Empowering Patients With a Shared Communication Tool: A Patient-Oriented Multimethods Pilot Study.

Not all patients feel empowered to take on the expanding role as active members in their healthcare journey. Healthcare services must shift attention to supporting patients and families in this emerging role. This support includes providing communication tools designed for patients and families to empower them to speak up. Two Plan-Do-Study-Act (PDSA) cycles were conducted to test a communication tool, the Jargon Alert!/WAIT card, with patients/families and providers in a Canadian rehabilitation hospital. After the first PDSA cycle, feedback from patients/families (n = 24), and providers (n = 4), informed modifications. The new Question Alert! card was retested in the same clinics. Patients/families (n = 13) reported the new card was a valuable tool enabling them to ask questions, although not all patients or family members expressed the need to use the card. The participating providers (n = 4) thought the Question Alert! card was helpful for quieter patients or family members who normally shy away from asking questions. The shared communication tool designed with patients improved the patient-centered experience and empowered patients/families to be more involved in their care.

Evidence of an Unusual Poly(A) RNA Signature Detected by High-Throughput Chemical Mapping.

Homopolymeric adenosine RNA plays numerous roles in both cells and noncellular genetic material. We report herein an unusual poly(A) signature in chemical mapping data generated by the Eterna Massive Open Laboratory. Poly(A) sequences of length seven or more show unexpected results in the selective 2'-hydroxyl acylation read out by primer extension (SHAPE) and dimethyl sulfate (DMS) chemical probing. This unusual signature first appears in poly(A) sequences of length seven and grows to its maximum strength at length ∼10. In a long poly(A) sequence, the substitution of a single A by any other nucleotide disrupts the signature, but only for the 6 or so nucleotides on the 5' side of the substitution.

bpRNA: large-scale automated annotation and analysis of RNA secondary structure.

While RNA secondary structure prediction from sequence data has made remarkable progress, there is a need for improved strategies for annotating the features of RNA secondary structures. Here, we present bpRNA, a novel annotation tool capable of parsing RNA structures, including complex pseudoknot-containing RNAs, to yield an objective, precise, compact, unambiguous, easily-interpretable description of all loops, stems, and pseudoknots, along with the positions, sequence, and flanking base pairs of each such structural feature. We also introduce several new informative representations of RNA structure types to improve structure visualization and interpretation. We have further used bpRNA to generate a web-accessible meta-database, 'bpRNA-1m', of over 100 000 single-molecule, known secondary structures; this is both more fully and accurately annotated and over 20-times larger than existing databases. We use a subset of the database with highly similar (≥90% identical) sequences filtered out to report on statistical trends in sequence, flanking base pairs, and length. Both the bpRNA method and the bpRNA-1m database will be valuable resources both for specific analysis of individual RNA molecules and large-scale analyses such as are useful for updating RNA energy parameters for computational thermodynamic predictions, improving machine learning models for structure prediction, and for benchmarking structure-prediction algorithms.

In Vivo Characterization of an AHR-Dependent Long Noncoding RNA Required for Proper Sox9b Expression.

Xenobiotic activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the proper formation of craniofacial cartilage and the heart in developing zebrafish. Downstream molecular targets responsible for AHR-dependent adverse effects remain largely unknown; however, in zebrafish sox9b has been identified as one of the most-reduced transcripts in several target organs and is hypothesized to have a causal role in TCDD-induced toxicity. The reduction of sox9b expression in TCDD-exposed zebrafish embryos has been shown to contribute to heart and jaw malformation phenotypes. The mechanisms by which AHR2 (functional ortholog of mammalian AHR) activation leads to reduced sox9b expression levels and subsequent target organ toxicity are unknown. We have identified a novel long noncoding RNA (slincR) that is upregulated by strong AHR ligands and is located adjacent to the sox9b gene. We hypothesize that slincR is regulated by AHR2 and transcriptionally represses sox9b. The slincR transcript functions as an RNA macromolecule, and slincR expression is AHR2 dependent. Antisense knockdown of slincR results in an increase in sox9b expression during both normal development and AHR2 activation, which suggests relief in repression. During development, slincR was expressed in tissues with sox9 essential functions, including the jaw/snout region, otic vesicle, eye, and brain. Reducing the levels of slincR resulted in altered neurologic and/or locomotor behavioral responses. Our results place slincR as an intermediate between AHR2 activation and the reduction of sox9b mRNA in the AHR2 signaling pathway.

Long noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer.

Long noncoding RNAs (lncRNAs) have emerged as important in cancer development and progression. The impact of diet on lncRNA expression is largely unknown. Sulforaphane (SFN), obtained from vegetables like broccoli, can prevent and suppress cancer formation. Here we tested the hypothesis that SFN attenuates the expression of cancer-associated lncRNAs. We analyzed whole-genome RNA-sequencing data of normal human prostate epithelial cells and prostate cancer cells treated with 15 µM SFN or dimethylsulfoxide. SFN significantly altered expression of ~100 lncRNAs in each cell type and normalized the expression of some lncRNAs that were differentially expressed in cancer cells. SFN-mediated alterations in lncRNA expression correlated with genes that regulate cell cycle, signal transduction and metabolism. LINC01116 was functionally investigated because it was overexpressed in several cancers, and was transcriptionally repressed after SFN treatment. Knockdown of LINC01116 with siRNA decreased proliferation of prostate cancer cells and significantly up-regulated several genes including GAPDH (regulates glycolysis), MAP1LC3B2 (autophagy) and H2AFY (chromatin structure). A four-fold decrease in the ability of the cancer cells to form colonies was found when the LINC01116 gene was disrupted through a CRISPR/CAS9 method, further supporting an oncogenic function for LINC01116 in PC-3 cells. We identified a novel isoform of LINC01116 and bioinformatically investigated the possibility that LINC01116 could interact with target genes via ssRNA:dsDNA triplexes. Our data reveal that chemicals from the diet can influence the expression of functionally important lncRNAs, and suggest a novel mechanism by which SFN may prevent and suppress prostate cancer.

Early childhood outcomes of infants born with gastroschisis.

PURPOSE: To describe neonatal and childhood outcomes of a contemporary cohort of infants with gastroschisis. METHODS: Observational, single center, inception cohort of children born with gastroschisis from January 2005 to December 2008. RESULTS: Of 63 infants, 61 survived to hospital discharge and 39 were seen for follow-up. Complications included sepsis (37%), necrotizing enterocolitis (10%), parenteral nutrition related cholestasis (25%), and short bowel syndrome (13%). Of survivors, 5% had visual impairment and 10% had hearing loss. No child tested had mental delay or cerebral palsy. Early gestational age predicted death or disability (OR 0.60, 95% CI 0.38, 0.96; p=0.033). There was a high incidence of prescription medications for presumed gastroesophageal reflux (90%). Some infants continued to require tube feeds (15%). There were improvements in longitudinal growth reflected in increasing z-scores. CONCLUSIONS: Although children with gastroschisis are at risk for disability, childhood outcomes are encouraging.