Mutagenesis and structural modeling implicate RME-8 IWN domains as conformational control points.

After endocytosis, transmembrane cargo is differentially sorted into degradative or recycling pathways. This process is facilitated by recruitment into physically distinct degradative or recycling microdomains on the limiting membrane of individual endosomes. Endosomal sorting complexes required for transport (ESCRT) mark the degradative microdomain, while the recycling domain is marked by the retromer complex and associated proteins RME-8 and SNX-1. The separation of endosomal microdomains is also controlled by RME-8 and SNX-1, at least in part via removal of degradative component HRS/HGRS-1 from the recycling microdomain. This activity is likely due to recruitment and activation of chaperone Hsc70 on the endosome by the RME-8 DNAJ domain. To better understand the mechanism of RME-8 function we performed a new phylogenetic analysis of RME-8 and identified new conserved sequence features. In a complementary approach, we performed structure-function analysis that identified the C-terminus as important for microdomain localization and likely substrate binding, while N-terminal sequences beyond the known single N-terminal PH-like domain are important for endosome recruitment. Random mutagenesis identified IWN4, and by analogy IWN3, to be important for the autoinhibitory DNAJ domain binding, with IWN3 playing a critical role in HRS uncoating activity. Combining AlphaFold structural predictions with in vivo mutation analysis of RME-8, we propose a model whereby SNX-1 and the IWN domains control the conformation of RME-8 and hence the productive exposure of the DNAJ domain. Furthermore, we propose that the activation of RME-8 is cyclical, with SNX-1 acting as an activator and a target of RME-8 uncoating activity.

Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor in Caenorhabditis elegans.

Tetraspanins are a unique family of 4-pass transmembrane proteins that play important roles in a variety of cell biological processes. We have previously shown that 2 paralogous tetraspanins in Caenorhabditis elegans, TSP-12 and TSP-14, function redundantly to promote bone morphogenetic protein (BMP) signaling. The underlying molecular mechanisms, however, are not fully understood. In this study, we examined the expression and subcellular localization patterns of endogenously tagged TSP-12 and TSP-14 proteins. We found that TSP-12 and TSP-14 share overlapping expression patterns in multiple cell types, and that both proteins are localized on the cell surface and in various types of endosomes, including early, late, and recycling endosomes. Animals lacking both TSP-12 and TSP-14 exhibit reduced cell-surface levels of the BMP type II receptor DAF-4/BMPRII, along with impaired endosome morphology and mislocalization of DAF-4/BMPRII to late endosomes and lysosomes. These findings indicate that TSP-12 and TSP-14 are required for the recycling of DAF-4/BMPRII. Together with previous findings that the type I receptor SMA-6 is recycled via the retromer complex, our work demonstrates the involvement of distinct recycling pathways for the type I and type II BMP receptors and highlights the importance of tetraspanin-mediated intracellular trafficking in the regulation of BMP signaling in vivo. As TSP-12 and TSP-14 are conserved in mammals, our findings suggest that the mammalian TSP-12 and TSP-14 homologs may also function in regulating transmembrane protein recycling and BMP signaling.

Identification with and Social Comparison to Teen Mothers on Teen Mom Over Time.

This study replicates from a cross-sectional study about how young Latina teen viewers identify with and socially compare to teen mothers on MTV's Teen Mom over time. Identification and social comparison effects on attitudes toward teen pregnancy were assessed among the same group of Latina teen viewers at two different time points approximately one year apart. Results determined that upward social comparison and identification were associated with positive attitudes toward teen pregnancy in eighth grade, whereas downward social comparison was associated with negative attitudes toward teen pregnancy in ninth grade. Implications for teen mom reality programming audiences are discussed.

Clinic screening for adverse childhood experiences in people living with HIV to Improve Care Delivery.

