Impact of scatter radiation on spectral quantification performance of first- and second-generation dual-layer spectral computed tomography.

OBJECTIVE: To assess the impact of scatter radiation on quantitative performance of first and second-generation dual-layer spectral computed tomography (DLCT) systems. METHOD: A phantom with two iodine inserts (1 and 2 mg/mL) configured to intentionally introduce high scattering conditions was scanned with a first- and second-generation DLCT. Collimation widths (maximum of 4 cm for first generation and 8 cm for second generation) and radiation dose levels were varied. To evaluate the performance of both systems, the mean CT numbers of virtual monoenergetic images (MonoEs) at different energies were calculated and compared to expected values. MonoEs at 50  versus 150 keV were plotted to assess material characterization of both DLCTs. Additionally, iodine concentrations were determined, plotted, and compared against expected values. For each experimental scenario, absolute errors were reported. RESULTS: An experimental setup, including a phantom design, was successfully implemented to simulate high scatter radiation imaging conditions. Both CT scanners illustrated high spectral accuracy for small collimation widths (1 and 2 cm). With increased collimation (4 cm), the second-generation DLCT outperformed the earlier DLCT system. Further, the spectral performance of the second-generation DLCT at an 8 cm collimation width was comparable to a 4 cm collimation on the first-generation DLCT. A comparison of the absolute errors between both systems at lower energy MonoEs illustrates that, for the same acquisition parameters, the second-generation DLCT generated results with decreased errors. Similarly, the maximum error in iodine quantification was less with second-generation DLCT (0.45  and 0.33 mg/mL for the first and second-generation DLCT, respectively). CONCLUSION: The implementation of a two-dimensional anti-scatter grid in the second-generation DLCT improves the spectral quantification performance. In the clinical routine, this improvement may enable additional clinical benefits, for example, in lung imaging.

Spectral performance evaluation of a second-generation spectral detector CT.

PURPOSE: The aim of this study was to characterize a second-generation wide-detector dual-layer spectral computed tomography (CT) system for material quantification accuracy, acquisition parameter and patient size dependencies, and tissue characterization capabilities. METHODS: A phantom with multiple tissue-mimicking and material-specific inserts was scanned with a dual-layer spectral detector CT using different tube voltages, collimation widths, radiation dose levels, and size configurations. Accuracy of iodine density maps and virtual monoenergetic images (MonoE) were investigated. Additionally, differences between conventional and MonoE 70 keV images were calculated to evaluate acquisition parameter and patient size dependencies. To demonstrate material quantification and differentiation, liver-mimicking inserts with adipose and iron were analyzed with a two-base decomposition utilizing MonoE 50 and 150 keV, and root mean square error (RMSE) for adipose and iron content was reported. RESULTS: Measured inserts exhibited quantitative accuracy across a wide range of MonoE levels. MonoE 70 keV images demonstrated reduced dependence compared to conventional images for phantom size (1 vs. 27 HU) and acquisition parameters, particularly tube voltage (4 vs. 37 HU). Iodine density quantification was successful with errors ranging from -0.58 to 0.44 mg/mL. Similarly, inserts with different amounts of adipose and iron were differentiated, and the small deviation in values within inserts corresponded to a RMSE of 3.49 ± 1.76% and 1.67 ± 0.84 mg/mL for adipose and iron content, respectively. CONCLUSION: The second-generation dual-layer CT enables acquisition of quantitatively accurate spectral data without compromises from differences in patient size and acquisition parameters.

Comparison of COVID-19 versus influenza on the incidence, features, and recovery from acute kidney injury in hospitalized United States Veterans.

