Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy Secondary to Age-related Macular Degeneration.

OBJECTIVE: To evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry age-related macular degeneration (AMD). DESIGN: Phase 1, open-label, single-center, first-in-human clinical study. SUBJECTS: Adult patients (aged ≥50 years) with GA secondary to AMD in the study-treated eye (treated eye) with a best corrected visual acuity (BCVA) Snellen equivalent of 20/200 or worse in the treated eye (20/80 or worse after the first 3 patients), a total GA lesion size between 5 and 20 mm2 (2-8 disc area), and BCVA of 20/800 or better in fellow, non-treated eye were included. METHODS: Patients (N=17) were sequentially enrolled into low (3.56×1010 viral genome [vg]/eye; n=3), intermediate (1.07×1011 vg/eye; n=3), and high (3.56×1011 vg/eye; n=11) dose cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months. MAIN OUTCOME MEASURES: Safety and tolerability outcomes included assessment of ocular and non-ocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate. RESULTS: Baseline patient characteristics were consistent with the disease under study, and all enrolled patients had foveal center-involved GA. JNJ-1887 was well tolerated across all cohorts, with no dose-limiting AEs. There were no serious or systemic AEs related to study intervention. Overall, 5/17 (29%) patients experienced 6 events of mild ocular inflammation related to study treatment; exam findings in all resolved, and AEs resolved in 4 of 5 patients following topical steroids or observation. One unresolved vitritis event, managed with observation, occurred in a patient with an unrelated fatal AE. No endophthalmitis or new-onset choroidal neovascularization was reported. GA lesion growth rate was similar among all cohorts over 24 months. For treated eyes in the high-dose cohort, GA lesion growth rate showed continued decline through 24 months, with a reduction in mean square root lesion growth from 0.211 mm at months 0-6 to 0.056 mm at months 18-24. CONCLUSIONS: All 3 studied doses of JNJ-1887 had a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted.

SARS-CoV-2 Inactivation on Hard Non-porous Airplane Cabin Material Surfaces was Limited After Exposure to Far UV-C (222 nm) Radiation.

AIMS: To test the efficacy of 222 nm Far UV-C for surface disinfection of SARS-CoV-2 on inanimate surfaces from airplane cabins. METHODS AND RESULTS: Two far ultraviolet (UV-C) irradiation light systems were evaluated for disinfection of SARS-CoV-2. Materials used for carriers (test surfaces) included polished stainless steel and used airplane materials including seatbelt latches, window dust covers, sidewall laminates, and tray tables. CONCLUSIONS: While demonstrating reasonable efficacy under some experimental conditions, the data indicated that 222 nm Far UV-C disinfection alone does not reliably provide a 3 log10 or 99.9% reduction of SARS-CoV-2 on inanimate surfaces from an airplane cabin. An Ushio (Cypress, CA) 1.7" x 2.3" Care222® 12W 222nm BI lamp module tested in triplicate at a low (⁓ 1.5 mJ cm-2), medium (⁓ 3.0 mJ cm-2), and high (⁓ 6 to 9 mJ cm-2) fluence did not provide a ≥ 3 log10 or 99.9% reduction of SARS-CoV-2. The reduction of SARS-CoV-2 was greatest on stainless steel. The result was a log10 reduction of 2.83, 1.33, 2.58, and 2.21 logs for virus samples containing saline, saline with 2.5 mg BSA, saline with 0.25 mg BSA, and artificial saliva respectively at a dosage of 5 to 9 mJ cm-2. The log10 reduction of SARS-CoV-2 in saline with 2.5 mg bovine serum albumin was lowest with 1.33 for stainless steel, 0.93 for belt latch, and 0.61 for tray table at a dosage of 5 to 6 mJ cm-2.The second UV lighting system tested was a prototype mobile wand with a built-in short-pass filtered krypton-chloride cylindrical lamp. One pass of the wand over a tray holding carriers inoculated with SARS-CoV-2 in artificial saliva at a rate of approximately 1 foot (1') per second (sec) exposed the carriers to 7.3 mJ cm-2. The log10 reductions determined for the single pass were 2.97, 3.75, 1.78, 1.91, and 1.28 logs for stainless steel, belt latch, dust cover, sidewall, and tray table respectively. Two passes of the wand generated 17.2 mJ cm-2 and resulted in log10 reductions of 4.04, 3.74, 4.24, 3.68, and 1.66 logs for stainless steel, belt latch, dust cover, sidewall, and tray table respectively. The combination of higher fluence from multiple passes of the wand, the close proximity (10 cm wand to the carrier), the exposure to elevated temperatures up to 35°C, and ozone from the bulb being blown directly onto the carriers contributed to effective viral inactivation on all surfaces except the airplane tray table. The impact of temperature and ozone on viral inactivation should be determined for future testing of the 222 nm UV-C wand.

