Surgical management of complicated Crohn's disease.

Surgical management of pediatric Crohn's disease is fundamentally palliative, aiming to treat the sequalae of complicated disease while preserving intestinal length. Multidisciplinary discussion of risk factors and quality of life should take place prior to operative intervention. Though the surgical management of pediatric Crohn's disease is largely based on the adult literature, there are considerations specific to the pediatric population - notably disease and treatment effects on growth and development. Intrabdominal abscess is approached with percutaneous drainage when feasible, reserving surgical intervention for the patient who is unstable or failing medical therapy. Pediatric patients with fibrostenotic disease should be considered for strictureplasty when possible, for maximum preservation of bowel length. Patients with medically refractory Crohn's proctocolitis should be treated initially with fecal diversion without proctocolectomy.

Does Delayed Diagnosis of Hirschsprung Disease Impact Post-operative and Functional Outcomes? A Multi-Center Review From the Pediatric Colorectal and Pelvic Learning Consortium.

BACKGROUND: Hirschsprung Disease (HD) is a rare cause of functional bowel obstruction in children. Patients are typically diagnosed in the neonatal period and undergo pull-through (PT) soon after diagnosis. The optimal management and post-operative outcomes of children who present in a delayed fashion are unknown. METHODS: A multi-center retrospective review of children with HD was performed at participating Pediatric Colorectal and Pelvic Learning Consortium sites. Children were stratified by age at diagnosis (neonates <29 days; infants 29 days-12 months; toddler 1 year-5 years and child >5 years). RESULTS: 679 patients with HD from 14 sites were included; Most (69%) were diagnosed in the neonatal period. Age at diagnosis was not associated with differences in 30-day complication rates or need for PT revision. Older age at diagnosis was associated with a greater likelihood of undergoing fecal diversion after PT (neonate 10%, infant 12%, toddler 26%, child 28%, P < 0.001) and a greater need for intervention for constipation or incontinence postoperatively (neonate 56%, infant 62%, toddler 78%, child 69%, P < 0.001). CONCLUSION: Delayed diagnosis of HD does not impact 30-day post-operative outcomes or need for revision surgery but, delayed diagnosis is associated with increased need for fecal diversion after pull-through. LEVEL OF EVIDENCE: III.

Hirschsprung disease: a cost analysis study of the direct, indirect costs and financial coping strategies for the surgical management in Western Uganda.

BACKGROUND: Surgical management of Hirschsprung disease (HD) in low- and middle-income countries is typically a staged procedure, necessitating multiple hospitalizations and clinic visits increasing family financial burden. Currently, there is limited information on the costs borne by caretakers of children with Hirschsprung disease seeking surgical intervention. This study seeks to measure the costs and economic burden of surgical treatment for Hirschsprung disease in western Uganda. METHODS: A cross-sectional study using cost analysis was conducted among caretakers of patients who completed surgical treatment of HD between January 2017 and December 2021 at two hospitals in western Uganda. The average direct and indirect costs incurred by caretakers presenting at a public and private hospital were computed. RESULTS: A total of 69 patients (M: F = 7:1) were enrolled in the study. The median age at diagnosis was 60.5 (IQR 3-151.25) days for children and two-staged pull-through procedure was the common surgery performed. The mean overall cost for treatment was US $960 (SD = $720), with the majority of costs coming from direct medical costs. Nearly half (48%) of participants resorted to distress financing to finance their child's surgical care. The overwhelming majority of patients (n = 64, 93%) incurred catastrophic expenditure from the total costs of surgery for HD, and 97% of participants fell below the international poverty line at the time treatment was completed. CONCLUSION: Despite the availability of 'free care' from government hospital and non-profit services, this study found that surgical management of Hirschsprung disease imposed substantial cost burden on families with Hirschsprung disease patients.

The Pediatric Emergency Surgery Course: Impact on Provider Practice in Rural Uganda.