Adverse childhood experiences (ACEs) are associated with negative health outcomes; however, screening for ACEs is not routinely performed among people living with HIV (PLWH). We conducted a single-center, cross-sectional pilot study to define the (1) prevalence of ACEs in PLWH and (2) acceptability of ACEs screening in routine out-patient clinical care. One hundred participants completed screening: median age of participants was 49 years (interquartile range: 38.5-59.5), 73% male, 66% Non-Hispanic Black/African American, and 47% gay/lesbian. Clinically significant ACEs score, defined as ≥4, was reported in 51%. High ACEs score was more common among participants <50 years old (64.7% vs. 36.7%; p < 0.01), but the prevalence of ACEs ≥4 did not differ by gender, race, ethnicity, or sexual orientation. Among participants with ≥4 ACEs, 44.4% screened negative on both PHQ-9 and PC-PTSD screens. The majority of participants (89%) reported a positive experience with ACEs screening. The prevalence of clinically significant ACEs in this clinic population of PLWH was more than twice that reported in the general population. Routine ACEs screening can improve delivery of trauma-informed care in the HIV primary care setting.

Analyzing the Cost of Hospital Contact Isolation Practices: Implications for Nursing Administrator Practice, Research, and Policy.

OBJECTIVES: This study aimed to determine the weekly costs of contact precaution (CP) use with medically stable patients infected/colonized with methicillin-resistant Staphylococcus aureus (MRSA) and to estimate the annual financial and environmental costs of CP. BACKGROUND: The increasing use of disposables for infection control contributes to increasing hospital costs and amounts of solid waste at rates that are becoming unsustainable. METHODS: A cost analysis was conducted using data from time/motion observations and previous waste audit study, along with hospital finance department values and US Department of Labor salary rates. RESULTS: Weekly and annual costs were $521.67 and $557 463 (5% hospital multidrug-resistant organism [MDRO] rate assumed). Personal protective equipment accounted for 43% of the waste produced (approximately 1600 pounds annually). CONCLUSIONS: Implications for nurse administrators include reevaluating activities that require personal protective equipment (PPE) and partnering with materials and human factor engineers to develop more financially and environmentally sustainable infection control practices.

Hispanic Mother-Daughter Communication About the Risks of Sex, Drugs, and Alcohol: Influences and the Strategies Mothers Use.

PURPOSE: U.S. Hispanic adolescents are at risk for negative health outcomes due to risk-taking behaviors involving sex, drugs, and alcohol. Mother-daughter communication can reduce these risk-taking behaviors and reinforce parents' expectations. The purpose of this study was to explore mothers' descriptions of their communication about risk-taking behaviors with their early adolescent Hispanic daughters. DESIGN AND METHODS: This qualitative descriptive study involved focus groups with 21 Hispanic mothers of 7th grade (12-14 years old) girls. Conventional content analysis was conducted to identify the strategies they used during these conversations. RESULTS: Strategies mothers used included warning, focusing on negative consequences, creating opportunities to express maternal expectations, and stressing the importance of positive influences. Communication was also influenced by daughters' physical development and social media. CONCLUSIONS: The mothers were concerned about their daughters' exposure to risk-taking behaviors but were unsure about how to talk to their daughters about how to avoid them, particularly regarding topics related to sex. PRACTICE IMPLICATIONS: Our study results have implications on how to facilitate parent-child conversations about risk-taking behaviors and to equip mothers and parents to teach their children how to avoid engaging in these behaviors.

SNX-1 and RME-8 oppose the assembly of HGRS-1/ESCRT-0 degradative microdomains on endosomes.

