Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- The Mre11-Rad50-Xrs2 Complex Is Required for Yeast DNA Postreplication Repair. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e109292.
Yeast DNA postreplication repair (PRR) bypasses replication-blocking lesions to prevent damage-induced cell death. PRR employs two different mechanisms to bypass damaged DNA, namely translesion synthesis (TLS) and error-free PRR, which are regulated via sequential ubiquitination of proliferating cell nuclear antigen (PCNA). We previously demonstrated that error-free PRR utilizes homologous recombination to facilitate template switching. To our surprise, genes encoding the Mre11-Rad50-Xrs2 (MRX) complex, which are also required for homologous recombination, are epistatic to TLS mutations. Further genetic analyses indicated that two other nucleases involved in double-strand end resection, Sae2 and Exo1, are also variably required for efficient lesion bypass. The involvement of the above genes in TLS and/or error-free PRR could be distinguished by the mutagenesis assay and their differential effects on PCNA ubiquitination. Consistent with the observation that the MRX complex is required for both branches of PRR, the MRX complex was found to physically interact with Rad18 in vivo. In light of the distinct and overlapping activities of the above nucleases in the resection of double-strand breaks, we propose that the interplay between distinct single-strand nucleases dictate the preference between TLS and error-free PRR for lesion bypass.
- Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury after Pediatric Cardiac Surgery. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110865.
The lack of early biomarkers for acute kidney injury (AKI) seriously inhibits the initiation of preventive and therapeutic measures for this syndrome in a timely manner. We tested the hypothesis that insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, function as early biomarkers for AKI after congenital heart surgery with cardiopulmonary bypass (CPB).We prospectively studied 51 children undergoing cardiac surgery with CPB. Serial urine samples were analyzed for [TIMP-2]•[IGFBP7]. The primary outcome measure was AKI defined by the pRIFLE criteria within 72 hours after surgery.12 children (24%) developed AKI within 1.67 (SE 0.3) days after surgery. Children who developed AKI after cardiac surgery had a significant higher urinary [TIMP-2]•[IGFBP7] as early as 4 h after the procedure, compared to children who did not develop AKI (mean of 1.93 ((ng/ml)2/1000) (SE 0.4) vs 0.47 ((ng/ml)2/1000) (SE 0.1), respectively; p<0.05). Urinary [TIMP-2]•[IGFBP7] 4 hours following surgery demonstrated an area under the receiver-operating characteristic curve of 0.85. Sensitivity was 0.83, and specificity was 0.77 for a cutoff value of 0.70 ((ng/ml)2/1000).Urinary [TIMP-2]•[IGFBP7] represent sensitive, specific, and highly predictive early biomarkers for AKI after surgery for congenital heart disease.www.germanctr.de/, DRKS00005062.
- Is local hypoperfusion the reason for transient neurological deficits after STA-MCA bypass for moyamoya disease? [JOURNAL ARTICLE]
- J Neurosurg 2014 Oct 24.:1-5.
OBJECT Hyperperfusion is believed to be the cause of transient neurological events (TNEs) in patients with moyamoya disease (MMD) who have undergone an extracranial-to-intracranial (EC-IC) bypass between the superficial temporal artery (STA) and the middle cerebral artery (MCA). The objective of this study was to evaluate this possibility by analyzing cerebral blood flow (CBF) data obtained with thermal diffusion probes used at the authors' center. METHODS The authors examined postoperative cerebral perfusion in 31 patients with MMD who underwent a direct EC-IC STA-MCA bypass. A Hemedex Q500 flow probe was placed in the frontal lobe adjacent to the bypass and connected to a Bowman cerebral perfusion monitor, and CBF data were statistically analyzed using JMP 8.0.2 software. Seven patients experienced a TNE after surgery in the left hemisphere (that is, after left-sided surgery), manifesting as dysphasia approximately 24 hours postoperatively and which had improved by 48 hours. No TNEs were observed after right-sided surgeries. Operative and postoperative CBFs in the left side with the TNE were compared with those in the left side with no TNE and on the right side. RESULTS A detailed analysis of 64,980 minute-by-minute flow observations showed that the initial postbypass CBF was higher on the left side where the TNEs occurred. This CBF increase was followed by a widely fluctuating pattern and a statistically significant and sharp drop in perfusion (p < 0.001, mean difference of CBF between groups, paired t-test) associated with a TNE not observed in the other 2 groups. CONCLUSIONS On the basis of the authors' initial observations, an early-onset altered pattern of CBF was identified. These findings suggest local hypoperfusion as the cause of the TNEs. This hypoperfusion may originate from competing blood flows resulting from impaired cerebral autoregulation and a fluctuating flow in cerebral microcirculation.
- Risk factors predictive of one-year mortality after lung transplantation. [JOURNAL ARTICLE]
- Eur J Cardiothorac Surg 2014 Oct 23.
