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Metabolic pathways are affected by the impacts of environmental contaminants underlying a large variability of toxic effects across different species. However, the systematic reconstruction of metabolic pathways remains limited in environmental sentinel species due to the lack of available genomic data in many taxa of animal diversity. In this study we used a multi-omics approach to reconstruct the most comprehensive map of metabolic pathways for a crustacean model in biomonitoring, the amphipod Gammarus fossarum in order to improve the knowledge of the metabolism of this sentinel species. We revisited the assembly of RNA-seq data by de novo approaches to reduce RNA contaminants and transcript redundancy. We also acquired extensive mass spectrometry shotgun proteomic data on several organs from a reference population of G. fossarum males and females to identify organ-specific metabolic profiles. The G. fossarum metabolic pathway reconstruction (available through the metabolic database GamfoCyc) was performed by adapting the genomic tool CycADS and we identified 377 pathways representing 7630 annotated enzymes, 2610 enzymatic reactions and the expression of 858 enzymes was experimentally validated by proteomics. To our knowledge, our analysis provides for the first time a systematic metabolic pathway reconstruction and the proteome profiles of these pathways at the organ level in this sentinel species. As an example, we show an elevated abundance in enzymes involved in ATP biosynthesis and fatty acid beta-oxidation indicative of the high-energy requirement of the gills, or the key anabolic and detoxification role of the hepatopancreatic caeca, as exemplified by the specific expression of the retinoid biosynthetic pathways and glutathione synthesis. In conclusion, the multi-omics data integration performed in this study provides new resources to investigate metabolic processes in crustacean amphipods and their role in mediating the effects of environmental contaminant exposures in sentinel species. This study provide the first evidence that it is possible to combine multiple omics data to exhaustively describe the metabolic network of a model species in ecotoxicology, Gammarus fossarum , for which a reference genome is not yet available. [Display omitted] • Metabolic pathway systematic reconstruction using transcriptomics of a sentinel freshwater amphipod, Gammarus fossarum. • Creation of an open-access molecular resource for G. fossarum metabolic network at http://arthropodacyc.cycadsys.org • Identification of organ-specific metabolic profiles using high resolution mass spectrometry proteomics [ABSTRACT FROM AUTHOR]

• Ventilator induced lung injuries are due to excessive stress, strain, or atelectrauma. • Driving pressure assesses the strain applied to the lungs during mechanical ventilation. • Mechanical power represents the energy load transferred from the ventilator to the respiratory system. • INTELLiVENT-ASV selected driving pressure and mechanical power considered in safe ranges for lung protection. Driving pressure (ΔP) and mechanical power (MP) are predictors of the risk of ventilation- induced lung injuries (VILI) in mechanically ventilated patients. INTELLiVENT-ASV® is a closed-loop ventilation mode that automatically adjusts respiratory rate and tidal volume, according to the patient's respiratory mechanics. This prospective observational study investigated ΔP and MP (and also transpulmonary ΔP (ΔP L) and MP (MP L) for a subgroup of patients) delivered by INTELLiVENT-ASV. Adult patients admitted to the ICU were included if they were sedated and met the criteria for a single lung condition (normal lungs, COPD, or ARDS). INTELLiVENT-ASV was used with default target settings. If PEEP was above 16 cmH2O, the recruitment strategy used transpulmonary pressure as a reference, and ΔP L and MP L were computed. Measurements were made once for each patient. Of the 255 patients included, 98 patients were classified as normal-lungs, 28 as COPD, and 129 as ARDS patients. The median ΔP was 8 (7 − 10), 10 (8 − 12), and 9 (8 − 11) cmH2O for normal-lungs, COPD, and ARDS patients, respectively. The median MP was 9.1 (4.9 – 13.5), 11.8 (8.6 – 16.5), and 8.8 (5.6 – 13.8) J/min for normal-lungs, COPD, and ARDS patients, respectively. For the 19 patients managed with transpulmonary pressure ΔP L was 6 (4 − 7) cmH2O and MP L was 3.6 (3.1 – 4.4) J/min. In this short term observation study, INTELLiVENT-ASV selected ΔP and MP considered in safe ranges for lung protection. In a subgroup of ARDS patients, the combination of a recruitment strategy and INTELLiVENT-ASV resulted in an apparently safe ΔP L and MP L. [ABSTRACT FROM AUTHOR]

Objective: Identifying objective risk-indicators for total joint replacement (TJR) is useful to enrich population at high risk in OA clinical trials. We investigate the association of urinary CTX-II, a biochemical marker of cartilage breakdown, with the risk of TJR.Method: 478 postmenopausal women (mean age 65.5 ± 7.5 yr) from the OFELY cohort were studied. CTX-II, serum CTX-I (bone resorption) and PINP (bone formation), were measured at baseline. Association between CTX-II and incidence of TJR was assessed by Cox Hazard Regression.Results: During a median (95%CI) 17.8 (15.0-18.1) years follow-up, 38 women sustained a TJR, including hip (n = 29) or knee (n = 9) replacement. CTX-II -but not CTX-I or PINP- was higher in patients with TJR (+34%, P = 0.001 vs women with no TJR). Increased baseline CTX-II levels were associated with a higher risk of TJR with a Hazard Ratio (HR) (95 CI) of 1.45 (1.13-1.85) per 1 SD increase after adjustment for age, BMI and total hip BMD. CTX-II remained significantly associated with the risk of TJR after further adjustment for total WOMAC, prevalent knee OA (KL ≥ 2) and self-reported hip OA [HR (95 CI): 1.31 (1.01-1.71), P = 0,04]. When women were categorized as low and high CTX-II (lower and above the 95 percentile of healthy premenopausal women, respectively), subjects with high levels had an age-BMI-hip BMD adjusted HR (95 CI) of 3.00 (1.54-5.85) compared to women with low levels which remained significant after further adjustment for WOMAC, knee and/or hip OA [HR (95 CI): 2.45 (1.25-4.89), P = 0.01].Conclusion: CTX-II is an independent risk indicator of TJR in postmenopausal women suggesting that it may be useful to identify subjects at high risk of TJR. [ABSTRACT FROM AUTHOR]

