A parental communication assessment initiative in the paediatric cardiovascular ICU.

OBJECTIVE: Challenges to communication between families and care providers of paediatric patients in intensive care units (ICU) include variability of communication preferences, mismatched goals of care, and difficulties carrying forward family preferences from provider to provider. Our objectives were to develop and test an assessment tool that queries parents of children requiring cardiac intensive care about their communication preferences and to determine if this tool facilitates patient-centred care and improves families' ICU experience. DESIGN: In this quality improvement initiative, a novel tool was developed, the Parental Communication Assessment (PCA), which asked parents with children hospitalised in the cardiac ICU about their communication preferences. Participants were prospectively randomised to the intervention group, which received the PCA, or to standard care. All participants completed a follow-up survey evaluating satisfaction with communication. MAIN RESULTS: One hundred thirteen participants enrolled and 56 were randomised to the intervention group. Participants who received the PCA preferred detail-oriented communication over big picture. Most parents understood the daily discussions on rounds (64%) and felt comfortable expressing concerns (68%). Eighty-six percent reported the PCA was worthwhile. Parents were generally satisfied with communication. However, an important proportion felt unprepared for difficult decisions or setbacks, inadequately included or supported in decision-making, and that they lacked control over their child's care. There were no significant differences between the intervention and control groups in their communication satisfaction results. CONCLUSIONS: Parents with children hospitalised in the paediatric ICU demonstrated diverse communication preferences. Most participants felt overall satisfied with communication, but individualising communication with patients' families according to their preferences may improve their experience.

Cardiac Dysfunction Identified by Strain Echocardiography Is Associated With Illness Severity in Pediatric Sepsis.

OBJECTIVES: Sepsis-induced myocardial dysfunction has been associated with illness severity and mortality in pediatrics. Although early sepsis-induced myocardial dysfunction diagnosis could aid in hemodynamic management, current echocardiographic metrics for assessing biventricular function are limited in detecting early impairment. Strain echocardiography is a validated quantitative measure that can detect subtle perturbations in left ventricular and right ventricular function. This investigation evaluates the utility of strain echocardiography in pediatric sepsis and compares with to conventional methods. DESIGN: Retrospective, observational study comparing left ventricular and right ventricular strain. Strain was compared with ejection fraction and fractional shortening and established sepsis severity of illness markers. SETTING: Tertiary care medical-surgical PICU from July 2013 to January 2018. PATIENTS: Seventy-nine septic children and 28 healthy controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared with healthy controls, patients with severe sepsis demonstrated abnormal left ventricular strain (left ventricular longitudinal strain: -13.0% ± 0.72; p = 0.04 and left ventricular circumferential strain: -16.5% ± 0.99; p = 0.046) and right ventricular (right ventricular longitudinal strain = -14.3% ± 6.3; p < 0.01) despite normal fractional shortening (36.0% ± 1.6 vs 38.1% ± 1.1; p = 0.5129) and ejection fraction (60.7% ± 2.2 vs 65.3% ± 1.5; p = 0.33). There was significant association between depressed left ventricular longitudinal strain and increased Vasotrope-Inotrope Score (r = 0.52; p = 0.034). Worsening left ventricular circumferential strain was correlated with higher lactate (r = 0.31; p = 0.03) and higher Pediatric Risk of Mortality-III score (r = 0.39; p < 0.01). Depressed right ventricular longitudinal strain was associated with elevated pediatric multiple organ dysfunction score (r = 0.44; p < 0.01) CONCLUSIONS:: Compared with healthy children, pediatric septic patients demonstrated abnormal left ventricular and right ventricular strain concerning for early signs of cardiac dysfunction. This was despite having normal ejection fraction and fractional shortening. Abnormal strain was associated with abnormal severity of illness markers. Strain echocardiography may have utility as an early indicator of sepsis-induced myocardial dysfunction in pediatric sepsis.

Two-Dimensional Strain is more Precise than Conventional Measures of Left Ventricular Systolic Function in Pediatric Patients.

