A comparison of different antibiotic regimens for the treatment of naturally acquired shigellosis in rhesus and pigtailed macaques (Macaca mulatta and nemestrina).

BACKGROUND: Shigella spp. are common enteric pathogens in captive non-human primates. Treatment of symptomatic infections involves supportive care and antibiotic therapy, typically with an empirical choice of antibiotic. METHODS: Twenty-four clinically ill, Shigella PCR-positive animals were randomly assigned to one of four treatment groups: single-dose ceftiofur crystalline free acid (CCFA), single-dose azithromycin gavage, a 5-day tapering azithromycin dose, or 7-day course of enrofloxacin. We hypothesized that all antimicrobial therapies would have similar efficacy. RESULTS: Animals in all groups cleared Shigella, based on fecal PCR, and had resolution of clinical signs 2 weeks after treatment. Eight out of nine clinically ill and PCR-positive animals tested negative by fecal culture. CONCLUSIONS: Single-dose CCFA, single-dose azithromycin, and a 5-day tapering course of azithromycin all performed as well as a 7-day course of enrofloxacin in eliminating Shigella infection. Fecal PCR may be a better diagnostic than culture for Shigella.

Exploring the Relationship between Foster Care Experiences and Social Network Engagement Among a Sample of Homeless Former Foster Youth.

INTRODUCTION: Recent research has begun to demonstrate high rates of poor behavioral health outcomes among homeless former foster, but with relatively little attention in the scientific literature. Because social networks have been shown to impact behavioral health outcomes, we need to better understand the network characteristics of homeless young adults with a history of foster care. METHODS: Data were collected from 184 homeless former foster youth at a drop-in center in Hollywood, California. A series of logistic regressions were conducted for network engagement behaviors that may be impacted by foster care experiences. RESULTS: Youth were largely African American, Latino, and Mixed race, approximately 22 years old, and majority male. Significant results from the logistic regressions indicated that youth experiencing homelessness for the first time before exiting foster care were more likely to have alters engaging in condomless sex, and youth with higher numbers of foster care placements were more likely to have alters engaging in methamphetamine use. CONCLUSION: These results suggest that certain foster care experiences impact the types of alters with which youths engage. Time spent in placement was significantly associated with alter behaviors, evident from homeless experiences and multiple foster care placements, negatively impacting the types of alters with which youths are connected, and thusly the risk factors for the youth themselves. Frequent network disruptions may be associated with engagement with risky alters. Included are intervention-based implications for providers as well as structural-based implications for child welfare systems.

Exploring the Relationship Between Foster Care Experiences and HIV Risk Behaviors Among a Sample of Homeless Former Foster Youth.

Recent research shows high rates of poor behavioral health outcomes among homeless former foster youth, including increased risk for HIV-risk behaviors. In the current study, data were collected from 184 youth at drop-in centers in Los Angeles using behavioral health questionnaires to explore the relationships between specific aspects of foster care experiences and engagement in HIV-risk behaviors. Results indicated that youth whose first homelessness experience occurred before leaving foster care were significantly more likely to engage in drug use with sex and exchange sex than those whose first homelessness experience occurred after leaving foster care. Intervention services targeting HIV-risk behaviors should consider the aspects of foster care placements that may increase the risk of these behaviors, such as long periods of placement or experiencing homelessness before exiting foster care, as well as those that may decrease the risk of these behaviors, such as exiting placement at an older age.

Gelation, Phase Separation, and Fibril Formation in Aqueous Hydroxypropylmethylcellulose Solutions.

The thermoresponsive behavior of a hydroxypropylmethylcellulose (HPMC) sample in aqueous solutions has been studied by a powerful combination of characterization tools, including rheology, turbidimetry, cryogenic transmission electron microscopy (cryoTEM), light scattering, small-angle neutron scattering (SANS), and small-angle X-ray scattering (SAXS). Consistent with prior literature, solutions with concentrations ranging from 0.3 to 3 wt % exhibit a sharp drop in the dynamic viscoelastic moduli G' and G″ upon heating near 57 °C. The drop in moduli is accompanied by an abrupt increase in turbidity. All the evidence is consistent with this corresponding to liquid-liquid phase separation, leading to polymer-rich droplets in a polymer-depleted matrix. Upon further heating, the moduli increase, and G' exceeds G″, corresponding to gelation. CryoTEM in dilute solutions reveals that HPMC forms fibrils at the same temperature range where the moduli increase. SANS and SAXS confirm the appearance of fibrils over a range of concentration, and that their average diameter is ca. 18 nm; thus gelation is attributable to formation of a sample-spanning network of fibrils. These results are compared in detail with the closely related and well-studied methylcellulose (MC). The HPMC fibrils are generally shorter, more flexible, and contain more water than with MC, and the resulting gel at high temperatures has a much lower modulus. In addition to the differences in fibril structure, the key distinction between HPMC and MC is that the former undergoes liquid-liquid phase separation prior to forming fibrils and associated gelation, whereas the latter forms fibrils first. These results and their interpretation are compared with the prior literature, in light of the relatively recent discovery of the propensity of MC and HPMC to self-assemble into fibrils on heating.

