Quantitative photothermal analysis and multispectral imaging of dental structures: insights into optical and thermal properties of carious and healthy teeth.

Significance: In the analysis of two-layered turbid dental tissues, the outer finite-thickness layer is modeled by an optical transport coefficient distinct from its underlying semi-infinite substrate layer. The optical and thermophysical parameters of healthy and carious teeth across the various wavelengths were measured leading to the determination of the degree of reliability of each of the fitted parameters, with most reliable being thermal diffusivity and conductivity, enamel thickness, and optical transport coefficient of the enamel layer. Quantitative pixel-by-pixel images of the key reliable optical and thermophysical parameters were constructed. Aim: We introduced a theoretical model of pulsed photothermal radiometry based on conduction-radiation theory and applied to quantitative photothermal detection and imaging of biomaterials. The theoretical model integrates a combination of inverse Fourier transformation techniques, avoiding the conventional cumbersome analytical Laplace transform method. Approach: Two dental samples were selected for analysis: the first sample featured controlled, artificially induced early caries on a healthy tooth surface, while the second sample exhibited natural defects along with an internal filling. Using an Nd:YAG laser and specific optical parametric oscillator (OPO) wavelengths (675, 700, 750, and 808 nm), photothermal transient signals were captured from different points on these teeth and analyzed as a function of OPO wavelength. Measurements were also performed with an 808-nm laser diode for comparison with the same OPO wavelength excitation, particularly for the second sample with natural defects. Results: The findings demonstrated that the photothermal transient signals exhibit a fast-decaying pattern at shorter wavelengths due to their higher scattering nature, while increased scattering and absorption in the carious regions masked conductive and radiative contributions from the underlayer. These observations were cross-validated using micro-computed tomography, which also enabled the examination of signal patterns at different tooth locations. Conclusions: The results of our study showed the impact of optical and thermal characteristics of two-layered turbid dental tissues via an inverse Fourier technique, as well as the interactions between these layers, on the patterns observed in depth profiles.

Physician Assistant Gender Differences in Research, Professional Goals, and Perceptions of Support.

PURPOSE: The majority of Physician assistant (PA) educators are women, yet men proportionately publish more and advance further in academic rank. This study examined if research interest, promotion goals, and perceptions of institutional support differed between PA educators with different gender identities. METHODS: This is a subset analysis of a previously published cross-sectional study. PA programs were stratified by region and Carnegie classification and were sampled by a stratified random sampling method. PA faculty from selected programs were invited to participate in an anonymous survey. Data were analyzed to account for the stratified sample design. Means and proportions with associated 95% confidence intervals are described. RESULTS: There was a 51% response rate (N = 110). Sixty-three percent of respondents identified as female and 36% as male. Men had a mean of 5.67 (0.17, 11.16) career research articles and women had 1.56 (0.68, 2.44) articles. Fifteen percent (3.7%, 26.3%) of men were full professor compared to 4.3% (0, 9.1%) of women. When transitioning to a faculty role, 72.5% (58.4%, 86.6%) of men and 52.9% (41%, 64.7%) of women felt supported by their institution. Both genders valued promotion, but 80% (67.6%, 92.4%) of men reported having clear 5-year goals compared to 58.8% (46.6%, 71%) of women (P = .034). CONCLUSION: There was no statistical difference in publications between men and women in this study. Women felt less supported when transitioning to a faculty role compared to men. Both men and women valued promotion equally, but men reported working towards that goal more intentionally. This study found few consistent differences in the attitudes and behaviors towards scholarship between men and women.

A versatile method for the identification of senolytic compounds.