Patterns of Gender Development Across Intersections of Age, Gender, and Ethnicity-Race.

Two components of gender identity are gender similarity, how one's self-concept relates to the major gender collectives (i.e., female, male), and felt pressure to conform to gender norms. The development of these components across ages and contexts has been understudied. The focus of this study was to examine variations in gender similarity and felt pressure across multiple intersecting contexts: developmental stage, gender, and ethnic-racial group. Six data sets were harmonized and means were compared across 2628 participants (51% girls, 49% boys) from four different developmental cohorts (childhood n = 678, early adolescence n = 1322, adolescence n = 415, and young adulthood n = 213) from diverse ethnic-racial backgrounds (45% White, 23% Latinx/Hispanic, 11% Black/African-American, 7% Asian-American, 5% American Indian, and 5% Multiracial). Results revealed nuanced patterns: Gender intensification was supported in early adolescence, primarily for boys. Young adult men reported lower levels of pressure and gender typicality than younger boys, but young adult women's levels were generally not different than younger girls. Surprisingly, young adult women's levels of own-gender similarity and pressure from parents were higher than adolescent girls. Expectations of gender differences in gender typicality and felt pressure were supported for all ages except young adults, with higher levels for boys. Finally, there were more similarities than differences across ethnic-racial groups, though when there were differences, minoritized participants reported heightened gender typicality and pressure (largely accounted for by higher scores for Black and Latinx participants and lower scores for White and Multiracial participants). These results add to what is understood about contextually dependent gender development.

Trajectories of parents' gendered play attitudes during early childhood and implications for children's gender development.

This study examined associations between parents' gendered attitudes about play and children's gender development. The sample was 501 families from a large US city followed annually for 4 years (501 mothers, 383 fathers; 69% White, 16% Latinx, 8% African American; children Mage = 5.67 months, 53% boys). Latent trajectories examined change in parents' attitudes toward same- and other-gender play during first 4 years of the child's life. On a subsample (n = 252), trajectories were examined in relation to children's later gender-typed preferences and gender constancy. Parents grew more gender-flexible in their attitudes, particularly parents of boys. Trajectories reflecting more stereotypic attitudes showed some associations (small in magnitude) with children's gender-typed preferences and gender constancy by age 4.

Feeding Saccharomyces cerevisiae fermentation postbiotic products alters immune function and the lung transcriptome of preweaning calves with an experimental viral-bacterial coinfection.

Bovine respiratory disease causes morbidity and mortality in cattle of all ages. Supplementing with postbiotic products from Saccharomyces cerevisiae fermentation (SCFP) has been reported to improve growth and provide metabolic support required for immune activation in calves. The objective of this study was to determine effects of SCFP supplementation on the transcriptional response to coinfection with bovine respiratory syncytial virus (BRSV) and Pasteurella multocida in the lung using RNA sequencing. Twenty-three calves were enrolled and assigned to 2 treatment groups: control (n = 12) or SCFP-treated (n = 11, fed 1 g/d SmartCare in milk and 5 g/d NutriTek on starter grain; both from Diamond V Mills Inc.). Calves were infected with ∼104 median tissue culture infectious dose per milliliter of BRSV, followed 6 d later by intratracheal inoculation with ∼1010 cfu of Pasteurella multocida (strain P1062). Calves were euthanized on d 10 after viral infection. Blood cells were collected and assayed on d 0 and 10 after viral infection. Bronchoalveolar lavage (BAL) cells were collected and assayed on d 14 of the feeding period (preinfection) and d 10 after viral infection. Blood and BAL cells were assayed for proinflammatory cytokine production in response to stimulation with lipopolysaccharide (LPS) or a combination of polyinosinic:polycytidylic acid and imiquimod, and BAL cells were evaluated for phagocytic and reactive oxygen species production capacity. Antemortem and postmortem BAL and lesioned and nonlesioned lung tissue samples collected at necropsy were subjected to RNA extraction and sequencing. Sequencing reads were aligned to the bovine reference genome (UMD3.1) and edgeR version 3.32.1 used for differential gene expression analysis. Supplementation with SCFP did not affect the respiratory burst activity or phagocytic activity of either lung or blood immune cells. Immune cells from the peripheral blood of SCFP-supplemented calves produced increased quantities of IL-6 in response to toll-like receptor stimulation, whereas cells from the BAL of SCFP-treated calves secreted fewer proinflammatory cytokines and less tumor necrosis factor-α (TNF-α) and IL-6 in response to the same stimuli. Transcriptional responses in lung tissues and BAL samples from SCFP-fed calves differed from the control group. The top enriched pathways in SCFP-treated lungs were associated with decreased expression of inflammatory responses and increased expression of plasminogen and genes involved in glutathione metabolism, supporting effective lung repair. Our results indicate that supplementing with SCFP postbiotics modulates both systemic and mucosal immune responses, leading to increased resistance to bovine respiratory disease.