Ejection fraction (EF) and fractional shortening (FS) are standard methods of quantifying left ventricular (LV) systolic function. 2D global longitudinal strain (2D GLS) is a well-established, but underutilized method for LV function quantification. The aim of this study was to assess precision of GLS compared to EF & FS in pediatrics. Echocardiograms were prospectively analyzed by 2 blinded observers. FS, EF, and GLS were calculated following standard methods. Bland-Altman was applied to assess agreement. Intraclass correlation coefficient (ICC) was used to measure reliability. Coefficient of variation was used to demonstrate relative variability between methods. 103 pediatric echos were evaluated for inter-observer reproducibility, and 15 patients for intra-observer reproducibility. GLS had higher inter-observer agreement and reliability (bias 7%, 95% LOA - 3.4 to + 3.5, ICC 0.86 CI 0.80-0.90) compared to EF (bias 27%, 95% LOA - 18.9 to + 19.5; ICC 0.25 CI 0.07-0.43) and FS (bias 12%, 95% LOA - 11.9 to + 12.2; ICC 0.53 CI 0.38-0.66). GLS also had higher intra-observer agreement (bias 4%, 95% LOA - 3.6 to + 3.7; ICC 0.87 CI 0.66-0.96) compared to EF (bias 11%, 95% LOA - 14.9 to + 15.1; ICC 0.26 CI - 0.28-0.67) and FS (bias 12%, 95% LOA - 12.2 to + 12.5; ICC 0.38 CI - 0.15-0.74). GLS is a more precise method for quantifying LV function in pediatrics, with lower variability compared to EF and FS. GLS provides a more reliable evaluation of LV systolic function and should be utilized more widely in pediatrics.

Maturational patterns of left ventricular rotational mechanics in pre-term infants through 1 year of age.

BACKGROUND: Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures. METHODS: Pre-term infants (<29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus. RESULTS: Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p < 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p < 0.05). CONCLUSION: This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact rotational mechanics during the neonatal period, but the myocardium recovers by 1-year corrected age.

Persistence of right ventricular dysfunction and altered morphometry in asymptomatic preterm Infants through one year of age: Cardiac phenotype of prematurity.

INTRODUCTION: Prematurity impacts myocardial development and may determine long-term outcomes. The objective of this study was to test the hypothesis that preterm neonates develop right ventricle dysfunction and adaptive remodelling by 32 weeks post-menstrual age that persists through 1 year corrected age. MATERIALS AND METHODS: A subset of 80 preterm infants (born <29 weeks) was selected retrospectively from a prospectively enrolled cohort and measures of right ventricle systolic function and morphology by two-dimensional echocardiography were assessed at 32 weeks post-menstrual age and at 1 year of corrected age. Comparisons were made to 50 term infants at 1 month and 1 year of age. Sub-analyses were performed in preterm-born infants with bronchopulmonary dysplasia and/or pulmonary hypertension. RESULT: In both term and preterm infants, right ventricle function and morphology increased over the first year (p < 0.01). The magnitudes of right ventricle function measures were lower in preterm-born infants at each time period (p < 0.01 for all) and right ventricle morphology indices were wider in all preterm infants by 1 year corrected age, irrespective of lung disease. Measures of a) right ventricle function were further decreased and b) morphology increased through 1 year in preterm infants with bronchopulmonary dysplasia and/or pulmonary hypertension (p < 0.01). CONCLUSION: Preterm infants exhibit abnormal right ventricle performance with remodelling at 32 weeks post-menstrual age that persists through 1 year corrected age, suggesting a less developed intrinsic myocardial function response following preterm birth. The development of bronchopulmonary dysplasia and pulmonary hypertension leave a further negative impact on right ventricle mechanics over the first year of age.

Evidence of Echocardiographic Markers of Pulmonary Vascular Disease in Asymptomatic Infants Born Preterm at One Year of Age.

