Assessing the effects of sunlight and water on asphalt binder and pavement leachability related to the environment.

Extensive global research conducted over 30 years explores asphalt leachability and stormwater runoff. Asphalt's widespread usage in construction materials underscores the importance of understanding its environmental consequences. This study aims to assess the influence of sunlight exposure on water quality, particularly regarding the release of hazardous organic compounds such as polycyclic aromatic compounds. We investigated the effect of concurrent versus sequential exposure to water and sunlight, and dark versus light trials utilizing thin films of asphalt binder as well as old and freshly prepared pavement cores for analysis. Initial laboratory experiments reveal significant water-soluble species when thin asphalt films are exposed to solar simulation while underwater. However, simulating environmental conditions found in roadways by exposing the asphalt binder to solar simulation followed by water immersion leads to a substantial decrease in compound formation. Leachate water from 17-year-old asphalt and 15-year-old concrete pavements exhibits complex compound compositions associated with atmospheric and/or vehicular deposition, posing challenges in deconvoluting their origins. Light and dark trials conducted on freshly prepared asphalt pavement under environmental conditions of sunlight and rain demonstrate minimal runoff variation, with semi-volatile organic compound levels resembling the background. Future investigations will focus on applying insights gained from this study to analyze larger sample sets, with an emphasis on inherent hazardous compound variations.

Intraoperative Methadone Reduces Postoperative Opioid Requirements in Nuss Procedure for Pectus Excavatum.

INTRODUCTION: Surgical correction of pectus excavatum by Nuss procedure, commonly referred to as minimally invasive repair of pectus excavatum (MIRPE), often results in significant postoperative pain. This study investigated whether adding intraoperative methadone would reduce the postoperative opioid requirement during admission for patients undergoing MIRPE. METHODS: A retrospective cohort chart review was conducted for 40 MIRPE patients between 2018 and 2020. Patients were stratified into 2 groups: those who received multimodal anesthesia (MM, n = 20) and those who received multimodal anesthesia with the addition of intraoperative methadone (MM + M, n = 20). Data collected included total opioid consumption during hospital stay (morphine milligram equivalents [MMEs]), hospital length of stay (LOS), pain scores, time to ambulation, and time to tolerating solid food. RESULTS: Addition of intraoperative methadone for patients undergoing MIRPE significantly reduced postoperative opioid requirements (MME/kg) during admission (P = .007). On average, patients in the MM group received 1.61 ± .55 MME/kg while patients in the MM + M group received 1.16 ± .44 MME/kg. Hospital opioid (non-methadone) total was also significantly reduced between the MM (1.87 ± .54) and MM + M group (1.37 ± .46), P = .003. There was no significant difference in hospital opioid total MME/kg administered between the groups. There were no significant differences observed in hospital LOS, pain scores, time to ambulation, or time to toleration of solid food. DISCUSSION: Incorporating intraoperative methadone for patients undergoing MIRPE reduced postoperative opioid requirements and hospital opioid (non-methadone) totals without a significant change in pain scores. Patients undergoing the Nuss procedure may benefit from the administration of intraoperative methadone.

Helicase-like transcription factor-deletion from the tumor microenvironment in a cell line-derived xenograft model of colorectal cancer reprogrammed the human transcriptome-S-nitroso-proteome to promote inflammation and redirect metastasis.