Main and interactive effects of discrimination, parent racial/ethnic socialization, and internalizing symptomology on BIPOC teens' ethnic-racial identity.

Research suggests that BIPOC (Black, Indigenous, People of Color) adolescents have the best developmental outcomes when strong, positive ethnic-racial identity (ERI) is acknowledged and embraced. This study investigated whether discrimination, internalizing symptomology, parent socialization, and/or interactions of these variables were associated with adolescent ERI, specifically in exploration, resolution, and affirmation, to illuminate nuanced ways BIPOC youth can achieve positive ERI. Recruited from third-party research panels, surveyed participants were adolescents (Mage = 15.28; 51.6% male) of diverse ethnic/racial groups and socioeconomic backgrounds from all regions of the United States. Overall, results showed that there were four significant main effects on ERI: a negative relation between internalizing symptomology and exploration, a positive relation between parent socialization and exploration, a positive relation between parent socialization and resolution, and a negative relation between internalizing symptomology and affirmation. There were also two significant interactive effects such that (1) discrimination had a stronger negative relation with affirmation under condition of high internalizing, and (2) parent socialization had a stronger positive relation with affirmation under condition of high internalizing. Results show development of ERI in adolescence is subject to multiple, interactive influences. Main and interactive effects highlight the contextual role that mental health implicates for youth of color. Implications for parents and practitioners are discussed.

Endorsement of Masculine-Typed Behaviors Decreases During Middle Adolescence: The Contextualizing Role of Peer Experiences for Adolescents Living in the United States.

While more research is emerging about the development of masculinity during adolescence, not much is known about how masculine-type behaviors develop over time in middle to late adolescence within the context of friendships and peer experiences. This study examined trajectories of masculine-typed behavior from ages 14 to 17. Multilevel modeling was used to account for cross-time and within-time variability in masculine-typed behavior and examined the role of positive and negative peer experiences in predicting this variability. This was done in a sample of 334 U.S. adolescents (51% boys; 50% White, 19% Black, 15% Latina/o/e). At the between-person level, boys and girls decreased in masculine-typed behavior over time. At the within-person level, negative peer experiences predicted fluctuations toward greater masculine-typed behavior, whereas friend support predicted fluctuations toward less masculine-typed behavior. Adolescence is a key period for navigating masculinity norms, and peer experiences are a key context for the development of masculine-typed behavior.

Associations Between Adolescents' Antisocial Behavior, Conflict Management Styles, and Romantic Relationship Breakup: An Observational Study.

Adolescents' antisocial behavior and negative conflict management styles are each associated with adverse romantic relationship outcomes, yet little research exists on their associations. We investigated whether adolescents' antisocial behavior was associated with conflict management styles, and whether it predicted breakup 3 months later. In total, 91 adolescent couples (Mage = 16.43, SD = 0.99; 41.2% Hispanic/Latinx) participated in videotaped conflict discussions coded for negotiation, coercion, and avoidance. Actor-partner interdependence models suggest adolescents' antisocial behavior is associated with decreased use of negotiation (couple pattern) and increased use of coercion (actor pattern). No significant associations were found for avoidance. Neither antisocial behavior nor conflict management styles predicted breakup. Findings are discussed in light of the unique developmental importance of adolescents' romantic relationships.

A Person-Centered Analysis of Adolescent Multicultural Socialization Niches and Academic Functioning.

