the Tfb1 subunit of TFIIH and Rad2. We show that deletion of either the PH domain of Tfb1 (Tfb1PH) or several segments of the Rad2 spacer region yield yeast with enhanced sensitivity to UV irradiation. Isothermal titration calorimetry studies demonstrate that two acidic segments of the Rad2 spacer bind to Tfb1PH with nanomolar affinity. Structure determination of a Rad2–Tfb1PH complex indicates that Rad2 binds to TFIIH using a similar motif as TFIIEα uses to bind TFIIH in the PIC. Together, these results provide a mechanistic bridge between the role of TFIIH in transcription and DNA repair

Whole-Genome Analysis of Temporal Gene Expression during Foregut Development

We have investigated the cis-regulatory network that mediates temporal gene expression during organogenesis. Previous studies demonstrated that the organ selector gene pha-4/FoxA is critical to establish the onset of transcription of Caenorhabditis elegans foregut (pharynx) genes. Here, we discover additional cis-regulatory elements that function in combination with PHA-4. We use a computational approach to identify candidate cis-regulatory sites for genes activated either early or late during pharyngeal development. Analysis of natural or synthetic promoters reveals that six of these sites function in vivo. The newly discovered temporal elements, together with predicted PHA-4 sites, account for the onset of expression of roughly half of the pharyngeal genes examined. Moreover, combinations of temporal elements and PHA-4 sites can be used in genome-wide searches to predict pharyngeal genes, with more than 85% accuracy for their onset of expression. These findings suggest a regulatory code for temporal gene expression during foregut development and provide a means to predict gene expression patterns based solely on genomic sequence

Electrostatic hot spot on DNA-binding domains mediates phosphate desolvation and the pre-organization of specificity determinant side chains

A major obstacle towards elucidating the molecular basis of transcriptional regulation is the lack of a detailed understanding of the interplay between non-specific and specific protein–DNA interactions. Based on molecular dynamics simulations of C2H2 zinc fingers (ZFs) and engrailed homeodomain transcription factors (TFs), we show that each of the studied DNA-binding domains has a set of highly constrained side chains in preset configurations ready to form hydrogen bonds with the DNA backbone. Interestingly, those domains that bury their recognition helix into the major groove are found to have an electrostatic hot spot for Cl− ions located on the same binding cavity as the most buried DNA phosphate. The spot is characterized by three protein hydrogen bond donors, often including two basic side chains. If bound, Cl− ions, likely mimicking phosphates, steer side chains that end up forming specific contacts with bases into bound-like conformations. These findings are consistent with a multi-step DNA-binding mechanism in which a pre-organized set of TF side chains assist in the desolvation of phosphates into well defined sites, prompting the re-organization of specificity determining side chains into conformations suitable for the recognition of their cognate sequence

A strong 13C chemical shift signature provides the coordination mode of histidines in zinc-binding proteins

International audienceZinc is the second most abundant metal ion incorporated in proteins, and is in many cases a crucial component of protein three-dimensional structures. Zinc ions are frequently coordinated by cysteine and histidine residues. Whereas cysteines bind to zinc via their unique Sγ atom, histidines can coordinate zinc with two different coordination modes, either Nδ1 or Nε2 is coordinating the zinc ion. The determination of this coordination mode is crucial for the accurate structure determination of a histidine-containing zinc-binding site by NMR. NMR chemical shifts contain a vast amount of information on local electronic and structural environments and surprisingly their utilization for the determination of the coordination mode of zinc-ligated histidines has been limited so far to 15N nuclei. In the present report, we observed that the 13C chemical shifts of aromatic carbons in zinc-ligated histidines represent a reliable signature of their coordination mode. Using a statistical analysis of 13C chemical shifts, we show that 13Cδ2 chemical shift is sensitive to the histidine coordination mode and that the chemical shift difference δ{13Cε1} - δ{13Cδ2} provides a reference-independent marker of this coordination mode. The present approach allows the direct determination of the coordination mode of zinc-ligated histidines even with non-isotopically enriched protein samples and without any prior structural information

ESRRA-C11orf20 Is a Recurrent Gene Fusion in Serous Ovarian Carcinoma

Many ovarian cancers have a chromosomal rearrangement that fuses two neighboring genes, ESRRA and c11orf20. Similar rearrangements may be common, important features of cancer genomes that have largely escaped detection