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).

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.

A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation.

Autophagosomes fuse with lysosomes, forming autolysosomes that degrade engulfed cargo. To maintain lysosomal capacity, autophagic lysosome reformation (ALR) must regenerate lysosomes from autolysosomes using a membrane tubule-based process. Maintaining lysosomal capacity is required to maintain cellular health, especially in neurons where lysosomal dysfunction has been repeatedly implicated in neurodegenerative disease. The DNA-J domain HSC70 co-chaperone RME-8/DNAJC13 has been linked to endosomal coat protein regulation and to neurological disease. We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on intact C. elegans mechanosensory neurons, and primary mouse cortical neurons in culture. Loss of RME-8/DNAJC13 in both systems results in accumulation of grossly elongated autolysosomal tubules. Further C. elegans analysis revealed a similar autolysosome tubule accumulation defect in mutants known to be required for ALR in mammals, including mutants lacking bec-1/BECN1/Beclin1 and vps-15/PIK3R4/p150 that regulate the class III phosphatidylinositol 3-kinase (PtdIns3K) VPS-34, and dyn-1/dynamin that severs ALR tubules. Clathrin is also an important ALR regulator implicated in autolysosome tubule formation and release. In C. elegans we found that loss of RME-8 causes severe depletion of clathrin from neuronal autolysosomes, a phenotype shared with bec-1 and vps-15 mutants. We conclude that RME-8/DNAJC13 plays a previously unrecognized role in ALR, likely affecting autolysosome tubule severing. Additionally, in both systems, loss of RME-8/DNAJC13 reduced macroautophagic/autophagic flux, suggesting feedback regulation from ALR to autophagy. Our results connecting RME-8/DNAJC13 to ALR and autophagy provide a potential mechanism by which RME-8/DNAJC13 could influence neuronal health and the progression of neurodegenerative disease.Abbreviation: ALR, autophagic lysosome reformation; ATG-13/EPG-1, AuTophaGy (yeast Atg homolog)-13; ATG-18, AuTophaGy (yeast Atg homolog)-18; AV, autophagic vacuole; CLIC-1, Clathrin Light Chain-1; EPG-3, Ectopic P Granules-3; EPG-6, Ectopic P Granules-6; LGG-1, LC3, GABARAP and GATE-16 family-1; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; PD, Parkinson disease; PtdIns3P, phosphatidylinositol-3-phosphate; PtdIns(4,5)P2, phosphatidylinositol-4,5-bisphosphate; RME-8, Receptor Mediated Endocytosis-8; SNX-1, Sorting NeXin-1; VPS-34, related to yeast Vacuolar Protein Sorting factor-34.

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.

Syndapin and GTPase RAP-1 control endocytic recycling via RHO-1 and non-muscle myosin II.

After endocytosis, many plasma membrane components are recycled via membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that Syndapin/PACSIN-family protein SDPN-1 is required in vivo for basolateral endocytic recycling in the C. elegans intestine. Here, we document an interaction between the SDPN-1 SH3 domain and a target sequence in PXF-1/PDZ-GEF1/RAPGEF2, a known exchange factor for Rap-GTPases. We found that endogenous mutations engineered into the SDPN-1 SH3 domain, or its binding site in the PXF-1 protein, interfere with recycling in vivo, as does the loss of the PXF-1 target RAP-1. In some contexts, Rap-GTPases negatively regulate RhoA activity, suggesting a potential for Syndapin to regulate RhoA. Our results indicate that in the C. elegans intestine, RHO-1/RhoA is enriched on SDPN-1- and RAP-1-positive endosomes, and the loss of SDPN-1 or RAP-1 elevates RHO-1(GTP) levels on intestinal endosomes. Furthermore, we found that depletion of RHO-1 suppressed sdpn-1 mutant recycling defects, indicating that control of RHO-1 activity is a key mechanism by which SDPN-1 acts to promote endocytic recycling. RHO-1/RhoA is well known for controlling actomyosin contraction cycles, although little is known about the effects of non-muscle myosin II on endosomes. Our analysis found that non-muscle myosin II is enriched on SDPN-1-positive endosomes, with two non-muscle myosin II heavy-chain isoforms acting in apparent opposition. Depletion of nmy-2 inhibited recycling like sdpn-1 mutants, whereas depletion of nmy-1 suppressed sdpn-1 mutant recycling defects, indicating that actomyosin contractility controls recycling endosome function.

A Conserved Requirement for RME-8/DNAJC13 in Neuronal Autolysosome Reformation.

