SWI as an Alternative to Contrast-Enhanced Imaging to Detect Acute MS Lesions.

BACKGROUND AND PURPOSE: Acute inflammatory activity of MS lesions is traditionally assessed through contrast-enhanced T1-weighted MR images. The aim of our study was to determine whether a qualitative evaluation of non-contrast-enhanced SWI of new T2-hyperintense lesions might help distinguish acute and chronic lesions and whether it could be considered a possible alternative to gadolinium-based contrast agents for this purpose. MATERIALS AND METHODS: Serial MR imaging studies from 55 patients with MS were reviewed to identify 169 new T2-hyperintense lesions. Two blinded neuroradiologists determined their signal pattern on SWI, considering 5 categories (hypointense rings, marked hypointensity, mild hypointensity, iso-/hyperintensity, indeterminate). Two different blinded neuroradiologists evaluated the presence or absence of enhancement in postcontrast T1-weighted images of the lesions. The Fisher exact test was used to determine whether each category of signal intensity on SWI was associated with gadolinium enhancement. RESULTS: The presence of hypointense rings or marked hypointensity showed a strong association with the absence of gadolinium enhancement (P < .001), with a sensitivity of 93.0% and a specificity of 82.9%. The presence of mild hypointensity or isohyperintensity showed a strong association with the presence of gadolinium enhancement (P < .001), with a sensitivity of 68.3% and a specificity of 99.2%. CONCLUSIONS: A qualitative analysis of the signal pattern on SWI of new T2-hyperintense MS lesions allows determining the likelihood that the lesions will enhance after administration of a gadolinium contrast agent, with high specificity albeit with a moderate sensitivity. While it cannot substitute for the use of contrast agent, it can be useful in some clinical settings in which the contrast agent cannot be administered.

Example of antimicrobial stewardship program in a community hospital in Italy.

BACKGROUND: Inappropriate use of antibiotics has caused the emergence of resistant strains of bacteria. The hospital of Alessandria, Italy, implemented an antimicrobial stewardship (AS) pilot program between 2013 and 2015 in the intensive care units (ICUs) and internal medicine departments of Casale Monferrato and Tortona. We aimed to describe the project, results at the end of the intervention, and its strengths and weaknesses. METHODS: The protocol, designed by the local infection control committee, included three consecutive steps: local guidelines for empirical antibiotic therapy and list of prescription antibiotics with justification, monitoring of antibiotic consumption and antimicrobial resistance trend, and peer-to-peer audit sessions in the wards. RESULTS: One thousand and eighty-five observations were made, corresponding to 850 patients admitted to the ICUs (16.7%) and internal medicine departments (83.3%). Appropriate antibiotic prescriptions increased by 6.4% between 2013 and 2015. The greatest improvement in appropriate prescriptions was observed for glycopeptides and fluoroquinolones (+17.4% and +16.2%, respectively). We reported 305 inappropriate prescriptions, with the most frequent errors being absence of an infectious process (33.3%), inadequate combination therapy (12.8%), and absence of microbiological investigations (8.5%). A reduced incidence of methicillin-resistant Staphylococcusaureus (MRSA) was also observed (p<0.0037). CONCLUSIONS: Antimicrobial stewardship programs contribute to improving antibiotic prescription and can be implemented in small community hospitals. Narrower interventions, focused on a single disease or single antibiotic should be encouraged.

THE DECADE OF THE RABiT (2005-15).

The RABiT (Rapid Automated Biodosimetry Tool) is a dedicated Robotic platform for the automation of cytogenetics-based biodosimetry assays. The RABiT was developed to fulfill the critical requirement for triage following a mass radiological or nuclear event. Starting from well-characterized and accepted assays we developed a custom robotic platform to automate them. We present here a brief historical overview of the RABiT program at Columbia University from its inception in 2005 until the RABiT was dismantled at the end of 2015. The main focus of this paper is to demonstrate how the biological assays drove development of the custom robotic systems and in turn new advances in commercial robotic platforms inspired small modifications in the assays to allow replacing customized robotics with 'off the shelf' systems. Currently, a second-generation, RABiT II, system at Columbia University, consisting of a PerkinElmer cell::explorer, was programmed to perform the RABiT assays and is undergoing testing and optimization studies.

Effects of short-term manipulation of serum FFA concentrations on left ventricular energy metabolism and function in patients with heart failure: no association with circulating bio-markers of inflammation.

