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Cytogenetic bands reflect genomic organization in large blocks of DNA with similar properties. Because banding patterns are invariant, this organization may often be assumed unimportant for genome regulation. Results here challenge that view. Findings here suggest cytogenetic bands reflect a visible framework upon which regulated genome architecture is built. Given Alu and L1 densities differ in cytogenetic bands, we examined their distribution after X-chromosome inactivation or formation of senescent-associated heterochromatin foci (SAHFs). Alu-rich regions remain outside both SAHFs and the Barr Body (BB), affirming that the BB is not the whole chromosome but a condensed, L1-rich core. Hi-C analysis of senescent cells demonstrates large (~10 Mb) G-bands remodel as a contiguous unit, gaining distal intrachromosomal interactions as syntenic G-bands coalesce into SAHFs. Striking peaks of Alu within R-bands strongly resist condensation. Thus, large-scale segmental genome architectur relates to dark versus light cytogenetic bands and Alu-peaks, implicating both in chromatin regulation.

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction. SAF-A has an N-terminal DNA binding domain and C-terminal RNA binding domain, and a prominent model has been that the protein provides a single-molecule bridge between XIST RNA and chromatin. Here analysis of the impact of SAF-A on broad RNA-chromatin interactions indicate greater biological complexity. We focus on SAF-A's role with repeat-rich C 0 T-1 hnRNA (repeat-rich heterogeneous nuclear RNA), shown recently to comprise mostly intronic sequences of pre-mRNAs and diverse long non-coding RNAs (lncRNAs). Our results show that SAF-A mutants cause dramatic changes to cytological chromatin condensation through dominant negative effects on C 0 T-1 RNA's association with euchromatin, and likely other nuclear scaffold factors. In contrast, depletion of SAF-A by RNA interference (RNAi) had no discernible impact on C 0 T-1 RNA, nor did it cause similarly marked chromatin changes as did three different SAF-A mutations. Overall results support the concept that repeat-rich, chromatin-associated RNAs interact with multiple RNA binding proteins (RBPs) in a complex dynamic meshwork that is integral to larger-scale chromatin architecture and collectively influences cytological-scale DNA condensation., (© 2021. The Author(s).)

