Deficiency in Galectin-3, -8, and -9 impairs immunity to chronic Mycobacterium tuberculosis infection but not acute infection with multiple intracellular pathogens.

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis (Mtb) and Salmonella enterica serovar Typhimurium (Stm) and localizes to Mtb in macrophages. To determine the combined contribution of membrane damage-sensing galectins to immunity, we generated Gal-3, -8, and -9 triple knockout (TKO) mice. Mtb infection of primary macrophages from TKO mice resulted in defective autophagic flux but normal bacterial replication. Surprisingly, these mice had no discernable defect in resistance to acute infection with Mtb, Stm or Listeria monocytogenes, and had only modest impairments in bacterial growth restriction and CD4 T cell activation during chronic Mtb infection. Collectively, these findings indicate that while Gal-3, -8, and -9 respond to an array of intracellular pathogens, together these membrane damage-sensing galectins play a limited role in host resistance to bacterial infection.

Virtual Reality Job Interview Training for Adults Receiving Prison-Based Employment Services: A Randomized Controlled Feasibility and Initial Effectiveness Trial.

Returning citizens struggle to obtain employment after release from prison, and navigating job interviews is a critical barrier they encounter. Implementing evidence-based interview training is a major gap in prison-based vocational services. We conducted a randomized controlled trial (RCT) to evaluate the feasibility and initial effectiveness of Virtual Reality Job Interview Training within two prisons. Forty-four male returning citizens were randomized to receive service-as-usual (SAU) with VR-JIT (SAU+VR-JIT, n = 28) or SAU (n = 16). Participants reported VR-JIT was highly acceptable and usable. SAU+VR-JIT, as compared to SAU, had significant improvements (with large effect sizes) in interview skills, interview training motivation, and interview anxiety (all p < .05; ηp2 > .15), and greater employment by 6-month follow-up (OR = 7.4, p = .045). VR-JIT can potentially help fill a major gap in prison-based services. Future research is needed to validate VR-JIT effectiveness and evaluate VR-JIT implementation strategies within prisons.

Mixed methods implementation evaluation of virtual interview training for transition-age autistic youth in pre-employment transition services.

BACKGROUND: Autistic transition-age youth are employed at rates far lower than their non-disabled peers as well as youth with other disabilities. Meanwhile, very few studies have evaluated the implementation of job interviewing practices within pre-employment transition services. OBJECTIVE: We conducted an initial implementation evaluation as part of a Type I hybrid randomized controlled effectiveness-implementation trial where we trained teachers to deliver Virtual Interview Training for Transition-Age Youth (VIT-TAY) within five pre-employment transition services programs. METHODS: We used mixed methods to evaluate leader (n=5), teacher (n=15) and autistic transition age youth (n=48) perceptions of VIT-TAY. We used descriptive statistics and thematic network analysis to evaluate survey data. Mixed methods integration was then performed to make comparisons between quantitative and qualitative results. RESULTS: Quantitative survey data revealed that leaders and teachers found VIT-TAY to be highly acceptable and appropriate for pre-employment transition services; findings which were confirmed via thematic network analysis of qualitative interview data. Autistic students reported via quantitative surveys that VIT-TAY was acceptable and usable, which was confirmed via thematic network analysis of open-ended survey data. CONCLUSIONS: This initial implementation evaluation can be used to inform a larger scale implementation evaluation of VIT-TAY in schools.

The relationship between individual-level deprivation and health-related quality of life.

