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We describe a 17-year-old boy with capillary malformation-arteriovenous malformation syndrome and a massive vascular malformation of the right chest wall, shoulder, and upper arm. Persistent growth of the malformation caused cutaneous ulcerations and recurrent massive bleeding episodes. We proceeded with a modified shoulder disarticulation preceded by ligation of the subclavian artery and innominate vein by median sternotomy. After a staged debulking resection of the residual chest wall arteriovenous malformation with rotational transverse rectus abdominis myocutaneous flap coverage, the patient was discharged home safely. This report demonstrates that a multidisciplinary approach is critical for management of life-threatening complications in capillary malformation-arteriovenous malformation patients.

Many youth programs focused on improving health outcomes have not examined parent/caregiver perceptions postparticipation even though they may significantly influence youth behaviors. The primary purpose of this study was to examine changes in adult perceptions of youth- and family-related behavior after youth participated in a 12-week out-of-school time food preparation, nutrition, and physical activity program with a treatment only design. A secondary objective was to assess differences in survey responses by demographic characteristics. The program targeted fourth- and fifth-grade youth at two Title I elementary schools while also engaging families. Pre- and postprogram surveys were administered to parent/caregivers ( n = 60) across four cohorts spanning the spring 2016 school semester to fall 2017 school semester. Adult demographic characteristics and perceptions of youth- and family-related outcomes were collected. Results demonstrated a significant increase ( p value

OBJECTIVES: Adapt and pilot Simple Suppers (SS)—a site-based 8-week family meals program for Head Start (HS) families offered in fall, winter, and spring—to an online platform using a community-based participatory approach, in response to COVID-19. METHODS: Researchers collaborated with community partners and HS families to adapt the core components (caregiver education; child education; family meal) of SS to an online format. Feasibility outcomes (demand: response rate, attendance, retention; acceptability: satisfaction; implementation: fidelity, cost; limited effectiveness: diet, weight status) were measured: pre, post, or throughout programming via count, survey, focus group, or direct measure. Baseline demographic data were also collected. RESULTS: The research-community team came to consensus on: a) utilizing e-methods families were accustomed to in local HS programs and elementary schools (Google Classroom; Zoom; YouTube videos) for the educational components; b) enhancing the educational components with a supplemental program-specific weekly magazine (“SS Digest”); c) creating a weekly meal kit delivery for the family meal component (“SS Chef's Crate”); and d) adding an additional week to programming (8 to 9) to orient families to the new online format. 13 of 40 families enrolled in HS participated in the fall session of SS-GO programming (32.5% response rate) and mean (SD) weekly attendance was 4.0 (0.86). 11 of the 13 families engaged in the research, and 10 of 11 completed pre- and post-test data collection (91% retention). Survey and focus group data revealed high levels of satisfaction for SS-GO. Weekly lessons were delivered as intended 92.8% of the time, and Chef's Crates were received by families 100% of the time. Mean (SD) food cost of programming was $212.33 (66.06) or $16.33 per family. Limited effectiveness data are forthcoming. Baseline mean (SD) caregiver age was 32.5 (9.32) years (n = 11), 100% (n = 11) female, 72.7% (n = 11) Black, mean (SD) BMI 36.3 (9.31), 36.4% (n = 4) low income, and 36.4% (n = 11) had low or very low food insecurity. Mean (SD) child age was 3.45 (0.69) (n = 11), 45.5% (n = 5) were female, and had a mean (SD) BMI z-score 0.63 (0.76) (n = 11). CONCLUSIONS: SS-GO demonstrates feasibility utilizing a community-based participatory approach. Data will guide future iterations of the program—in COVID-19 and after. FUNDING SOURCES: USDA NIFA CYFAR