Acute kidney injury is a common complication in patients hospitalized with SARSCoV-2 (COVID-19), with prior studies implicating multiple potential mechanisms of injury. Although COVID-19 is often compared to other respiratory viral illnesses, few formal comparisons of these viruses on kidney health exist. In this retrospective cohort study, we compared the incidence, features, and outcomes of acute kidney injury among Veterans hospitalized with COVID-19 or influenza and adjusted for baseline conditions using weighted comparisons. A total of 3402 hospitalizations for COVID-19 and 3680 hospitalizations for influenza admitted between October 1, 2019 and May 31, 2020 across 127 Veterans Administration hospitals nationally were studied using the electronic medical record. Acute kidney injury occurred more frequently among those with COVID-19 compared to those with influenza (40.9% versus 29.4%, weighted analysis) and was more severe. Patients with COVID-19 were more likely to require mechanical ventilation and vasopressors and experienced higher mortality. Proteinuria and hematuria were frequent in both groups but more common in COVID-19. Recovery of kidney function was less common in patients with COVID-19 and acute kidney injury but was similar among survivors. Thus, findings from this study confirm that acute kidney injury is more common and severe among patients hospitalized with COVID-19 compared to influenza, a finding that may be driven largely by illness severity. Hence, the combined impact of these two illnesses on kidney health may be significant and have important implications for resource allocation.

Renin-angiotensin aldosterone inhibitor use at hospital discharge among patients with moderate to severe acute kidney injury and its association with recurrent acute kidney injury and mortality.

Recurrent episodes of acute kidney injury (AKI) are common among AKI survivors. Renin-angiotensin aldosterone inhibitors (RAASi) are often indicated for these patients but may increase the risk for recurrent AKI. Here, we examined whether RAASi associates with a higher risk for recurrent AKI and mortality among survivors of moderate to severe AKI in a retrospective cohort of Veterans who survived Stage II or III AKI. The primary exposure was RAASi at hospital discharge and the primary endpoint was recurrent AKI within 12 months. Cox proportional hazards models were fit on a propensity score-weighted cohort to compare time to recurrent AKI and mortality by RAASi exposure. Among 96,983 patients, 40% were on RAASi at discharge. Compared to patients who continued RAASi use, those discontinuing use experienced no difference in risk for recurrent AKI but had a significantly higher risk of mortality [hazard ratio 1.33 (95% confidence interval1.26-1.41)]. No differences in recurrent AKI risk was observed for non-users started or not on RAASi compared to prevalent users who continued RAASi. Subgroup analyses among those with diabetes, chronic kidney disease, heart failure, and malignancy were similar with exception of a modest reduction in recurrent AKI risk among RAASi discontinuers with chronic kidney disease. Thus, RAASi use among survivors of moderate to severe AKI was associated with little to no difference in risk for recurrent AKI but was associated with improved survival. Reinitiating or starting RAASi among patients with strong indications is warranted but should be balanced with individual overall risk for recurrent AKI and with adequate monitoring.

Assessment of neuroinflammation in the aging hippocampus using large-molecule microdialysis: Sex differences and role of purinergic receptors.

Aging is associated with an enhanced neuroinflammatory response to acute immune challenge, often termed "inflammaging." However, there are conflicting reports about whether baseline levels of inflammatory markers are elevated under ambient conditions in the aging brain, or whether such changes are observed predominantly in response to acute challenge. The present studies utilized two distinct approaches to assess inflammatory markers in young and aging Fischer 344 rats. Experiment 1 examined total tissue content of inflammatory markers from hippocampus of adult (3 month), middle-aged (12 month), and aging (18 month) male Fischer (F) 344 rats using multiplex analysis (23-plex). Though trends emerged for several cytokines, no significant differences in basal tissue content were observed across the 3 ages examined. Experiment 2 measured extracellular concentrations of inflammatory factors in the hippocampus from adult (3 month) and aging (18 month) males and females using large-molecule in vivo microdialysis. Although few significant aging-related changes were observed, robust sex differences were observed in extracellular concentrations of CCL3, CCL20, and IL-1α. Experiment 2 also evaluated the involvement of the P2X7 purinergic receptor in neuroinflammation using reverse dialysis of the selective agonist BzATP. BzATP produced an increase in IL-1α and IL-1ß release and rapidly suppressed the release of CXCL1, CCL2, CCL3, CCL20, and IL-6. Other noteworthy sex by aging trends were observed in CCL3, IL-1ß, and IL-6. Together, these findings provide important new insight into late-aging and sex differences in neuroinflammation, and their regulation by the P2X7 receptor.