OBJECTIVE: To examine the association between individual-level deprivation and health-related quality of life (HRQL) in the general population. METHODS: Data from a population-based survey in the Canadian province of Alberta were used. Individual-level deprivation was assessed using the Canadian Deprivation Index (CDI) and the Ontario Deprivation Index (ODI). HRQL was assessed using the EQ-5D-5 L. Differences in problems in the EQ-5D-5 L dimensions, index and visual analogue scale (VAS) scores across levels of deprivation were examined. Multivariate logistic and linear regression models adjusted for socio-demographic and other characteristics were used to examine the independent association between deprivation and HRQL. RESULTS: Of the 6314 respondents, 39% were aged between 18 and 44 years and 38% between 45 and 64 years; 60% were female. Mean EQ-5D-5 L index and VAS scores were 0.85 (standard deviation [SD] 0.14) and 79.6 (SD 17.7), respectively. Almost one-third (30.6%) of respondents reported no problems on all EQ-5D-5 L dimensions. Few participants reported some problems with mobility (23.8%), self-care (6.2%) and usual activities (25.2%), while 59.3 and 35.5% reported some levels of pain/discomfort and anxiety/depression, respectively. Differences between the most and least deprived in reporting problems in EQ-5D-5 L dimensions, index and VAS scores were statistically significant and clinically important. In adjusted regression models for both deprivation indices, the least well-off, compared to the most well-off, had higher likelihood of reporting problems in all EQ-5D-5 L dimensions. Compared to the most well-off, the least well-off had an EQ-5D-5 L index score decrement of 0.18 (p < 0.01) and 0.17 (p < 0.01) for the CDI and ODI, respectively. Similarly, an inverse association was found between the VAS score and the CDI (ß = - 17.3, p < 0.01) as well as the ODI (ß = - 13.3, p < 0.01). CONCLUSION: Individual-level deprivation is associated with worse HRQL. Poverty reduction strategies should consider the effects of not only neighbourhood-level deprivation, but also that of individual-level deprivation to improve overall health.

A scaffold protein connects type IV pili with the Chp chemosensory system to mediate activation of virulence signaling in Pseudomonas aeruginosa.

Type IV pili (TFP) function as mechanosensors to trigger acute virulence programs in Pseudomonas aeruginosa. On surface contact, TFP retraction activates the Chp chemosensory system phosphorelay to upregulate 3', 5'-cyclic monophosphate (cAMP) production and transcription of virulence-associated genes. To dissect the specific interactions mediating the mechanochemical relay, we used affinity purification/mass spectrometry, directed co-immunoprecipitations in P. aeruginosa, single cell analysis of contact-dependent transcriptional reporters, subcellular localization and bacterial two hybrid assays. We demonstrate that FimL, a Chp chemosensory system accessory protein of unknown function, directly links the integral component of the TFP structural complex FimV, a peptidoglycan binding protein, with one of the Chp system output response regulators PilG. FimL and PilG colocalize at cell poles in a FimV-dependent manner. While PilG phosphorylation is required for TFP function and mechanochemical signaling, it is not required for polar localization or binding to FimL. Phylogenetic analysis reveals other bacterial species simultaneously encode TFP, the Chp system, FimL, FimV and adenylate cyclase homologs, suggesting that surface sensing may be widespread among TFP-expressing bacteria. We propose that FimL acts as a scaffold enabling spatial colocalization of TFP and Chp system components to coordinate signaling leading to cAMP-dependent upregulation of virulence genes on surface contact.

First-trimester sonographic prediction of obstetric and neonatal outcomes in monochorionic diamniotic twin pregnancies.

OBJECTIVES: The purpose of this study was to investigate whether discordant nuchal translucency and crown-rump length measurements in monochorionic diamniotic twins are predictive of adverse obstetric and neonatal outcomes. METHODS: We conducted a multicenter retrospective cohort study including all monochorionic diamniotic twin pregnancies with two live fetuses at the 11-week to 13-week 6-day sonographic examination who had serial follow-up sonography until delivery. Isolated nuchal translucency, crown-rump length, and combined discordances were correlated with adverse obstetric outcomes, individually and in composite, including the occurrence of 1 or more of the following in either fetus: intrauterine growth restriction (IUGR), twin-twin transfusion syndrome (TTTS), intrauterine fetal death (IUFD), growth discordance (≥ 20%), and preterm birth before 28 weeks' gestation. Correlations with adverse composite neonatal outcomes were also studied. A receiver operating characteristic curve analysis and a logistic regression analysis with a generalized estimating equation were conducted. RESULTS: Fifty-four of the 177 pregnancies included (31%) had an adverse composite obstetric outcome, with TTTS in 19 (11%), IUGR in 21 (12%), discordant growth in 14 (8%), IUFD in 14 (8%), and preterm birth before 28 weeks in 10 (6%). Of the 254 neonates included in the study, 69 (27%) were complicated by adverse composite neonatal outcomes, with respiratory distress syndrome being the most common (n = 59 [23%]). The areas under the curve for the combined discordances to predict composite obstetric and neonatal outcomes were 0.62 (95% confidence interval, 0.52-0.72), and 0.54 (95% confidence interval, 0.46-0.61), respectively. CONCLUSIONS: In our population, nuchal translucency, crown-rump length, and combined discordances in monochorionic diamniotic twin pregnancies were not predictive of adverse composite obstetric and neonatal outcomes.

