Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure.

Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant connection exists between inflammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In this study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring. To accomplish this, we developed a model of maternal aAb exposure in rats based on the clinical phenomenon of maternal autoantibody-related ASD (MAR-ASD). Following confirmation of aAb production in rat dams and antigen-specific immunoglobulin G (IgG) transfer to offspring, we assessed offspring behavior and brain structure longitudinally. MAR-ASD rat offspring displayed a reduction in pup ultrasonic vocalizations and a pronounced deficit in social play behavior when allowed to freely interact with a novel partner. Additionally, longitudinal in vivo structural magnetic resonance imaging (sMRI) at postnatal day 30 (PND30) and PND70, conducted in a separate cohort of animals, revealed sex-specific differences in total and regional brain volume. Treatment-specific effects by region appeared to converge on midbrain and cerebellar structures in MAR-ASD offspring. Simultaneously, in vivo 1H magnetic resonance spectroscopy (1H-MRS) data were collected to examine brain metabolite levels in the medial prefrontal cortex. Results showed that MAR-ASD offspring displayed decreased levels of choline-containing compounds and glutathione, accompanied by increased taurine compared to control animals. Overall, we found that rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and neurometabolites; reminiscent of findings observed in clinical ASD.

The Perceived Value of Same-Sex or Same-Race Mentors and Role Models in Academic Medicine.

This study aims to describe the perception of need for same-sex and same-race mentorship and role models at evolving stages of a medical career and to explore whether these differences affect career choices within the field of medicine. A total of 326 medical students, 309 resident physicians, and 200 faculty attending physicians at the University of California, Davis School of Medicine completed an online survey focused on their perceived value of same-sex and same-race mentorship throughout their stages of medical training and practice. The top three factors influencing specialty choice were lifestyle, time commitment, and supportive department. Although most respondents did not believe same-sex or same-race mentors or role models influenced their specialty choice, there were significant differences in the perceived importance and value of gender or race concordance between male versus female and white versus nonwhite populations. (Journal of Surgical Orthopaedic Advances 33(1):041-048, 2024).

Burn Resuscitation Practices in North America: Results of the Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT).

OBJECTIVES: ABRUPT was a prospective, noninterventional, observational study of resuscitation practices at 21 burn centers. The primary goal was to examine burn resuscitation with albumin or crystalloids alone, to design a future prospective randomized trial. SUMMARY BACKGROUND DATA: No modern prospective study has determined whether to use colloids or crystalloids for acute burn resuscitation. METHODS: Patients ≥18 years with burns ≥ 20% total body surface area (TBSA) had hourly documentation of resuscitation parameters for 48 hours. Patients received either crystalloids alone or had albumin supplemented to crystalloid based on center protocols. RESULTS: Of 379 enrollees, two-thirds (253) were resuscitated with albumin and one-third (126) were resuscitated with crystalloid alone. Albumin patients received more total fluid than Crystalloid patients (5.2 ± 2.3 vs 3.7 ± 1.7 mL/kg/% TBSA burn/24 hours), but patients in the Albumin Group were older, had larger burns, higher admission Sequential Organ Failure Assessment (SOFA) scores, and more inhalation injury. Albumin lowered the in-to-out (I/O) ratio and was started ≤12 hours in patients with the highest initial fluid requirements, given >12 hours with intermediate requirements, and avoided in patients who responded to crystalloid alone. CONCLUSIONS: Albumin use is associated with older age, larger and deeper burns, and more severe organ dysfunction at presentation. Albumin supplementation is started when initial crystalloid rates are above expected targets and improves the I/O ratio. The fluid received in the first 24 hours was at or above the Parkland Formula estimate.

HipScreen mobile app for the measurement of hip migration percentage in children with cerebral palsy: Accuracy, reliability, and discriminatory ability.

