Mortality in hypotensive combat casualties who require emergent laparotomy in the forward deployed environment.

INTRODUCTION: Mortality rates among hypotensive civilian patients requiring emergent laparotomy exceed 40%. Damage control (DCR) principles were incorporated into the military's Clinical Practice Guidelines (CPG) in 2008. We examined combat casualties requiring emergent laparotomy to characterize how mortality rates compare to hypotensive civilian trauma patients. METHODS: The DoD Trauma Registry (2004-2020) was queried for adults who underwent combat laparotomy. Patients who were hypotensive were compared to normotensive patients. Mortality was the outcome of interest. Mortality rates before (2004-2007) and after (2009-2020) DCR CPG implementation were analyzed. RESULTS: 1051 patients were studied. Overall mortality was 6.5% for normotensive casualties and 28.7% for hypotensive casualties. Mortality decreased in normotensive patients but remained unchanged in hypotensive patients following the implementation of the DCR CPG. CONCLUSION: Hypotensive combat casualties undergoing emergent laparotomy demonstrated a mortality rate of 29.5%. Despite many advances, mortality rates remain high in hypotensive patients requiring emergent laparotomy.

Predicting postoperative systolic dysfunction in mitral regurgitation: CT vs. echocardiography.

Introduction: Volume overload from mitral regurgitation can result in left ventricular systolic dysfunction. To prevent this, it is essential to operate before irreversible dysfunction occurs, but the optimal timing of intervention remains unclear. Current echocardiographic guidelines are based on 2D linear measurement thresholds only. We compared volumetric CT-based and 2D echocardiographic indices of LV size and function as predictors of post-operative systolic dysfunction following mitral repair. Methods: We retrospectively identified patients with primary mitral valve regurgitation who underwent repair between 2005 and 2021. Several indices of LV size and function measured on preoperative cardiac CT were compared with 2D echocardiography in predicting post-operative LV systolic dysfunction (LVEFecho <50%). Area under the curve (AUC) was the primary metric of predictive performance. Results: A total of 243 patients were included (mean age 57 ± 12 years; 65 females). The most effective CT-based predictors of post-operative LV systolic dysfunction were ejection fraction [LVEFCT; AUC 0.84 (95% CI: 0.77-0.92)] and LV end systolic volume indexed to body surface area [LVESViCT; AUC 0.88 (0.82-0.95)]. The best echocardiographic predictors were LVEFecho [AUC 0.70 (0.58-0.82)] and LVESDecho [AUC 0.79 (0.70-0.89)]. LVEFCT was a significantly better predictor of post-operative LV systolic dysfunction than LVEFecho (p = 0.02) and LVESViCT was a significantly better predictor than LVESDecho (p = 0.03). Ejection fraction measured by CT demonstrated significantly greater reproducibility than echocardiography. Discussion: CT-based volumetric measurements may be superior to established 2D echocardiographic parameters for predicting LV systolic dysfunction following mitral valve repair. Validation with prospective study is warranted.

Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study.

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.

The use of mobile thermal imaging and machine learning technology for the detection of early surgical site infections.

BACKGROUND: Surgical Site Infections (SSI) yield subtle, early signs that are not readily identifiable. This study sought to develop a machine learning algorithm that could identify early SSIs based on thermal images. METHODS: Images were taken of surgical incisions on 193 patients who underwent a variety of surgical procedures. Two neural network models were generated to detect SSIs, one using RGB images, and one incorporating thermal images. Accuracy and Jaccard Index were the primary metrics by which models were evaluated. RESULTS: Only 5 patients in our cohort developed SSIs (2.8%). Models were instead generated to demarcate the wound site. The models had 89-92% accuracy in predicting pixel class. The Jaccard indices for the RGB and RGB â€‹+ â€‹Thermal models were 66% and 64%, respectively. CONCLUSIONS: Although the low infection rate precluded the ability of our models to identify surgical site infections, we were able to generate two models to successfully segment wounds. This proof-of-concept study demonstrates that computer vision has the potential to support future surgical applications.

I saw the "atoll sign" - and now I need a tropical vacation.

The atoll sign describes ring-shaped opacities surrounding central ground glass attenuation seen on chest CT and was first associated with organizing pneumonia. The name is derived from the Maldives' language, denoting a ring or crescentic-shaped coral reef island surrounding a central lagoon. Although biopsy is usually required for diagnosis, understanding some of the more common pathologies associated with the atoll sign may help narrow a differential and guide management.