Methylation of the HLTF gene in colorectal cancer (CRC) cells occurs more frequently in men than women. Progressive epigenetic silencing of HLTF in tumor cells is accompanied by negligible expression in the tumor microenvironment (TME). Cell line-derived xenografts (CDX) were established in control (Hltf+/+) and Hltf-deleted male Rag2-/-IL2rg-/- mice by direct orthotopic cell microinjection (OCMI) of HLTF+/+HCT116 Red-FLuc cells into the submucosa of the cecum. Combinatorial induction of IL6 and S100A8/A9 in the Hltf-deleted TME with ICAM-1 and IL8 in the primary tumor activated a positive feedback loop. The proinflammatory niche produced a major shift in CDX metastasis to peritoneal dissemination compared to controls. Inducible nitric oxide (iNOS) gene expression and transactivation of the iNOS-S100A8/A9 signaling complex in Hltf-deleted TME reprogrammed the human S-nitroso-proteome. POTEE, TRIM52 and UN45B were S-nitrosylated on the conserved I/L-X-C-X2-D/E motif indicative of iNOS-S100A8/A9-mediated S-nitrosylation. 2D-DIGE and protein identification by MALDI-TOF/TOF mass spectrometry authenticated S-nitrosylation of 53 individual cysteines in half-site motifs (I/L-X-C or C-X-X-D/E) in CDX tumors. POTEE in CDX tumors is both a general S-nitrosylation target and an iNOS-S100A8/A9 site-specific (Cys638) target in the Hltf-deleted TME. REL is an example of convergence of transcriptomic-S-nitroso-proteomic signaling. The gene is transcriptionally activated in CDX tumors with an Hltf-deleted TME, and REL-SNO (Cys143) was found in primary CDX tumors and all metastatic sites. Primary CDX tumors from Hltf-deleted TME shared 60% of their S-nitroso-proteome with all metastatic sites. Forty percent of SNO-proteins from primary CDX tumors were variably expressed at metastatic sites. Global S-nitrosylation of proteins in pathways related to cytoskeleton and motility was strongly implicated in the metastatic dissemination of CDX tumors. Hltf-deletion from the TME played a major role in the pathogenesis of inflammation and linked protein S-nitrosylation in primary CDX tumors with spatiotemporal continuity in metastatic progression when the tumor cells expressed HLTF.

Quantitative measurements of prostate capsule and gland density and their correlation to prostate size: possible clinical implications in prostate cancer.

PURPOSE: To study histo-anatomical imaging features and possible association between prostate volume, capsule thickness and glandular density within the peripheral zone (PZ) of prostates of different sizes. METHODS: Patients were selected who had undergone radical prostatectomy. Specimen selection was based on two factors: first, easy reconstruction of prostate anatomy by the histological slides; and second, based on prostate size. Specimens were chosen with small (< 35 cc) and also with large size (> 80 cc). A total of 20 patients were selected. None of these patients had undergone previous treatment. Computer-based imaging for quantitative measurements of capsule thickness and glandular density within the PZ were performed. Multiple regression analysis was performed to determine the relationship between these measured parameters and the clinical characteristics of these patients. RESULTS: Multiple regression analysis revealed a strong, positive association between prostate size and average capsule thickness; on the contrary, we found a negative correlation between prostate volume and average glandular density. Fibrotic thickness of the capsule was associated with gland atrophy and decreased gland density within the PZ. CONCLUSIONS: The results suggest that BPH may be associated with the development of fibrosis and gland atrophy within the peripheral zone. As 80% of prostate cancer originates from the glandular epithelium within the peripheral zone, this observed phenomenon may explain the inverse relationship between BPH and incidence of prostate cancer well documented in the literature.

Helicase-like transcription factor (Hltf) gene-deletion promotes oxidative phosphorylation (OXPHOS) in colorectal tumors of AOM/DSS-treated mice.

The helicase-like transcription factor (HLTF) gene-a tumor suppressor in human colorectal cancer (CRC)-is regulated by alternative splicing and promoter hypermethylation. In this study, we used the AOM/DSS-induced mouse model to show Hltf-deletion caused poor survival concomitant with increased tumor multiplicity, and dramatically shifted the topographic distribution of lesions into the rectum. Differential isoform expression analysis revealed both the truncated isoform that lacks a DNA-repair domain and the full length isoform capable of DNA damage repair are present during adenocarcinoma formation in controls. iPathwayGuide identified 51 dynamically regulated genes of 10,967 total genes with measured expression. Oxidative Phosphorylation (Kegg: 00190), the top biological pathway perturbed by Hltf-deletion, resulted from increased transcription of Atp5e, Cox7c, Uqcr11, Ndufa4 and Ndufb6 genes, concomitant with increased endogenous levels of ATP (p = 0.0062). Upregulation of gene expression, as validated with qRT-PCR, accompanied a stable mtDNA/nDNA ratio. This is the first study to show Hltf-deletion in an inflammation-associated CRC model elevates mitochondrial bioenergetics.

Possible clinical implications of peripheral zone changes depending on prostate size.