Autophagosomes fuse with lysosomes, forming autolysosomes that degrade engulfed cargo. To maintain lysosomal capacity, autolysosome reformation (ALR) must regenerate lysosomes from autolysosomes using a membrane tubule-based process. Maintaining lysosomal capacity is required to maintain proteostasis and cellular health, especially in neurons where lysosomal dysfunction has been repeatedly implicated in neurodegenerative disease. Cell biological studies have linked the DNA-J domain Hsc70 co-chaperone RME-8/DNAJC13 to endosomal coat protein regulation, while human genetics studies have linked RME-8/DNAJC13 to neurological disease, including Parkinsonism and Essential Tremor. We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on C. elegans mechanosensory neurons in the intact animal, and in primary mouse cortical neurons in culture. We find that loss of RME-8/DNAJC13 in both systems results in accumulation of grossly elongated autolysosomal tubules. Further C. elegans analysis revealed a similar autolysosome tubule accumulation defect in mutants known to be required for ALR in mammals, including bec-1/beclin and vps-15/PIK3R4/p150 that regulate type-III PI3-kinase VPS-34, and dyn-1/dynamin that severs ALR tubules. Clathrin is also an important ALR regulator implicated in autolysosome tubule formation and release. In C. elegans we found that loss of RME-8 causes severe depletion of clathrin from neuronal autolysosomes, a phenotype shared with bec-1 and vps-15 mutants. We conclude that RME-8/DNAJC13 plays a conserved but previously unrecognized role in autolysosome reformation, likely affecting ALR tubule initiation and/or severing. Additionally, in both systems, we found that loss of RME-8/DNAJC13 appeared to reduce autophagic flux, suggesting feedback regulation from ALR to autophagy. Our results connecting RME-8/DNAJC13 to ALR and autophagy provide a potential mechanism by which RME-8/DNAJC13 could influence neuronal health and the progression of neurodegenerative disease.

Syndapin Regulates the RAP-1 GTPase to Control Endocytic Recycling via RHO-1 and Non-Muscle Myosin II.

After endocytosis, many plasma membrane components are recycled via narrow-diameter membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that the F-BAR and SH3 domain Syndapin/PACSIN-family protein SDPN-1 is required in vivo for basolateral endocytic recycling in the C. elegans intestine. Here we sought to determine the significance of a predicted interaction between the SDPN-1 SH3 domain and a target sequence in PXF-1/PDZ-GEF1/RAPGEF2, a known exchange factor for Rap-GTPases. We found that endogenous mutations we engineered into the SDPN-1 SH3 domain, or its binding site in the PXF-1 protein, interfere with recycling in vivo , as does loss of the PXF-1 target RAP-1. Rap-GTPases have been shown in several contexts to negatively regulate RhoA activity. Our results show that RHO-1/RhoA is enriched on SDPN-1 and RAP-1 positive endosomes in the C. elegans intestine, and loss of SDPN-1 or RAP-1 elevates RHO-1(GTP) levels on intestinal endosomes. Furthermore, we found that depletion of RHO-1 suppressed sdpn-1 mutant recycling defects, indicating that control of RHO-1 activity is a key mechanism by which SDPN-1 acts to promote endocytic recycling. RHO-1/RhoA is well-known for controlling actomyosin contraction cycles, although little is known of non-muscle myosin II on endosomes. Our analysis found that non-muscle myosin II is enriched on SDPN-1 positive endosomes, with two non-muscle myosin II heavy chain isoforms acting in apparent opposition. Depletion of nmy-2 inhibited recycling like sdpn-1 mutants, while depletion of nmy-1 suppressed sdpn-1 mutant recycling defects, indicating actomyosin contractility in controlling recycling endosome function.

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.

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.

Cultural Influences on Hispanic Mother-Daughter Communication About Sex.

INTRODUCTION: Hispanic adolescents are at high risk of engaging in sexual risk-taking behaviors. Parent-child communication protects against such behaviors. Among Hispanic families, it is critical to explore how cultural characteristics influence mothers-daughter communication about sex. The purpose of this qualitative study was to understand how cultural values influence mothers' communication about sex with their early adolescent Hispanic daughters. METHODOLOGY: Twenty-one Hispanic mothers of seventh-grade daughters participated in this focus group study. Directed content analysis was used to analyze the data. RESULTS: Four Hispanic cultural values (familismo, machismo, marianismo, and respeto) and how each value influences mother-daughter communication about sex were identified. While mothers want to protect their daughters, there are multiple cultural norms that made it challenging for them to have critical conversations. DISCUSSION: The study informs researchers and clinicians how to facilitate parent-child conversations about sex and to equip parents to teach their children how to avoid engaging in sexual risk-taking behaviors.

The Measurement of Female Early Adolescent Sexual Desire.

