Παρασκευή 29 Δεκεμβρίου 2017
Climate change and landscape development in post-closure safety assessment of solid radioactive waste disposal: Results of an initiative of the IAEA
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): T. Lindborg, M. Thorne, E. Andersson, J. Becker, J. Brandefelt, T. Cabianca, M. Gunia, A.T.K. Ikonen, E. Johansson, V. Kangasniemi, U. Kautsky, G. Kirchner, R. Klos, R. Kowe, A. Kontula, P. Kupiainen, A.-M. Lahdenperä, N.S. Lord, D.J. Lunt, J.-O. Näslund, M. Nordén, S. Norris, D. Pérez-Sánchez, A. Proverbio, K. Riekki, A. Rübel, L. Sweeck, R. Walke, S. Xu, G. Smith, G. Pröhl
The International Atomic Energy Agency has coordinated an international project addressing climate change and landscape development in post-closure safety assessments of solid radioactive waste disposal. The work has been supported by results of parallel on-going research that has been published in a variety of reports and peer reviewed journal articles. The project is due to be described in detail in a forthcoming IAEA report. Noting the multi-disciplinary nature of post-closure safety assessments, here, an overview of the work is given to provide researchers in the broader fields of radioecology and radiological safety assessment with a review of the work that has been undertaken. It is hoped that such dissemination will support and promote integrated understanding and coherent treatment of climate change and landscape development within an overall assessment process.The key activities undertaken in the project were: identification of the key processes that drive environmental change (mainly those associated with climate and climate change), and description of how a relevant future may develop on a global scale; development of a methodology for characterising environmental change that is valid on a global scale, showing how modelled global changes in climate can be downscaled to provide information that may be needed for characterising environmental change in site-specific assessments, and illustrating different aspects of the methodology in a number of case studies that show the evolution of site characteristics and the implications for the dose assessment models.Overall, the study has shown that quantitative climate and landscape modelling has now developed to the stage that it can be used to define an envelope of climate and landscape change scenarios at specific sites and under specific greenhouse-gas emissions assumptions that is suitable for use in quantitative post-closure performance assessments. These scenarios are not predictions of the future, but are projections based on a well-established understanding of the important processes involved and their impacts on different types of landscape. Such projections support the understanding of, and selection of, plausible ranges of scenarios for use in post-closure safety assessments.
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Understanding EMS Scheduling Software & The Web of Information That Runs Your Business
There are many different web-based products for just about any service you can imagine in the EMS and public service industry. Most organizations use an HR Management system for on-boarding employees, managing their employment status and providing benefit enrollment. There are more and more HRIS vendors that have "do it all" systems with the addition of online time clock & attendance ...
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Platinum Educational Group Prepares for New CoAEMSP Requirements
GRAND RAPIDS, MI — Platinum Educational Group understands the struggles and obstacles that are presented to EMS educators when it pertains to accreditation. EMS training institutes, particularly paramedic programs, face stringent challenges like the NREMT Portfolio (where applicable), on-site reviews, and most recently the upcoming Appendix G requirements from Committee on Accreditation of Educational ...
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Sequencing of Linkage Region on Chromosome 12p11 Identifies PKP2 as a Candidate Gene for Left Ventricular Mass in Dominican Families
Increased left ventricular mass (LVM) is an intermediate phenotype for cardiovascular disease (CVD) and a predictor of stroke. Using families from the Dominican Republic, we have previously shown LVM to be heritable and found evidence for linkage to chromosome 12p11. Our current study aimed to further characterize the QTL by sequencing the 1 LOD unit down region in ten families from the Dominican Republic with evidence for linkage to LVM. Within this region, we tested 5,477 common variants (CVs; minor allele frequency [MAF] ≥5%) using the QTDT test. Gene-based analyses were performed to test rare variants (RVs; MAF<5%) in 181 genes using the family-based sequence kernel association test. A sample of 618 unrelated Dominicans from the Northern Manhattan Study (NOMAS) and 12 Dominican families with Exome Array data were used for replication analyses. The most strongly associated CV with evidence for replication was rs1046116 (Discovery families p=9.0x10-4; NOMAS p=0.03; replication families p=0.46), a missense variant in PKP2. In non-synonymous RV analyses, PKP2 was one of the most strongly associated genes (p=0.05) with suggestive evidence for replication in NOMAS (p=0.05). PKP2 encodes the plakophilin 2 protein and is a desmosomal gene implicated in arrythmogenic right ventricular cardiomyopathy and recently in arrhythmogenic left ventricular cardiomyopathy, which makes PKP2 an excellent candidate gene for LVM. In conclusion, sequencing of our previously reported QTL identified common and rare variants within PKP2 to be associated with LVM. Future studies are necessary to elucidate the role these variants play in influencing LVM.
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Case series: Slowing alpha rhythm in late-stage ALS patients
Source:Clinical Neurophysiology, Volume 129, Issue 2
Author(s): Matthias R. Hohmann, Tatiana Fomina, Vinay Jayaram, Theresa Emde, Jennifer Just, Matthis Synofzik, Bernhard Schölkopf, Ludger Schöls, Moritz Grosse-Wentrup
The alpha peak frequency (APF) of the human electroencephalogram (EEG) is a reliable neurophysiological marker for cognitive abilities. In these case series, we document a shift of the APF towards the lower end of the EEG spectrum in two completely locked-in ALS patients. In not completely locked-in ALS patients, the alpha rhythm lies within the common frequency range. We discuss potential implications of this shift for the largely unknown cognitive state of completely locked-in ALS patients.