A real-world assessment of mycophenolate mofetil for remission induction in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of ANCA-associated vasculitis (AAV). Clinical trials demonstrating the efficacy of mycophenolate mofetil (MMF) for remission induction in AAV excluded patients with EGPA. Despite this, MMF is commonly used in these patients. The objective of this study was to evaluate, for the first time, the effectiveness and tolerance of MMF in EGPA remission induction. A retrospective, two-center, real-world study was conducted in patients with EGPA who received MMF in addition to prednisolone for newly diagnosed or relapsing disease between 2009 and 2019. Baseline, 3-, 6- and 12-month outcome data were extracted from electronic health records. The primary outcome was disease remission, defined as a Birmingham Vasculitis Activity Score of 0 at 6 months. Secondary outcomes included disease relapse, median prednisolone dose at 12 months and drug tolerance. In total, 15 patients (73% male, median age 57) with EGPA (11 newly diagnosed/4 relapsing) were identified. At 6 months, 67% had achieved disease remission. At 12 months, this was maintained (66.7%) and 4 patients had relapsed. All but one patient remained on MMF at study completion and all patients tolerated MMF. Our real-world data suggest that MMF is an effective and well-tolerated agent for achieving disease remission in EGPA. A future randomized controlled trial of MMF in this neglected orphan disease is now warranted.

Timing of Recovery From Moderate to Severe AKI and the Risk for Future Loss of Kidney Function.

RATIONALE & OBJECTIVE: The extent of recovery of kidney function following acute kidney injury (AKI) is known to be associated with future chronic kidney disease. Less is known about how the timing of recovery affects the rate of future loss of kidney function. STUDY DESIGN: We performed a retrospective cohort study examining the independent association between the timing of recovery from moderate to severe AKI and future loss of kidney function. SETTING & PARTICIPANTS: 47,903 adult US veterans with stage 2 or 3 AKI who recovered to within 120% of baseline creatinine level within 90 days of peak injury. EXPOSURE: The timing of recovery of kidney function from peak inpatient serum creatinine level grouped into 1 to 4, 5 to 10, 11 to 30, and 31 to 90 days. OUTCOME: A sustained 40% decline in estimated glomerular filtration rate below that calculated from the last serum creatinine level available during the 90-day recovery period or kidney failure (2 outpatient estimated glomerular filtration rates<15mL/min/1.73m2, dialysis procedures > 90 days apart, kidney transplantation, or registry within the US Renal Data System). ANALYTICAL APPROACH: Time to the primary outcome was examined using multivariable Cox proportional hazards regression. RESULTS: Among 47,903 patients, 29,316 (61%), 10,360 (22%), 4,520 (9%), and 3,707 (8%) recovered within 1 to 4, 5 to 10, 11 to 30, and 31 to 90 days, respectively. With a median follow-up of 42 months, unadjusted incidence rates for the kidney outcome were 2.01, 3.55, 3.86, and 3.68 events/100 person-years, respectively. Compared with 1 to 4 days, recovery within 5 to 10, 11 to 30, and 31 to 90 days was associated with increased rates of the primary outcome: adjusted HRs were 1.33 (95% CI, 1.24-1.43), 1.41 (95% CI, 1.28-1.54), and 1.58 (95% CI, 1.43-1.75), respectively. LIMITATIONS: Predominately male population, residual confounding, and inability to make causal inferences because of the retrospective observational study design. CONCLUSIONS: The timing of recovery provides an added dimension to AKI phenotyping and prognostic information regarding the future occurrence of loss of kidney function. Studies to identify effective interventions on the timing of recovery from AKI are warranted.

Predicting 30-Day Hospital Readmission Risk in a National Cohort of Patients with Cirrhosis.