OBJECTIVES: Simple Suppers is a 10-week evidence-based intervention (EBI) designed to improve family mealtime routines and child weight status among racially diverse elementary-age children from low-income households. Results from a previous trial demonstrated effectiveness, thereby warranting a scale-out study to reach other child populations (i.e., preschool-age children). In the current study, Southside Simple Suppers Scale-Up (S4), we propose a hybrid type 2 effectiveness-implementation trial, which has a dual focus on effectiveness and implementation outcomes. This type of trial will allow facilitation of the research translation process to develop effective solutions to promote the health of preschool-age children. METHODS: S4 is occurring during the 2019–20 school year (fall, winter, spring) at 3 Head Start sites (school readiness program for low-income children). Effectiveness outcomes (child food preparation skills, family meal routines) are collected at pre- and post-programming via direct measure and survey. Child food preparation skills are rated on 4-point Likert scale (strongly disagree to strongly agree). Family mealtime routines (i.e., eating meals together, TV on while eating) are reported by number of days per week. Implementation outcomes (adoption, fidelity, fiscal efficiency) are collected throughout programming. Adoption is assessed by weekly attendance. Fidelity is assessed with a program-specific checklist and videotaping. Fiscal efficiency is evaluated by assessing cost of programming per family. RESULTS: Nineteen caregivers completed data collection for the fall session. 55.6% families were low-income. Mean(SD) caregiver age was 37.6(12.1) yr, 94.7% were female, 84.2% were Black, and mean(SD) BMI was 35.3(11.2) kg/m2. Mean(SD) child age was 3.4(0.5) yr, 47.6% were female, and mean (SD) BMI z-score was 1.16(1.38). Child food preparation skills significantly increased from pre- to post-test (P

OBJECTIVES: Assess the impact of an 8-week Head Start family meals intervention (Simple Suppers) on participating caregiver's weight status and health outcomes. METHODS: This is a single arm pre- to post-test study. The intervention is occurring during the 2019–20 school year (fall, winter, and spring sessions) at 3 Head Start sites. Caregiver outcomes include: BMI (kg/m(2)), waist circumference (cm), blood pressure (mm Hg), and mental health measures (depression (Patient Health Questionnaire-9 (PHQ-9)), perceived stress (Perceived Stress Scale (PSS)), and anxiety (Generalized Anxiety Disorder-7 (GAD-7))). Regression models factoring in attendance will be used to examine pre- to post-test changes. RESULTS: Nineteen caregivers completed data collection for the fall session. 55.6% of families were low-income and 21.1% had low/very low food security. Mean (SD) caregiver age was 37.6 (12.1) yr, 94.7% were female, and 84.2% were non-Hispanic Black. There were no significant changes in BMI, blood pressure, waist circumference, depression, or perceived stress from pre- to post-test according to attendance level, however anxiety significantly decreased with increasing attendance (P

Background and aims Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end-stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end-stage liver disease requiring liver transplantation for survival. Approach and results In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling human BA and has been used to study mechanistic aspects of the disease. Unfortunately, nearly all RRV-infected pups succumb by day of life 14. Thus, in this study we generated an RRV-TUCH rotavirus reassortant (designated as TR(VP2,VP4) ) that when injected into newborn mice causes an obstructive jaundice phenotype with lower mortality rates. Of the mice that survived, 63% developed Ishak stage 3-5 fibrosis with histopathological signs of inflammation/fibrosis and bile duct obstruction. Conclusions This model of rotavirus-induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies with an objective to identify therapeutic targets that may alter the course of BA.

Although it is not a new idea, discourse continues to be a topic of discussion among teachers, teacher educators, and researchers in mathematics education. NCTM (1989; 2000) and the Common Core State Standards for Mathematics (CCSSM 2010) describe mathematics classrooms as discourse communities in which whole-class discussions give students opportunities to share their thinking. In such discourse communities, different problem-solving approaches become explicit topics of conversation that can challenge, extend, and support all students' understanding. Further, opportunities to engage in discourse support students in becoming more confident problem solvers (Ball 1993; Kazemi and Stipek 2001).

Biliary atresia (BA), a neonatal obstructive cholangiopathy, remains the most common indication for pediatric liver transplantation in the United States. In the murine model of BA, Rhesus rotavirus (RRV) VP4 surface protein determines biliary duct tropism. In this study, we investigated how VP4 governs induction of murine BA. Newborn mice were injected with 16 strains of rotavirus and observed for clinical symptoms of BA and mortality. Cholangiograms were performed to confirm bile duct obstruction. Livers and bile ducts were harvested 7 days postinfection for virus titers and histology. Flow cytometry assessed mononuclear cell activation in harvested cell populations from the liver. Cytotoxic NK cell activity was determined by the ability of NK cells to kill noninfected cholangiocytes. Of the 16 strains investigated, the 6 with the highest homology to the RRV VP4 (>87%) were capable of infecting bile ducts in vivo. Although the strain Ro1845 replicated to a titer similar to RRV in vivo, it caused no symptoms or mortality. A Ro1845 reassortant containing the RRV VP4 induced all BA symptoms, with a mortality rate of 89%. Flow cytometry revealed that NK cell activation was significantly increased in the disease-inducing strains and these NK cells demonstrated a significantly higher percentage of cytotoxicity against noninfected cholangiocytes. Rotavirus strains with >87% homology to RRV's VP4 were capable of infecting murine bile ducts in vivo. Development of murine BA was mediated by RRV VP4-specific activation of mononuclear cells, independent of viral titers.