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Custom Fabrication of 3D Printed Helmet for Improved Socialization and Subjective Self-Assessment in a case of Acquired Cranial Defect: A Case Report
Traumatic injury and subsequent residual cosmetic deformity are subject of intense scrutiny for their effects on objective health measures assessing patient morbidity and mortality. While these remain principle concern of all members of the treatment team, of less immediate yet lasting importance to the patient are the social costs of such disfigurement. Subjective feelings of unease and embarrassment can hinder social reintegration and encourage deteriorating psychosocial health. The following presents a case of one such individual who sustained traumatic brain injury and associated pneumocephalus and osteomyelitis requiring surgical debridement with bifrontal craniectomy and lobotomy.
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Acceptability and Feasibility of Examining Physical Activity in Young Children with Type 1 Diabetes
Physical activity is important but may be difficult to evaluate in young children (YC) with Type 1 diabetes (T1D) because of parents' fears of hypoglycemia, difficulties engaging YC in physical activity, and use of assessment devices. This study aimed to explore the acceptability and feasibility of an in-lab exercise session for YC with T1D. Ten YC ages 3 through7 years with T1D participated in a 20-minute exercise session while wearing blinded continuous glucose monitors and accelerometers. High acceptability was found for participation in the exercise session; high feasibility and acceptability were reported for the assessments.
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Opioid Use Dependency in the Mother Who Desires to Breastfeed Her Newborn: A Case Study
The number of infants born to mothers with opioid dependence is increasing at an alarming rate, indicating a 5-fold increase for women using opiates and a 3-fold increase in infants born with neonatal abstinence syndrome (NAS; Tsai & Doan, 2016 ). Pediatric Nurse Practitioners providing primary care, who lack experience with this clinical presentation, require evidence-based knowledge to provide the appropriate care to infants born with neonatal abstinence syndrome. Mothers with opioid dependence often desire to breastfeed their newborns, and the PNP may unknowingly discourage them from breastfeeding.
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Which clinical and radiological variables could predict clinical outcomes of percutaneous endoscopic lumbar discectomy for treatment of patients with lumbosacral disc herniation?
Percutaneous endoscopic lumbar discectomy (PELD) is one of minimal invasive techniques to treat the patients with low back and/or radiating pain resulted from lumbosacral disc herniation(LDH).
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Male-specific Association Between Fat-Free Mass Index and Fecal Microbiota in 2- to 3-Year-Old Australian Children
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Neonatal Exposure to Hepatitis C Virus Antigens in Uninfected Children Born to Infected Mothers
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Probiotics for the Prevention of Nosocomial Diarrhea in Children
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Neuropathic Pain as Potential Source of Feed-induced Dystonia in Children With Severe Central Nervous System Disorders
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Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial
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Variceal Hemorrhage and Adverse Liver Outcomes in Patients With Cystic Fibrosis Cirrhosis
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Development of the Aim to Decrease Anxiety and Pain Treatment for Pediatric Functional Abdominal Pain Disorders
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Unusual Presentation of Giant Omental Cystic Lymphangioma Mimicking Hemorrhagic Ascites in a Child
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Long-term Follow-up of Adolescents Treated for Rumination Syndrome in an Inpatient Setting
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Mimicking Own Mother's Milk for Preterms: Are We Getting Closer?
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Retrospective Comparison of Fluticasone Propionate and Oral Viscous Budesonide in Children With Eosinophilic Esophagitis
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Cholangiocarcinoma Among Children and Adolescents: A Review of the Literature and Surveillance, Epidemiology, and End Results Program Database Analysis
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Unsedated In-office Transgastrostomy Esophagoscopy to Monitor Therapy in Pediatric Esophageal Disease
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Randomized Trial of a Yogurt-type Amino Acid−based Formula in Infants and Children With Severe Cow's Milk Allergy
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Novel Pressure-Impedance Parameters for Evaluating Esophageal Function in Pediatric Achalasia
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Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee
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Peroral Endoscopic Myotomy in Children: First Experience With a New Triangular Knife
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Fatal Central Nervous System Post-Transplant Lymphoproliferative Disease in a Patient Who Underwent Liver Transplantation for Hepatoblastoma
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Safety and Efficacy of the Push Endoscopic Technique in the Management of Esophageal Food Bolus Impactions in Children
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Proton Pump Inhibitors May Not Be the First Line of Treatment for GERD in Infants
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FirstNet now available for first responders across the U.S.
All 50 states, two territories and Washington, D.C. have joined FirstNet in order to give first responders access to the wireless broadband network
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Comprehensive measurement of stroke gait characteristics with a single accelerometer in the laboratory and community: a feasibility, validity and reliability study
Application of objective measurement of stroke gait with accelerometer-based wearable technology and associated algorithms is increasing, despite reports questioning the accuracy of this technique in quantifyi...