PURPOSE: Although numerous studies have observed an inverse relationship between the size of benign prostate hypertrophy (BPH) and the incidence of prostate cancer (PCa), few studies have explored specific mechanisms by which BPH and PCa may influence one another. In a recent study, one possibility has been brought up that growth in the transition zone due to BPH may cause pressure-induced fibrotic changes in the peripheral zone, an area where 80% of cancer occurs, leading to gland atrophy and the thickening of the prostatic capsule. To shed more light on this phenomenon, we conducted a pilot study examining the quantitative and qualitative histo-anatomical changes that occur in the peripheral zone associated with BPH. METHODS: Thirty-nine prostate specimens of various sizes were selected from patients who had undergone radical prostatectomies. Each prostate was evaluated in six different locations along the dorsal aspect of the peripheral zone by measuring the thickness of the peripheral fibrotic zone (prostate capsule) and its association with gland atrophy. Multiple regression analysis was performed to determine the relationship between prostate size and the average thickness of the prostate capsule. RESULTS: Multiple regression analysis revealed a strong, positive relationship between prostate size and average capsule thickness with a Pearson coefficient of 0.707 (p < 0.05). Fibrotic histo-anatomical changes were spatially associated with gland atrophy: glands found within the peripheral fibrotic zone appeared elongated and atrophic. CONCLUSION: The results suggest that BPH may be associated with the development of fibrotic material and atrophy of glands within the peripheral zone. Because this atrophy involves glands where 80% of prostate cancer originates, this potentially explains the inverse relationship between PCa and BPH.

Histological changes of the peripheral zone in small and large prostates and possible clinical implications.

INTRODUCTION: It is well documented in literature that most prostate carcinomas (PCa) arise in the peripheral zone (PZ). Additionally, an inverse relationship between prostate size and the incidence of PCa has been demonstrated in recent studies. However, little is known about gland distribution in the peripheral zone of larger prostates compared to smaller prostates. In this study, we examined the histo-anatomical gland distribution within the peripheral zone in small and large prostates and discuss possible clinical implications. METHODS: A semi-quantitative analysis of gland density and capsule thickness was performed using light microscopy on 10 large (≥80 g) prostate specimens and 10 small (<30 g) prostate specimens from patients who underwent radical prostatectomy at Texas Tech University Health Sciences Center between the years 2010 and 2016. Samples from radical prostatectomies were used to ensure a whole, preserved prostate with an intact surgical capsule. Gland counts were performed on five random fields under 100 × magnification, while capsule thickness was measured on three random fields per case; thus, a total 50 fields and 30 fields were analyzed for each of the two groups for gland counts and capsule thickness measurements, respectively. Microscopy was standardized to the posterior aspect of the prostate, between 4 o'clock and 6 o'clock along the equatorial region between the apex and base. RESULTS: Large prostates possessed a significantly lower mean gland count per field compared to small prostates (10.34±4.15, n=50 vs 18.00±5.41, n=50; t=8.16, df=49, P<0.001). Additionally, large prostates showed a significantly higher average capsule thickness in millimeters compared to small prostates (1.80 mm, ±1.12 mm, n=30 vs 0.90 mm, ±0.56, n=30; t=8.16, df=49, P<0.001). CONCLUSION: The results demonstrate that prostate hypertrophy leads to both decreased gland density in the peripheral zone and increased capsule thickness, suggesting that growth-induced expansion of the prostate against its capsule leads to compression-induced atrophy and fibrosis of glandular tissue within the peripheral zone (PZ). A decrease in gland density within the PZ may have clinical implications shedding light, for instance, on the reduction in PCa incidence in patients with large prostates as compared to smaller prostates, a phenomenon well documented in the literature.

Video-assisted transumbilical Meckel's diverticulectomy in children.

The treatment of Meckel's diverticulum (MD) in children is resection. Some data exist for the use of laparoscopic resection. The Video-Assisted Transumbilical (VAT) single-trocar technique has been recently described for appendectomy. We also have used this technique for the resection of MD. The purpose of this study is to report our experience with laparoscopic-assisted resection of MD using both the three-trocar and the single-trocar techniques. The Institutional Review Board approved our retrospective chart review of all patients with the diagnosis of MD. Only the cases that were treated via laparoscopy were included. Technique of resection was at the discretion of the surgeon. Nine patients underwent laparoscopic resection of an MD from 2000 to 2005. Four patients underwent the three-trocar technique (LAP n = 4) and the remaining five underwent the video-assisted transumbilical single-trocar technique (VAT n = 5) procedure. Indications for surgery included gastrointestinal bleeding (VAT n = 3; LAP n = 2), malrotation (LAP n = 2), intussusception (VAT n = 1), and abdominal pain (VAT n = 1). All patients were male, and ages ranged from 7 months to 17 years for the VAT group and 8 months to 15 years for the LAP group. The average length of surgery for the LAP versus VAT was 128 minutes (94-170 minutes) and 81.4 minutes (42-96 minutes) respectively. Of the five patients undergoing LAP, two Ladd's procedures and three appendectomies were included during the same anesthesia. Only a single appendectomy procedure was performed during a VAT. The average time until full feeds with the LAP and VAT was 4.3 days (2-8 days) and 2.0 days (1-3 days) respectively. The overall length of stay with LAP versus VAT was 4.3 days (2-8 days) and 3.7 days (2-5 days). Only one case using the LAP method required conversion to an open laparotomy. Though no randomized trial for the removal of MD exists, our data suggest that the use of laparoscopy for removal of both symptomatic and asymptomatic MD is safe and effective. Additionally, the one trocar technique is feasible and may be beneficial in terms of fewer incisions and operative costs; however, more patients need to be studied.

