Comparing MRI and arthroscopic appearances of common knee pathologies: A pictorial review.

Knee pathology, including anterior cruciate ligament (ACL) tears, meniscal tears, articular cartilage lesions, and intra-articular masses or cysts are common clinical entities treated by orthopedic surgeons with arthroscopic surgery. Preoperatively, magnetic resonance imaging (MRI) is now standard in confirming knee pathology, particularly detecting pathology less evident with history and physical examination alone. The radiologist's MRI interpretation becomes essential in evaluating intra-articular knee structures. Typically, the radiologist that interprets the MRI does not have the opportunity to view the same pathology arthroscopically. Thus, the purpose of this article is to illustratively reconcile what the orthopedic surgeon sees arthroscopically with what the radiologist sees on magnetic resonance imaging when viewing the same pathology. Correlating virtual and actual images can help better understand pathology, resulting in more accurate MRI interpretations. In this article, we present and review a series of MR and correlating arthroscopic images of ACL tears, meniscal tears, chondral lesions, and intra-articular masses and cysts. Short teaching points are included to highlight the importance of radiological signs and pathological MRI appearance with significant clinical and arthroscopic findings.

Efficiency of charge transfer in changing the dissociation dynamics of OD+ transients formed after the photo-fragmentation of D2O.

We present an investigation of the relaxation dynamics of deuterated water molecules after direct photo-double ionization at 61 eV. We focus on the very rare D+ + O+ + D reaction channel in which the sequential fragmentation mechanisms were found to dominate the dynamics. Aided by theory, the state-selective formation and breakup of the transient OD+(a1Δ, b1Σ+) is traced, and the most likely dissociation path-OD+: a1Δ or b1Σ+ → A 3Π â†’ X 3Σ- → B 3Σ--involving a combination of spin-orbit and non-adiabatic charge transfer transitions is determined. The multi-step transition probability of this complex transition sequence in the intermediate fragment ion is directly evaluated as a function of the energy of the transient OD+ above its lowest dissociation limit from the measured ratio of the D+ + O+ + D and competing D+ + D+ + O sequential fragmentation channels, which are measured simultaneously. Our coupled-channel time-dependent dynamics calculations reproduce the general trends of these multi-state relative transition rates toward the three-body fragmentation channels.

Atomic autoionization in the photo-dissociation of super-excited deuterated water molecules fragmenting into D+ + O+ + D.

We present the relaxation dynamics of deuterated water molecules via autoionization, initiated by the absorption of a 61 eV photon, producing the very rare D+ + O+ + D breakup channel. We employ the COLd target recoil ion momentum spectroscopy method to measure the 3D momenta of the ionic fragments and emitted electrons from the dissociating molecule in coincidence. We interpret the results using the potential energy surfaces extracted from multi-reference configuration interaction calculations. The measured particle energy distributions can be related to a super-excited monocationic state located above the double ionization threshold of D2O. The autoionized electron energy shows a sharp distribution centered around 0.5 eV, which is a signature of the atomic oxygen autoionization occurring in the direct and sequential dissociation processes of D2O+* at a large internuclear distance. In this way, an O+ radical fragment and a low-energy electron are created, both of which can trigger secondary reactions in their environment.

Core-satellite nanoreactors based on cationic photosensitizer modified hollow CuS nanocage for ROS diffusion enhanced phototherapy of hypoxic tumor.