BACKGROUND AND AIMS: We wanted to assess the effects of short-term changes in serum free fatty acids (FFAs) on left ventricular (LV) energy metabolism and function in patients with heart failure and whether they correlated with circulating markers of inflammation. METHODS AND RESULTS: LV function and phosphocreatine (PCr)/ATP ratio were assessed using MR imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) in 11 men with chronic heart failure in two experimental conditions 7 days apart. Study 1: MRI and 31P-MRS were performed before and 3-4 h after i.v. bolus + continuous heparin infusion titrated to achieve a serum FFA concentration of 1.20 mM. Study 2: The same protocol was performed before and after the oral administration of acipimox titrated to achieve a serum FFA concentration of 0.20 mM. Serum concentrations of IL6, TNF-α, PAI-1, resistin, visfatin and leptin were simultaneously assessed. Serum glucose and insulin concentrations were not different between studies. The PCr/ATP ratio (percent change from baseline: +6.0 ± 16.9 and -16.6 ± 16.1 % in Study 1 and Study 2, respectively; p = 0.005) and the LV ejection fraction (-1.5 ± 4.0 and -6.9 ± 6.3 % in Study 1 and Study 2, respectively; p = 0.044) were reduced during low FFA when compared to high FFA. Serum resistin was higher during Study 1 than in Study 2 (p < 0.05 repeated measures ANOVA); meanwhile, the other adipocytokines were not different. CONCLUSION: FFA deprivation, but not excess, impaired LV energy metabolism and function within hours. Cautions should be used when sudden iatrogenic modulation of energy substrates may take place in vulnerable patients.

Incretins or anti-incretins? A new model for the "entero-pancreatic axis".

The role of incretins in glucose homeostasis is well known. Yet, in recent years, the sustained weight loss and rapid glycemic control following bariatric surgery has challenged our understanding of the intestinal-pancreatic interaction. This in turn led to the introduction of metabolic surgery, an innovative medical discipline in which a surgical manipulation of the gastrointestinal tract (e. g., through a Roux-en-Y gastric bypass, RYGB, or Bilio-Pancreatic-Diversion, BPD) yields a sustained remission of diabetes mellitus. The pathophysiological background of this metabolic effect is, amongst other things, based on the anti-incretin theory. This theory postulates that in addition to the well-known incretin effect, nutrient passage through the GI-tract could also activate negative feedback mechanisms (anti-incretins) to balance the effects of incretins and other postprandial glucose-lowering mechanisms (i. e., suppression of ghrelin, glucagon, and hepatic glucose production via activation of nutrient sensing). This in turn prevents postprandial hyperinsulinemic hypoglycemia. The bypass of the duodenum, the entire jejunum and the first portion of the ileum by BPD induce normalization of peripheral insulin sensitivity, while the bypass of a shorter intestinal tract by RYGB mainly improves the hepatic insulin sensitivity. In addition, RYGB greatly increases insulin secretion. Therefore, metabolic surgery highlights the important role of the small intestine in glucose homeostasis, while until few years ago, it was only the pancreas and the liver that were thought to represent the regulatory organs for glucose disposal.

Bladder urothelial neoplasms in pediatric age: experience at three tertiary centers.