OBJECTIVE: To test the hypothesis that echocardiographic markers of pulmonary vascular disease (PVD) exist in asymptomatic infants born preterm at 1-year corrected age. STUDY DESIGN: We conducted a prospective cohort study of 80 infants born preterm (<29 weeks of gestation) and 100 age- and weight-matched infants born at term and compared broad-based conventional and quantitative echocardiographic measures of pulmonary hemodynamics at 1-year corrected age. Pulmonary artery acceleration time (PAAT), a validated index of pulmonary vascular resistance, arterial pressure, and compliance, was used to assess pulmonary hemodynamics. Lower PAAT is indicative of PVD. Subanalyses were performed in infants with bronchopulmonary dysplasia (BPD, n = 48, 59%) and/or late-onset pulmonary hypertension (n = 12, 15%). RESULTS: At 1 year, there were no differences between conventional measures of pulmonary hypertension in the infants born at term and preterm. All infants born preterm had significantly lower values of PAAT than infants born at term (73 ± 8 milliseconds vs 98 ± 5 milliseconds, P < .001). Infants born preterm with BPD had even lower PAAT than those without BPD (69 ± 5 milliseconds vs 79 ± 4 milliseconds, P < .01). The degree of PVD at 1-year corrected age was inversely related to gestation in all infants born preterm. Data analysis included adjustment for ventricular function and other confounding factors. CONCLUSIONS: In comparison with infants born at term, infants born preterm exhibit abnormal PAAT at 1-year corrected age irrespective of neonatal lung disease status, suggesting the existence of PVD beyond infancy. PAAT measurements offer a reliable, noninvasive tool for screening and longitudinal monitoring of pulmonary hemodynamics in infants.

Regulation of Mutagenic DNA Polymerase V Activation in Space and Time.

Spatial regulation is often encountered as a component of multi-tiered regulatory systems in eukaryotes, where processes are readily segregated by organelle boundaries. Well-characterized examples of spatial regulation are less common in bacteria. Low-fidelity DNA polymerase V (UmuD'2C) is produced in Escherichia coli as part of the bacterial SOS response to DNA damage. Due to the mutagenic potential of this enzyme, pol V activity is controlled by means of an elaborate regulatory system at transcriptional and posttranslational levels. Using single-molecule fluorescence microscopy to visualize UmuC inside living cells in space and time, we now show that pol V is also subject to a novel form of spatial regulation. After an initial delay (~ 45 min) post UV irradiation, UmuC is synthesized, but is not immediately activated. Instead, it is sequestered at the inner cell membrane. The release of UmuC into the cytosol requires the RecA* nucleoprotein filament-mediated cleavage of UmuD→UmuD'. Classic SOS damage response mutants either block [umuD(K97A)] or constitutively stimulate [recA(E38K)] UmuC release from the membrane. Foci of mutagenically active pol V Mut (UmuD'2C-RecA-ATP) formed in the cytosol after UV irradiation do not co-localize with pol III replisomes, suggesting a capacity to promote translesion DNA synthesis at lesions skipped over by DNA polymerase III. In effect, at least three molecular mechanisms limit the amount of time that pol V has to access DNA: (1) transcriptional and posttranslational regulation that initially keep the intracellular levels of pol V to a minimum; (2) spatial regulation via transient sequestration of UmuC at the membrane, which further delays pol V activation; and (3) the hydrolytic activity of a recently discovered pol V Mut ATPase function that limits active polymerase time on the chromosomal template.

Gia/Mthl5 is an aorta specific GPCR required for Drosophila heart tube morphology and normal pericardial cell positioning.