After endocytosis, transmembrane cargo reaches endosomes, where it encounters complexes dedicated to opposing functions: recycling and degradation. Microdomains containing endosomal sorting complexes required for transport (ESCRT)-0 component Hrs [hepatocyte growth factor-regulated tyrosine kinase substrate (HGRS-1) in Caenorhabditis elegans] mediate cargo degradation, concentrating ubiquitinated cargo and organizing the activities of ESCRT. At the same time, retromer associated sorting nexin one (SNX-1) and its binding partner, J-domain protein RME-8, sort cargo away from degradation, promoting cargo recycling to the Golgi. Thus, we hypothesized that there could be important regulatory interactions between retromer and ESCRT that balance degradative and recycling functions. Taking advantage of the naturally large endosomes of the C. elegans coelomocyte, we visualized complementary ESCRT-0 and RME-8/SNX-1 microdomains in vivo and assayed the ability of retromer and ESCRT microdomains to regulate one another. We found in snx-1(0) and rme-8(ts) mutants increased endosomal coverage and intensity of HGRS-1-labeled microdomains, as well as increased total levels of HGRS-1 bound to membranes. These effects are specific to SNX-1 and RME-8, as loss of other retromer components SNX-3 and vacuolar protein sorting-associated protein 35 (VPS-35) did not affect HGRS-1 microdomains. Additionally, knockdown of hgrs-1 had little to no effect on SNX-1 and RME-8 microdomains, suggesting directionality to the interaction. Separation of the functionally distinct ESCRT-0 and SNX-1/RME-8 microdomains was also compromised in the absence of RME-8 and SNX-1, a phenomenon we observed to be conserved, as depletion of Snx1 and Snx2 in HeLa cells also led to greater overlap of Rme-8 and Hrs on endosomes.

Parent Communication and Bullying Among Hispanic Adolescent Girls.

In this article, we report findings regarding parent communication and daughter's experiences of bullying and victimization in a sample of Hispanic families with seventh-grade daughters. About 57% of daughters reported experiencing any form of victimization and 37% reported engaging in some type of bullying behavior. Overall, the most common type of victimization reported was verbal/emotional bullying (36%). Nearly all parents agreed they had spoken with their daughters about the dangers of bullying perpetration (95%) and how to handle being victimized (96%), but there was no association between the frequency with which parents spoke with their daughters about bullying perpetration and their child's victimization experiences. Additionally, the gap between parent and child acculturation did not appear to moderate this association. The high incidence of self-reported bullying perpetration and victimization experiences underscores the need for school nurses, parents, and school personnel to address bullying behavior.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

Implementation Quality: Implications for Intervention and Translational Science.

PURPOSE: Implementation quality (IQ), a critical concept for translational science, measures the discrepancy between an intervention's intended design and its implementation. Quantifying the impact of IQ on intervention outcomes informs efforts to improve intervention translatability. The purpose of this article is to define and describe IQ and its dimensions (content adherence, quality of delivery, and engagement) with a focus on individualized interventions being delivered in research and practice settings. APPROACH: We apply IQ concepts from intervention science in two contexts: (a) an intervention currently being investigated in an efficacy trial, and (b) a practice situation involving the application of evidence-based practice guidelines during clinic visits. IQ measurement approaches are presented using a study protocol, progress notes, interdisciplinary meeting notes, or clinical guidelines, depending upon whether the intervention is delivered during a research study or a clinical encounter. CONCLUSIONS: The investigators describe the necessary infrastructure and support for capturing IQ data and the subsequent complexities and challenges of collecting, measuring, and analyzing these data. Understanding IQ is critical to advancing translational science. Such understanding informs application of appropriate IQ measures, and promotes effective translation of evidence-based interventions into practice. Policy changes are needed to promote IQ assessment to ensure high-quality clinical encounters during which interventions are effectively delivered. CLINICAL RELEVANCE: In both research and practice settings, the conceptualization and measurement of IQ will improve patient outcomes by advancing translational science and integrating evidence-based interventions into nursing practice.

Silent information regulator 3: the Goldilocks of the silencing complex.