Does early second-trimester sonography predict adverse perinatal outcomes in monochorionic diamniotic twin pregnancies?

OBJECTIVES: To determine whether intertwin discordant abdominal circumference, femur length, head circumference, and estimated fetal weight sonographic measurements in early second-trimester monochorionic diamniotic twins predict adverse obstetric and neonatal outcomes. METHODS: We conducted a multicenter retrospective cohort study involving 9 regional perinatal centers in the United States. We examined the records of all monochorionic diamniotic twin pregnancies with two live fetuses at the 16- to 18-week sonographic examination who had serial follow-up sonography until delivery. The intertwin discordance in abdominal circumference, femur length, head circumference, and estimated fetal weight was calculated as the difference between the two fetuses, expressed as a percentage of the larger using the 16- to 18-week sonographic measurements. An adverse composite obstetric outcome was defined as the occurrence of 1 or more of the following in either fetus: intrauterine growth restriction, twin-twin transfusion syndrome, intrauterine fetal death, abnormal growth discordance (≥20% difference), and very preterm birth at or before 28 weeks. An adverse composite neonatal outcome was defined as the occurrence of 1 or more of the following: respiratory distress syndrome, any stage of intraventricular hemorrhage, 5-minute Apgar score less than 7, necrotizing enterocolitis, culture-proven early-onset sepsis, and neonatal death. Receiver operating characteristic and logistic regression-with-generalized estimating equation analyses were constructed. RESULTS: Among the 177 monochorionic diamniotic twin pregnancies analyzed, intertwin abdominal circumference and estimated fetal weight discordances were only predictive of adverse composite obstetric outcomes (areas under the curve, 79% and 80%, respectively). Receiver operating characteristic curves showed that intertwin discordances in abdominal circumference, femur length, head circumference, and estimated fetal weight were not acceptable predictors of twin-twin transfusion syndrome or adverse neonatal outcomes. CONCLUSIONS: In our cohort, only second-trimester abdominal circumference and estimated fetal weight discordances in monochorionic diamniotic twin pregnancies were predictive of adverse composite obstetric outcomes. Twin-twin transfusion syndrome and adverse neonatal outcomes were not predicted by any of the intertwin discordances measured.

Implementing Virtual Interview Training for Transition-Age Youth: Practical Strategies for Educators.

This column shares strategies for implementing a technology-based intervention within secondary special education transition services. Virtual Interview Training for Transition-Age Youth is a web-based job interview training that uses educational content and virtual hiring managers (Rita and Travis) to help teach job interview skills. Eight strategies were assembled by research staff, teachers, and administrators during two research studies conducted across n=47 schools that delivered the program (commonly called "Rita and Travis") to n=561 students in secondary special education transition programs. Eight support strategies for implementing Rita and Travis are described. Strategies include: prepare for implementation, ensure administrative support, prioritize training and support, address logistical challenges, integrate the program into the curriculum, take advantage of the administrative center, individualize student support, and offer virtual delivery. The purpose of this column is to prepare others for successful implementation of Virtual Interview Training for Transition-Age Youth within special education transition programs.

A Mixed-Methods Implementation Evaluation of Virtual Reality Job Interview Training in IPS Supported Employment.