Dissemination of methicillin-resistant-Staphylococcus aureus/(MRSA) is a worldwide concern both in hospitals [healthcare-associated-(HA)-MRSA] and communities [community-associated-(CA)-MRSA]. Knowledge on when and where MRSA colonization is acquired and what clones are involved is necessary, to focus efforts for prevention of hospital-acquired MRSA-infections.Methods: A prospective/longitudinal cohort study was performed in eight Argentina hospitals (Cordoba/ October-December/2014). Surveillance cultures for MRSA (nose-throat-inguinal) were obtained on admission and at discharge. MRSA strains were genetically typed as CA-MRSAG and HA-MRSAG genotypes.Results: Overall, 1419 patients were screened and 534 stayed at hospital for ≥3 days. S. aureus admission prevalence was 30.9% and 4.2% for MRSA. Overall MRSA acquisition rate was 2.3/1000 patient-days-at-risk with a MRSA acquisition prevalence of 1.96% (95%CI: 1.0%-3.4%); 3.2% of patients were discharged back to community with MRSA. CA-MRSAG accounted for 84.6% of imported, 100.0% of hospital-acquired and 94% of discharged MRSA strains. Most imported and acquired MRSA strains belonged to two major epidemic CA-MRSA clones spread in Argentina: PFGEtypeI-ST5-IVa-t311-PVL+ and PFGEtypeN/ST30-IVc-t019-PVL+.Conclusions: CA-MRSA clones, particularly ST5-IV-PVL+ and ST30-IV-PVL+, with main reservoir in the community, not only enter but also are truly acquired within hospital, causing healthcare-associated-hospital-onset infections, having a transmission capacity greater or similar than HA-MRSAG. This information is essential to develop appropriate MRSA infection prevention-control programs, considering hospital and community. [ABSTRACT FROM AUTHOR]

La progression de la destruction articulaire dans la polyarthrite arthrite rhumatoïde (PR) débutante est variable d'un patient à l'autre et elle est difficile à prédire par les facteurs de risque classiques (ACPA, CRP, DAS28, score radiologique). L'objectif de cette étude est d'analyser la valeur prédictive du dosage sérique de Col3-4, un nouveau marqueur biologique de la dégradation des collagènes synoviaux (type III et IV), chez les patients atteints de PR débutante de la cohorte ESPOIR. La concentration sérique de Col 3-4 a été mesurée au temps de base par dosage ELISA (brevet INSERM, reproductibilité intra et inter dosage < 10 et 15 %) chez la totalité des patients de la cohorte ESPOIR disposant d'un prélèvement sérique (n = 788, 82 % de PR, 18 % de patients avec une arthrite indifférenciée, présence de symptômes < 6 mois, naïfs de traitements par DMARDs et corticoïdes). Les associations entre les valeurs de base de Col3-4 et la progression radiologique (score de Sharp/van der Heijde, > 1 unité à 1 an et 5 unités à 5 ans) ont été analysées par régression logistique avant et après ajustement par les facteurs de risque classiques. Au temps de base, Col3-4 était plus élevé chez les PR (p = 0,0001) et chez les patients ACPA positifs (p = 0,0001). Col3-4 était significativement corrélé à la protéine C-réactive (CRP) (p < 0,0001), au DAS28 (p < 0,0001) et très faiblement au score d'érosion (r2 = 0,0081, p = 0,017). Le Tableau 1 montre le risque de progression radiologique à 5 ans pour une augmentation d'un écart-type du Col 3-4 sérique au temps de base. Les patients avec les taux de Col3-4 les plus élevés (5e quintile de la population) avaient un odds-ratio (OR, 95 % CI) de progression du score total à 5 ans de 2,93 (1,79–4,73) par rapport aux autres malades (quintiles 1 à 4) ; ceux présentant une érosion osseuse un OR (95 % CI) de 2,26 (1,38–3,70). Les patients présentant à la fois un Col3-4 élevé et une érosion osseuse avaient un OR (95 %CI) de progression à 5 ans de 7,16 (2,31–22) par rapport à l'ensemble des autres malades. Des résultats similaires ont été observés pour la prédiction de la progression à 1 an et lorsque les analyses étaient limitées aux patients PR. Des taux sériques augmentés de Col3-4 sont associés à un risque élevé de progression structurale à 1 et 5 ans dans la PR débutante, indépendamment des facteurs de risque classiques. En association avec le score radiologique d'érosion, Col 3-4 pourrait être utile pour améliorer l'identification des patients à risque élevé de destruction. L'utilité de cette combinaison pour la prise en charge individuelle de la maladie reste à être testée de manière prospective. [ABSTRACT FROM AUTHOR]

By Berge's theorem, finding a maximum matching in a graph relies on the use of augmenting paths . When no further constraint is added, Edmonds' algorithm allows to compute a maximum matching in polynomial time by sequentially augmenting such paths. Motivated by applications in the scheduling of airline operations, we consider a similar problem where only paths of bounded length can be augmented. Precisely, let k ≥ 1 be an odd integer, and M a matching of a graph G . What is the maximum size of a matching that can be obtained from M by using only augmenting paths of length at most k ? We first prove that this problem can be solved in polynomial time for k ≤ 3 in any graph and that it is NP-complete for any fixed k ≥ 5 in the class of planar bipartite graphs of degree at most 3 and arbitrarily large girth. We then prove that this problem is in P, for any k , in several subclasses of trees such as caterpillars or trees with all vertices of degree at least 3 “far appart”. Moreover, this problem can be solved in time O ( n ) in the class of n -node trees when k and the maximum degree are fixed parameters. Finally, we consider a more constrained problem where only paths of length exactly k can be augmented. We prove that this latter problem becomes NP-complete for any fixed k ≥ 3 and in trees when k is part of the input. [ABSTRACT FROM AUTHOR]

