The prognostic importance of nonsignificant left main coronary artery disease in patients undergoing percutaneous coronary intervention.

OBJECTIVES: The purpose of this research was to study the association between nonsignificant (<50%) left main coronary artery disease (LMCAD) and short- and long-term survival in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: The prognostic importance of nonsignificant LMCAD is unknown; however, the co-existence of nonsignificant LMCAD may influence revascularization decisions. METHODS: We analyzed mortality and repeat catheterization rates of 11,855 patients in a prospective cardiac registry database who underwent single-vessel or multivessel PCI from January 1996 through December 2001. Of this cohort, 11.7% (n = 1,385) had nonsignificant (<50%) LMCAD. Outcomes were compared with those without LMCAD. A secondary analysis was performed on a larger cohort of 34,586 patients undergoing cardiac catheterization, irrespective of mode of revascularization therapy. RESULTS: Patients with nonsignificant LMCAD had more co-morbidities, and a significantly higher crude mortality rate at 1 year compared with those without LMCAD (4.4% vs. 3.4%; p = 0.05). The 7-year crude mortality hazard ratio (HR) of PCI patients with <50% LMCAD versus those with no LMCAD was 1.18 (95% confidence interval [CI] 0.94 to 1.46). After risk adjustment for differences in baseline clinical profile, however, the HR decreased to 0.98 (95% CI 0.79 to 1.23). Repeat catheterization rates at 1 year did not differ between groups. The secondary analysis in all patients with nonsignificant LMCAD showed an adjusted HR of 1.03 (95% CI 0.94 to 1.14). CONCLUSIONS: Patients undergoing single-vessel or multivessel PCI who have <50% LMCAD have a nonsignificantly increased 18% relative risk for mortality compared with those without detectable LMCAD that appears to be related to these patients' higher incidence of co-morbidities rather than the left main stenosis itself.     

Molecular phylogeny of a newfound hantavirus in the Japanese shrew mole (Urotrichus talpoides)

Recent molecular evidence of genetically distinct hantaviruses in shrews, captured in widely separated geographical regions, corroborates decades-old reports of hantavirus antigens in shrew tissues. Apart from challenging the conventional view that rodents are the principal reservoir hosts, the recently identified soricid-borne hantaviruses raise the possibility that other soricomorphs, notably talpids, similarly harbor hantaviruses. In analyzing RNA extracts from lung tissues of the Japanese shrew mole (Urotrichus talpoides), captured in Japan between February and April 2008, a hantavirus genome, designated Asama virus (ASAV), was detected by RT-PCR. Pairwise alignment and comparison of the S-, M-, and L-segment nucleotide and amino acid sequences indicated that ASAV was genetically more similar to hantaviruses harbored by shrews than by rodents. However, the predicted secondary structure of the ASAV nucleocapsid protein was similar to that of rodent- and shrew-borne hantaviruses, exhibiting the same coiled-coil helix at the amino terminus. Phylogenetic analyses, using the maximum-likelihood method and other algorithms, consistently placed ASAV with recently identified soricine shrew-borne hantaviruses, suggesting a possible host-switching event in the distant past. The discovery of a mole-borne hantavirus enlarges our concepts about the complex evolutionary history of hantaviruses.     

Distinct Patterns of Sirtuin Expression During Progression of Alzheimer’s Disease

Aging is one of the major risk factors for Alzheimer’s disease (AD). Sirtuins are associated with prolonged life span. To examine whether the expression levels of sirtuins associate with the progression of AD or not, we performed a comparative immunoblotting and immunohistochemical study of SIRT1, 3, and 5 in the entorhinal cortex and hippocampal subregions and white matter in 45 cases grouped according to Braak and Braak stages of neurofibrillary degeneration. In addition, we compared the expression levels with the local load of tau and amyloid-beta deposits, evaluated using morphometry. Our study revealed that (1) the neuronal subcellular redistribution of SIRT1 parallels the decrease in its expression, suggesting stepwise loss of neuroprotection dependent on the neuronal population; (2) in contrast to SIRT1 and 3, expression of SIRT5 increases during the progression of AD; (3) which might be related to its appearance in activated microglial cells. The complex patterns of the expression of sirtuins in relation to tissue damage should be taken into account when searching for therapies interacting with sirtuins.     

What do Australian patients with inflammatory arthritis value in treatment? A discrete choice experiment

Clinical Rheumatology - The purpose of this study was to develop an understanding of treatment preferences in patients with inflammatory arthritis (IA) [rheumatoid arthritis (RA), ankylosing...     

Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes

Diabetic nephropathy is the leading cause of end-stage renal failure and accounts for 30–40 % of patients entering renal transplant programmes. The nephroprotective effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) against diabetes have been shown previously, but the molecular mechanisms responsible for these effects remain unknown. In the present study, we showed that PACAP treatment counteracted the diabetes-induced increase in the level of the proapoptotic pp38MAPK and cleaved caspase-3 and also decreased the p60 subunit of NFκB. The examined antiapoptotic factors, including pAkt and pERK1/2, showed a slight increase in the diabetic kidneys, while PACAP treatment resulted in a notable elevation of these proteins. PCR and Western blot revealed the downregulation of fibrotic markers, like collagen IV and TGF-β1 in the kidney. PACAP treatment resulted in increased expression of the antioxidant glutathione. We conclude that the nephroprotective effect of PACAP in diabetes is, at least partly, due to its antiapoptotic, antifibrotic and antioxidative effect in addition to the previously described antiinflammatory effect.     

Discordant and heterogeneous clinically relevant genomic alterations in circulating tumor cells vs plasma DNA from men with metastatic castration resistant prostate cancer

Circulating tumor cell (CTC) and cell‐free (cf) DNA‐based genomic alterations are increasingly being used for clinical decision‐making in oncology. However, the concordance and discordance between paired CTC and cfDNA genomic profiles remain largely unknown. We performed comparative genomic hybridization (CGH) on CTCs and cfDNA, and low‐pass whole genome sequencing (lpWGS) on cfDNA to characterize genomic alterations (CNA) and tumor content in two independent prospective studies of 93 men with mCRPC treated with enzalutamide/abiraterone, or radium‐223. Comprehensive analysis of 69 patient CTCs and 72 cfDNA samples from 93 men with mCRPC, including 64 paired samples, identified common concordant gains in FOXA1, AR, and MYC, and losses in BRCA1, PTEN, and RB1 between CTCs and cfDNA. Concordant PTEN loss and discordant BRCA2 gain were associated with significantly worse outcomes in Epic AR‐V7 negative men with mCRPC treated with abiraterone/enzalutamide. We identified and externally validated CTC‐specific genomic alternations that were discordant in paired cfDNA, even in samples with high tumor content. These CTC/cfDNA‐discordant regions included key genomic regulators of lineage plasticity, osteomimicry, and cellular differentiation, including MYCN gain in CTCs (31%) that was rarely detected in cfDNA. CTC MYCN gain was associated with poor clinical outcomes in AR‐V7 negative men and small cell transformation. In conclusion, we demonstrated concordance of multiple genomic alterations across CTC and cfDNA platforms; however, some genomic alterations displayed substantial discordance between CTC DNA and cfDNA despite the use of identical copy number analysis methods, suggesting tumor heterogeneity and divergent evolution associated with poor clinical outcomes.     

Quantification of periaortic adipose tissue in contrast-enhanced CT angiography: technical feasibility and methodological considerations

The International Journal of Cardiovascular Imaging - To examine the feasibility of the quantification of abdominal periaortic fat tissue (PaFT) (tissue within −&nbsp;45 to...