Performance comparison of two commercial BGO-based PET/CT scanners using NEMA NU 2-2001.

Combined positron emission tomography and computed tomography (PET/CT) scanners play a major role in medicine for in vivo imaging in an increasing number of diseases in oncology, cardiology, neurology, and psychiatry. With the advent of short-lived radioisotopes other than 18F and newer scanners, there is a need to optimize radioisotope activity and acquisition protocols, as well as to compare scanner performances on an objective basis. The Discovery-LS (D-LS) was among the first clinical PET/CT scanners to be developed and has been extensively characterized with older National Electrical Manufacturer Association (NEMA) NU 2-1994 standards. At the time of publication of the latest version of the standards (NU 2-2001) that have been adapted for whole-body imaging under clinical conditions, more recent models from the same manufacturer, i.e., Discovery-ST (D-ST) and Discovery-STE (D-STE), were commercially available. We report on the full characterization both in the two- and three-dimensional acquisition mode of the D-LS according to latest NEMA NU 2-2001 standards (spatial resolution, sensitivity, count rate performance, accuracy of count losses, and random coincidence correction and image quality), as well as a detailed comparison with the newer D-ST widely used and whose characteristics are already published.

10-year follow-up of a prospective randomized trial comparing bare-metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial

OBJECTIVES: This study was designed to compare the long-term clinical outcome of coronary artery bypass grafting (CABG) with intracoronary stenting of patients with isolated proximal left anterior descending coronary artery. BACKGROUND: Although numerous trials have compared coronary angioplasty with bypass surgery, none assessed the clinical evaluation in the long term. METHODS: We evaluated the 10-year clinical outcome in the SIMA (Stent versus Internal Mammary Artery grafting) trial. Patients were randomly assigned to stent implantation versus CABG. RESULTS: Of 123 randomized patients, 59 underwent CABG and 62 received a stent (2 patients were excluded). Follow-up after 10 years was obtained for 98% of the randomized patients. Twenty-six patients (42%) in the percutaneous coronary intervention group and 10 patients (17%) in the CABG group reached an end point (p < 0.001). This difference was due to a higher need for additional revascularization. The incidences of death and myocardial infarction were identical at 10%. Progression of the disease requiring additional revascularization was rare (5%) and was similar for the 2 groups. Stent thrombosis occurred in 2 patients (3%). Angina functional class showed no significant differences between the 2 groups. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective in relieving symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Stenting with bare-metal stents is associated with a higher need for repeat interventions. The long-term prognosis for these patients is excellent with either mode of revascularization.

A statistical methodology for the comparison of blue gel pen inks analyzed by laser desorption/ionization mass spectrometry

A statistical methodology for the objective comparison of LDI-MS mass spectra of blue gel pen inks was evaluated. Thirty-three blue gel pen inks previously studied by RAMAN were analyzed directly on the paper using both positive and negative mode. The obtained mass spectra were first compared using relative areas of selected peaks using the Pearson correlation coefficient and the Euclidean distance. Intra-variability among results from one ink and inter-variability between results from different inks were compared in order to choose a differentiation threshold minimizing the rate of false negative (i.e. avoiding false differentiation of the inks). This yielded a discriminating power of up to 77% for analysis made in the negative mode. The whole mass spectra were then compared using the same methodology, allowing for a better DP in the negative mode of 92% using the Pearson correlation on standardized data. The positive mode results generally yielded a lower differential power (DP) than the negative mode due to a higher intra-variability compared to the inter-variability in the mass spectra of the ink samples.

State of genomics and epigenomics research in the perspective of HIV cure.