AIM: To assess the accuracy, reliability, and discriminatory ability of a mobile app for measurement of migration percentage in hip surveillance radiographs of children with cerebral palsy (CP). METHOD: The free mobile app HipScreen (www.hipscreen.org) was utilized by a diverse group of users to measure the migration percentage of 40 hips at two time points after completing an online tutorial and competency test. The mean absolute error (MAE) was calculated against the reference standard obtained on a radiology workstation. Statistical analyses included linear regression, intraclass correlation coefficient (ICC), and area under receiver-operating characteristic curve (AUC). RESULTS: Thirty-seven users completed the study, with 30 having a healthcare professional background, but only 15 with x-ray interpretation expertise. The overall MAE of migration percentage measurement using the HipScreen app was 5.72% (95% confidence interval [CI]: 5.38-6.06), with good reliability between time points (ICC = 0.83). With a migration percentage less than 30% considered as a positive case, the HipScreen app had a sensitivity of 94% (95% CI: 87-97), specificity of 66% (95% CI: 61-77), and an AUC of 0.92 (95% CI: 0.88-0.96). INTERPRETATION: Users from a broad range of backgrounds can utilize the HipScreen app to measure hip surveillance radiographs with clinically acceptable accuracy, reliability, and discriminatory ability. WHAT THIS PAPER ADDS: The HipScreen app can accurately and reliably measure migration percentage. As a screening tool, HipScreen has excellent sensitivity and discriminatory ability. A broad range of HipScreen users achieve clinically acceptable performance.

Long-Term Outcomes of Biceps Rerouting for Flexible Supination Contractures in Children With Brachial Plexus Birth Injuries.

PURPOSE: Forearm supination contractures occur in 7% of children with brachial plexus birth injuries (BPBI). Biceps rerouting is proposed when pronation has deteriorated but is passively correctable to at least 0° (neutral). The purpose of this investigation was to evaluate long-term outcomes of biceps rerouting for this indication, including magnitude and maintenance of correction, complications, and subsequent osteotomy. METHODS: We conducted a retrospective review of all children with BPBI and forearm supination contractures treated with biceps rerouting alone, for the above indications, from 1993 to 2017 with at least 2 years follow-up. Demographic information, BPBI characteristics, surgical details, and ranges of motion were obtained from medical records. Pre- and postoperative active pronation (AP) and supination (AS), elbow flexion contracture, and arc of forearm rotation (Arc) were analyzed using linear mixed-effect models. RESULTS: Twenty-five children (13 females; 13 left forearms; 15 global BPBI) underwent biceps rerouting at age 7 ± 3 years and were followed for 6 ± 3 years. Before surgery, the mean AP and AS were 6° ± 29° and 62° ± 27°, respectively. At the final follow-up, the mean AP, AS, and Arc were 39° ± 36°, 18° ± 34°, and 57° ± 42°, respectively. AP was significantly improved and AS was significantly decreased by 2 years after surgery and at the final follow-up. Neither Arc nor elbow flexion contracture changed significantly. Two of 25 (8%) children underwent subsequent forearm osteotomy. CONCLUSIONS: Biceps rerouting in children with BPBI improves the forearm position when pronation is deteriorating by shifting the arc from supination to pronation without decreasing the arc of motion or worsening elbow flexion contractures. There is a low risk of complications and a limited need for subsequent forearm osteotomy. These results are maintained over time. When performed before passive pronation is reduced beyond neutral, this procedure may prevent severe supination contractures and reduce the need for forearm osteotomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

A Prospective Comparison of Frailty Scores and Fall Prediction in Acutely Injured Older Adults.

BACKGROUND: Elderly (65 and older) fall-related injuries are a significant cause of morbidity and mortality. Although frailty predicts poor outcomes in geriatric trauma, literature comparing frailty scoring systems remains limited. Herein, we evaluated which frailty scoring system best predicts falls over time in the elderly. MATERIALS AND METHODS: Acute surgical patients 65 y and older were enrolled and prospectively observed. Demographics and frailty, assessed using the FRAIL Scale, Trauma Specific Frailty Index (TSFI), and Canadian Frailty Scale (CSHA-CFS), were collected at enrollment and 3 mo intervals following discharge for 1 y. Surveys queried the total number and timing of falls. Changes in frailty over time were assessed by logistic regression and area under the curve (AUC). RESULTS: Fifty-eight patients were enrolled. FRAIL Scale and CSHA-CFS scores did not change over time, but TSFI scores did (P ≤ 0.01). Worsening frailty was observed using TSFI at 6 (P ≤ 0.01) and 12 mo (P ≤ 0.01) relative to baseline. Mortality did not differ based on frailty using any frailty score. Increasing frailty scores and time postdischarge was associated with increased odds of a fall. AUC estimates with 95% CI were 0.72 [0.64, 0.80], 0.81 [0.74, 0.88], and 0.76 [0.68, 0.84] for the FRAIL Scale, TSFI, and CSHA-CFS, respectively. CONCLUSIONS: The risk of falls postdischarge were associated with increased age, time postdischarge, and frailty in our population. No scale appeared to significantly outperform the other by AUC estimation. Further study on the longitudinal effects of frailty is warranted.