Social Networking Technology Use and Engagement in HIV-Related Risk and Protective Behaviors Among Homeless Youth.

Preliminary studies with homeless youth have found surprisingly pervasive social media use and suggest that youth's online interactions may be associated with their HIV-related risk and protective behaviors. As homeless youth are transient and difficult to engage in place-based services, social media may represent a novel venue for intervention. A critical 1st step in intervention development is gaining greater understanding of how homeless youth use social media, especially as it relates to who they connect to and around what topics. Given the salience of social networking sites in the lives of these otherwise difficult-to-reach adolescents, and their potential to disseminate prevention interventions, this study assessed associations between online social networking technology use and HIV risk behaviors among homeless youth in Los Angeles, California. Homeless youth ages 13 through 24 (N = 1,046) were recruited through 3 drop-in centers and surveyed about their social media use and self-reported HIV-related risk behaviors. Results suggest that social media use is widely prevalent among this population, and the content of these online interactions is associated with whether youth engage in risk or protective behaviors. Implications for interventions and further research are discussed.

Sociometric network structure and its association with methamphetamine use norms among homeless youth.

Homeless youths' social networks are consistently linked with their substance use. Social networks influence behavior through several mechanisms, especially social norms. This study used sociometric analyses to understand whether social norms of drug use behaviors are clustered in network structures and whether these perceived norms (descriptive and injunctive) influence youths' drug use behaviors. An event-based approach was used to delineate boundaries of the two sociometric networks of homeless youth, one in Los Angeles, CA (n = 160) and the other in Santa Monica, CA (n = 130). Network characteristics included centrality (i.e., popularity) and cohesiveness (location in dense subnetworks). The primary outcome was recent methamphetamine use. Results revealed that both descriptive and injunctive norms influenced methamphetamine use. Network cohesion was found to be associated with perception of both descriptive and injunctive norms in both networks, however in opposite directions. Network interventions therefore might be effective if designed to capitalize on social influence that naturally occurs in cohesive parts of networks.

Functional brain networks associated with the urge for action: Implications for pathological urge.

Tics in Tourette syndrome (TS) are often preceded by sensory urges that drive the motor and vocal symptoms. Many everyday physiological behaviors are associated with sensory phenomena experienced as an urge for action, which may provide insight into the neural correlates of this pathological urge to tic that remains elusive. This study aimed to identify a brain network common to distinct physiological behaviors in healthy individuals, and in turn, examine whether this network converges with a network we previously localized in TS, using novel 'coordinate network mapping' methods. Systematic searches were conducted to identify functional neuroimaging studies reporting correlates of the urge to micturate, swallow, blink, or cough. Using activation likelihood estimation meta-analysis, we identified an 'urge network' common to these physiological behaviors, involving the bilateral insula/claustrum/inferior frontal gyrus/supplementary motor area, mid-/anterior- cingulate cortex (ACC), right postcentral gyrus, and left thalamus/precentral gyrus. Similarity between the urge and TS networks was identified in the bilateral insula, ACC, and left thalamus/claustrum. The potential role of the insula/ACC as nodes in the network for bodily representations of the urge to tic are discussed.

Combined islet and kidney xenotransplantation for diabetic nephropathy: an update in ongoing research for a clinically relevant application of porcine islet transplantation.

Combined islet and kidney xenotransplantation for the treatment of diabetic nephropathy represents a compelling and increasingly relevant therapeutic possibility for an ever-growing number of patients who would benefit from both durable renal replacement and cure of the underlying cause of their renal insufficiency: diabetes. Here we briefly review immune barriers to islet transplantation, highlight preclinical progress in the field, and summarize our experience with combined islet and kidney xenotransplantation, including both challenges with islet-kidney composite grafts as well as our recent success with sequential kidney followed by islet xenotransplantation in a pig-to-baboon model.

Preventing severe and fatal child maltreatment: making the case for the expanded use and integration of data.

In this article we examine risk factors for severe and fatal child maltreatment. These factors emerge from studies based on different data sources, including official child maltreatment data, emergency department and hospitalization data, death certificates, and data from child death review teams. The empirical literature reflects a growing effort to overcome the measurement uncertainties of any one individual data system. After review and reflection upon what is known, we consider how integrating this information can advance efforts to protect children, providing examples where the use and linkage of multiple sources of data may enhance surveillance, improve front-end decisionmaking, and support cost-effective research and evaluation.

Integrated cognitive behavioral intervention for functional tics (I-CBiT): case reports and treatment formulation.