Despite the growing cultural diversity worldwide, there is scarce research on how socialization processes prepare youth to respond to increasing multicultural demands and the degree to which these socialization opportunities inform youth academic functioning. This study used a person-centered approach to identify profiles or niches based on the degree and consistency of multicultural socialization experiences across school, peer, and family settings and to examine the associations between identified niches and markers of academic functioning (i.e., emotional and behavioral academic engagement, academic aspirations and expectations) in a sample of adolescents (N = 717; Mage = 13.73 years). Participants (49.9% girls) were from the U.S. Southwest and represented multiple ethno-racial backgrounds (31.8% Hispanic/Latinx, 31.5% Multiethnic, 25.7% White, 7.3% Black or African American, 1.4% Asian American or Pacific Islander, 1.4% American Indian or Alaska Native, and 1% Arab, Middle Eastern, or North African). Six distinct multicultural socialization niches were identified. Three niches had similar patterns across school-peer-family but ranged in the degree of socialization. The cross-setting similar higher socialization niche (Niche 6) demonstrated greater socialization than the cross-setting similar moderate (Niche 5) and lower socialization (Niche 4) niches, which had moderate and lower socialization, respectively. Three niches demonstrated cross-setting dissimilarity which ranged in the type of cross-setting contrast and the degree of socialization. The cross-setting dissimilar school contrast socialization niche (Niche 3) had greater dissimilarities between socialization opportunities in the school setting compared to the peer and family settings and demonstrated the lowest levels of socialization of all niches. The other two niches, the cross-setting dissimilar peer contrast (Niche 1) and greater peer contrast socialization (Niche 2) niches had larger dissimilarities between socialization opportunities in the peer setting than the school and family settings. In the former, however, the contrast was lower, and socialization ranged between very low to low. In the latter, the contrast was higher and socialization ranged from very low to moderate. Most adolescents were in the cross-setting similar lower socialization niche or in the cross-setting dissimilar niches. Adolescents in the cross-setting similar higher multicultural socialization demonstrated greater emotional and behavioral academic engagement than adolescents in most of the other niches. Adolescents in the cross-setting dissimilar school contrast niches demonstrated lower emotional and behavioral academic engagement and lower academic expectations than adolescents in some of the other niches. The results emphasize the collective role of school, peer, and family multicultural socialization on emotional and behavioral academic engagement.

Is My Femininity a Liability? Longitudinal Associations between Girls' Experiences of Gender Discrimination, Internalizing Symptoms, and Gender Identity.

Gender discrimination is a common experience for adolescent girls and has implications for their mental health and identity development. Guided by Phenomenological Variant of Ecological Systems Theory (PVEST; Spencer et al. 1997), this study examined the longitudinal and bidirectional associations between adolescent girls' experiences of gender discrimination, their internalizing symptoms, and gender identity. The sample was 161 adolescent girls (ages 14-17; Mage = 15.90) from across the United States (51% White; 17% African American, 11% Hispanic/Latina) who participated in a short-term longitudinal study of adolescent development. The results showed a reciprocal, longitudinal association between discrimination and internalizing symptoms. Discrimination also predicted longitudinal declines in gender identity, which was explained indirectly through internalizing symptoms. The findings implicate gender discrimination as a distinct risk factor during girls' developmental years, and underscore the importance of helping girls learn adaptive responses to sexism, while also reducing actual occurrence and exposure.

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4+ T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8+ T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.

Masculine gender-role adherence indicates conflict resolution patterns in heterosexual adolescent couples: A dyadic, observational study.

INTRODUCTION: Conflict resolution in romantic relationships is a critical skillset that relates to individual and relational well-being. In adolescence, heterosexual romantic relationships are highly gendered, and norms for traditional masculinity (a bravado focused on interpersonal dominance) may be relevant in shaping how adolescents navigate disagreements. Therefore, we examined the associations between adolescents' conformity to norms for traditional masculinity and their conflict resolution in their romantic relationships. METHOD: Using a sample of 91 heterosexual adolescent couples from the Southwest United States (Mage = 16.50, SD = .90; 44% White, 42% Latinx), we examined how self-reported conformity to traditional masculinity predicted independent observer ratings of negotiation, coercion, and avoidance strategies during a lab-based conflict and jealousy discussion task. RESULTS: Results of actor-partner interdependence models (APIMs) indicated that more highly masculine adolescents generally displayed less conflict negotiation and more coercion during the discussion task. Dyadic and gendered patterns characterized masculinity's associations with negotiation and coercion. Masculinity was unassociated with conflict avoidance. CONCLUSIONS: Adolescents in heterosexual relationships that adhere more rigidly to gendered norms for traditional masculinity may be challenged in acquiring skills for constructive conflict resolution with a romantic partner. Adolescent romantic relationships are a socialization context in which many individuals develop the skills for future romantic relationships, including those into young adulthood. Addressing masculine gender roles in adolescence may help promote the development of positive conflict management and overall romantic functioning in youth.