Classification of neoplastic and inflammatory brain disease using MRI texture analysis in 119 dogs.

Magnetic resonance imaging is the primary method used to diagnose canine glial cell neoplasia and noninfectious inflammatory meningoencephalitis. Subjective differentiation of these diseases can be difficult due to overlapping imaging characteristics. This study utilizes texture analysis (TA) of intra-axial lesions both as a means to quantitatively differentiate these broad categories of disease and to help identify glial tumor grade/cell type and specific meningoencephalitis subtype in a group of 119 dogs with histologically confirmed diagnoses. Fifty-nine dogs with gliomas and 60 dogs with noninfectious inflammatory meningoencephalitis were retrospectively recruited and randomly split into training (n = 80) and test (n = 39) cohorts. Forty-five of 120 texture metrics differed significantly between cohorts after correcting for multiple testing (false discovery rate < 0.05). After training the random forest algorithm, the classification accuracy for the test set was 85% (sensitivity 89%, specificity 81%). TA was only partially able to differentiate the inflammatory subtypes (granulomatous meningoencephalitis [GME], necrotizing meningoencephalitis [NME], and necrotizing leukoencephalitis [NLE]) (out-of-bag error rate of 35.0%) and was unable to identify metrics that could correctly classify glioma grade or cell type (out-of-bag error rate of 59.6% and 47.5%, respectively). Multiple demographic differences, such as patient age, sex, weight, and breed were identified between disease cohorts and subtypes which may be useful in prioritizing differential diagnoses. TA of MR images with a random forest algorithm provided classification accuracy of inflammatory and neoplastic brain disease approaching the accuracy of previously reported subjective radiologist evaluation.

Opportunistic muscle measurements on staging chest CT for extremity and truncal soft tissue sarcoma are associated with survival.

BACKGROUND AND OBJECTIVES: Computed tomography (CT) measurements of sarcopenia have been proposed as biomarkers associated with outcomes in various cancers and have typically been evaluated at the L3 vertebral level. However, staging imaging for patients with extremity and truncal soft tissue sarcoma (STS) often only includes chest CT imaging which precludes evaluation at L3. Therefore, we sought to evaluate muscle metrics at T12 on standard staging chest CT scans and evaluate for correlation with overall and event-free survival in patients with STS. METHODS: CT chest imaging for 89 patients with intermediate and high-grade STS (53 male, 36 female; 58.5 ± 19.0 years old, follow-up 37.4 ± 27.1 months) was reviewed on PACS at T12 for skeletal muscle density (SMD) and skeletal muscle index (SMI). RESULTS: Overall survival increased with increased SMD on univariate (hazard ratio [HR] = 0.61 [0.43, 0.86]) and age-adjusted analysis (HR = 0.65 [0.42, 0.89]. Event-free survival also increased with increased SMD in univariate analyses (HR = 0.68 [0.49, 0.95]) but did not maintain significance after adjusting for age (HR = 0.68 [0.43, 1.07]). SMI was not a predictor of overall or event-free survival. CONCLUSIONS: Higher SMD measured on routinely obtained staging chest CTs in STS patients is associated with improved survival.

Dose-Area Product-to-Effective Dose Conversion Coefficients for Pelvic Radiography Using a Monte Carlo Program.

OBJECTIVE. The purpose of this study was to determine dose-area product-to-effective dose (DAP/E) conversion coefficients for a five-view pelvic radiograph series. DAP/E conversion coefficients may be used for radiation dose optimization when designing institutional protocols for pelvic trauma evaluation. MATERIALS AND METHODS. We conducted a retrospective record review of 25 patients at a level 1 trauma center who had sustained pelvic fractures and required a five-view pelvic radiograph series during workup. E values given in International Commission on Radiological Protection Publication 103 were simulated with a PC-based Monte Carlo program in conjunction with anthropomorphic phantoms adjusted on the basis of patient height and weight. Inputs included tube voltage (in kV), tube filtration (in millimeters of aluminum), anode angle, x-ray beam collimation, geometric distances, and angle of projection for each radiograph in the series. An incident polychromatic x-ray spectrum was generated and matched to the corresponding DAP values of each radiograph, and regression analysis was performed for the DAP/E conversion coefficients. RESULTS.E was strongly correlated with DAP independent from body mass index, with a mean global DAP/E conversion coefficient of 0.0125 mSv/dGy · cm2 for all radiographs (R2 = 0.95). Mean DAP/E conversion coefficients were 0.0133, 0.0110, 0.0143, 0.0113, and 0.0101 mSv/dGy · cm2 for anteroposterior, inlet, outlet, Judet left, and Judet right views, respectively (all R2 ≥ 0.94). CONCLUSION. DAP/E conversion coefficients are provided for a five-view pelvic radiograph series to allow reliable estimation of E. Measurement of cumulative E may affirm protocol design changes for the management of pelvic trauma.