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The Effect of the Removal of User Fees for Delivery at Public Health Facilities on Institutional Delivery in Urban Kenya
Abstract
Objectives In 2013, Kenya removed delivery fees at public health facilities in an effort to promote equity in access to health services and address high maternal mortality. This study determines the effect of the policy to remove user fees on institutional delivery in a population-based sample of women from urban Kenya. Methods Longitudinal data were collected from a representative sample of 8500 women from five cities in Kenya in 2010 with a follow-up interview in 2014 (response rate 58.9%). Respondents were asked about their most recent birth since 2008 at baseline and 2012 at endline, including the delivery location. Multinomial logistic regression is used, controlling for the temporal time trend and background characteristics, to determine if births which occurred after the national policy change were more likely to occur at a public facility than at home or a private facility. Results Multivariate findings show that women were significantly more likely to deliver at a public facility as compared to a private facility after the policy. Among the poor, the results show that poor women were significantly more likely to deliver in a public facility compared to home or a private facility after policy change. Conclusions for Practice These findings show Kenya's progress towards achieving universal access to delivery services and meeting its national development targets. The removal of delivery fees in the public sector is leading to increased use of facilities for delivery among the urban poor; this is an important first step in reducing maternal death.
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Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes
Abstract
Purpose
Propofol infusion syndrome (PRIS) is a lethal condition caused by propofol overdose. Previous studies suggest that pathophysiological mechanisms underlying PRIS involve mitochondrial dysfunction; however, these mechanisms have not been fully elucidated. This study aimed to establish an experimental model of propofol-induced cytotoxicity using cultured human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to determine the mechanisms behind propofol-induced mitochondrial dysfunction, and to evaluate the protective effects of coenzyme Q10 (CoQ10).
Methods
Human iPSC-derived cardiomyocytes were exposed to propofol (0, 2, 10, or 50 µg/ml) with or without 5 µM CoQ10. Mitochondrial function was assessed by measuring intracellular ATP, lactate concentrations in culture media, NAD+/NADH ratio, and the mitochondrial membrane potential. Propofol-induced cytotoxicity was evaluated by analysis of cell viability. Expression levels of genes associated with mitochondrial energy metabolism were determined by PCR. Intracellular morphological changes were analyzed by confocal microscopy.
Results
Treatment with 50 µg/ml propofol for 48 h reduced cell viability. High concentrations of propofol (≥ 10 µg/ml) induced mitochondrial dysfunction accompanied by downregulation of gene expression of PGC-1alpha and its downstream targets (NDUFS8 and SDHB, which are involved in the respiratory chain reaction; and CPT1B, which regulates beta-oxidation). Cardiomyocytes co-treated with 5 µM CoQ10 exhibited resistance to propofol-induced toxicity through recovery of gene expression.
Conclusions
Propofol-induced cytotoxicity in human iPSC-derived cardiomyocytes may be associated with mitochondrial dysfunction via downregulation of PGC-1alpha-regulated genes associated with mitochondrial energy metabolism. Co-treatment with CoQ10 protected cardiomyocytes from propofol-induced cytotoxicity.
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Understanding climate's influence on the extinction of Oreopithecus (late Miocene, Tusco-Sardinian paleobioprovince, Italy)
Source:Journal of Human Evolution, Volume 116
Author(s): Daniel DeMiguel, Lorenzo Rook
Despite its long history of scientific study, the causes underlying the extinction of the insular hominoid Oreopithecus bambolii are still a matter of ongoing debate. While some authors consider intense tectonism and invading species the cause of its extinction ca. 6.7 Ma, others propose climatic change as the main contributing factor. We rely on long-term patterns of tooth wear and hypsodonty of the Baccinello and Fiume Santo herbivore-faunas to reconstruct changes in habitat prior to, during and after the extinction. While a mosaic of habitats was represented in Baccinello V1 (as shown by a record of browsers, mixed feeders and species engaged in grazing), more closed forests (higher proportion of browsers, shortage of mixed feeders and lack of grazers) characterised Baccinello V2. Finally, there was a partial loss of canopy cover and development of open-patches and low-abrasive grasses in Baccinello V3 (as denoted by new records of taxa involved in grazing)—although still dominated by a forested habitat (since browse was a component in all diets). Our results provide evidence for two perceptible shifts in climate, one between 8.1 and 7.1 Ma and other ca. 6.7 Ma, though this latter was not drastic enough to lead to intensive forest loss, substantially alter the local vegetation or affect Oreopithecus lifestyle—especially if considering the growing evidence of its versatile diet. Although the disappearance of Oreopithecus is complex, our data reject the hypothesis of environmental change as the main factor in the extinction of Oreopithecus and Maremma fauna. When our results are analysed together with other evidence, faunal interaction and predation by invading species from mainland Europe seems to be the most parsimonious explanation for this extinction event. This contrasts with European hominoid extinctions that were associated with major climatic shifts that led to environmental uniformity and restriction of the preferred habitats of Miocene apes.
