The cellular response to DNA damage is crucial for maintaining the integrity and stability of molecular structure. To maintain genome stability, DNA-damaged cells should be arrested so that mutations can be repaired before replication. selleck Although several key components required for this arrest have been discovered, the majority of the pathways are still unclear. Through a number of assays, including cell viability, colony formation, and apotheosis assay, we found that AKR1B10 protected cells from UVC-induced DNA damage. Surprisingly, UVC-induced γH2AX foci and DNA double-strand breaks in the AKR1B10-overexpressing cells were ∼4-5 folds lower than those in the control group. The expression levels of AKR1B10, p53, chk1, chk2, nuclear factor (NF)-κB, and p65 showed dynamic changes in response to UVC irradiation. Our results suggested that AKR1B10 is involved in the pathway of cell cycle checkpoint and NF-κB in DNA damage. Taken together, our results suggest that AKR1B10 is involved in the repair of the DNA double-strand break, which provides a new insight into the role of AKR1B10 in DNA damage repair and indicates a new trail in tumorigenesis and cancer drug resistance.
Although early coagulopathy increases mortality in adults with traumatic brain injury (TBI), less is known about pediatric TBI.
To describe the prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet levels of children with moderate to severe TBI to identify predictors of early coagulopathy and study the association with clinical outcomes.
Using the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) TBI retrospective cohort, we identified patients <16yr old with a Glasgow Coma Scale (GCS) ≤13. We compared PT, APTT, platelets, and outcomes between children with isolated TBI and multiple trauma with TBI. We performed logistic regressions to identify predictors of early coagulopathy and study the association with mortality and poor functional outcomes.
Among 370 children analyzed, 53/370 (14.3%) died and 127/370 (34.3%) had poor functional outcomes. PT was commonly deranged in both isolated TBI (53/173, 30.6%) and multiple trauma (101/197, 51.3%). Predictors for early coagulopathy were young age (adjusted odds ratio [aOR] 0.94, 95% CI 0.88-0.99, P=.023), GCS <8 (aOR 1.96, 95% CI 1.26-3.06, P=.003), and presence of multiple trauma (aOR 2.21, 95% confidence interval [CI] 1.37-3.60, P=.001). After adjusting for age, gender, GCS, multiple traumas, and presence of intracranial bleed, children with early coagulopathy were more likely to die (aOR 7.56, 95% CI 3.04-23.06, P <.001) and have poor functional outcomes (aOR 2.16, 95% CI 1.26-3.76, P=.006).
Early coagulopathy is common and independently associated with death and poor functional outcomes among children with TBI.
Early coagulopathy is common and independently associated with death and poor functional outcomes among children with TBI.Radiomics is an emerging discipline that aims to make intelligent predictions and derive medical insights based on quantitative features extracted from medical images as a means to improve clinical diagnosis or outcome. Pertaining to glioblastoma, radiomics has provided powerful, noninvasive tools for gaining insights into pathogenesis and therapeutic responses. Radiomic studies have yielded meaningful biological understandings of imaging features that are often taken for granted in clinical medicine, including contrast enhancement on glioblastoma magnetic resonance imaging, the distance of a tumor from the subventricular zone, and the extent of mass effect. They have also laid the groundwork for noninvasive detection of mutations and epigenetic events that influence clinical outcomes such as isocitrate dehydrogenase (IDH) and O6-methylguanine-DNA methyltransferase (MGMT). In this article, we review advances in the field of glioblastoma radiomics as they pertain to prediction of IDH mutation status and MGMT promoter methylation status, as well as the development of novel, higher order radiomic parameters.
We aimed at investigating the relationship between particulate matter (PM) and daily admissions for cardiovascular diseases (CVDs) at national level in Italy.
Daily numbers of cardiovascular hospitalizations were collected for all 8084 municipalities of Italy, in the period 2013-2015. A satellite-based spatiotemporal model was used to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km2 resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and cardiovascular admissions. Flexible functions were estimated to explore the shape of the associations at low PM concentrations, also in non-urban areas. We analysed 2154810 acute hospitalizations for CVDs (25% stroke, 24% ischaemic heart diseases, 22% heart failure, and 5% atrial fibrillation). Relative increases of total cardiovascular admissions, per 10 µg/m3 variation in PM10 and PM2.5 at lag 0-5 (average of last 6 days since admission), were 0.55% (95% confidence intervals 0.32%, 0.77%) and 0.97% (0.67%, 1.27%), respectively. The corresponding estimates for heart failure were 1.70% (1.28%, 2.13%) and 2.66% (2.09%, 3.23%). We estimated significant effects of PM10 and PM2.5 also on ischaemic heart diseases, myocardial infarction, atrial fibrillation, and ischaemic stroke. Associations were similar between less and more urbanized areas, and persisted even at low concentrations, e.g. below WHO guidelines.
PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.
PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.
Occasionally, the symptoms reported by patients disagree with those documented in the medical record. We designed the Patient Centered Assessment of Symptoms (PCAS) registry to measure discrepancies between patient-reported and clinician-documented symptoms.
Use patient-derived symptoms data to measure discrepancies with clinical documentation.
The PCAS registry captured data from a prospective cohort of patients undergoing myocardial perfusion imaging (MPI) and includes free response and structured questions to gauge symptoms. Clinician-documented symptoms were extracted from the patients' medical records. The appropriateness of testing was determined twice once using the patient-reported symptoms and once using the clinician-documented symptoms.
A total of 90 subjects were enrolled, among whom diabetes (36.7%), prior coronary disease (28.9%), hypertension (80.0%) and hyperlipidemia (85.6%) were common. Percentage of patient-reported symptoms compared to clinician-documented symptoms and agreement were as follows chest pain (patient 29.selleck
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