Effects of imputation on correlation: implications for analysis of mass spectrometry data from multiple biological matrices.

With expanded access to, and decreased costs of, mass spectrometry, investigators are collecting and analyzing multiple biological matrices from the same subject such as serum, plasma, tissue and urine to enhance biomarker discoveries, understanding of disease processes and identification of therapeutic targets. Commonly, each biological matrix is analyzed separately, but multivariate methods such as MANOVAs that combine information from multiple biological matrices are potentially more powerful. However, mass spectrometric data typically contain large amounts of missing values, and imputation is often used to create complete data sets for analysis. The effects of imputation on multiple biological matrix analyses have not been studied. We investigated the effects of seven imputation methods (half minimum substitution, mean substitution, k-nearest neighbors, local least squares regression, Bayesian principal components analysis, singular value decomposition and random forest), on the within-subject correlation of compounds between biological matrices and its consequences on MANOVA results. Through analysis of three real omics data sets and simulation studies, we found the amount of missing data and imputation method to substantially change the between-matrix correlation structure. The magnitude of the correlations was generally reduced in imputed data sets, and this effect increased with the amount of missing data. Significant results from MANOVA testing also were substantially affected. In particular, the number of false positives increased with the level of missing data for all imputation methods. No one imputation method was universally the best, but the simple substitution methods (Half Minimum and Mean) consistently performed poorly.

Effects of Hormone Therapy on List and Story Recall in Post-Menopausal Women.

Background/Study Context: A number of longitudinal randomized controlled trials (LRCT) have used free verbal recall tests to study the effects of post-menopausal estrogen hormone therapy (HT) on episodic memory, but none have explicitly explored contrasts between list and story recall, in spite of cognitive differences between the tasks. For example, list recall provides little support for the use of gist, while story recall emphasizes it, and there is evidence that estrogen produces gist bias. Moreover, we present a literature tabulation that also suggests a task-specific HT effect. METHODS: In an LRCT with up to eight yearly test sessions, post-menopausal women were randomly assigned either to placebo (N = 56) or to an estrogen formulation (N = 44); subgroups received either estrogen alone (hysterectomy; E-alone; N = 16) or with progestin (intact uterus; E + P; N = 28). Participants were tested on the immediate and delayed list and story recall at each session. RESULTS: Linear mixed effects analyses of longitudinal trajectories showed that relative to placebo, the HT group declined significantly faster on immediate list recall and slower on immediate story recall. Separate analyses produced a sharpened version of this pattern for the E-alone subgroup but found no significant effects for the E + P subgroup. No significant effects were found in delayed testing. CONCLUSION: The dissociation we found for immediate list and story recall is similar to the pattern of results in our literature tabulation. Fuzzy-Trace Theory posits parallel verbatim and gist traces plus a meta-cognitive review which becomes more gist-biased with age. Our results suggest that: (1) estrogen increases gist bias, hastening the normal age-related decline of list recall but slowing the decline of story recall relative to placebo; (2) decay of the verbatim trace over time generally causes a shift to gist, thereby accounting for the absence of a delayed recall difference; and (3) progestin weakens the effects of estrogen, thereby accounting for why the dissociation found in E-alone was absent in the E + P subgroup.

The Effects of Storage Age of Blood in Massively Transfused Burn Patients: A Secondary Analysis of the Randomized Transfusion Requirement in Burn Care Evaluation Study.

