•2020 USA maternal morbidity and mortality uncovered areas for systematic improvement.•Anesthesiology research should focus on health disparities, mental health and pain management.•Policy and health ...systems are also important areas for researchers.
Advances in obstetric anesthesiology have historically exemplified how scientific progress can have a transformational impact on patient safety practices. Profound reductions in anesthesia-related maternal mortality in the 20th century highlighted the specialty of anesthesiology as a leader in safety and care quality. In 2020, maternal health faces new crises: preventable maternal mortality trends worldwide continue to stagnate, and in the United States of America, mortality rates are increasing, attributable to structural care limitations, systemic racism, and social determinants of health. Postpartum health offers improvement opportunities given high rates of maternal deaths occurring within the first postpartum year, particularly in the areas of mental health, cognition, and recovery. Obstetric anesthesiologists have unique perspectives on systems of care, education and training, and device innovation. An interdisciplinary team approach to research and innovation, as well as systems based and health policy work, presents an opportunity for anesthesiologists to contribute to solutions that reduce maternal morbidity and mortality and improve postpartum health for all people.
Aggressive cancers and embryonic stem (ES) cells share a common gene expression signature. Identifying the key factors/pathway(s) within this ES signature responsible for the aggressiveness of ...cancers can lead to a potential cure. In this study, we find that SALL4, a gene involved in the maintenance of ES cell self-renewal, is aberrantly expressed in 47.7% of primary human endometrial cancer samples. It is not expressed in normal or hyperplastic endometrial. More importantly, SALL4 expression is positively correlated with worse patient survival and aggressive features such as metastasis in endometrial carcinoma. Further functional studies have shown that loss of SALL4 inhibits endometrial cancer cell growth in vitro and tumorigenicity in vivo, as a result of inhibition of cell proliferation and increased apoptosis. In addition, downregulation of SALL4 significantly impedes the migration and invasion properties of endometrial cancer cells in vitro and their metastatic potential in vivo. Furthermore, manipulation of SALL4 expression can affect drug sensitivity of endometrial cancer cells to carboplatin. Moreover, we show that SALL4 specifically binds to the c-Myc promoter region in endometrial cancer cells. While downregulation of SALL4 leads to a decreased expression of c-Myc at both protein and mRNA levels, ectopic SALL4 overexpression causes increased c-Myc protein and mRNA expression, indicating that c-Myc is one of the SALL4 downstream targets in endometrial tumorigenesis. In summary, we are the first to demonstrate that SALL4 has functional role(s) in metastasis and drug resistance in aggressive endometrial cancer. As a consequence of its functional roles in cancer cell and absence in normal tissue, SALL4 is a potential novel therapeutic target for the high-risk endometrial cancer patient population.
The Western Siberia Lowland (WSL), the world's largest permafrost peatland, is of importance for understanding the high-latitude carbon (C) cycle and its response to climate change. Warming ...temperatures increase permafrost thaw and production of greenhouse gases. Also, permafrost thaw leads to the formation of lakes which are hotspots for atmospheric C emissions. Although lakes occupy ~6% of WSL, lake C emissions from WSL remain poorly quantified. Here we show high C emissions from lakes across all permafrost zones of WSL. The C emissions were especially high in shoulder seasons and in colder permafrost-rich regions. The total C emission from permafrost-affected lakes of WSL equals ~12 ± 2.6 Tg C yr
and is 2-times greater than region's C export to the Arctic coast. The results show that C emission from WSL lakes is a significant component in the high-latitude C cycle, but also suggest that C emission may decrease with warming.
This article proposes and tests a social-cognitive framework for examining the joint influence of situational factors and the centrality of moral identity on moral intentions and behaviors. The ...authors hypothesized that if a situational factor increases the current accessibility of moral identity within the working self-concept, then it strengthens the motivation to act morally. In contrast, if a situational factor decreases the current accessibility of moral identity, then it weakens the motivation to act morally. The authors also expected the influence of situational factors to vary depending on the extent to which moral identity was central to a person's overall self-conception. Hypotheses derived from the framework were tested in 4 studies. The studies used recalling and reading a list of the Ten Commandments (Study 1), writing a story using morally laden terms (Study 4), and the presence of performance-based financial incentives (Studies 2 and 3) as situational factors. Participants' willingness to initiate a cause-related marketing program (Study 1), lie to a job candidate during a salary negotiation (Studies 2 and 3), and contribute to a public good (Study 4) were examined. Results provide strong support for the proposed framework.
Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss ...during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD.
Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease.
Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively.
Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.
Treatment of 171 patients with hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, ...serological, and biochemical improvement compared with placebo. The long‐term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty‐five patients given ADV 10 mg in year 1 elected to continue in a long‐term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 × upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log10 copies/mL and −50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow‐up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV. Conclusion: Treatment with ADV beyond 48 weeks was well tolerated and produced long‐term virological, biochemical, serological, and histological improvement. (HEPATOLOGY 2008;48:750–758.)
Reactive oxygen species (ROS) and mitophagy are profoundly implicated in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). Several studies have suggested that ROS are ...not involved in mitochondrial translocation of Parkin which primes mitochondria for autophagic elimination. However, whether ROS play a role in the execution of mitophagy is unknown. In the present study, we show that carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment induced both mitochondrial depolarization and generation of ROS that were needed for the mitophagy process. Cells failed to proceed to complete mitophagy if CCCP treatment was discontinued even after recruitment of Parkin and autophagy machinery to mitochondria. Notably, treatment of pro-oxidant was able to replace CCCP treatment to take mitophagy forward, while it alone was insufficient to induce translocation of Parkin to mitochondria or autophagic clearance of mitochondria. In addition, an SOD mimetic that attenuated the superoxide level suppressed mitophagy, while an SOD inhibitor accumulated cellular superoxide and promoted mitophagy. Furthermore, blockage of the p38 signaling pathway inhibited mitophagy induced by ROS, suggesting that it may contribute to the activation of ROS-mediated mitophagy. Together, our study sheds light on the link between ROS and mitophagy at a molecular level, and suggests the therapeutic potential of regulating mitophagy through the superoxide-p38-mitophagy axis.
The final results of the search for the lepton flavour violating decay
μ
+
→
e
+
γ
based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009–2013 and ...totalling
7.5
×
10
14
stopped muons on target are presented. No significant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of
B
(
μ
+
→
e
+
γ
)
<
4.2
×
10
-
13
(90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.
Edible Gelidium corneum-gelatin (GCG) blend films containing grapefruit seed extract (GFSE) or green tea extract (GTE) were manufactured, and the quality of pork loins packed with the film during ...storage was determined. Tensile strength (TS) and water vapor permeability (WVP) of the films containing GFSE or GTE were better than those of the control. The film's antimicrobial activity against Escherichia coli O157:H7 and Listeria monocytogenes increased with increasing antimicrobial concentration, resulting in a decrease in the populations of bacteria by 0.77 to 2.08 and 0.91 to 3.30 log CFU/g, respectively. Pork loin samples were inoculated with E. coli O157:H7 and L. monocytogenes. The samples packed with the GCG film containing GFSE (0.08%) or GTE (2.80%) had a decrease in the populations of E. coli O157:H7 and L. monocytogenes of 0.69 to 1.11 and 1.05 to 1.14 log CFU/g, respectively, compared to the control after 4 d of storage. The results showed that the quality of pork loins during storage could be improved by packaging them with the GCG film containing GFSE or GTE.
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