Near-infrared fluorescent dyes for enhanced contrast in optical mammography: phantom experiments

Optical mammography with near-infrared (NIR) light using time-domain, frequency-domain, or continuous-wave techniques is a novel imaging modality to locate human breast tumors. By investigating excised specimens of normal and diseased mamma tissue we were able to demonstrate that differences in their scattering properties are a poor predictive parameter for normal and diseased mamma tissue. This paper describes the application of a NIR dye to improve the differentiation between breast tumors and normal tissue in a rat model. The NIR dye furnished a high tumor-to-tissue contrast ratio (6:1) in fluorescence images. Furthermore, this dye was used to develop liquid scattering phantoms with absorbing and fluorescent inhomogeneities. Using frequency-domain and time-domain instrumentation these inhomogeneities were localized at sufficient contrast by their increased absorption and fluorescence. Contrast between inhomogeneities and surrounding medium could be improved by combining fluorescence and transmittance images.     

Improved Detection and Analysis of Sensed and Paced Events in Dual Chamber Pacemakers with Extended Memory Function A Prospective Multicenter Trial in 626 Patients

PATIENTS AND METHODS: This prospective study analyzed the incidence of atrial arrhythmias in a population of 626 patients in 173 medical centers of eleven European countries and Japan with indication for a dual chamber pacemaker system. The accuracy of the new Automatic Interpretation for Diagnosis Assistance (AIDA) program which is included in Chorus pacemakers was evaluated and the AIDA analysis was compared to and proven with Holter monitoring. Data stored in the pacemakers' memories for the first 24 hours (D1) were compared with simultaneously recorded 24-hour surface electrocardiograms, and data stored over the following 28 days (D28) were examined against reported intercurrent symptoms. RESULTS: At D1, atrial arrhythmias were detected by AIDA in 60 of 626 patients (12%), consisting of atrial fibrillation (n = 29), atrial flutter (n = 4), and miscellaneous arrhythmias (n = 17), and closely corroborated by Holter monitoring (sensitivity 93.7%, specificity 94.9%). At D28, 149 of 386 patients (49%) had had episodes of automatic mode switch prompted by atrial arrhythmias. Symptoms were reported by 81 patients (54%), 92 (62%) had no histories of atrial arrhythmias, and 57 patients (38%) were neither symptomatic nor had histories of atrial arrhythmias. An inverse relationship was found between the number of atrial paced events and the occurrence of atrial arrhythmias (p < 0.001). A history of atrial arrhythmias and older age were associated with a higher risk of atrial arrhythmias (p < 0.05). In contrast, gender, hypertension, concomitant heart disease, or type of atrial lead fixation system were not related with the occurrence of atrial arrhythmias. CONCLUSION: AIDA allowed to confirm, or disprove, the occurrence of atrial arrhythmias as a source of symptoms reported during long-term follow-up. It could also be used to examine the efficacy of antiarrhythmic therapy, and be of assistance when weighing the needs for anticoagulation in patients experiencing asymptomatic atrial arrhythmias.     

Clinical significance of the corrected orthogonal ECG (Frank) in comparison with conventional ECG for the detection of coronary heart disease

The clinical evidence of the two derivation systems is of the same value concerning the recognition of the coronary heart disease. Their information range does not significantly differ from each other statistically, when scale and vectorial parameters of the corrected orthogonal ECG after Frank are taken into consideration. But in individual cases clear differences may be present, such as the insufficient representation of localized precordial potential losses in the corrected orthogonal ECG. With the help of the discriminance analysis the high number of falsely negative findings of the ECG after resting can be reduced from about 45% to 15% to 20%. Within a diagnostic stage programme from the recognition and care of particularly endangered patients with coronary heart disease the corrected orthogonal ECG is suited, when a discriminance-analytic valuation with scale and vectorial parameters is made. In contrast to the conventional ECG it has the advantage that it is more rapidly and less expensively to be evaluated by computers.     

Genomic and Functional Portrait of a Highly Virulent,CTX-M-15-Producing H30-Rx Subclone of Escherichia coli Sequence Type 131

Escherichia coli sequence type 131 (ST131) is a pandemic clone associated with multidrug-resistant, extraintestinal infections, attributable to the presence of the CTX-M-15 extended-spectrum β-lactamase gene and mutations entailing fluoroquinolone resistance. Studies on subclones within E. coli ST131 are critically required for targeting and implementation of successful control efforts. Our study comprehensively analyzed the genomic and functional attributes of the H30-Rx subclonal strains NA097 and NA114, belonging to the ST131 lineage. We carried out whole-genome sequencing, comparative analysis, phenotypic virulence assays, and profiling of the antibacterial responses of THP1 cells infected with these subclones. Phylogenomic analysis suggested that the strains were clonal in nature and confined entirely to a single clade. Comparative genomic analysis revealed that the virulence and resistance repertoires were comparable among the H30-Rx ST131 strains except for the commensal ST131 strain SE15. Similarly, seven phage-specific regions were found to be strongly associated with the H30-Rx strains but were largely absent in the genome of SE15. Phenotypic analysis confirmed the virulence and resistance similarities between the two strains. However, NA097 was found to be more robust than NA114 in terms of virulence gene carriage (dra operon), invasion ability (P < 0.05), and antimicrobial resistance (streptomycin resistance). RT² gene expression profiling revealed generic upregulation of key proinflammatory responses in THP1 cells, irrespective of ST131 lineage status. In conclusion, our study provides comprehensive, genome-inferred insights into the biology and immunological properties of ST131 strains and suggests clonal diversification of genomic and phenotypic features within the H30-Rx subclone of E. coli ST131.     

Bilayers merge even when exocytosis is transient

During exocytosis, the lumen of secretory vesicles connects with the extracellular space. In some vesicles, this connection closes again, causing the vesicle to be recaptured mostly intact. The degree to which the bilayers of such vesicles mix with the plasma membrane is unknown. Work supporting the kiss-and-run model of transient exocytosis implies that synaptic vesicles allow neither lipid nor protein to escape into the plasma membrane, suggesting that the two bilayers never merge. Here, we test whether neuroendocrine granules behave similarly. Using two-color evanescent field microscopy, we imaged the lipid probe FM4-64 and fluorescent proteins in single dense core granules. During exocytosis, granules lost FM4-64 into the plasma membrane in small fractions of a second. Although FM4-64 was lost, granules retained the membrane protein, GFP-phogrin. By using GFP-phogrin as a probe for resealing, it was found that even granules that reseal lose FM4-64. We conclude that the lipid bilayers of the granule and the plasma membrane become continuous even when exocytosis is transient.