PURPOSE OF REVIEW: One of the seven key scientific priorities identified in the road map on HIV cure research is to 'determine the host mechanisms that control HIV replication in the absence of therapy'. This review summarizes the recent work in genomics and in epigenetic control of viral replication that is relevant for this mission. RECENT FINDINGS: New technologies allow the joint analysis of host and viral transcripts. They identify the patterns of antisense transcription of the viral genome and its role in gene regulation. High-throughput studies facilitate the assessment of integration at the genome scale. Integration site, orientation and host genomic context modulate the transcription and should also be assessed at the level of single cells. The various models of latency in primary cells can be followed using dynamic study designs to acquire transcriptome and proteome data of the process of entry, maintenance and reactivation of latency. Dynamic studies can be applied to the study of transcription factors and chromatin modifications in latency and upon reactivation. SUMMARY: The convergence of primary cell models of latency, new high-throughput quantitative technologies applied to the study of time series and the identification of compounds that reactivate viral transcription bring unprecedented precision to the study of viral latency.

Efforts to standardise Ki-67 counting in breast cancer. A pilot study of the Swiss Working Group of Gyneco- and Breast Pathologists

Goals: Adjuvant chemotherapy decisions in breast cancer are increasing based on the pathologist's assessment of the proliferation fraction in the tumor. Yet, how good and how reproducible are we pathologists at providing reliable Ki-67 readings on breast carcinomas. Exactly how to count and in which areas to count within a tumor remains inadequately standardized. The Swiss Working Group of Gyneco- and Breast Pathologists has tried to appreciate this dilemma and to propose ways to obtain more reproducible results.Methods: In a first phase, 5 pathologists evaluated Ki67 counts in 10 breast cancers by exact counting (500 cells) and by eyeballing. Pathologists were free to select the region in which Ki67 was evaluated. In a second phase 16 pathologists evaluated Ki-67 counts in 3 breast cancers also by exact counting and eyeballing, but in predefined fields of interest. In both phases, Ki67 was assessed in centrally immunostained slides (ZH) and on slides immunostained in the 11 participating laboratories. In a third phase, these same 16 pathologists were once again asked to read the 3 cases from phase 2, plus three new cases, and this time exact guidelines were provided as to what exactly is considered a Ki-67 positive nucleus.Results: Discordance of Ki67 assessment was due to each of the following 4 factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique/protocol/antibody, and (iv) the selection of the area in which to count.Conclusion: Providing guidelines as to where to count (representative field in the tumor periphery and omitting hot spots) and what nuclei to count (even faintly immunostained nuclei count as positive) reduces the discordance rates of Ki67 readings between pathologists. Laboratory technique is only of minor importance (even over a large antibody dilution range), and counting nuclei does not improve accuracy, but rather aggravates deviations from the group mean values.Disclosure of Interest: None Declared

Ecology and evolution of social-organization: insights from fire ants and other highly eusocial insects

Social organisms exhibit conspicuous intraspecific variation in all facets of their social organization. A prominent example of such variation in the highly eusocial Hymenoptera is differences in the number of reproductive queens per colony, Differences in queen number in ants are associated with differences in a host of reproductive and social traits, including queen phenotype and breeding strategy, mode of colony reproduction, and pattern of sex allocation. We examine the causes and consequences of changes in colony queen number and associated traits using the fire ant Solenopsis invicta as a principal model. Ecological constraints on mode of colony founding may act as important selective forces causing the evolution of queen number in this and many other ants, with social organization generally perpetuated across generations by means of the social environment molding appropriate queen phenotypes and reproductive strategies. Shifts in colony queen number have profound effects on genetic structure within nests and may also influence genetic structure at higher levels (aggregations of nests or local demes) because of the association of queen number with particular mating and dispersal habits. Divergence of breeding habits between populations with different social organizations has the potential to promote genetic differentiation between these social variants. Thus, evolution of social organization can be important in generating intrinsic selective regimes that channel subsequent social evolution and in initiating the development of significant population genetic structure, including barriers to gene flow important in cladogenesis.