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Principles and methods of in-silico prioritization of non-coding regulatory variants
Abstract
Over a decade of genome-wide association, studies have made great strides toward the detection of genes and genetic mechanisms underlying complex traits. However, the majority of associated loci reside in non-coding regions that are functionally uncharacterized in general. Now, the availability of large-scale tissue and cell type-specific transcriptome and epigenome data enables us to elucidate how non-coding genetic variants can affect gene expressions and are associated with phenotypic changes. Here, we provide an overview of this emerging field in human genomics, summarizing available data resources and state-of-the-art analytic methods to facilitate in-silico prioritization of non-coding regulatory mutations. We also highlight the limitations of current approaches and discuss the direction of much-needed future research.
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High levels of serum Mac-2-binding protein glycosylation isomer (M2BPGi) predict the development of hepatocellular carcinoma in hepatitis B patients treated with nucleot(s)ide analogues
Abstract
Background
Nucleot(s)ide analogues (NA) can reduce the risk of hepatocellular carcinoma (HCC), but not completely prevent its development.
Methods
Two hundred and thirty-four chronic hepatitis B patients virologically well controlled with entecavir or tenofovir disoproxil fumarate for more than 1 year were enrolled in this study. Over the median observation period of 51 (12–142) months, 24 of 234 patients developed HCC. We quantified HBV markers, alpha-fetoprotein (AFP) and Mac-2-binding protein glycosylation isomer (M2BPGi) at baseline and 48 weeks after therapy.
Results
Serum AFP and M2BPGi tended to decline from baseline to 48 weeks after treatment both in patients who did and those who did not develop HCC. Univariate Cox regression analysis indicated that serum M2BPGi levels ≥ 1.215 COI at 48 weeks were associated with HCC development [hazard ratio (HR) 5.73; p ≤ 0.001]. Multivariate analysis showed that male sex (HR 5.6; p = 0.01), AFP ≥ 9.65 ng/ml (HR 22.01; p ≤ 0.001), M2BPGi ≥ 1.215 (HR 5.07; p = 0.004) at 48 weeks were significant independent predictive factors for HCC development. Based on a scoring system consisting of three factors above described, Kaplan–Meier analysis for four groups (score 0, 1, 2, ≥ 3), revealed significant differences in cumulative HCC occurrence for each group within 2 years. The rate of incidence of HCC was 0, 5.4, 23.4, and 75% in each group, respectively.
Conclusions
In patients receiving NA therapy, higher M2BPGi at 48 weeks, as well as male sex and higher AFP at 48 weeks were independent risk factors for HCC development.
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The Changing Landscape of Lynch Syndrome due to PMS2 Mutations
Abstract
DNA repair pathways are essential for cellular survival as our DNA is constantly under assault from both exogenous and endogenous DNA damaging agents. Five major mammalian DNA repair pathways exist within a cell to maintain genomic integrity. Of these, the DNA mismatch repair (MMR) pathway is highly conserved among species and is well documented in bacteria. In humans, the importance of MMR is underscored by the discovery that a single mutation in any one of four genes within the MMR pathway (MLH1, MSH2, MSH6 and PMS2) results in Lynch syndrome (LS). LS is an autosomal dominant condition that predisposes individuals to a higher incidence of many malignancies including colorectal, endometrial, ovarian, and gastric cancers. In this review, we discuss the role of PMS2 in the MMR pathway, the evolving testing criteria used to identify variants in the PMS2 gene, the LS phenotype as well as the autosomal recessive condition called Constitutional Mismatch Repair Deficiency syndrome, and current methods used to elucidate the clinical impact of PMS2 mutations.
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Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice
Abstract
Although genetic revolution of recent years has vastly expanded a list of genes implicated in epilepsies, complex architecture of epilepsy genetics is still largely unknown, consequently, universally accepted workflows for epilepsy genetic testing in a clinical practice are missing. We present a comprehensive NGS-based diagnostic approach addressing both the clinical and genetic heterogeneity of disorders involving epilepsy or seizures. A bioinformatic panel of 862 epilepsy- or seizure-associated genes was applied to Mendeliome (4813 genes) or whole-exome sequencing data as a first stage, while the second stage included untargeted variant interpretation. Eighty-six consecutive patients with epilepsy or seizures associated with neurodevelopmental disorders and/or congenital malformations were investigated. Of the 86 probands, 42 harbored pathogenic and likely pathogenic variants, giving a diagnostic yield of 49%. Two patients were diagnosed with pathogenic copy number variations and two had causative mitochondrial DNA variants. Eleven patients (13%) were diagnosed with diseases with specific treatments. Besides, genomic approach in diagnostics had multiple additional benefits due to mostly non-specific, overlapping, not full-blown phenotypes and abilities to diagnose novel and ultra rare epilepsy-associated diseases. Likely pathogenic variants were identified in SOX5 gene, not previously associated with epilepsy, and UBA5, a recently associated with epilepsy gene.
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Psychological Outcomes of Within-Group Sexual Violence: Evidence of Cultural Betrayal
Abstract
Cultural betrayal trauma theory is a new framework for understanding trauma-related mental health outcomes in immigrant and minority populations. The purpose of the current study is to empirically test cultural betrayal trauma theory. We hypothesized that the association between within-group sexual violence and mental health outcomes would be stronger for minorities. Participants (N = 368) were minority and majority college students, who completed online measures of sexual violence victimization and mental health outcomes. A MANOVA revealed that the link between within-group sexual violence and total trauma symptoms, depression, sexual abuse sequelae, sleep disturbance, and sexual problems was stronger for minorities. This study provides evidence for cultural betrayal trauma theory, as the findings suggest that outcomes from the same experience—within-group sexual violence—is affected by minority status. This work has implications for how mental health is understood, investigated, and treated in immigrant and minority populations.