Engineering Human Cells Expressing CRISPR/Cas9-Synergistic Activation Mediators for Recombinant Protein Production.

Recombinant engineering for protein production commonly employs plasmid-based gene templates for introduction and expression of genes in a candidate cell system in vitro. Challenges to this approach include identifying cell types that can facilitate proper post-translational modifications and difficulty expressing large multimeric proteins. We hypothesized that integration of the CRISPR/Cas9-synergistic activator mediator (SAM) system into the human genome would be a powerful tool capable of robust gene expression and protein production. SAMs are comprised of a "dead" Cas9 (dCas9) linked to transcriptional activators viral particle 64 (VP64), nuclear factor-kappa-B p65 subunit (p65), and heat shock factor 1 (HSF1) and are programmable to single or multiple gene targets. We integrated the components of the SAM system into human HEK293, HKB11, SK-HEP1, and HEP-g2 cells using coagulation factor X (FX) and fibrinogen (FBN) as proof of concept. We observed upregulation of mRNA in each cell type with concomitant protein expression. Our findings demonstrate the capability of human cells stably expressing SAM for user-defined singleplex and multiplex gene targeting and highlight their broad potential utility for recombinant engineering as well as transcriptional modulation across networks for basic, translational, and clinical modeling and applications.

Clinical and health care resource use burden of hospitalizations for oral factor Xa inhibitor-associated major bleeding: A real-world analysis of Medicare beneficiaries.

Objective: To characterize the burden of illness associated with oral factor Xa (FXa) inhibitor-related bleeding in the US Medicare population. Methods: This retrospective cohort study used the full 20% Medicare random sample claims database to identify patients who experienced their first hospitalization for an FXa inhibitor-related major bleed between October 2013 and September 2017. Bleeding types were classified as intracranial hemorrhage (ICH), gastrointestinal (GI), and other. Associations between risk factors and outcomes (in-hospital and 30-day mortality, 30-day readmission, and discharge to a location other than home) adjusted for patient demographic characteristics, baseline clinical conditions, index event characteristics, treatment with hemostatic/factor replacement agents or transfusion (ie, usual care prereversal agent availability), multicompartment ICH and neurosurgical procedures (ICH cohort), and endoscopy (GI cohort) were assessed using multivariable regression and reported as crude incidences and adjusted odds ratios (ORs) stratified by bleed type. Results: Of the 11,593 patients identified, 2737 (23.6%) had ICH, 8169 (70.5%) had GI bleeds, and 687 (5.9%) had other bleeds. The incidences of in-hospital mortality, 30-day mortality, need for postdischarge out-of-home care, and 30-day readmission were 15.7%, 29.1%, 78.3%, and 20.3% in the single-compartment ICH cohort, respectively; and 1.7%, 6.8%, 41.3%, and 18.8% in the GI bleeds cohort, respectively. Increased odds of both in-hospital mortality and 30-day mortality were significantly associated with: multicompartment ICH (reference, single compartment ICH; OR = 3.35 [95% confidence interval (CI): 2.41-4.66]; 2.18 [95% CI: 1.63-2.91]), loss of consciousness during index hospitalization (yes vs no; OR = 2.03 [95% CI: 1.38-2.97]; 1.49 [95% CI: 1.11-2.02]), receiving usual care (yes vs no; OR = 1.55 [95% CI: 1.22-1.98]; 1.33 [95% CI: 1.09-1.63]) during index hospitalization, and increasing number of Elixhauser comorbidities at baseline (OR = 1.07 [95% CI: 1.03-1.10]; 1.09 [95% CI: 1.06-1.12]) in the ICH cohort; intensive care unit admission (yes vs no; OR = 1.88 [95% CI: 1.32-2.67]; 1.51 [95% CI: 1.26-1.81]), increasing number of Elixhauser comorbidities at baseline (OR = 1.12 [95% CI: 1.07-1.18]; 1.15 [1.12-1.18]), and increasing age on index date (OR = 1.04 [95% CI: 1.02-1.07]; 1.05 [95% CI: 1.04-1.07]) in the GI bleeds cohort. Conclusions: In this large sample of Medicare patients, FXa inhibitor-related major bleeding was associated with substantial burden in terms of adverse clinical outcomes and health care resource use. Incidence of ICH was lower than GI bleeds; however, burden of illness was notably higher with ICH.

Airborne! UAV delivery of blood products and medical logistics for combat zones.