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Objective: Our aim was to investigate the relationships between serum periostin (POSTN) and both prevalence and incidence/progression of knee osteoarthritis (OA) in women.Methods: We investigated 594 women (62.7 ± 11.2 yr) from the OFELY cohort. Knee radiographs were scored according to the Kellgren & Lawrence (KL) grading system at baseline and 4 years later. Spine, hip and hand OA were assessed at baseline. Prevalent knee OA was defined by a KL score higher or equal in 2. Progression of KL was defined as an increase of the KL score ≥1 during the 4 years follow-up. Serum POSTN was measured at baseline by ELISA.Results: By non-parametric tests, POSTN was significantly lower in 83 women with a KL score ≥2 at baseline, compared to those with a KL score <2 (n = 511; 1101 ± 300 vs 1181 ± 294 ng/ml, P = 0.002) after adjustment for age, body mass index (BMI), treatments and diseases, prevalent hand OA and prevalent lumbar spine OA. By logistic regression analyses, the odds-ratio of knee OA incidence/progression was significantly reduced by 21% (P = 0.043) for each quartile increase in serum POSTN at baseline, after adjustment for age, BMI, prevalent knee OA, prevalent hand OA and prevalent lumbar spine OA.Conclusions: We show for the first time that serum POSTN is associated with prevalence and the risk of development/progression of knee OA in women. [ABSTRACT FROM AUTHOR]

One of the best approaches for improving the assessment of metal toxicity in aquatic organisms is to study their organotropism (i.e., the distribution of metals among organs) through a dynamical approach (i.e., via kinetic experiments of metal bioaccumulation), to identify the tissues/organs that play a key role in metal regulation (e.g., storage or excretion). This study aims at comparing the organ-specific metal accumulation of a non-essential (Cd) and an essential metal (Zn), at their environmentally relevant exposure concentrations, in the gammarid Gammarus fossarum. Gammarids were exposed for 7 days to 109Cd- or 65Zn-radiolabeled water at a concentration of 52.1 and 416 ng.L−1 (stable equivalent), respectively, and then placed in clean water for 21 days. At different time intervals, the target organs (i.e., caeca, cephalons, intestines, gills, and remaining tissues) were collected and 109Cd or 65Zn contents were quantified by gamma-spectrometry. A one-compartment toxicokinetic (TK) model was fitted by Bayesian inference to each organ/metal dataset in order to establish TK parameters. Our results indicate: i) a contrasting distribution pattern of concentrations at the end of the accumulation phase (7th day): gills > caeca ≈ intestines > cephalons > remaining tissues for Cd and intestines > caeca > gills > cephalons > remaining tissues for Zn; ii) a slower elimination of Cd than of Zn by all organs, especially in the gills in which the Cd concentration remained constant during the 21-day depuration phase, whereas Zn concentrations decreased sharply in all organs after 24 h in the depuration phase; iii) a major role of intestines in the uptake of waterborne Cd and Zn at environmentally relevant concentrations. [Display omitted] • Uptake and depuration kinetics parameters were assessed by one-compartment TK modelling. • The k u and k e were significantly lower for Cd than for Zn, except for k u of gills. • In depuration, Cd is slowly eliminated by organs and Zn decreases sharply in 24 h. • No elimination of Cd was measured in gills after a 21-day depuration phase. • Intestine is dominant uptake and depuration path for Cd and Zn in dissolved exposure. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) burden is increasing worldwide in hospitals [healthcare-associated (HA)-MRSA] and in communities [community-associated (CA)-MRSA]. However, the impact of CA-MRSA within hospitals remains limited, particularly in Latin America. A countrywide representative survey of S. aureus infections was performed in Argentina by analyzing 591 clinical isolates from 66 hospitals in a prospective cross-sectional, multicenter study (Nov-2009). This work involved healthcare-onset infections-(HAHO, >48 hospitalization hours) and community-onset (CO) infections [including both, infections (HACO) in patients with healthcare-associated risk-factors (HRFs) and infections (CACO) in those without HRFs]. MRSA strains were genetically typed as CA-MRSA and HA-MRSA genotypes (CA-MRSA G and HA-MRSA G ) by SCC mec - and spa -typing, PFGE, MLST and virulence genes profile by PCR. Considering all isolates, 63% were from CO-infections and 55% were MRSA [39% CA-MRSA G and 16% HA-MRSA G ]. A significantly higher MRSA proportion among CO- than HAHO- S. aureus infections was detected (58% vs 49%); mainly in children (62% vs 43%). The CA-MRSA G /HA-MRSA G have accounted for 16%/33% of HAHO-, 39%/13% of HACO- and 60.5%/0% of CACO-infections. Regarding the epidemiological associations identified in multivariate models for patients with healthcare-onset CA-MRSA G infections, CA-MRSA G behave like HA-MRSA G within hospitals but children were the highest risk group for healthcare-onset CA-MRSA G infections. Most CA-MRSA G belonged to two major clones: PFGE-type N-ST30-SCC mec IVc-t019-PVL + and PFGE-type I-ST5-IV-SCC mec IVa-t311-PVL + (45% each). The ST5-IV-PVL + /ST30-IV-PVL + clones have caused 31%/33% of all infections, 20%/4% of HAHO-, 43%/23% of HACO- and 35%/60% of CACO- infections, with significant differences by age groups (children/adults) and geographical regions. Importantly, an isolate belonging to USA300-0114-(ST8- SCCmec IVa- spa t008-PVL + -ACME + ) was detected for the first time in Argentina. Most of HA-MRSA G (66%) were related to the Cordobes/Chilean clone-(PFGE-type A-ST5-SCC mec I-t149) causing 18% of all infections (47% of HAHO- and 13% of HACO-infections). Results strongly suggest that the CA-MRSA clone ST5-IV-PVL + has begun to spread within hospitals, replacing the traditional Cordobes/Chilean-HA-MRSA clone ST5-I-PVL − , mainly in children. Importantly, a growing MRSA reservoir in the community was associated with spreading of two CA-MRSA clones: ST5-IV-PVL + , mainly in children with HRFs, and ST30-IV-PVL + in adults without HRFs. This is the first nationwide study in Argentina providing information about the molecular and clinical epidemiology of CA-MRSA, particularly within hospitals, which is essential for designing effective control measures in this country and worldwide. [ABSTRACT FROM AUTHOR]