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The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial ischemia reperfusion injury
Source:Journal of Genetics and Genomics
Author(s): Lingchen Gao, Yichao Zhao, Huan Tong, Yang Yan, Longwei Xu, Nan Lin, Qingqi Ji, Renyang Tong, Yanan Fu, Yu Gao, Yuanyuan Su, Ancai Yuan, Ben He, Jun Pu
Sentrin-specific protease 3 (SENP3), a member of the desumoylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, its implication in myocardial ischemia reperfusion (MIR) injury is unclear. Here, we observed that SENP3 was expressed and upregulated in the mouse heart depending on reactive oxygen species (ROS) production in response to MIR injury. By utilizing siRNA-mediated cardiac specific gene silencing, SENP3 knockdown was demonstrated to significantly reduce MIR-induced infarct size and improve cardiac function. Mechanistic studies indicated that SENP3 silencing ameliorated myocardial apoptosis mainly via suppression of endoplasmic reticulum (ER) stress and mitochondrial-mediated apoptosis pathways. By contrast, adenovirus-mediated cardiac SENP3 overexpression significantly exaggerated MIR injury. Further molecular analysis revealed that SENP3 promoted mitochondrial translocation of dynamin-related protein 1 (Drp1) in reperfused myocardium. In addition, mitochondrial division inhibitor-1 (Mdivi-1), a pharmacological inhibitor of Drp1, significantly attenuated the exaggerated mitochondrial abnormality and cardiac injury by SENP3 overexpression after MIR injury. Taken together, we provide the first direct evidence that SENP3 upregulation pivotally contributes to MIR injury in a Drp1-dependent manner, and suggest that SENP3 suppression may hold therapeutic promise for constraining MIR injury.
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Does a History of Gestational Diabetes Mellitus Affect Key Outcomes in Women Participating in a Diabetes Prevention Program?
Abstract
Objectives To evaluate lifestyle change outcomes among women with and without a history of gestational diabetes mellitus (GDM) enrolled in the Montana Diabetes Prevention Program (DPP). Methods Participation, self-monitoring behavior, weight loss, and cardiometabolic risk reduction were compared among 5091 women at high-risk for type 2 diabetes, with and without a history of GDM, enrolled in the Montana DPP between 2008 and 2015. Results Women with a history of GDM (6% of enrolled women, n = 283) were significantly younger than women without GDM. No significant differences in participation, self-monitoring fat intake, achievement of the physical activity goal, or weight loss were found among women with and without a history of GDM. Overall, women lost an average of 5.0 kg (± 6.5), and 45 and 29% of women achieved 5 and 7% weight loss, respectively. Both groups lost significant and comparable amounts of weight. After adjusting for age and other factors, no differences were found in achievement of ≥ 5% weight loss (AOR 0.84; 95% CI 0.61–1.16) or the ≥ 7% weight loss goal (AOR 1.04; 95% CI 0.73–1.47) among women with and without a history of GDM. Conclusions for Practice Our findings suggest that women with and without a history of GDM successfully participate in and achieve significant weight loss in the DPP. Health care providers should identify and refer women with risk factors for type 2 diabetes, including a history of GDM, to a DPP within their community.
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Sorafenib and fluvastatin synergistically alleviate hepatic fibrosis via inhibiting the TGFβ1/Smad3 pathway
Effective strategies for the treatment of hepatic fibrosis are urgently in need.
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Paramedic - Cole County EMS
Job Title: Paramedic Exempt: No Reports To: Assistant Chief/Deputy Chief/Chief Date Revised: February 14, 2017 Summary: Paramedics are accountable for responding to all assigned calls in the most appropriate, efficient, and professional manner, providing the highest standards of patient care while maintaining a safe and hazard-free environment. The Paramedic contributes to overall patient care in the ...
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Molecular mechanisms of bacterial infections of the central nervous system
Central nervous system (CNS) infections may involve the meninges, brain and/or spinal cord. The most common etiologic agents are Streptococcus pneumoniae, group B Streptococci, Neisseria meningitidis, Haemophilus influenzae, and Listeria monocytogenes. CNS is characterized by specific structure and function. Despite a unique system of brain barriers and autonomous immune system, CNS is very susceptible to microorganisms which may invade directly, via the blood, or less frequently by reverse axonal transport. The complex process of bacteria and activated polymorphonuclear leukocyte transfer to the subarachnoid space, which is devoid of natural immune defence mechanisms, initiates an inflammatory response that subsequently spreads to the brain tissue. Consequences of these changes include damage to the blood-brain barrier, development of vasogenic cerebral oedema, and intracranial pressurevolume disturbances leading to impaired CNS perfusion.