INTRODUCTION: Urothelial bladder neoplasms (UBN) typically occur in patients in their sixth or seventh decade of life while they are infrequent in children and young adults. They occur in 0.1-0.4% of the population in the first two decades of life. Their management is controversial and paediatric guidelines are currently unavailable. OBJECTIVE: To further expound the available data on the outcome of patients younger than 18 year old diagnosed with UBN. STUDY DESIGN: We retrospectively reviewed the files of all the consecutive paediatric patients with UBN treated in three tertiary paediatric urology units from January 1999 to July 2013. Lesions were classified according to the 2004 WHO/ISUP criteria as urothelial papillomas (UP), papillary urothelial neoplasm of low malignant potential (PUNLMP), low-grade urothelial carcinoma (LGUC), and high-grade urothelial carcinoma (HGUC). RESULTS: The table shows the results. Management after TURB varied among centres. One centre recommended only follow-up US at increasing intervals whereas another follow-up US plus urine cytologies and endoscopies, every three months in the first year, and at increasing intervals thereafter. After a median follow-up of 5 years (range 9 months-14.5 years), none of the patients showed disease recurrence or progression. DISCUSSION: UBN is an uncommon condition in children and adolescents and, unlike in adults, its incidence, follow-up and outcome still controversial. Paediatric guidelines are currently lacking and management varies among centres. Gross painless haematuria is the most common presenting symptom. Therefore, this symptom should never be underestimated. US is generally the first investigation and additional imaging seems unnecessary. TURB often allows for complete resection. Lesions are generally solitary, non-muscle invasive, and low-grade (mainly UP and PUNLMP). Ideal follow-up protocol is the most controversial point. Reportedly, recurrence or progression during follow-up is uncommon in patients under 20 years, recurrence rate 7% and a single case of progression reported so far. Accordingly, a follow-up mainly based on serial US might be considered in this age group compared to adults where also serial endoscopies and urine cytologies are recommended. In the selection of the follow-up investigations, it should also be taken into consideration that urine cytology has a low sensibility in the detection of low-grade lesions while cystoscopy in young patients requires a general anaesthesia and hospitalization, and carries an increased risk of urethral manipulation. CONCLUSION: UBN is a rare condition in children. Ultrasound is generally accurate in order to visualize the lesion, and TURB can treat the condition. Lesions are generally low-grade and non-muscle invasive, but high-grade lesions can also be detected. In present series, after TURB, follow-up US monitoring at increasing intervals was used at all centres, follow-up cystoscopies were added in two centres, but with different schedules. Urine cytologies were considered only at one centre. After a median follow-up of 5 years (range 9 months-14.5 years), none of the patients showed recurrence or progression of the disease.

Three-dimensional cellular distribution in polymeric scaffolds for bone regeneration: a microCT analysis compared to SEM, CLSM and DNA content.

In orthopaedic surgery the tissues damaged by injury or disease could be replaced using constructs based on biocompatible materials, cells and growth factors. Scaffold design, porosity and early colonization are key components for the implant success. From biological point of view, attention may be also given to the number, type and size of seeded cells, as well as the seeding technique and cell morphological and volumetric alterations. This paper describes the use of the microCT approach (to date used principally for mineralized matrix quantification) to observe construct colonization in terms of cell localization, and make a direct comparison of the microtomographic sections with scanning electron microscopy images and confocal laser scanning microscope analysis. Briefly, polycaprolactone scaffolds were seeded at different cell densities with MG63 osteoblastic-like cells. Two different endpoints, 1 and 2 weeks, were selected for the three-dimensional colonization and proliferation analysis of the cells. By observing all images obtained, in addition to a more extensive distribution of cells on scaffolds surfaces than in the deeper layers, cell volume increased at 2 weeks compared to 1 week after seeding. Combining the cell number quantification by deoxyribonucleic acid analysis and the single cell volume changes by confocal laser scanning microscope, we validated the microCT segmentation method by finding no statistical differences in the evaluation of the cell volume fraction of the scaffold. Furthermore, the morphological results of this study suggest that an effective scaffold colonization requires a precise balance between different factors, such as number, type and size of seeded cells in addition to scaffold porosity.

Modular polylactic acid microparticle-based scaffolds prepared via microfluidic emulsion/solvent displacement process: fabrication, characterization, and in vitro mesenchymal stem cells interaction study.

The present study reports a novel approach for the design and fabrication of polylactic acid (PLA) microparticle-based scaffolds with microstructural properties suitable for bone and cartilage regeneration. Macroporous PLA scaffolds with controlled shape were fabricated by means of a semicontinuous process involving (1) microfluidic emulsification of a PLA/ethyl lactate solution (5% w/v) in a span 80/paraffin oil solution (3% v/v) followed by (2) particles coagulation/assembly in an acetone/water solution for the development of a continuous matrix. Porous scaffolds prepared from particles with monomodal or bimodal size distribution, overall porosity ranges from 93 to 96%, interparticles porosity from 41 to 54%, and static compression moduli from 0.3 to 1.4 MPa were manufactured by means of flow rate modulation of of the continuous phase during emulsion. The biological response of the scaffolds was assessed in vitro by using bone marrow-derived rat mesenchymal stem cells (MSCs). The results demonstrated the ability of the scaffolds to support the extensive and uniform three-dimensional adhesion, colonization, and proliferation of MSCs within the entire construct.

Processing/structure/property relationship of multi-scaled PCL and PCL-HA composite scaffolds prepared via gas foaming and NaCl reverse templating.