A recent explosion of work surrounds the interactions between Sir3p (Silent Information Regulator 3) and chromatin. We review here the Sir3p functions related to its role in silencing in Saccharomyces cerevisiae. This unusual protein, which is absolutely required for silencing, is distantly related to the highly conserved replication initiator Orc1p, but is itself phylogenetically limited to "post-genome-duplicated" budding yeasts. Several recent studies revise earlier models for Sir3p action. Specifically, the N-terminal bromo-adjacent homology (BAH) domain plays a now well-defined role in silencing, and a picture is emerging in which both termini of Sir3p bind two locations on the nucleosome: (1) the loss of ribosomal DNA silencing (LRS) surface in the nucleosome core, and (2) the N-terminal histone tails for effective silencing at telomeres. We relate Sir3p structure and function, and summarize recent molecular studies of Sir3p/chromatin binding, Sir3p/Dot1p competition, and the possible role of O-Acetyl ADP ribose (O-AADPR) in Sir3p/chromatin binding. We emphasize recent genetic data that provide important new insights and settle controversies created by in vitro work. Finally, we synthesize these ideas to revise the model for how Sir3p mediates silent chromatin formation in yeast, in part through its affinity for the LRS region of the nucleosome, which must be "just right."

Improving the Care of Patients with Chronic Kidney Disease Using Group Visits: A Pilot Study to Reflect an Emphasis on the Patients Rather Than the Disease.

This two-group, repeated-measures experimental study assessed the efficacy of a nurse practitioner-facilitated chronic kidney disease (CKD) group visit (GV) model versus usual nephrology care for patients with Stage 4 CKD. The study enrolled patients from two sites of an outpatient nephrology practice (n = 30) and randomized subjects to usual care (n = 14) or to the GV model (n = 16). Data regarding CKD knowledge, self-efficacy/disease self-management, and physiologic measures were collected at baseline, 6 months, and 9 months. Satisfaction was obtained at 6 months and 9 months. Usual nephrology office visit components were maintained during six monthly GVs, with group discussions of CKD-related topies. Results indicated a statistical improvement in CKD knowledge for both groups (F[1.498, 34.446] = 6.363, p = 0.008). An upward trend in mean scores for self-management subscales and self-efficacy scores was demonstrated in the GV patients, with no improvement found in the usual care group. Twenty-six of 30 patients completed the study, with 92% attendance in the GV group. GV satisfaction was high.

Resisting pressure from peers to engage in sexual behavior: What communication strategies do early adolescent Latino Girls use?

A content analysis of early adolescent (M=12.02 years) Latino girls' (n=44) responses to open-ended questions imbedded in an electronic survey was conducted to explore strategies girls may use to resist peer pressure with respect to sexual behavior. Analysis yielded 341 codable response units, 74% of which were consistent with the REAL typology (i.e., refuse, explain, avoid, and leave) previously identified in adolescent substance use research. However, strategies reflecting a lack of resistance (11%) and inconsistency with communication competence (e.g., aggression, involving authorities) were also noted (15%). Frequency of particular strategies varied according to offer type, suggesting a variety of strategies may be needed to resist the peer pressure that puts early adolescent girls at risk for engaging in sexual behavior. Findings argue for universality of the REAL typology, building communication competence skills for conflict resolution in dating situations, and including peer resistance strategies in adolescent pregnancy prevention programs.

Cardiac autonomic dysfunction and arterial stiffness among children and adolescents with attention deficit hyperactivity disorder treated with stimulants.

OBJECTIVE: To compare markers of cardiovascular health in youth diagnosed with attention deficit hyperactivity disorder (ADHD) by the use of stimulant medication with healthy controls. STUDY DESIGN: Children and adolescents (n = 85; mean age 11.2 ± 2.8 years; 66 boys) diagnosed with ADHD using a stimulant and 53 siblings without ADHD (mean age 11.1 ± 3.8 years; 28 boys) were included in this cross-sectional study. Measured variables included blood pressure, heart rate (HR), HR variability: SD of the RR interval and low frequency to high frequency ratio, carotid-radial pulse wave velocity, carotid artery augmentation index (AIx), radial artery AIx, brachial artery flow-mediated dilation, and digital reactive hyperemic index. RESULTS: Compared with control patients, participants with ADHD had greater resting systolic blood pressure (3.9 mm Hg, 95% CI [1.2-6.7], P = .005), diastolic blood pressure (5.5 mm Hg, 95% CI [3.2-7.8], P < .001), HR (9.2 beats/min, 95% CI [6.0-12.3], P < .001), low frequency to high frequency ratio (0.55, 95% CI [0.22-0.89], P = .001), carotid AIx (7.2%, 95% CI [1.9-12.5], P = .008), and pulse wave velocity (0.36 m/s, 95% CI [-0.05, 0.78], P = .089), and lower SD of the RR interval (-33.7 milliseconds, 95% CI [-46.1, -21.3], P < .001). Neither flow-mediated dilation nor reactive hyperemic index was significantly different. CONCLUSIONS: Children and adolescents being treated with a stimulant medication for ADHD exhibited signs of altered cardiac autonomic function, characterized by increased sympathetic tone, and showed evidence of arterial stiffening.