The increased burden of senescent cells is as a well-established hallmark of aging and age-related diseases. This finding sparked significant interest in the identification of molecules capable of selectively eliminating senescent cells, so-called senolytics. Here, we fine-tuned a method for the identification of senolytics that is compatible with high-content fluorescence microscopy. We used spectral detector imaging to measure the emission spectrum of unlabeled control or senescent cells. We observed that senescent cells exhibited higher levels of autofluorescence than their non-senescent counterparts, particularly in the cytoplasmic region. Building on this result, we devised a senolytic assay based on co-culturing quiescent and senescent cells, fluorescently tagged in the nuclear region through the overexpression of H2B-GFP and H2B-RFP, respectively. We validated this approach by showing that first generation senolytics were effective in reducing the number of RFP+ nuclei leaving the count of GFP+ nuclei unaffected. The result was confirmed by flow cytometry analysis of nuclei isolated from these quiescent-senescent cell co-cultures. We found that this system enables to capture cell type-specific effects of senolytics as in the case of fisetin, which kills senescent Mouse Embryonic Fibroblasts but not senescent human melanoma SK-MEL-103 cells. This approach is amenable to genetic and chemical screening for the discovery of senolytic compounds in that it overcomes the limitations of current methods, which rely upon costly chemical reagents or fluorescence microscopy using cells labeled with fluorescent cytoplasmic probes that overlap with the autofluorescence signal emitted by senescent cells.

The Effect of a Flipped Classroom Learning Model Versus Traditional Lecture Model on Resident's Knowledge Acquisition for Atraumatic Back Pain in the Emergency Department.

Objective: The effectiveness of lecture-based (LB) formats for residency education has recently been challenged as the gold standard. Studies suggest a flipped classroom (FC) lecture improves resident satisfaction, but evidence that showing improved knowledge acquisition is lacking. To determine whether the flipped classroom model improves knowledge acquisition compared to traditional LB model. Methods: Emergency medicine resident physicians at 2 academic programs were included in December 2019; at Sinai-Grace Hospital, a traditional lecture was the teaching method and at Detroit Receiving Hospital, FC was utilized. Residents completed prelecture and postlecture content tests. The primary outcome was change in test results (pretest to post-test). A noninferiority design comparing the changes between intervention and control groups was utilized (1-sided t-test, noninferiority margin of -0.5; 1-sided alpha = 0.05). Results: Results were available for 31 residents (17 controls and 14 interventions) out of 83 enrolled. There were 14 postgraduate year 1 (PGY-1), 9 PGY-2, and 8 PGY-3 residents. The mean difference in score was +0.71 (SD 1.38) and +0.77 (SD 1.48) for the FC and LB groups, respectively. This resulted in a mean difference between groups of -0.05 (lower bound of the upper 95% confidence interval -0.93 and therefore crossing the noninferiority margin of -0.05; P = .20). Conclusions: This study of resident education at 2 training programs was unable to demonstrate noninferiority of an FC format compared to standard lecture. Surprisingly, there was little improvement in test results after both teaching formats. Larger studies are needed to power results.

Pediatric hand sanitizer exposures reported to United States poison centers, 2017-2021.

INTRODUCTION: The COVID-19 pandemic increased demand for alcohol-based hand sanitizers. We aimed to describe the epidemiological trends in pediatric alcohol-based hand sanitizer cases reported to United States poison centers. We characterized clinically significant pediatric reports involving alcohol-based hand sanitizer products before and during the pandemic and methanol-containing hand sanitizers during the pandemic. METHODS: We included all single-substance cases involving alcohol-based hand sanitizers reported to the National Poison Data System among children ≤ 19 years from 1 January 2017 to 31 December 2021, and methanol-containing hand sanitizers from 23 June 2020 to 31 December 2021. Multiple product exposures and non-human exposures were excluded. Clinically significant outcomes included moderate or major effects or death. RESULTS: There were 95,718 alcohol-based hand sanitizer pediatric cases during the study period. Most (n = 89,521; 94%) were unintentional, occurred by ingestion (n = 89,879; 93.9%), occurred at home, and were managed at the exposure site (n = 89,774; 93.8%). Common symptoms were vomiting (n = 2,969; 3.1%), coughing (n = 1,102; 1.2%), ocular irritation (n = 1,244; 1.3%), and drowsiness (n = 981; 1.0%). Most children (n = 3,937; 66.2%) managed at a health care facility were treated and released; a minority were admitted (n = 527; 9.0%). Few children (n = 81; 1.4%) were admitted to the intensive care unit. The prevalence of clinically significant cases increased in 2020 and 2021, compared to 2017. Population-adjusted rates, by state, of alcohol-based hand sanitizer cases ranged from 280 to 2,700 per million children. Of the 540 reported cases involving methanol-containing hand sanitizers, the majority (n = 255) occurred in July 2020. Thirteen cases (2.4%) had clinically significant outcomes. The prevalence of clinically significant cases remained similar in 2020 and 2021 and exhibited lower prevalence compared to alcohol-based products. Population-adjusted rates, by state, ranged from fewer than 0.9 to 40 per million children. CONCLUSIONS: Clinically significant pediatric cases involving alcohol-based hand sanitizers increased during the pandemic and remained elevated in 2021. Cases involving methanol-containing products were less frequent. Our findings may inform heightened product quality control and regulatory oversight.

