Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study

The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.     

Automated 3D Ιnterstitial Lung Disease Εxtent Quantification: Performance Evaluation and Correlation to PFTs

In this study, the performance of a recently proposed computer-aided diagnosis (CAD) scheme in detection and 3D quantification of reticular and ground glass pattern extent in chest computed tomography of interstitial lung disease (ILD) patients is evaluated. CAD scheme performance was evaluated on a dataset of 37 volumetric chest scans, considering five representative axial anatomical levels per scan. CAD scheme reliability analysis was performed by estimating agreement (intraclass correlation coefficient, ICC) of automatically derived ILD pattern extent to semi-quantitative disease extent assessment in terms of 29-point rating scale provided by two expert radiologists. Receiver operating characteristic (ROC) analysis was employed to assess CAD scheme accuracy in ILD pattern detection in terms of area under ROC curve (A_z). Correlation of reticular and ground glass volumetric pattern extent to pulmonary function tests (PFTs) was also investigated. CAD scheme reliability was substantial for ILD extent (ICC = 0.809) and distinct reticular pattern extent (0.806) and moderate for distinct ground glass pattern extent (0.543), performing within inter-observer agreement. CAD scheme demonstrated high accuracy in detecting total ILD (A_z = 0.950 ± 0.018), while accuracy in detecting distinct reticular and ground glass patterns was 0.920 ± 0.023 and 0.883 ± 0.024, respectively. Moderate and statistically significant negative correlation was found between reticular volumetric pattern extent and diffusing capacity, forced expiratory volume in 1 s, forced vital capacity, and total lung capacity (R = −0.581, −0.513, −0.494, and −0.446, respectively), similar to correlations found between radiologists’ semi-quantitative ratings with PFTs. CAD-based quantification of disease extent is in agreement with radiologists’ semi-quantitative assessment and correlates to specific PFTs, suggesting a potential imaging biomarker for ILD staging and management.     

Serum lipids in preterm infants fed a formula supplemented with nucleotides

BACKGROUND: The effect of dietary nucleotides on lipid metabolism has been the subject of clinical studies with conflicting results. We measured serum triglycerides, total cholesterol (total-C), and lipoprotein cholesterol levels (HDL-C, LDL-C, and VLDL-C) in preterm neonates fed formula with and without nucleotide supplements. METHODS: This prospective, randomized, controlled study included 150 healthy preterm neonates (gestational age, 33.0 +/- 1.9 weeks) matched for gestational age, birth weight, and gender. Subjects were assigned at birth to receive either a standard milk formula supplemented with nucleotides (group F-NT) or the same formula without nucleotides (group F). Serum was obtained before discharge (29.1 +/- 10.0 days of life) and triglycerides, total-C, and HDL-C were determined enzymatically. LDL-C and VLDL-C were estimated by the Friedewald formula. For statistical analysis t test, Mann Whitney-U test, two-way ANOVA, and chi2 test were used, as appropriate. The influence of several factors on serum lipid levels was evaluated by linear regression analysis. RESULTS: Serum triglycerides, total-C, and VLDL-C levels did not differ between groups. HDL-C levels (median; 25th-75th percentiles) were significantly higher (P < 0.001) in group F-NT (48.0 mg/dL; 40.5-57.0 mg/dL) than in group F (34.5 mg/dL; 27.2-44.0 mg/dL). On the contrary, LDL-C levels (median; 25th-75th percentiles) were significantly lower (P < 0.001) in group F-NT (39.0 mg/dL; 26.0-54.0 mg/dL) than in group F (65.0 mg/dL; 41.0-73.0 mg/dL). In the multiple regression analysis, nucleotide supplementation was identified as one of the controlled independent factors influencing serum HDL-C and LDL-C levels. CONCLUSIONS: Preterm neonates fed from birth with formula supplemented with nucleotides have significantly higher HDL-C and lower LDL-C serum levels than do neonates fed unsupplemented formula. The clinical relevance of these results remains to be elucidated.     