BACKGROUND: Early hospital readmission for patients with cirrhosis continues to challenge the healthcare system. Risk stratification may help tailor resources, but existing models were designed using small, single-institution cohorts or had modest performance. AIMS: We leveraged a large clinical database from the Department of Veterans Affairs (VA) to design a readmission risk model for patients hospitalized with cirrhosis. Additionally, we analyzed potentially modifiable or unexplored readmission risk factors. METHODS: A national VA retrospective cohort of patients with a history of cirrhosis hospitalized for any reason from January 1, 2006, to November 30, 2013, was developed from 123 centers. Using 174 candidate variables within demographics, laboratory results, vital signs, medications, diagnoses and procedures, and healthcare utilization, we built a 47-variable penalized logistic regression model with the outcome of all-cause 30-day readmission. We excluded patients who left against medical advice, transferred to a non-VA facility, or if the hospital length of stay was greater than 30 days. We evaluated calibration and discrimination across variable volume and compared the performance to recalibrated preexisting risk models for readmission. RESULTS: We analyzed 67,749 patients and 179,298 index hospitalizations. The 30-day readmission rate was 23%. Ascites was the most common cirrhosis-related cause of index hospitalization and readmission. The AUC of the model was 0.670 compared to existing models (0.649, 0.566, 0.577). The Brier score of 0.165 showed good calibration. CONCLUSION: Our model achieved better discrimination and calibration compared to existing models, even after local recalibration. Assessment of calibration by variable parsimony revealed performance improvements for increasing variable inclusion well beyond those detectable for discrimination.

Propofol Versus Dexmedetomidine for Procedural Sedation in a Pediatric Population.

OBJECTIVES: Frequently, infants and children require sedation to facilitate noninvasive procedures and imaging studies. Propofol and dexmedetomidine are used to achieve deep procedural sedation in children. The objective of this study was to compare the clinical safety and efficacy of propofol versus dexmedetomidine in pediatric patients undergoing sedation in a pediatric sedation unit. METHODS: A retrospective analysis of patients sedated with either propofol or dexmedetomidine in a pediatric sedation unit by pediatric emergency physicians was performed. Both medications were dosed per protocol with propofol 2 mg/kg induction and 150 µg · kg-1 · min-1 maintenance and dexmedetomidine 3 µg/kg induction for 10 minutes and 2 µg · kg-1 · h-1maintenance. The variables collected included drug dose, sedation time (time that the drug was given to the completion of the procedure), recovery time (end of the study to the return to the presedation sedation score for 15 minutes), need for dose rate changes, airway management, and adverse events. RESULTS: A total of 2432 children were included- 1503 who received propofol and 929 who received dexmedetomidine. Propofol and dexmedetomidine resulted in successful completion of the study in 98.8% and 99.7%, respectively (P = 0.02). The mean recovery time for propofol was 34.3 minutes, compared with 65.6 minutes for dexmedetomidine (P < 0.001). The need for unexpected airway management was 9.7% for propofol and 2.2% for dexmedetomidine (P < 0.001). Adverse events occurred in 8.6% and 6% of patients in the propofol and dexmedetomidine groups, respectively (P = 0.02). CONCLUSIONS: Propofol use led to significantly shorter recovery times, with an increased need for airway management, but rates of bag-mask ventilation (2.3%), airway obstruction (1.1%), and desaturation (1.6%) were low. No patients required intubation. Propofol is a reasonable alternative to dexmedetomidine, with a clinically acceptable safety profile.

Acute Kidney Injury and Risk of Incident Heart Failure Among US Veterans.

BACKGROUND: Acute kidney injury (AKI) is common and associated with poor outcomes. Heart failure is a leading cause of cardiovascular disease among patients with chronic kidney disease. The relationship between AKI and heart failure remains unknown and may identify a novel mechanistic link between kidney and cardiovascular disease. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied a national cohort of 300,868 hospitalized US veterans (2004-2011) without a history of heart failure. PREDICTOR: AKI was the predictor and was defined as a 0.3-mg/dL or 50% increase in serum creatinine concentration from baseline to the peak hospital value. Patients with and without AKI were matched (1:1) on 28 in- and outpatient covariates using optimal Mahalanobis distance matching. OUTCOMES: Incident heart failure was defined as 1 or more hospitalization or 2 or more outpatient visits with a diagnosis of heart failure within 2 years through 2013. RESULTS: There were 150,434 matched pairs in the study. Patients with and without AKI during the index hospitalization were well matched, with a median preadmission estimated glomerular filtration rate of 69mL/min/1.73m2. The overall incidence rate of heart failure was 27.8 (95% CI, 19.3-39.9) per 1,000 person-years. The incidence rate was higher in those with compared with those without AKI: 30.8 (95% CI, 21.8-43.5) and 24.9 (95% CI, 16.9-36.5) per 1,000 person-years, respectively. In multivariable models, AKI was associated with 23% increased risk for incident heart failure (HR, 1.23; 95% CI, 1.19-1.27). LIMITATIONS: Study population was primarily men, reflecting patients seen at Veterans Affairs hospitals. CONCLUSIONS: AKI is an independent risk factor for incident heart failure. Future studies to identify underlying mechanisms and modifiable risk factors are needed.