OBJECTIVE: Employment rates among individuals with serious mental illness may be improved by engagement in the individual placement and support (IPS) model of supported employment. Results from a recent randomized controlled trial (RCT) indicate that virtual reality job interview training (VR-JIT) improves employment rates among individuals with serious mental illness who have been actively engaged in IPS for at least 90 days. This study reports on an initial implementation evaluation of VR-JIT during the RCT in a community mental health agency. METHODS: A sequential, complementary mixed-methods design included use of qualitative data to improve understanding of quantitative findings. Thirteen IPS staff trained to lead VR-JIT implementation completed VR-JIT acceptability, appropriateness, and feasibility surveys. Participants randomly assigned to IPS with VR-JIT completed acceptability (N=42) and usability (N=28) surveys after implementation. The authors also conducted five focus groups with IPS staff (N=11) and VR-JIT recipients (N=13) and semistructured interviews with IPS staff (N=9) and VR-JIT recipients (N=4), followed by an integrated analysis process. RESULTS: Quantitative results suggest that IPS staff found VR-JIT to be highly acceptable, appropriate for integration with IPS, and feasible for delivery. VR-JIT was highly acceptable to recipients. Qualitative results add important context to the quantitative findings, including benefits of VR-JIT for IPS staff as well as adaptations for delivering technology-based interventions to individuals with serious mental illness. CONCLUSIONS: These qualitative and quantitative findings are consistent with each other and were influenced by VR-JIT's adaptability and perceived benefits. Tailoring VR-JIT instruction and delivery to individuals with serious mental illness may help optimize VR-JIT implementation within IPS.

Identifying Sex-Specific Differences in Young-Onset Metabolic Syndrome Using Primary Care Electronic Medical Record.

Objectives: To apply a case definition to a Northern Alberta-based primary care practice population and to assess the sex-specific characteristics of young-onset metabolic syndrome (MetS). Design: We carried out a cross-sectional study to identify and estimate the prevalence of MetS using electronic medical record (EMR) data and perform descriptive comparative analyses of demographic and clinical characteristics between males and females. Setting: Northern Alberta Primary Care Research Network (NAPCReN) consists of EMR patient data from 77 physicians among 18 clinics. Participants: Patients with one or more clinic visit between 2015 and 2018, between 18 and 40 years old, residing in Northern Alberta. Main Outcome Measures: Comparison of prevalence in MetS between sexes as well as sex-specific distribution of MetS characteristics [body mass index (BMI), fasting blood glucose, glycated hemoglobin, triglycerides, and high-density lipoprotein cholesterol (HDL-C), presence of hypertension, and presence of diabetes]. Results: Of 15,766 patients, 4.4% (n = 700) had young-onset MetS based on recorded data, prevalence was nearly twice as high in males (6.1%, n = 354) compared with females (3.5%, n = 346). The most prevalent risk factor for MetS consisted of having an elevated BMI for both females (90.9%) and males (91.5%). In the presence of MetS, more females had lower HDL-C [68.2% females (F) vs. 52.5% males (M)], and higher prevalence of diabetes (21.4% F vs. 9.0% M), whereas more males had hypertriglyceridemia (60.4% F vs. 79.7% M) and hypertension (12.4% F vs. 15.8% M). Females also had consistently higher percentages of absent laboratory data compared with males when identified as having MetS and BMI ≥25 kg/m2. Conclusions: Males have nearly twice the prevalence of young-onset MetS compared with females, with notable sex-specific differences in the manifestation of MetS, although we suspect that this is partially due to underreporting where the absence of anthropomorphic and laboratory investigations point to a lack of testing. Sex-specific screening for MetS, especially among young females of childbearing years, is important for downstream prevention.

Extracranial Microvascular Complications of Moyamoya Disease Leading to Left Ventricular Systolic Dysfunction.

