Culture-Negative Fibrinous Peritonitis in a Postpartum Female.

Peritonitis is inflammation of the peritoneum that can arise from a number of complications affecting the lining of the abdominal wall and organs. Acute abdomen and peritonitis is a rare complication in a previously healthy woman following a seemingly uncomplicated normal full-term vaginal delivery. We report such a case in a 20-year-old gravida 2 para 2 (G2P2) woman of Guatemalan descent, who presented nine days postpartum following an uncomplicated delivery, to the emergency room with acute abdomen and associated systemic inflammatory reaction. Interventional radiology paracentesis was performed, yielding a milky, purulent peritoneal fluid with no visible organisms and negative cultures. Antibiotics and paracentesis were insufficient in managing her condition, which continued to worsen over the course of several days. Given her continued deterioration despite clinical intervention, she underwent an exploratory laparotomy and peritoneal lavage along with continued broad-spectrum antibiotics. Cultures continued to be negative but operative findings included diffuse fibrinous peritonitis with no obvious abscess or perforated abdominal viscus. Following surgical laparotomy, she recovered fully without any complications. We review the available literature regarding peritonitis, discuss its management, and speculate as to its cause in this case.

A Rare Case of Varicella-Zoster Virus Encephalitis Presenting With Lost Ability to Play the Piano in an Immunocompetent Pediatric Patient.

Varicella-zoster virus (VZV) is a member of the alpha-herpesvirus family, which can occasionally cause severe neurological complications such as encephalitis. In this case report, we discuss a rare finding of VZV encephalitis in which an immunocompetent pediatric patient, vaccinated against varicella, presented with altered mental status and no vesicular rash. A 15-year-old male presented to the Emergency Department with progressively worsening altered mental status over the past three days. The patient's mother stated that he was exhibiting frequent memory lapses as well as the sudden loss of the ability to play the piano. After admission to the pediatric general floor, lumbar puncture was performed and cerebrospinal fluid analysis returned positive for VZV, confirmed by polymerase chain reaction. The patient was then started on intravenous (IV) acyclovir at a dose of 650 mg every 8 hours to treat VZV-induced encephalitis. While the patient continued to have intermittent episodes of confusion and headaches, his overall condition improved, and by day 4, he was able to resume playing the piano and ukulele. The patient was discharged on day 8 with no home medications, and a follow-up with this primary care physician was scheduled. This patient is one of only four recorded cases of VZV encephalitis in immunocompetent children. It is extremely rare to encounter pediatric patients with this diagnosis and, as such, can elude physicians when developing differential diagnoses. If VZV is suspected, a lumbar puncture should be performed promptly, and, if confirmed, IV acyclovir should be started. Furthermore, this case highlights the need for future research with regard to VZV and potential predisposing factors in immunocompetent patients.

Metabolic and quality of life effects of growth hormone replacement in patients with TBI and AGHD: A pilot study.

OBJECTIVE: Traumatic brain injury (TBI), a common cause of adult growth hormone deficiency (AGHD), affects 20% of Veterans returning from Iraq and Afghanistan (OEF/OIF/OND). Growth hormone replacement therapy (GHRT) improves quality of life (QoL) in AGHD but remains unexplored in this population. This pilot, observational study investigates the feasibility and efficacy of GHRT in AGHD following TBI. DESIGN: In this 6-month study of combat Veterans with AGHD and TBI starting GHRT (N = 7), feasibility (completion rate and rhGH adherence) and efficacy (improvements in self-reported QoL) of GHRT were measured (primary outcomes). Secondary outcomes included body composition, physical and cognitive function, psychological and somatic symptoms, physical activity, IGF-1 levels and safety parameters. It was hypothesized that participants would adhere to GHRT and that QoL would significantly improve after six months. RESULTS: Five subjects (71%) completed all study visits. All patients administered daily rhGH injections, 6 (86%) of whom consistently administered the clinically-prescribed dose. While QoL demonstrated numeric improvement, this change did not reach statistical significance (p = 0.17). Significant improvements were observed in total lean mass (p = 0.02), latissimus dorsi strength (p = 0.05), verbal learning (Trial 1, p = 0.02; Trial 5, p = 0.03), attention (p = 0.02), short-term memory (p = 0.04), and post-traumatic stress disorder (PTSD) symptoms (p = 0.03). Body weight (p = 0.02) and total fat mass (p = 0.03) increased significantly. CONCLUSION: GHRT is a feasible and well-tolerated intervention for U.S. Veterans with TBI-related AGHD. It improved key areas impacted by AGHD and symptoms of PTSD. Larger, placebo-controlled studies testing the efficacy and safety of this intervention in this population are warranted.