Urgent Care Transfers to an Academic Pediatric Emergency Department.

OBJECTIVES: The aim of this study was to investigate the hypothesis that a significant percentage of urgent care center to pediatric ED transfers can be discharged home without emergency department (ED) resource utilization. METHODS: A retrospective chart review was completed for a 6-month period on all patients transferred from urgent care centers. A data collection tool focusing on demographics, diagnoses, reason for transfer, ED resource utilization, ED disposition, and 72-hour ED return was used. Each encounter was classified as "urgent" or "nonurgent" based on resource utilization criteria. Descriptive statistics were reported for demographics, encounter data, and 72-hour ED return stratified by nonurgent versus urgent classification. Two-sample t, χ, and Fisher exact tests were used to assess differences in characteristics between the nonurgent and urgent groups. RESULTS: One hundred nine patients met inclusion criteria. Of these, 93 (85%) were discharged from the ED. Twenty nine (27%) of the transferred patients were discharged without ED resource utilization. Seventy-two-hour return was noted for only 1 patient who was again discharged at the subsequent encounter. CONCLUSIONS: A large proportion of patients transferred from urgent care centers were directly discharged from the ED without any ED resource utilization. Eliminating or reducing such transfers has the potential to limit the amount of nonurgent ED visits, thus producing cost savings and better patient care.

Childhood obesity in pediatric patients with difficult-to-control asthma in a tertiary pediatric subspecialty clinic.

BACKGROUND: Identifying clinical features associated with difficult-to-control asthma will help address overall control and more-effective asthma management. OBJECTIVE: To evaluate our clinical observation that the proportion of patients who are overweight or obese is significantly higher in patients with difficult-to-control asthma than in patients with well-controlled asthma. METHODS: This was a retrospective chart review of 400 patients, ages 5 to 18 years. Cases (n = 200) were identified as 100 subjects with difficult-to-control asthma and an inhaled corticosteroid dose of ≥1000 µg/day and 100 subjects with well-controlled asthma and an inhaled corticosteroid dose of ≤500 µg/day. The control group included 200 subjects without asthma. Multivariable logistic regression models were used to assess the relationships between asthma status and weight status, age, race, and sex. RESULTS: The mean body mass index percentile (± standard deviation at 95% confidence interval) was significantly higher in the difficult-to-control asthma group versus the well-controlled asthma group versus the control group (74.66 ± 28.19 versus 54.25 ± 29.92 versus 55.19 ± 32.54; p < 0.001). Thirty-six percent of the difficult-to-control patients with asthma were obese (versus 6% of the patients with well-controlled asthma [p < 0.001] versus 13% of patients without asthma [p = 0.002]), and 47% normal weight (versus 79% of the patients with well-controlled asthma versus 75% of patients without asthma; p < 0.001). The mean age and the proportion of African Americans in the difficult-to-control asthma group were significantly higher than in the well-controlled asthma group and in the control group (p < 0.001). CONCLUSION: The results of this study demonstrated a significant association between severe persistent difficult-to-control asthma and obesity, age, and race. Patients who are obese and have difficult-to-control asthma need treatment approaches that address both asthma control and weight management.

Activity of the porcine gonadotropin-releasing hormone receptor gene promoter is partially conferred by a distal gonadotrope specific element (GSE) within an upstream enhancing region, two proximal GSEs and a retinoid X receptor binding site.