Lung transplantation (LTx) is a life-saving therapy for patients with end-stage lung disease. However, there remains a significant postoperative complication rate and mortality in this extreme patient group. The aim of the present study was to identify donor, recipient and perioperative risk factors for one-year mortality after LTx.A total of 252 LTxs were performed in our institution between 2007 and 2013. Donor and recipient demographics and clinical characteristics of 1-year survivors and non-survivors were collected and compared retrospectively. Multivariate logistic regression analysis was performed on univariate predictors for 1-year mortality with an entry criterion of P < 0.05.Multivariate analysis revealed female-to-male transplantation (95% CI: 0.088-0.767; P = 0.015), lower pO2/FiO2-ratio at 72 h postoperatively (95% CI: 0.988-0.999; P = 0.024), need for postoperative extracorporeal membrane oxygenation (ECMO) support (95% CI: 0.035-0.658; P = 0.012) and on-pump technique (95% CI: 0.007-0.944; P = 0.045) as the only independent predictors for 1-year mortality. Mainly unplanned intraoperative conversion to cardiopulmonary bypass contributed to poorer survival in patients who underwent LTx using cardiopulmonary bypass (P < 0.001).Our results show that the unplanned use of CPB (conversion from off- to on-pump) might adversely affect outcome after LTx. Also, the negative impact of female-to-male transplantation should not be underestimated during recipient selection. Furthermore, poor early postoperative oxygenation, particularly with the need for extracorporeal oxygenation, might be a very strong negative prognostic factor after LTx.
- Designing a new scoring system (QualyP Score) correlating the management of cardiopulmonary bypass to postoperative outcomes. [JOURNAL ARTICLE]
- Perfusion 2014 Oct 23.
The aim of this study was to ascertain if a score, directly derived from CPB records, could correlate to major postoperative outcomes.An additive score (QualyP Score) was created from 10 parameters: peak lactate value during CPB, peak VCO2i, lowest DO2i/VCO2i, peak respiratory quotient, CPB time, cross-clamp time, lowest CPB temperature, circulatory arrest, ultrafiltration during CPB, number of packed red cells transfused intraoperatively. The PerfSCORE was calculated, as well. Multivariable logistic regression models were built to detect the independent predictors of: peak lactate >3 mmol/L during the first three postoperative days; the incidence of acute kidney injury network (AKIN) 1-2-3; respiratory insufficiency; mortality.The mean score was 4.8±2.6 (0-10). A QualyP Score ≥1 was predictive of postoperative acidosis (OR=1.595). A score ≥2 was predictive of AKIN 2 (OR=1.268) and respiratory insufficiency (OR=1.526). A score ≥5 was predictive of AKIN 3 (OR=1.848) and mortality (OR=1.497).QualyP Score may help to provide a quality marker of perfusion, emphasizing the need for goal-directed perfusion strategies.
- Nutrient Control of Energy Homeostasis Via Gut-Brain Neural Circuits. [JOURNAL ARTICLE]
- Neuroendocrinology 2014 Oct 20.
Intestinal gluconeogenesis is a recently described function in intestinal glucose metabolism. In particular, the intestine contributes around 20-25% of total endogenous glucose production during fasting. Intestinal gluconeogenesis appears to regulate energy homeostasis via a neurally-mediated mechanism linking the entero-hepatic portal system with the brain. The periportal neural system is able to sense glucose produced by intestinal gluconeogenesis in the portal vein walls, which sends a signal to the brain to modulate energy and glucose homeostasis. Dietary proteins mobilize intestinal gluconeogenesis as a mandatory link between the sensing of these proteins in the portal vein and their well-known effect of satiety. Comparably, dietary soluble fibers exert their anti-obesity and anti-diabetic effects via the induction of intestinal gluconeogenesis. Finally, intestinal gluconeogenesis might be involved in the rapid metabolic improvements in energy homeostasis induced by gastric bypass surgeries of obesity. © 2014 S. Karger AG, Basel.
- The association between early arterial oxygenation in the ICU and mortality following cardiac surgery. [JOURNAL ARTICLE]
- Anaesth Intensive Care 2014 Nov; 42(6):730-735.
Many studies have been conducted to investigate the relationship between hyperoxia and mortality in cohorts of intensive care unit (ICU) patients with varied and often contradictory results. The impact of early hyperoxia post ischaemia remains uncertain in various ICU cohorts. We aimed to investigate the association between arterial oxygenation (PaO2) in the first 24 hours in ICU and mortality in patients following cardiac surgery, using a retrospective cohort study of data from the Australian and New Zealand Intensive Care Society adult patient database. Participants were adults admitted to the ICU following cardiac surgery in Australia and New Zealand between 2003 and 2012. Patients were divided according to worst PaO2 level or alveolar-arterial O2 gradient in the 24 hours from admission. We defined 'hyperoxia' as PaO2 ≥300 mmHg, 'hypoxia/poor O2 transfer' as either PaO2 <60 mmHg or ratio of PaO2 to fraction of inspired oxygen <300 and 'normoxia' as between hypoxia and hyperoxia. The primary outcome was mortality at hospital discharge. Secondary outcomes were ICU mortality and ICU and hospital length-of-stay. Of the 83,060 patients, 12,188 (14.7%) had hyperoxia, 54,420 (65.5%) had hypoxia/poor O2 transfer and 16,452 (19.8%) had normoxia. There was no association between hyperoxia and in-hospital or ICU mortality compared to normoxia. There was a small increased hospital and ICU length-of-stay for hyperoxic compared to normoxic patients. We concluded that there was no association between mortality and hyperoxia in the first 24 hours in ICU after cardiac surgery.