In this study, we investigated the processing/structure/property relationship of multi-scaled porous biodegradable scaffolds prepared by combining the gas foaming and NaCl reverse templating techniques. Poly(ε-caprolactone) (PCL), hydroxyapatite (HA) nano-particles and NaCl micro-particles were melt-mixed by selecting different compositions and subsequently gas foamed by a pressure-quench method. The NaCl micro-particles were finally removed from the foamed systems in order to allow for the achievement of the multi-scaled scaffold pore structure. The control of the micro-structural properties of the scaffolds was obtained by the optimal combination of the NaCl templating concentration and the composition of the CO2-N2 mixture as the blowing agent. In particular, these parameters were accurately selected to allow for the fabrication of PCL and PCL-HA composite scaffolds with multi-scaled open pore structures. Finally, the biocompatibility of the scaffolds has been assessed by cultivating pre-osteoblast MG63 cells in vitro, thus demonstrating their potential applications for bone regeneration.

Experimental validation of a reach-and grasp optimization algorithm inspired to human arm-hand control.

Taking inspiration from neurophysiological studies on synergies in the human grasping action, this paper tries to demonstrate that it is possible to find a general rule for performing a stable, human-like cylindrical grasp with a robotic hand. To this purpose, the theoretical formulation and the experimental validation of a reach-and-grasp algorithm for determining the optimal hand position and the optimal finger configuration for grasping a cylindrical object with known features are presented. The proposed algorithm is based on the minimization of an objective function expressed by the sum of the distances of the hand joints from the object surface. Algorithm effectiveness has preliminarily been tested by means of simulation trials. Experimental trials on a real arm-hand robotic system have then been carried out in order to validate the approach and evaluate algorithm performance.

NYHA Class II subgrouping: correlation with left ventricular dysfunction questionnaire (LVD-36) and ejection fraction.

AIM: NYHA classification divides into four classes. Although subjective and lacking of standardization, NYHA class II is in clinical practice often further subgrouped in IIA and IIB, where IIA class can be defined as dyspnea after running or climbing ≥ 2 ramps of stairs, and IIB class as dyspnea after fast walking or climbing 2 ramps of stairs. Validation of NYHA IIA and IIB sub-grouping was performed with left ventricular dysfunction questionnaire (LVD-36) results and echocardiographic left ventricular ejection fraction. METHODS: The study includes a total of 127 patients with both systolic and diastolic heart failure (mean age 65 ± 17, range 38-85 years). Sixteen patients were in NYHA class I, 81 patients in NYHA class II (45 in class IIA and 36 in class IIB) and 30 in class III. RESULTS: In class IIA patients' mean age was 64 ± 9 years, LVD-36 score 31.79 ± 14.06, EF 43 ± 10% (P = ns, P<0.001 and P=ns, respectively, vs. class I patients). In class IIB patients' mean age was 67 ± 10 years, LVD-36 score 48.90 ± 15.51, EF 39 ± 12% (P = ns, P < 0.0001 and P = ns, respectively, vs. IIA patients). In class III patients' mean age was 65 ± 11 years, LVD-36 score 65.17 ± 16.35, EF 32.77 ± 12.91% (P = ns, P < 0.01 and P = ns, respectively, compared with class IIB). CONCLUSION: NYHA class II sub-grouping appears an accurate method of classification and could represent a further useful tool in monitoring functional capacity of heart failure patients. NYHA class II sub-grouping correlates well with patients functional impairment and can therefore be implemented as an accurate method to better characterize heart failure patients.

Phenotypic characterization and putative virulence factors of human, animal and environmental isolates of Plesiomonas shigelloides.

Plesiomonas shigelloides (a bacterium widely distributed in aquatic ecosystems causing both intestinal and extra-intestinal diseases) shows a host of putative virulence markers, such as hemolysins, cytotoxins, production of exoenzymes associated with pathogenicity, adhesive ability and vacuolation of cell lines in vitro. Technical difficulties in detecting some of these virulence factors together with scantiness of epidemiological information, due to the lack of routine analysis for P. shigelloides as etiological agent of gastroenteritis, lead to sporadic and occasional finding of these bacteria. All this casts doubt on the real virulence potential of P. shigelloides and fuels a debate about assignment of these bacteria to the list of human pathogens. Here we demonstrated the phenotypic diversity and the putative virulence markers by examining serotype biochemical and virulence properties of 60 strains of P. shigelloides isolated from human, animal and environmental samples in different countries, which showed the unpredictable occurrence of the above properties depending on various locations and diverse sources.

