Enhancing Public Access to Relevant and Valued Medical Information: Fresh Directions for RadiologyInfo.org.

RadiologyInfo.org is a public information portal designed to support patient care and broaden public awareness of the essential role radiology plays in overall patient health care. Over the past 14 years, RadiologyInfo.org has evolved considerably to provide access to more than 220 mixed-media descriptions of tests, treatments, and diseases through a spectrum of mobile and desktop platforms, social media, and downloadable documents in both English and Spanish. In 2014, the RSNA-ACR Public Information Website Committee, which stewards RadiologyInfo.org, developed 3- to 5-year strategic and implementation plans for the website. The process was informed by RadiologyInfo.org user surveys, formal stakeholder interviews, focus groups, and usability testing. Metrics were established as key performance indicators to assess progress toward the stated goals of (1) optimizing content to enhance patient-centeredness, (2) enhancing reach and engagement, and (3) maintaining sustainability. Major changes resulting from this process include a complete redesign of the website, the replacement of text-rich PowerPoint presentations with conversational videos, and the development of an affiliate network. Over the past year, visits to RadiologyInfo.org have increased by 60.27% to 1,424,523 in August 2016 from 235 countries and territories. Twenty-two organizations have affiliated with RadiologyInfo.org with new organizations being added on a monthly basis. RadiologyInfo provides a tangible demonstration of how radiologists can engage directly with the global public to educate them on the value of radiology in their health care and to allay concerns and dispel misconceptions. Regular self-assessment and responsive planning will ensure its continued growth and relevance.

Pediatric restless legs syndrome and periodic limb movement disorder: parent-child pairs.

OBJECTIVE: Although recent publications have reported the occurrence of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children and adolescents, the literature is relatively limited. The goals of this retrospective study were to (1) apply the recent International Classification of Sleep Disorders 2nd edition (ICSD-2) diagnostic criteria for RLS and PLMD in pediatric cases where periodic limb movements in sleep (PLMS) 5 per hour were found; (2) review parental history of RLS; and (3) further define the clinical characteristics of RLS and PLMD in a pediatric subgroup where each child had a parent with clinically assessed RLS. METHODS: This was a retrospective analysis of consecutive polysomnograms (PSGs) with PLMS >5 per hour in patients 19 years of age from a single pediatric sleep/neurology practice over 11 years. Excluded were cases with sleep apnea, narcolepsy, or medication that might induce or aggravate PLMS or RLS. ICSD-2 diagnostic criteria for definite RLS and PLMD were applied to the pediatric cases, and parental history for RLS was assessed. A subset of cases was included for detailed review if the child or adolescent had RLS or PLMD and a biological parent met RLS criteria and had a formal sleep evaluation. RESULTS: There were 204 cases that met the initial inclusion criteria. A positive parental history of RLS was found in 53% of pediatric RLS cases and in 52% of pediatric PLMD cases. A subset of 37 children or adolescents and 36 biological parents, from 33 different families, met full inclusion criteria and are presented in detail. Of these 37, 10 had a diagnosis of RLS and 27 a diagnosis of PLMD. Over this same period of time, PLMS >5 per hour were found in 74% of pediatric definite RLS cases assessed by PSG. CONCLUSIONS: This case series adds to the growing literature describing RLS and PLMD in children and adolescents using recently revised diagnostic criteria. The similar prevalence of parental RLS in both pediatric RLS and pediatric PLMD cases suggests a close association between PLMD and RLS in some cases. This supports the emerging view that PLMS may be a marker or endophenotype for a specific, common RLS genotype.

Primary mucosa-associated lymphoid tissue lymphoma of the breast.

Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal indolent lymphoma with histopatholigic features similar to those of marginal zone B-cell lymphomas. Primary breast MALT lymphomas were first described by Lamovec and Jancar as a low-grade B-cell lymphoma in 1987. Herein, a case is presented of a patient with primary MALT lymphoma of the breast. Issues in diagnosis and breast-conservation treatment, as it pertains to primary MALT lymphoma of the breast, will be discussed.

Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation.

The antineoplastic drug sorafenib (BAY 43-9006) is a multikinase inhibitor that targets the serine-threonine kinase B-Raf as well as several tyrosine kinases. Given the numerous molecular targets of sorafenib, there are several potential anticancer mechanisms of action, including induction of apoptosis, cytostasis, and antiangiogenesis. We observed that sorafenib has broad activity in viability assays in several human tumor cell lines but selectively induces apoptosis in only some lines. Sorafenib was found to decrease Mcl-1 levels in most cell lines tested, but this decrease did not correlate with apoptotic sensitivity. Sorafenib slows cell cycle progression and prevents irradiated cells from reaching and accumulating at G2-M. In synchronized cells, sorafenib causes a reversible G1 delay, which is associated with decreased levels of cyclin D1, Rb, and phosphorylation of Rb. Although sorafenib does not affect intrinsic radiosensitivity using in vitro colony formation assays, it significantly reduces colony size. In HCT116 xenograft tumor growth delay experiments in mice, sorafenib alters radiation response in a schedule-dependent manner. Radiation treatment followed sequentially by sorafenib was found to be associated with the greatest tumor growth delay. This study establishes a foundation for clinical testing of sequential fractionated radiation followed by sorafenib in gastrointestinal and other malignancies.

Regulation of nuclear receptor transcriptional activity by a novel DEAD box RNA helicase (DP97).

We have identified a novel DEAD box RNA helicase (97 kDa, DP97) from a breast cancer cDNA library that interacts in a hormone-dependent manner with nuclear receptors and represses their transcriptional activity. DP97 has RNA-dependent ATPase activity, and mapping studies localize the interacting regions of DP97 and nuclear receptors to the C-terminal region of DP97 and the hormone binding/activation function-2 region of estrogen receptors (ER), as well as several other nuclear receptors. Repression by DP97 maps to a small region (amino acids 589-631) that has homology to a repression domain in the corepressor protein NCoR2/SMRTe. This region of DP97 is necessary and sufficient for its intrinsic repression activity. The N-terminal helicase region of DP97 is, however, dispensable for its transcriptional repressor activity. The knockdown of endogenous cellular DP97 by antisense DP97 or RNA interference (siRNA for DP97) results in significant enhancement of the expression of estradiol-ER-stimulated genes and attenuation of the repression of genes inhibited by the estradiol-ER. This implies that endogenous DP97 normally dampens stimulation and intensifies repression of estradiol-ER-regulated genes. Our findings add to the growing evidence that RNA helicases can associate with nuclear receptors and function as coregulators to modulate receptor transcriptional activity.

Alteration of large-scale chromatin structure by estrogen receptor.

The estrogen receptor (ER), a member of the nuclear hormone receptor superfamily important in human physiology and disease, recruits coactivators which modify local chromatin structure. Here we describe effects of ER on large-scale chromatin structure as visualized in live cells. We targeted ER to gene-amplified chromosome arms containing large numbers of lac operator sites either directly, through a lac repressor-ER fusion protein (lac rep-ER), or indirectly, by fusing lac repressor with the ER interaction domain of the coactivator steroid receptor coactivator 1. Significant decondensation of large-scale chromatin structure, comparable to that produced by the approximately 150-fold-stronger viral protein 16 (VP16) transcriptional activator, was produced by ER in the absence of estradiol using both approaches. Addition of estradiol induced a partial reversal of this unfolding by green fluorescent protein-lac rep-ER but not by wild-type ER recruited by a lac repressor-SRC570-780 fusion protein. The chromatin decondensation activity did not require transcriptional activation by ER nor did it require ligand-induced coactivator interactions, and unfolding did not correlate with histone hyperacetylation. Ligand-induced coactivator interactions with helix 12 of ER were necessary for the partial refolding of chromatin in response to estradiol using the lac rep-ER tethering system. This work demonstrates that when tethered or recruited to DNA, ER possesses a novel large-scale chromatin unfolding activity.