Highlights: [•] We quantify land use changes and spatial patterns during the period 1954–2000 in NW Italy. [•] Orchards expanded at the expenses of field crops (55%), vineyards (24%) and forests (15%). [•] We finally discuss the potential effects of European and local agricultural policies on the rural landscape of Langhe region. [Copyright &y& Elsevier]

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Abstract: Osteoarthritis (OA) is considered as a chronic disease with a long “silent” period. The diagnosis is generally based on clinical symptoms and radiographic changes. However X-ray has a poor sensitivity and a relatively large precision error that does not allow an early detection of OA or the monitoring of joint damage progression. The limitations of the tools that are currently available for OA assessment have been the impetus to identify specific biological markers that reflect quantitative and dynamic variations in joint remodeling. Research has focused on the structural components of cartilage matrix, especially type II collagen degradation markers. In spite of a significant increase of some markers in individuals with early stage of OA, the large overlap with control subjects indicates that the current biomarkers used alone have limited diagnostic potential. However, the combination of specific markers seems to improve the prediction of disease progression at the individual level. Several types of treatment have been investigated but the lack of medications with definitively demonstrated chondroprotective activity has limited the assessment of the potential role of biomarkers for monitoring patients'' responses to the treatment of OA. In this review, we will use the BIPED classification that appeared in 2006 for OA markers to describe the potential usage of a given marker [5]. This article is part of a Special Issue entitled "Osteoarthritis". [Copyright &y& Elsevier]

Objectives: Serum bone turnover markers (sBTM) are used in clinical practice for patients undergoing postmenopausal osteoporosis therapy. The aim of this study was to systematically analyze the literature on the ability of sBTM to monitor therapy, focusing on the following 5 objectives: (1) pretreatment values and treatment choice; (2) short-term changes and clinical response; (3) sBTM effect on persistence to therapy; (4) sBTM ability to predict fracture risk after withdrawal of therapy; and (5) the prediction of serious adverse effects. Methods: A systematic search on Medline completed manually was performed until November 2010 and was limited to postmenopausal osteoporosis and marketed therapies. Results: Following the PRISMA statement for systematic reviews, 48 studies were selected. Baseline sBTM levels were not able to predict fracture risk reduction with either treatment. There was more evidence for the prediction of fracture risk reduction with bone formation sBTM including PINP than with sCTX. Most of the studies found correlations between sBTM and bone mineral density (BMD) changes under antiresorptive therapies, although inconsistently. The only published study on the impact of sBTM on persistence to therapy showed negative results. There was no evidence that sBTM allow the prediction of adverse effects, especially osteonecrosis of the jaw. Conclusions: sBTM reflect the skeletal effects of anti-osteoporotic treatments. Pretreatment values are not recommended for selecting therapy. Short-term changes are significantly correlated with BMD variation, but there is no published evidence that they predict benefit on fracture risk at the individual level. [Copyright &y& Elsevier]

Summary: Objective: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). Results: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1–2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. [Copyright &y& Elsevier]

Copyright of IRBM is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of IRBM is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of IRBM is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Objective: To ascertain the predictive role of longitudinally acquired biochemical measures of cartilage turnover in relation to X-ray defined knee osteoarthritis (OAK), knee pain and functioning. Methods: This is a feasibility study based on 72 enrollees of the Michigan site of Study of Women''s Health Across the Nation (SWAN), a longitudinal, population-based cohort study with 11 annual visits to characterize health at the mid-life. At visits in 1996, 1998 and 2007, radiographs were evaluated for the presence of OAK [≥2 on the Kellgren and Lawrence (K–L) scale]. Knee pain and stiffness were assessed by interview. Functioning was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Cartilage oligomeric matrix protein (COMP) and Type II collagen telopeptides (CTX-II) were assayed in serum and urine samples collected on alternate years from 1997 to 2006. We related trajectories of the cartilage biochemical markers from these five time points to OAK severity (no OAK, K–L score<2; mild OAK, K–L score=2; moderate/severe OAK, K–L score=3 or 4), pain, stiffness, or functioning, using longitudinal non-linear mixed modeling. Results: The 2007 prevalence of X-ray defined OAK was 50% in these 72 women. Upward trajectories of COMP (P =0.02) and CTX-II (P =0.006) were associated with increased OAK severity and body size. COMP trajectories were associated with pain and stiffness, but not functioning. CTX-II trajectories were associated with stiffness scores, but not knee pain or functioning scores. Conclusion: Multiple, biennial measures of COMP or CTX-II taken over a 10-year period were predictive of subsequent OAK and knee stiffness. [Copyright &y& Elsevier]