Trajectories of Perceived Parental Psychological Control across Adolescence and Implications for the Development of Depressive and Anxiety Symptoms.

Theory and research indicate considerable changes in parental control across adolescence (e.g., declining behavioral control), but the developmental course and significance of psychological control remains largely unknown. This study examined trajectories of adolescents' reports of mothers' and fathers' psychological control from ages 12 to 19, predictors of occupying distinct trajectories, and the developmental significance of these trajectories for adolescents' development of depressive and anxiety symptoms. It used eight waves of survey data on 500 adolescents (Mage = 11.83, SD = 1.03; 52% female; 67% White, 12% African American) and their parents from the Pacific Northwest United States. Most adolescents (about 90%) reported low but increasing levels of parental psychological control over time, with a small but significant subset (about 10%) perceiving perpetually elevated levels. Mothers' (but not fathers') depressive symptoms, reported at the age 12 assessment, predicted adolescents' membership in the elevated psychological control trajectory. Adolescents occupying these elevated trajectories showed more problematic growth in depressive and anxiety symptoms across adolescence. Taken together, the findings suggest that many adolescents experience increased parental psychological control as they age, and that variability in these trends indicates individual differences in their development of depressive and anxiety symptoms over time.

Recombinant Porcine Reproductive and Respiratory Syndrome Virus Expressing Membrane-Bound Interleukin-15 as an Immunomodulatory Adjuvant Enhances NK and γδ T Cell Responses and Confers Heterologous Protection.

Cytokines are often used as adjuvants to improve vaccine immunogenicity, since they are important in initiating and shaping the immune response. The available commercial modified live-attenuated vaccines (MLVs) against porcine reproductive and respiratory syndrome virus (PRRSV) are unable to mount sufficient heterologous protection, as they typically induce weak innate and inadequate T cell responses. In this study, we investigated the immunogenicity and vaccine efficacy of recombinant PRRSV MLVs incorporated with the porcine cytokine interleukin-15 (IL-15) or IL-18 gene fused to a glycosylphosphatidylinositol (GPI) modification signal that can anchor the cytokines to the cell membrane. We demonstrated that both cytokines were successfully expressed on the cell membrane of porcine alveolar macrophages after infection with recombinant MLVs. Pigs vaccinated with recombinant MLVs or the parental Suvaxyn MLV had significantly reduced lung lesions and viral RNA loads in the lungs after heterologous challenge with the PRRSV NADC20 strain. The recombinant MLVs SUV-IL-15 and SUV-IL-18 recovered the inhibition of the NK cell response seen with Suvaxyn MLV. The recombinant MLV SUV-IL-15 significantly increased the numbers of gamma interferon (IFN-γ)-producing cells in circulation at 49 days postvaccination (dpv), especially for IFN-γ-producing CD4- CD8+ T cells and γδ T cells, compared to the Suvaxyn MLV and SUV-IL-18. Additionally, MLV SUV-IL-15-vaccinated pigs also had elevated levels of γδ T cell responses observed at 7 dpv, 49 dpv, and 7 days postchallenge. These data demonstrate that the recombinant MLV expressing membrane-bound IL-15 enhances NK and T cell immune responses after vaccination and confers improved heterologous protection, although this was not statistically significant compared to the parental MLV.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) has arguably been the most economically important global swine disease, causing immense economic losses worldwide. The available commercial modified live-attenuated vaccines (MLVs) against PRRS virus (PRRSV) are generally effective against only homologous or closely related virus strains but are ineffective against heterologous strains, partially due to the insufficient immune response induced by the vaccine virus. To improve the immunogenicity of MLVs, in this study, we present a novel approach of using porcine IL-15 or IL-18 as an adjuvant by directly incorporating its encoding gene into a PRRSV MLV and expressing it as an adjuvant. Importantly, we directed the expression of the incorporated cytokines to the cell membrane surface by fusing the genes with a membrane-targeting signal from CD59. The recombinant MLV virus expressing the membrane-bound IL-15 cytokine greatly enhanced NK cell and γδ T cell responses and also conferred improved protection against heterologous challenge with the PRRSV NADC20 strain.

