A 'PEaRL' of Support and Cooperative Learning: A Pilot Study Shifting the Sands of the Dreaded Morbidity and Mortality Conference.

BACKGROUND: When unanticipated and/or poor patient outcomes occur, clinicians frequently experience guilt, anger, psychological distress, and fear, which can be intensified by traditional morbidity and mortality conferences. METHODS: The Pediatric Event Review and Learning (PEaRL) curriculum was developed to discuss unanticipated and/or poor patient outcomes and foster support while highlighting foundational safety concepts. Pre- and post-implementation evaluations of quarterly cased-based sessions were completed. RESULTS: All respondents endorsed that unanticipated and/or poor patient outcomes affected their mood, well-being, and functioning. Post-implementation of the PEaRL curriculum, significantly more respondents endorsed existence of a safe environment and structured format to discuss these outcomes, as well as feeling more supported. DISCUSSION: The PEaRL curriculum provides a valuable opportunity for trainees and experienced clinicians alike to explore and discuss unanticipated and/or poor patient outcomes while addressing key patient safety principles.

Perfusion Methods and Modifications to the Cardiopulmonary Bypass Circuit for Midline Unifocalization Procedures.

Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs) is a rare form of congenital heart disease. The midline unifocalization procedure has been developed for the treatment of PA/VSD/MAPCAs. These are complex and very lengthy procedures that require an entirely different method of perfusion. The purpose of this study was to review our perfusion modifications to support these unifocalization procedures. Sixty-four unifocalization procedures have been performed at our institution during the past 3 years. The median age was 4.1 months (range 1 month-3.5 years) and the median weight at surgery was 4.5 kg (range 3.5-19 kg). The median duration of cardiopulmonary bypass was 352 minutes (range 128-629 minutes), and the median duration of cross-clamp was 24 minutes (range 14-72 minutes). The conduct of surgery included cooling to a rectal perfusion temperature of 25° and a flow rate of 100 mL/kg/min. A pH-stat strategy and del Nido cardioplegia were used. Modifications to the cardiopulmonary bypass circuit include upsizing the oxygenator, reservoir, cannulae, vent catheter, and tubing. All circuits were modified to include the capability of performing an intraoperative flow study. This study is used to determine whether the VSD can be closed during surgery. A collateral flow study circuit is also set up for first-time operations to measure the residual collateral flow after all of the MAPCAs have been harvested. Patients who require midline unifocalization will invariably require very lengthy periods of support on cardiopulmonary bypass. We have adapted our perfusion circuitry to prepare for the demands on the bypass circuit to meet the requirements of this patient population. Our institution has developed a systematic approach for the conduct of perfusion to best serve our patients presenting with PA/VSD/MAPCAs.

A case series involving young children presenting with accidental ingestion of amphetamine based stimulants.

•Attention Deficity Hyperactivity Disorder (ADHD) affects adults and children.•Stimulant prescribing for ADHD is increasing.•Overdose of amphetamine based stimulants results in a sympathomimetic toxidrome.•Lisdexamfetamine dimesylate is the first prodrug stimulant developed to treat ADHD.

Herpes Simplex Proctitis Mimicking Inflammatory Bowel Disease in a Teenaged Male.

We report the case of a 17-year-old male who was initially assessed for pain with defecation, bloody rectal discharge, and diarrhea, consistent with proctitis. Though proctitis is most commonly due to inflammatory bowel disease (IBD), infectious etiologies must also be considered, including sexually transmitted causes of infectious proctitis. In discussion of his sexual history, he identified as homosexual and acknowledged engaging in receptive anal intercourse. Rectal biopsies obtained via colonoscopy were culture-positive for herpes simplex virus (HSV), leading to a diagnosis of HSV proctitis and treatment with an appropriate antiviral medication. HSV proctitis is more common in individuals with high-risk sexual practices, including men who have sex with men. While this may be an uncommon diagnosis for pediatricians to make in practice, a high clinical index of suspicion for sexually transmitted infectious proctitis in those with risk factors must be maintained in order to facilitate appropriate testing, treatment, and counseling of affected individuals.

Impact of Growth Restriction and Other Prenatal Risk Factors on Cord Blood Iron Status in Prematurity.

OBJECTIVE: To determine whether prenatal risk factors (RFs) that predict cord blood iron status in term newborns also predict iron status of premature newborns. STUDY DESIGN: Cord blood iron indices from 80 preterm newborns were compared with historical and demographic RFs for developing iron deficiency if born at term. RESULT: The presence of multiple RFs did not incrementally interfere with cord iron status in preterm newborns. Poorer iron status accompanied being small for gestational age in prematurity, but other RFs, including diabetes, had relatively little impact. CONCLUSION: Growth-restricted preterm newborns are at risk for poor iron endowment, likely due to uteroplacental insufficiency. Other RFs were less impactful on iron status of premature newborns than in term newborns, likely reflecting that disruptive effects of RFs are more impactful in the third trimester. Understanding RFs for poor iron endowment is important for clinical recognition and treatment of premature babies.

Shutoff of BZLF1 gene expression is necessary for immortalization of primary B cells by Epstein-Barr virus.