Hydropneumothorax as a Presentation of Birt-Hogg-Dubé Syndrome.

Birt-Hogg-Dubé syndrome (BHDS) is a rare genetic disorder characterized by cutaneous, pulmonary, and renal manifestations. We present a unique case in which a combination of multiple chronic illnesses, genetic testing, and significant family history led to a diagnosis of BHDS. A 72-year-old male patient presented to their primary care physician with a persistent cough of four months and was admitted to the emergency department after the discovery of a left hydropneumothorax. The patient's medical history was significant for recurrent spontaneous bilateral pneumothoraces diagnosed over 20 years ago, chronic obstructive pulmonary disease (COPD), and many other systemic illnesses. A combination of the patient's significant past medical and family history led to a diagnosis of BHDS. Genetic testing was also done to confirm the diagnosis. Despite benign skin lesions being the most common finding, they are not always present, as seen in our case, which can result in missed diagnosis. Due to the autosomal dominant nature of BHDS, it is vital to make an accurate diagnosis to allow for proper genetic counseling, as the development of renal cancer is the leading cause of mortality.

State of the Evidence for Proximal Junctional Kyphosis Prevention in Adult Spinal Deformity Surgery: A Systematic Review of Current Literature.

OBJECTIVE: Proximal junctional kyphosis (PJK) is a widely recognized complication of adult spinal deformity surgery, and various PJK prevention strategies have been reported in recent years. The goal of the present study was to perform a systematic review of the PJK prevention strategies, report on their effectiveness, and delineate future directions for investigation regarding PJK prevention. METHODS: A systematic review was conducted using PubMed, Embase, and Scopus to identify studies examining PJK prevention techniques. The titles and abstracts were screened, and those studies progressing to the full text review were screened using prespecified inclusion and exclusion criteria. The studies were organized thematically for analysis. RESULTS: The search identified a total of 382 studies, 23 of which were included. The overall quality of evidence was level III. The reported PJK prevention strategies included optimization of postoperative sagittal alignment by avoiding over- or undercorrection, prophylactic vertebral cement augmentation, the use of a transverse process hook at upper instrumented vertebra, the use of more flexible rod constructs, novel pedicle screw insertion techniques, the use of junctional tethers, and teriparatide therapy, which seemed to reduce the PJK rates. CONCLUSIONS: The reports of PJK prevention strategies were heterogeneous, and high-level evidence regarding any particular technique remains limited. Further development of additional PJK prevention techniques and validation of their efficacy in clinical practice are needed to optimize the outcomes of adult spinal deformity surgery.

The Association Between the Number of Prehospital Providers On-Scene and Out-of-Hospital Cardiac Arrest Outcomes.