Moyamoya disease (MMD) was first used as a descriptor for a steno-occlusive process that affects primarily the internal carotid arteries (ICA) in a bilateral fashion in 1969. Characterized by recurrent ischemic events in the developing brains of young patients, the process is one that often decimates the quality of life of affected individuals. The vascular changes in MMD have been demonstrated to occur in an extracranial manner, thus it is logical to assume that the same steno-occlusive mechanism could induce dysfunction and ischemia in other organ systems. Our case presents a patient with MMD with cardiac manifestations that we suspect may be related to extracranial manifestations of MMD.

The role of quantitative MRI-based prostate zonal parameters in predicting clinically significant prostate cancer A U.S. cohort.

INTRODUCTION: We aimed to investigate the clinical utility of quantitative prostatic zonal measurements on multiparametric magnetic resonance imaging (mpMRI) for the predication of clinically significant prostate cancer (csPCa). METHODS: A retrospective, single-institution study included 144 men who underwent mpMRI from 2015-2017. Prostate zone parameters were measured on mpMRI. Correlation and multivariable analysis evaluated the relationship between prostate zone parameters and the presence of csPCa. RESULTS: The mean age was 66.9±7.8 years old. The median (interquartile range [IQR]) prostate volume and prostate-specific antigen (PSA) were 51.6 ml (37.1-74.5) and 6.1 ng/ ml (4.5-8.2), respectively. Men with csPCa had significantly smaller total prostate volume (TPV), transitional zone volume (TZV), and transitional zone thickness (TZT), and larger transitional zone density (TZD) compared to those without PCa; however, on multivariate variable analysis, only TZD maintained significance. TZD had a comparable area under the curve to PSA density (PSAD) and PSA (0.74 vs. 0.73 vs. 0.60, respectively). In a subgroup analysis of men with PCa, PSAD and TZD were significantly higher in men with Gleason grade group (GG) ≥2 compared to those with GG <2 (p=0.002); however, this significance is not maintained on logistic regression in predicting GG. CONCLUSIONS: Quantitative features of prostate zones on MRI may aid in identifying better predictors of csPCa. Zonal-based PSA density (TZD) may be a useful marker in identifying csPCa. Further exploration is needed to understand the clinical application of larger TZV in men with csPCa compared to those with insignificant disease.

Preference-based SF-6D scores derived from the SF-36 and SF-12 have different discriminative power in a population health survey.

OBJECTIVE: To compare the discriminative power of the SF-6D index scores derived from the SF-36 (SF-6D36) and SF-12 (SF-6D12) in the general population. METHODS: Data from the National Health Measurement Study were used. The F statistic was used to compare the relative efficiency of the SF-6D36 and SF-6D12, as well as the EQ-5D, HUI2, and HUI3 index scores, in discriminating between respondents with and without 1 of the 11 chronic medical conditions. The efficiency of the multiattribute health classification systems of the study instruments was measured using the Shannon index (H'). The relative efficiency of the SF-6D36 and SF-6D12 was also compared in respondents who were on the ceilings of the EQ-5D, HUI2, and HUI3 scales. RESULTS: The SF-6D36 score was systematically lower than the SF-6D12 score at the group level (range, 0.022-0.036). The SF-6D36 exhibited higher discriminative power in 8 and 5 conditions than the SF-6D12 and all other index scores, respectively. The SF-6D36 had higher H' values than the SF-6D12 in the dimensions of physical functioning (1.73 vs. 0.78), mental health (1.70 vs. 1.39), and bodily pain (2.16 vs. 1.56) as well as than all other instruments in similar health dimensions. In respondents reporting full health on the EQ-5D, HUI2, or HUI3, the SF-6D36 better discriminated between those with and without medical conditions than the SF-6D12. CONCLUSIONS: The SF-6D derived from the SF-36 is more discriminative than that derived from the SF-12 and is therefore preferred for use in population health surveys where a preference-based health index is needed.

Management of Coronary Artery Disease.

This article reviews the surgical management of coronary artery disease (CAD). The authors cover the background, presentation, diagnosis, heart team evaluation, and development of treatment strategies tailored to individual patients with significant CAD. Special attention is given to conduit selection and configuration as well as alternative revascularization approaches that differ from traditional coronary artery bypass grafting.