Narrative and Behavioral Engagement as Indicators for the Effectiveness of Intentionally Designed Virtual Simulations of Interpersonal Interactions.

Interventions involving simulated interactions aimed at mimicking real situations must be engaging to maximize their effectiveness. This study aimed to assess how a sample of middle school girls displayed behavioral and cognitive indicators of engagement when interacting with avatars representing game characters that were controlled by a human digital puppeteer. The simulation game, DRAMA-RAMA, is a component of an intervention intended to reduce at-risk girls' sexual and other risky behaviors. We used verbal/nonverbal behaviors and surveys to assess the game players' cognitive and behavioral involvement (N = 131). Participants perceived the game scenarios and interactions as realistic and the characters as similar to people in real life. Participants' behavior indicated their involvement and interest in interacting with the game characters. Finally, participants tended to be appropriate but not effective when attempting to advise/support the characters. These findings have implications for assessing successful operationalization of communication designs in interactive virtual learning environments.

Outbreak of multidrug-resistant Salmonella infections in people linked to pig ear pet treats, United States, 2015-2019: results of a multistate investigation.

Background: International distribution of contaminated foods can be a source of Salmonella infections in people and can contribute to the spread of antimicrobial-resistant bacteria across countries. We report an investigation led by the United States Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and state governmental officials into a multistate outbreak of salmonellosis linked to pig ear pet treats. Methods: Pig ear treats and companion dogs were tested for Salmonella by state officials and the FDA. Products were traced back to the country of origin when possible. Cases were defined as outbreak illnesses in people associated with one of seven Salmonella serotypes genetically related to samples from pig ear pet treats, with isolation dates from June 2015 to September 2019. Whole genome sequencing (WGS) of isolates was used to predict antimicrobial resistance. Findings: The outbreak included 154 human cases in 34 states. Of these, 107 of 122 (88%) patients reported dog contact, and 65 of 97 (67%) reported contact with pig ear pet treats. Salmonella was isolated from 137 pig ear treats, including some imported from Argentina, Brazil, and Colombia, and from four dogs. WGS predicted 77% (105/137) of human and 43% (58/135) of pig ear treat isolates were resistant to ≥3 antimicrobial classes. Interpretation: This was the first documented United States multistate outbreak of Salmonella infections linked to pig ear pet treats. This multidrug-resistant outbreak highlights the interconnectedness of human health and companion animal ownership and the need for zoonotic pathogen surveillance to prevent human illness resulting from internationally transported pet food products. Funding: Animal Feed Regulatory Program Standards award. Animal and product testing conducted by FDA Vet-LIRN was funded by Vet-LIRN infrastructure grants (PAR-22-063).

Randomized trial of a peer resistance skill-building game for Hispanic early adolescent girls.