G-protein signaling is known to be required for cell-cell contacts during the development of the Drosophila dorsal vessel. However, the identity of the G protein-coupled receptor (GPCR) that regulates this signaling pathway activity is unknown. Here we describe the identification of a novel cardiac specific GPCR, called Gia, for "GPCR in aorta". Gia is the only heart-specific GPCR identified in Drosophila to date and it is specifically expressed in cardioblasts that fuse at the dorsal midline to become the aorta. Gia is the only Drosophila gene so far identified for which expression is entirely restricted to cells of the aorta. Deletion of Gia led to a broken-hearted phenotype, characterized by pericardial cells dissociated from cardioblasts and abnormal distribution of cell junction proteins. Both phenotypes were similar to those observed in mutants of the heterotrimeric cardiac G proteins. Lack of Gia also led to defects in the alignment and fusion of cardioblasts in the aorta. Gia forms a protein complex with G-αo47A, the alpha subunit of the heterotrimeric cardiac G proteins and interacts genetically with G-αo47A during cardiac morphogenesis. Our study identified Gia as an essential aorta-specific GPCR that functions upstream of cardiac heterotrimeric G proteins and is required for morphological integrity of the aorta during heart tube formation. These studies lead to a redefinition of the bro phenotype, to encompass morphological integrity of the heart tube as well as cardioblast-pericardial cell spatial interactions.

RecA acts as a switch to regulate polymerase occupancy in a moving replication fork.

This report discovers a role of Escherichia coli RecA, the cellular recombinase, in directing the action of several DNA polymerases at the replication fork. Bulk chromosome replication is performed by DNA polymerase (Pol) III. However, E. coli contains translesion synthesis (TLS) Pols II, IV, and V that also function with the helicase, primase, and sliding clamp in the replisome. Surprisingly, we find that RecA specifically activates replisomes that contain TLS Pols. In sharp contrast, RecA severely inhibits the Pol III replisome. Given the opposite effects of RecA on Pol III and TLS replisomes, we propose that RecA acts as a switch to regulate the occupancy of polymerases within a moving replisome.

Can we become better robot surgeons through simulator practice?

INTRODUCTION: There is significant growth in the use of the robotic surgery platform in the general surgery community. Current pre-requisites for robot surgery training include performing basic tasks on a simulator and achieving a minimum overall score for each task. However, there is limited information about these tasks related to performance and time required to become proficient. We focused on critical tasks that have the highest potential for preventing inadvertent injuries, and constructed models to predict how many attempts would be needed to master the tasks depending on the user's initial attempt. METHODS AND PROCEDURES: This study was conducted using de-identified data collected over 12 months from the dV-Trainers® simulator at our institution. We analyzed tasks used in institutional surgical robot credentialing that focused on camera manipulation and energy use. Data were extracted from the Camera Targeting, Energy Dissection, and Energy Switching exercises focusing on individual metrics such as Time to Complete Exercise, Economy of Motion, Misapplied Energy Time, and Blood Volume Loss. Mixed linear models looking at sequential attempts and specific performance metrics were constructed using IBM SPSS Statistics version 20. RESULTS: Over 26,000 overall minutes of recorded use was logged in our simulator by more than 30 unique users across all exercises. An average of 15 users performed each of the analyzed exercises, with an average of eight attempts per exercise. Based on our models, on average most users would need four to five attempts to achieve 80 % proficiency for any given metric. CONCLUSION: Virtual reality robotic simulators such as the dv-Trainer® can be used by general surgeons to become better robotic surgeons. Our data suggests that it can be used by a surgeon to predict how much time and effort one would need to spend on the simulator in order to become proficient with the robot, especially in critical metrics such as camera manipulation and energy application. Surgeons who require more attempts to successfully complete tasks may want to consider additional training methods, such as proctoring or hands-on laboratories, to improve robot surgery proficiency.

Correlations among MRI-based cervical and thoracic vertebral bone quality score, CT-based Hounsfield Unit score, and DEXA t-score in assessment of bone mineral density.