Alternative splicing of helicase-like transcription factor (Hltf): Intron retention-dependent activation of immune tolerance at the feto-maternal interface.

Hltf is regulated by intron retention, and global Hltf-deletion causes perinatal lethality from hypoglycemia. In heart, full-length Hltf is a transcriptional regulator of Hif-1α that controls transport systems. Thus, we tested the hypothesis that Hltf deletion from placenta caused or exacerbated neonatal hypoglycemia via Hif-1α regulation of nutrient transporters. RNA-seq data analyses identified significant changes in transcript expression and alternative splicing (AS) in E18.5 placentome. iPathwayGuide was used for gene ontology (GO) analysis of biological processes, molecular functions and cellular components. Elim pruning algorithm identified hierarchical relationships. The methylome was interrogated by Methyl-MiniSeq Epiquest analysis. GO analysis identified gene enrichment within biological processes. Protein expression was visualized with immunohistochemistry. Although two Hltf mRNA isoforms are quantifiable in most murine tissues, only the truncated Hltf isoform is expressed in placenta. The responsible intron retention event occurs in the absence of DNA methylation. iPathwayGuide analysis identified 157 target genes of 11,538 total genes with measured expression. These were obtained using a threshold of 0.05 for statistical significance (p-value) and a long fold change of expression with absolute value of at least 0.6. Hltf deletion altered transcription of trophoblast lineage-specific genes, and increased transcription of the Cxcr7 (p = 0.004) gene whose protein product is a co-receptor for human and simian immunodeficiency viruses. Concomitant increased Cxcr7 protein was identified with immunolabeling. Hltf deletion had no effect on transcription or site-specific methylation patterns of Hif-1α, the major glucose transporters, or System A amino acid transporters. There was no measureable evidence of uteroplacental dysfunction or fetal compromise. iPathGuide analysis revealed Hltf suppresses cytolysis (10/21 genes; p-value 1.900e-12; p-value correction: Elim pruning; GO:019835) including the perforin-granzyme pathway in uterine natural killer cells. Our findings 1) prove the truncated Hltf protein isoform is a transcription factor, 2) establish a functional link between AS of Hltf and immunosuppression at the feto-maternal interface, 3) correlate intron retention with the absence of DNA methylation, and 4) underscore the importance of differential splicing analysis to identify Hltf's functional diversity.

Enhanced fear memories and brain glucose metabolism (18F-FDG-PET) following sub-anesthetic intravenous ketamine infusion in Sprague-Dawley rats.

Ketamine is a multimodal dissociative anesthetic, which provides powerful analgesia for victims with traumatic injury. However, the impact of ketamine administration in the peri-trauma period on the development of post-traumatic stress disorder (PTSD) remains controversial. Moreover, there is a major gap between preclinical and clinical studies because they utilize different doses and routes of ketamine administration. Here, we investigated the effects of sub-anesthetic doses of intravenous (IV) ketamine infusion on fear memory and brain glucose metabolism (BGluM) in rats. Male Sprague-Dawley rats received an IV ketamine infusion (0, 2, 10, and 20 mg/kg, 2 h) or an intraperitoneal (IP) injection (0 and 10 mg/kg) following an auditory fear conditioning (3 pairings of tone and foot shock [0.6 mA, 1 s]) on day 0. Fear memory retrieval, fear extinction, and fear recall were tested on days 2, 3, and 4, respectively. The effects of IV ketamine infusion (0 and 10 mg/kg) on BGluM were measured using 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT). The IV ketamine infusion dose-dependently enhanced fear memory retrieval, delayed fear extinction, and increased fear recall in rats. The IV ketamine (10 mg/kg) increased BGluM in the hippocampus, amygdala, and hypothalamus, while decreasing it in the cerebellum. On the contrary, a single ketamine injection (10 mg/kg, IP) after fear conditioning facilitated fear memory extinction in rats. The current findings suggest that ketamine may produce differential effects on fear memory depending on the route and duration of ketamine administration.