Two‐ and three‐dimensional multinuclear stray‐field imaging of rotating samples with magic‐angle spinning (STRAFI‐MAS): From bio to inorganic materials

Purpose:

To revisit and illustrate the potential of a simple and effective multidimensional stray‐field imaging technique with magic‐angle spinning, known as STRAFI‐MAS.

Materials and Methods:

STRAFI‐MAS images are acquired with a standard NMR magnet and a traditional magic‐angle sample spinning (MAS) probe. The stray‐field gradients are achieved by placing the MAS probe, along the z‐direction, at a distance from the center of the magnet. No pulsed‐field gradients are applied. The multidimensional spatial encoding is carried out by synchronizing the radiofrequency pulses with the sample MAS rotation.

Results:

Two‐dimensional (2D) and 3D multinuclear images of various phantoms, including a tibia bone and silicon carbide, are recorded. Images of inorganic solids containing quadrupolar nuclei, ²³Na and ²⁷Al, are also explored for the first time by STRAFI‐MAS.

Conclusion:

We have demonstrated that STRAFI‐MAS is a simple and user‐friendly technique for multidimensional imaging without the need of imaging equipment. With the current advancements in NMR and MRI methodologies, STRAFI‐MAS is expected to be further developed and improved. We anticipate that STRAFI‐MAS can spark a wide spectrum of interest, from material to bio science, where can benefit from high‐resolution images. J. Magn. Reson. Imaging 2010;32:418–423. © 2010 Wiley‐Liss, Inc.     

Laparoscopic versus open appendectomy in men: a prospective randomized trial

Background  

The role of laparoscopic treatment in acute appendicitis still is unclear. Although some evidence in the literature suggests diagnostic benefits from laparoscopy for young women with suspected acute appendicitis, there is scepticism about the utility of this approach for men. This study aimed to compare open and laparoscopic appendectomy performed for men with suspected acute appendicitis.     

Inefficient clustering of tyrosine-phosphorylated proteins at the immunological synapse in response to an antagonist peptide

Interactions of T cells with MHC plus peptide in the peripheral lymphoid system are important for their survival. In this study we investigated further the molecular consequences of such interactions using F5 TCR transgenic mice and peptides previously shown to induce either negative or positive selection in the thymus. Following TCR ligation with the negatively selecting agonist peptide, mature CD8(+) cells proliferated and up-regulated the activation marker CD69. Interestingly, ligation of this TCR with MHC molecules loaded with high concentrations of the positively selecting peptide also resulted in the aforementioned changes, but with slower kinetics. Analysis of the biochemical changes that occur following stimulation with these peptides showed that phosphorylation of key signaling molecules, such as ZAP-70, CD3zeta, Vav, SLP-76, LAT, and ERK-1 and 2, could be detected after exposure to agonist but not antagonist peptide. Confocal microscopy, however, revealed infrequent phosphorylation 'patches' at the site of contact between T cells and APC presenting the antagonist peptide. Our data suggest that peptides capable of inducing positive selection in the thymus can be recognized by mature T cells and cause proliferation, up-regulation of CD69 and accumulation of phosphorylated proteins at the immunological synapse with low efficiency; however no phosphorylation of signaling molecules can be detected using conventional biochemical assays.     

Measurements of primary off-axis ratios in wedged asymmetric photon fields: a formalism for dose and monitor unit calculations

Asymmetric collimators or heavily blocked fields with physical wedges are still encountered in daily practice. In such cases, a reliable dosimetry system is necessary to perform manual dose and monitor unit calculations in order to independently verify the calculations of commercial treatment planning systems. In this work, primary wedged off-axis ratios (POAR(w)s) that account for changes in the beam intensity along both the wedge gradient and perpendicular directions of the photon field, when asymmetric collimators are applied, were measured experimentally at specific depths. The measurements were made in phantom with an ion chamber along the wedge gradient and the perpendicular directions under 'good geometry' conditions. A consistent formalism was presented that could easily be implemented in the clinical environment as an independent verification of the calculations by a treatment planning system. The accuracy of the method was found to be dependent on the specific wedge used, off-axis distance and depth in the phantom. In our study, the accuracy was within 2% in most cases for both energies. We concluded that the primary wedged off-axis ratios when used along with open symmetric field dosimetric parameters could provide adequate accuracy for manual monitor unit calculations.     

