Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.

Introduction: We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.

Methods: We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.

Results: We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts.

Improved emergency myelopoiesis and survival in neonatal sepsis by caspase-1/11 ablation.

Over one million newborns die annually from sepsis with the highest mortality in premature and low-birthweight infants. The inflammasome plays a central role in the regulation of innate immunity and inflammation, and is presumed to be involved in protective immunity, in large part through the caspase-1-dependent activation of interleukin-1β (IL-1β) and IL-18. Studies in endotoxic shock, however, suggest that endogenous caspase-1 activity and the inflammasome contribute to mortality primarily by promoting excessive systemic inflammatory responses.

Structural characterization of new defective molecules in poly(amidoamide) dendrimers by combining mass spectrometry and nuclear magnetic resonance.

A new side-reaction occurring during divergent synthesis of PAMAM dendrimers (generations G0-G2) was revealed by mass spectrometric detection of defective molecules with a net gain of a single carbon atom as compared to expected compounds. Combining MS/MS experiments performed on different electrosprayed precursor ions (protonated molecules and lithiated adducts) with NMR analyses allowed the origin of these by-products to be elucidated. Modification of one ethylenediamine end-group of perfect dendrimers into a cyclic imidazolidine moiety was induced by formaldehyde present at trace level in the methanol solvent used as the synthesis medium.

Brief Intervention for Truant Youth Sexual Risk Behavior and Marijuana Use.

Substance use and sexual risk behaviors are common among adolescents. Although attention has focused primarily on alcohol use, less is known about the relationship between marijuana use and sexual risk behavior among high-risk youth. Since truant youth often experience problems in school, troubled family situations, and other psychosocial problems, they represent an important group of high-risk youth to study.

Impact of Brief Intervention Services on Drug Using Truant Youth Arrest Charges over Time.

School truancy is a serious concern in the U.S., with far-reaching negative consequences.

Brief Intervention Impact on Truant Youth Attitudes to School and School Behavior Problems: A Longitudinal Study.

Truancy continues to be a major problem, affecting most school districts in the U.S. Truancy is related to school dropout, with associated adverse consequences, including unemployment and delinquency.

Brief Intervention for Truant Youth Sexual Risk Behavior and Alcohol Use: A Parallel Process Growth Model Analysis.

Truant youths represent a challenging, yet very promising group of at-risk youth to study. In addition to problems in school, they frequently experience troubled family situations, emotional/ psychological problems, involvement in substance use, and delinquency. Given the problems often experienced by truant youth, it is likely they are engaging in alcohol use and sexual risk behavior at a higher rate, than the general youth population.

Antibiotics associated with increased risk of new-onset Crohn's disease but not ulcerative colitis: a meta-analysis.

Objectives: The objective of this study was to perform a meta-analysis investigating antibiotic exposure as a risk factor for developing inflammatory bowel disease (IBD).

Methods: A literature search using Medline, Embase, and Cochrane databases was performed to identify studies providing data on the association between antibiotic use and newly diagnosed IBD. Included studies reported Crohn's disease (CD), ulcerative colitis (UC), or a composite of both (IBD) as the primary outcome and evaluated antibiotic exposure before being diagnosed with IBD.

Protective immunity and defects in the neonatal and elderly immune response to sepsis.

Populations encompassing extremes of age, including neonates and elderly, have greater mortality from sepsis. We propose that the increased mortality observed in the neonatal and elderly populations after sepsis is due to fundamental differences in host-protective immunity and is manifested at the level of the leukocyte transcriptome. Neonatal (5-7 d), young adult (6-12 wk), or elderly (20-24 mo) mice underwent a cecal slurry model of intra-abdominal sepsis.

A better understanding of why murine models of trauma do not recapitulate the human syndrome.

Objective: Genomic analyses from blood leukocytes have concluded that mouse injury poorly reflects human trauma at the leukocyte transcriptome. Concerns have focused on the modest severity of murine injury models, differences in murine compared with human age, dissimilar circulating leukocyte populations between species, and whether similar signaling pathways are involved. We sought to examine whether the transcriptomic response to severe trauma in mice could be explained by these extrinsic factors, by utilizing an increasing severity of murine trauma and shock in young and aged mice over time, and by examining the response in isolated neutrophil populations.

Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma.

Background: We recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level.

Methods: We performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma.

Aged mice are unable to mount an effective myeloid response to sepsis.

The elderly have increased morbidity and mortality following sepsis; however, the cause(s) remains unclear. We hypothesized that these poor outcomes are due in part to defects in innate immunity, rather than to an exaggerated early inflammatory response. Young (6-12 wk) or aged (20-24 mo) mice underwent polymicrobial sepsis, and subsequently, the aged mice had increased mortality and defective peritoneal bacterial clearance compared with young mice.

Point-of-Care Ultrasound and the Rapid Response System.

Over the years, the use of ultrasound has moved solely from the domain of the radiologist to that of the intensivist and emergentologist for use in acute care settings. By virtue of its ease of use and rapid learning curve to proficiency, we are now seeing an increased desire by internists to learn the modality and apply it at the patient's bedside. The rapid response system represents a rational starting point for the introduction of point-of-care ultrasound to the inpatient ward setting.

