Redundant and Cryptic Enhancer Activities of the Drosophilayellow Gene.

Cis-regulatory sequences known as enhancers play a key role in regulating gene expression. Evolutionary changes in these DNA sequences contribute to phenotypic evolution. The Drosophilayellow gene, which is required for pigmentation, has emerged as a model system for understanding how cis-regulatory sequences evolve, providing some of the most detailed insights available into how activities of orthologous enhancers have diverged between species. Here, we examine the evolution of yellow cis-regulatory sequences on a broader scale, by comparing the distribution and function of yellow enhancer activities throughout the 5' intergenic and intronic sequences of Drosophila melanogaster, D. pseudoobscura, and D. willistoni We find that cis-regulatory sequences driving expression in a particular tissue are not as modular as previously described, but rather have many redundant and cryptic enhancer activities distributed throughout the regions surveyed. Interestingly, cryptic enhancer activities of sequences from one species often drove patterns of expression observed in other species, suggesting that the frequent evolutionary changes in yellow expression observed among Drosophila species may be facilitated by gaining and losing repression of preexisting cis-regulatory sequences.

Feasibility of Emergency Department-initiated, Mobile Health Blood Pressure Intervention: An Exploratory, Randomized Clinical Trial.

OBJECTIVES: We aimed to assess the feasibility of a text messaging intervention by determining the proportion of emergency department (ED) patients who responded to prompted home blood pressure (BP) self-monitoring and had persistent hypertension. We also explored the effect of the intervention on systolic blood pressure (sBP) over time. METHODS: We conducted a randomized, controlled trial of ED patients with expected discharge to home with elevated BP. Participants were identified by automated alerts from the electronic health record. Those who consented received a BP cuff to take home and enrolled in the 3-week screening phase. Text responders with persistent hypertension were randomized to control or weekly prompted BP self-monitoring and healthy behavior text messages. RESULTS: Among the 104 patients enrolled in the ED, 73 reported at least one home BP over the 3-week run-in (screening) period. A total of 55 of 73 reported a home BP of ≥140/90 and were randomized to SMS intervention (n = 28) or control (n = 27). The intervention group had significant sBP reduction over time with a mean drop of 9.1 mm Hg (95% confidence interval = 1.1 to 17.6). CONCLUSIONS: The identification of ED patients with persistent hypertension using home BP self-monitoring and text messaging was feasible. The intervention was associated with a decrease in sBP likely to be clinically meaningful. Future studies are needed to further refine this approach and determine its efficacy.

The role of depression and social support on readmission rates within one year of traumatic injury.

OBJECTIVE: Hospital readmission rates have become a quality metric-particularly in trauma and acute care, where up to one third of individuals with traumatic injury return to the hospital. Thus, identifying predictors of readmission is a priority in an effort to reduce readmissions. Based on previous theoretical work, this study tests the utility of social support and depression in predicting readmissions up to one year after initial injury. METHOD: Data from 180 injured individuals admitted to a large, urban Level 1 trauma center were matched to a regional readmissions database. Logistic regression was used to assess whether social support levels or positive depression screens during initial trauma visit predicted unplanned (a) readmissions or (b) emergency/urgent outpatient visits. RESULTS: Within the sample, there were 32 total readmissions and 50 total emergency outpatient encounters following initial injury. Depression continued to be a risk factor for emergency outpatient visits only (OR = 2.75). Patients with greater social integration (OR = 0.78), more guidance (advice or information; OR = 0.72) and more reliable alliance (OR = 0.72) as forms of social support were less likely to readmit. CONCLUSIONS: This study demonstrates the utility of screening for depression and social support in predicting readmission within one year after traumatic injury. Future efforts should continue emphasizing the impact of initial depression and the need for patients to have trusted individuals in their lives to whom they can turn during recovery; doing so may lower the probability that patients return to hospital. (PsycINFO Database Record

Reach Out Churches: A Community-Based Participatory Research Pilot Trial to Assess the Feasibility of a Mobile Health Technology Intervention to Reduce Blood Pressure Among African Americans.