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Unanticipated difficult airway management in children — the consensus statement of the Paediatric Anaesthesiology and Intensive Care Section and the Airway Management Section of the Polish Society of Anaesthesiology and Intensive Therapy and the Polish So
Tracheal intubation may be defined as an artificial airway established in order to provide mechanical ventilation of the lungs during surgical procedures under general anaesthesia, treatment in an intensive care unit, as well as in emergency situations. Difficulties encountered during intubation may cause hypoxia, hypoxic brain injury and, in extreme situations, may result in the patient's death. There may be unanticipated and anticipated difficult airway. Children form a specific group of patients as there are significant differences in both anatomy and physiology. There are some limitations in equipment used for the airway management in children. There are only few paediatric difficult airway guidelines available, some of which have significant limitations. The presented algorithm was created by a group of specialists who represent the Polish Society of Anaesthesiology and Intensive Therapy, as well as the Polish Neonatology Society. This algorithm is intended for the unanticipated difficult airway in children and can be used in all age groups. It covers both elective intubation, as well as rescue techniques. A guide forms an integral part of the algorithm. It describes in detail all stages of the algorithm considering some modifications in a specific age group, e.g. neonates. The main aim of Stage I is to optimise conditions for face mask ventilation, laryngoscopy and intubation. Stage IIA focuses on maximising the chances of successful intubation when face mask ventilation is possible. Stage IIB outlines actions aimed at improving face mask ventilation. Stage IIIA describes the use of a SAD (Supraglottic Airway Device) during effective face mask ventilation or in a CICV (Cannot Intubate, Cannot Ventilate) situation. Stage IIIB outlines intubation through a SAD. Stage IV describes rescue techniques and outlines possible options of either proceeding with surgery or postponing it, depending on clinical situation.
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Executive summary on the use of ultrasound in the critically ill: consensus report from the 3rd Course on Acute Care Ultrasound (CACU)
Over the past decades, ultrasound (US) has gained its place in the armamentarium of monitoring tools in the intensive care unit (ICU). Critical care ultrasonography (CCUS) is the combination of general CCUS (lung and pleural, abdominal, vascular) and CC echocardiography, allowing prompt assessment and diagnosis in combination with vascular access and therapeutic intervention. This review summarises the findings, challenges lessons from the 3rd Course on Acute Care Ultrasound (CACU) held in November 2015, Antwerp, Belgium. It covers the different modalities of CCUS; touching on the various aspects of training, clinical benefits and potential benefits. Despite the benefits of CCUS, numerous challenges remain, including the delivery of CCUS training to future intensivists. Some of these are discussed along with potential solutions from a number of national European professional societies. There is a need for an international agreed consensus on what modalities are necessary and how best to deliver training in CCUS.
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The state of critical care ultrasound training in Europe: A survey of trainers and a comparison of available accreditation programmes
Background: Although critical care ultrasound (CCUS) in the Intensive Care Unit has been increasing exponentially for diagnostic and therapeutic purposes, the lack of a uniform formal training structure and programme has posed the question of whether scans have been appropriately performed or reported, and whether there exists proper clinical governance to ensure a high standard of care. Methods: An online survey was sent to the representatives of various national intensive care societies via the European Society of Intensive Care Medicine CoBaTrICE committee. A comparison between 5 worldwide accreditation programmes was also made. Results: Twenty-seven out of 42 countries replied our survey. Five countries had a nationally accredited programme in ICM Echocardiography while six were in the process of developing one. Three countries had a CCUS-accredited programme. Most had local programmes. Transthoracic echocardiography, lung and vascular ultrasound were considered essential. Although CCUS training programmes should incorporate a combination of theoretical and practical teaching, it is not clear which is the best format. The main barriers to delivering CCUS training included a lack of formally agreed competencies, as well as a lack of trainers and time. There is also a lack of agreement between the five accreditation programmes. Conclusions: There is a need for a well-structured and competent CCUS training program. The use of ultrasound in critical care for diagnostic and therapeutic purposes has been increasing exponentially. Once the remit of radiologists and cardiologists, point-of-care ultrasound and focused echocardiography is becoming an increasingly routine instrument for all acute specialties including intensive care medicine, despite the lack of evidence that it improves patient mortality in the ICU setting.
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The role of point-of-care ultrasound in intra-abdominal hypertension management
Background: Intra-abdominal hypertension is a common complication in critically ill patients. Recently the Abdominal Compartment Society (WSACS) developed a medical management algorithm with a stepwise approach according to the evolution of the intra-abdominal pressure and aiming to keep IAP ≤ 15 mm Hg. With the increased use of ultrasound as a bedside modality in both emergency and critical care patients, we hypothesized that ultrasound could be used as an adjuvant point-of-care tool during IAH management. This may be particularly relevant to the first and second basic stages of the algorithm. The objective of this paper is to test the use of POCUS as an adjuvant tool in the management of patients with IAH/ACS. Methods: Seventy-three consecutive adult critically ill patients admitted to the surgical intensive care unit (ICU) of a single urban institution with risk factor for IAH/ACS were enrolled. Those who met the inclusion criteria were allocated to undergo POCUS as an adjuvant tool in their IAH/ACS management. Results: A total of 50 patients met the inclusion criteria and were included in the study. The mean age of study participants was 55 ± 22.6 years, 58% were men, and the most frequent admission diagnosis was post-operative care following abdominal intervention. All admitted patients presented with a degree of IAH during their ICU stay. Following step 1 of the WSACS IAH medical management algorithm, ultrasound was used for NGT placement, confirmation of correct positioning, and evaluation of stomach contents. Ultrasound was comparable to abdominal X-ray, but shown to be superior in determining the gastric content (fluid vs. solid). Furthermore, POCUS allowed faster determination of correct NGT positioning in the stomach (antrum), avoiding bedside radiation exposure. Ultrasound also proved useful in: 1) evaluation of bowel activity; 2) identification of large bowel contents; 3) identification of patients that would benefit from bowel evacuation (enema) as an adjuvant to lower IAP; 4) and in the diagnosis of moderate to large amounts of free intra-abdominal fluid. Conclusion: POCUS is a powerful systematic ultrasound technique that can be used as an adjuvant in intra-abdominal hypertension management. It has the potential to be used in both diagnosis and treatment during the course of IAH.