Photodynamic therapy (PDT) efficiency is directly affected by the reactive oxygen species (ROS) generated by photosensitizers. However, ROSs' ultrashort life span and limited diffusion distance restrict the PDT efficiency. Therefore, it is important to control the delivery strategy of photosensitizers for PDT treatment. Herein, the core-satellite nanoreactors were fabricated with oxygen generation and ROS diffusion properties. The hollow CuS encapsulating horseradish peroxidase (HRP) was combined with the cationic photosensitizers (PEI-Ce6). The unique photosensitizers delivery strategy makes the nanoreactors achieve ROS diffusion-enhanced PDT effect. First, HRP in "core" (HRP@CuS) can decompose hydrogen peroxide (H2O2) to O2, increasing O2 levels on the surface of the nanoreactor. Second, the Ce6 molecules covalent-linked with PEI are uniformly dispersed on the surface of CuS as a "satellite", avoiding Ce6 aggregation and causing more Ce6 molecules be activated to produce more 1O2. Due to the Ce6 was on the surface of the CuS nanocages, the generated ROS may ensure a larger diffusion range. Meanwhile, the inherently CuS nanocages exhibit photothermal and photoacoustic (PA) effect. The photothermal effect further enhances the ROS diffusion. Under the guidance of PA imaging, nanoreactors exhibit highly efficient hypoxic tumor ablation via photodynamic and photothermal effect. Overall, the core-satellite nanoreactors provide an effective strategy for tumor therapy, further promoting the research of photosensitizers delivery.

Endothelial barrier function is co-regulated at vessel bifurcations by fluid forces and sphingosine-1-phosphate.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networks in vivo consist of vessel bifurcations, and this geometry generates hemodynamic forces at the bifurcation point distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations with in situ quantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which is characterized by approximately zero shear stress and 38 dyn•cm-2 stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of S1P with 3 dyn•cm-2 laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to bifurcated fluid flow and laminar shear stress is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.

Synthesis and Biological Evaluations of Electrophilic Steroids Inspired by the Taccalonolides.

Natural products have served as inspirational scaffolds for the design and synthesis of novel antineoplastic agents. Here we present our preliminary efforts on the synthesis and biological evaluation of a new class of electrophilic steroids inspired by the naturally occurring taccalonolides. We demonstrate that these simplified analogs exhibit highly persistent antiproliferative properties similar to the taccalonolides and retain activity against resistant cancer cell lines that warrants further preclinical development.

Randomized clinical trial of negative pressure wound therapy as an adjunctive treatment for small-area thermal burns in children.

BACKGROUND: The efficacy of negative pressure wound therapy (NPWT) in the acute management of burns remains unclear. The purpose of this trial was to compare standard Acticoat™ and Mepitel™ dressings with combined Acticoat™, Mepitel™ and continuous NPWT to determine the effect of adjunctive NPWT on re-epithelialization in paediatric burns. METHODS: This two-arm, single-centre RCT recruited children with acute thermal burns covering less than 5 per cent of their total body surface area. The primary outcome was time to re-epithelialization. Blinded assessments were performed using photographs captured every 3-5 days until discharge. Secondary measures included pain, itch, grafting, perfusion and scar management referrals. RESULTS: Some 114 patients were randomized. Median time to re-epithelialization was 8 (i.q.r. 7-11) days in the NPWT group and 10 (8-14) days in the control group. In a multivariable model, NPWT decreased the expected time to wound closure by 22 (95 per cent c.i. 7 to 34) per cent (P = 0·005). The risk of referral to scar management was reduced by 60 (18 to 81) per cent (P = 0·013). Four participants in the control group and one in the NPWT group underwent grafting. There were no statistically significant differences between groups in pain, itch or laser Doppler measures of perfusion. Adverse events were rare and minor, although NPWT carried a moderate treatment burden, with ten patients discontinuing early. CONCLUSION: Adjunctive NPWT hastened re-epithelialization in small-area burn injuries in children, but had a greater treatment burden than standard dressings alone. Registration number: ACTRN12618000256279 ( http://ANZCTR.org.au).