BACKGROUND: Regulation of gonadotropin-releasing hormone (GnRH) receptor (GnRHR) numbers on gonadotropes within the anterior pituitary gland represents a critical point for control of reproductive function. Binding of GnRH to its receptor regulates follicle stimulating hormone (FSH) and luteinizing hormone (LH) release and levels of this G-protein coupled receptor on the surface of gonadotropes determines their sensitivity to GnRH pulses. While transcriptional regulation of this gene has been studied in mice, rats, humans and sheep, little is known about its regulation in the pig, an important agricultural species and human research model. METHODS: We isolated 5118 bp of 5' flanking sequence for the porcine GnRHR gene and generated luciferase reporter vectors. Deletion and mutation constructs were evaluated in gonadotrope-derived alphaT3-1 cells to determine regions important for gene transcription. Additionally, electrophoretic mobility shift assays (EMSAs) were performed to identify transcription factors binding to the GnRHR promoter. RESULTS: Transient transfections revealed that the GnRHR promoter was functional in alphaT3-1 cells but not in cells of non-gonadotrope origin. Mutation of the highly conserved gonadotrope specific element (GSE) located at -179/-171 of proximal promoter completely ablated luciferase activity, whereas mutation of another GSE at -315/-310 reduced activity by 34%. Consistent with this, EMSAs using alphaT3-1 nuclear extracts and a steroidogenic factor (SF)1 antibody confirmed SF1 binding to both GSEs. EMSAs also demonstrated that a retinoid X receptor (RXR) binding site at -279/-274 binds RXRalpha and RXRbeta and mutation of this site eliminated promoter activity. Transient transfection of alphaT3-1 cells with reporter vectors containing selective removal of 5' flanking region for the porcine GnRHR gene indicated that the -1915/-1431 segment was important for promoter activity. Definition of this region via transfection assays and EMSAs revealed an upstream enhancing region located at -1779/-1667 that increases porcine GnRHR gene expression in alphaT3-1 cells and includes a SF1 binding site at -1760/-1753. CONCLUSIONS: Porcine GnRHR promoter activity in alphaT3-1 cells is partially conferred by a distal GSE, two proximal GSEs and a RXR binding site. Basal gonadotrope expression of the porcine GnRHR gene uniquely involves three GSEs and RXR is newly identified as a regulator of GnRHR promoter activity.

Expedited Delivery of Pain Medication for Long-Bone Fractures Using an Intranasal Fentanyl Clinical Pathway.

OBJECTIVE: This study aims to determine whether a pathway designed to facilitate the use of intranasal (IN) fentanyl for long-bone fractures will expedite the delivery of pain medication, decrease the total length of emergency department (ED) stay, and provide faster analgesia compared with intravenous (IV) morphine. METHODS: A pain pathway for IN fentanyl in long-bone fractures was instituted in our ED in July 2011. We performed a retrospective and prospective chart review of patients aged 3 to 21 years who presented to the ED with a clinically suspected long-bone fracture and either received IV morphine or were placed on IN fentanyl pain pathway. RESULTS: A total of 94 patients met our inclusion criteria; 71 received IV morphine, and 23 received IN fentanyl, per pathway protocol. The mean length of time to pain medication administration was statistically significantly faster for IN fentanyl (37 minutes) than for IV morphine (62 minutes) (P = 0.002). The mean total length of stay for patients who received IN fentanyl versus patients who received IV morphine was not statistically significantly different after excluding patients who needed reduction or surgery. Effectiveness of pain control was not statistically significantly different between the IN fentanyl group and the IV morphine group. CONCLUSIONS: Use of the IN fentanyl pain pathway significantly decreases time to pain medication administration in pediatric patients with suspected long-bone fractures.

Intensive care unit readmission during childhood after preterm birth with respiratory failure.