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pharmacokinetics/pharmacodynamics; renal replacement therapy, continuous; antibiotics; antifungals
Continuous renal replacement therapy (CRRT) is progressively supplanting intermittent haemodialysis (IHD) in critically ill patients. Although CRRT indeed offers more appropriate haemodynamic, fluid, and metabolic stability, concern is rising about its impact on concomitant drugs and, in particular, antimicrobial treatment. Antimicrobial dose recommendations have been elaborated to avoid drug accumulation and toxicity in patients undergoing IHD. However, these dosing regimens have resulted in significant underdosing in patients undergoing CRRT, thereby increasing the risk of treatment failure and development of resistance. Applying pharmacokinetic/pharmacodynamic (PK/PD) principles may aid one to obtain more adequate antimicrobial therapy during CRRT. Much progress has been made in recent years resulting in relevant changes in particular antimicrobial therapies. In this review, we discuss antimicrobials that are frequently used in an intensive care setting. Drugs are divided according to their PK/PD characteristics and, wherever possible, dose recommendations during CRRT are provided. Of course, while therapeutic drug monitoring remains the best way to cope with PK/PD variability within a critically ill CRRT population, its bedside use is actually limited to some specific antibiotics.
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Introducing TOPMAST, the first double-blind randomized clinical trial specifically dedicated to perioperative maintenance fluid therapy in adults
Background: Although prescribed to every patient undergoing surgery, maintenance fluid therapy is a poorly researched part of perioperative fluid therapy. The tonicity of the chosen solutions, could be an important cause of morbidity, with hyponatremia being a potential side effect of hypotonic solutions, where isotonic solution could lead to fluid overload. Methods: The TOPMAST-trial is an ongoing prospective single-center double-blind randomized trial comparing an isotonic and a hypotonic maintenance fluid strategy during and after surgery in patients undergoing different types of major thoracic surgery. Patients receive NaCl 0.9% in glucose 5% with an added 40 mmol L-1 of potassium chloride or a premixed solution containing 54 mmol L-1 sodium, 55 mmol L-1 chloride and 26 mmol of potassium at a rate of 27 mL per kg of body weight per day. The primary hypothesis is that isotonic maintenance solutions cause a more positive perioperative fluid balance than hypotonic fluids. Different secondary safety endpoints will be explored, especially the effect of the study treatments on the occurrence electrolyte disturbances (e.g. hyponatremia, hyperchloremia) and a set of clinical endpoints. Efficacy endpoints include the need for resuscitation fluids and assessment of renal and hormonal adaptive mechanisms. An anticipated 68 patients will be included between March 2017 and January 2018. Discussion: The study will provide the most comprehensive evaluation of clinically important outcomes associated with the choice of perioperative maintenance fluid therapy.
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Re-operative abdominal predictive score: a prognostic model combining Acute Re-intervention Predictive Index and intra-abdominal pressure
Background: The decision to re-operate after abdominal surgery is still difficult, especially in the setting of intraabdominal sepsis. Mathematical models provide a good aid to both diagnosis and decision-making. Methods: A prospective observational study was conducted with 300 patients consecutively admitted to the intensive care unit of an academic institution affiliated to Calixto García Medical Faculty following abdominal surgery from January 2008 to January 2010. The patients were randomly separated (2:1) into estimation and validation groups. Logistic regression analysis was used in the estimation group to develop three models for decision-making related to re-operation including related factors such as age, ARPI, IAP, type of surgery (elective or emergency), and the duration of surgery. The three models developed were validated on the other group. Results: The acute re-operation predictive index-intra-abdominal pressure (ARPI-IAP) model was the best of the three models, with an excellent calibration, using the Hossmer-Lemeshow goodness-of-fit statistical test (C = 9.976, P = 0.267), as well as discrimination (AUC = 0.989; 95% CI: 0.976–1.000). Conclusion: The combination of IAP with ARPI in a mathematical model can add accuracy to the prediction of need for re-operation related to intra-abdominal infectious complications in patients following abdominal surgery. This may be useful in all medical settings, but especially those with limited resources.