Objective: The ideal number of emergency medical services (EMS) providers needed on-scene during an out-of-hospital cardiac arrest (OHCA) resuscitation is unknown. Our objective was to evaluate the association between the number of providers on-scene and OHCA outcomes. Methods: This was a secondary analysis of adults (≥18 years old) with non-traumatic OHCA from a 10-site North American prospective cardiac arrest registry (Resuscitation Outcomes Consortium) including a 2005-2011 cohort and a 2011-2015 cohort. The primary outcome was survival to hospital discharge. We calculated the median number of EMS providers on-scene during the first 10 minutes of the resuscitation and used multivariable logistic regression adjusting for age, sex, witness status, bystander CPR, arrest location, initial rhythm, and dispatch to EMS arrival time. Results: There were 30,613 and 41,946 patients with necessary variables in the 2005-2011 and 2011-2015 cohorts, respectively. Survival to hospital discharge (95% CI) was higher with 9 or more providers on-scene (17.2% [15.8-18.5] and 14.0% [12.6-15.4]) compared to 7-8 (14.1% [13.4-14.8] and 10.5% [9.9-11.1]), 5-6 (10.0% [9.5-10.5] and 8.5% [8.1-8.9]), 3-4 (10.5% [9.3-11.6] and 9.3% [8.5-10.1]), and 1-2 (8.6% [7.2-10.0] and 8.0% [7.1-9.0]) providers for the 2005-2011 and 2011-2015 cohorts, respectively. In multivariable logistic regressions, compared to 5-6 providers, there were no significant differences in survival to hospital discharge for 1-2 or 3-4 providers, while having 7-8 (adjusted odds ratios (aORs) 1.53 [1.39-1.67] and 1.31 [1.20-1.44]) and 9 or more (aORs 1.76 [1.56-1.98] and 1.63 [1.41-1.89]) providers were associated with improved survival in both the 2005-2011 and 2011-2015 cohorts, respectively. Conclusions: The presence of seven or more prehospital providers on-scene was associated with significantly greater adjusted odds of survival to hospital discharge after OHCA compared to fewer on-scene providers.

Association of Advanced Airway Insertion Timing and Outcomes After Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: While often prioritized in the resuscitation of patients with out-of-hospital cardiac arrest, the optimal timing of advanced airway insertion is unknown. We evaluated the association between the timing of advanced airway (laryngeal tube and endotracheal intubation) insertion attempt and survival to hospital discharge in adult out-of-hospital cardiac arrest. METHODS: We performed a secondary analysis of the Pragmatic Airway Resuscitation Trial (PART), a clinical trial comparing the effects of laryngeal tube and endotracheal intubation on outcomes after adult out-of-hospital cardiac arrest. We stratified the cohort by randomized airway strategy (laryngeal tube or endotracheal intubation). Within each subset, we defined a time-dependent propensity score using patients, arrest, and emergency medical services systems characteristics. Using the propensity score, we matched each patient receiving an initial attempt of laryngeal tube or endotracheal intubation with a patient at risk of receiving laryngeal tube or endotracheal intubation attempt within the same minute. RESULTS: Of 2,146 eligible patients, 1,091 (50.8%) and 1,055 (49.2%) were assigned to initial laryngeal tube and endotracheal intubation strategies, respectively. In the propensity score-matched cohort, timing of laryngeal tube insertion attempt was not associated with survival to hospital discharge: 0 to lesser than 5 minutes (risk ratio [RR]=1.35, 95% confidence interval [CI] 0.53 to 3.44); 5 to lesser than10 minutes (RR=1.07, 95% CI 0.66 to 1.73); 10 to lesser than 15 minutes (RR=1.17, 95% CI 0.60 to 2.31); or 15 to lesser than 20 minutes (RR=2.09, 95% CI 0.35 to 12.47) after advanced life support arrival. Timing of endotracheal intubation attempt was also not associated with survival: 0 to lesser than 5 minutes (RR=0.50, 95% CI 0.05 to 4.87); 5 to lesser than10 minutes (RR=1.20, 95% CI 0.51 to 2.81); 10 to lesser than15 minutes (RR=1.03, 95% CI 0.49 to 2.14); 15 to lesser than 20 minutes (RR=0.85, 95% CI 0.30 to 2.42); or more than/equal to 20 minutes (RR=0.71, 95% CI 0.07 to 7.14). CONCLUSION: In the PART, timing of advanced airway insertion attempt was not associated with survival to hospital discharge.