BACKGROUND: Adolescents can use peer resistance skills to avoid being pressured into risky behavior, such as early sexual behavior. Avatar-based virtual reality technology offers a novel way to help build these skills. OBJECTIVES: The aims of this study were to evaluate the feasibility of an avatar-based virtual reality peer resistance skill building game (DRAMA-RAMA), to explore the impact of game play on peer resistance self-efficacy, and to assess how positively the game was perceived. METHODS: Forty-four low-income early adolescent Hispanic girls were assigned randomly to either the intervention (DRAMA-RAMA) or attention control game (Wii Dancing With the Stars) condition. All participants were offered a five-session curriculum that included peer resistance skill content before playing their respective game for 15 minutes, once a week, for 2 weeks. Participants completed electronic surveys at baseline, after game play, and at 2 months to assess demographics, peer resistance self-efficacy, and sexual behavior. They also completed a paper-pencil game experience questionnaire immediately after game play. Data were analyzed using descriptive statistics, t test, chi-square, and analyses of covariance. RESULTS: Separate analyses of covariance showed a significant game effect at posttest for the peer resistance self-efficacy measure (F = 4.21, p < .05), but not at follow-up (F = 0.01, p = .92). DRAMA-RAMA was rated as positively as the Wii Dancing With the Stars (p > .26). DISCUSSION: This randomized control trial provides preliminary support for the hypothesis that playing an avatar-based virtual reality technology game can strengthen peer resistance skills, and early adolescent Hispanic girls will have a positive response to this game.

The Impact of an Infectious Diseases Transition Service on the Care of Outpatients on Parenteral Antimicrobial Therapy.

BACKGROUND: Many hospitalized patients with complicated infections are discharged on outpatient parenteral antimicrobial therapy (OPAT). However, little is known about how to improve the postdischarge care of OPAT patients. OBJECTIVE: The impact of an infectious diseases transitions service (IDTS) on OPAT patient readmissions, as well as on processes of care, was evaluated. METHODS: We performed a controlled, quasi-experimental evaluation over 15 months in an academic medical center. Intervention-arm patients, before and after the introduction of an IDTS, were seen by the general infectious diseases consult teams, while control-arm patients (discharged on OPAT after hospitalization with bacteremia) were not. The IDTS prospectively tracked all OPAT patients and coordinated follow-up. The impact of the IDTS was calculated using a differences-in-differences approach where the interaction between time (before vs after the IDTS intervention) and study arm (intervention vs control arm) was the variable of interest. The control arm was used only in primary outcome analyses (readmissions and emergency department visits). Secondary outcomes included process of care measures and non-readmission clinical outcomes. RESULTS: Of 488 consecutive patients requiring OPAT, 362 were in the intervention arm (215 pre-intervention and 147 post-intervention) and 126 in the control arm (70 pre-intervention and 56 post-intervention). Compared to the control arm, the IDTS was not associated with changes in 60-day readmissions and/or emergency department visits (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI] = 0.13-1.79). In the intervention arm, implementation of the IDTS was associated with fewer antimicrobial therapy errors (OR = 0.062; 95% CI = 0.015-0.262), increased laboratory test receipt (OR = 27.85; 95% CI = 12.93-59.99), and improved outpatient follow-up (OR = 2.44; 95% CI = 1.50-3.97). CONCLUSIONS: In a controlled evaluation, the IDTS did not affect readmissions despite improving process of care measures for targeted patients. Care coordination services may improve OPAT quality of care, but their relationship to readmissions is unclear.

Infección de Amor (Infectious Love): Development and Acceptability of a Telenovela/Soap Opera Intervention for HIV Prevention For Latinas.

Latinas continue to be disproportionately affected by HIV in the United States. Effective interventions to address HIV-related disparities among Latinas are available; however, they have not achieved widespread dissemination due to implementation challenges for real-world settings. A culturally tailored intervention that increases access to HIV prevention is urgently needed. The objective of this study was to develop a culturally tailored telenovela (i.e., a soap opera) to promote HIV prevention behaviors (condom use; HIV testing; and pre-exposure prophylaxis awareness, access, and use) among Latinas. The study was conducted in community organizations throughout South Florida. A total of 44 Spanish-speaking Latinas, 18-35 years old, and sexually active with a man in the past 6 months participated in the study. The final product was an HIV prevention telenovela that incorporated Latinas' ideas and feedback and was produced as four 10-minute filmed episodes. This study aimed to develop innovative approaches to reduce HIV-related disparities for Latinas.