Summary: Objectives: Nitric oxide (NO) is a major mediator of joint tissue inflammation and damage in osteoarthritis (OA) and mediates the nitration of tyrosine (Y*) residues in proteins. We investigated the nitration of type III collagen, a major constituent of synovial membrane, in knee OA. Methods: A polyclonal antibody directed against the nitrated QY*DSY*DVKSG sequence from type III collagen N-telopeptide was generated. Synovial tissues from patients with knee OA (n =4) and rheumatoid arthritis (RA, n =4) were analyzed by immunohistochemistry for IIINys. Serum IIINys levels were measured by enzyme-linked immunosorbent assay in 87 patients with painful knee OA (mean age: 63.0±8.0 years, Kellgren–Lawrence score II–III) and in 40 sex and age-matched healthy controls. Results: Competition experiments using various nitrated and un-nitrated type III collagen and derived sequences, showed that the antibody was highly specific for the nitrated IIINys sequence. High IIINys immunoreactivity was detected in the synovial tissues from all patients with OA and RA with a preferential localization in the intimal layer. Serum IIINys levels were on average 1.5-fold higher (P <0.0001) in patients with knee OA than in healthy controls and significantly correlated with C-reactive protein values (r =0.40, P <0.005). Conclusions: Nitration of tyrosine residues of type III collagen N-telopeptide is increased in the synovial tissue of patients with knee OA. Measurements of serum IIINys level may be useful for the clinical investigation of oxidative-related alterations of synovial tissue metabolism in OA. [Copyright &y& Elsevier]

Summary: Objective: To test the hypothesis that early knee and hand osteoarthritis (OA) development is characterized by detectable changes in serum proteins relevant to inflammation, cell growth, activation, and metabolism several years before OA becomes radiographically evident. Methods: Using microarray platforms that simultaneously test 169 proteins relevant to inflammation, cell growth, activation and metabolism, we conducted a case–control study nested within the Baltimore Longitudinal Study of Aging (BLSA). Subjects included 22 incident cases of OA and 66 age-, sex- and body mass index (BMI)-matched controls. Serum samples tested were obtained at the time of radiographic classification as either case or control, and up to 10 years earlier at a time when all participants were free of radiographic OA. Proteins with mean signal intensities fourfold higher than background were compared between cases and controls using multivariate techniques. Results: Sixteen proteins were different between OA cases compared to controls. Four of these proteins [matrix metalloproteinase (MMP)-7, interleukin (IL)-15, plasminogen activator inhibitor (PAI)-1 and soluble vascular adhesion protein (sVAP)-1] were already different in samples obtained 10 years before radiographic classification and remained different at the time of diagnosis. Six additional proteins were only associated with subsequent OA development and not with established OA. Conclusions: Changes in serum proteins implicated in matrix degradation, cell activation, inflammation and bone collagen degradation products accompany early OA development and can precede radiographic detection by several years. [Copyright &y& Elsevier]

Summary: Objective: Serum levels of procollagen type IIA N-terminal propeptide (sPIIANP) and type-II collagen helical peptide (sHELIXII) biomarkers were evaluated for variation diurnally and with physical activity and food in participants with osteoarthritis (OA) of the knee. Methods: Forty participants with OA of at least one knee were admitted overnight to the General Clinical Research Center for serial serum sampling. Samples were obtained on the evening (6–8 pm) of Day 1 (T3, n =40); prior to rising (8 am) from bed (T0, n =40); 1h after rising (9 am) without food consumption (T1a, n =20); 1–2h after rising (9–10 am) with food consumption (T1, n =40); and additionally at noon, 4h after rising (T2, n =20). sPIIANP and sHELIXII were measured by enzyme-linked immunosorbent assay. Results were analyzed using non-parametric Freidman''s test with Dunn''s post-hoc multiple comparison test. Results: Normalized mean concentrations for sPIIANP and sHELIXII increased significantly from T0 to T1 (P <0.05). Conclusions: This is the first study to demonstrate diurnal variation of these collagen-II biomarkers in individuals with knee OA. These results suggest that serum sampling for these markers should be standardized for purposes of clinical trials. [Copyright &y& Elsevier]

Summary: Objective: Cartilage degradation in osteoarthritis (OA) generates the type II collagen fragments, Helix-II and CTX-II that can be used as clinical biological markers. Helix-II and C-telopeptide of type II collagen (CTX-II) levels are associated independently with progression of OA suggesting that they may be generated through different collagenolytic pathways. In this study we analyzed the release of Helix-II and CTX-II from human cartilage collagen by the proteinases reported to play a role in cartilage degradation. Methods: In vitro, human articular cartilage extract was incubated with activated human recombinant cathepsins (Cats) and matrix-metalloproteases (MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage sections were then incubated for up to 84h in the presence or absence of E-64 and GM6001, inhibitors of cysteine proteases and MMPs, respectively. Results: In vitro, Cats K, L and S generated large amount of Helix-II, but not CTX-II. Cat B generated CTX-II fragment, but destroyed Helix-II immunoreactivity. Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA cartilage explants, E-64 blunted the release of Helix-II whereas the release of CTX-II could be completely abrogated by GM6001 and only partly by E-64. Conclusion: These in vitro and ex vivo experiments of human cartilage suggest that Helix-II and CTX-II could be released in part by different enzymatic pathways. Helix-II and CTX-II alone reflect only partially overall cartilage collagen degradation. These findings may explain why these two biological markers could provide complementary information on disease progression in OA. [Copyright &y& Elsevier]

Summary: Objective: To investigate whether early changes in biochemical markers of bone (NTX-I) and cartilage (CTX-II [C-terminal crosslinking telopeptide of type II collagen]) degradation are associated with radiological progression in patients with knee osteoarthritis (OA) receiving risedronate. Design: Two thousand four hundred and eighty three patients with medial compartment knee OA were randomized in two 24-month studies in North America (NA) and European Union (EU). Studies evaluated risedronate 5mg/day, 35mg/week (EU), 50mg/week (NA), and 15mg/day (NA and EU), compared to placebo in reducing signs and symptoms and in slowing radiographic progression. One thousand eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed. Results: Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months. Patients who had CTX-II levels returned to low levels (<150ng/mmol creatinine) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [odds-ratio (95% confidence interval): 0.57 (0.39–0.85) after adjustment for demographics and joint space width]. The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [odds-ratio 0.36 (0.21–0.63)]. No significant association between NTX-I levels and radiological progression was observed. Conclusion: CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months. Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression. [Copyright &y& Elsevier]