- A cohort and database study of airway management in patients undergoing thyroidectomy for retrosternal goitre. [JOURNAL ARTICLE]
- Anaesth Intensive Care 2014 Nov; 42(6):700-708.
Patients undergoing thyroid surgery with retrosternal goitre may raise concerns for the anaesthetist, especially airway management. We reviewed a multicentre prospective thyroid surgery database and extracted data for those patients with retrosternal goitre. Additionally, we reviewed the anaesthetic charts of patients with retrosternal goitre at our institution to identify the anaesthetic induction technique and airway management. Of 4572 patients in the database, 919 (20%) had a retrosternal goitre. Two cases of early postoperative tracheomalacia were reported, one in the retrosternal group. Despite some very large goitres, no patient required tracheostomy or cardiopulmonary bypass and there were no perioperative deaths. In the subset of 133 patients managed at our institution over six years, there were no major adverse anaesthetic outcomes and no patient had a failed airway or tracheomalacia. In the latter cohort, of 32 (24%) patients identified as having a potentially difficult airway, 17 underwent awake fibreoptic tracheal intubation, but two of these were abandoned and converted to intravenous induction and general anaesthesia. Eleven had inhalational induction; two of these were also abandoned and converted to intravenous induction and general anaesthesia. Of those suspected as having a difficult airway, 28 (87.5%) subsequently had direct laryngoscopy where the laryngeal inlet was clearly visible. We found no good evidence that thyroid surgery patients with retrosternal goitre, with or without symptoms and signs of tracheal compression, present the experienced anaesthetist with an airway that cannot be managed using conventional techniques. This does not preclude the need for multidisciplinary discussion and planning.
- Multiplexed microfluidic blotting of proteins and nucleic acids by parallel, serpentine microchannels. [JOURNAL ARTICLE]
- Lab Chip 2014 Oct 24.
This work develops a high-throughput, high-efficiency and straightforward microfluidic blotting method for analyzing proteins and nucleic acids. Sample solutions containing antibodies (for protein detection) or hybridization probes (for nucleic acid detection) are introduced into the parallel, serpentine microchannels to specifically recognize the immobilized targets on the substrate, achieving the identification of multiple targets in multiple samples simultaneously. The loading control, molecular weight markers, and antigen/antibody titration are designed and integrated into the microfluidic chip, thus allowing for the quantification of proteins and nucleic acids. Importantly, we could easily distinguish the adjacent blotting bands inside parallel microchannels, which may be difficult to achieve in conventional blotting. The small dimensions of microfluidic channels also help to reduce the amount of probing molecules and to accelerate the biochemical reaction. Our microfluidic blotting could bypass the steps of blocking and washing, further reducing the operation time and complexity.
- Prasugrel, a Third-Generation P2Y12 Receptor Antagonist, in Patients With Coronary Artery Disease Undergoing Elective Percutaneous Coronary Intervention. [JOURNAL ARTICLE]
- Circ J 2014 Oct 21.
Background:Prasugrel is being developed in Japan as an antiplatelet therapy for use during percutaneous coronary intervention (PCI). Up to 70% of Japanese patients with coronary artery disease undergo elective PCI. The PRASugrel For Japanese PatIenTs with Coronary Artery Diseases Undergoing Elective PCI (PRASFIT-Elective) study investigated the efficacy and safety of different prasugrel dosing regimens in Japanese patients undergoing elective PCI.Methods and Results:A total of 742 patients scheduled for elective coronary artery stenting were enrolled. Patients were randomized to receive either prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg) in a double-blind manner. Endpoints, including cardiovascular events and bleeding, were assessed at weeks 24-48. The incidence rate of major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke) up to week 24 was 4.1% (15/370) and 6.7% (25/372) in the prasugrel and clopidogrel groups, respectively. Other incidence rates were: non-coronary artery bypass graft-related major bleeding, 0% and 2.2%; major/minor bleeding, 1.6% and 3.0%; and all bleeding events, 38.1% and 34.4% in the prasugrel and clopidogrel groups, respectively. The incidence rate of bleeding-related adverse events was similar in both groups, being 40.8% and 35.8% in the prasugrel and clopidogrel groups, respectively.Conclusions:These results support the risk-benefit profile of an adjusted dosing regimen of prasugrel in Japanese patients undergoing PCI. Larger studies are required to confirm these findings.