Design of porous polymeric scaffolds by gas foaming of heterogeneous blends.

One of the challenges in tissue engineering scaffold design is the realization of structures with a pre-defined multi-scaled porous network. Along this line, this study aimed at the design of porous scaffolds with controlled porosity and pore size distribution from blends of poly(epsilon-caprolactone) (PCL) and thermoplastic gelatin (TG), a thermoplastic natural material obtained by de novo thermoplasticization of gelatin. PCL/TG blends with composition in the range from 40/60 to 60/40 (w/w) were prepared by melt mixing process. The multi-phase microstructures of these blends were analyzed by scanning electron microscopy and dynamic mechanical analysis. Furthermore, in order to prepare open porous scaffolds for cell culture and tissue replacement, the TG and PCL were selectively extracted from the blends by the appropriate combination of solvent and extraction parameters. Finally, with the proposed combination of gas foaming and selective polymer extraction technologies, PCL and TG porous materials with multi-scaled and highly interconnected porosities were designed as novel scaffolds for new-tissue regeneration.

Calibration of the thermoelastic constants for quantitative thermoelastic stress analysis on composites.

The application of thermoelastic stress analysis in composite materials is particularly complicated because of the anisotropy of the material, that determines the thermoelastic constant to be dependent on the direction of the fibers. A further difficulty depends on the constructive stratification of the material, whose mechanical properties vary with the depth from the surface and this causes thermoelastic constants to be dependent on the frequency of the load applied. By using an analytical two layer model, it has been possible to interpret experimental data, thus proposing an explanation of the dependence on the frequency of the measured thermoelastic constants. This has shown that the practical use of the thermoelastic effect for quantitative stress analysis on composites needs constants calibrated at the correct frequency, also considering the thin layer of superficial resin present in every composite material.

Analysis of memory and effector CD8+ T cell subsets in chronic graft-versus-host disease.

In humans, the selective depletion of CD8+ cells may prevent GVHD after allogeneic transplantation. These cells can infiltrate and damage target tissues. It is of interest to investigate the phenotypical characteristics and cytotoxic properties of the different CD8+ subsets in cGVHD patients. In a preliminary study we found that patients with cGVHD had a markedly elevated percentage of peripheral blood CCR7-/CD45RA+ cells compared to patients without cGVHD; conversely, the CCR7+/CD45RA+ subsets of CD8+ cells was significantly decreased. In this study, we report in depth on the phenotype of effector T cell subsets in cGVHD patients, as well as their proliferative capability, cytotoxic properties and cellular turnover. We confirm a predominance of effector T cell subsets in cGVHD patients and show that a large fraction of these cells down-regulate CCR7 and re-express CD45RA, thus approaching end-stage differentiation. Moreover CD8+ cells of cGVHD patients have low CD8 coreceptor expression, reduced proliferative potential and a high content of perforin and granzyme A. They also have a lower cell turnover and have more propensity to apoptosis, as demonstrated by BrdU incorporation. Taken together, our findings indicate a perturbation of the balance between naive/memory and effector/CD45RA+ CD8+ T cells, and suggest an involvement of the latter compartment characterized by a high content of cytotoxic equipment, in the pathogenesis of cGVHD.

Engineered mu-bimodal poly(epsilon-caprolactone) porous scaffold for enhanced hMSC colonization and proliferation.

The use of scaffold-based strategies in the regeneration of biological tissues requires that the design of the microarchitecture of the scaffold satisfy key microstructural and biological requirements. Here, we examined the ability of a porous poly(epsilon-caprolactone) (PCL) scaffold with novel bimodal-micron scale (mu-bimodal) porous architecture to promote and guide the in vitro adhesion, proliferation and three-dimensional (3-D) colonization of human mesenchymal stem cells (hMSCs). The mu-bimodal PCL scaffold was prepared by a combination of gas foaming (GF) and selective polymer extraction (PE) from co-continuous blends. The microarchitectural properties of the scaffold, in particular its morphology, porosity distribution and mechanical compression properties, were analyzed and correlated with the results of the in vitro cell-scaffold interaction study, carried out for 21days under static conditions. Alamar Blue assay, scanning electron microscopy, confocal laser scanning microscopy and histological analyses were performed to assess hMSC adhesion, proliferation and 3-D colonization. The results showed that the combined GF-PE technique allowed the preparation of PCL scaffold with a unique multiscaled and highly interconnected microarchitecture that was characterized by mechanical properties suitable for load-bearing applications. Study of the cell-scaffold interaction also demonstrated the ability of the scaffold to support hMSC adhesion and proliferation, as well as the possibility to promote and guide 3-D cell colonization by appropriately designing the microarchitectural features of the scaffold.