Introduction: The onset of the COVID-19 pandemic saw a global surge in functional tic-like behaviors (FTLBs). FTLBs are unique from primary tic disorders. They are thought to manifest through a complex interplay between environmental and personal factors, including the stress-arousal system, and are characterized by their sudden and explosive onset. Accordingly, common interventions for tic disorders show limited efficacy in this population. We present an Integrated Cognitive Behavioral Intervention for Functional Tics (I-CBiT) that uses an urge acceptance model to manage tics and related stress and anxiety. Methods: We describe the treatment outcomes of eight young people presenting with new and sudden onset FTLBs who underwent I-CBiT, which integrates traditional behavioral tic interventions with third-wave cognitive behavioral therapies. All cases completed the three-phase intervention involving core components of psychoeducation, exposure and response prevention with urge acceptance, sensory grounding strategies, and cognitive behavioral intervention targeting the stress-arousal system. Tic severity and impairment were assessed prior to treatment and at completion. Results: All cases showed a significant reduction in tic severity post I-CBiT and an improvement in overall daily living function. These cases highlight the role of urge acceptance in managing both tic urges and the underlying stress-arousal system to bring about long-term change. Conclusion: We demonstrated the efficacy of I-CBiT for managing FTLBs. Our findings illustrate the importance of treating underlying stress and anxiety in this population and, therefore, a need for greater interaction between multidisciplinary services in managing FTLBs to comprehensively cover the varied symptom presentations linked to thoughts, emotions, bodily sensations, and stress responses.

An ex vivo model of interactions between extracellular vesicles and peripheral mononuclear blood cells in whole blood.

Extracellular vesicles (EVs) can be loaded with therapeutic cargo and engineered for retention by specific body sites; therefore, they have great potential for targeted delivery of biomolecules to treat diseases. However, the pharmacokinetics and biodistribution of EVs in large animals remain relatively unknown, especially in primates. We recently reported that when cell culture-derived EVs are administered intravenously to Macaca nemestrina (pig-tailed macaques), they differentially associate with specific subsets of peripheral blood mononuclear cells (PBMCs). More than 60% of CD20+ B cells were observed to associate with EVs for up to 1 h post-intravenous administration. To investigate these associations further, we developed an ex vivo model of whole blood collected from healthy pig-tailed macaques. Using this ex vivo system, we found that labelled EVs preferentially associate with B cells in whole blood at levels similar to those detected in vivo. This study demonstrates that ex vivo blood can be used to study EV-blood cell interactions.

Exposure to e-cigarette content on social media and e-cigarette use: An ecological momentary assessment study.

This pilot ecological momentary assessment (EMA) study tested the associations between exposure to anti-e-cigarette content on social media and e-cigarette use behavior. For exposure to anti-e-cigarette posts, participants were asked to follow the study account on Instagram, on which anti-e-cigarette content were posted regularly. In addition, we assessed participants' exposure to pro-e-cigarette content in their daily lives and examined the effects of such exposure on behavior. Participants were 29 diverse young adult current e-cigarette users (18-30 year olds; 54% women), who provided data 3 times daily, for 3 weeks via a mobile phone based EMA application. Relative to no exposure, exposure to anti-e-cigarette content was associated with decreased recent e-cigarette use frequency at the next assessment time-point (p < 0.05; 2-tailed). In addition, a statistically significant concurrent association was found between exposure to pro-e-cigarette content (relative to no exposure) and higher e-cigarette use (p < 0.05; 2-tailed). The current data are some of the first to show that exposure to anti-e-cigarette content on social media may have real time effects on decreased e-cigarette use among young adults as they go about their daily lives. Policies and efforts designed to regulate pro-e-cigarette and promote anti-e-cigarette content on social media may help reduce e-cigarette use among young people.

Exploring the impact of network characteristics on substance use outcomes among homeless former foster youth.

OBJECTIVES: This study examined network structure differences between homeless youth with and without a history of foster care and the impact of network position and location on substance use outcomes among former foster youth specifically. METHODS: Sociometric and individual-level data were collected from a cross-sectional community-based sample (n = 814) of homeless youth from drop-in centers in Los Angeles across three points in time. To determine the structure and position of foster youth in the larger homeless network, structural variables and regressions examining the impact of network structure on substance use were calculated. RESULTS: Results indicated that former foster youth were more likely to have low connectivity compared to homeless youth without a history of foster care. Furthermore, the impact of structure on substance use among former foster youth varied by panel; location in the core was significantly associated with recent and lifetime rates of substance use. CONCLUSIONS: Results highlight the need for a more in-depth understanding of the impact of network changes over time and their effect on substance use outcomes in this population.

Common Brain Structure Findings Across Children with Varied Reading Disability Profiles.

