Reuse of Explanted Pacemakers: An Option for Economically Underprivileged Patients in Developing Countries

Permanent pacemaker implantation is an established mode of life saving therapy for patients with symptomatic bradycardia. As the human population is aging world-over, the need for pacemakers are also increasing. Reviewing the results of the 2001 World Survey on Cardiac Pacing and Implantable Cardioverter Defibrillators (Table 1), it is evident that not all patients who require pacemakers are receiving them, particularly in the Asia-Pacific region. The largest implanting country per head of population is Germany, although the largest numbers implanted are in the United States of America. In contrast, the countries of Asia have much smaller numbers with Myanmar having less than one implant per million population per year1

Investigation of the role of gravity waves in the generation of equatorial bubbles

The following areas of interest in this progress report are: (1) the continuation of software development in the examination of F-region gravity-wave power using in-situ data from the Atmosphere Explorer (AE-E); (2) the inquiry into the use of the San Marco data for the study of the initiation and growth of bubbles, particularly when the satellite passes through the early evening hours at relatively high altitudes, and the development of bubbles using not only the San Marco data but includes the use of airglow observations made in Hawaii; and (3) the promising development in the observation of distinct well formed waves at about 400 km altitude in the equatorial region. These waves look very much like waves seen over the polar cap that are attributed to internal gravity waves in the neutral atmosphere driving ionization up and down the magnetic field lines. These equatorial waves show no modulation of the total ion concentration

Incorporation of 3-Aminobenzanthrone into 2′-Deoxyoligonucleotides and Its Impact on Duplex Stability

3-Nitrobenzanthrone (3NBA), an environmental pollutant and potent mutagen, causes DNA damage via the reaction of its metabolically activated form with the exocyclic amino groups of purines and the C-8 position of guanine. The present work describes a synthetic approach to the preparation of oligomeric 2′-deoxyribonucleotides containing a 2-(2′-deoxyguanosin-N2-yl)-3-aminobenzanthrone moiety, one of the major DNA adducts found in tissues of living organisms exposed to 3NBA. The NMR spectra indicate that the damaged oligodeoxyribonucleotide is capable of forming a regular double helical structure with the polyaromatic moiety assuming a single conformation at room temperature; the spectra suggest that the 3ABA moiety resides in the duplex minor groove pointing toward the 5′-end of the modified strand. Thermodynamic studies show that the dG(N2)-3ABA lesion has a stabilizing effect on the damaged duplex, a fact that correlates well with the long persistence of this damage in living organisms

Lack of recognition by global-genome nucleotide excision repair accounts for the high mutagenicity and persistence of aristolactam-DNA adducts

Exposure to aristolochic acid (AA), a component of Aristolochia plants used in herbal remedies, is associated with chronic kidney disease and urothelial carcinomas of the upper urinary tract. Following metabolic activation, AA reacts with dA and dG residues in DNA to form aristolactam (AL)-DNA adducts. These mutagenic lesions generate a unique TP53 mutation spectrum, dominated by A : T to T : A transversions with mutations at dA residues located almost exclusively on the non-transcribed strand. We determined the level of AL-dA adducts in human fibroblasts treated with AA to determine if this marked strand bias could be accounted for by selective resistance to global-genome nucleotide excision repair (GG-NER). AL-dA adduct levels were elevated in cells deficient in GG-NER and transcription-coupled NER, but not in XPC cell lines lacking GG-NER only. In vitro, plasmids containing a single AL-dA adduct were resistant to the early recognition and incision steps of NER. Additionally, the NER damage sensor, XPC-RAD23B, failed to specifically bind to AL-DNA adducts. However, placing AL-dA in mismatched sequences promotes XPC-RAD23B binding and renders this adduct susceptible to NER, suggesting that specific structural features of this adduct prevent processing by NER. We conclude that AL-dA adducts are not recognized by GG-NER, explaining their high mutagenicity and persistence in target tissues

The Prograde Orbit of Exoplanet TrES-2b

We monitored the Doppler shift of the G0V star TrES-2 throughout a transit of its giant planet. The anomalous Doppler shift due to stellar rotation (the Rossiter-McLaughlin effect) is discernible in the data, with a signal-to-noise ratio of 2.9, even though the star is a slow rotator. By modeling this effect we find that the planet's trajectory across the face of the star is tilted by -9 +/- 12 degrees relative to the projected stellar equator. With 98% confidence, the orbit is prograde.Comment: ApJ, in press [15 pages

Effects of Time of Deoxyribonucleic Acid Microinjection on Gene Detection and In Vitro Development of Bovine Embryos

In vivo fertilized embryos were surgically collected from superovulated dairy cows to evaluate microinjection on embryo development and utilized the polymerase chain reaction technique for selection of transgenic embryos. Seventy-two percent of the embryos with visible pronuclei or nuclei were microinjected with DNA, and the remaining 28% served as uninjected controls. All embryos were cocultured with bovine oviductal epithelial cells. Mean final development scores of embryos within the same initial cell stage at collection were unaffected by microinjection. After 144 h of culture, 45% of the microinjected embryos developed to the morula or blastocyst stage. The transgene was detected in 50, 10, and 9% of demimorulae from embryos microinjected at the 1-, 2-, and 4-cell stages. Frequency of transgene detection was higher in morulae from 1-cell embryos than in morulae from 2- and 4-cell embryos. Use of in vitro coculture, embryo bisection, and polymerase chain reaction technique facilitated selection of bovine embryos that carried the transgene

The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis

Background: Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM. Methods: 101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM (Nottingham, UK). 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the NHLBI LAM Registry (USA). Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control sera using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and SNPs in GC encoding Vitamin D Binding Protein (VTDB) genotyped. Results: Proteomic analysis showed VTDB was 2.6 fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity (p=0.01). Median time to death or lung transplant was reduced by 46 months in those with CC genotypes at rs4588 and 38 months in those with non-A containing haplotypes at rs7041/4588 (p=0.014 and 0.008 respectively). Conclusions: The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant free survival in LAM

3D excretory MR urography: Improved image quality with intravenous saline and diuretic administration

Purpose To assess the effect of diuretic administration on the image quality of excretory magnetic resonance urography (MRU) obtained following intravenous hydration, and to determine whether intravenous hydration alone is sufficient to produce diagnostic quality studies of nondilated upper tracts. Materials and Methods A total of 22 patients with nondilated upper tracts were evaluated with contrast-enhanced MRU. All patients received 250 mL of saline intravenously immediately prior to the examination. A total of 11 patients received 10–20 mg furosemide in addition to saline. Imaging was performed with a three-dimensional (3D) and two-dimensional (2D) breathhold spoiled gradient-echo sequences. Excretory MRU images were acquired five minutes after the administration of 0.1 mmol/kg gadolinium and were independently reviewed by two radiologists, who were blinded to the MRU technique. Readers evaluated the calyces, renal pelvis, and ureters qualitatively for degree of opacification, distention, and artifacts on a four-point scale. Statistical analysis was performed using a permutation test. Results There was no significant disagreement between the two readers ( P = 0.14). Furosemide resulted in significant improvement in calyceal and renal pelvis distention ( P < 0.005), and significant artifact reduction in all upper tract segments ( P < 0.001) compared to the effect of saline alone. Conclusion Intravenous furosemide significantly improves the image quality of excretory MRU studies obtained following intravenous hydration. Intravenous saline alone is insufficient to produce diagnostic quality studies of the non-dilated upper tracts. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56023/1/20875_ftp.pd