What do consumers and healthcare providers in West Virginia think of long-term care?

In recent years, the media has portrayed long-term care in a negative light, with exposè news stories on skilled nursing facilities, personal care homes, and hospitals that provide long-term care. There have been few positive news stories to counter the negative ones, and there is concern that the public perception of long-term care is inaccurate. The authors conducted the following study to evaluate how the West Virginia consumer perceives and defines long-term care and if there is a difference in that perception as compared with healthcare workers' perceptions and definitions of long-term care. The results of the study indicate that the respondents' education level, not occupation, has the most significant influence on respondents' definitions and perceptions of long-term care. Respondents felt that although media articles are informative, they are not accurate, and that long-term care is a needed service they would consider both for themselves and for a loved one. The results of the study suggest that current marketing strategies employed by nursing homes are working, as respondents largely believe that long-term care is provided in nursing homes and that they would likely seek care there if needed.

Injuries in pediatric patients with seatbelt contusions.

Children restrained with lap belts may sustain severe injuries. We investigated the frequency of each type of injury associated with seatbelt contusions. The medical records of all trauma patients with ICD-9 codes for abdominal wall contusions from January 1, 1999, to December 31, 2001, were reviewed. All patients with seatbelt contusions were included in the study. Age, seat position, weight, restraint-type, sex, and mechanism of injury were noted. There were 1447 admissions for trauma over the 3-year period. Forty-six patients (ages 4-13) had a seatbelt contusion. Thirty-three wore lap belts, and 13 wore lap and shoulder harnesses. Twenty-two children required abdominal exploration. Small bowel injuries were the most common intra-abdominal injuries. Facial injuries were the most common associated injuries. Forty-eight per cent of children with seatbelt contusions in our institution required surgery. The smaller patients tend to have higher frequency of abdominal injuries. The presence of seatbelt contusion indicates the possibility of severe internal injuries.

Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone.

PURPOSE: Persistent androgen signaling is implicated in castrate-resistant prostate cancer (CRPC) progression. This study aimed to evaluate androgen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations. PATIENTS AND METHODS: This was an open-label, observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010. Patients received oral abiraterone acetate (1 g) once daily and prednisone (5 mg) twice daily. Androgen receptor (AR) and CYP17 expression were assessed by immunohistochemistry, testosterone concentration by mass spectrometry, AR copy number by polymerase chain reaction, and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues. RESULTS: Median overall survival was 555 days (95% CI, 440 to 965+ days). Maximal prostate-specific antigen decline ≥ 50% occurred in 28 (50%) of 56 patients. Homogeneous, intense nuclear expression of AR, combined with ≥ 10% CYP17 tumor expression, was correlated with longer time to treatment discontinuation (> 4 months) in 25 patients with tumor-infiltrated bone marrow samples. Pretreatment CYP17 tumor expression ≥ 10% was correlated with increased bone marrow aspirate testosterone. Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression. CONCLUSION: The observed pretreatment androgen-signaling signature is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels. Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone.

Overexpression of defense response genes in transgenic wheat enhances resistance to Fusarium head blight.

Fusarium head blight (FHB) of wheat, caused by Fusarium graminearum and other Fusarium species, is a major disease problem for wheat production worldwide. To combat this problem, large-scale breeding efforts have been established. Although progress has been made through standard breeding approaches, the level of resistance attained is insufficient to withstand epidemic conditions. Genetic engineering provides an alternative approach to enhance the level of resistance. Many defense response genes are induced in wheat during F. graminearum infection and may play a role in reducing FHB. The objectives of this study were (1) to develop transgenic wheat overexpressing the defense response genes alpha-1-purothionin, thaumatin-like protein 1 (tlp-1), and beta-1,3-glucanase; and (2) to test the resultant transgenic wheat lines against F. graminearum infection under greenhouse and field conditions. Using the wheat cultivar Bobwhite, we developed one, two, and four lines carrying the alpha-1-purothionin, tlp-1, and beta-1,3-glucanase transgenes, respectively, that had statistically significant reductions in FHB severity in greenhouse evaluations. We tested these seven transgenic lines under field conditions for percent FHB disease severity, deoxynivalenol (DON) mycotoxin accumulation, and percent visually scabby kernels (VSK). Six of the seven lines differed from the nontransgenic parental Bobwhite line for at least one of the disease traits. A beta-1,3-glucanase transgenic line had enhanced resistance, showing lower FHB severity, DON concentration, and percent VSK compared to Bobwhite. Taken together, the results showed that overexpression of defense response genes in wheat could enhance the FHB resistance in both greenhouse and field conditions.