Detection of Bacteria-Induced Early-Stage Dental Caries Using Three-Dimensional Mid-Infrared Thermophotonic Imaging.

Tooth decay, or dental caries, is a widespread and costly disease that is reversible when detected early in its formation. Current dental caries diagnostic methods including X-ray imaging and intraoral examination lack the sensitivity and specificity required to routinely detect caries early in its formation. Thermophotonic imaging presents itself as a highly sensitive and non-ionizing solution, making it suitable for the frequent monitoring of caries progression. Here, we utilized a treatment protocol to produce bacteria-induced caries lesions. The lesions were imaged using two related three-dimensional photothermal imaging modalities: truncated correlation photothermal coherence tomography (TC-PCT) and its enhanced modification eTC-PCT. In addition, micro-computed tomography (µ-CT) and visual inspection by a clinical dentist were used to validate and quantify the severities of the lesions. The observational findings demonstrate the high sensitivity and depth profiling capabilities of the thermophotonic modalities, showcasing their potential use as a non-ionizing clinical tool for the early detection of dental caries.

Barriers to Research: A National Survey of Physician Assistant Faculty.

INTRODUCTION: Success in research is a well-known challenge for physician assistant (PA) educators. Multiple barriers to research productivity have been proposed. This study examines potential barriers to PA research productivity. METHODS: Two hundred forty-seven PA programs were stratified by region and Carnegie classification, creating 28 strata. One program was randomly sampled from each stratum, and faculty from sampled programs were invited to participate (N = 214). An electronic survey was deployed via Qualtrics. Data were analyzed, accounting for the stratified survey sample design. Reported are proportions with associated 95% confidence intervals. RESULTS: Survey response rate was 53% (N = 114). The mean age was 46.7 years [44.5, 48.8 years] and 61% [52.4, 70.4] of respondents were female. Most respondents (53.5%; [44.2, 62.8]) were assistant professors and reported being employed as PA faculty for a mean of 12.4 years [11.2, 13.7 years]. Most respondents (68.1%; [59.7, 76.6]) reported 0 peer-reviewed research articles regardless of number of years as faculty. Few reported an interest in research (22.3%; [14.3, 29.9]) or felt internally driven to perform research (35.4%; [26.6, 44.2]). Most pursued a faculty position to teach (78.1%; [70.5, 85.7]) and spent little time pursuing research. Only 15.8% ([9.7, 21.9]) received research mentorship. DISCUSSION: This study identified lack of interest in research by faculty and lack of mentorship engagement as important factors underlying the profession's poor scholarly output. Initiatives to increase scholarship must first focus on fostering individual interest and increasing motivation.

Lysophosphatidylcholine acyltransferase 1 protein is present in maternal blood in the third trimester and is upregulated by antenatal corticosteroids.

OBJECTIVES: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is involved in the production of fetal lung surfactant. We have shown that LPCAT1 mRNA is present in amniotic fluid and maternal plasma and that its quantity correlates with the amniotic fluid lamellar body count. The purpose of the present study was to assay maternal plasma for the LPCAT1 protein in term and preterm pregnancies; and to measure the impact of antenatal corticosteroids. METHODS: Maternal and newborn plasma samples were obtained from 7 women admitted to the hospital for induction of labor. Maternal plasma was also obtained before administration of corticosteroids and 24 h after the second dose of corticosteroids from 12 women with premature labor and premature rupture of membranes. After sample preparation, LPCAT1 protein levels were determined using sandwich ELISA. RESULTS: We discovered LPCAT1 protein in maternal plasma in measurable quantities after 32 weeks gestation. Further, there was a rise of maternal plasma LPCAT1 in response to the clinical administration of antenatal corticosteroids. CONCLUSIONS: Quantitation of maternal plasma LPCAT1 protein offers promise in the ongoing study of fetal lung maturation.