OBJECTIVES: Major trials examining storage age of blood transfused to critically ill patients administered relatively few blood transfusions. We sought to determine if the storage age of blood affects outcomes when very large amounts of blood are transfused. DESIGN: A secondary analysis of the multicenter randomized Transfusion Requirement in Burn Care Evaluation study which compared restrictive and liberal transfusion strategies. SETTING: Eighteen tertiary-care burn centers. PATIENTS: Transfusion Requirement in Burn Care Evaluation evaluated 345 adults with burns greater than or equal to 20% of the body surface area. We included only the 303 patients that received blood transfusions. INTERVENTIONS: The storage ages of all transfused red cell units were collected during Transfusion Requirement in Burn Care Evaluation. A priori measures of storage age were the the mean storage age of all transfused blood and the proportion of all transfused blood considered very old (stored ≥ 35 d). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the severity of multiple organ dysfunction. Secondary outcomes included time to wound healing, the duration of mechanical ventilation, and in-hospital mortality. There were 6,786 red cell transfusions with a mean (± SD) storage age of 25.6 ± 10.2 days. Participants received a mean of 23.4 ± 31.2 blood transfusions (range, 1-219) and a mean of 5.3 ± 10.7 units of very old blood. Neither mean storage age nor proportion of very old blood had any influence on multiple organ dysfunction severity, time to wound healing, or mortality. Duration of ventilation was significantly predicted by both mean blood storage age and the proportion of very old blood, but this was of questionable clinical relevance given extreme variability in duration of ventilation (adjusted r ≤ 0.01). CONCLUSIONS: Despite massive blood transfusion, including very old blood, the duration of red cell storage did not influence outcome in burn patients. Provision of the oldest blood first by Blood Banks is rational, even for massive transfusion.

Multivariate two-part statistics for analysis of correlated mass spectrometry data from multiple biological specimens.

MOTIVATION: High through-put mass spectrometry (MS) is now being used to profile small molecular compounds across multiple biological sample types from the same subjects with the goal of leveraging information across biospecimens. Multivariate statistical methods that combine information from all biospecimens could be more powerful than the usual univariate analyses. However, missing values are common in MS data and imputation can impact between-biospecimen correlation and multivariate analysis results. RESULTS: We propose two multivariate two-part statistics that accommodate missing values and combine data from all biospecimens to identify differentially regulated compounds. Statistical significance is determined using a multivariate permutation null distribution. Relative to univariate tests, the multivariate procedures detected more significant compounds in three biological datasets. In a simulation study, we showed that multi-biospecimen testing procedures were more powerful than single-biospecimen methods when compounds are differentially regulated in multiple biospecimens but univariate methods can be more powerful if compounds are differentially regulated in only one biospecimen. AVAILABILITY AND IMPLEMENTATION: We provide R functions to implement and illustrate our method as supplementary information CONTACT: sltaylor@ucdavis.eduSupplementary information: Supplementary data are available at Bioinformatics online.

Transfusion Requirement in Burn Care Evaluation (TRIBE): A Multicenter Randomized Prospective Trial of Blood Transfusion in Major Burn Injury.

OBJECTIVE: Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. BACKGROUND: Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. METHODS: This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS: Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3 ±â€Š32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8 ±â€Š44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, χ test). CONCLUSIONS: A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).

High-volume hemofiltration in adult burn patients with septic shock and acute kidney injury: a multicenter randomized controlled trial.

BACKGROUND: Sepsis and septic shock occur commonly in severe burns. Acute kidney injury (AKI) is also common and often results as a consequence of sepsis. Mortality is unacceptably high in burn patients who develop AKI requiring renal replacement therapy and is presumed to be even higher when combined with septic shock. We hypothesized that high-volume hemofiltration (HVHF) as a blood purification technique would be beneficial in this population. METHODS: We conducted a multicenter, prospective, randomized, controlled clinical trial to evaluate the impact of HVHF on the hemodynamic profile of burn patients with septic shock and AKI involving seven burn centers in the United States. Subjects randomized to the HVHF were prescribed a dose of 70 ml/kg/hour for 48 hours while control subjects were managed in standard fashion in accordance with local practices. RESULTS: During a 4-year period, a total of nine subjects were enrolled for the intervention during the ramp-in phase and 28 subjects were randomized, 14 each into the control and HVHF arms respectively. The study was terminated due to slow enrollment. Ramp-in subjects were included along with those randomized in the final analysis. Our primary endpoint, the vasopressor dependency index, decreased significantly at 48 hours compared to baseline in the HVHF group (p = 0.007) while it remained no different in the control arm. At 14 days, the multiple organ dysfunction syndrome score decreased significantly in the HVHF group when compared to the day of treatment initiation (p = 0.02). No changes in inflammatory markers were detected during the 48-hour intervention period. No significant difference in survival was detected. No differences in adverse events were noted between the groups. CONCLUSIONS: HVHF was effective in reversing shock and improving organ function in burn patients with septic shock and AKI, and appears safe. Whether reversal of shock in these patients can improve survival is yet to be determined. TRIAL REGISTRATION: Clinicaltrials.gov NCT01213914 . Registered 30 September 2010.

Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients.

Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis.

Assessment of 3 Bowel Preparation Protocols for Computed Tomography Pneumocolonography in Normal Dogs.