A unified framework for haplotype inference in nuclear families

Many large genome-wide association studies include nuclear families with more than one child (trio families), allowing for analysis of differences between siblings (sib pair analysis). Statistical power can be increased when haplotypes are used instead of genotypes. Currently, haplotype inference in families with more than one child can be performed either using the familial information or statistical information derived from the population samples but not both. Building on our recently proposed tree-based deterministic framework (TDS) for trio families, we augment its applicability to general nuclear families. We impose a minimum recombinant approach locally and independently on each multiple children family, while resorting to the population-derived information to solve the remaining ambiguities. Thus our framework incorporates all available information (familial and population) in a given study. We demonstrate that using all the constraints in our approach we can have gains in the accuracy as opposed to breaking the multiple children families to separate trios and resorting to a trio inference algorithm or phasing each family in isolation. We believe that our proposed framework could be the method of choice for haplotype inference in studies that include nuclear families with multiple children. Our software (tds2.0) is downloadable from www.ee.columbia.edu/～anastas/tds.     

Differential release of mast cell mediators and the pathogenesis of inflammation

Summary:  Mast cells are well known for their involvement in allergic and anaphylactic reactions, during which immunoglobulin E (IgE) receptor (FcɛRI) aggregation leads to exocytosis of the content of secretory granules (1000 nm), commonly known as degranulation, and secretion of multiple mediators. Recent findings implicate mast cells also in inflammatory diseases, such as multiple sclerosis, where mast cells appear to be intact by light microscopy. Mast cells can be activated by bacterial or viral antigens, cytokines, growth factors, and hormones, leading to differential release of distinct mediators without degranulation. This process appears to involve de novo synthesis of mediators, such as interleukin-6 and vascular endothelial growth factor, with release through secretory vesicles (50 nm), similar to those in synaptic transmission. Moreover, the signal transduction steps necessary for this process appear to be largely distinct from those known in FcɛRI-dependent degranulation. How these differential mast cell responses are controlled is still unresolved. No clinically available pharmacological agents can inhibit either degranulation or mast cell mediator release. Understanding this process could help develop mast cell inhibitors of selective mediator release with novel therapeutic applications.     

Long-term verifiability of the electronic healthcare records' authenticity

PURPOSE: To investigate whether the long-term preservation of the authenticity of electronic healthcare records (EHR) is possible. To propose a mechanism that enables the secure validation of an EHR for long periods, far beyond the lifespan of a digital signature and at least as long as the lifetime of a patient. APPROACH: The study is based on the fact that although the attributes of data authenticity, i.e. integrity and origin verifiability, can be preserved by digital signatures, the necessary period for the retention of EHRs is far beyond the lifespan of a simple digital signature. It is identified that the lifespan of signed data is restricted by the validity period of the relevant keys and the digital certificates, by the future unavailability of signature-verification data, and by suppression of trust relationships. In this paper, the notarization paradigm is exploited, and a mechanism for cumulative notarization of signed EHR is proposed. RESULTS: The proposed mechanism implements a successive trust transition towards new entities, modern technologies, and refreshed data, eliminating any dependency of the relying party on ceased entities, obsolete data, or weak old technologies. The mechanism also exhibits strength against various threat scenarios. CONCLUSIONS: A future relying party will have to trust only the fresh technology and information provided by the last notary, in order to verify the authenticity of an old signed EHR. A Cumulatively Notarized Signature is strong even in the case of the compromise of a notary in the chain.