Vaccination of sows with a dendritic cell-targeted porcine epidemic diarrhea virus S1 protein-based candidate vaccine reduced viral shedding but exacerbated gross pathological lesions in suckling neonatal piglets.

Porcine epidemic diarrhea virus (PEDV) poses a serious threat to swine worldwide as evidenced by its recent introduction into the USA and the devastating economic impact it caused to the USA swine industry. Commercial vaccines against PEDV are available but their efficacies are inadequate. Therefore, vaccines with improved efficacy are needed to effectively control PEDV infections. We previously determined the immunogenicity of a novel dendritic cell (DC)-targeted PEDV S1 protein-based subunit vaccine in weaned piglets in which the PEDV antigen was targeted to DCs through a porcine Langerin-specific antibody. In this study, we evaluated the protective efficacy of this DC-targeting vaccine by immunizing sows at 5 and 2 weeks prior to farrowing and by challenging the 5-day-old piglets with PEDV. The results showed that immunization of sow with DC-targeted PEDV vaccine did not eliminate faecal virus shedding in piglets but significantly reduced faecal viral RNA levels in the early days after virus challenge. The vaccine also reduced the amount of PEDV antigen in intestinal tissues presented with intestinal villi regrowth. However, the DC-targeted vaccine neither mitigated PEDV clinical signs nor affected viral RNA loads in intestinal tissues of piglets. In the vaccinated sow, DC-targeted PEDV vaccine enhanced T helper 1-like cluster of differentiation (CD)4 T cell responses and induced IgG but not IgA-specific immune responses. The suckling piglets in the DC-targeted vaccine group showed increased gross pathological lesions in the small intestine. Results in this study provide insights into the effects of sow cellular immune responses to PEDV infection in suckling piglets.

ISG15 Modulates Type I Interferon Signaling and the Antiviral Response during Hepatitis E Virus Replication.

Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals, especially in solid-organ transplant recipients. Innate immunity, via the type I interferon (IFN) response, plays an important role during the initial stages of a viral infection. IFN-stimulated gene 15 (ISG15), an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role and can have a direct antiviral effect on a wide spectrum of virus families. In the present study, we investigated the antiviral effect as well as the potential immunomodulatory role of ISG15 during HEV replication. The results revealed that HEV induced high levels of ISG15 production both in vitro (Huh7-S10-3 liver cells) and in vivo (liver tissues from HEV-infected pigs); however, ISG15 is not required for virus replication. We also demonstrated that ISG15 silencing potentiates enhanced type I IFN-mediated signaling, resulting in an increase in the type I IFN-mediated antiviral effect during HEV replication. This observed enhanced type I IFN signaling correlated with an increase in IFN-stimulated gene expression levels during HEV replication. Furthermore, we showed that PKR and OAS1 played important roles in the ISG15-mediated type I IFN sensitivity of HEV. Taken together, the results from this study suggest that ISG15 plays an important immunomodulatory role and regulates HEV sensitivity to exogenous type I IFN.IMPORTANCE Hepatitis E virus (HEV) infection typically causes self-limiting acute viral hepatitis. However, chronic HEV infection has recently become a significant clinical problem in immunocompromised patients. Pegylated interferon (IFN) has been used to treat chronic HEV infection in solid-organ transplant patients with some success. However, the mechanism behind the type I IFN-mediated antiviral effect against HEV remains unclear. This report demonstrates that ISG15 induced by HEV replication in Huh7-S10-3 human liver cells plays an immunomodulatory role by negatively regulating type I IFN signaling and, thus, HEV sensitivity to type I IFN. Our results also show that PKR and OAS1 play important roles in the ISG15-mediated type I IFN sensitivity of HEV.

A Meta-Analysis of Parenting Practices and Child Psychosocial Outcomes in Trauma-Informed Parenting Interventions after Violence Exposure.