BACKGROUND: Further optimization of the validated vertebral bone quality (VBQ) score using magnetic resonance imaging (MRI) may expand its clinical utility for bone mineral density (BMD) assessment. This study evaluated the correlations among cervical and thoracic VBQ scores, the validated Hounsfield Unit (HU) measured on computed tomography (CT), and dual-energy x-ray absorptiometry (DEXA) values. METHODS: We retrieved the medical and radiographic records of 165 patients who underwent synchronous MRI of the cervical and thoracic spine, as well as DEXA and CT imaging of the spine obtained within 1 year of each other between 2015 and 2022. Radiographic data consisted of the MRI-based cervical and thoracic VBQ scores, CT-based HU, and DEXA T-scores of the spine and hip. Patient age, sex, body mass index (BMI), and ethnicity were also obtained. RESULTS: Mean cervical and thoracic VBQ scores were 3.99 ± 1.68 and 3.82 ± 2.11, respectively. Mean HU and DEXA T-scores of the spine and hip were 135.75 ± 60.36, -1.01 ± 1.15, and -0.47 ± 2.27. All correlations among VBQ, HU, and DEXA were insignificant except for weak correlations between cervical and thoracic VBQ, and cervical VBQ and HU. No correlations were observed between radiographic scores and patient age or BMI. No differences based on ethnicity or sex were observed with respect to cervical or thoracic VBQ, HU, or DEXA. CONCLUSION: Cervical and thoracic VBQ scores are distinct from Hounsfield Unit and DEXA values. VBQ scoring in the cervical and thoracic spine is not influenced by patient age, ethnicity, sex, or BMI.

Association Between Vertebral Bone Quality Score and Dual-Energy X-ray Absorptiometry for the Assessment of Bone Mineral Density in Adolescent Patients.

BACKGROUND: The MRI-based vertebral bone quality (VBQ) score is an assessment tool for bone mineral density (BMD) that has been validated in adults against the clinical standard of dual-energy X-ray absorptiometry (DEXA). However, VBQ has yet to be validated against DEXA for use in adolescents. This study evaluated the associations between adolescent VBQ scores, DEXA Z-scores, and BMD values. METHODS: The radiographic records of 63 consecutive patients between the ages of 11 and 21 who underwent MRI of the abdomen and pelvis and DEXA of the spine and hip were retrieved. The collected radiographic data consisted of the MRI-based VBQ score, DEXA Z-score, and BMD values of the femoral neck, L1-4 vertebrae, and total body. The VBQ score was calculated by taking the median signal intensity (MSI) from L1-L4 and the SI of the L3 cerebrospinal fluid (CSF). The VBQ score was derived as the quotient of MSIL1-L4 divided by SICSF. RESULTS: A mean VBQ score of 2.41 ± 0.29 was observed. Strong correlations of -0.749 (p<0.0001) and -0.780 (p<0.0001) were detected between the VBQ score and DEXA femoral neck and spine Z-scores, respectively. Correlations between VBQ score and DEXA femoral neck, spine, and total body BMD scores were -0.559 (p<0.0001), -0.611 (p<0.0001), and -0.516 (p<.0001), respectively. No significant correlations were found between the VBQ score and age, BMI, weight, or height. A mean difference in VBQ score of -0.155 (p=0.035) was observed between sexes. VBQ demonstrated moderate predictive ability for DEXA-derived Z-scores and BMD scores. CONCLUSIONS: VBQ scores were strongly correlated with DEXA Z-scores and moderately correlated with BMD values. The VBQ score can also be used by adolescent patients as an accessory tool to assess bone health.

Comparative activities of telavancin combined with nafcillin, imipenem, and gentamicin against Staphylococcus aureus.

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V.

In Escherichia coli, cell survival and genomic stability after UV radiation depends on repair mechanisms induced as part of the SOS response to DNA damage. The early phase of the SOS response is mostly dominated by accurate DNA repair, while the later phase is characterized with elevated mutation levels caused by error-prone DNA replication. SOS mutagenesis is largely the result of the action of DNA polymerase V (pol V), which has the ability to insert nucleotides opposite various DNA lesions in a process termed translesion DNA synthesis (TLS). Pol V is a low-fidelity polymerase that is composed of UmuD'(2)C and is encoded by the umuDC operon. Pol V is strictly regulated in the cell so as to avoid genomic mutation overload. RecA nucleoprotein filaments (RecA*), formed by RecA binding to single-stranded DNA with ATP, are essential for pol V-catalyzed TLS both in vivo and in vitro. This review focuses on recent studies addressing the protein composition of active DNA polymerase V, and the role of RecA protein in activating this enzyme. Based on unforeseen properties of RecA*, we describe a new model for pol V-catalyzed SOS-induced mutagenesis.