We used the developmental systems model to deduce a definition of female early adolescent sexual desire. We evaluated a measure of this phenomenon with a secondary analysis of data from a randomized group sexual health intervention trial involving low-income, English-speaking, seventh grade Latinas enrolled in a Miami-Dade County public school (n = 542). As part of this study, girls completed a four-item early adolescent sexual desire (EASD) measure. Study findings supported internal consistency (Cronbach's alpha = .81 to .82) and stability over a 1-month period (r = .74). Developmental sensitivity was supported by a decline in stability over 12- (r = .66) and 24-month periods (r = .56). Validity was supported by correlations with puberty changes, sexual intentions, sexting, and sexual behavior, and hypothesized mean differences associated with dating and preference for shoes culturally associated with female sexual attractiveness (p < .01). Research implications include validation work with other ethnic/racial groups and using the EASD as a starting point for a measurement continuum tracking development of sexual desire across adolescence and into adulthood. Directions for future research also include measuring the development of sexual desire in boys and transgendered youth across adolescence and into adulthood.

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.

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.

Multicultural Adaptation of Mighty Girls for Widespread Dissemination: Pilot Study, App Development and Usability Testing, and Gauging Parent Support With Focus Groups.

BACKGROUND: Taking evidence-based interventions to scale is a challenge for prevention science. Mighty Girls is an evidence-based sexual health intervention program that combines classroom sessions with novel, cutting-edge technology (digital puppetry). The program was developed for 7th grade Latinas, but US school and community demographics rarely allow interventions targeting a single ethnic group. Additionally, digital puppetry is costly to scale up, and parent disapproval often prevents successful dissemination of adolescent sexual health programs. Intervening steps along the scaling-up pathway are needed to adapt the program prior to scaling up for dissemination. OBJECTIVE: The aims of this study were to create a multicultural adaptation of the Mighty Girls program using a mobile app that is less costly to disseminate and is acceptable to parents of 7th grade girls. METHODS: This study used a three-phase process to adapt Mighty Girls into Mighty Teens. All phases used purposive (nonprobability) sampling of low-income, multicultural, urban metropolitan groups (7th grade girls and their parents) within central Florida. Phase 1 involved two videotaped implementations of a multicultural adaptation of the classroom sessions, one involving focus groups (N=14) and the other serving as a single-group pretest-posttest pilot study (N=23). Phase 2 involved development of a narrative cell phone app prototype, which was subjected to usability testing (N=25). App usability and engagement were assessed qualitatively (observation, focus group, open-ended questions) and quantitatively. Phase 3 used focus groups to assess parent support for the program (N=6). Qualitative data were analyzed using descriptive content analysis. Quantitative data were analyzed using descriptive statistics and paired t tests. RESULTS: Qualitative findings supported classroom sessions being multicultural, and identified simple changes to improve engagement and learning. Quantitative findings from the second classroom session implementation pilot study indicated a significant pre-post difference in intention to delay sexual intercourse (P=.04). App usability and appeal were supported by a System Usability Scale score of 76 (exceeding 68 per the industry standard) and 83% (20/24) of participants agreeing they would recommend the app to friends. Parents (mothers) expressed only positive regard for program goals, and classroom session and app activities. CONCLUSIONS: This study adapted Mighty Girls into an engaging, easier-to-disseminate, multicultural program, termed Mighty Teens, that uses a narrative-generating app to support behavior change, and is likely to be accepted by parents of 7th grade girls. This study also provides evidence of the preliminary effectiveness of Mighty Teens classroom sessions. The sampling method and sample size were appropriate for adaptation, but research involving a more representative US sample is needed to confirm multicultural fit, parent receptivity, and program effectiveness. Study implications include integrating app use throughout the classroom sessions to build narrative-generating skills across the program and increasing the number of narratives produced, which should in turn increase the program's behavior change potency.

Behavioral interventions to improve population health outreach for hepatitis C screening: randomized clinical trial.