Over half of all youth are exposed to violence, which a growing body of literature suggests is associated with a broad range of negative developmental outcomes over the life course. However, best practices for supporting parenting are not widely applied to parents with children exposed to violence-related trauma. This meta-analyses seeks to synthesize the literature base of trauma-informed parenting interventions to better understand their potential impact on parenting and child outcomes. Specifically, 21 trauma-informed parenting interventions were identified that quantitatively assessed intervention effects on parenting and child outcomes. Six meta-analyses were conducted to assess intervention effects on (1) positive parenting practices, (2) negative parenting practices, (3) parenting stress, (4) children's internalizing problems, (5) children's externalizing problems, and (6) trauma symptoms, respectively. Moderate to large effect sizes were found for positive parenting practices (d = 0.62) as well as child internalizing problems, externalizing problems, and trauma symptoms (d = 0.48-0.59). Validity tests indicated robust findings for positive parenting and for all child outcomes. Additional moderator analyses support the importance of informed intervention design, showing differential findings by trauma type as well as by duration of the intervention. These findings indicate the value of evidence-based parenting interventions for violence-related trauma and support models of trauma-informed care that situate treatment in the broader social context, particularly the family. Results are discussed with respect to which parenting practices hold the most promise for supporting children exposed to violence-related trauma.

Adolescents' Daily Romantic Experiences and Negative Mood: A Dyadic, Intensive Longitudinal Study.

Romantic relationships, although increasingly normative during adolescence, also present unique developmental challenges that can portend psychological difficulties. Underlying these difficulties may be the degree to which daily romantic transactions potentiate fluctuations in negative mood. The present study examined associations between adolescents' daily romantic relationship experiences and their same-day negative affective states (i.e., fluctuations in high-arousal, aversive mood). Using a dyadic ecological momentary assessment (EMA) design, this study followed an ethnically and socioeconomically diverse sample of 98 adolescent romantic couples twice weekly for 12 weeks (n = 196 individuals; Mage = 16.74 years, SD = 0.90; 45% Latina/o, 45% White; 55% receiving free or reduced meals). The results indicated that various daily romantic experiences (e.g., conflict, feelings about the relationship) predicted greater same-day negative affect. Beyond the effects of these romantic experiences, adolescent couples were also synchronized in their fluctuating negative affective states, evidencing the presence of emotional contagion. Overall, the findings indicate the salience of romantic relationships in the everyday lives of adolescents.

Proximal and Distal Effects of Sensation Seeking and Parenting Environments on Alcohol Use Trajectories from Early Adolescence to Early Adulthood.

Adolescent alcohol use is related to disinhibition traits and family environments. However, research is scarce on whether these factors predict alcohol use trajectories distally, from early adolescence into early adulthood. We examined whether sensation seeking and parenting environments in early adolescence predicted adolescents' alcohol use trajectories proximally (middle-adolescence) and distally (early adulthood). Using four waves of data from 345 adolescents (51.3% female; 80% white) and their primary caregivers, we estimated adolescents' alcohol use trajectories and examined variability in these by sensation seeking and parental control. The findings revealed distal, positive associations between sensation seeking and alcohol use; and negative, proximal associations between parental control and alcohol use. Also proximally, there was a significant interaction between sensation seeking and parental control. We discuss implications for theory and practice.

Traditional Masculinity During the Middle School Transition: Associations with Depressive Symptoms and Academic Engagement.

Culturally prescribed social scripts for traditional masculinity that emphasize social dominance are frequently linked to diminished well-being for men across a variety of psychological domains. However, few studies have examined the role of traditional masculinity scripts in the lives of early adolescent boys and girls, despite their relevance during this period and their potential developmental implications. To address this need, we examined the development of early adolescents' conformity to traditional masculinity across the middle school transition, as well as its links with depressive symptoms and academic engagement. Using a diverse sample of 280 adolescents (M age = 11.13, SD = 0.51; 54.3 % Female; 44 % Latina/o) assessed at the beginning (fall 2014) and end (spring 2015) of their first year of middle school, we found an increase in conformity to traditional masculinity scripts among boys, but not among girls. For boys and girls alike, conformity to traditional masculinity predicted greater depressive symptoms and decreased academic engagement. Depressive symptoms also mediated the association between traditional masculinity and academic engagement for boys and girls. This study is among the first to study conformity to traditional masculinity from a developmental lens. The findings suggest that traditional masculinity scripts are relevant for early adolescents (particularly boys) transitioning to middle school. However, for both boys and girls, conformity to these scripts can compromise psychological and academic well-being.