PURPOSE: The Pediatric Emergency Surgery Course (PESC) trains rural Ugandan providers to recognize and manage critical pediatric surgical conditions. 45 providers took PESC between 2018 and 2019. We sought to assess the impact of the course at three regional hospitals: Fort Portal, Kabale, and Kiwoko. METHODS: We conducted a retrospective cohort study. Diagnosis, procedure, and patient outcome data were collected twelve months before and after PESC from admission and theater logbooks. We also assessed referrals from these institutions to Uganda's two pediatric surgery hubs: Mulago and Mbarara Hospitals. Wilcoxon rank-sum and Pearson's chi-squared tests compared pre- and post-PESC measures. Interrupted time-series-analysis assessed referral volume before and after PESC. RESULTS: 1534 admissions and 2148 cases were documented across the three regional hospitals. Kiwoko made 539 referrals, while pediatric surgery hubs received 116 referrals. There was a statistically significant immediate increase in the number of referrals from Fort Portal, from 0.5 patients/month pre-PESC to 0.8 post-PESC (95 % CI 0.03-1.51). Moving averages of the combined number of pyloromyotomy, intussusception reductions, and hernia repairs at the rural hospitals also increased post-course. Neonatal time to referral and referred patient age were significantly lower after PESC delivery. CONCLUSION: Our data suggest that PESC increased referrals to tertiary centers and operative volume of selected cases at rural hospitals and shortened time to presentation at sites receiving referrals. PESC is a locally-driven, validated, clinical education intervention that improves timely care of pediatric surgical emergencies and merits further support and dissemination. TYPE OF STUDY: Retrospective Cohort Study. LEVEL OF EVIDENCE: III.

Does Length of Extended Resection Beyond Transition Zone Change Clinical Outcome for Hirschsprung Pull-Through?

INTRODUCTION: A proximal resection margin greater than 5 cm from the intra-operative histologically determined transition zone has been deemed necessary to minimize the risk of transition zone pull-through. This extended resection may require the sacrifice of vascular supply and even further bowel resection. The impact of extended proximal resection margin on post-operative complications and functional outcomes is unclear. METHODS: A retrospective chart review of patients who underwent primary pull-through for Hirschsprung disease at a single institution between January 2008 and December 2022 was performed. An adequate proximal margin was defined by a circumferential normally ganglionated ring and absence of hypertrophic nerves. The extended margin was defined as the total length of proximal colon with normal ganglion cells and without hypertrophic nerves. Fecal incontinence severity was assessed with the Pediatric Fecal Incontinence Severity Score (PFISS). RESULTS: Eighty seven patients met criteria for inclusion. Median age at primary pull-through was 17 days (IQR 10-92 days), 55% (n = 48) of patients had an extended proximal margin (EPM) ≤ 5 cm, and 45% (n = 39) had an EPM > 5 cm. An EPM ≤5 cm was not associated with increased rates of Hirschsprung associated enterocolitis (≤5 cm 43%, >5 cm 39%, P = 0.701), diversion post pull-through (≤5 cm 10%, >5 cm 5%, P = 0.367) or reoperation for transition zone pull-through (≤5 cm 3%, >5 cm 0%, P = 0.112). EPM ≤5 cm had more frequent involuntary daytime bowel movements (P = 0.041) and more frequent voluntary bowel movements (P = 0.035). There were no differences in other measures of fecal incontinence severity. CONCLUSIONS: Shorter proximal extended margins beyond the adequate ganglionated margin do not significantly impact post-operative complication rates and have an unclear effect on fecal incontinence. TYPE OF STUDY: Case Control. LEVEL OF EVIDENCE: Level III.

In utero delivery of miRNA induces epigenetic alterations and corrects pulmonary pathology in congenital diaphragmatic hernia.