Fat oxidation kinetics : effect of exercise

ABSTRACT Fat oxidation kinetics: effect of exercise. During graded exercise, absolute whole body fat oxidation rates increase from low to moderate intensities, and then markedly decline at high intensities, implying an exercise intensity (Fatmax) at which the fat oxidation rate is maximal (MFO). The main aim of the present work was to examine the effect of exercise on whole body fat oxidation kinetics. For this purpose, a sinusoidal mathematical model (SIN) has been developped in the first study to provide an accurate description of the shape of fat oxidation kinetics during graded exercise, represented as a function of exercise intensity, and to determine Fatmax and MFO. The SIN model incorporates three independent variables (i.e., dilatation, symmetry, and translation) that correspond to main expected modulations of the basic fat oxidation curve because of factors such as mode of exercise or training status. The results of study 1 showed that the SIN model was a valuable tool to determine Fatmax and MFO, and to precisely characterize and quantify the different shape of fat oxidation kinetics through its three variables. The effectiveness of the SIN model to detect differences in fat oxidation kinetics induced by a specific factor was then confirmed in the second study, which quantitatively described and compared fat oxidation kinetics in two different popular modes of exercise: running and cycling. It was found that the mean fat oxidation kinetics during running was characterized by a greater dilatation and a rightward asymmetry compared with the symmetric parabolic curve in cycling. In the two subsequent studies, the effect of a prior endurance exercise of different intensities and durations on whole body fat oxidation kinetics was examined. Study 3 determined the impact of a 1-h continuous exercise bout at an exercise intensity corresponding to Fatmax on fat oxidation kinetics during a subsequent graded test, while study 4 investigated the effect of an exercise leading to a more pronounced muscle glycogen depletion. The results of these two latter studies showed that fat oxidation rates, MFO, and Fatmax were enhanced following endurance exercise, but were increased to a greater extent with a more severe mucle glycogen depletion, inducing therefore modifications in the postexercise fat oxidation kinetics (i.e., greater dilatation and rightward asymmetry). In perspective, further studies have been suggested 1) to assess physiological meaning of the three independent variables of the SIN model; and 2) to compare the effect of two different training programs on fat oxidation kinetics in obese subjects.

Effect of abscisic acid on maize root growth. A critical examination

The effect of abscisic acid (ABA) on the growth of maize roots maintained in the dark is investigated in relation to the root varieties and the root age, the mode of application, the concentration used and the duration of both the treatment and the culture. In all the assays, when ABA produces a significant change in root elongation, it shows an inhibitory effect which is enhanced with increasing ABA concentration. The data strongly support the hypothesis that ABA could be one of the growth inhibitors which are formed in or released from the root cap.

The caveolin-binding motif of the pathogen-related yeast protein Pry1, a member of the CAP protein superfamily, is required for in vivo export of cholesteryl acetate.

Proteins belonging to the CAP superfamily are present in all kingdoms of life and have been implicated in different physiological processes. Their molecular mode of action, however, is poorly understood. Saccharomyces cerevisiae expresses three members of this superfamily, pathogen-related yeast (Pry)1, -2, and -3. We have recently shown that Pry function is required for the secretion of cholesteryl acetate and that Pry proteins bind cholesterol and cholesteryl acetate, suggesting that CAP superfamily members may generally act to bind sterols or related small hydrophobic compounds. Here, we analyzed the mode of sterol binding by Pry1. Computational modeling indicates that ligand binding could occur through displacement of a relatively poorly conserved flexible loop, which in some CAP family members displays homology to the caveolin-binding motif. Point mutations within this motif abrogated export of cholesteryl acetate but did not affect binding of cholesterol. Mutations of residues located outside the caveolin-binding motif, or mutations in highly conserved putative catalytic residues had no effect on export of cholesteryl acetate or on lipid binding. These results indicate that the caveolin-binding motif of Pry1, and possibly of other CAP family members, is crucial for selective lipid binding and that lipid binding may occur through displacement of the loop containing this motif.

The small RNA PhrS stimulates synthesis of the Pseudomonas aeruginosa quinolone signal.