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Lung ultrasound in the critically ill (LUCI): A translational discipline
In the early days of ultrasound, it was not a translational discipline. The heart was claimed by cardiologists, with others, such as gynaecologists, urologists and vascular surgeons claiming their part while the rest was given to radiologists. Only recently, ultrasound transgressed and crossed the usual borders between the different disciplines, such as emergency and critical care medicine. The advent of portable machines in the early 1980s, allowed the critical care physician to perform bedside ultrasound, and the development of whole body critical care ultrasound (CCUS) was born. It may sound cynical that radiologists were the first to state that diagnostic sonography was truly the next stethoscope: poorly utilized by many but understood by few. Exactly the same radiologists then abandoned the use of ultrasound outside the radiology department, leaving a vast domain to other disciplines eager to welcome the modern stethoscope. In this review, we list the possibilities of lung ultrasound as a translational holistic discipline.
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Focus on focus: lack of coherence between systemic and microvascular indices of oedema formation
Background: Fluid therapy remains a cornerstone of therapy in shock states. However, fluid overloading ultimately results in oedema formation which is related to excess morbidity and mortality. Handheld microscopes are now frequently used to study the sublingual microcirculation. As a corollary, these devices measure focal distance, or surface to capillary distance. Physiologically, this could represent a microvascular index of oedema formation and could have the potential to guide fluid therapy. This potential tool should be investigated, especially given the frequently reported lack of coherence between systemic and microvascular parameters in the critically ill. Therefore, we set out to assess the correlation between microvascular focal distance and systemic indices of oedema formation, specifically fluid balance and weight gain. Methods: Following ex vivo testing of focal distance measurement reliability, we conducted a prospective observational cohort study in patients admitted to the intensive care unit of our university teaching hospital. We determined surface to capillary distance using sidestream dark field (SDF) and incident dark field (IDF) imaging by assessing the focal distance point or object distance range at which a sharp recording could be made. Measurements were performed in post-cardiac surgery patients and in patients following emergency admission at two time points separated by at least several hours. Data on fluid balance, weight and weight gain were collected simultaneously. Results: Sixty patients were included. The focal setting, focus point for SDF and the object distance range for IDF did not differ significantly between time points. Focus was not correlated with difference in fluid balance or weight gain. Conclusions: There is a lack of coherence between surface to capillary distance as determined by SDF or IDF imaging and fluid balance or weight gain. Thus, focal distance as a microvascular index of oedema formation cannot currently be used as a proxy for systemic indices of oedema formation. However, given the lack of coherence, further research should determine whether focal distance may provide better guidance for fluid therapy than traditional markers of overzealous fluid administration. RESULTS: Sixty patients were included. Focal setting, focus point for SDF and an object distance range for IDF did not differ significantly between time points. Focus was not correlated with difference in fluid balance or weight gain. CONCLUSIONS: There is a lack of coherence between surface to capillary distance as determined by SDF or IDF imaging and fluid balance or weight gain. Thus, focal distance as a microvascular index of edema formation cannot currently be used as a proxy for systemic indices of edema formation. However, given the lack of coherence, further research should determine whether focal distance may provide better guidance for fluid therapy than traditional markers of overzealous fluid administration.
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Management of arrhythmia in sepsis and septic shock
The occurrence of supraventricular arrhythmias is associated with an unfavourable prognosis in septic shock. Available trials are difficult to apply in sepsis and septic shock patients due to included cohorts, control groups and because "one size does not fit all". The priorities in the critically ill are maintenance of the sinus rhythm and diastolic ventricular filling. The rate control modality should be reserved for chronic AF and in situations when the sinus rhythm is difficult to maintain due to extreme stress conditions resulting from a high dosage of vasoactive agents. Electric cardioversion is indicated in unstable patients with an absence of contraindications and is more feasible in combination with an antiarrhythmic agent. Besides amiodarone being preferred for its lower cardiodepressant side effect compared to other agents, drugs with a different degree of betablocking activity are very useful in supraventricular arrhythmias and septic shock, providing echocardiography is routinely used to support their indications within the current summary of product characteristics. A typical patient benefiting from propafenone is without significant structural heart disease, i.e. typically with normal to moderately reduced left ventricular systolic function. Future research should be channelled towards echocardiography-guided prospective controlled trials on antiarrhythmic therapy which may clarify the issue of rhythm versus rate control, the effects of various antiarrhythmic drugs, and a place for electric cardioversion in critically ill patients in septic shock.
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Implementing clinical practice changes in critical care: lessons learned in a national collaborative of over 60 ICU teams
Improving care in the intensive care unit (ICU) is a global area of focus for clinicians worldwide. The complexity of the ICU environment, compounded by multiple patient comorbidities and high acuity levels, makes the ICU a unique and challenging area of clinical practice. The essence of quality improvement — designing and implementing strategies to enhance care — fit well with the ICU setting. However, implementing clinical change is challenging, regardless of the clinical setting. A national collaborative targeting ICU settings was initiated which provided a number of lessons learned regarding implementing quality of care initiatives in critical care. This article highlights quality improvement strategies for implementing clinical practice changes in the ICU to enhance care, based on reports from over 60 ICUs participating in the collaborative.
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Correction to: Expanding the genetic heterogeneity of intellectual disability
Abstract
Variant nomenclature discrepancy was identified in the article.
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