Capturing the Experiences and Challenges of Emerging Adults in College During the COVID-19 Pandemic.

Emerging adulthood (ages 18-30 years) coincides with "aging out" of pediatric care. As a result, combined internal medicine and pediatrics (Med-Peds) providers are tasked with promoting the health and well-being of this population during and post-coronavirus disease 2019 (COVID-19). In order to inform the response efforts, we aimed to capture emerging adults' COVID-19 experiences and challenges during a two-week period of the pandemic in June 2020. We administered items from the California Health Interview Survey and an open-ended qualitative item via Qualtrics to 242 diverse emerging adults enrolled in a large US public university (mean age = 20.10, SD = 1.26). More than 90% of all students reported that they or their families or close friends experienced difficulties coping with the stressors and challenges presented by COVID-19. Almost half experienced financial difficulties and more than three-fourths experienced household disruptions during the pandemic. Qualitative findings underscored that these challenges were compounded by mental health and broader social issues. Recommendations for Med-Peds providers are provided to promote emerging adulthood health during and post-pandemic.

Heart Rate Variability and Its Ability to Detect Worsening Suicidality in Adolescents: A Pilot Trial of Wearable Technology.

OBJECTIVE: Suicide is the 2nd leading cause of death in adolescence, and acute pediatric mental health emergency department (ED) visits have doubled in the past decade. The objective of this study was to evaluate physiologic parameters relationship to suicide severity. METHODS: This was a prospective, observational study from April 2018 thru November 2019 in a tertiary care pediatric emergency department (ED) and inpatient pediatric psychiatric unit enrolling acutely suicidal adolescent patients. Patients wore a wrist device that used photoplethysmography for 7 days during their acute hospitalization to measure heart rate variability (HRV). During that time, Columbia Suicide Severity Scores (CSSRS) were assessed at 3 time points. RESULTS: There was complete device data and follow-up for 51 patients. There was an increase in the high frequency (HF) component of HRV in patients that had a 25% or greater decrease in their CSSRS (mean difference 11.89 ms/ Hz ; p-value 0.005). Patients with a CSSRS≥15 on day of enrollment had a lower, although not statistically significant, HF component (mean difference -8.34 ms/ Hz; p-value 0.071). CONCLUSION: We found an inverse correlation between parasympathetic activity measured through the HF component and suicidality in an acutely suicidal population of adolescents. Wearable technology may have the ability to improve outpatient monitoring for earlier detection and intervention.

Cluster cross-over randomised trial of paediatric airway management devices in the simulation lab and operating room among paramedic students.

OBJECTIVES: The objective of this study was to compare paediatric emergency airway management strategies in the simulation lab and operating room environments. METHODS: This was a two-part cluster cross-over randomised trial including simulation lab and operating room environments conducted between January 2017 and June 2018 in Portland, Oregon, USA. In simulated infant cardiac arrests, paramedic students placed an endotracheal tube, an i-gel or a laryngeal mask airway in random order. In the operating room, paramedic students placed a laryngeal mask airway or i-gel device in random order in sequential patients. The primary outcome for both portions of the study was time to ventilation. In the operating room portion, we also evaluated leak pressures and average initial tidal volumes. RESULTS: There were 58 paramedic students who participated in the simulation lab and 22 who participated in the operating room study. The mean time to airway placement in the simulation lab was 48.5 s for the i-gel, 68.9 s for the laryngeal mask and 129.5 s for the endotracheal tube. In the operating room, mean time to i-gel placement was 34.3 s with 45.2 s for the laryngeal mask. In multivariable analysis of the simulation study, the laryngeal mask and i-gel were significantly faster than the endotracheal tube, and the i-gel was faster than the laryngeal mask. In the operating room, there was no significant difference in time to placement, leak pressure and average volume of the first five breaths between the i-gel and laryngeal mask. CONCLUSIONS: We found that paramedic students were able to place supraglottic devices rapidly with high success rates in simulation lab and operating room environments. Supraglottic devices, particularly the i-gel, were rated as easy to use. The i-gel may be easiest to use since it lacks an inflable cuff and requires fewer steps to place.