Structural fetal diseases, such as congenital diaphragmatic hernia (CDH) can be diagnosed prenatally. Neonates with CDH are healthy in utero as gas exchange is managed by the placenta, but impaired lung function results in critical illness from the time a baby takes its first breath. MicroRNA (miR) 200b and its downstream targets in the TGF-ß pathway are critically involved in lung branching morphogenesis. Here, we characterize the expression of miR200b and the TGF-ß pathway at different gestational times using a rat model of CDH. Fetal rats with CDH are deficient in miR200b at gestational day 18. We demonstrate that novel polymeric nanoparticles loaded with miR200b, delivered in utero via vitelline vein injection to fetal rats with CDH results in changes in the TGF-ß pathway as measured by qRT-PCR; these epigenetic changes improve lung size and lung morphology, and lead to favorable pulmonary vascular remodeling on histology. This is the first demonstration of in utero epigenetic therapy to improve lung growth and development in a pre-clinical model. With refinement, this technique could be applied to fetal cases of CDH or other forms of impaired lung development in a minimally invasive fashion.

Clinical Practices Following Train-The-Trainer Trauma Course Completion in Uganda: A Parallel-Convergent Mixed-Methods Study.

BACKGROUND: Despite the growth of trauma training courses worldwide, evidence for their impact on clinical practice in low- and middle-income countries (LMICs) is sparse. We investigated trauma practices by trained providers in Uganda using clinical observation, surveys, and interviews. METHODS: Ugandan providers participated in the Kampala Advanced Trauma Course (KATC) from 2018 to 2019. Between July and September of 2019, we directly evaluated guideline-concordant behaviors in KATC-exposed facilities using a structured real-time observation tool. We conducted 27 semi-structured interviews with course-trained providers to elucidate experiences of trauma care and factors that impact adoption of guideline-concordant behaviors. We assessed perceptions of trauma resource availability through a validated survey. RESULTS: Of 23 resuscitations, 83% were managed without course-trained providers. Frontline providers inconsistently performed universally applicable assessments: pulse checks (61%), pulse oximetry (39%), lung auscultation (52%), blood pressure (65%), pupil examination (52%). We did not observe skill transference between trained and untrained providers. In interviews, respondents found KATC personally transformative but not sufficient for facility-wide improvement due to issues with retention, lack of trained peers, and resource shortages. Resource perception surveys similarly demonstrated profound resource shortages and variation across facilities. CONCLUSIONS: Trained providers view short-term trauma training interventions positively, but these courses may lack long-term impact due to barriers to adopting best practices. Trauma courses should include more frontline providers, target skill transference and retention, and increase the proportion of trained providers at each facility to promote communities of practice. Essential supplies and infrastructure in facilities must be consistent for providers to practice what they have learned.

Improving Surgical Research Capacity in Low- and Middle-Income Countries: Can Episodic Data Collection Reliably Estimate Perioperative Mortality?

OBJECTIVE: The aim of this study was to empirically determine the optimal sample size needed to reliably estimate perioperative mortality (POMR) in different contexts. SUMMARY BACKGROUND DATA: POMR is a key metric for measuring the quality and safety of surgical systems and will need to be tracked as surgical care is scaled up globally. Continuous collection of outcomes for all surgical cases is not the standard in high-income countries and may not be necessary in low- and middle-income countries. METHODS: We created simulated datasets to determine the sampling frame needed to reach a given precision. We validated our findings using data collected at Mulago National Referral Hospital in Kampala, Uganda. We used these data to create a tool that can be used to determine the optimal sampling frame for a population based on POMR rate and target POMR improvement goal. RESULTS: Precision improved as the sampling frame increased. However, as POMR increased, lower sampling percentages were needed to achieve a given precision. A total of 357 eligible cases were identified in the Mulago database with an overall POMR rate of 14%. Precision of ±10% was achieved with 34% sampling, and precision of ±25% was obtained at 9% sampling. Using simulated datasets, a tool was created to determine the minimum sample percentage needed to detect a given mortality improvement goal. CONCLUSIONS: Reliably tracking POMR does not require continuous data collection. Data driven sampling strategies can be used to decrease the burden of data collection to track POMR in resource-constrained settings.

Cryptogenic acute lower extremities and multiorgan ischemia in an 8-year-old girl.