Introduction: The authors compared pediatric thoracic patients in the Joint Theatre Trauma Registry (JTTR) to those in the National Trauma Data Bank (NTDB) to assess differences in patient mortality rates and mortality risk accounting for age, injury patterns, and injury severity., Materials and Methods: Patients less than 19 years of age with thoracic trauma were identified in both the JTTR and NTDB. Multiple logistic regression, χ2, Student's t-test, or Mann-Whitney U test were used as indicated to compare the two groups., Results: Pediatric thoracic trauma patients seen in Iraq and Afghanistan (n = 955) had a significantly higher mortality rate (15.1 vs. 6.0%, P <.01) than those in the NTDB (n = 9085). After controlling for covariates between the JTTR and the NTDB, there was no difference in mortality (odds ratio for mortality for U.S. patients was 0.74, 95% CI 0.52-1.06, P = .10). The patients seen in Iraq or Afghanistan were significantly younger (8 years old, interquartile ratio (IQR) 2-13 vs. 15, IQR 10-17, P <.01) had greater severity of injuries (injury severity score 17, IQR 12-26 vs. 12, IQR 8-22, P <.01), had significantly more head injuries (29 vs. 14%, P <.01), and over half were exposed to a blast., Discussion: Pediatric patients with thoracic trauma in Iraq and Afghanistan in the JTTR had similar mortality rates compared to the civilian population in the NTDB after accounting for confounding covariates. These findings indicate that deployed military medical professionals are providing comparable quality of care in extremely challenging circumstances. This information has important implications for military preparedness, medical training, and casualty care., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Repetitive sequences including transposable elements and transposon-derived fragments account for nearly half of the human genome. While transposition-competent transposable elements must be repressed to maintain genomic stability, mutated and fragmented transposable elements comprising the bulk of repetitive sequences can also contribute to regulation of host gene expression and broader genome organization. Here, we analyzed published ChIP-seq data sets to identify proteins broadly enriched on transposable elements in the human genome. We show 2 of the proteins identified, C2H2 zinc finger-containing proteins ZNF146 (also known as OZF) and ZNF507, are targeted to distinct sites within LINE-1 ORF2 at thousands of locations in the genome. ZNF146 binding sites are found at old and young LINE-1 elements. In contrast, ZNF507 preferentially binds at young LINE-1 sequences correlated to sequence changes in LINE-1 elements at ZNF507's binding site. To gain further insight into ZNF146 and ZNF507 function, we disrupt their expression in HEK293 cells using CRISPR/Cas9 and perform RNA sequencing, finding modest gene expression changes in cells where ZNF507 has been disrupted. We further identify a physical interaction between ZNF507 and PRMT5, suggesting ZNF507 may target arginine methylation activity to LINE-1 sequences., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Introduction Pediatric hospitalists are expected to lead resuscitative efforts for cardiopulmonary arrests, but the infrequency of these events and pediatric advanced life support (PALS) re-certifications are insufficient to maintain skill proficiency.We created a novel resuscitation refresher curriculum for pediatric hospitalists with strategic pauses during simulations for expert and peer coaching of procedural skills. Methods In a tertiary care academic pediatric hospital between September 2018 to June 2019, pediatric hospitalists and fellows voluntarily participated in a series of three quarterly two-hour training sessions taught by expert peer facilitators. Sessions focused on the thirty-second rapid cardiopulmonary assessment and each of the pediatric advanced life support (PALS) algorithms. Scenarios were strategically paused to practice critical hands-on skills. Cases centered on the themes of shock, respiratory, and cardiac emergencies and took place in a high-fidelity simulation lab requiring a technician and expert peer facilitator. Participants anonymously completed Likert scale-based evaluations after each session and again at the end of the year that focused on participants' own perceived change in their comfort levels in performing various resuscitation skills and in knowing basic resuscitation steps. As part of our institutional and personal assessment of the curriculum, an end-of-year survey additionally asked participants to reflect on the overall simulation curriculum and resultant changes in their clinical practice. Results Comfort in all skills practiced across the three sessions increased. The end-of-year survey showed a significant rise in comfort above baseline but some decrements when compared to that immediately post-training. Ninety-six percent of pediatric hospitalists rated the overall quality of the training "better" or "much better" than other resuscitation training (including PALS classes and traditional simulations with skills training after the scenario). The overall effect of the curriculum on perceived knowledge, skills, and confidence levels was significant (p <0.0001). Conclusion Serial resuscitation skills refreshers with expert peer coaching and strategic pauses for hands-on skills practice can result in significant improvements in perceived knowledge and comfort with skill performance as well as the leadership role among pediatric hospitalists., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ismail et al.)

Nuclear chromosomes transcribe far more RNA than required to encode protein. Here we investigate whether non-coding RNA broadly contributes to cytological-scale chromosome territory architecture. We develop a procedure that depletes soluble proteins, chromatin, and most nuclear RNA from the nucleus but does not delocalize XIST, a known architectural RNA, from an insoluble chromosome "scaffold." RNA-seq analysis reveals that most RNA in the nuclear scaffold is repeat-rich, non-coding, and derived predominantly from introns of nascent transcripts. Insoluble, repeat-rich (C 0 T-1) RNA co-distributes with known scaffold proteins including scaffold attachment factor A (SAF-A), and distribution of these components inversely correlates with chromatin compaction in normal and experimentally manipulated nuclei. We further show that RNA is required for SAF-A to interact with chromatin and for enrichment of structurally embedded "scaffold attachment regions" prevalent in euchromatin. Collectively, the results indicate that long nascent transcripts contribute a dynamic structural role that promotes the open architecture of active chromosome territories., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Introduction: The objective of this study is to review available data on pediatric thoracic trauma seen at U.S. military treatment facilities in Iraq and Afghanistan and describe the scope of injuries, patterns seen, and associated mortality. The results were compared with adults injured in Iraq and Afghanistan and other reports of pediatric thoracic trauma in the literature., Materials and Methods: The investigators received approval from the Uniformed Services University of the Health Sciences' institutional review board before the study. The Joint Theatre Trauma Registry was queried for all patients with an ICD-9 code for thoracic trauma. Two-tailed Student's t-test, Mann-Whitney rank sum, χ2, ANOVA, or multiple logistic regression was used as indicated., Results: There were 955 patients under the age of 18 yr, just over 12% of all thoracic trauma. Penetrating injuries were common (73.6%), including gunshot wounds. The most common pediatric diagnoses were contusions (45%), pneumothorax (40%), and rib and/or sternal fractures (18%). The overall mortality for children was 15.2% compared with 13.8% and 9% for civilian adults and Coalition members with thoracic trauma, respectively. Mortality was inversely related to age among pediatric patients. Children under 2 yr of age had the highest mortality (25.1%). Patients under 12 yr of age were more likely to die than those between 12 and 18 (OR 2.02, 95% CI 1.27-3.22) yr. Thoracic vascular injuries and cardiac injuries resulted in the highest mortality among pediatric patients. The presence of a hemothorax was independently associated with an increased risk for mortality (OR 1.78, 95% CI 1.06-2.99) as was a concomitant head injury (OR 2.17, 95% CI 1.33-3.54). There was a 2.7% incidence of burns among pediatric patients with a high associated mortality (46.2%). Nearly one-half of all the children identified required a transfusion (47%)., Conclusion: Penetrating injuries predominated and these children commonly required a transfusion. Mortality was inversely related to age. Children with a hemothorax or a concomitant head injury had significant increases in mortality. Children with thoracic injury as the result of a burn suffered the highest mortality.