Summary: Objective: To investigate whether type II collagen turnover markers used for osteoarthritis (OA) activity evaluation in body fluids can be detected at the level of specific histological features of OA cartilage tissue, as well as how they relate with each other at this level. Methods: Adjacent sections were obtained from full-depth cartilage biopsies from 32 OA knees. Immunohistochemistry was performed for Helix-II and CTX-II, which are type II collagen fragments originating from the triple helix and the telopeptide region, respectively, and believed to reflect distinct breakdown events, as well as for type IIA N propeptide (PIIANP), a biochemical marker reflecting synthesis of type IIA collagen. Results: Helix-II and CTX-II were detected in areas where collagen damage was reported previously, most frequently around chondrocytes, but also frequently in regions not previously investigated such as the margin area and close to subchondral bone, including vascularization sites and bone–cartilage interface. The latter is CTX-II''s prevailing position and shows rarely Helix-II. PIIANP co-localized with Helix-II and CTX-II on a limited number of features, mainly in deep zone cartilage. Overall, our analysis highlights clear patterns of association of the markers with specific histological features, and shows that they spread to these features in an ordered way. Conclusion: Helix-II and CTX-II show to some degree differential selectivity for specific features in cartilage tissue. CTX-II detection close to bone may be relevant to the possible role of subchondral bone in OA. The restricted co-localization of breakdown markers and PIIANP suggests that collagen fragments can result only partially from newly synthesized collagen. Our study strengthens the interest for the question whether combining several markers reflecting different regional cartilage contributions or metabolic processes should allow a broader detection of OA activity. [Copyright &y& Elsevier]

Abstract: Introduction: Biochemical markers of bone turnover (BTMs) are important in determining fracture risk in postmenopausal women; high levels being associated with increased risk. A proposed goal of anti-resorptive therapy is to reduce BTMs to the lower half of the reference range for healthy young pre-menopausal women. Our aims were a) to establish reference ranges for bone alkaline phosphatase (bone ALP), crosslinked C- and N-telopeptides of type I collagen (βCTX, NTX), osteocalcin (OC) and procollagen type I N propeptide (PINP) in pre-menopausal women and b) to investigate the determinants of these BTMs. Methods: BTMs were measured in peripheral blood and second morning void urine collected from 200 healthy pre-menopausal women ages 30 to 45 years. Each subject completed a short medical and lifestyle questionnaire. Results: BTMs were higher before the age of 35 years than after it. BTMs were higher in women with low BMI (βCTX and OC), low alcohol consumption (PINP), current smoking habit (bone ALP and NTX), and around time of ovulation (NTX). Conclusions: We recommend that the age range 35 to 45 years should be used when establishing BTM reference ranges in women. [Copyright &y& Elsevier]

Summary: The investigation of the molecular mechanisms involved in carcinogenesis and tumor progression has led to the development of numerous biochemical markers. Biochemical markers may serve for early prediction of tumor recurrence, progression and development of metastases including bone metastases and for prediction of response to therapy. Tumor antigens have been used for more than a decade and although they have shown promising clinical results, their sensitivity and specificity remain limited. A lot of knowledge on the key molecules which control cell cycle, apoptosis and angiogenesis has been acquired during recent years, but their clinical value remains uncertain. Molecular markers which are linked to malignant transformation may provide a non-surgical therapeutic approach by targeting these molecules through gene therapy or antisense molecules. Because of the complexity of the physiopathogical processes involved in tumorogenesis and metastases, we first provide a review on the molecular basis of the various tumor markers and then discuss their potential clinical utility for the major cancers. The review of the current literature indicates that at the exception of a few examples, such as the use of Her-2 to predict response of the targeted Herceptin therapy, no single marker is sensitive and specific enough to perform an accurate diagnosis, predict disease progression or response to treatment. A combination of different biochemical and imaging markers appears to be the most promising strategy to monitor patients with cancer. [Copyright &y& Elsevier]

Objective: To assess the relationship of biochemical markers and radiographic signs of osteoarthritis (ROA) in the subjects with symptomatic osteoarthritis (OA) at multiple sites of the Genetics osteoARthritis and Progression (GARP) study.Methods: We have measured eight biochemical markers, representing tissue turnover of cartilage, bone, synovium, and inflammation. ROA was assessed in the knees, hips, hands, vertebral facet joints and spinal disc degeneration (DD) by using the Kellgren score. A proportionate score was subsequently made for each joint location based on the number of joints with ROA. Principal component and linear mixed model analyses were applied to analyze the data.Results: Three different clusters of markers were identified that may reflect different pathophysiological processes of OA. The first component appeared to be reflected by structural markers of cartilage and bone turnover and associated especially in subjects with hip ROA. The second component was reflected by a marker of inflammation and was associated with knee ROA, high Western Ontario and McMaster Universities (WOMAC) scores and body mass index (BMI). The third component included markers of cartilage turnover and was associated with ROA at hands, spine as well as age. High familial aggregation was observed for serum cartilage oligomeric matrix protein (S-COMP) (70%) and serum N-propeptide of collagen type IIA (S-PIIANP) (62%).Conclusion: Using a large well-characterized study and eight biochemical markers, we were able to observe three components that may reflect different molecular mechanisms (bone, cartilage, synovium turnover and inflammation). Our data suggested that these components contribute differently to ROA at different joint sites. [ABSTRACT FROM AUTHOR]