ANTECEDENTES: La eficacia del tratamiento de las heridas con presión negativa (negative pressure wound therapy, NPWT) en el tratamiento agudo de las quemaduras sigue sin estar claro. El propósito de este ensayo clínico fue comparar los apósitos estándar del tipo Acticoat™ y Mepitel™ con la combinación de Acticoat™, Mepitel™ y NPWT continua para determinar el efecto de la adición de NPWT en la reepitelización de las quemaduras en pediatría. MÉTODOS: Ensayo controlado y aleatorizado, con dos brazos y unicéntrico, que reclutó niños con quemaduras térmicas agudas que afectaban < 5% de la superficie corporal total. El resultado primario fue el tiempo hasta la reepitelización. Se realizaron evaluaciones a ciegas utilizando fotografías tomadas cada 3-5 días hasta el alta hospitalaria. Las medidas secundarias incluían dolor, picor, injerto, perfusión y derivación para el tratamiento de las cicatrices. RESULTADOS: Se aleatorizaron un total de 114 pacientes. La mediana de tiempo hasta la reepitelización fue 8 días (rango intercuartílico, interquartile range, IQR 7-11) en el grupo NPWT y 10 días (8-14) en el grupo control. En el modelo multivariable, el uso de NPWT disminuyó los días previstos hasta el cierre de la herida en un 22% (i.c. del 95% 7-34%; P = 0,005). El riesgo de ser derivado para el tratamiento de la cicatriz se redujo en un 60% (18-81%; P = 0,013). Cuatro participantes en el grupo control y uno en el grupo NPWT fueron sometidos a injertos. No hubo diferencias estadísticamente significativas en el dolor, picor, o mediciones de la perfusión con Doppler laser. Los eventos adversos fueron raros y menores, aunque NPWT conllevó una carga de tratamiento moderada con 10 pacientes que lo suspendieron precozmente. CONCLUSIÓN: El tratamiento complementario de la herida con presión negativa acelera el tiempo hasta la reepitelización en quemaduras de pequeña extensión en niños, pero implica una mayor carga de tratamiento.

Efficacy and cultural appropriateness of psychosocial interventions for paediatric burn patients and caregivers: a systematic review.

BACKGROUND: Paediatric burns are highly painful and traumatising injuries that are overrepresented among Aboriginal and Torres Strait Islander people. Paediatric burn patients' pain remains poorly managed by pharmacological interventions, leading to increased anxiety, distress, and trauma in patients and their caregivers. Non-pharmacological psychosocial interventions have been suggested as effective in reducing pain and psychological morbidities among paediatric burn patients and their caregivers; however, their degree of effectiveness and appropriateness for Aboriginal and Torres Strait Islander people is unclear. METHODS: A non-date restricted systematic review was conducted through four databases. Studies published in English assessing psychosocial interventions on paediatric burn patients' physical pain along with theirs and/or their caregiver's anxiety, distress, or trauma symptoms were identified and included in this review. Included studies were assessed for their ability to reduce one of the outcomes of interests and for their reflection of Aboriginal and Torres Strait Islander peoples' perspectives of health. RESULTS: Of the 3178 identified references, 17 were eligible. These include distraction based techniques (n = 8), hypnosis/familiar imagery (n = 2), therapeutic approaches (n = 4), and patient preparation/procedural control (n = 3). Distraction techniques incorporating procedural preparation reduced pain, while discharge preparation and increased 'patient control' reduced patient and caregiver anxiety; and internet based Cognitive Behaviour Therapy reduced short-term but not long-term post-traumatic stress symptoms. No interventions reflected Aboriginal and Torres Strait Islander peoples' perspectives of health; and few targeted caregivers or focused on reducing their symptoms. CONCLUSIONS: The development and assessment of psychosocial interventions to appropriately meet the needs of Aboriginal and Torres Strait Islander paediatric burn patients is required.

Competing Fluid Forces Control Endothelial Sprouting in a 3-D Microfluidic Vessel Bifurcation Model.