XIST RNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, how XIST RNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering of XIST into a trisomic autosome demonstrates remarkable capacity of XIST RNA to localize and comprehensively silence that autosome. Thus, XIST does not require X chromosome-specific sequences but operates on mechanisms available genome-wide. Prior results suggested XIST localization is controlled by attachment to the insoluble nuclear scaffold. Our recent work affirms that scaffold attachment factor A (SAF-A) is involved in anchoring XIST , but argues against the view that SAF-A provides a unimolecular bridge between RNA and the chromosome. Rather, we suggest that a complex meshwork of architectural proteins interact with XIST RNA. Parallel work studying the territory of actively transcribed chromosomes suggests that repeat-rich RNA 'coats' euchromatin and may impact chromosome architecture in a manner opposite of XIST A model is discussed whereby RNA may not just recruit histone modifications, but more directly impact higher-order chromatin condensation via interaction with architectural proteins of the nucleus.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'., (© 2017 The Authors.)

Maintenance of the correct level and organisation of nucleosomes is crucial for genome function. Here, we uncover a role for a conserved bromodomain AAA-ATPase, Abo1, in the maintenance of nucleosome architecture in fission yeast. Cells lacking abo1(+) experience both a reduction and mis-positioning of nucleosomes at transcribed sequences in addition to increased intragenic transcription, phenotypes that are hallmarks of defective chromatin re-establishment behind RNA polymerase II. Abo1 is recruited to gene sequences and associates with histone H3 and the histone chaperone FACT. Furthermore, the distribution of Abo1 on chromatin is disturbed by impaired FACT function. The role of Abo1 extends to some promoters and also to silent heterochromatin. Abo1 is recruited to pericentromeric heterochromatin independently of the HP1 ortholog, Swi6, where it enforces proper nucleosome occupancy. Consequently, loss of Abo1 alleviates silencing and causes elevated chromosome mis-segregation. We suggest that Abo1 provides a histone chaperone function that maintains nucleosome architecture genome-wide., (© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Component balanced resuscitation and avoidance of crystalloids in traumatically injured adults requiring massive transfusion are beneficial. Evidence for children is lacking., Methods: After institutional review board approval was obtained, the Department of Defense Trauma Database identified 1,311 injured children 14 years or younger requiring transfusion after an injury and admitted to a deployed US military hospital from 2002 to 2012. Logistic regression determined risk factors for high-volume (≥40 mL/kg) or massive (≥70 mL/kg) transfusions. The effects of crystalloid and balanced component resuscitation in the first 24 hours were assessed., Results: Nine hundred seven patients had recorded data sufficient for analysis. Two hundred twenty-four children received high-volume transfusion, and 77 received massive transfusions. Mortality was significantly higher for massive transfusions and high-volume transfusions than others (25% vs. 10% and 19% vs. 9%, respectively). Age of less than 4 years, penetrating injury, and Injury Severity Score (ISS) greater than 15 were associated with high-volume transfusions; an ISS greater than 15 and penetrating injury were associated with massive transfusions. Increased crystalloid administration showed a significant positive association with hospital days and intensive care unit days for both massive and high-volume transfusions, as well as a significant positive association with increased ventilator days in patients with high-volume transfusions. Balanced component resuscitation was not associated with improved measured outcomes and was independently associated with a higher mortality when all transfused patients were considered., Conclusion: In this cohort, heavy reliance on crystalloid for resuscitation had an adverse effect on outcomes. Balanced component resuscitation did not improve outcomes and was associated with higher mortality when all transfused patients were considered. Further study is needed regarding efficacy and clinical triggers for the implementation of massive transfusion in children., Level of Evidence: Prognostic study, level IV.

Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/histone deacetylase (HDAC) repressor complex (SHREC) and is known to repress transcription at regions of heterochromatin. However, how Mit1 modifies chromatin to silence transcription is largely unknown. Here we report that Mit1 mobilizes histone octamers in vitro and requires ATP hydrolysis and conserved chromatin tethering domains, including a previously unrecognized chromodomain, to remodel nucleosomes and silence transcription. Loss of Mit1 remodeling activity results in nucleosome depletion at specific DNA sequences that display low intrinsic affinity for the histone octamer, but its contribution to antagonizing RNA polymerase II (Pol II) access and transcription is not restricted to these sites. Genetic epistasis analyses demonstrate that SHREC subunits and the transcription-coupled Set2 histone methyltransferase, which is involved in suppression of cryptic transcription at actively transcribed regions, cooperate to silence heterochromatic transcripts. In addition, we have demonstrated that Mit1's remodeling activity contributes to SHREC function independently of Clr3's histone deacetylase activity on histone H3 K14. We propose that Mit1 is a chromatin remodeling factor that cooperates with the Clr3 histone deacetylase of SHREC and other chromatin modifiers to stabilize heterochromatin structure and to prevent access to the transcriptional machinery.

In this issue of Molecular Cell, Ishida et al. (2012) and Keller et al. (2012) show distinct outcomes for heterochromatic RNAs that bind different chromodomain proteins; Chp1 tethers transcripts to centromeres, whereas Swi6(HP1)-bound transcripts are evicted from chromatin and destroyed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule (MT) dynamics to ensure accurate chromosome segregation. In this paper, we characterize a new kinetochore substrate of fission yeast Cdk1, Nsk1, which promotes proper kinetochore-MT (k-MT) interactions and chromosome movements in a phosphoregulated manner. Cdk1 phosphorylation of Nsk1 antagonizes Nsk1 kinetochore and spindle localization during early mitosis. A nonphosphorylatable Nsk1 mutant binds prematurely to kinetochores and spindle, cementing improper k-MT attachments and leading to high rates of lagging chromosomes that missegregate. Accordingly, cells lacking nsk1 exhibit synthetic growth defects with mutations that disturb MT dynamics and/or kinetochore structure, and lack of proper phosphoregulation leads to even more severe defects. Intriguingly, Nsk1 is stabilized by binding directly to the dynein light chain Dlc1 independently of the dynein motor, and Nsk1-Dlc1 forms chainlike structures in vitro. Our findings establish new roles for Cdk1 and the Nsk1-Dlc1 complex in regulating the k-MT interface and chromosome segregation., (© 2011 Chen et al.)

In recent years, a bevy of evidence has been unearthed indicating that 'silent' heterochromatin is not as transcriptionally inert as once thought. In the unicellular yeast Schizosaccharomyces pombe, the processing of transcripts derived from centromeric repeats into homologous short interfering RNA (siRNA) is essential for the formation of centromeric heterochromatin. Deletion of genes required for siRNA biogenesis showed that core components of the canonical RNA interference (RNAi) pathway are essential for centromeric heterochromatin assembly as well as for centromere function. Subsequent purification of the RNA-induced initiation of transcriptional gene silencing (RITS) complex provided the critical link between siRNAs and heterochromatin assembly, with RITS acting as a physical bridge between noncoding RNA scaffolds and chromatin. Here, we review current understanding of how RITS promotes heterochromatin formation and how it participates in transcription-coupled silencing. WIREs RNA 2011 2 632-646 DOI: 10.1002/wrna.80 For further resources related to this article, please visit the WIREs website., (Copyright © 2011 John Wiley & Sons, Ltd.)