Abstract: Introduction : Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D3 have yielded conflicting results. The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D (25-OH D), bone turnover markers, bone mineral density (BMD), radius bone loss and incidence of fracture in postmenopausal women. Methods : 669 postmenopausal women (mean age: 62.2 years) belonging to a population-based cohort were followed prospectively for a median of 11.2 years. At baseline, 25-OH D levels, BMD, bone turnover markers and clinical risk factors of osteoporosis were assessed. BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs. Results : 73% and 35% of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention. 11% of women had levels below 30 nmol/l. Serum 25-OH D correlated modestly with intact PTH (r 2 =0.023, p <0.0001), but not with bone turnover markers or BMD at the hip and radius after adjustment for age. When levels of 25-OH D were considered as a continuous variable, there was no significant association between 25-OH D levels and radius BMD loss or fracture risk. After adjustment for age, there was no significant difference in incidence of fracture, BMD, radius BMD loss, bone turnover markers, grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75, 50 or 30 nmol/l. Conclusions: In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency, vitamin D status may not be an important determinant of bone health. [Copyright &y& Elsevier]

Abstract: In the skeleton of elderly men, two opposite activities occur: bone loss at the endosteal envelope, which increases bone fragility, and periosteal apposition, which improves bending strength of bone. Both may contribute to serum bone formation markers although they have an opposite effect on bone fragility. The aim of this study was to determine if circulating bone formation markers reflect periosteal bone formation and endosteal bone remodelling in 640 men aged 55–85 years belonging to the MINOS cohort. We measured biochemical markers of bone formation (osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen) and bone resorption (urinary and serum β-isomerised C-terminal telopeptide of collagen type I, total and free deoxypyridinoline). Parameters of bone size (cross-sectional surface of third lumbar vertebral body measured by X-ray, projected areas of total hip, femoral neck, radius and ulna measured by dual-energy X-ray absorptiometry) increased with age (r = 0.20–0.32, P &#60; 0.0001). In contrast, parameters related to bone loss (areal bone mineral density [aBMD], volumetric bone mineral density [vBMD] and cortical thickness) and determined mainly by bone resorption, decreased with ageing (r = −0.14 to −0.23, P &#60; 0.005–0.0001). Men in the highest quartile of bone resorption markers had lower aBMD (3.8–10.2%, P &#60; 0.05–0.0001), lower vBMD (3.9–13.0%, P &#60; 0.05–0.0001), and lower cortical thickness (1.5–9.6%, P &#60; 0.05–0.0001) than men in the lowest quartile. Markers of bone resorption were not significantly associated with estimates of bone size at any skeletal site. Markers of bone formation were not associated with estimates of periosteal formation after adjustment for covariates. In contrast, men in the highest quartile of the bone formation markers had significantly lower aBMD (4.0–11.7%, P &#60; 0.05–0.0001), lower vBMD (4.2–16.3, P &#60; 0.05–0.0001) and lower cortical thickness (4.0–7.4%, P &#60; 0.05–0.0001) than men in the lowest quartile. In summary, serum levels of bone formation markers are negatively correlated with the estimates of endosteal bone loss. In contrast, they disclose no association with parameters reflecting periosteal apposition. Thus, in elderly men, bone formation markers reflect endosteal bone remodelling, probably because of the coupling between resorption and formation activities. In contrast, they do not reflect the periosteal bone formation, probably because the periosteal surface is smaller and has a slower remodelling rate than the endosteal surface. [Copyright &y& Elsevier]

Type I collagen fragments are the most sensitive markers of bone resorption in osteoporosis. Currently, all available type I collagen-related bone resorption markers detect in serum and/or urine fragments arising from the telopeptide region of the molecule. Our aim was to evaluate the technical and clinical performances of a new assay detecting in urine a degradation fragment originating from the helical part of type I collagen and consisting of the 620–633 sequence of the α1 chain. Urinary helical peptide was measured with a new ELISA (Metra Helical peptide, Quidel Corporation). Results were compared with those of urinary C-terminal cross-linking type I collagen of type I collagen (CTX), an established bone resorption marker. We measured urinary helical peptide levels in 89 healthy women (age 31–89 years) and in 59 postmenopausal women involved in two randomized studies of the efficacy of alendronate (10 mg/day; n = 20) and transdermal 17β estradiol (50 μg/day; n = 39). The within-run and between-run CVs were ≤ 7.3 and 8.7%, respectively. In 59 healthy women, urinary helical peptide levels highly correlated with those of urinary CTX (r = 0.78, P < 0.0001). The long-term intraindividual variability assessed over 6 months in 18 untreated postmenopausal women was 24%. Compared to 24 premenopausal women, urinary helical peptide was 42% (P < 0.0001) higher in 65 postmenopausal women (mean age, 60 years), an increase comparable to that of urinary CTX (+ 47%, P < 0.0001). Urinary helical peptide levels decreased by 72% (P < 0.0001) after 3 months of alendronate treatment and by 59% (P < 0.0001) after 6 months of transdermal estrogen therapy. These changes were of similar magnitude to those of urinary CTX (−69 and −62%, respectively; NS compared with changes in helical peptide). In women treated with transdermal 17β estradiol, the percentage of change of urinary helical peptide and urinary CTX at 6 months significantly correlated with the change in spinal bone mineral density after 2 years (r = −0.58, P = 0.002, and r = −0.52, P = 0.006, for urinary helical peptide and CTX, respectively). This new assay for type I collagen helical peptide has demonstrated adequate analytical performance and was highly correlated with urinary CTX, an established type I collagen C-telopeptide bone resorption marker. The test was a sensitive indicator of the antiresorptive effects of bisphosphonate and estrogens in postmenopausal women. This new bone resorption marker should be useful for the clinical investigation of patients with osteoporosis. [Copyright &y& Elsevier]