Sprouting angiogenesis-the infiltration and extension of endothelial cells from pre-existing blood vessels-helps orchestrate vascular growth and remodeling. It is now agreed that fluid forces, such as laminar shear stress due to unidirectional flow in straight vessel segments, are important regulators of angiogenesis. However, regulation of angiogenesis by the different flow dynamics that arise due to vessel branching, such as impinging flow stagnation at the base of a bifurcating vessel, are not well understood. Here we used a recently developed 3-D microfluidic model to investigate the role of the flow conditions that occur due to vessel bifurcations on endothelial sprouting. We observed that bifurcating fluid flow located at the vessel bifurcation point suppresses the formation of angiogenic sprouts. Similarly, laminar shear stress at a magnitude of ~3 dyn/cm2 applied in the branched vessels downstream of the bifurcation point, inhibited the formation of angiogenic sprouts. In contrast, co-application of ~1 µm/s average transvascular flow across the endothelial monolayer with laminar shear stress induced the formation of angiogenic sprouts. These results suggest that transvascular flow imparts a competing effect against bifurcating fluid flow and laminar shear stress in regulating endothelial sprouting. To our knowledge, these findings are the first report on the stabilizing role of bifurcating fluid flow on endothelial sprouting. These results also demonstrate the importance of local flow dynamics due to branched vessel geometry in determining the location of sprouting angiogenesis.

Regulation of biosimilar medicines and current perspectives on interchangeability and policy.

Competition arising from the increasing availability of biosimilar medicines has resulted in healthcare savings and has provided greater patient access to high cost therapeutics in Europe. The biosimilar market in the USA is relatively new so the full impact of biosimilar availability remains to be seen. Educational initiatives relating to the use of biosimilar medicines are currently being undertaken by regulators, policy makers and industry. The debate on biosimilars has moved on from the appropriateness of the regulatory framework which governs their approval, to the practice of interchangeability. Interchangeability is an important issue for healthcare professionals but different definitions and regulatory frameworks exist in the USA and Europe. In the USA, an interchangeable biological product is a biosimilar which may be substituted by a pharmacist, subject to local State policies. The interchangeability of a biosimilar with its reference medicine will be evaluated by the United States Food and Drug Administration (FDA) in cases where approval as an 'interchangeable product' is sought. In contrast, the European Medicines Agency (EMA) does not assess or make recommendations on interchangeability, therefore, in Europe, interchangeability does not mean substitution but is generally physician-led or driven by national policy. This paper provides an overview of the regulation of biosimilar medicines. Challenges associated with the demonstration of interchangeability and practical considerations relating to switching are also discussed. Finally, we present policies that have been adopted to date in several European countries, the USA and Australia, which aim to promote the use of biosimilar medicines.

Elevated high density lipoprotein cholesterol and low grade systemic inflammation is associated with increased gut permeability in normoglycemic men.

BACKGROUND & AIMS: Serum lipids and lipoproteins are established biomarkers of cardiovascular disease risk that could be influenced by impaired gut barrier function via effects on the absorption of dietary and biliary cholesterol. The aim of this study was to examine the potential relationship between gut barrier function (gut permeability) and concentration of serum lipids and lipoproteins, in an ancillary analysis of serum samples taken from a previous study. METHODS AND RESULTS: Serum lipids, lipoproteins and functional gut permeability, as assessed by the percentage of the urinary recovery of 51Cr-labelled EDTA absorbed within 24 h, were measured in a group of 30 healthy men. Serum lipopolysaccharide, high sensitivity C-reactive protein and interleukin-6 were also measured as markers of low-grade inflammation. The group expressed a 5-fold variation in total gut permeability (1.11-5.03%). Gut permeability was unrelated to the concentration of both serum total and low density lipoprotein (LDL)-cholesterol, but was positively associated with serum high density lipoprotein (HDL)-cholesterol (r = 0.434, P = 0.015). Serum HDL-cholesterol was also positively associated with serum endotoxaemia (r = 0.415, P = 0.023). CONCLUSION: The significant association between increased gut permeability and elevated serum HDL-cholesterol is consistent with the role of HDL as an acute phase reactant, and in this situation, potentially dysfunctional lipoprotein. This finding may have negative implications for the putative role of HDL as a cardio-protective lipoprotein.

Knowledge of Adverse Drug Reaction Reporting and the Pharmacovigilance of Biological Medicines: A Survey of Healthcare Professionals in Ireland.