Innovative strategies are needed to reduce the hypertension epidemic among African Americans. Reach Out was a faith-collaborative, mobile health, randomized, pilot intervention trial of four mobile health components to reduce high blood pressure (BP) compared to usual care. It was designed and tested within a community-based participatory research framework among African Americans recruited and randomized from churches in Flint, Michigan. The purpose of this pilot study was to assess the feasibility of the Reach Out processes. Feasibility was assessed by willingness to consent (acceptance of randomization), proportion of weeks participants texted their BP readings (intervention use), number lost to follow-up (retention), and responses to postintervention surveys and focus groups (acceptance of intervention). Of the 425 church members who underwent BP screening, 94 enrolled in the study and 73 (78%) completed the 6-month outcome assessment. Median age was 58 years, and 79% were women. Participants responded with their BPs on an average of 13.7 (SD = 10.7) weeks out of 26 weeks that the BP prompts were sent. All participants reported satisfaction with the intervention. Reach Out, a faith-collaborative, mobile health intervention was feasible. Further study of the efficacy of the intervention and additional mobile health strategies should be considered.

Development and Validation of a Bilingual Stroke Preparedness Assessment Instrument.

BACKGROUND AND PURPOSE: Stroke preparedness interventions are limited by the lack of psychometrically sound intermediate end points. We sought to develop and assess the reliability and validity of the video-Stroke Action Test (video-STAT) an English and a Spanish video-based test to assess people's ability to recognize and react to stroke signs. METHODS: Video-STAT development and testing was divided into 4 phases: (1) video development and community-generated response options, (2) pilot testing in community health centers, (3) administration in a national sample, bilingual sample, and neurologist sample, and (4) administration before and after a stroke preparedness intervention. RESULTS: The final version of the video-STAT included 8 videos: 4 acute stroke/emergency, 2 prior stroke/nonemergency, 1 nonstroke/emergency, and 1 nonstroke/nonemergency. Acute stroke recognition and action response were queried after each vignette. Video-STAT scoring was based on the acute stroke vignettes only (score range 0-12 best). The national sample consisted of 598 participants, 438 who took the video-STAT in English and 160 who took the video-STAT in Spanish. There was adequate internal consistency (Cronbach α=0.72). The average video-STAT score was 5.6 (SD=3.6), whereas the average neurologist score was 11.4 (SD=1.3). There was no difference in video-STAT scores between the 116 bilingual video-STAT participants who took the video-STAT in English or Spanish. Compared with baseline scores, the video-STAT scores increased after a stroke preparedness intervention (6.2 versus 8.9, P<0.01) among a sample of 101 black adults and youth. CONCLUSIONS: The video-STAT yields reliable scores that seem to be valid measures of stroke preparedness.

Potential Direct Regulators of the Drosophila yellow Gene Identified by Yeast One-Hybrid and RNAi Screens.

The regulation of gene expression controls development, and changes in this regulation often contribute to phenotypic evolution. Drosophila pigmentation is a model system for studying evolutionary changes in gene regulation, with differences in expression of pigmentation genes such as yellow that correlate with divergent pigment patterns among species shown to be caused by changes in cis- and trans-regulation. Currently, much more is known about the cis-regulatory component of divergent yellow expression than the trans-regulatory component, in part because very few trans-acting regulators of yellow expression have been identified. This study aims to improve our understanding of the trans-acting control of yellow expression by combining yeast-one-hybrid and RNAi screens for transcription factors binding to yellow cis-regulatory sequences and affecting abdominal pigmentation in adults, respectively. Of the 670 transcription factors included in the yeast-one-hybrid screen, 45 showed evidence of binding to one or more sequence fragments tested from the 5' intergenic and intronic yellow sequences from D. melanogaster, D. pseudoobscura, and D. willistoni, suggesting that they might be direct regulators of yellow expression. Of the 670 transcription factors included in the yeast-one-hybrid screen, plus another TF previously shown to be genetically upstream of yellow, 125 were also tested using RNAi, and 32 showed altered abdominal pigmentation. Nine transcription factors were identified in both screens, including four nuclear receptors related to ecdysone signaling (Hr78, Hr38, Hr46, and Eip78C). This finding suggests that yellow expression might be directly controlled by nuclear receptors influenced by ecdysone during early pupal development when adult pigmentation is forming.

Stroke Ready Intervention: Community Engagement to Decrease Prehospital Delay.

