Pre‐Liver Transplant Cardiac Catheterization is Associated with Low Rate of Myocardial Infarction and Cardiac Mortality

Background A previous study at Indiana University demonstrated a reduction in myocardial infarction (MI) incidence with increased frequency of cardiac catheterization (CATH) in liver transplant (LT) candidates. A strict protocol for performing CATH based upon predefined risk factors, rather than non‐invasive testing alone, was applied to a subgroup (2009‐2010) from that study. CATH was followed by percutaneous coronary intervention (PCI) in cases of significant coronary artery disease (CAD; ≥50% stenosis). The current study applies this screening protocol to a larger cohort (2010‐2016) to assess post‐LT clinical outcomes. Results Among 811 LT patients, 766 underwent stress testing (94%), and 559 underwent CATH (69%) of whom 10% had CAD requiring PCI. The sensitivity of stress echocardiography in detecting significant CAD was 37%. Predictors of PCI included increasing age, male gender and personal history of CAD (p<0.05 for all). Compared to patients who had no CATH, patients who underwent CATH had higher mortality (p=0.07), and the hazard rates (HR) for mortality increased with CAD severity [normal CATH (HR: 1.35 [95% CI: 0.79, 2.33], p=0.298); non‐obstructive CAD (HR: 1.53 [95% CI: 0.84, 2.77], p=0.161); and significant CAD (HR: 1.96 [95% CI: 0.93, 4.15], p=0.080)]. Post‐LT outcomes were compared to the 2009‐2010 subgroup from the previous study and showed similar 1‐year overall mortality (8% and 6%, p=0.48); 1‐year MI incidence (<1% and <1%, p=0.8); and MI deaths as portion of all deaths (3% and 9%, p=0.35). Conclusion Stress echocardiography alone is not reliable in screening LT patients for CAD. Aggressive CAD screening with CATH is associated with low rate of MI and cardiac mortality and validates the previously published protocol when extrapolated over a larger sample and longer follow‐up period

Impact of a Prohibitive Versus Restrictive Tobacco Policy on Liver Transplant Candidate Outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150602/1/lt25497_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150602/2/lt25497.pd

Stented ureterovesical anastomosis in renal transplantation: does it influence the rate of urinary tract infections?

<p>Abstract</p> <p>Objective</p> <p>Our objective was to evaluate the impact of routine use of double-J stents on the incidence of urinary tract infection after renal transplantation.</p> <p>Methods</p> <p>We conducted a retrospective-comparative single-centre study in 310 consecutive adult deceased donor kidney recipients transplanted from 2002 to 2006. Patients were divided in two groups, with or without urinary stent implantation. To evaluate the predictive factors for UTI, donor and recipients pre- and post-transplantation data were analysed. Early urological complications and renal function within 12 months of transplantation were included as well.</p> <p>Results</p> <p>A total of 157 patients were enrolled to a stent (ST) and 153 patients to a no-stent (NST) group. The rate of urinary tract infection at three months was similar between the two groups (43.3% ST vs. 40.1% NST, p = 0.65). Of the identified pathogens Enterococcus and Escherichia coli were the most common species. In multivariate analysis neither age nor immunosuppressive agents, BMI or diabetes seemed to have influence on the rate of UTI. When compared to males, females had a significantly higher risk for UTI (54.0% vs. 33.5%).</p> <p>Conclusion</p> <p>Prophylactic stenting of the ureterovesical anastomosis does not increase the risk of urinary tract infection in the early postoperative period.</p

Degradation of YRA1 Pre-mRNA in the Cytoplasm Requires Translational Repression, Multiple Modular Intronic Elements, Edc3p, and Mex67p

The yeast YRA1 pre-mRNA contains multiple intronic elements that regulate transcript decay and translatability via the Edc3p decapping activator and the Mex67p/Mtr2p export receptor

The incidence of smoking and risk factors for smoking initiation in medical faculty students: cohort study

BACKGROUND: Medical education requires detailed investigation because it is a period during which the attitudes and behaviors of physicians develop. The purpose of this study was to calculate the yearly smoking prevalence and incidence rates of medical faculty students and to identify the risk factors for adopting smoking behaviour. METHODS: This is a cohort study in which every student was asked about their smoking habits at the time of first registration to the medical faculty, and was monitored every year. Smoking prevalence, yearly incidence of initiation of smoking and average years of smoking were calculated in analysis. RESULTS: At the time of registration, 21.8% of the students smoked. At the end of six years, males had smoked for an average of 2.6 ± 3.0 years and females for 1.0 ± 1.8 years (p < 0.05). Of the 93 medical students who were not smokers at the time of registration, 30 (32.3%) were smokers at the end of the 6 years of the course. CONCLUSION: The first 3 years of medical education are the most risky period for initiation of smoking. We found that factors such as being male, having a smoking friend in the same environment and having a high trait anxiety score were related to the initiation of smoking. Targeted smoking training should be mandatory for students in the Medical Faculty