Early echocardiographic assessment of cardiac function may be prognostically informative in unresuscitated patients with sepsis: A prospective observational study.

PURPOSE: The goal of this study was to explore the association cardiac function at Emergency Department (ED) presentation prior to the initiation of resuscitation, and its change at 3-hours, with adverse outcomes in patients with sepsis. METHODS: This was a prospective observational study of patients presenting to an urban ED with suspected sepsis. Patients had a point-of-care echocardiogram performed prior to initiation of resuscitation and again 3 hours later. Left-ventricular (LV) parameters recorded included e', and E/e', and ejection fraction (EF); right-ventricular (RV) function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Logistic and generalized linear regression were used to assess the association of echocardiographic parameters and ≥ 2-point increase in SOFA score at 24 hours (primary outcome) and 24-hours SOFA score and in-hospital mortality (secondary outcomes). RESULTS: For ΔSOFA ≥ 2 and 24-hour SOFA score, declining LVEF was associated with better outcomes in patients with greater baseline SOFA scores, but worse outcomes in patients with lower baseline scores. A similar relationship was found for ΔTAPSE at 3 hours. Reduced LVEF at presentation was associated with increased mortality after adjusting for ED SOFA score (odds-ratio (OR) 0.76 (CI 0.60-0.96). No relationship between diastolic parameters and outcomes was found. IVF administration was similar across ΔLVEF/TAPSE sub-groups. CONCLUSIONS: Our results suggest that early change in LV and RV systolic function are independently prognostic of sepsis illness severity at 24-hours. Further study is needed to determine if this information can be used to guide treatment and improve outcomes.

Multispectral truncated-correlation photothermal coherence tomography imaging modality for detection of early stage dental caries.

One of the major oral health conditions worldwide is dental caries. Light-absorption-based thermophotonic diagnostic imaging is well positioned for this challenge thanks to its speed, safety, and high molecular contrast advantages. In this work, a multispectral (MS) truncated-correlation photothermal coherence tomography (TC-PCT) imaging modality is introduced for the detection of bacterial-induced dental caries. MS TC-PCT provided thorough information about optimal lesion contrast and type of dental defects such as caries in teeth. The experimental results were validated using micro-computed tomography (µCT) including quantitative lesion depth profiles at wavelengths in the 675-700 nm range. MS TC-PCT gives rise to hard-tissue biomedical diagnostic applications such as bone and dental imaging.

Increasing illness severity is associated with global myocardial dysfunction in the first 24 hours of sepsis admission.

BACKGROUND: Septic cardiomyopathy was recognized more than 30 years ago, but the early phase remains uncharacterized as no existing studies captured patients at the time of Emergency Department (ED) presentation, prior to resuscitation. Therapeutic interventions alter cardiac function, thereby distorting the relationship with disease severity and outcomes. The goal of this study was to assess the impact of illness severity on cardiac function during the first 24 h of sepsis admission. METHODS: This was a pre-planned secondary analysis of a prospective observational study of adults presenting to the ED with suspected sepsis (treatment for infection plus either lactate > 2 mmol/liter or systolic blood pressure < 90 mm/Hg) who received < 1L IV fluid before enrollment. Patients had 3 echocardiograms performed (presentation, 3, and 24 h). The primary outcome was the effect of increasing sepsis illness severity, defined by ED Sequential Organ Failure Assessment (SOFA) score, on parameters of cardiac function, assessed using linear mixed-effects models. The secondary goal was to determine whether cardiac function differed between survivors and non-survivors, also using mixed-effects models. RESULTS: We enrolled 73 patients with a mean age of 60 (SD 16.1) years and in-hospital mortality of 23%. For the primary analysis, we found that increasing ED SOFA score was associated with worse cardiac function over the first 24 h across all assessed parameters of left-ventricular systolic and diastolic function as well as right-ventricular systolic function. While baseline strain and E/e' were better in survivors, in the mixed models analysis, the trajectory of Global Longitudinal Strain and septal E/e' over the first 24 h of illness differed between survivors and non-survivors, with improved function at 24 h in non-survivors. CONCLUSIONS: In the first study to capture patients prior to the initiation of resuscitation, we found a direct relationship between sepsis severity and global myocardial dysfunction. Future studies are needed to confirm these results, to identify myocardial depressants, and to investigate the link with adverse outcomes so that therapeutic interventions can be developed.