Pediatric acute limb ischemia is rare but can have devastating effects on children. The most common causes of acute limb ischemia in the pediatric age group are iatrogenic injury during cardiac catheterization and traumatic vessel injury. Embolic events have been described less often. We present the case of an 8-year-old girl with cryptogenic extensive bilateral lower extremity ischemia and embolization to multiple visceral organs. Our findings have highlighted the importance of interdisciplinary workup, timely intervention, and the advantage of intraoperative imaging for revascularization.

Relevance and Regulation of Alternative Splicing in Plant Heat Stress Response: Current Understanding and Future Directions.

Alternative splicing (AS) is a major mechanism for gene expression in eukaryotes, increasing proteome diversity but also regulating transcriptome abundance. High temperatures have a strong impact on the splicing profile of many genes and therefore AS is considered as an integral part of heat stress response. While many studies have established a detailed description of the diversity of the RNAome under heat stress in different plant species and stress regimes, little is known on the underlying mechanisms that control this temperature-sensitive process. AS is mainly regulated by the activity of splicing regulators. Changes in the abundance of these proteins through transcription and AS, post-translational modifications and interactions with exonic and intronic cis-elements and core elements of the spliceosomes modulate the outcome of pre-mRNA splicing. As a major part of pre-mRNAs are spliced co-transcriptionally, the chromatin environment along with the RNA polymerase II elongation play a major role in the regulation of pre-mRNA splicing under heat stress conditions. Despite its importance, our understanding on the regulation of heat stress sensitive AS in plants is scarce. In this review, we summarize the current status of knowledge on the regulation of AS in plants under heat stress conditions. We discuss possible implications of different pathways based on results from non-plant systems to provide a perspective for researchers who aim to elucidate the molecular basis of AS under high temperatures.

Intra-amniotic Injection of Poly(lactic-co-glycolic Acid) Microparticles Loaded with Growth Factor: Effect on Tissue Coverage and Cellular Apoptosis in the Rat Model of Myelomeningocele.

BACKGROUND: Myelomeningocele (MMC) is a devastating congenital neurologic disorder that can lead to lifelong morbidity and has limited treatment options. This study investigates the use of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) loaded with fibroblast growth factor (FGF) as a platform for in utero treatment of MMC. STUDY DESIGN: Intra-amniotic injections of PLGA MPs were performed on gestational day 17 (E17) in all-trans retinoic acid-induced MMC rat dams. MPs loaded with fluorescent dye (DiO) were evaluated 3 hours after injection to determine incidence of binding to the MMC defect. Fetuses were then treated with PBS or PLGA particles loaded with DiO, bovine serum albumin, or FGF and evaluated at term (E21). Fetuses with MMC defects were evaluated for gross and histologic evidence of soft tissue coverage. The effect of PLGA-FGF treatment on spinal cord cell death was evaluated using an in situ cell death kit. RESULTS: PLGA-DiO MPs had a binding incidence of 86% and 94% 3 hours after injection at E17 for doses of 0.1 mg and 1.2 mg, respectively. Incidence of soft tissue coverage at term was 19% (4 of 21), 22% (2 of 9), and 83% (5 of 6) for PLGA-DiO, PLGA-BSA, and PLGA-FGF, respectively. At E21, the percentage of spinal cord cells positive for in situ cell death was significantly higher in MMC controls compared with wild-type controls or MMC pups treated with PLGA-FGF. CONCLUSION: PLGA MPs are an innovative minimally invasive platform for induction of soft tissue coverage in the rat model of MMC and may reduce cellular apoptosis.

Financing Pediatric Surgery: A Provider's Perspective from the Global Initiative for Children's Surgery.