The BZLF1 gene controls the switch between latent and lytic infection by Epstein-Barr virus (EBV). We previously reported that both the ZV and ZIIR elements within the BZLF1 promoter, Zp, are potent transcription silencers within the context of an intact EBV genome. We report here identification of another sequence element, ZV', which synergized with ZV in repressing Zp via binding ZEB1 or ZEB2. We then determined the phenotype of a variant of EBV strain B95.8 in which the ZV, ZV', and ZIIR elements were concurrently mutated. HEK293 cell lines infected with this triple mutant (tmt) virus spontaneously synthesized 6- to 10-fold more viral BZLF1, BRLF1, BMRF1, and BLLF1 RNAs, 3- to 6-fold more viral Zta, Rta, and EAD proteins, 3- to 5-fold more viral DNA, and 7- to 9-fold more infectious virus than did 293 cell lines latently infected with either the ZV ZV' double mutant (dmt) or ZIIR mutant (mt) virus. While ZV ZV' ZIIR tmt EBV efficiently infected human primary blood B cells in vitro, it was highly defective in immortalizing them. Instead of the nearly complete silencing of BZLF1 gene expression that occurs within 4 days after primary infection with wild-type EBV, the ZV ZV' ZIIR tmt-infected cells continued to synthesize BZLF1 RNA, with 90% of them dying within 9 days postinfection. BL41 cells infected with this "superlytic" virus also exhibited increased synthesis of BZLF1 and BMRF1 RNAs. Thus, we conclude that the ZV, ZV', and ZIIR silencing elements act synergistically to repress transcription from Zp, thereby tightly controlling BZLF1 gene expression, which is crucial for establishing and maintaining EBV latency.

The ZIIR element of the Epstein-Barr virus BZLF1 promoter plays a central role in establishment and maintenance of viral latency.

The Epstein-Barr virus (EBV) BZLF1 gene encodes the immediate-early (IE) protein Zta, which plays a central role in regulating the switch between viral latency and lytic replication. A silencing element, ZIIR, is located between the ZID and ZII positive regulatory elements in the BZLF1 promoter Zp. We report here the phenotypes of variants of EBV strain B95.8 containing base substitution mutations in this ZIIR element. HEK293 cells infected with ZIIR mutant (ZIIRmt) virus produced at least 20-fold more viral IE Zta and Rta and early (E) EAD protein than did cells infected with the parental wild-type (WT) virus, leading to viral DNA replication and production of infectious virus. However, ZIIR mutant virus was 1/10 as efficient as WT virus in establishing proliferating B-cell clones following infection of human primary blood B cells. The ZIIRmt-infected lymphoblastoid cell lines (LCLs) that did grow out exhibited a phenotype similar to the one observed in 293 cells, including marked overproduction of IE and E gene products relative to WT-infected LCLs and lytic replication of the viral genome. Incubation of the ZIIRmt-infected LCLs with the chemical inducer 12-O-tetradecanoyl-phorbol-13-acetate (TPA) led to much greater activation of Zp than did the same treatment of WT- or ZVmt-infected LCLs. Furthermore, a protein kinase C (PKC) inhibitor, bis-indolylmaleimide, eliminated this activation by TPA. Thus, we conclude that ZIIR is a potent silencing element of Zp; it plays a key role in establishment and maintenance of EBV latency by inhibiting activation of Zp through the PKC signal transduction pathway.

High star formation rates as the origin of turbulence in early and modern disk galaxies.

Observations of star formation and kinematics in early galaxies at high spatial and spectral resolution have shown that two-thirds are massive rotating disk galaxies, with the remainder being less massive non-rotating objects. The line-of-sight-averaged velocity dispersions are typically five times higher than in today's disk galaxies. This suggests that gravitationally unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos. These accreting flows, however, have not been observed, and cosmic accretion cannot power the observed level of turbulence. Here we report observations of a sample of rare, high-velocity-dispersion disk galaxies in the nearby Universe where cold accretion is unlikely to drive their high star formation rates. We find that their velocity dispersions are correlated with their star formation rates, but not their masses or gas fractions, which suggests that star formation is the energetic driver of galaxy disk turbulence at all cosmic epochs.

Frequency of localization of the painful tooth by patients presenting for an endodontic emergency.

INTRODUCTION: Endodontic pain patients sometimes have difficulty in accurately identifying the painful tooth. We determined the frequency in which patients presenting with endodontic pain can correctly localize the painful tooth and the effect of periradicular symptoms. METHODS: The frequency of localization of the painful tooth in 79 endodontic emergency patients was assessed by using patient and dentist assessment of presenting pain along with the verbal numeric rating scale (VNRS). RESULTS: The results show that patients presenting with odontogenic pain can localize the painful tooth 73.3% of the time. Patients experiencing periradicular pain can localize the painful tooth (89%) significantly more often than patients with pain without periradicular symptoms (30%, p < 0.0001). CONCLUSIONS: The presence of periradicular pain increases the accuracy of pain localization. The VNRS is highly correlated with other pain scales and is an acceptable initial pain-assessment tool for endodontic emergency patients.

A high abundance of massive galaxies 3-6 billion years after the Big Bang.

Hierarchical galaxy formation is the model whereby massive galaxies form from an assembly of smaller units. The most massive objects therefore form last. The model succeeds in describing the clustering of galaxies, but the evolutionary history of massive galaxies, as revealed by their visible stars and gas, is not accurately predicted. Near-infrared observations (which allow us to measure the stellar masses of high-redshift galaxies) and deep multi-colour images indicate that a large fraction of the stars in massive galaxies form in the first 5 Gyr (refs 4-7), but uncertainties remain owing to the lack of spectra to confirm the redshifts (which are estimated from the colours) and the role of obscuration by dust. Here we report the results of a spectroscopic redshift survey that probes the most massive and quiescent galaxies back to an era only 3 Gyr after the Big Bang. We find that at least two-thirds of massive galaxies have appeared since this era, but also that a significant fraction of them are already in place in the early Universe.