BACKGROUND: Innovative solutions to resupply critical medical logistics and blood products may be required in future near-peer conflicts. Unmanned aerial vehicles (UAVs) are increasingly being used in austere environments and may be a viable platform for medical resupply and the transport of blood products. METHODS: A literature review on PubMed and Google Scholar up to March of 2022 yielded a total of 27 articles that were included in this narrative review. The objectives of this article are to discuss the current limitations of prehospital blood transfusion in military settings, discuss the current uses of UAVs for medical logistics, and highlight the ongoing research surrounding UAVs for blood product delivery. DISCUSSION: UAVs allow for the timely delivery of medical supplies in numerous settings and have been utilized for both military and civilian purposes. Investigations into the effects of aeromedical transportation on blood products have found minimal blood product degradation when appropriately thermoregulated and delivered in a manner that minimizes trauma. UAV delivery of blood products is now actively being explored by numerous entities around the globe. Current limitations surrounding the lack of high-quality safety data, engineering constraints over carrying capacity, storage capability, and distance traveled, as well as air space regulations persist. CONCLUSION: UAVs may offer a novel solution for the transport of medical supplies and blood products in a safe and timely manner for the forward-deployed setting. Further research on optimal UAV design, optimal delivery techniques, and blood product safety following transport should be explored prior to implementation.

Investigations of the Cobalt Hexamine Uranyl Carbonate System: Understanding the Influence of Charge and Hydrogen Bonding on the Modification of Vibrational Modes in Uranyl Compounds.

Hydrogen bonding networks within hexavalent uranium materials are complex and may influence the overall physical and chemical properties of the system. This is particularly true if hydrogen bonding takes places between the donor and the oxo group associated with the uranyl cation (UO22+). In the current study, we evaluate the impact of charge-assisted hydrogen bonding on the vibrational modes of the uranyl cation using uranyl tricarbonate [UO2(CO3)3]4- interactions with [Co(NH3)6]3+ as the model system. Herein, we report the synthesis and structural characterization of five novel compounds, [Co(NH3)6]Cl(CO3) (Co_Cl_CO3), [Co(NH3)6]4[UO2(CO3)3]3(H2O)11.67 (Co4U3), [Co(NH3)6]3[UO2(CO3)3]2Cl (H2O)7.5 (Co3U2_Cl), [Co(NH3)6]2[UO2(CO3)3]Cl2 (Co2U_Cl), and [Co(NH3)6]2[UO2(CO3)3]CO3 (Co2U_CO3), which contain differences in the crystalline packing and extended hydrogen bonding networks. We show that these slight changes in the supramolecular assembly and hydrogen bonding networks result in the modification of modes as observed by infrared and Raman spectroscopy. We use density functional theory calculations to assign the vibrational modes and provide an understanding about how uranyl bond perturbation and changes in hydrogen bonding interactions can impact the resulting spectroscopic signals.

Quantitative CT and machine learning classification of fibrotic interstitial lung diseases.

OBJECTIVES: To evaluate quantitative computed tomography (QCT) features and QCT feature-based machine learning (ML) models in classifying interstitial lung diseases (ILDs). To compare QCT-ML and deep learning (DL) models' performance. METHODS: We retrospectively identified 1085 patients with pathologically proven usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonitis (NSIP), and chronic hypersensitivity pneumonitis (CHP) who underwent peri-biopsy chest CT. Kruskal-Wallis test evaluated QCT feature associations with each ILD. QCT features, patient demographics, and pulmonary function test (PFT) results trained eXtreme Gradient Boosting (training/validation set n = 911) yielding 3 models: M1 = QCT features only; M2 = M1 plus age and sex; M3 = M2 plus PFT results. A DL model was also developed. ML and DL model areas under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were compared for multiclass (UIP vs. NSIP vs. CHP) and binary (UIP vs. non-UIP) classification performances. RESULTS: The majority (69/78 [88%]) of QCT features successfully differentiated the 3 ILDs (adjusted p ≤ 0.05). All QCT-ML models achieved higher AUC than the DL model (multiclass AUC micro-averages 0.910, 0.910, 0.925, and 0.798 and macro-averages 0.895, 0.893, 0.925, and 0.779 for M1, M2, M3, and DL respectively; binary AUC 0.880, 0.899, 0.898, and 0.869 for M1, M2, M3, and DL respectively). M3 demonstrated statistically significant better performance compared to M2 (∆AUC: 0.015, CI: [0.002, 0.029]) for multiclass prediction. CONCLUSIONS: QCT features successfully differentiated pathologically proven UIP, NSIP, and CHP. While QCT-based ML models outperformed a DL model for classifying ILDs, further investigations are warranted to determine if QCT-ML, DL, or a combination will be superior in ILD classification. KEY POINTS: • Quantitative CT features successfully differentiated pathologically proven UIP, NSIP, and CHP. • Our quantitative CT-based machine learning models demonstrated high performance in classifying UIP, NSIP, and CHP histopathology, outperforming a deep learning model. • While our quantitative CT-based machine learning models performed better than a DL model, additional investigations are needed to determine whether either or a combination of both approaches delivers superior diagnostic performance.