Dyslexia is a developmental disorder in reading that exhibits varied patterns of expression across children. Here we examined the degree to which different kinds of reading disabilities (defined as profiles or patterns of reading problems) contribute to brain morphology results in Jacobian determinant images that represent local brain shape and volume. A matched-pair brain morphometry approach was used to control for confounding from brain size and research site effects in this retrospective multi-site study of 134 children from eight different research sites. Parietal operculum, corona radiata, and internal capsule differences between cases and controls were consistently observed across children with evidence of classic dyslexia, specific comprehension deficit, and language learning disability. Thus, there can be common brain morphology findings across children with quite varied reading disability profiles that we hypothesize compound the developmental difficulties of children with unique reading disability profiles and reasons for their reading disability.

Bidirectional Intimate Partner Violence and Drug Use Among Homeless Youth.

Intimate partner violence (IPV) among homeless youth (HY) is common, yet it has continuously been understudied, especially in relation to substance use. As part of a longitudinal study of Los Angeles area HY, drop-in service seeking youth completed a self-administered questionnaire. The presented results are from the third panel of data collection ( N = 238), and the Revised Conflict Tactics Scale (CTS2) was used to assess IPV behavior regarding the participant's most recent intimate relationship. Approximately 38% of participants reported IPV behavior in their most recent relationship, and the majority of this behavior was bidirectional. It was unlikely that a HY was only a victim or only a perpetrator. Multivariable models revealed that bidirectional IPV was related to increased odds of recent methamphetamine; whereas sole perpetration was associated with an increased likelihood of ecstasy use. Specific substance use and IPV are closely related to risk behaviors for HY. Comprehensive interventions should be developed to address both these risk behaviors.

Echocardiographic Characterization of a Murine Model of Hypertrophic Obstructive Cardiomyopathy Induced by Cardiac-specific Overexpression of Epidermal Growth Factor Receptor 2.

Although rare, hypertrophic cardiomyopathy (HCM) with midventricular obstruction is often associated with severe symptoms and complications. None of the existing HCM animal models display this particular phenotype. Our group developed a mouse line that overexpresses the ErbB2 receptor (ErbB2(tg)) in cardiomyocytes; we previously showed that the ErbB2 receptor induces cardiomyocyte hypertrophy, myocyte disarray, and fibrosis compatible with HCM. In the current study, we sought to further echocardiographically characterize the ErbB2(tg) mouse line as a model of HCM. Compared with their wild-type littermates, ErbB2(tg) mice show increased left ventricular (LV) mass, concentric LV hypertrophy, and papillary muscle hypertrophy. This hypertrophy was accompanied by diastolic dysfunction, expressed as reduced E:A ratio, prolonged deceleration time, and elevated E:e' ratio. In addition, ErbB2(tg) mice consistently showed midcavity obstruction with elevated LV gradients, and the flow profile revealed a prolonged pressure increase and a delayed peak, indicating dynamic obstruction. The ejection fraction was increased in ErbB2(tg) mice, due to reduced end-diastolic and end-systolic LV volumes. Furthermore, systolic radial strain and systolic radial strain rate but not systolic circumferential strain and longitudinal strain were decreased in ErbB2(tg) compared with wild-type mice. In conclusion, the phenotype of the ErbB2(tg) mouse model is consistent with midventricular HCM in many important aspects, including massive LV hypertrophy, diastolic dysfunction, and midcavity obstruction. This pattern is unique for a small animal model, suggesting that ErbB2(tg) mice may be well suited for research into the hemodynamics and treatment of this rare form of HCM.

Methamphetamine Use among Homeless Former Foster Youth: The Mediating Role of Social Networks.

OBJECTIVES: Social network analysis can provide added causal insight into otherwise confusing epidemiologic findings in public health research. Although foster care and homelessness are risk factors for methamphetamine use, current research has failed to explicate why homeless youth with foster care experience engage in methamphetamine use at higher rates than other homeless young adults. This study examined the mediating effect of network engagement and time spent homeless on the relationship between foster care experience and recent methamphetamine use among homeless youth in Los Angeles. METHODS: Egocentric network data from a cross-sectional community-based sample (n = 652) of homeless youth aged 13-25 were collected from drop-in centers in Los Angeles. Questions addressed foster care experience, time spent homeless, methamphetamine use, and perceived drug use in social networks. Path analysis was performed in SAS to examine mediation. RESULTS: Controlling for all other variables, results of path analysis regarding recent methamphetamine use indicated a direct effect between foster care experience and recent methamphetamine use (B = .269, t = 2.73, p < .01). However, this direct effect became statistically nonsignificant when time spent homeless and network methamphetamine use were added to the model, and indirect paths from time spent homeless and network methamphetamine use became statistically significant. CONCLUSIONS: Foster care experience influenced recent methamphetamine use indirectly through time spent homeless and methamphetamine use by network members. Efforts to reduce methamphetamine use should focus on securing stable housing and addressing network interactions among homeless former foster youth.