Formation of centromeric heterochromatin in fission yeast requires the combined action of chromatin modifying enzymes and small RNAs derived from centromeric transcripts. Positive feedback mechanisms that link the RNAi pathway and the Clr4/Suv39h1 histone H3K9 methyltransferase complex (Clr-C) result in requirements for H3K9 methylation for full siRNA production and for siRNA production to achieve full histone methylation. Nonetheless, it has been proposed that the Argonaute protein, Ago1, is the key initial trigger for heterochromatin assembly via its association with Dicer-independent "priRNAs." The RITS complex physically links Ago1 and the H3-K9me binding protein Chp1. Here we exploit an assay for heterochromatin assembly in which loss of silencing by deletion of RNAi or Clr-C components can be reversed by re-introduction of the deleted gene. We showed previously that a mutant version of the RITS complex (Tas3(WG)) that biochemically separates Ago1 from Chp1 and Tas3 proteins permits maintenance of heterochromatin, but prevents its formation when Clr4 is removed and re-introduced. Here we show that the block occurs with mutants in Clr-C, but not mutants in the RNAi pathway. Thus, Clr-C components, but not RNAi factors, play a more critical role in assembly when the integrity of RITS is disrupted. Consistent with previous reports, cells lacking Clr-C components completely lack H3K9me2 on centromeric DNA repeats, whereas RNAi pathway mutants accumulate low levels of H3K9me2. Further supporting the existence of RNAi-independent mechanisms for establishment of centromeric heterochromatin, overexpression of clr4(+) in clr4Δago1Δ cells results in some de novo H3K9me2 accumulation at centromeres. These findings and our observation that ago1Δ and dcr1Δ mutants display indistinguishable low levels of H3K9me2 (in contrast to a previous report) challenge the model that priRNAs trigger heterochromatin formation. Instead, our results indicate that RNAi cooperates with RNAi-independent factors in the assembly of heterochromatin., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Over 3,500 infants and children, many critically ill and injured, have been admitted to military combat support hospitals (CSH) in Afghanistan and Iraq, which are not doctrinally staffed or equipped to provide their care. This report details how the military medical system is adapting to create a data driven and comprehensive response to optimize the medical and surgical pediatric care being provided., Methods: Information from multiple sources was used over time to craft the military medical response to the pediatric wartime mission. Pediatric data from both the Joint Theater Trauma Registry (JTTR) and the Patient Administration Systems and Biostatistics Activity (PASBA) database were utilized extensively. The resulting educational, supply, and personnel adaptations implemented by the U.S. military will be highlighted, and innovations currently under development will also be described on the basis of this demonstrated need., Results: This information helped drive pediatric-specific, just-in-time education for CSH personnel, modified CSH equipment and supply lists, inspired the 24/7 pediatric critical care teleconsultation service, and resulted in new initiatives in the predeployment training for CSH personnel., Conclusion: Military physicians are routinely asked to perform outside their traditional scopes of practice while deployed. Given this reality, military pediatric specialists in medicine and surgery have initiated several successful multidisciplinary programs designed to improve in-theater care of injured children. These innovative efforts include drafting a pediatric addendum to the Army's "Emergency War Surgery" manual, development of instructional compact discs, augmenting and refining the pediatric portion of the Joint Forces Combat Trauma Management course, formation of a pediatric augmentation team to the CSH, and a comprehensive hyperlinked Web-based pediatric critical care and trauma educational platform.