Predicting Usual Interstitial Pneumonia Histopathology From Chest CT Imaging With Deep Learning.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal form of interstitial lung disease (ILD) characterized by the absence of a known cause and usual interstitial pneumonitis (UIP) pattern on chest CT imaging and/or histopathology. Distinguishing UIP/IPF from other ILD subtypes is essential given different treatments and prognosis. Lung biopsy is necessary when noninvasive data are insufficient to render a confident diagnosis. RESEARCH QUESTION: Can we improve noninvasive diagnosis of UIP be improved by predicting ILD histopathology from CT scans by using deep learning? STUDY DESIGN AND METHODS: This study retrospectively identified a cohort of 1,239 patients in a multicenter database with pathologically proven ILD who had chest CT imaging. Each case was assigned a label based on histopathologic diagnosis (UIP or non-UIP). A custom deep learning model was trained to predict class labels from CT images (training set, n = 894) and was evaluated on a 198-patient test set. Separately, two subspecialty-trained radiologists manually labeled each CT scan in the test set according to the 2018 American Thoracic Society IPF guidelines. The performance of the model in predicting histopathologic class was compared against radiologists' performance by using area under the receiver-operating characteristic curve as the primary metric. Deep learning model reproducibility was compared against intra-rater and inter-rater radiologist reproducibility. RESULTS: For the entire cohort, mean patient age was 62 ± 12 years, and 605 patients were female (49%). Deep learning performance was superior to visual analysis in predicting histopathologic diagnosis (area under the receiver-operating characteristic curve, 0.87 vs 0.80, respectively; P < .05). Deep learning model reproducibility was significantly greater than radiologist inter-rater and intra-rater reproducibility (95% CI for difference in Krippendorff's alpha did not include zero). INTERPRETATION: Deep learning may be superior to visual assessment in predicting UIP/IPF histopathology from CT imaging and may serve as an alternative to invasive lung biopsy.

Use of vibrational spectroscopy to identify the formation of neptunyl-neptunyl interactions: a paired density functional theory and Raman spectroscopy study.

Actinyl-Actinyl interactions (AAIs) occur in pentavalent actinide systems, particularly for neptunium (Np), and lead to complex vibrational signals that are challenging to analyze and interpret. Previous studies have focused on neptunyl-neptunyl dimeric species, but trimers and tetramers have been identified as the primary motif for extended topologies observed in solid-state materials. Our hypothesis is that trimeric and tetrameric AAIs lead to the additional signals in the vibrational spectra, but this has yet to be explored systematically. Herein, we investigate three different neptunyl-neptunyl subunits (dimeric, trimeric, tetrameric) and determine the vibrational frequencies of the ONpO stretches using both computational and experimental approaches. Density Functional Theory (DFT) was used to identify distinct vibrational motions related to specific neptunyl oligomers and compared to previous literature precedent from Np(V) in HClO4 and HCl systems. The vibrational behavior of Np(V) in HNO3 was then evaluated via Raman spectroscopy. As the solution evaporated signals were linked to trimeric and tetrameric models. Solid phases produced in the evaporation include (NpO2)2(NO3)2(H2O)5 and newly identified crystalline phase, Na(NpO2)(NO3)2·4H2O (NpNa). The combined computational studies and vibrational analysis provide evidence for unique observable vibrational bands for each polymerized subunit, allowing us to assign spectral features to trimeric and tetrameric models within three different simple anionic systems.

Utility of COVID-19 antigen testing in the emergency department.