Three-dimensional thermophotonic image optimization modalities of truncated correlation photothermal coherence tomography.

Truncated correlation photothermal coherence tomography (TC-PCT) is a pulse-compression, matched-filter-based photothermal diffusion-wave imaging modality with a proven track record in non-destructive evaluation of biomedical, dental, art-object and industrial applications. This is a study of the effect thermal transient truncation plays in the TC-PCT algorithm. It introduces a new phase channel which was coined the name Linear Iso Phase (LIOP) and improves the conventional TC-PCT phase by redevising its matched-filter sampling scheme and removing the effect of circular aliasing artifacts introduced in the frequency-domain-transformed cross-correlation (CC) calculations. A previously introduced computationally simplified adaptation to TC-PCT based on conventional CC signal processing, named enhanced truncated correlation photothermal coherence tomography (eTC-PCT), which does not utilize thermal transient truncation is also investigated: The TC-PCT and eTC-PCT algorithms and the LIOP channel are used to produce three-dimensional reconstructions of a complex multi-layered marquetry art sample and a tooth with a bacterial-induced lesion.

Comparison of Long-Wave and Mid-Wave Infrared Imaging Modalities for Photothermal Coherence Tomography of Human Teeth.

The ability to detect dental caries at early stages lies at the heart of minimal intervention dentistry, enabling the curing or arresting of carious lesions before they advance to the cavity stage. Enhanced truncated-correlation photothermal coherence tomography (eTC-PCT) using mid-wave infrared (MWIR) cameras has recently been shown to offer tomographic visualization of early caries. The tomographic slicing ability of such systems, however, is believed to be limited by direct radiative thermal emission through the translucent dental enamel in the 3-5 µm MWIR spectral range. Such radiative emissions can dominate the delayed conductive thermal contributions needed for tomographic reconstruction of internal dental defects. It has been hypothesized that long-wave infrared (LWIR) eTC-PCT systems may offer better tomographic performance by taking advantage of the intrinsic attenuation of direct radiative emission by dental enamel in the LWIR spectral range, enabling more effective delayed conductive thermal contributions from subsurface caries. More than an order of magnitude lower cost of the system is another key attribute of LWIR eTC-PCT which can open the door for downstream translation of the technology to clinics. In this report, we offer a systematic comparison of the performance/effectiveness of caries detection with LWIR and MWIR eTC-PCT systems for detecting natural caries, bacterial caries, and artificially demineralized enamel surfaces. Our results suggest that the low-cost LWIR based eTC-PCT system provides 3D visualization and 2D slice-by-slice images of early caries and internal micro-cracks similar to those obtained from the more expensive MWIR-based eTC-PCT system, albeit with ∼1.3dB lower signal-to-noise ratio.

Right ventricular dysfunction in acute heart failure from emergency department to discharge: Predictors and clinical implications.