A 2-week-old infant developed respiratory failure due to a mediastinal Kaposiform hemangioendothelioma that was complicated by thrombocytopenia and consumptive coagulopathy. Initial surgery was unsuccessful at removing the tumorous infiltration of mediastinal structures. Multiple transfusions with fresh frozen plasma, platelets, and red blood cells were needed for the consumptive coagulopathy, and ventilatory support was required for 5 months. Therapy for the tumor included methylprednisolone, aminocaproic acid, and vincristine, but a sustained response was achieved only after the initiation of alpha interferon. The patient was monitored closely and did not develop neurologic toxicity. This case demonstrates that interferon can be used to treat infants with Kaposiform hemangioendothelioma in life-threatening situations that do not respond to other forms of treatment.

This single blinded observational study compared the bispectral index (BIS) monitor with a validated pediatric sedation scale, the University of Michigan Sedation Scale (UMSS), to evaluate whether the BIS score can be used to judge the depth of sedation in pediatric outpatients. Thirty-eight children, with a mean age of 5.8 years, undergoing routine sedation for both noninvasive and gastrointestinal procedures, had simultaneous BIS and UMSS scores recorded. Sedation categories were defined as light, moderate, and deep for both UMSS and BIS. There was a moderate correlation between BIS and the UMSS, Spearman's r < -0.499. The correlation was poor for children receiving chloral hydrate, r < -0.213. The BIS score was not predictive of any specific UMSS score. The UMSS and BIS categories of sedation matched only 36% of the time. BIS underestimated the clinical level of sedation.

Background: Family presence during cardiopulmonary resuscitation is becoming a more common and accepted practice., Objectives: We wanted to determine the views held by pediatricians on family presence during pediatric cardiopulmonary resuscitation. We hypothesized that physicians who had more experience with critical illness and death would be more willing to allow parental presence. Additionally, we hypothesized that recently trained physicians, who may have had more educational exposure to family presence, would be more open to the practice than physicians who had been practicing longer., Methods: A 10-question survey was distributed to attendees of the American Academy of Pediatrics annual Uniformed Services Pediatric Seminar meeting, as well as pediatric staff and residents at both Tripler Army Medical Center and Kapiolani Women's and Children's Medical Center, Honolulu, Hawaii. Responses were compared using chi analysis, with significance indicated by a value < 0.05., Results: Of the 245 respondents, 65% indicated that they would not allow parental presence. There was no significant difference in the responses based on gender, military affiliation, or years of experience. Those involved in inpatient-oriented specialties and residents were significantly more likely to allow parental presence during resuscitation than respondents involved in outpatient-oriented specialties (57.5%, 50%, and 26.4%, respectively; < 0.01). Although only one third of respondents had been involved in a resuscitation during which parents were allowed to be present, the majority (63%) indicated that they would be willing to repeat the practice., Conclusions: Although in the minority, one third of the pediatricians surveyed are comfortable allowing parental presence during cardiopulmonary resuscitation. We conclude that pediatricians who have more frequent contact with seriously ill children are more likely to accept parental presence. Additionally, the exposure to parental presence during resuscitation efforts increases the likelihood of allowing parental presence in future resuscitation efforts.

Objective: To develop a pathway to provide safe, effective, and efficient sedation for pediatric diagnostic imaging studies using non-radiology personnel., Materials and Methods: A multidisciplinary team considered manpower and training requirements and national sedation standards before designing a sedation pathway, which included scheduling, pre-sedation history and physical, medication protocols, and monitoring. Oral and IV medication protocols were developed based on patient age and weight. Sedation delays were defined as >15 min (IV) or >30 min (PO) from start of sedation to start of imaging. A sedation failure resulted in an incomplete diagnostic imaging study. Failure rates of 124 sedations before and 388 sedations after the pathway were compared., Results: The sedation failure rate for 7 months prior to pathway initiation was 15% (19/124). In the first 25 months after pathway initiation, failures were significantly reduced to 1.5% (6/388) ( P<0.0001). Three (50%) of the six failures after pathway initiation were long examinations (>55 min). Deviation from the recommended medication protocol accounted for most of the 115 delays. Only minor adverse events were seen (12/388, 3.1%)., Conclusion: Implementing a pediatric sedation pathway significantly decreases the sedation failure rate. Pediatric residents and nurses can safely, effectively and efficiently sedate pediatric patients for routine diagnostic imaging procedures without the need for a radiology department sedation team in a department with a small-to-moderate volume of pediatric patients.