BACKGROUND: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis. METHODS: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of care platform by emergency department staff. RESULTS: From July 20 to October 28, 2020, 767 patients were enrolled, of which 735 had evaluable samples. Their mean (SD) age was 46.8 (16.6) years, and 422 (57.4%) were women. A total of 623 (84.8%) patients had COVID-19 symptoms, most commonly shortness of breath (n = 404; 55.0%), cough (n = 314; 42.7%), and fever (n = 253; 34.4%). Although 460 (62.6%) had symptoms ≤7 days, the mean (SD) time since symptom onset was 8.1 (14.0) days. Positive tests occurred in 173 (23.5%) and 141 (19.2%) with the gold standard versus BinaxNOW test, respectively. Those with symptoms >2 weeks had a positive test rate roughly half of those with earlier presentations. In patients with symptoms ≤7 days, the sensitivity, specificity, and negative and positive predictive values for the BinaxNOW test were 84.6%, 98.5%, 94.9%, and 95.2%, respectively. CONCLUSIONS: The BinaxNOW point-of-care test has good sensitivity and excellent specificity for the detection of COVID-19. We recommend using the BinasNOW for patients with symptoms up to 2 weeks.

Postnatal development alters functional compartmentalization of myosin light chain kinase in ovine carotid arteries.

The rate-limiting enzyme for vascular contraction, myosin light chain kinase (MLCK), phosphorylates regulatory myosin light chain (MLC20) at rates that appear faster despite lower MLCK abundance in fetal compared with adult arteries. This study explores the hypothesis that greater apparent tissue activity of MLCK in fetal arteries is due to age-dependent differences in intracellular distribution of MLCK in relation to MLC20. Under optimal conditions, common carotid artery homogenates from nonpregnant adult female sheep and near-term fetuses exhibited similar values of Vmax and Km for MLCK. A custom-designed, computer-controlled apparatus enabled electrical stimulation and high-speed freezing of arterial segments at exactly 0, 1, 2, and 3 s, calculation of in situ rates of MLC20 phosphorylation, and measurement of time-dependent colocalization between MLCK and MLC20. The in situ rate of MLC20 phosphorylation divided by total MLCK abundance averaged to values 147% greater in fetal (1.06 ± 0.28) than adult (0.43 ± 0.08) arteries, which corresponded, respectively, to 43 ± 10% and 31 ± 3% of the Vmax values measured in homogenates. Confocal colocalization analysis revealed in fetal and adult arteries that 33 ± 6% and 20 ± 5% of total MLCK colocalized with pMLC20, and that MLCK activation was greater in periluminal than periadventitial regions over the time course of electrical stimulation in both age groups. Together, these results demonstrate that the catalytic activity of MLCK is similar in fetal and adult arteries, but that the fraction of total MLCK in the functional compartment involved in contraction is significantly greater in fetal than adult arteries.

Acute appendiceal diverticulitis: a case report.

Acute appendiceal diverticulitis is a difficult prospective diagnosis due to both its rarity and clinical overlap with other ileocecal diseases, such as acute appendicitis. Few preoperative radiological images of acute appendiceal diverticulitis have been presented in the literature. We report a case of acute appendiceal diverticulitis initially diagnosed with outpatient ultrasound and confirmed with contrast-enhanced computed tomography in an 85-year-old male who presented with right lower quadrant pain. Appendiceal diverticulitis is an often overlooked diagnosis, and given its association with appendiceal neoplasms and relatively high rate of perforation, it is important to consider this entity in patients with right lower quadrant pain in order to ensure that they are managed appropriately. The addition of high quality ultrasound and computed tomography (CT) images to the literature may heighten awareness of this rare condition and facilitate accurate preoperative diagnosis and management in these patients.

Hypoxic modulation of fetal vascular MLCK abundance, localization, and function.

Changes in vascular contractility are among the most important physiological effects of acute and chronic fetal hypoxia. Given the essential role of myosin light-chain kinase (MLCK) in smooth muscle contractility and its heterogeneous distribution, this study explores the hypothesis that subcellular changes in MLCK distribution contribute to hypoxic modulation of fetal carotid artery contractility. Relative to common carotid arteries from normoxic term fetal lambs (FN), carotids from fetal lambs gestated at high altitude (3,802 m) (FH) exhibited depressed contractility without changes in MLCK mRNA or protein abundance. Patterns of confocal colocalization of MLCK with α-actin and 20-kDa regulatory myosin light chain (MLC20) enabled calculation of subcellular MLCK fractions: 1) colocalized with the contractile apparatus, 2) colocalized with α-actin distant from the contractile apparatus, and 3) not colocalized with α-actin. Chronic hypoxia did not affect MLCK abundance in the contractile fraction, despite a concurrent decrease in contractility. Organ culture for 72 h under 1% O2 decreased total MLCK abundance in FN and FH carotid arteries, but decreased the contractile MLCK abundance only in FH carotid arteries. Correspondingly, culture under 1% O2 depressed contractility more in FH than FN carotid arteries. In addition, hypoxia appeared to attenuate ubiquitin-independent proteasomal degradation of MLCK, as reported for other proteins. In aggregate, these results demonstrate that the combination of chronic hypoxia followed by hypoxic culture can induce MLCK translocation among at least three subcellular fractions with possible influences on contractility, indicating that changes in MLCK distribution are a significant component of fetal vascular responses to hypoxia.