OBJECTIVE: To evaluate whether opt out framing, messaging incorporating behavioral science concepts, or electronic communication increases the uptake of hepatitis C virus (HCV) screening in patients born between 1945 and 1965. DESIGN: Pragmatic randomized controlled trial. SETTING: 43 primary care practices from one academic health system (Philadelphia, PA, USA) between April 2019 and May 2020. PARTICIPANTS: Patients born between 1945 and 1965 with no history of screening and at least two primary care visits in the two years before the enrollment period. INTERVENTIONS: This multilevel trial was divided into two studies. Substudy A included 1656 eligible patients of 17 primary care clinicians who were randomized in a 1:1 ratio to a mailed letter about HCV screening (letter only), or a similar letter with a laboratory order for HCV screening (letter+order). Substudy B included the remaining 19 837 eligible patients followed by 417 clinicians. Active electronic patient portal users were randomized 1:5 to receive a mailed letter about HCV screening (letter), or an electronic patient portal message with similar content (patient portal); inactive patient portal users were mailed a letter. In a factorial design, patients in substudy B were also randomized 1:1 to receive standard content (usual care), or content based on principles of social norming, anticipated regret, reciprocity, and commitment (behavioral content). MAIN OUTCOME MEASURES: Proportion of patients who completed HCV testing within four months. RESULTS: 21 303 patients were included in the intention-to-treat analysis. Among the 1642 patients in substudy A, 19.2% (95% confidence interval 16.5% to 21.9%) completed screening in the letter only arm and 43.1% (39.7% to 46.4%) in the letter+order arm (P<0.001). Among the 19 661 patients in substudy B, 14.6% (13.9% to 15.3%) completed screening with usual care content and 13.6% (13.0% to 14.3%) with behavioral science content (P=0.06). Among active patient portal users, 17.8% (16.0% to 19.5%) completed screening after receiving a letter and 13.8% (13.1% to 14.5%) after receiving a patient portal message (P<0.001). CONCLUSIONS: Opt out framing and effort reduction by including a signed laboratory order with outreach increased screening for HCV. Behavioral science messaging content did not increase uptake, and mailed letters achieved a greater response rate than patient portal messages. TRIAL REGISTRATION: ClinicalTrials.gov NCT03712553.

Post-Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High-Flux Hemodialysis.

Patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (IHD) are at increased risk of infection, which represents a leading cause of mortality in this population. The use of additional vascular access devices such as peripherally inserted central catheters to treat such infections should be minimized in patients with ESRD requiring IHD in order to mitigate complications such as infection and thrombosis and to maintain venous patency for hemodialysis access. Intravenous antimicrobial dosing following IHD has the advantages of avoiding additional access devices and providing convenience for patients and providers. Vancomycin, cefazolin, and aminoglycosides have historically been regarded as the primary intravenous antimicrobials administered with IHD given their relatively low cost, convenient dosing, and longevity of clinical use. Despite this, a growing body of literature is evaluating the use of an expanded list of antimicrobials that may be employed using post-dialysis dosing for patients requiring IHD; however, the available data are largely limited to pharmacokinetic studies and small cohorts of infected patients or uninfected subjects. Post-dialytic dosing of intravenous antimicrobials may be considered on a patient-by-patient basis after careful consideration of clinical, microbiological, and logistical factors that may influence the probability of treatment success. This document reviews and evaluates currently available information on the post-dialytic administration of an expanded list of intravenous antimicrobials in the setting of thrice-weekly, high-flux IHD.

Teen Dating Violence and Suicide Risk Among Bisexual Adolescents.

PURPOSE: Suicide is a public health problem that disproportionately affects bisexual youth more than heterosexual, lesbian/gay, and other sexual minority youth. Teen dating violence (TDV) consists of physically, emotionally, and/or psychologically aggressive behavior in adolescent relationships and has been linked to increased suicidality among sexual minority youth. Although biological sex differences in suicide and TDV have been noted, limited research currently exists regarding the importance of these differences in bisexual youth. METHODS: This study employed a cross-sectional descriptive design to investigate the relationship between biological sex, TDV, and suicide risk among bisexual youth in grades 9-12. This study used structural equation modeling to conduct a secondary analysis of pooled 2015 and 2017 national Youth Risk Behavior Surveillance Survey data that examined whether TDV mediated the relationship between biological sex and suicide risk among bisexual youth. RESULTS: Results indicated that TDV did not mediate the relationship between biological sex and suicide risk among bisexual youth. Biological sex was a significant predictor of suicide risk with male youth reporting lower suicide risk than female youth, when controlling for dating history, TDV, age, and race. TDV predicted suicide risk, with youth reporting TDV having higher suicide risk, when controlling for dating history, biological sex, age, and race. In addition, black and Hispanic youth reported lower suicide risk compared to white youth. CONCLUSION: There is a dire need for research that addresses issues of TDV and suicide among bisexual youth. Understanding factors influencing suicide risk following TDV experiences among bisexual youth will inform interventions to mitigate negative mental health outcomes.

Endosomal microdomains: Formation and function.

It is widely recognized that after endocytosis, internalized cargo is delivered to endosomes that act as sorting stations. The limiting membrane of endosomes contain specialized subregions, or microdomains, that represent distinct functions of the endosome, including regions competing for cargo capture leading to degradation or recycling. Great progress has been made in defining the endosomal protein coats that sort cargo in these domains, including Retromer that recycles transmembrane cargo, and ESCRT (endosomal sorting complex required for transport) that degrades transmembrane cargo. In this review, we discuss recent work that is beginning to unravel how such coat complexes contribute to the creation and maintenance of endosomal microdomains. We highlight data that indicates that adjacent microdomains do not act independently but rather interact to cross-regulate. We posit that these interactions provide an agile means for the cell to adjust sorting in response to extracellular signals and intracellular metabolic cues.

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.