Spt2p Defines a New Transcription-Dependent Gross Chromosomal Rearrangement Pathway

Large numbers of gross chromosomal rearrangements (GCRs) are frequently observed in many cancers. High mobility group 1 (HMG1) protein is a non-histone DNA-binding protein and is highly expressed in different types of tumors. The high expression of HMG1 could alter DNA structure resulting in GCRs. Spt2p is a non-histone DNA binding protein in Saccharomyces cerevisiae and shares homology with mammalian HMG1 protein. We found that Spt2p overexpression enhances GCRs dependent on proteins for transcription elongation and polyadenylation. Excess Spt2p increases the number of cells in S phase and the amount of single-stranded DNA (ssDNA) that might be susceptible to cause DNA damage and GCR. Consistently, RNase H expression, which reduces levels of ssDNA, decreased GCRs in cells expressing high level of Spt2p. Lastly, high transcription in the chromosome V, the location at which GCR is monitored, also enhanced GCR formation. We propose a new pathway for GCR where DNA intermediates formed during transcription can lead to genomic instability

Model Organisms Reveal Insight into Human Neurodegenerative Disease: Ataxin-2 Intermediate-Length Polyglutamine Expansions Are a Risk Factor for ALS

Model organisms include yeast Saccromyces cerevisae and fly Drosophila melanogaster. These systems have powerful genetic approaches, as well as highly conserved pathways, both for normal function and disease. Here, we review and highlight how we applied these systems to provide mechanistic insight into the toxicity of TDP-43. TDP-43 accumulates in pathological aggregates in ALS and about half of FTD. Yeast and fly studies revealed an interaction with the counterparts of human Ataxin-2, a gene whose polyglutamine repeat expansion is associated with spinocerebellar ataxia type 2. This finding raised the hypothesis that repeat expansions in ataxin-2 may associate with diseases characterized by TDP-43 pathology such as ALS. DNA analysis of patients revealed that intermediate-length polyglutamine expansions in ataxin-2 are a risk factor for ALS, such that repeat lengths are greater than normal, but lower than that associated with spinocerebellar ataxia type 2 (SCA2), and are more frequent in ALS patients than in matched controls. Moreover, repeat expansions associated with ALS are interrupted CAA-CAG sequences as opposed to the pure CAG repeat expansions typically associated with SCA2. These studies provide an example of how model systems, when extended to human cells and human patient tissue, can reveal new mechanistic insight into disease

microRNA-Mediated Messenger RNA Deadenylation Contributes to Translational Repression in Mammalian Cells

Animal microRNAs (miRNAs) typically regulate gene expression by binding to partially complementary target sites in the 3′ untranslated region (UTR) of messenger RNA (mRNA) reducing its translation and stability. They also commonly induce shortening of the mRNA 3′ poly(A) tail, which contributes to their mRNA decay promoting function. The relationship between miRNA-mediated deadenylation and translational repression has been less clear. Using transfection of reporter constructs carrying three imperfectly matching let-7 target sites in the 3′ UTR into mammalian cells we observe rapid target mRNA deadenylation that precedes measureable translational repression by endogenous let-7 miRNA. Depleting cells of the argonaute co-factors RCK or TNRC6A can impair let-7-mediated repression despite ongoing mRNA deadenylation, indicating that deadenylation alone is not sufficient to effect full repression. Nevertheless, the magnitude of translational repression by let-7 is diminished when the target reporter lacks a poly(A) tail. Employing an antisense strategy to block deadenylation of target mRNA with poly(A) tail also partially impairs translational repression. On the one hand, these experiments confirm that tail removal by deadenylation is not strictly required for translational repression. On the other hand they show directly that deadenylation can augment miRNA-mediated translational repression in mammalian cells beyond stimulating mRNA decay. Taken together with published work, these results suggest a dual role of deadenylation in miRNA function: it contributes to translational repression as well as mRNA decay and is thus critically involved in establishing the quantitatively appropriate physiological response to miRNAs