Quorum sensing, a cell-to-cell communication system based on small signal molecules, is employed by the human pathogen Pseudomonas aeruginosa to regulate virulence and biofilm development. Moreover, regulation by small trans-encoded RNAs has become a focal issue in studies of virulence gene expression of bacterial pathogens. In this study, we have identified the small RNA PhrS as an activator of PqsR synthesis, one of the key quorum-sensing regulators in P. aeruginosa. Genetic studies revealed a novel mode of regulation by a sRNA, whereby PhrS uses a base-pairing mechanism to activate a short upstream open reading frame to which the pqsR gene is translationally coupled. Expression of phrS requires the oxygen-responsive regulator ANR. Thus, PhrS is the first bacterial sRNA that provides a regulatory link between oxygen availability and quorum sensing, which may impact on oxygen-limited growth in P. aeruginosa biofilms.

Potentiation of polarized intestinal Caco-2 cell responsiveness to probiotics complexed with secretory IgA.

The precise mechanisms underlying the interaction between intestinal bacteria and the host epithelium lead to multiple consequences that remain poorly understood at the molecular level. Deciphering such events can provide valuable information as to the mode of action of commensal and probiotic microorganisms in the gastrointestinal environment. Potential roles of such microorganisms along the privileged target represented by the mucosal immune system include maturation prior, during and after weaning, and the reduction of inflammatory reactions in pathogenic conditions. Using human intestinal epithelial Caco-2 cell grown as polarized monolayers, we found that association of a Lactobacillus or a Bifidobacterium with nonspecific secretory IgA (SIgA) enhanced probiotic adhesion by a factor of 3.4-fold or more. Bacteria alone or in complex with SIgA reinforced transepithelial electrical resistance, a phenomenon coupled with increased phosphorylation of tight junction proteins zonula occludens-1 and occludin. In contrast, association with SIgA resulted in both enhanced level of nuclear translocation of NF-κB and production of epithelial polymeric Ig receptor as compared with bacteria alone. Moreover, thymic stromal lymphopoietin production was increased upon exposure to bacteria and further enhanced with SIgA-based complexes, whereas the level of pro-inflammatory epithelial cell mediators remained unaffected. Interestingly, SIgA-mediated potentiation of the Caco-2 cell responsiveness to the two probiotics tested involved Fab-independent interaction with the bacteria. These findings add to the multiple functions of SIgA and underscore a novel role of the antibody in interaction with intestinal bacteria.

La fibrose rétropéritonéale, une maladie inflammatoire méconnue. Observations cliniques et revue de la littérature [Retroperitoneal fibrosis, an unrecognized inflammatory disease. Clinical observations and review of the literature]

Retroperitoneal fibrosis (RF) is a rare disease, typically with an insidious clinical course. The peak incidence is seen in patients 40 to 60 years of age and mostly in man. The characteristic finding in this disease is a periaortic fibrous mass that often surrounds the ureters. Although usually regarded as an obstructive uropathy, there has been growing recognition of the condition as a generalized disease. It may have a wide variety of manifestations including mediastinitis, thyroiditis and sclerosing cholangitis. The most common mode of presentation remains abdominal or flank pain with uremia, anemia and a high sedimentation rate. Although ultrasound and renal scintigraphy may contribute to the general evaluation of patients with RF, CT-scanner is the preferred imaging method. The multiplanar imaging capability of magnetic resonance may facilitate assessment of disease extent. The pathogenesis of the disease remains unknown. Steroids and, more recently tamoxifen, appear to be effective in the treatment of the RF. In most instances, RF does not lead to long-term morbidity or affect survival. The three cases of RF reported herein illustrate the varied mode of presentation and the response to the treatment.

Calcineurin-Mediated Regulation of Hyphal Growth, Septation, and Virulence in Aspergillus fumigatus.

Calcineurin is a heterodimeric protein phosphatase complex composed of catalytic (CnaA) and regulatory (CnaB) subunits and plays diverse roles in regulating fungal stress responses, morphogenesis, and pathogenesis. Fungal pathogens utilize the calcineurin pathway to survive in the host environment and cause life-threatening infections. The immunosuppressive calcineurin inhibitors (FK506 and cyclosporine A) are active against fungi, making calcineurin a promising antifungal drug target. Here, we review novel findings on calcineurin localization and functions in Aspergillus fumigatus hyphal growth and septum formation through regulation of proteins involved in cell wall biosynthesis. Extensive mutational analysis in the functional domains of A. fumigatus CnaA has led to an understanding of the relevance of these domains for the localization and function of CnaA at the hyphal septum. An evolutionarily conserved novel mode of calcineurin regulation by phosphorylation in filamentous fungi was found to be responsible for virulence in A. fumigatus. This finding of a filamentous fungal-specific mechanism controlling hyphal growth and virulence represents a potential target for antifungal therapy.