BACKGROUND: Among acute heart failure (AHF) inpatients, right ventricular dysfunction (RVD) predicts clinical outcomes independent of left ventricular (LV) dysfunction. Prior studies have not accounted for congestion severity, show conflicting findings on echocardiography (echo) timing, and excluded emergency department (ED) patients. We describe for the first time the epidemiology, predictors, and outcomes of RVD in AHF starting with earliest ED treatment. METHODS: Point-of-care echo and 10-point lung ultrasound (LUS) were obtained in 84 prospectively enrolled AHF patients at two EDs, ≤1 h after first intravenous diuresis, vasodilator, and/or positive pressure ventilation (PPV). Echo and LUS were repeated at 24, 72, and 168 h, unless discharged sooner (n = 197 exams). RVD was defined as <17 mm tricuspid annulus plane systolic excursion (TAPSE), our primary measure. To identify correlates of RVD, a multivariable linear mixed model (LMM) of TAPSE through time was fit. Possible predictors were specified a priori and/or with p ≤ 0.1 difference between patients with/without RVD. Data were standardized and centered to facilitate comparison of relative strength of association between predictors of TAPSE. Survival curves for a 30-day death or AHF readmission primary outcome were assessed for RVD, LUS severity, and LVEF. A multivariable generalized linear mixed model (GLMM) for the outcome was used to adjust RVD for LVEF and LUS. RESULTS: 46% (n = 39) of patients at ED arrival showed RVD by TAPSE (median 18 mm, interquartile range 13-23). 18 variables with p ≤ 0.1 unadjusted difference with/without RVD, and 12 a priori predictors of RVD were included in the multivariable LMM model of TAPSE through time (R2 = 0.76). Missed antihypertensive medication (within 7 days), ED PPV, chronic obstructive pulmonary disease history, LVEF, LUS congestion severity, and right ventricular systolic pressure (RVSP) were the strongest multivariable predictors of RVD, respectively, and the only to reach statistical significance (p < 0.05). 30-day death or AHF readmission was associated with RVD at ED arrival (hazard ratio {HR} 3.31 {95%CI: 1.28-8.53}, p = 0.009), ED to discharge decrease in LUS (HR 0.11 {0.01-0.85}, p < 0.0001 for top quartile Δ), but not LVEF (quartile 2 vs. 1 HR 0.78 {0.22-2.68}, 3 vs. 1 HR 0.55 {0.16-1.92}, 4 vs. 1 HR 0.32 {0.09-1.22}, p = 0.30). The area under the receiver operating curve on GLMM for the primary outcome by TAPSE (p = 0.0012), ΔLUS (p = 0.0005), and LVEF (p = 0.8347) was 0.807. CONCLUSION: In this observational study, RVD was common in AHF, and predicted by congestion on LUS, LVEF, RVSP, and comorbidities from ED arrival through discharge. 30-day death or AHF-rehospitalization was associated with RVD at ED arrival and ΔLUS severity, but not LVEF.

Multi-institutional intervention to improve patient perception of physician empathy in emergency care.

BACKGROUND: Physician empathy has been linked to increased patient satisfaction, improved patient outcomes and reduced provider burnout. Our objective was to test the effectiveness of an educational intervention to improve physician empathy and trust in the ED setting. METHODS: Physician participants from six emergency medicine residencies in the US were studied from 2018 to 2019 using a pre-post, quasi-experimental non-equivalent control group design with randomisation at the site level. Intervention participants at three hospitals received an educational intervention, guided by acognitivemap (the 'empathy circle'). This intervention was further emphasised by the use of motivational texts delivered to participants throughout the course of the study. The primary outcome was change in E patient perception of resident empathy (Jefferson scale of patient perception of physician empathy (JSPPPE) and Trust in Physicians Scale (Tips)) before (T1) and 3-6 months later (T2). RESULTS: Data were collected for 221 residents (postgraduate year 1-4.) In controls, the mean (SD) JSPPPE scores at T1 and T2 were 29 (3.8) and 29 (4.0), respectively (mean difference 0.8, 95% CI: -0.7 to 2.4, p=0.20, paired t-test). In the intervention group, the JSPPPE scores at T1 and T2 were 28 (4.4) and 30 (4.0), respectively (mean difference 1.4, 95% CI: 0.0 to 2.8, p=0.08). In controls, the TIPS at T1 was 65 (6.3) and T2 was 66 (5.8) (mean difference -0.1, 95% CI: -3.8 to 3.6, p=0.35). In the intervention group, the TIPS at T1 was 63 (6.9) and T2 was 66 (6.3) (mean difference 2.4, 95% CI: 0.2 to 4.5, p=0.007). Hierarchical regression revealed no effect of time×group interaction for JSPPPE (p=0.71) nor TIPS (p=0.16). CONCLUSION: An educational intervention with the addition of text reminders designed to increase empathic behaviour was not associated with a change in patient-perceived empathy, but was associated with a modest improvement in trust in physicians.