Obesity and Pregnancy.

The worldwide rates of obesity have increased significantly in recent decades. In the United States, more than 50% of pregnant women are overweight or obese. Obese gravid women are more prone to adverse pregnancy outcomes, including gestational diabetes, hypertensive disorders, and cardiovascular diseases. The adverse outcomes extend beyond the pregnant obese woman; offspring of obese women are themselves at increased risk of prematurity, fetal death, injury during birth, and transient respiratory problems and metabolic effects (ie, neonatal hypoglycemia). Furthermore, maternal obesity can predispose their offspring to long-term health problems, potentially generating an intergenerational cycle of obesity and insulin resistance.

Cardiothoracic Surgical Volume Within the Military Health System: Fiscal Years 2007 to 2017.

BACKGROUND: Cardiothoracic surgical services have been provided at 7 military treatment facilities over the past decade. Accurate case volume data for adult cardiac and general thoracic surgical service lines in the Military Health System is unknown. METHODS: We queried the Military Health System Data Repository for adult cardiac and general thoracic cases performed at military treatment facilities in the Military Health System and surrounding purchased care markets for fiscal years 2007 to 2017. Cases were filtered and classified into major cardiac and major general thoracic categories. Five military treatment facility markets had sufficient cardiac case data to perform cost analysis. RESULTS: Institutional major cardiac case volume was low across the Military Health System with less than 100 cardiopulmonary bypass cases per year (range, 17-151 cases per year) performed most years at each military treatment facility. Similarly, general thoracic surgical case volume was universally low, with less than 30 anatomic lung resections (range, 0-26) and fewer than 5 esophageal resections (range, 0-4) performed at each military treatment facility annually. Cost analysis revealed that provision of cardiac surgical services is significantly more expensive at most military treatment facilities compared with their surrounding purchased care markets. CONCLUSIONS: Adult cardiac and general thoracic surgical volume within the Military Health System is low across all institutions and inadequate to provide clinical readiness for active-duty surgeons. Recapture of major cases from the purchased care market is unlikely and would not significantly increase military treatment facility or individual surgeon case volume.

Acceptability and Feasibility of Peer Specialist-Delivered Virtual Reality Job Interview Training for Individuals with Serious Mental Illness: A Qualitative Study.

This study explored peer specialists' perspectives on delivering vocational interventions, especially Virtual Reality Job Interview Training (VR-JIT). Five focus groups of peer specialists (N = 34) explored their beliefs about vocational services, including VR-JIT. We trained eight peer specialists to be VR-JIT "instructors" and interviewed them about using VR-JIT in their mental health practice. Generally, participants discussed tailoring their vocational services to include sharing their story of recovery. Specifically, participants perceived VR-JIT as acceptable and feasibly implemented within their practice. Overall, participants viewed VR-JIT as a higher level of service and they would be uniquely qualified to support consumers using the tool.

Effect of sterol carrier protein-2 gene ablation on HDL-mediated cholesterol efflux from cultured primary mouse hepatocytes.