Carotid-subclavian arteries Index (CSI), a new echocardiographic index to recognize coarctation of the aorta in neonates and infants

Introduction: Coarctation of the aorta is a common congenital heart malformation. Mode of diagnosis changed from clinically to almost exclusively by echocardiogram and MRI. We claim to find a new echocardiographic index, based on simple and reliable morphologic measurements, to facilitate the diagnosis of aortic coarctation in the newborn.We reproduce the same procedure for older child to validate this new index. Material and Methods: We reviewed echocardiographic studies of 47 neonates with diagnosis of coarctation who underwent cardiac surgery between January 1997 and February 2003 and compared them with a matched control group. We measured 12 different sites of the aorta, aortic arch and the great vessels on the echocardiographic bands. In a second time we reviewed 23 infants for the same measurements and compare them with a matched control group. Results: 47 neonates with coarctation were analysed, age 11.8 _ 10 days,weight 3.0 _ 0.6 kg, body surface 0.20 _ 0.02m2. The control group was of 16 newborns aged 15.8 _ 10 days,weight 3.2 _ 0.9 kg and body surface 0.20 _ 0.04m2. A significant difference was noted in many morphologic measurement between the both groups, the most significant being the distance between the left carotid artery and the left subclavian artery (coarctation vs control: 7.3 _ 3mm vs 2.4 _ 0.8mm, p _ 0.0001). We then defined a new index, the carotid-subclavian arteries index (CSI) as the diameter of the distal tranverse aortic arch divided to the distance left carotid artery to left subclavian artery being also significaly different (coarctation vs control: 0.76 _ 0.86 vs 2.95 _ 1.24, p _ 0.0001). With the cutoff value of this index of 1.5 the sensitivity for aortic coarctation was 98% and the specificity of 92%. In an older group of infant with coarctation (16 patients) we apply the same principle and find for a cut-off value of 1.5 a sensitivity of 95% and a specificity of 100%. Conclusions: The CSI allows to evaluate newborns and infants for aortic coarctation with simple morphologic measurement that are not depending of the left ventricular function, presence of a patent ductus arteriosus or not. Further aggressive evaluation of these patient with a CSI _ 1.5 is indicated.

Continuous recording intrarectal pressures during the second phase of labor.

Parameters of intrarectal pressure (surface area under pressure curve and peak pressure) recorded with a microsystem device during the second phase of labor showed no significant correlations with baby's weight or mode of delivery. AIM OF THE STUDY: Was to assess the biomechanical pressures delivered against pelvic floor structures during the second phase of labor in nulliparae women, and to correlate them with obstetrics parameters, i.e. baby'sweight and mode of delivery. MATERIAL: Using a microsystem device placed into the rectum at the beginning of the second phase of labor, two parameters were assessed during the bearing efforts in 59 nulliparae women: the surface area under the pressure curve and the peak pressure. RESULTS: During 11.5±9 bearing efforts of 99.1±16s duration, the mean value of surface area under the pressure curve was 32677±26058cm/s and the mean value of the peak pressure was 60.7±24cmH(2)O, exceeding 100cmH(2)O in 10% of women. These two parameters were not correlated with baby's weight (R: 0.19, P: 0.15 and R: 0.05, P: 0.71). In the same way, these two parameters were not correlated with the mode of delivery (spontaneous or forceps/vacuum-assisted). Furthermore, the individual values of these two parameters showed great variation from one woman to another. CONCLUSION: This study has showed that parameters of biomechanical pressures recorded into the rectum during second phase of labor had no significant correlations with obstetricals parameters, explaining why these latter have poor predicitive value of further pelvic floor problems.