To summarize the current standards and guidelines for the diagnosis and management of hepatoblastoma, a rare pediatric liver tumor.Hepatoblastoma is the most common malignant liver tumor in childhood. International collaborative efforts have led to uniform implementation of the pretreatment extent of disease (PRETEXT) staging system as a means to establish consensus classification and assess upfront resectability. Additionally, current histopathological classification, in light of more advanced molecular profiling and immunohistochemical techniques and integration of tumor biomarkers into risk stratification, is reviewed. Multimodal therapy is composed of chemotherapy and surgical intervention. Achievement of complete surgical resection plays a key role in successful treatment for hepatoblastoma. Overall, outcomes have greatly improved over the past four decades because of advances in chemotherapeutic agents and administration protocols as well as innovations of surgical approach, including the use of vascular exclusion, ultrasonic dissection techniques, and liver transplantation. Challenges remain in management of high-risk patients as well as patients with recurrent or metastatic disease.Eventually, a more individualized approach to treating the different types of the heterogeneous spectrum of hepatoblastoma, in terms of different chemotherapeutic protocols and timing as well as type and extent of surgery, may become the basis of successful treatment in the more complex or advanced types of hepatoblastoma.

Objective To assess whether adult involvement in a youth cooking intervention program resulted in improvements of adult perceptions of youth nutrition and activity knowledge and behaviors and family-related outcomes. A second objective was to examine adult responses for differences by income, food assistance use, and household size. Use of Theory or Research Many strategies for childhood obesity prevention have included experiential cooking programs involving parents in various ways. However, evidence is lacking on parent involvement, perceptions, and outcomes. Target Audience Fourth and 5th grade youth at two Title I elementary schools and their families. Program Description The WeCook: Fun with Food and Fitness program was a 12-week, out-of-school time food preparation, nutrition and physical activity program that also engaged families in a comprehensive, multifaceted approach. Evaluation Methods Pre- and post-surveys were administered to youth and their parent/caregiver. Sixty matched youth and adult surveys were included in the analysis. The program was a treatment-only design. Results Results demonstrated a significant increase in adults’ perceptions of their youth's ability to choose healthy snacks and be more active. Further analysis demonstrated significant differences between adult reported demographic characteristics. Lower income adults reported increased youth sedentary habits, adults using food assistance reported decreased family breakfast frequency, and adults with smaller household sizes reported decreased youth activity before school. Youth reported increases in their nutrition and physical activity knowledge, ability to choose healthy snacks, and consumption of sweets post-program. Adult and youth responses at post-assessment were positively correlated in the areas of healthy eating and activity behaviors, such as the perceived ability of youth to eat fruit and healthy snacks, choose water instead of sweetened beverages, and be active after school. Conclusions Further research is needed on adult and family outcomes from youth cooking programs to understand the adult and youth health relationship and encourage obesity prevention programs to increase their focus on the family component and associated assessments. Funding USDA.

The outcomes of hepatic undifferentiated embryonal sarcoma (HUES) have historically been limited by persistent, unresectable disease and the subsequent development of disease resistance and dissemination. We present our institutional experience with HUES and assess current treatment trends and outcomes in the era of liver transplantation. We conducted a retrospective chart review of cases presenting with HUES at our institution over the past 10 years. The collected data included age, sex, presenting symptoms, imaging and the associated Pretreatment Extent of Disease (PRETEXT) score, pathology, chemotherapy, surgical interventions, and outcomes. Approval was obtained from the institutional review board of the Cincinnati Children's Hospital Medical Center. HUES was identified in 6 patients (4 males and 2 females) with a median age at diagnosis of 11 years (range = 7-13 years). Initial imaging was available for all but 1 patient. The PRETEXT stage for these patients ranged from II to III. One patient was diagnosed with lung metastases. Two patients underwent upfront resection, and 1 patient received neoadjuvant therapy and then conventional resection. Three patients were treated with orthotopic liver transplantation (OLT) after neoadjuvant chemotherapy (primary OLT in 2 cases and salvage OLT for local recurrence in 1 case). Two patients received posttransplant adjuvant chemotherapy. All 6 patients remained in clinical remission with a mean follow-up of 35 months (range = 12-84 months). In conclusion, OLT has rarely been reported as a treatment option for HUES. The addition of liver transplantation as a surgical option for treating patients with HUES can result in improved survival for patients whose tumors are initially unresectable or recur. Liver Transpl 20:191-199, 2014. © 2013 AASLD.

