Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

The effect of media reporting of a homicide committed by a patient with schizophrenia on the public stigma and knowledge of psychosis among the general population of Hong Kong

Social Psychiatry and Psychiatric Epidemiology - This study aimed to investigate the effects of media reporting of a homicide committed by a patient with schizophrenia on the knowledge about and...     

Müller Glia Are a Major Cellular Source of Survival Signals for Retinal Neurons in Diabetes

To dissect the role of vascular endothelial growth factor receptor-2 (VEGFR2) in Müller cells and its effect on neuroprotection in diabetic retinopathy (DR), we disrupted VEGFR2 in mouse Müller glia and determined its effect on Müller cell survival, neuronal integrity, and trophic factor production in diabetic retinas. Diabetes was induced with streptozotocin. Retinal function was measured with electroretinography. Müller cell and neuronal densities were assessed with morphometric and immunohistochemical analyses. Loss of VEGFR2 caused a gradual reduction in Müller glial density, which reached to a significant level 10 months after the onset of diabetes. This observation was accompanied by an age-dependent decrease of scotopic and photopic electroretinography amplitudes and accelerated loss of rod and cone photoreceptors, ganglion cell layer cells, and inner nuclear layer neurons and by a significant reduction of retinal glial cell line–derived neurotrophic factor and brain-derived neurotrophic factor. Our results suggest that VEGFR2-mediated Müller cell survival is required for the viability of retinal neurons in diabetes. The genetically altered mice established in this study can be used as a diabetic animal model of nontoxin-induced Müller cell ablation, which will be useful for exploring the cellular mechanisms of neuronal alteration in DR.     

100 Million Views of Electronic Cigarette YouTube Videos and Counting: Quantification,Content Evaluation,and Engagement Levels of Videos

BackgroundThe video-sharing website, YouTube, has become an important avenue for product marketing, including tobacco products. It may also serve as an important medium for promoting electronic cigarettes, which have rapidly increased in popularity and are heavily marketed online. While a few studies have examined a limited subset of tobacco-related videos on YouTube, none has explored e-cigarette videos’ overall presence on the platform.ObjectiveTo quantify e-cigarette-related videos on YouTube, assess their content, and characterize levels of engagement with those videos. Understanding promotion and discussion of e-cigarettes on YouTube may help clarify the platform’s impact on consumer attitudes and behaviors and inform regulations.MethodsUsing an automated crawling procedure and keyword rules, e-cigarette-related videos posted on YouTube and their associated metadata were collected between July 1, 2012, and June 30, 2013. Metadata were analyzed to describe posting and viewing time trends, number of views, comments, and ratings. Metadata were content coded for mentions of health, safety, smoking cessation, promotional offers, Web addresses, product types, top-selling brands, or names of celebrity endorsers.ResultsAs of June 30, 2013, approximately 28,000 videos related to e-cigarettes were captured. Videos were posted by approximately 10,000 unique YouTube accounts, viewed more than 100 million times, rated over 380,000 times, and commented on more than 280,000 times. More than 2200 new videos were being uploaded every month by June 2013. The top 1% of most-viewed videos accounted for 44% of total views. Text fields for the majority of videos mentioned websites (70.11%); many referenced health (13.63%), safety (10.12%), smoking cessation (9.22%), or top e-cigarette brands (33.39%). The number of e-cigarette-related YouTube videos was projected to exceed 65,000 by the end of 2014, with approximately 190 million views.ConclusionsYouTube is a major information-sharing platform for electronic cigarettes. YouTube appears to be used unevenly for promotional purposes by e-cigarette brands, and our analyses indicated a high level of user engagement with a small subset of content. There is evidence that YouTube videos promote e-cigarettes as cigarette smoking cessation tools. Presence and reach of e-cigarette videos on YouTube warrants attention from public health professionals and policymakers.     

Explicit scoring criteria for the Rey-Osterrieth and Taylor complex figures

Explicit scoring criteria based on the Taylor-Osterrieth method were developed for the Rey-Osterrieth and Taylor Complex Figure Tests. Without such criteria, clinicians and researchers are left to develop their own idiographic scoring systems, leading to low interrater reliability, especially in the middle range of scores. Criteria were applied to the copy and 30-min recall protocols of 101 subjects infected with HIV. Results indicate that the criteria presented are reliable across a wide range of scores, making them useful for tracking subtle changes over time. Independent raters were within two points of each other on 90.1 % of the copy and 88.1% of recall scores, with a maximum disagreement of five points on two copy protocols. The Taylor figure was also found to be more easily remembered than the Rey-Osterrieth, calling into question their interchangeability. Explicit criteria are particularly useful in research settings. They ensure interrater reliability over time and across examiners in longitudinal studies, enhance the detection of subtle differences within the normal range, and allow comparison of results obtained by different investigators.     

Cannabis use motives and personality risk factors

According to the model of substance abuse of Conrod, Pihl, Stewart, and Dongier (2000), four personality factors (i.e., anxiety sensitivity [AS], introversion/hopelessness [I/H], sensation seeking [SS], and impulsivity [IMP]) are associated with elevated risk for substance use/misuse, with each personality factor being related to preference for particular drugs of abuse (e.g., AS with anxiolytics). However, cannabis use has not been consistently linked to any one of these personality factors. This may be due to the heterogeneity in cannabis use motives. The present study explored the association between these four personality risk factors and different cannabis use motives. Cannabis users completed an interview about their motives for cannabis use as well as the self-report Substance Use Risk Profile Scale (SURPS; Woicik, Conrod, Stewart, & Pihl, 2009), which measures the four personality risk factors. Results showed that AS was associated with conformity motives and I/H was associated with coping motives for cannabis use. SS was positively associated with expansion motives and IMP was associated with drug availability motives. Thus, personality risk factors in the model of Conrod et al. (2000) are associated with distinct cannabis use motives in a pattern consistent with theory.     

13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS)

Cellular metabolism of glucose is required for stimulation of insulin secretion from pancreatic beta cells, but the precise metabolic coupling factors involved in this process are not known. In an effort to better understand mechanisms of fuel-mediated insulin secretion, we have adapted 13C NMR and isotopomer methods to measure influx of metabolic fuels into the tricarboxylic acid (TCA) cycle in insulinoma cells. Mitochondrial metabolism of [U-13C3]pyruvate, derived from [U-13C6]glucose, was compared in four clonal rat insulinoma cell 1-derived cell lines with varying degrees of glucose responsiveness. A 13C isotopomer analysis of glutamate isolated from these cells showed that the fraction of acetyl-CoA derived from [U-13C6]glucose was the same in all four cell lines (44 +/- 5%, 70 +/- 3%, and 84 +/- 4% with 3, 6, or 12 mM glucose, respectively). The 13C NMR spectra also demonstrated the existence of two compartmental pools of pyruvate, one that exchanges with TCA cycle intermediates and a second pool derived from [U-13C6]glucose that feeds acetyl-CoA into the TCA cycle. The 13C NMR spectra were consistent with a metabolic model where the two pyruvate pools do not randomly mix. Flux between the mitochondrial intermediates and the first pool of pyruvate (pyruvate cycling) varied in proportion to glucose responsiveness in the four cell lines. Furthermore, stimulation of pyruvate cycling with dimethylmalate or its inhibition with phenylacetic acid led to proportional changes in insulin secretion. These findings indicate that exchange of pyruvate with TCA cycle intermediates, rather than oxidation of pyruvate via acetyl-CoA, correlates with glucose-stimulated insulin secretion.