BACKGROUND: Half the world's population is at risk of catastrophic health expenditure (CHE, out-of-pocket spending of more than 10% of annual expenditure) should they require surgery. Protection against CHE is a key indicator of successful health care delivery and has been identified as a priority area by the Global Initiative for Children's Surgery (GICS). Data specific to pediatric surgical patients is limited. This study examines the financial risks for pediatric surgical patients and their families from a provider's perspective. METHODS: We surveyed GICS members about the existing financial protection mechanisms and estimated expenditures for their patients. Questions were structured based on the National Surgical, Obstetric and Anesthesia Planning Surgical Indicators and finalized based on multi-institutional consensus between high-income country and low-and middle-income country (LMIC) providers. Chi-squared test, Fisher's exact test and student's t-test were used as appropriate. RESULTS: Among 107 respondents, 72.4% were from low income or lower-middle income (LIC/LMIC) countries, and 55.1% were attending or consultant physicians. Families were most likely to decline surgery in LIC/LMIC due to inability to afford treatment (mean Likert = 3.77 ± 1.06). The odds of incurring CHE after children's surgery are up to 17 times greater in LIC/LMIC (P = 0.001, unadjusted OR 17.28, 95%CI 2.13-140.02). Over 50% of families of children undergoing major surgery in these settings face CHE. An estimated 5.1% of providers in LIC/LMIC and 56.2% (P < 0.001) of providers in UMIC/HIC reported that families are able to pay for their direct medical costs with the assistance available to them and were more likely to sell assets (74.4% vs. 33.3%, P = 0.005). CONCLUSION: Patients in LMICs are at greater risk for CHE and have less financial risk protection than their HIC counterparts. Given this disparity, intervention is needed to make safe surgery affordable for children worldwide.

HsfA7 coordinates the transition from mild to strong heat stress response by controlling the activity of the master regulator HsfA1a in tomato.

Plants respond to higher temperatures by the action of heat stress (HS) transcription factors (Hsfs), which control the onset, early response, and long-term acclimation to HS. Members of the HsfA1 subfamily, such as tomato HsfA1a, are the central regulators of HS response, and their activity is fine-tuned by other Hsfs. We identify tomato HsfA7 as capacitor of HsfA1a during the early HS response. Upon a mild temperature increase, HsfA7 is induced in an HsfA1a-dependent manner. The subsequent interaction of the two Hsfs prevents the stabilization of HsfA1a resulting in a negative feedback mechanism. Under prolonged or severe HS, HsfA1a and HsfA7 complexes stimulate the induction of genes required for thermotolerance. Therefore, HsfA7 exhibits a co-repressor mode at mild HS by regulating HsfA1a abundance to moderate the upregulation of HS-responsive genes. HsfA7 undergoes a temperature-dependent transition toward a co-activator of HsfA1a to enhance the acquired thermotolerance capacity of tomato plants.

Pediatric surgical quality improvement in low- and middle-income countries: What data to collect?

BACKGROUND: As surgical access expands in low- and middle-income countries, risk-adjusted outcomes data are needed to measure and improve surgical quality. Existing data collection tools in high-income countries are complex and may be burdensome to implement in low and middle income countries. This study determined the minimum dataset needed for adequate risk adjustment to predict perioperative mortality using data collected in a low- and middle-income countries. METHODS: All patients admitted to the pediatric surgery ward at Mulago National Referral Hospital in Kampala, Uganda, from January 1, 2014 through December 31, 2018 were included. Studies were performed modelling the effects of reducing data granularity and reducing number of variables on the area under the receiver operating curve. RESULTS: Of the 3,194 patients included, 1,941(61%) were male, 957(30%) were neonates, 1,714 (54%) had an operation, and the overall mortality rate was 14%. Granularity reduction analyses found that measuring age in ranges was equivalent to recording age in days (area under the receiver operating curve = 0.776; 95% confidence interval, 0.754%-0.798%, vs 0.815, 95% confidence interval, 0.794%-0.837%). Variable reduction analyses found that models with 3 predictor variables (diagnosis, procedure, and district) reached a maximum area under the receiver operating curve of 0.915 (95% confidence interval, 0.903%-0.928%), which was equivalent to the model using all available predictor variables (area under the receiver operating curve = 0.932; 95% confidence interval, 0.922%-0.943%). For all 3-variable models, the primary diagnosis contributed most to predictive ability (P < .001). CONCLUSION: Effective risk adjustment for perioperative mortality can be performed in low and middle income countries using minimal, objective variables often already part of the patient's medical record. This approach can be used by clinicians, hospital administrators, and policymakers low- and middle-income countries looking to begin data collection to track and improve patient outcomes.