Background Biliary atresia (BA) is a unique neonatal disease resulting from inflammatory and fibrosing obstruction of the extrahepatic biliary tree. Previous studies have demonstrated the critical role of innate immunity and the Th1 response to activated inflammatory cells and overexpressed cytokines in the pathogenesis of BA. Myeloid differentiation factor 88 (MyD88) is a critical adaptor molecule that has been shown to play a crucial role in immunity. We investigated the role of MyD88 in the inflammatory response and development of cholangiopathy in murine BA. Methods MyD88 knockout (MyD88−/−) and wild-type (WT) BALB/c pups were injected with Rhesus rotavirus or saline on day 1 of life. The mice were monitored for clinical symptoms of BA, including jaundice, acholic stools, bilirubinuria, and death. The liver and extrahepatic bile ducts were harvested for histologic evaluation and the quantification of viral content, determination of cytokine expression, and detection of inflammatory cells. Results Rhesus rotavirus infection produced symptoms in 100% of both MyD88−/− and WT pups, with survival of 18% of WT and 0% of MyD88−/− mice. Histologic analysis demonstrated bile duct obstruction in both MyD88−/− and WT mice. Viral titers obtained 7 d after infection and expression of interferon-γ and tumor necrosis factor-α at day 3, 5, 8, and 12 after infection revealed no significant differences between the WT and MyD88−/− mice. Flow cytometry demonstrated similar levels of activated CD8+ T cells and natural killer cells. Conclusions The pathogenesis of murine BA is independent of the MyD88 signaling inflammatory pathway, suggesting alternative mechanisms are crucial in the induction of the model.

Biliary atresia (BA) is a neonatal obstructive cholangiopathy which progresses to end stage liver disease, often requiring transplantation. The murine model of BA, employing rhesus rotavirus (RRV), parallels human disease and has been used to elucidate mechanistic aspects of a virus induced biliary cholangiopathy. We previously reported that RRV VP4 gene plays an integral role in activating the immune system and induction of BA. Utilizing rotavirus binding and blocking assays, this study elucidated how RRV VP4 protein governs cholangiocyte susceptibility to infection both in vitro and in vivo in the murine model of BA. We identified the amino acid sequence on VP4 and its cholangiocyte binding protein, finding that the sequence is specific to those rotavirus strains which cause an obstructive cholangiopathy. Pretreatment of murine and human cholangiocytes with this VP4 derived peptide (TRTRVSRLY), significantly reduced RRV's ability to bind and infect the cells. However, the peptide did not block cholangiocyte binding of TUCH and Ro1845, strains which do not induce murine BA. The SRL sequence within TRTRVSRLY is required for cholangiocyte binding and viral replication. The cholangiocyte membrane protein bound by SRL was found to be Hsc70. Inhibition of Hsc70 by siRNAs reduced RRV's ability to infect cholangiocytes. This virus-cholangiocyte interaction is also seen in vivo in the murine model of BA, where inoculation of mice with TRTRVSRLY peptide significantly reduced symptoms and mortality in RRV-injected mice. Conclusion: The tri-peptide SRL on RRV VP4 binds to the cholangiocyte membrane protein Hsc70 defining a novel binding site governing VP4 attachment. Investigations are underway to determine the cellular response following this interaction to understand how it contributes to the pathogenesis of BA. This article is protected by copyright. All rights reserved.