Do septic patients with reduced left ventricular ejection fraction require a low-volume resuscitative strategy?

BACKGROUND: Many clinicians are wary of administering 30 cc/kg of intravenous fluid (IVF) to septic patients with reduced left-ventricular ejection fraction (rLVEF), fearing volume overload. Prior studies have used history of heart failure, rather than LVEF measured at presentation, thereby potentially distorting the relationship between rLVEF, IVF, and adverse outcomes. Our goal was to assess the relationship between IVF volume and outcomes in patients with, versus without, rLVEF. METHODS: This was a prospective observational study performed at an urban Emergency Department (ED). Included patients were adults with suspected sepsis, defined as being treated for infection plus either systolic blood pressure <90 mm/Hg or lactate >2 mmol/L. All patients had LVEF assessed by ED echocardiogram, prior to receipt of >1 l IVF. MEASUREMENTS AND MAIN RESULTS: We enrolled 73 patients, of whom 33 had rLVEF, defined as <40%. Patients with rLVEF were older, had greater initial lactate, more ICU admission, and more vasopressor use. IVF volume was similar between LVEF groups at 3-h (2.2 (IQR 0.8) vs 2.0 (IQR 2.4) liters) while patients with rLVEF were more likely to achieve 30 cc/kg (61% (CI 44-75) vs 45% (CI 31-60). In the reduced versus not-reduced LVEF groups, hospital days, ICU days, and ventilator days were similar: 8 (IQR 7) vs 6.5 (8.5) days, 7 (IQR 7) vs 5 (4) days, and 4 (IQR 8) vs. 5 (10) days, respectively. CONCLUSIONS: Septic patients with rLVEF at presentation received similar volume of IVF as those without rLVEF, without an increase in adverse outcomes attributable to volume overload. While validation is needed, our results suggest that limiting IVF administration in the setting of rLVEF is not necessary.

Defining Acute Traumatic Encephalopathy: Methods of the "HEAD Injury Serum Markers and Multi-Modalities for Assessing Response to Trauma" (HeadSMART II) Study.

Despite an estimated 2.8 million annual ED visits, traumatic brain injury (TBI) is a syndromic diagnosis largely based on report of loss of consciousness, post-traumatic amnesia, and/or confusion, without readily available objective diagnostic tests at the time of presentation, nor an ability to identify a patient's prognosis at the time of injury. The recognition that "mild" forms of TBI and even sub-clinical impacts can result in persistent neuropsychiatric consequences, particularly when repetitive, highlights the need for objective assessments that can complement the clinical diagnosis and provide prognostic information about long-term outcomes. Biomarkers and neurocognitive testing can identify brain injured patients and those likely to have post-concussive symptoms, regardless of imaging testing results, thus providing a physiologic basis for a diagnosis of acute traumatic encephalopathy (ATE). The goal of the HeadSMART II (HEAD injury Serum markers and Multi-modalities for Assessing Response to Trauma) clinical study is to develop an in-vitro diagnostic test for ATE. The BRAINBox TBI Test will be developed in the current clinical study to serve as an aid in evaluation of patients with ATE by incorporating blood protein biomarkers, clinical assessments, and tools to measure, identify, and define associated pathologic evidence and neurocognitive impairments. This protocol proposes to collect data on TBI subjects by a multi-modality approach that includes serum biomarkers, clinical assessments, neurocognitive performance, and neuropsychological characteristics, to determine the accuracy of the BRAINBox TBI test as an aid to the diagnosis of ATE, defined herein, and to objectively determine a patient's risk of developing post-concussive symptoms.

Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury.