OBJECTIVE: To determine the incidence and risk factors for readmission to the intensive care unit (ICU) among preterm infants who required mechanical ventilation at birth. STUDY DESIGN: We studied preterm newborns (birth weight 500-1250 g) who required mechanical ventilation at birth and were enrolled in a multicenter trial of inhaled nitric oxide therapy. Patients were assessed up to 4.5 years of age via annual in-person evaluations and structured telephone interviews. Univariate and multivariable analyses of baseline and birth hospitalization predictors of ICU readmission were performed. RESULTS: Of 512 subjects providing follow-up data, 58% were readmitted to the hospital (51% of these had multiple readmissions, averaging 3.9 readmissions per subject), 19% were readmitted to an ICU, and 12% required additional mechanical ventilation support. In univariate analyses, ICU readmission was more common among male subjects (OR 2.01; 95% CI 1.27-3.18), infants with grade 3-4 intracranial hemorrhage (OR 2.13; 95% CI 1.23-3.69), increasing duration of birth hospitalization (OR 1.01 per day; 95% CI 1.00-1.02), and prolonged oxygen therapy (OR 1.01 per day; 95% CI 1.00-1.01). In the first year after birth hospitalization, children readmitted to an ICU incurred greater health care costs (median $69,700 vs $30,200 for subjects admitted to the ward and $9600 for subjects never admitted). CONCLUSIONS: Small preterm infants who were mechanically ventilated at birth have substantial risk for readmission to an ICU and late mechanical ventilation, require extensive health care resources, and incur high treatment costs.

Natural genetic variation underlying differences in Peromyscus repetitive and social/aggressive behaviors.

Peromyscus maniculatus (BW) and P. polionotus (PO) are interfertile North American species that differ in many characteristics. For example, PO exhibit monogamy and BW animals are susceptible to repetitive behaviors and thus a model for neurobehavioral disorders such as Autism. We analyzed these two stocks as well as their hybrids, a BW Y(PO) consomic line (previously shown to alter glucose homeostasis) and a natural P. maniculatus agouti variant (A(Nb) = wide band agouti). We show that PO animals engage in far less repetitive behavior than BW animals, that this trait is dominant, and that trait distribution in both species is bi-modal. The A(Nb) allele also reduces such behaviors, particularly in females. PO, F1, and A(Nb) animals all dig significantly more than BW. Increased self-grooming is also a PO dominant trait, and there is a bimodal trait distribution in all groups except BW. The inter-stock differences in self-grooming are greater between males, and the consomic data suggest the Y chromosome plays a role. The monogamous PO animals engage in more social behavior than BW; hybrid animals exhibit intermediate levels. Surprisingly, A(Nb) animals are also more social than BW animals, although A(Nb) interactions led to aggressive interactions at higher levels than any other group. PO animals exhibited the lowest incidence of aggressive behaviors, while the hybrids exhibited BW levels. Thus this group exhibits natural, genetically tractable variation in several biomedically relevant traits.

Knowledge regarding hymens and the sex education of parents.

The objective of this study was to ascertain beliefs and knowledge of pediatricians and parents regarding the hymen and to evaluate parental and pediatrician attitudes regarding sex education by pediatricians. Surveys were distributed anonymously to parents and pediatricians. Survey questions included knowledge of the female hymen and questions regarding attitudes toward sexual health education. There was a statistically significant difference in mean knowledge scores between pediatricians and parents regarding the hymen (3.7 versus 1.3; p < 0.0001). Almost two-thirds of pediatricians (63%) felt comfortable providing sexual health education directly to their patients, but only 41% felt comfortable educating parents. Pediatricians and parents demonstrate knowledge gaps about the hymen.

Prenatal alcohol exposure alters expression of genes involved in cell adhesion, immune response, and toxin metabolism in adolescent rat hippocampus.