OBJECTIVE: To investigate the effects of 3 different bowel preparation protocols on interpretation of computed tomography (CT) pneumocolonography images. STUDY DESIGN: Experimental crossover design. ANIMALS: Intact male, hound-cross, research colony dogs (n=4). METHODS: All dogs received the 3 different bowel preparation protocols for CT pneumocolonography in the same order, with a minimum of 2 weeks between protocols. For each segment of large bowel, the subjective adequacy of bowel cleansing was assessed, residual fecal and bowel volumes were calculated, and the density of fecal material in the bowel lumen was measured. Linear mixed effect models that included a random dog effect were used to evaluate mean differences in outcome measures across protocols. RESULTS: No dogs experienced any clinical problems associated with the protocols or CT pneumocolonography. Bowel cleansing was considered adequate for CT pneumocolonography interpretation for all 3 protocols. There was a significant effect of protocol on residual fecal volumes and the fecal:bowel volume ratio, with the 2 protocols that included an extended fast producing the lowest total residual fecal volumes. There was a significant effect of protocol on maximum measured density of residual fecal material with the 2 protocols including iodinated contrast having the highest density. CONCLUSIONS: All protocols were sufficient for CT pneumocolonography interpretation and contrast-tagging of residual fecal material was successful with oral iopamidol administration. An at-home bowel cleansing protocol may provide adequate bowel cleansing for CT pneumocolonography image interpretation.

Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue.

To decrease the mortality of lung cancer, better screening and diagnostic tools as well as treatment options are needed. Protein glycosylation is one of the major post-translational modifications that is altered in cancer, but it is not exactly clear which glycan structures are affected. A better understanding of the glycan structures that are differentially regulated in lung tumor tissue is highly desirable and will allow us to gain greater insight into the underlying biological mechanisms of aberrant glycosylation in lung cancer. Here, we assess differential glycosylation patterns of lung tumor tissue and nonmalignant tissue at the level of individual glycan structures using nLC-chip-TOF-MS. Using tissue samples from 42 lung adenocarcinoma patients, 29 differentially expressed (FDR < 0.05) glycan structures were identified. The levels of several oligomannose type glycans were upregulated in tumor tissue. Furthermore, levels of fully galactosylated glycans, some of which were of the hybrid type and mostly without fucose, were decreased in cancerous tissue, whereas levels of non- or low-galactosylated glycans mostly with fucose were increased. To further assess the regulation of the altered glycosylation, the glycomics data was compared to publicly available gene expression data from lung adenocarcinoma tissue compared to nonmalignant lung tissue. The results are consistent with the possibility that the observed N-glycan changes have their origin in differentially expressed glycosyltransferases. These results will be used as a starting point for the further development of clinical glycan applications in the fields of imaging, drug targeting, and biomarkers for lung cancer.

Electronic alerts for triage protocol compliance among emergency department triage nurses: a randomized controlled trial.

BACKGROUND: Alerts embedded in electronic health records (EHRs) are designed to improve processes at the point of care. OBJECTIVE: The aim of this study was to determine if an EHR alert-at emergency department (ED) triage-increases the ED triage nurse's utilization of triage protocols. METHODS: ED triage nurses were randomized to receive either a passive EHR alert or no intervention for patients with the following complaints: minor trauma with extremity injuries or female patients with abdominal pain. The EHR alert notified the nurse that the patient was eligible for diagnostic testing: radiographs for patients with injured extremities or urinalysis for female patients with abdominal pain. RESULTS: Twenty-eight nurses triaged 20,410 patients in the 6 months before the intervention and 19,157 in the 6 months after the intervention. Before the intervention, the urinalysis protocol was implemented in 101/624 (16.2%) patients triaged by the intervention group and 116/711 (16.3%) triaged by the control group. After the intervention, the urinalysis protocol was implemented in 146/530 (27.6%) patients triaged by the intervention group and 174/679 (25.6%) triaged by the control group. Before the intervention, the radiograph protocol was implemented in 58/774 (7.5%) patients triaged by the intervention group and 45/684 (6.6%) triaged by the control group. After the intervention, the radiograph protocol was implemented in 78/614 (12.7%) patients triaged by the intervention group and 79/609 (13.0%) triaged by the control group. CONCLUSION: The use of a passive EHR alert to promote ED triage protocols showed little benefit. Before the widespread implementation of EHR alerts for patient care, rigorous studies are required to determine the best alert methods and the impacts of such interventions.