OBJECTIVE: The objective was to determine the accuracy of a new, rapid blood test combining measurements of both glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) for predicting acute traumatic intracranial injury (TII) on head CT scan after mild traumatic brain injury (mTBI). METHODS: Analysis of banked venous plasma samples from subjects completing the Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) trial, enrolled 2012-2014 at 22 investigational sites in the United States and Europe. All subjects were ≥18 years old, presented to an emergency department (ED) with a nonpenetrating head injury and Glasgow Coma Scale score (GCS) 9-15 (mild to moderate TBI), underwent head CT scanning as part of their clinical care, and had blood sampling within 12 h of injury. Plasma concentrations of GFAP and UCH-L1 were measured using i-STAT Alinity and TBI plasma cartridge and compared to acute TII on head CT scan. RESULTS: Of the 2011 subjects enrolled in ALERT-TBI, 1918 had valid CT scans and plasma specimens for testing and 1901 (99.1%) had GCS 13-15 (mTBI), for which the rapid test was intended. Among these subjects, the rapid test had a sensitivity of 0.958 (95% confidence interval [CI] = 0.906 to 0.982), specificity of 0.404 (95% CI = 0.382 to 0.427), negative predictive value of 0.993 (95% CI = 0.985 to 0.997), and positive predictive value of 0.098 (95% CI = 0.082 to 0.116) for acute TII. CONCLUSIONS: A rapid i-STAT-based test had high sensitivity for prediction of acute TII, comparable to lab-based platforms. The speed, portability, and high accuracy of this test may facilitate clinical adoption of brain biomarker testing as an aid to head CT decision making in EDs.

Long-Acting Reversible Contraception: Placement, Continuation, and Removal Rates at an Inner-City Academic Medical Center Clinic.

Long-Acting Reversible Contraception (LARCs) has the potential to decrease unintended pregnancies but only if women can easily access a requested method. Retrospective electronic chart review identified women desiring LARC placement over a one-year period ending 31 December 2016. Most of the 311 insertions were for family planning, with 220 new insertions and 60 replacements. Delays occurred in 38% (n = 118) of patients, averaged 5 ± 5 weeks, and 47% received interval contraception. Reasons included absence of qualified provider (n = 44, 37%), pending cultures (n = 31, 26%), and Mirena availability. Teenage LARC use favored Nexplanon whereas older women preferred Mirena (p < 0.01). Of the 11% choosing early LARC removal, a significant number were African Americans (p = 0.040) or teenagers (p = 0.048). Retention time varied by device type; most patients switched to other contraceptives. No patients experienced IUD expulsion. Understanding barriers, attempting to remedy them, and addressing the side effects associated with LARC use is of importance in this inner-city patient population in the United States.

Molecular mechanisms regulating lysophosphatidylcholine acyltransferase 1 (LPCAT1) in human pregnancy.

INTRODUCTION: Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) is necessary for surfactant production in fetal lungs. Mechanisms responsible for its regulation during gestation remain to be elucidated. Our goal is to evaluate molecular mechanisms regulating LPCAT1 expression during gestation and after glucocorticoid administration. METHODS: Placentas throughout gestation were assayed for LPCAT1 protein levels. A placental cell line, HTR-8/SVneo (HTR), was used as a model to test the effects of placental oxygen tension found during pregnancy as well as the effects of dexamethasone used therapeutically in the clinic. RESULTS: LPCAT1 protein levels are maximal in late third trimester placental samples and are expressed strongly on the basal plate. LPCAT1 was maximally upregulated at 4% O2 (P < 0.01), corresponding to oxygen tension found in placenta at term. Mitochondrial nuclear retrograde regulator 1 (MNRR1), a bi-organellar (mitochondria and nucleus) regulator, transcriptionally activates LPCAT1. Antenatal corticosteroids (ACS) upregulate LPCAT1, at least in part, by an MNRR1-dependent pathway. HTR cells treated with 25 nM dexamethasone for 24 h exhibited a 2-fold increase in LPCAT1 levels compared to controls. In MNRR1 knockout cells, the response to ACS is significantly blunted. DISCUSSION: LPCAT1 appears to be induced by MNRR1. Hypoxia and corticosteroids increase LPCAT1 expression through an MNRR1 dependent pathway. LPCAT1 protein levels can be measured in maternal plasma and rise throughout gestation and in response to ACS.