This study aims to investigate differences in imaging, procedure utilization, and clinical outcomes of severely injured adolescents treated at adult versus pediatric trauma centers.The National Trauma Data Bank was queried retrospectively for adolescents, 15-19years old, with a length of stay (LOS)1day and Injury Severity Score (ISS)25 treated at adult (ATC) or pediatric (PTC) Level 1 trauma centers from 2007 to 2011. Patient demographics and utilization of imaging and procedures were analyzed. Univariate and multivariate regression analysis was used to compare outcomes.Of 12,861 adolescents, 51% were treated at ATC. Older age and more nonwhites were seen at ATC (p0.01). Imaging and invasive procedures were more common at ATC (p0.01). Shorter LOS (p=0.03) and higher home discharge rates (p0.01) were seen at PTC. ISS and mortality did not differ. Age, race, ATC care (all p0.01), and admission systolic blood pressure (SBP) (p=0.03) were predictors of CT utilization. ISS, SBP, and race (p0.01) were risk factors for overall mortality; SBP (p=0.03) and ISS (p0.01) predicted death from penetrating injury.Severely injured adolescents experience improved outcomes and decreased imaging and invasive procedures without additional mortality risk when treated at PTC. PTC is an appropriate destination for severely injured adolescents.

Kidney transplantation is the optimal treatment of ESRD in children. Some studies have reported inferior outcomes in recipients of LDN allografts who are ≤ 5 yr of age. We performed a retrospective review of pediatric recipient outcomes of 110 LDN allografts at our institution and examined predictors of adverse outcomes. Subgroup analysis was performed by dividing recipients into three age categories: 0-5 yr, 6-17 yr, and ≥ 18 yr. There was no significant difference between incidences of DGF or ARE between groups. Kaplan-Meier analysis demonstrated 100% allograft survival in 0- to 5-yr-old recipients, nearly reaching statistical significance (p = 0.07) for outcome superior to that of the two older age groups. Pretransplant HD was associated with increased risk of DGF (p = 0.05). Significant risk factors for ARE were recipient weight >15 kg (p = 0.033) and multiple renal arteries (p = 0.047). Previous ARE was associated with an increased risk of allograft failure (p = 0.02). LDN is not associated with increased risk of DGF, ARE, or allograft failure in the youngest recipients. These findings support an aggressive pursuit of preemptive transplantation even in the youngest pediatric allograft recipients.

The optimal treatment facility for adolescent trauma patients is controversial. We sought to investigate risk-adjusted outcomes of adolescents treated at adult-only trauma centers (ATCs) versus pediatric-only trauma centers (PTCs) in a state system with legislated American College of Surgeons-verified institutions to determine ideal prehospital referral patterns.The Ohio Trauma Registry was queried for patients 15 years to 19 years with a length of stay (LOS) greater than 1 day at ATC (Level 1) or PTC (Levels 1 and 2) from 2008 to 2012. Race, sex, emergency department vital signs, Injury Severity Score (ISS), computed tomography, and ultrasound imaging were reviewed. Outcomes by mechanism of injury included ventilator days, intensive care unit LOS, hospital LOS, and mortality. Statistical analysis was performed using χ test, t test, and Wilcoxon rank-sum test. Propensity score-based risk adjustment matching was used to compare groups (propensity score within 0.01, ISS within 5).Of 5,793 adolescents examined, (84% blunt, 16% penetrating) 66% were treated at an ATC. In unmatched comparisons, age, ISS, vital signs, and mortality differed significantly between centers (p0.01). For adolescents with blunt injury, more males (71.6% vs. 66.3%, p0.01) and nonwhites (19.2% vs. 15.8%, p0.01) were seen at PTCs. For penetrating trauma, more males (88.6% vs. 50.8%, p0.01) and nonwhites (66.4% vs. 34.3%, p0.01) were admitted to ATCs. In 873 propensity-matched pairs for blunt trauma and 95 propensity-matched pairs of penetrating injuries, no differences were seen in a priori outcomes. Imaging (blunt, head computed tomography and abdominal ultrasound, p0.01; penetrating, abdominal ultrasound, p = 0.02) was more common at ATCs.Major outcome differences for injured adolescents do not exist between ATCs and PTCs, regardless of injury pattern. Imaging remains more prevalent at ATCs. In a state system with mandatory American College of Surgeons-verified centers, injury patterns need not dictate triage decisions for adolescents.Epidemiologic study, level III.