Validation of radioimmunoassay screening methods for beta-agonists in bovine liver according to Commission Decision 2002/657/EC.

Validation studies were carried out on a multi-residue screening method for anilinic type beta-agonists (clenbuterol, mabuterol, brombuterol, cimaterol, cimbuterol, mapenterol, clenpenterol) and a method for the phenolic type beta-agonist, salbutamol, in bovine liver. The validation was performed according to the European Union Commission Decision 2002/657/EC (European Commission 2002), which establishes criteria and procedures for the determination of parameters such as the detection capability (CCbeta), specificity, stability of standard solutions and stability of the analyte in matrix. CCbeta values for the eight target compounds were between 0.25 and 0.5 microg kg(-1). The stability of standard solutions and analytes in matrix and the specificity of the antibody were characterized. The methods are applicable for qualitative screening of beta-agonists for regulatory programmes according to European Union performance requirements, or as a semi-quantitative research tool for known target compounds.

Immunomodulating role of bisphosphonates on human gamma delta T cells: an intriguing and promising aspect of their antitumour activity.

Vgamma9Vdelta2 T cells have the ability to produce inflammatory cytokines involved in protective immunity against intracellular pathogens and tumours and to display strong cytolytic as well as bactericidal activities. This suggests a direct involvement of Vgamma9Vdelta2 T lymphocytes in immune control of cancer and infections. These observations have recently aided development of novel immunotherapeutic approaches aimed at Vgamma9Vdelta2 T cell activation. Nitrogen-containing bisphosphonates (N-BPs) play a crucial role in Vgamma9Vdelta2 T lymphocyte activation and in the acquisition of effector functions. The preliminary results of these innovative strategies are encouraging. Moreover, compelling evidence in the literature supports the hypothesis that the antitumour effect of bisphosphonates is exerted through direct as well as indirect mechanisms. An additional and not yet well explored mechanism by which N-BPs may display antineoplastic effect is related to their immunomodulatory properties. It is fascinating that N-BPs influence the immune system in various but interrelated ways, being able to enhance the innate and to promote the adaptive immune responses. For all these reasons, Vgamma9Vdelta2 T lymphocytes represent a particularly interesting target for immunotherapeutic protocols based on N-BP administration. All these unexpected effects of N-BPs on the immune system have opened new and intriguing possibilities of therapeutic use for these drugs.

Overexpression of apolipoprotein CIII increases and CETP reverses diet-induced obesity in transgenic mice.

OBJECTIVE: We recently described that hypertriglyceridemic apolipoprotein (apo) CIII transgenic mice show increased whole body metabolic rate. In this study, we used these apo CIII-expressing mice, combined or not with the expression of the natural promoter-driven CETP gene, to test the hypothesis that both proteins modulate diet-induced obesity. MEASUREMENTS AND RESULTS: Mice expressing apo CIII, CIII/CETP, CETP and nontransgenic (NonTg) mice were maintained on a high-fat diet (14% fat by weight) during 20 weeks after weaning. At the end of this period, all groups exhibited the expected lipemic phenotype. Fasting glucose levels were neither affected by the high-fat diet nor by the distinct genotypes. However, apo CIII mice showed significantly higher glycemia ( approximately 35%) and lower insulin levels ( approximately 45%) in the fed state, compared with the NonTg mice. The apo CIII mice presented significantly increased body weight, lipid content of the carcass ( approximately 25%), visceral adipose tissue mass (about twofold) and adipocyte size ( approximately 25%) compared with the CETP and NonTg mice. The CETP expression in the apo CIII background normalized the subcutaneous adipose depot and visceral adipocyte size to the levels of NonTg mice. Plasma leptin levels were lower in CETP groups (25-50%) and higher in the apo CIII mice. Similar core body temperature in all groups and similar liver mitochondrial resting respiration rates in CIII and NonTg mice indicate no differences in basal energy expenditure rates among these mice fed a high-fat diet. CONCLUSION: The elevation of plasma apo CIII levels aggravates diet-induced obesity and the expression of physiological levels of circulating CETP reverses this adipogenic effect, indicating a novel role for CETP in modulating adiposity.