Video-assisted transumbilical appendectomy in children.

BACKGROUND: Video-assisted transumbilical appendectomy (VATA) is a combination of laparoscopic and open techniques and is not widely used in children. We are reporting our most recent experience with this technique. METHODS: After the institutional review board approval, the charts of patients who underwent VATA between December 2003 and October 2004 were retrospectively reviewed. All children presenting with a preoperative diagnosis of appendicitis were candidates. A 10-mm trocar was placed in the umbilicus. An operating laparoscope was used for mobilizing the appendix. The appendix was delivered through the umbilicus. A standard extracorporeal appendectomy was performed. The umbilical ring was closed and the wound irrigated. Demographic and outcome data were collected and is presented as mean +/- SD. RESULTS: Sixty-one males and 50 females underwent VATA (n = 111). Age and weight were 11 +/- 3.2 years and 49 +/- 22 kg, respectively. Six patients had previous abdominal surgery. Operative time was 36 +/- 24 minutes (range, 9-140 minutes). An additional trocar was placed in 2 patients, and 2 patients were converted to open. Five patients had additional procedures. Appendicitis was classified intraoperatively as acute (n = 44), suppurative (n = 5), gangrenous (n = 8), ruptured (n = 30), appendiceal colic (n = 13), and other (n = 11). Preoperative antibiotics were given to 95 patients and were continued in 35 patients postoperatively. Length of stay was 1.8 +/- 1.7 days (range, 1-11 days). Length of follow-up was 13 +/- 6.3 days (n = 90). Complications included intra-abdominal abscess (n = 1) and wound infection (n = 7). CONCLUSIONS: Video-assisted transumbilical appendectomy minimizes equipment needs, thus, potentially reducing cost. Simple and complex appendectomies can be performed even if the patient has had previous abdominal surgery. Our complication rate was low, and our operating times and length of stay were short. Video-assisted transumbilical appendectomy is a safe and effective technique in children and can be used in lieu of the 3-trocar laparoscopic technique.

Investigation of in vivo fatty acid metabolism in AFABP/aP2(-/-) mice.

The metabolic impact of the murine adipocyte fatty acid-binding protein (AFABP/aP2) on lipid metabolism was investigated in the AFABP/aP2(-/-) mouse and compared with wild-type C57BL/6J littermates. Mice were weaned on a high-fat diet (59% of energy from fat) and acclimated to meal feeding. Stable isotopes were administered, and indirect calorimetry was performed to quantitate fatty acid flux, dietary fatty acid utilization, and substrate oxidation. Consistent with previous in situ and in vitro studies, fasting serum nonesterified fatty acid (NEFA) release was significantly reduced in AFABP/aP2(-/-) (17.1 +/- 9.0 vs. 51.9 +/- 22.9 mg.kg(-1).min(-1)). AFABP/aP2(-/-) exhibited higher serum NEFA (1.4 +/- 0.6 vs. 0.8 +/- 0.4 mmol/l, AFABP/aP2(-/-) vs. C57BL/6J, respectively) and triacylglycerol (TAG; 0.23 +/- 0.09 vs. 0.13 +/- 0.10 mmol/l) and accumulated more TAG in liver tissue (2.9 +/- 2.3 vs. 1.1 +/- 0.8% wet wt) in the fasted state. For the liver-TAG pool, 16.4 +/- 7.3% of TAG-fatty acids were derived from serum NEFA in AFABP/aP2(-/-). In contrast, a significantly greater portion of C57BL/6J liver-TAG was derived from serum NEFA (42.3 +/- 25.5%) during tracer infusion. For adipose-TAG stores, only 0.29 +/- 0.04% was derived from serum NEFA in AFABP/aP2(-/-), and, in C57BL/6J, 1.85 +/- 0.97% of adipose-TAG was derived from NEFA. In addition, AFABP/aP2(-/-) preferentially oxidized glucose relative to fatty acids in the fed state. These data demonstrate that in vivo disruption of AFABP/aP2(-/-) leads to changes in the following two major metabolic processes: 1) decreased adipose NEFA efflux and 2) preferential utilization of glucose relative to fatty acids.