Background To determine if patients with clinical stage III rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) and surgery have an improved survival when the response to treatment results in a pathologic T3 tumor with a microscopic focus (≤5 mm) compared with a larger (>5 mm) invasion of the perirectal tissue. Methods A retrospective review was conducted of 56 consecutive patients clinically diagnosed as T3N1M0 rectal cancer before treatment, who completed neoadjuvant CRT followed by surgical resection. Those with residual pathologic T3 disease ( n = 28) were analyzed separately. Clinicopathologic data including T stage, lymph node status, k-ras status, and differentiation were reviewed. Results Among all 56 patients, there was no identified predictor of survival following neoadjuvant CRT and surgery. Among those with residual T3 disease, tumors extending >5 mm invasion into the perirectal tissue were associated with a higher risk of recurrence (50% vs 17%) and worse overall survival (4.3 vs 6.8 years, P = .015) when compared to tumors with ≤5 mm invasion into the perirectal tissue. Conclusion The depth of residual T3 tumor invasion into the perirectal tissue correlates with recurrence and overall survival in patients who underwent neoadjuvant therapy followed by surgical resection for clinically staged T3N1M0 rectal cancer.

The outcomes of hepatic undifferentiated embryonal sarcoma (HUES) have historically been limited by persistent, unresectable disease and the subsequent development of disease resistance and dissemination. We present our institutional experience with HUES and assess current treatment trends and outcomes in the era of liver transplantation. We conducted a retrospective chart review of cases presenting with HUES at our institution over the past 10 years. The collected data included age, sex, presenting symptoms, imaging and the associated Pretreatment Extent of Disease (PRETEXT) score, pathology, chemotherapy, surgical interventions, and outcomes. Approval was obtained from the institutional review board of the Cincinnati Children's Hospital Medical Center. HUES was identified in 6 patients (4 males and 2 females) with a median age at diagnosis of 11 years (range = 7-13 years). Initial imaging was available for all but 1 patient. The PRETEXT stage for these patients ranged from II to III. One patient was diagnosed with lung metastases. Two patients underwent upfront resection, and 1 patient received neoadjuvant therapy and then conventional resection. Three patients were treated with orthotopic liver transplantation (OLT) after neoadjuvant chemotherapy (primary OLT in 2 cases and salvage OLT for local recurrence in 1 case). Two patients received posttransplant adjuvant chemotherapy. All 6 patients remained in clinical remission with a mean follow-up of 35 months (range = 12-84 months). In conclusion, OLT has rarely been reported as a treatment option for HUES. The addition of liver transplantation as a surgical option for treating patients with HUES can result in improved survival for patients whose tumors are initially unresectable or recur.

Renal rhabdomyosarcoma (RMS) is a rare pediatric tumor. Pancake kidneys are unusual anatomic anomalies resulting when both upper and lower poles of the embryonic kidney become fused. We report on a 4-year-old boy who was discovered to have a stage 4, group IV renal embryonal RMS arising from a pancake kidney with metastases to the lung, pelvis, and bone marrow. Treatment included multimodal therapy, consisting of neoadjuvant chemotherapy, complete surgical resection, and adjuvant chemotherapy. He remains in clinical remission 7 months after resection.

Biliary atresia (BA) is a neonatal disease that results in obliteration of the biliary tree. The murine model of BA, which mirrors the human disease, is based upon infection of newborn mice with rhesus rotavirus (RRV), leading to an obstructive cholangiopathy. The purpose of this study was to characterize the temporal relationship between viral infection and the induction of this model. BALB/c mice were infected with RRV on day of life (DOL) 0, 3, 5, and 7. Groups were characterized as early-infection (infection by DOL 3) or late-infection (infection after DOL 5). Early RRV infection induced symptoms in 95% of pups with a mortality rate of 80%. In contrast, late infection caused symptoms in only 50% of mice, and 100% of pups survived. The clinical findings correlated with histological analysis of extrahepatic biliary trees, cytokine expression, and viral titers. Primary murine cholangiocytes isolated, cultured, and infected with RRV yielded higher titers of infectious virus in those harvested from DOL 2 versus DOL 9 mice. Less interferon alpha and beta was produced in DOL 2 versus DOL 9 RRV infected primary cholangiocytes. Injection of BALB/c interferon alpha/beta receptor knockout (IFN-αβR(-/-)) pups at DOL 7 showed increased symptoms (79%) and mortality (46%) when compared to late infected wild type mice. In conclusion, the degree of injury sustained by relatively immature cholangiocytes due to more robust RRV replication correlated with more severe clinical manifestations of cholangiopathy and higher mortality. Interferon alpha production by cholangiocytes appears to play a regulatory role. These findings confirm a temporal dependence of RRV infection in murine BA and begin to define a pathophysiologic role of the maturing cholangiocyte.