Yoga vs Cognitive Processing Therapy for Military Sexual Trauma-Related Posttraumatic Stress Disorder: A Randomized Clinical Trial.

Importance: First-line treatment for posttraumatic stress disorder (PTSD) in the US Department of Veterans Affairs (VA), ie, trauma-focused therapy, while effective, is limited by low treatment initiation, high dropout, and high treatment refraction. Objective: To evaluate the effectiveness of Trauma Center Trauma-Sensitive Yoga (TCTSY) vs first-line cognitive processing therapy (CPT) in women veterans with PTSD related to military sexual trauma (MST) and the hypothesis that PTSD outcomes would differ between the interventions. Design, Setting, and Participants: This multisite randomized clinical trial was conducted from December 1, 2015, to April 30, 2022, within 2 VA health care systems located in the southeast and northwest. Women veterans aged 22 to 71 years with MST-related PTSD were enrolled and randomized to TCTSY or CPT. Interventions: The TCTSY intervention (Hatha-style yoga focusing on interoception and empowerment) consisted of 10 weekly, 60-minute group sessions, and the CPT intervention (cognitive-based therapy targeting modification of negative posttraumatic thoughts) consisted of 12 weekly, 90-minute group sessions. Main Outcome and Measures: Sociodemographic data were collected via self-report survey. The primary outcome, PTSD symptom severity, was assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD Checklist for DSM-5 (PCL-5). Assessments were conducted at baseline, midintervention, 2 weeks post intervention, and 3 months post intervention. Results: Of 200 women veterans who consented to participate, the intent-to-treat sample comprised 131 participants (mean [SD] age, 48.2 [11.2] years), with 72 randomized to TCTSY and 59 randomized to CPT. Treatment was completed by 47 participants (65.3%) in the TCTSY group and 27 (45.8%) in the CPT group, a 42.6% higher treatment completion rate in the TCTSY group (P = .03). Both treatment groups improved over time on the CAPS-5 (mean [SD] scores at baseline: 36.73 [8.79] for TCTSY and 35.52 [7.49] for CPT; mean [SD] scores at 3 months: 24.03 [11.55] for TCTSY and 22.15 [13.56]) and the PCL-5 (mean [SD] scores at baseline: 49.62 [12.19] for TCTSY and 48.69 [13.62] for CPT; mean [SD] scores at 3 months: 36.97 [17.74] for TCTSY and 31.76 [12.47]) (P < .001 for time effects). None of the group effects or group-by-time effects were significant. Equivalence analyses of change scores were not significantly different between the TCTSY and CPT groups, and the two one-sided test intervals fell within the equivalence bounds of plus or minus 10 for CAPS-5 for all follow-up time points. Conclusions and Relevance: In this comparative effectiveness randomized clinical trial, TCTSY was equivalent to CPT in reducing PTSD symptom severity, with both groups improving significantly. The higher treatment completion rate for TCTSY indicates its higher acceptability as an effective and acceptable PTSD treatment for women veterans with PTSD related to MST that could address current VA PTSD treatment limitations. Trial Registration: ClinicalTrials.gov Identifier: NCT02640690.

Dramatic expansion and developmental expression diversification of the methuselah gene family during recent Drosophila evolution.

Functional studies of the methuselah/methuselah-like (mth/mthl) gene family have focused on the founding member mth, but little is known regarding the developmental functions of this receptor or any of its paralogs. We undertook a comprehensive analysis of developmental expression and sequence divergence in the mth/mthl gene family. Using in situ hybridization techniques, we detect expression of six genes (mthl1, 5, 9, 11, 13, and 14) in the embryo during gastrulation and development of the gut, heart, and lymph glands. Four receptors (mthl3, 4, 6, and 8) are expressed in the larval central nervous system, imaginal discs, or both, and two receptors (mthl10 and mth) are expressed in both embryos and larvae. Phylogenetic analysis of all mth/mthl genes in five Drosophila species, mosquito and flour beetle structured the mth/mthl family into several subclades. mthl1, 5, and 14 are present in most species, each forming a separate clade. A newly identified Drosophila mthl gene (CG31720; herein mthl15) formed another ancient clade. The remaining Drosophila receptors, including mth, are members of a large "superclade" that diversified relatively recently during dipteran evolution, in many cases within the melanogaster subgroup. Comparing the expression patterns of the mth/mthl "superclade" paralogs to the embryonic expression of the singleton ortholog in Tribolium suggests both subfunctionalization and acquisition of novel functionalities. Taken together, our findings shed novel light on mth as a young member of an adaptively evolving developmental gene family.