Association of Intra-arrest Transport vs Continued On-Scene Resuscitation With Survival to Hospital Discharge Among Patients With Out-of-Hospital Cardiac Arrest.

Importance: There is wide variability among emergency medical systems (EMS) with respect to transport to hospital during out-of-hospital cardiac arrest (OHCA) resuscitative efforts. The benefit of intra-arrest transport during resuscitation compared with continued on-scene resuscitation is unclear. Objective: To determine whether intra-arrest transport compared with continued on-scene resuscitation is associated with survival to hospital discharge among patients experiencing OHCA. Design, Setting, and Participants: Cohort study of prospectively collected consecutive nontraumatic adult EMS-treated OHCA data from the Resuscitation Outcomes Consortium (ROC) Cardiac Epidemiologic Registry (enrollment, April 2011-June 2015 from 10 North American sites; follow-up until the date of hospital discharge or death [regardless of when either event occurred]). Patients treated with intra-arrest transport (exposed) were matched with patients in refractory arrest (at risk of intra-arrest transport) at that same time (unexposed), using a time-dependent propensity score. Subgroups categorized by initial cardiac rhythm and EMS-witnessed cardiac arrests were analyzed. Exposures: Intra-arrest transport (transport initiated prior to return of spontaneous circulation), compared with continued on-scene resuscitation. Main Outcomes and Measures: The primary outcome was survival to hospital discharge, and the secondary outcome was survival with favorable neurological outcome (modified Rankin scale <3) at hospital discharge. Results: The full cohort included 43 969 patients with a median age of 67 years (interquartile range, 55-80), 37% were women, 86% of cardiac arrests occurred in a private location, 49% were bystander- or EMS-witnessed, 22% had initial shockable rhythms, 97% were treated by out-of-hospital advanced life support, and 26% underwent intra-arrest transport. Survival to hospital discharge was 3.8% for patients who underwent intra-arrest transport and 12.6% for those who received on-scene resuscitation. In the propensity-matched cohort, which included 27 705 patients, survival to hospital discharge occurred in 4.0% of patients who underwent intra-arrest transport vs 8.5% who received on-scene resuscitation (risk difference, 4.6% [95% CI, 4.0%- 5.1%]). Favorable neurological outcome occurred in 2.9% of patients who underwent intra-arrest transport vs 7.1% who received on-scene resuscitation (risk difference, 4.2% [95% CI, 3.5%-4.9%]). Subgroups of initial shockable and nonshockable rhythms as well as EMS-witnessed and unwitnessed cardiac arrests all had a significant association between intra-arrest transport and lower probability of survival to hospital discharge. Conclusions and Relevance: Among patients experiencing out-of-hospital cardiac arrest, intra-arrest transport to hospital compared with continued on-scene resuscitation was associated with lower probability of survival to hospital discharge. Study findings are limited by potential confounding due to observational design.

BCOR Binding to MLL-AF9 Is Essential for Leukemia via Altered EYA1, SIX, and MYC Activity.