Engineering alginate microparticles for optimized accumulation in fetal rat myelomeningocele.

INTRODUCTION: Intraamniotic microparticle injection is a novel technique for the treatment of myelomeningocele (MMC) in which microparticles are delivered in-utero in a minimally invasive fashion to bind to and protect the exposed spinal cord. This technique could offer earlier intervention and greater access to prenatal treatment of MMC. Here we demonstrate progress on the engineering of the microparticles to promote binding to the MMC defect. We hypothesized that when the particle's surface charge was decreased and delivery concentration increased, particles would bind to the MMC defect more frequently and more specifically. METHODS: Alginate microparticles underwent surface modification to alter the particle charge. Dye-loaded alginate, alginate- dextran sulfate, and alginate- chitosan were injected on e17 into the amnion of a rat model of MMC and the incidence of successful binding and specificity of particle binding to the MMC defect were calculated. Specificity of binding was described using a defect-to-skin brightness ratio based on specimen imaging. Comparisons were made with chi-square, p< 0.05 marked significance. RESULTS: There was no difference in the incidence of successful binding at e17 with 0.6 mg/fetal kg between the three tested alginate particles. However, alginate- dextran sulfate bound most specifically to the defect (p< 0.05). Alginate-dextran sulfate also demonstrated more frequent binding at higher doses than lower doses (79% at 1.2 mg/kg vs 38% at 0.6 mg/kg and 24% at 0.8 mg/kg, p< 0.01 for both). Specificity was not sacrificed at higher dose injections: defect-to-skin brightness ratio of 5.4 at 1.2 mg/kg vs 1.8 at 0.6 mg/kg (p< 0.05) CONCLUSION: We demonstrate that the intraamniotic injection of alginate-dextran sulfate microparticles at high concentration bind more frequently and more specifically to MMC defects than the previously tested unmodified alginate microparticles.

A narrative review of in utero gene therapy: advances, challenges, and future considerations.

The field of in utero gene therapy (IUGT) represents a crossroad of technologic advancements and medical ethical boundaries. Several strategies have been developed for IUGT focusing on either modifying endogenous genes, replacing missing genes, or modifying gene transcription products. The list of candidate diseases such as hemoglobinopathies, cystic fibrosis, lysosomal storage disorders continues to grow with new strategies being developed as our understanding of their respective underlying molecular pathogenesis increases. Treatment in utero has several distinct advantages to postnatal treatment. Biologic and physiologic phenomena enable the delivery of a higher effective dose, generation of immune tolerance, and the prevention of phenotypic onset for genetic diseases. Therapeutic technology for IUGT including CRISPR-Cas9 systems, zinc finger nucleases (ZFN), and peptide nucleic acids (PNAs) has already shown promise in animal models and early postnatal clinical trials. While the ability to detect fetal diagnoses has dramatically improved with developments in ultrasound and next-generation sequencing, treatment options remain experimental, with several translational gaps remaining prior to implementation in the clinical realm. Complicating this issue, the potential diseases targeted by this approach are often debilitating and would otherwise prove fatal if not treated in some manner. The leap from small animals to large animals, and subsequently, to humans will require further vigorous testing of safety and efficacy.

Diffusion weighted imaging as a biomarker of retinoic acid induced myelomeningocele.