BACKGROUND: In Europe, changes to pharmacovigilance legislation, which include additional monitoring of medicines, aim to optimise adverse drug reaction (ADR) reporting systems. The legislation also makes provisions related to the traceability of biological medicines. OBJECTIVE: The objective of this study was to assess (i) knowledge and general experience of ADR reporting, (ii) knowledge, behaviours, and attitudes related to the pharmacovigilance of biologicals, and (iii) awareness of additional monitoring among healthcare professionals (HCPs) in Ireland. METHODS: Hospital doctors (n = 88), general practitioners (GPs) (n = 197), nurses (n = 104) and pharmacists (n = 309) completed an online questionnaire. RESULTS: There were differences in mean knowledge scores relating to ADR reporting and the pharmacovigilance of biologicals among the HCP groups. The majority of HCPs who use biological medicines in their practice generally record biologicals by brand name but practice behaviours relating to batch number recording differed between some professions. HCPs consider batch number recording to be valuable but also regard it as being more difficult than brand name recording. Most respondents were aware of the concept of additional monitoring but awareness rates differed between some groups. Among those who knew about additional monitoring, there was higher awareness of the inverted black triangle symbol among pharmacists (> 86.4%) compared with hospital doctors (35.1%), GPs (35.6%), and nurses (14.9%). Hospital pharmacists had more experience and knowledge of ADR reporting than other practising HCPs. CONCLUSION: This study highlights the important role hospital pharmacists play in post-marketing surveillance. There is a need to increase pharmacovigilance awareness of biological medicines and improve systems to support their batch traceability.

Flow dynamics control endothelial permeability in a microfluidic vessel bifurcation model.

Endothelial barrier function is known to be regulated by a number of molecular mechanisms; however, the role of biomechanical signals associated with blood flow is comparatively less explored. Biomimetic microfluidic models comprised of vessel analogues that are lined with endothelial cells (ECs) have been developed to help answer several fundamental questions in endothelial mechanobiology. However, previously described microfluidic models have been primarily restricted to single straight or two parallel vessel analogues, which do not model the bifurcating vessel networks typically present in physiology. Therefore, the effects of hemodynamic stresses that arise due to bifurcating vessel geometries on ECs are not well understood. Here, we introduce and characterize a microfluidic model that mimics both the flow conditions and the endothelial/extracellular matrix (ECM) architecture of bifurcating blood vessels to systematically monitor changes in endothelial permeability mediated by the local flow dynamics at specific locations along the bifurcating vessel structure. We show that bifurcated fluid flow (BFF) that arises only at the base of a vessel bifurcation and is characterized by stagnation pressure of ∼38 dyn cm-2 and approximately zero shear stress induces significant decrease in EC permeability compared to the static control condition in a nitric oxide (NO)-dependent manner. Similarly, intravascular laminar shear stress (LSS) (3 dyn cm-2) oriented tangential to ECs located downstream of the vessel bifurcation also causes a significant decrease in permeability compared to the static control condition via the NO pathway. In contrast, co-application of transvascular flow (TVF) (∼1 µm s-1) with BFF and LSS rescues vessel permeability to the level of the static control condition, which suggests that TVF has a competing role against the stabilization effects of BFF and LSS. These findings introduce BFF at the base of vessel bifurcations as an important regulator of vessel permeability and suggest a mechanism by which local flow dynamics control vascular function in vivo.

High-Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin.

A translational need exists to understand and predict vancomycin-induced kidney toxicity. We describe: (i) a vancomycin high-performance liquid chromatography (HPLC) method for rat plasma and kidney tissue homogenate; (ii) a rat pharmacokinetic (PK) study to demonstrate utility; and (iii) a catheter retention study to enable future preclinical studies. Rat plasma and pup kidney tissue homogenate were analyzed via HPLC for vancomycin concentrations ranging from 3-75 and 15.1-75.5 µg/mL, respectively, using a Kinetex Biphenyl column and gradient elution of water with 0.1% formic acid: acetonitrile (70:30 v/v). Sprague-Dawley rats (n = 10) receiving 150 mg/kg of vancomycin intraperitoneally had plasma sampled for PK. Finally, a catheter retention study was performed on polyurethane catheters to assess adsorption. Precision was <6.1% for all intra-assay and interassay HPLC measurements, with >96.3% analyte recovery. A two-compartment model fit the data well, facilitating PK exposure estimates. Finally, vancomycin was heterogeneously retained by polyurethane catheters.