Prenatal alcohol exposure (PAE) can result in mild to severe consequences for children throughout their lives, with this range of symptoms referred to as Fetal Alcohol Spectrum Disorders (FASD). These consequences are thought to be linked to changes in gene expression and transcriptional programming in the brain, but the identity of those changes, and how they persist into adolescence are unclear. In this study, we isolated RNA from the hippocampus of adolescent rats exposed to ethanol during prenatal development and compared gene expression to controls. Briefly, dams were either given free access to standard chow ad libitum (AD), pair-fed a liquid diet (PF) or were given a liquid diet with ethanol (6.7% ethanol, ET) throughout gestation (gestational day (GD) 0-20). All dams were given control diet ad libitum beginning on GD 20 and throughout parturition and lactation. Hippocampal tissue was collected from adolescent male and female offspring (postnatal day (PD) 35-36). Exposure to ethanol caused widespread downregulation of many genes as compared to control rats. Gene ontology analysis demonstrated that affected pathways included cell adhesion, toxin metabolism, and immune responses. Interestingly, these differences were not strongly affected by sex. Furthermore, these changes were consistent when comparing ethanol-exposed rats to pair-fed controls provided with a liquid diet and those fed ad libitum on a standard chow diet. We conclude from this study that changes in genetic architecture and the resulting neuronal connectivity after prenatal exposure to alcohol continue through adolescent development. Further research into the consequences of specific gene expression changes on neural and behavioral changes will be vital to our understanding of the FASD spectrum of diseases.

Age-related decline in social interaction is associated with decreased c-Fos induction in select brain regions independent of oxytocin receptor expression profiles.

Social behavior decreases with aging, and we have previously found a substantial decline in social investigative behavior of old female rats. In this study we examined the neural activation pattern (c-Fos mRNA) of young (3 month) and old (18 month) female rats after brief 10 min exposure to a novel female rat in order to identify forebrain regions that show selective age-related alterations in their neural response to social investigation. We also measured relative oxytocin receptor expression (Oxtr mRNA) as a possible factor in age-related declines in c-Fos induction after social interaction. Young rats exposed to a social partner had a greater c-Fos mRNA response than those exposed to novel context alone in the lateral septum and septohypothalamic area, with blunted increases evident in old rats. In addition, c-Fos mRNA levels in the lateral septum were positively correlated with social investigative behavior. Interestingly, age-related differences in c-Fos gene induction were unrelated to the local amount of Oxtr expression within specific brain regions, although we found an age-related decline in Oxtr expression in the ventromedial hypothalamus. This functional neuroanatomical characterization may point to certain brain regions that are especially sensitive to age-related declines associated with social interaction behavior.

Lifelike PixelPrint phantoms for assessing clinical image quality and dose reduction capabilities of a deep learning CT reconstruction algorithm.

Deep learning CT reconstruction (DLR) has become increasingly popular as a method for improving image quality and reducing radiation exposure. Due to their nonlinear nature, these algorithms result in resolution and noise performance which are object-dependent. Therefore, traditional CT phantoms, which lack realistic tissue morphology, have become inadequate for assessing clinical imaging performance. We propose to utilize 3D-printed PixelPrint phantoms, which exhibit lifelike attenuation profiles, textures, and structures, as a better tool for evaluating DLR performance. In this study, we evaluate a DLR algorithm (Precise Image (PI), Philips Healthcare) using a custom PixelPrint lung phantom and perform head-to-head comparisons between DLR, iterative reconstruction, and filtered back projection (FBP) with scans acquired at a broad range of radiation exposures (CTDIvol: 0.5, 1, 2, 4, 6, 9, 12, 15, 19, and 20 mGy). We compared the performance of each resultant image using noise, peak signal to noise ratio (PSNR), structural similarity index (SSIM), feature-based similarity index (FSIM), information theoretic-based statistic similarity measure (ISSM) and universal image quality index (UIQ). Iterative reconstruction at 9 mGy matches the image quality of FBP at 12 mGy (diagnostic reference level) for all metrics, demonstrating a dose reduction capability of 25%. Meanwhile, DLR matches the image quality of diagnostic reference level FBP images at doses between 4 - 9 mGy, demonstrating dose reduction capabilities between 25% and 67%. This study shows that DLR allows for reduced radiation dose compared to both FBP and iterative reconstruction without compromising image quality. Furthermore, PixelPrint phantoms offer more realistic testing conditions compared to traditional phantoms in the evaluation of novel CT technologies. This, in turn, promotes the translation of new technologies, such as DLR, into clinical practice.