Non transferrin bound iron: nature, manifestations and analytical approaches for estimation.

Iron is an essential trace element and plays a number of vital roles in biological system. It also leads the chains of pathological actions if present in excess and/or present in free form. Major portion of iron in circulation is associated with transferrin, a classical iron transporter, which prevent the existence of free iron. The fraction of iron which is free of transferrin is known as "non transferrin bound iron". Along with the incidence in iron over loaded patient non transferrin bound iron has been indicated in patients without iron overload. It has been suggested as cause as well as consequence in a number of pathological conditions. The major organs influenced by iron toxicity are heart, pancreas, kidney, organs involved in hematopoiesis etc. The most commonly suggested way for iron mediated pathogenesis is through increased oxidative stress and their secondary effects. Generation of free oxygen radicals by iron has been well documented in Fenton chemistry and Haber-Weiss reaction. Non transferrin bound iron has obvious chance to generate the free reactive radicals as it is not been shielded by the protective carrier protein apo transferrin. The nature of non transferrin bound iron is not clear at present time but it is definitely a group of heterogenous iron forms free from transferrin and ferritin. A variety of analytical approaches like colorimetry, chromatography, fluorimetry etc. have been experimented in different research laboratories for estimation of non transferrin bound iron. However the universally accepted gold standard method which can be operated in pathological laboratories is still to be developed.

Health Disparities in Recruitment and Enrollment in Research.

Despite advances in thoracic oncology research, the benefits of new discoveries are not universally experienced. A lack of representation of racial/ethnic minorities and individuals of low socioeconomic status in clinical trials and thoracic research contributes to persistent health care disparities. It is critical that improved racial, ethnic, and socioeconomic diversity is achieved in our trials and research, if we are to attain generalizability of findings and reduction of health care disparities. Culturally tailored and community-based approaches can help improve recruitment and enrollment of marginalized groups in thoracic research, which is an essential step toward achieving health equity and advancing medical science.

A Lung Cancer Screening Education Program Impacts both Referral Rates and Provider and Medical Assistant Knowledge at Two Federally Qualified Health Centers.

BACKGROUND: Federally Qualified Health Centers (FQHCs) serve minority and low-socioeconomic populations and provide care to high-risk smokers. These centers frequently experience barriers, including low provider and medical assistant (MA) knowledge around lung cancer screening (LCS). Subsequent low LCS referral rates by providers at FQHCs limit utilization of LCS in eligible, high-risk, underserved patients. METHODS: Providers and MAs from two FQHCs participated in a LCS educational session. A pre-educational survey was administered at the start of the session and a post-educational survey at the end. The intervention included a presentation with education around non-small cell lung cancer, LCS, tobacco cessation, and shared-decision making. Both surveys were used to evaluate changes in provider and MA ability to determine eligible patients for LCS. The Pearson's Chi-squared test with Yates' continuity correction was used to measure the impact. RESULTS: A total of 29 providers and 28 MAs enrolled in the study from two FQHCs. There was an improvement, P < .009 and P < .015 respectively, in provider and MA confidence in identifying patients for LCS. Additionally, one year prior to the program, 9 low-dose computed tomography (LDCTs) were ordered at one of the FQHCs and 0 at the other. After the program, over 100 LDCTs were ordered at each FQHC. CONCLUSIONS: A targeted LCS educational program improves provider and MAs' ability to identify eligible LCS patients and is associated with an increase in the number of patients referred to LDCT at FQHCs.