MLL is a target of chromosomal translocations in acute leukemias with poor prognosis. The common MLL fusion partner AF9 (MLLT3) can directly bind to AF4, DOT1L, BCOR, and CBX8. To delineate the relevance of BCOR and CBX8 binding to MLL-AF9 for leukemogenesis, here we determine protein structures of AF9 complexes with CBX8 and BCOR, and show that binding of all four partners to AF9 is mutually exclusive. Using the structural analyses, we identify point mutations that selectively disrupt AF9 interactions with BCOR and CBX8. In bone marrow stem/progenitor cells expressing point mutant CBX8 or point mutant MLL-AF9, we show that disruption of direct CBX8/MLL-AF9 binding does not impact in vitro cell proliferation, whereas loss of direct BCOR/MLL-AF9 binding causes partial differentiation and increased proliferation. Strikingly, loss of MLL-AF9/BCOR binding abrogated its leukemogenic potential in a mouse model. The MLL-AF9 mutant deficient for BCOR binding reduces the expression of the EYA1 phosphatase and the protein level of c-Myc. Reduction in BCOR binding to MLL-AF9 alters a MYC-driven gene expression program, as well as altering expression of SIX-regulated genes, likely contributing to the observed reduction in the leukemia-initiating cell population.

Prospective evaluation of airway management in pediatric out-of-hospital cardiac arrest.

OBJECTIVE: The objective of the study was to identify the association between airway management modality and time to the initial dose of epinephrine in pediatric out-of-hospital cardiac arrest (OHCA). METHODS: This was a prospective observational study conducted between April 2016 to April 2018. Ten Emergency Medical Services (EMS) agencies in 2 US metropolitan areas, which were part of the Resuscitation Outcomes Consortium research network, participated in the study. We included all EMS-treated OHCA patients less than 18 years of age during the study period. Study outcomes included time to the initial dose of epinephrine, airway management success rates, rescue techniques, and complications (e.g. pneumothorax, pneumonia). RESULTS: The study included a total of 155 patients, 67% were male, and 55% were less than age one. The airway management modality (TI, SGA, BMV) was not associated with the time to the intial dose of epinephrine in the adjusted analysis. Tracheal intubation (TI) was the most common airway management modality (47.1%) followed by bag-mask-ventilation (BMV) (40.7%), and supraglottic airways (SGA) (12.3%). Success was 65.7% for TI and 94.7% for SGA. We found a significant difference in the proportion of initial survivors diagnosed with pneumonia on chest X-ray between those with BMV (1/19) versus TI (13/21) p < 0.001. CONCLUSIONS: In this prospective study, the airway management modality was not associated with the time to the initial dose of epinephrine. Unexpectedly, pneumonia was significantly more common among children treated with TI compared to BMV. SGAs had high first-attempt success rates, while intubation success rates were low.

Zwitterionic amino acid-based Poly(ester urea)s suppress adhesion formation in a rat intra-abdominal cecal abrasion model.

Hernia repair outcomes have improved with more robust material options for surgeons and optimized surgical techniques. However, ventral hernia repairs remain challenging with an inherent risk of post-surgical adhesions in the peritoneal space which can occur regardless of interventional material or its surgical placement. Herein, amino acid-based poly(ester urea)s (PEUs) with varied amount of an allyl ether side chains were modified post polymerization modification with the zwitterionic sulfnate group (3-((3-((3-mercaptopropanoyl)oxy)propyl) dimethylammonio)propane-1-sulfonate) to promote anti-adhesive properties. These alloc-PEUs were processed using roll-to-roll fabrication methods to afford films that were amenable to surface functionalization via a zwitterion-thiol. Functional group availability on the surface was confirmed via fluorescence microscopy, x-ray photoelectron spectroscopy (XPS), and quartz crystal microbalance (QCM) measurements. Zwitterionic treated PEUs exhibited reduced fibrinogen adsorption in vitro when compared to unfunctionalized control polymer. A rat intrabdominal cecal abrasion adhesion model was used to assess the extent and tenacity of adhesion formation in the presence of the PEUs. The 10% alloc-PEU zwitterion functionalized material was found to reduce the extent and tenacity of adhesions when compared to adhesion controls and the unfunctionalized PEU controls.

Effect of initial airway strategy on time to epinephrine administration in patients with out-of-hospital cardiac arrest.

