Search

AbstractDamaged 2’-deoxyribonucleotides cause mutations, cancer, cell death, and aging. The Escherichia coli Orf135 (NudG) protein catalyzes the hydrolysis of various 2’-deoxyribonucleotides including an oxidized form of dATP, 2-oxo-1,2-dihydro-2’-deoxyadenosine 5’-triphosphate (dAOTP, 2-hydroxy-2’-deoxyadenosine 5’-triphosphate). The best substrate is 5-methyl-2’-deoxycytidine 5’-triphosphate (dCmTP), and the protein prefers dCmTP over dAOTP by ∼200-fold in vitro. To make the enzyme specific for the mutagenic nucleotide dAOTP, a double mutant protein (E33A plus D118E) was designed and produced in E. coli. The purified mutant protein showed one order of magnitude higher dAOTP preference over dCmTP. The split protein based on this mutant may potentially be used to detect dAOTP in living cells. [ABSTRACT FROM AUTHOR]

Inhalation exposures to dihydroxyacetone (DHA) occur through spray tanning and e-cigarette aerosols. Several studies in skin models have demonstrated that millimolar doses of DHA are cytotoxic, yet the genotoxicity was unclear. We examined the genotoxicity of DHA in cell models relevant to inhalation exposures. Human bronchial epithelial cells BEAS-2B, lung carcinoma cells A549, cardiomyocyte Ac16, and hepatocellular carcinoma HepG3 were exposed to DHA, and low millimolar doses of DHA were cytotoxic. IC90 DHA doses induced cell cycle arrest in all cells except the Ac16. We examined DHA's genotoxicity using strand break markers, DNA adduct detection by Repair Assisted Damage Detection (RADD), metaphase spreads, and a forward mutation assay for mutagenesis. Similar to results for skin, DHA did not induce significant levels of strand breaks. However, RADD revealed DNA adducts were induced 24 h after DHA exposure, with BEAS-2B and Ac16 showing oxidative lesions and A549 and HepG3 showing crosslink-type lesions. Yet, only low levels of reactive oxygen species or advanced glycation end products were detected after DHA exposure. Metaphase spreads revealed significant increases in chromosomal aberrations in the BEAS-2B and HepG3 with corresponding changes in ploidy. Finally, we confirmed the mutagenesis observed using the supF reporter plasmid. DHA increased the mutation frequency, consistent with methylmethane sulfonate, a mutagen and clastogen. These data demonstrate DHA is a clastogen, inducing cell-specific genotoxicity and chromosomal instability. The specific genotoxicity measured in the BEAS-2B in this study suggests that inhalation exposures pose health risks to vapers, requiring further investigation. [ABSTRACT FROM AUTHOR]

Background This study explored if long-distance transfer was safe for patients suffering from acute aortic dissection type A (AADA) and also analyzed the effectiveness of helicopter transfer and cloud-type imaging transfer systems for such patients in northern Hokkaido, Japan. Methods and Results The study included 112 consecutive patients who underwent emergency surgical treatment for AADA from April 2014 to September 2020. The patients were divided into two groups according to the location of referral source hospitals: the Asahikawa city group (group A, n = 49) and the out-of-the-city group (group O, n = 63). Use of helicopter transfer (n = 13) and cloud-type telemedicine (n = 20) in group O were reviewed as subanalyses. Transfer distance differed between groups (4.2 ± 3.5 km in group A vs 107.3 ± 69.2 km in group O; p = 0.0001), but 30-day mortality (10.2% in group A vs 7.9% in group O; p = 0.676) and hospital mortality (12.2% in group A vs 9.5% in group O; p = 0.687) did not differ. Operative outcomes did not differ with or without helicopter and cloud-type telemedicine, but diagnosis-to-operation time was shorter with helicopter (240.0 ± 70.8 vs 320.0 ± 78.5 minutes; p = 0.031) and telemedicine (242.0 ± 75.2 vs 319.0 ± 83.8 minutes; p = 0.007). Conclusion We found that long-distance transfer did not impair surgical outcomes in AADA patients, and both helicopter transfer and cloud-type telemedicine system could contribute to the reduction of diagnosis-to-operation time in the large Hokkaido area. Further studies are mandatory to investigate if both the systems will improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Minimally invasive cardiac surgery off-pump coronary artery bypass (MICSOPCAB) has become increasingly prevalent, with devices like the heart positioner aiding in surgical precision. However, rare complications such as epicardial hematoma can occur. Here, we present a case of a 75-year-old man undergoing MICSOPCAB who developed an epicardial hematoma due to the heart positioner. The hematoma was successfully repaired intraoperatively with direct suturing and large felts. Postoperative recovery was uneventful, highlighting the importance of vigilant monitoring and prompt management of such complications. This case underscores the need for careful attention during the use of cardiac positioners to minimize adverse events and ensure favorable patient outcomes. [ABSTRACT FROM AUTHOR]