Genetic factors play an important role in determining bone mass and several genes are involved in this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone mineral density (BMD) and it has been suggested recently that novel IL-6 −174 G/C allelic variants may be associated with peak BMD in young men and with bone resorption in elderly women. In this study, we assessed the relationships between IL-6 gene polymorphism, peak BMD, rate of postmenopausal BMD loss, and bone turnover in women. BMD was measured by dual-energy X-ray absorptiometry in 255 healthy premenopausal women, aged 31–57 years. BMD loss at the forearm was measured over 4 years in 298 healthy untreated postmenopausal women, 50–88 years (mean 64 years). We also measured levels of serum osteocalcin, bone alkaline phosphatase, and N-propeptide of type I collagen for bone formation and three markers of bone resorption, including urinary and serum C-terminal cross-linking telopeptide of type I collagen and urinary N-terminal telopeptide of type I collagen, in both pre- and postmenopausal women at baseline. In premenopausal women we found a significant association between IL-6 genotypes and BMD at the whole body (analysis of variance [ANOVA], p = 0.03), femoral neck (p = 0.03), trochanter (p = 0.014), Ward’s triangle (p = 0.03), and total hip (p = 0.006), with subjects having the CC genotype showing 3%–7% higher BMD levels than their GG counterparts. However, after matching women with CC and GG genotypes for body height the differences decreased (2%–4%), and were no longer significant (p = 0.10–0.23). In postmenopausal women the mean rate of loss at the ultradistal radius was significantly associated with IL-6 genotypes (ANOVA, p = 0.049), with women having the CC genotype showing a significantly greater rate of bone loss (p < 0.05) compared with their GC and GG counterparts. After adjustment for weight changes, the difference in the rate of ultradistal radius bone loss between genotypes decreased and was not significant (p = 0.06 for CC vs. GG). A similar trend was observed for distal radius bone loss (p = 0.10, ANOVA), but not for the middle radius. We found no significant association between genotypes, bone turnover markers in premenopausal women, and either bone turnover or BMD in postmenopausal women. We conclude that this new functional IL-6 polymorphism was weakly associated with level of peak BMD and the rate of forearm trabecular postmenopausal bone loss in this cohort of healthy French women. IL-6 genotypes accounted only for a small proportion of the interindividual variation of both peak BMD and rate of bone loss and were not significant after adjustment for height and changes in body weight, respectively, suggesting that part of the effect may have been due to the differences in body size. Larger long-term studies are necessary to assess adequately the relationships between IL-6 genotype, rate of bone loss, and risk of fracture. [Copyright &y& Elsevier]

Purpose Aim of this study was to evaluate the performance of PSF reconstruction algorithm of a PET-TC TOF scanner. Comparison in term of image quality was performed in order to investigate potentialities and differences between PSF algorithm and the standard OSEM algorithm routinely applied in the clinical use. Methods The phantom NEMA 2012 Body Image Quality (18F, 213 kBq/ml, □ 10 mm 13 mm 17 mm 22 mm hot spheres (background ratio 4 ÷ 1), □ 28 mm 37 mm cold spheres) was acquired with Philips IngenuityTF PET-TC scanner (TOF, AC-SC). Raw data were reconstructed both with standard OSEM 3D and with PSF, using 20 different paired iteration values (1–500) and regularization levels (1–20). Seven regions of interest (ROIs) were contoured: 4 centred on "hot" spheres, 2 on "cold" spheres and 1 on background. Mean value (MV) and standard deviation (SD) of every ROI were calculated: signal to noise ratio (SNR) and contrast to noise ratio (CNR) were compared. Spatial resolution was evaluated as steepness of the 10 mm-sphere profile. Results PSF images showed resolution higher (e.g. 3 mm for 30 iterations) than the standard OSEM (6 mm). As shown in figure 1a the more iteration number the higher artifacts presence, especially in the background region. MV and SD values relative to the "hot spheres" strongly depend on iteration number and regularization level; variations up to +1000% were found (500 iterations and 20 regularization) both on MV and SD values. No variations were noticed on background MV, but SD values increase up to +600%. As consequence SNR and CNR are affected by reconstruction parameters (Fig. 1b). Conclusions PSF images showed resolution higher than standard OSEM, but also huge artifacts and unacceptable variations in measured activity (and SUV). The use of PSF reconstruction for quantitative purposes is not recommended and its use should be designed for specific uses. [ABSTRACT FROM AUTHOR]

Purpose Aim of this study was to evaluate the performance of PSF reconstruction algorithm of a new PET-TC TOF scanner. Comparison in term of image quality was performed in order to investigate potentialities and differences between PSF algorithm and the standard OSEM algorithm routinely applied in the clinical use. Methods The phantom NEMA 2012 Body Image Quality (18 F, 213 kBq/ml, diameter 10 mm, 13 mm, 17 mm and 22 mm hot spheres (background ratio 4  ÷  1), diameter 28 mm and 37 mm cold spheres) was acquired with Philips Ingenuity TF PET-TC scanner (TOF, AC-SC). Raw data were reconstructed both with standard OSEM 3D and with PSF, using 20 different paired iteration values (1–500) and regularization levels (1–20). Seven regions of interest (ROIs) were contoured: 4 centered on ”hot” spheres, 2 on ”cold” spheres and 1 on background. Mean value (MV) and standard deviation (SD) of every ROI were calculated: signal to noise ratio (SNR) and contrast to noise ratio (CNR) were compared. Spatial resolution was evaluated as steep of the 10 mm-sphere profile. Results PSF images showed resolution higher (e.g. 3 mm for 30 iterations) than the standard OSEM (6 mm). The more iteration number the higher artifacts presence, especially in the background region. MV and SD values relative to the ”hot spheres” strongly depend on iteration number and regularization level; variations up to +1000% were found (500 iterations and 20 regularization) both on MV and SD values. No variations were noticed on background MV, but SD values increase up to +600%. As consequence SNR and CNR are strongly affected by reconstruction parameters. Conclusions PSF images showed resolution higher than standard OSEM, but also huge artifacts and unacceptable variations in measured activity (and SUV). The use of PSF reconstruction for quantitative purposes is not recommended and its use should be designed for specific uses. [ABSTRACT FROM AUTHOR]