INTRODUCTION: Epinephrine and advanced airway management are commonly used during treatment of out-of-hospital cardiac arrest (OHCA). Recent studies suggest that early but not late administration of epinephrine is associated with improved survival. The purpose of this study was to evaluate the effect of initial airway strategy on timing to the first epinephrine dose in OHCA. METHODS: This is a secondary analysis of patients enrolled in the Pragmatic Airway Resuscitation Trial who had an advanced airway attempted. We examined differences in time to epinephrine administration by randomly assigned airway strategy, laryngeal tube (LT) or endotracheal tube (ETI); by the duration of airway attempt; and by number of attempts. We used survival methods to account for interval censoring due to unknown administration time. We also examined the association of epinephrine administration timing with survival to hospital discharge. RESULTS: Among 2652 subjects (1299 ETI and 1353 LT), 2579 received epinephrine.There were no significant differences between ETI and LT in median time to initial epinephrine administration (min) (ETI - 9.0 vs. LT - 8.6, p = 0.55). There was no significant association between the duration of airway attempt or number of attempts and time to initial epinephrine administration (p = 0.12 and 0.66, respectively). Early administration of epinephrine (<10 min from EMS arrival) was significantly associated with survival compared to administration ≥10 min (OR 1.36, 95% CI: 1.05, 1.77). CONCLUSIONS: There was no significant association between airway strategy and time to initial epinephrine administration. Earlier administration of epinephrine (< 10 min from EMS arrival) was associated with improved survival.

NKG2D signaling certifies effector CD8 T cells for memory formation.

BACKGROUND: The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). This process of certification assures that the memory compartment is filled with CD8 T cells that have demonstrated their ability to kill their cognate targets through a two-step process that utilizes T cell receptor (TCR) and NKG2D signaling. METHODS: One week after immunization with peptide-pulsed dendritic cells, NKG2D signaling was transiently blocked in vivo with a single injection of neutralizing antibodies. Under such conditions, we determined the importance of NKG2D signaling during the effector phase for memory formation without compromising NKG2D signaling at the memory phase. Both open (polyclonal) and closed (monoclonal) CD8 T cell repertoires were studied. RESULTS: We show that signaling through NKG2D mediated this certification. Temporary blockade of NKG2D signaling during the effector phase resulted in the formation of highly defective memory CD8 T cells characterized by altered expression of the ribosomal protein S6 and epigenetic modifiers, suggesting modifications in the T cell translational machinery and epigenetic programming. Finally, these uncertified memory cells were not protective against a B16 tumor challenge. CONCLUSION: Signaling through NKG2D during the effector phase (certification) favors the development of functional memory CD8 T cells, a previously undescribed role for NKG2D. Temporary blockade of NKG2D signaling during the effector phase results in the formation of highly defective memory CD8 T cells potentially by affecting the expression of the ribosomal protein S6 and epigenetic modifiers, suggesting alterations in T cell translational machinery and epigenetic programming.

Theophylline and Caffeine as Alternatives During an Aminophylline Shortage.

The latest aminophylline shortage has prompted a need for alternative reversal agents for pharmacological stress testing. Cardiac stress testing is common for diagnosis and prognosis in patients with coronary heart disease. Options for pharmacological stress test agents include adenosine, regadenoson, dipyridamole, and dobutamine, whereas aminophylline is the recommended reversal agent. Adenosine and dobutamine can be used as alternatives to regadenoson and dipyridamole to decrease or eliminate the use of aminophylline. Alternatives to aminophylline include theophylline and caffeine. It is important to efficiently identify alternatives during a drug shortage to maintain optimal patient outcomes.

Publisher Correction: miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia.

This corrects the article DOI: 10.1038/ncomms1681.

Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.

Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring.

One Step Forward in the Challenging Arena of MLL-AF4 Leukemia.

MLL-AF4 leukemia is the predominant infant acute leukemia and has a poor prognosis. No current experimental models accurately reflect the human disease. Lin et al., in this issue of Cancer Cell, describe their model that recapitulates multiple key aspects of this aggressive disease, facilitating future mechanistic and preclinical studies.