Microfluidic approaches to the study of angiogenesis and the microcirculation.

Microfluidic systems have emerged as a new class of perfusable in vitro culture models that have helped advance and refine our understanding of microvascular function. Cutting-edge microfluidic models have successfully integrated principles from quantitative analysis of vascular function, in vitro flow chambers, microfabrication techniques, and 3D tissue scaffolds. Here, we review the evolution of microfluidic systems, namely their progression from 2D planar microchannel arrays to 3D microtissue analogs, and highlight their recent contributions in elucidating the role of biomolecular transport and fluid mechanical stimuli in controlling angiogenesis. Further advancement of microfluidic systems in recapitulating tissue-level phenomena in vitro, controlling important physiochemical and biological parameters, and integrating cellular and molecular analysis will help further enhance their application within the microcirculation research community.

Relevance of liver fat to the impact of dietary extrinsic sugars on lipid metabolism.

In contrast to the decline in mortality from many non-infectious, chronic diseases in the UK, death from liver disease has increased exponentially in men and women over the past 40 years. This is primarily because of the over consumption of alcohol, but also the increased prevalence of obesity, which is linked to early pathology through the accumulation of liver fat. Supra-physiological intakes of fructose-containing sugar can produce acute, adverse effects on lipid metabolism, and deliver excess energy that increases bodyweight and the deposition of fat in sites other than adipose tissue, including the liver. This review addresses the variable metabolic origins of liver fat, and the key importance of postprandial lipid metabolism in this respect. The effects of supra-physiological intakes of sugar are also considered in context of the real world and established threshold for the adverse effects of sugar on cardio-metabolic risk factors. The review concludes that while the average intake of sugar in the UK falls well below this critical threshold, intakes in subgroups of adults, and especially adolescents, may be cause for concern. There is also evidence to suggest that raised liver fat, acquired, in part, through an impaired removal of postprandial lipaemia, can increase sensitivity to the adverse effects of sugar at all ages.

How FlAsH got its sparkle: historical recollections of the biarsenical-tetracysteine tag.

The biarsenical-tetracysteine tagging system was the first of (and inspiration for) the now numerous methods for site-specifically labeling proteins in living cells with small molecules such as fluorophores. This historical recollection describes its conception and the trial-and-error chemical development required to become a versatile technique.

Epi-illumination diffraction phase microscopy with white light.

We demonstrate the first reflection-based epi-illumination diffraction phase microscope with white light (epi-wDPM). The epi-wDPM system combines the off-axis, common-path, and white light approaches, in a reflection geometry enabling sub-nanometer spatial and temporal noise levels, while providing single-shot acquisition for opaque samples. We verified the epi-wDPM results by measuring control samples with known dimensions and comparing them to measurements from other well-established techniques. We imaged gold-coated HeLa cells to illustrate the tradeoffs between epi-wDPM with low and high spatial coherence.

Plasma free fatty acids do not provide the link between obesity and insulin resistance or ß-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study.

AIMS: To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and ß-cell function. METHODS: An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. RESULTS: After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: ß = -0.357; waist circumference: ß = -0.380; body fat mass: ß = -0.375) and disposition index (BMI: ß = -0.215; waist circumference: ß = -0.248; body fat mass: ß = -0.221) and positively associated with acute insulin response to glucose [BMI: ß = 0.200; waist circumference: ß = 0.195; body fat mass ß = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (ß = -0.133), acute insulin response to glucose (ß = -0.148) and disposition index [ß = -0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. CONCLUSIONS: Plasma free fatty acid levels have a modest negative association with insulin sensitivity, ß-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or ß-cell dysfunction.