BACKGROUND: Time-limited acute stroke treatments are underused, primarily due to prehospital delay. One approach to decreasing prehospital delay is to increase stroke preparedness, the ability to recognize stroke, and the intention to immediately call emergency medical services, through community engagement with high-risk communities. METHODS AND RESULTS: Our community-academic partnership developed and tested "Stroke Ready," a peer-led, workshop-based, health behavior intervention to increase stroke preparedness among African American youth and adults in Flint, Michigan. Outcomes were measured with a series of 9 stroke and nonstroke 1-minute video vignettes; after each video, participants selected their intended response (primary outcome) and symptom recognition (secondary outcome), receiving 1 point for each appropriate stroke response and recognition. We assessed differences between baseline and posttest appropriate stroke response, which was defined as intent to call 911 for stroke vignettes and not calling 911 for nonstroke, nonemergent vignettes and recognition of stroke. Outcomes assessments were performed before workshop 1 (baseline), at the conclusion of workshop 2 (immediate post-test), and 1 month later (delayed post-test). A total of 101 participants completed the baseline assessment (73 adults and 28 youths), 64 completed the immediate post-test, and 68 the delayed post-test. All participants were African American. The median age of adults was 56 (interquartile range 35-65) and of youth was 14 (interquartile range 11-16), 65% of adults were women, and 50% of youths were women. Compared to baseline, appropriate stroke response was improved in the immediate post-test (4.4 versus 5.2, P<0.01) and was sustained in the delayed post-test (4.4 versus 5.2, P<0.01). Stroke recognition did not change in the immediate post-test (5.9 versus 6.0, P=0.34), but increased in the delayed post-test (5.9 versus 6.2, P=0.04). CONCLUSIONS: Stroke Ready increased stroke preparedness, a necessary step toward increasing acute stroke treatment rates. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01499173.

Creating a Novel Video Vignette Stroke Preparedness Outcome Measure Using a Community-Based Participatory Approach.

Evaluating the efficacy of behavioral interventions for rare outcomes is a challenge. One such topic is stroke preparedness, defined as inteventions to increase stroke symptom recognition and behavioral intent to call 911. Current stroke preparedness intermediate outcome measures are centered on written vignettes or open-ended questions and have been shown to poorly reflect actual behavior. Given that stroke identification and action requires aural and visual processing, video vignettes may improve on current measures. This article discusses an approach for creating a novel stroke preparedness video vignette intermediate outcome measure within a community-based participatory research partnership. A total of 20 video vignettes were filmed of which 13 were unambiguous (stroke or not stroke) as determined by stroke experts and had test discrimination among community participants. Acceptable reliability, high satisfaction, and cultural relevance were found among the 14 community respondents. A community-based participatory approach was effective in creating a video vignette intermediate outcome. Future projects should consider obtaining expert and community feedback prior to filming all the video vignettes to improve the proportion of vignettes that are usable. While content validity and preliminary reliability were established, future studies are needed to confirm the reliability and establish construct validity.

Lymphedema in a 7-year-old boy infected with Wuchereria bancrofti in Sierra Leone: a case report.

We present a case of congenital lymphedema in a 7-year-old boy in Sierra Leone with active filarial infection and penile edema. The genital edema with onset at 6 months of age may have been due to a congenital abnormality in lymphatic drainage. Other possible causes of childhood lymphedema, including Milroy's disease, are discussed.

µ-Opioid receptors within subregions of the striatum mediate pair bond formation through parallel yet distinct reward mechanisms.

The prairie vole is a socially monogamous rodent that is an excellent animal model for studies of the neurobiology of social attachment. Such studies have demonstrated that activation of reward circuitry during social interactions facilitates pair bond formation. Within this circuitry, µ-opioid receptors (MORs) modulate naturally rewarding behavior in an anatomically segregated manner; MORs located throughout the striatum (dorsal striatum, NAc core, and the entire NAc shell) are implicated in general motivational processes, whereas those located specifically within the dorsomedial NAc shell mediate positive hedonics (and are referred to as a "hedonic hotspot"). The purpose of the present study was to determine whether MORs within these distinct subregions differentially mediate pair bond formation. We first used receptor autoradiography to compare MOR binding densities between these regions. MOR binding was significantly higher in the NAc core and dorsomedial NAc shell compared with the ventral NAc shell. We next used partner preference testing to determine whether MORs within these subregions differentially mediate pair bonding. Blockade of MORs using 1 or 3 µg of H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 within the dorsal striatum decreased mating during the cohabitation period and inhibited partner preference formation. In contrast, blockade of MORs within dorsomedial NAc shell inhibited partner preference formation without effecting mating behavior, whereas other regions were not involved. Thus, MORs within the dorsal striatum mediate partner preference formation via impairment of mating, whereas those in the dorsomedial NAc shell appear to mediate pair bond formation through the positive hedonics associated with mating.