Impacts of hydrogen bonding interactions with Np(v/vi)O2Cl4 complexes: vibrational spectroscopy, redox behavior, and computational analysis.

The neptunyl (Np(v)O2+/Np(vi)O22+) cation is the dominant form of 237Np in acidic aqueous solutions and the stability of the Np(v) and Np(vi) species is driven by the specific chemical constituents present in the system. Hydrogen bonding with the oxo group may impact the stability of these species, but there is limited understanding of how these intermolecular interactions influence the behavior of both solution and solid-state species. In the current study, we systematically evaluate the interactions between the neptunyl tetrachloride species and hydrogen donors in coordination complexes and in the related aqueous solutions. Both Np(v) compounds (N2C4H12)2[Np(v)O2Cl4]Cl (Np(V)pipz) and (NOC4H10)3[Np(v)O2Cl4] (Np(V)morph) exhibit directional hydrogen bonding to the neptunyl oxo group while Np(vi) compounds (NC5H6)2[Np(vi)O2Cl4] (Np(VI)pyr) and (NOC4H10)4[Np(vi)O2Cl4]·2Cl (Np(VI)morph) assemble via halogen interactions. The Raman spectra of the solid-state phases indicate the activation of vibrational bands when there is asymmetry of the neptunyl bond, while these spectral features are not observed within the related solution phase spectra. Density functional theory calculations of the Np(V)pipz system suggest that activation of the ν3 asymmetric stretch and other combination modes lead to additional complexity within the solid-state spectra. Electrochemical analyses of complexes in the solution phases are consistent with the results of the crystallization experiments as the voltammetric potentials of Np(v)/Np(vi) complexes in the presence of protonated heterocycles differ from the potentials of pure Np(v) and may correlate with the hydrogen bonding interactions.

Exploring crown-ether functionalization on the stabilization of hexavalent neptunium.

Crown-ether molecules are used in radiochemical separations due to their high selectivity for a range of metal cations. Previous investigations regarding the interactions of 18-crown-6 (18C6) with 237Np suggested the formation of a Np(v) inclusion complex, but also reported rapid reduction of Np(vi) to Np(v) in the presence of the ether molecule. Herein, we investigate the impact of crown ether functionalization by exploring the Np(v) and Np(vi) dicyclohexano-18-crown-6 (DCH-18C6) systems. Two [X(DCH-18C6)]2[Np(vi)O2Cl4] compounds (X = K (1) and Na (2)) were crystallized and characterized by single crystal X-ray diffraction and Raman spectroscopy. Additional studies of Np(vi), Np(v), and Np(v)/Np(vi) in solution indicated redox stability in the presence of functionalized crowns and preferential crystallization of Np(vi) DCH-18C6 solids. These results indicate that functionalization of the crown can lead to higher resistance to radiolysis and increased stability of the Np(vi) oxidation state in solution.

A Guide to Competencies, Educational Goals, and Learning Objectives for Teaching Medical Histology in an Undergraduate Medical Education Setting.

Horizontal and vertical integration within medical school curricula, truncated contact hours available to teach basic biomedical sciences, and diverse assessment methods have left histology educators searching for an answer to a fundamental question-what ensures competency for medical students in histology upon completion of medical school? The Liaison Committee for Medical Education (LCME) and the Commission on Osteopathic College Accreditation (COCA) advocate faculty to provide medical students with a list of learning objectives prior to any educational activities, regardless of pedagogy. It is encouraged that the learning objectives are constructed using higher-order and measurable action verbs to ensure student-centered learning and assessment. A survey of the literature indicates that there is paucity of knowledge about competencies, goals, and learning objectives appropriate for histology education in preclinical years. To address this challenge, an interactive online taskforce, comprising faculty from across the United States, was assembled. The outcome of this project was a desired set of competencies for medical students in histology with educational goals and learning objectives to achieve them.