Although HDL-mediated cholesterol transport to the liver is well studied, cholesterol efflux from hepatocytes back to HDL is less well understood. Real-time imaging of efflux of 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-cholesterol), which is poorly esterified, and [(3)H]cholesterol, which is extensively esterified, from cultured primary hepatocytes of wild-type and sterol carrier protein-2 (SCP-2) gene-ablated mice showed that 1) NBD-cholesterol efflux was affected by the type of lipoprotein acceptor, i.e., HDL3 over HDL2; 2) NBD-cholesterol efflux was rapid (detected in 1-2 min) and resolved into fast [half time (t((1/2))) = 2.4 min, 6% of total] and slow (t((1/2)) = 26.5 min, 94% of total) pools, consistent with protein- and vesicle-mediated cholesterol transfer, respectively; 3) SCP-2 gene ablation increased efflux of NBD-cholesterol, as well as [(3)H]cholesterol, albeit less so due to competition by esterification of [(3)H]cholesterol, but not NBD-cholesterol; and 4) SCP-2 gene ablation increased initial rate (2.3-fold) and size (9.7-fold) of rapid effluxing sterol, suggesting an increased contribution of molecular cholesterol transfer. In addition, colocalization, double-immunolabeling fluorescence resonance energy transfer, and electron microscopy, as well as cross-linking coimmunoprecipitation, indicated that SCP-2 directly interacted with the HDL receptor, scavenger receptor class B type 1 (SRB1), in hepatocytes. Other membrane proteins in cholesterol efflux [SRB1 and ATP-binding cassettes (ABC) A-1, ABCG-1, ABCG-5, and ABCG-8] and several soluble/vesicle-associated proteins facilitating intracellular cholesterol trafficking (StARDs, NPCs, ORPs) were not upregulated. However, loss of SCP-2 elicited twofold upregulation of liver fatty acid-binding protein (L-FABP), a protein with lower affinity for cholesterol but higher cytosolic concentration than SCP-2. Ablation of SCP-2 and L-FABP decreased HDL-mediated NBD-cholesterol efflux. These results indicate that SCP-2 expression plays a significant role in HDL-mediated cholesterol efflux by regulating the size of rapid vs. slow cholesterol efflux pools and/or eliciting concomitant upregulation of L-FABP in cultured primary hepatocytes.

Comparison of direct body composition assessment methods in patients with chronic heart failure.

BACKGROUND: We examined the validity of leg-to-leg bioelectrical impedance analysis (BIA) and near-infrared interactance (NIR) to assess body composition in chronic heart failure (CHF) patients. METHODS AND RESULTS: A total of 140 patients with CHF were enrolled in this cross-sectional study between June 2008 and July 2009. Dual energy x-ray absorptiometry (DEXA) served as the reference standard. A priori, desired precision levels were set at ± 3.5% body fat and ± 3.5 kg lean body mass. Mean age was 63, 74% were male, and 90% were Caucasian. BIA- and NIR-ascertained percent body fat and lean body mass were highly correlated to DEXA. Mean differences and limits of agreement for NIR were -0.3% ± 5.1% for percent body fat and 2.9 kg ± 4.3 kg for lean body mass. Mean difference and limits of agreement for BIA percent body fat was 0.8% ± 5.8%. BIA lean body mass showed poor agreement with DEXA because of variable limits of agreement across the range of measurement (Pitman's test P < .0001). CONCLUSIONS: In patients with CHF, both NIR and BIA accurately measure body fat. However, both methods were imprecise. NIR overestimated lean body mass and BIA was not useful to assess this parameter. Further study is required, including examination of the utility of these field methods in serially assessing body composition.

Host Wnt5a Potentiates Microenvironmental Regulation of Ovarian Cancer Metastasis.

The noncanonical Wnt ligand Wnt5a is found in high concentrations in ascites of women with ovarian cancer. In this study, we elucidated the role of Wnt5a in ovarian cancer metastasis. Wnt5a promoted ovarian tumor cell adhesion to peritoneal mesothelial cells as well as migration and invasion, leading to colonization of peritoneal explants. Host components of the ovarian tumor microenvironment, notably peritoneal mesothelial cells and visceral adipose, secreted Wnt5a. Conditional knockout of host WNT5A significantly reduced peritoneal metastatic tumor burden. Tumors formed in WNT5A knockout mice had elevated cytotoxic T cells, increased M1 macrophages, and decreased M2 macrophages, indicating that host Wnt5a promotes an immunosuppressive microenvironment. The Src family kinase Fgr was identified as a downstream effector of Wnt5a. These results highlight a previously unreported role for host-expressed Wnt5a in ovarian cancer metastasis and suggest Fgr as a novel target for inhibition of ovarian cancer metastatic progression.Significance: This study establishes host-derived Wnt5a, expressed by peritoneal mesothelial cells and adipocytes, as a primary regulator of ovarian cancer intraperitoneal metastatic dissemination and identifies Fgr kinase as novel target for inhibition of metastasis.