The Mental Health, Substance Use, and Delinquency among Truant Youths in a Brief Intervention Project: A Longitudinal Study.

The relationship between substance use, mental health disorders, and delinquency among youth is well documented. What has received far less attention from researchers is the relationship between these issues among truant youth, in spite of studies that document truants are a population at-risk for negative outcomes. The present study bridges this gap by (1) examining psychosocial functioning and delinquency among truants, and (2) assessing the efficacy of a Brief Intervention (BI) in reducing delinquent behavior over time.

Emotional/psychological and related problems among truant youths: An exploratory latent class analysis.

Latent class analysis was conducted on the psychosocial problems experienced by truant youths. Data were obtained from baseline interviews completed on 131 youths and their parents/guardians involved in a NIDA-funded, Brief Intervention Project. Results identified two classes of youths: Class 1(n=94): youths with low levels of delinquency, mental health and substance abuse issues, Class 2(n=37): youths with high levels of these problems.

Arginine clustering on calix[4]arene macrocycles for improved cell penetration and DNA delivery.

Cell-penetrating peptides are widely used as molecular transporters for the internalization inside cells of various cargo, including proteins and nucleic acids. A special role is played by arginine-rich peptides and oligoarginines covalently linked or simply mixed with the cargo. Here we report cell-penetrating agents in which arginine units are clustered on a macrocyclic scaffold.

Identification and description of a novel murine model for polytrauma and shock.

Objective: To develop a novel polytrauma model that better recapitulates the immunologic response of the severely injured patient by combining long-bone fracture, muscle tissue damage, and cecectomy with hemorrhagic shock, resulting in an equivalent Injury Severity Score of greater than 15. We compared this new polytrauma/shock model to historically used murine trauma-hemorrhage models.

Design: Pre-clinical controlled in vivo laboratory study.

Development of a genomic metric that can be rapidly used to predict clinical outcome in severely injured trauma patients.

Objective: Many patients have complicated recoveries following severe trauma due to the development of organ injury. Physiological and anatomical prognosticators have had limited success in predicting clinical trajectories. We report on the development and retrospective validation of a simple genomic composite score that can be rapidly used to predict clinical outcomes.

Soybean oil: a potentially new intravascular perfusate.

Background: Given that micelles of lipids are colloids, the hypothesis was generated that the rapid administration of large volumes of soybean oil micelles would be an effective perfusion fluid. We also hypothesized that oxygen loading would be enhanced due to the greater solubility of oxygen in lipids compared to water.

Methods: A 100% lethal mouse model of blood loss was used to compare the ability of soybean oil micelles to that of Ringer's lactate, blood and other fluids, with respect to raising and maintaining the blood pressure for one hour.

Psychosocial Problems Among Truant Youth: A Multi-Group, Exploratory Structural Equation Modeling Analysis.

Truant youth represent a critical group needing problem-oriented research and involvement in effective services. The limited number of studies on the psychosocial functioning of truant youths have focused on one or a few problem areas, rather than examining co-morbid problem behaviors. The present study addresses the need to examine the interrelationships of multiple domains of psychosocial functioning, including substance involvement, mental health, and delinquency, among truant youth.

The acute immunological response to blood transfusion is influenced by polymicrobial sepsis.

Blood transfusion is a well-established risk factor for adverse outcomes during sepsis. The specific mechanisms responsible for this effect remain elusive, and few studies have investigated this phenomenon in a model that reflects not only the clinical circumstances in which blood is transfused, but also how packed red blood cells (PRBCs) are created and stored. Using a cecal ligation and puncture model of polymicrobial sepsis as well as creating murine allogeneic and stored PRBCs in a manner that replicates the clinical process, we have demonstrated that transfusion of PRBCs induces numerous effects on leukocyte subpopulations.

Prevalence of migraine in patients with celiac disease and inflammatory bowel disease.

Objective: To assess the prevalence of headache in clinic and support group patients with celiac disease and inflammatory bowel disease (IBD) compared with a sample of healthy controls.

Background: European studies have demonstrated increased prevalence of headache of patients with celiac disease compared with controls.

Methods: Subjects took a self-administered survey containing clinical, demographic, and dietary data, as well as questions about headache type and frequency.

ATP cleavage by cone tetraguanidinocalix[4]arene.

The upper rim cone tetraguanidinocalix[4]arene 1 is a highly effective catalyst of ATP hydrolysis. The catalytically most active species is the triprotonated form of the catalyst. The three protonated guanidinium groups provide the electrostatic driving force for substrate binding and activation, while the neutral guanidine most likely acts as a nucleophilic catalyst.

Protein-losing enteropathy in ulcerative colitis.

Protein-losing enteropathy (PLE) is a debilitating potential complication of ulcerative colitis (UC). We report a case of PLE in a 26-year-old male patient with UC. The patient lost 50 pounds in the setting of a UC flare and was found to have an albumin level of 1.