Objective: We hypothesized that pentoxifylline, administered after phorbol myristate acetate (PMA), would diminish the severity of lung injury., Setting: Animal research laboratory., Design: Comparative study., Subjects: Mongrel dogs (n = 33)., Interventions: Baseline measurements were obtained from the isolated blood-perfused dog lung lobes after 1 h of stable perfusion and ventilation. Four different measures of lung compliance were obtained along with WBC and neutrophil counts. Pulmonary vascular resistance (PVR) and capillary filtration coefficient (Kf) were calculated, and the ratio of a normalized maximal enzymatic conversion rate to the Michaelis-Menten constant (Amax/Km) was used to assess perfused capillary surface area. The control lobes (n = 8) were ventilated and perfused for an additional 40 min while the injured lobes (n = 17) received PMA (0.1 microg/mL of perfusate). The pentoxifylline-protected lobes (n = 8) were treated with pentoxifylline (1 mg/mL of perfusate) 10 min after injury with PMA. All measurements were then repeated., Measurement and Main Results: The three groups did not differ significantly at baseline. The control lobes remained relatively stable over time. The injured lobes demonstrated marked deterioration in compliance: 8.79 +/- 0.7 to 5.97 +/- 0.59 mL/cm H(2)O (p < 0.05) vs 10.1 +/- 1.0 to 8.07 +/- 0.72 mL/cm H(2)O and 9.6 +/- 1.1 to 9.9 +/- 0.85 mL/cm H(2)O in the control and protected lobes, respectively. Both groups receiving PMA had similar drops in WBC and neutrophil counts, but the pentoxifylline-protected lobes had preservation of all four compliance measures. PVR increased from 37.8 +/- 1.8 to 118.6 +/- 12.7 cm H(2)O/L/min (p < 0.05) in the injured lobes vs 35.4 +/- 0.5 to 36.3 +/- 2.8 cm H(2)O/L/min and 40.4 +/- 0.04 to 46.7 +/- 2.8 cm H(2)O/L/min (p < 0.05) in the control and protected lobes, respectively. Kf increased < 25% in the protected group but more than tripled in the injured group. Amax/Km dropped from 559 +/- 36 to 441 +/- 33 mL/min (p < 0.05) in the injured lobes vs 507 +/- 14 to 490 +/- 17 mL/min and 609 +/- 34 to 616 +/- 37 mL/min in the control and pentoxifylline-protected lobes, respectively., Conclusions: The use of pentoxifylline as a rescue agent prevented the PMA-induced deterioration of lung compliance, vascular integrity, and endothelial metabolic function in this acute lung injury model, despite significant pulmonary neutrophil sequestration.

The aim of this study was to determine the relationship of pulmonary vascular resistance (PVR) hysteresis and lung volume, with special attention to the effects of ventilation around closing volume (CV). Isolated, blood-perfused canine left lower lung lobes (LLL) were incrementally inflated and deflated. Airway and pulmonary artery pressures (PAP) were recorded after each stepwise volume change. Constant blood flow was provided (600 ml/min) and the pulmonary vein pressure (PVP) was held constant at 5 cm H2O. PAP changes, therefore, were a direct index of PVR changes. Group 1 lobes underwent a full inflation from complete collapse to total lobe capacity (TLC) followed by a full deflation. Group 2 lobes underwent two deflation/inflation cycles, after an initial full inflation. These cycles, both beginning at TLC, had deflation end above and below CV, respectively. Significant PVR hysteresis was noted when the first inflation and deflation were compared. The maximum difference in PAP on deflation was 3.3 cm H2O or 11%. The mean decrease was 2.7 cm H2O for 18 lobes (p < 0.0001). The PAPs on all subsequent inflations or deflations that began above CV remained 9% lower than the initial inflation (n = 9, p < 0.0001), but were not different from each other. However, the final inflation which began from below CV resulted in a 30% return of PVR hysteresis (mean increase in PAP of 0.8 cm H2O, n = 7, p < 0.004). We conclude that there is hysteresis in the PVR response during ventilation, with decreased PVR during deflation relative to the initial inflation, that this hysteresis is absent when lung volume is maintained greater than CV, and that hysteresis returns when inflation occurs after deflation below CV.