Neural tube defects are a common congenital anomaly involving incomplete closure of the spinal cord. Myelomeningocele (MMC) is a severe form in which there is complete exposure of neural tissue with a lack of skin, soft tissue, or bony covering to protect the spinal cord. The all-trans retinoic acid (ATRA) induced rat model of (MMC) is a reproducible, cost-effective means of studying this disease; however, there are limited modalities to objectively quantify disease severity, or potential benefits from experimental therapies. We sought to determine the feasibility of detecting differences between MMC and wild type (WT) rat fetuses using diffusion magnetic resonance imaging techniques (MRI). Rat dams were gavage-fed ATRA to produce MMC defects in fetuses, which were surgically delivered prior to term. Average diffusion coefficient (ADC) and fractional anisotropy (FA) maps were obtained for each fetus. Brain volumes and two anatomically defined brain length measurements (D1 and D2) were significantly decreased in MMC compared to WT. Mean ADC signal was significantly increased in MMC compared to WT, but no difference was found for FA signal. In summary, ADC and brain measurements were significantly different between WT and MMC rat fetuses. ADC could be a useful complementary imaging biomarker to current histopathologic analysis of MMC models, and potentially expedite therapeutic research for this disease.

Stance leg and surface stability modulate cortical activity during human single leg stance.

Mobile Electroencephalography (EEG) provides insights into cortical contributions to postural control. Although changes in theta (4-8 Hz) and alpha frequency power (8-12 Hz) were shown to reflect attentional and sensorimotor processing during balance tasks, information about the effect of stance leg on cortical processing related to postural control is lacking. Therefore, the aim was to examine patterns of cortical activity during single-leg stance with varying surface stability. EEG and force plate data from 21 healthy males (22.43 ± 2.23 years) was recorded during unipedal stance (left/right) on a stable and unstable surface. Using source-space analysis, power spectral density was analyzed in the theta, alpha-1 (8-10 Hz) and alpha-2 (10-12 Hz) frequency bands. Repeated measures ANOVA with the factors leg and surface stability revealed significant interaction effects in the left (p = 0.045, ηp2 = 0.13) and right motor clusters (F = 16.156; p = 0.001, ηp2 = 0.41). Furthermore, significant main effects for surface stability were observed for the fronto-central cluster (theta), left and right motor (alpha-1), as well as for the right parieto-occipital cluster (alpha-1/alpha-2). Leg dependent changes in alpha-2 power may indicate lateralized patterns of cortical processing in motor areas during single-leg stance. Future studies may therefore consider lateralized patterns of cortical activity for the interpretation of postural deficiencies in unilateral lower limb injuries.

Nanoparticles for delivery of agents to fetal lungs.

Fetal treatment of congenital lung disease, such as cystic fibrosis, surfactant protein syndromes, and congenital diaphragmatic hernia, has been made possible by improvements in prenatal diagnostic and interventional technology. Delivery of therapeutic agents to fetal lungs in nanoparticles improves cellular uptake. The efficacy and safety of nanoparticle-based fetal lung therapy depends on targeting of necessary cell populations. This study aimed to determine the relative distribution of nanoparticles of a variety of compositions and sizes in the lungs of fetal mice delivered through intravenous and intra-amniotic routes. Intravenous delivery of particles was more effective than intra-amniotic delivery for epithelial, endothelial and hematopoietic cells in the fetal lung. The most effective targeting of lung tissue was with 250nm Poly-Amine-co-Ester (PACE) particles accumulating in 50% and 44% of epithelial and endothelial cells. This study demonstrated that route of delivery and particle composition impacts relative cellular uptake in fetal lung, which will inform future studies in particle-based fetal therapy.

Pulmonary Metastasis of Low-risk Perinatal Neuroblastoma After Resection: Implications for Surveillance.

In the wake of the Children's Oncology Group (COG) ANBL00P2 trial and the ongoing ANBL1232 trial, an increasing number of children with neonatal neuroblastoma are being managed nonoperatively. We report the case of a patient with low-risk, non-MYCN amplified, neuroblastoma that was diagnosed and resected in the neonatal period but subsequently developed pulmonary metastases by the age of 7 months. Though rare, the possibility of low-risk disease metastasizing during surveillance should be recognized and may not be identified by current protocols.