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

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Publication date: March 2018
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

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Publication date: February 2018
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

imageABSTRACTObjectives:Maturation of the gut microbiota has been shown to influence childhood growth, whereas alterations in microbiota composition are proposed to be causally related to the development of overweight and obesity. The objective of this study is to explore the association between microbiota profile, body size, and body composition in young children.Methods:Fecal microbiota was examined by 16S rRNA gene sequencing, whereas body composition was assessed using the deuterium oxide dilution technique in a cohort of 37 well-nourished 2- to 3-year-old Australian children.Results:Microbiota composition (weighted UniFrac distance) was shown to be significantly associated with FFMI (fat-free mass index) z score (P = 0.027, adonis) in boys but not girls. In boys, FFMI z score was significantly correlated with the relative abundance of an OUT (Operational Taxonomic Unit) belonging to the Ruminococcaceae family (Rho = 0.822, P 

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Neonatal Exposure to Hepatitis C Virus Antigens in Uninfected Children Born to Infected Mothers

imageABSTRACTObjective:Vertical transmission of hepatitis C virus (HCV) infection is uncommon and occurs in approximately 5% of births from HCV-infected mothers. The reason for the low transmission rate is unclear. We aimed to investigate whether there is evidence of HCV exposure also in the noninfected children born to HCV-infected mothers by the presence of a detectable immune response.Methods:Serum and peripheral blood mononuclear cells from 9 HCV vertically infected children, 32 uninfected children born to HCV infected mothers, and 15 HCV chronically infected mothers, were analyzed. HCV-RNA-negative adults and children were used as controls. HCV-specific T cell responses were analyzed by interferon gamma using an enzyme-linked immunospot assay and 3H-thymidine incorporation assay. HCV antibodies were also analyzed.Results:An HCV-specific T cell response was detected in 73% (11/15) of the HCV-infected mothers, 67% (6/9) of the vertically infected children, 56% (18/32) of the exposed but uninfected children and in 10% and 20% of the control groups, respectively. The 2 groups of HCV-exposed children both had a significantly higher proportion of HCV-specific T cell responders compared to pediatric controls (P = 0.01 and P = 0.02).Conclusions:HCV-specific immune responses were more common in children born to HCV-infected mothers, regardless of the presence of HCV RNA. We conclude that noninfected children born to HCV-infected mothers may have been exposed to HCV antigens. Objective: Vertical transmission of hepatitis C virus (HCV) infection is uncommon and occurs in approximately 5% of births from HCV-infected mothers. The reason for the low transmission rate is unclear. We aimed to investigate whether there is evidence of HCV exposure also in the noninfected children born to HCV-infected mothers by the presence of a detectable immune response. Methods: Serum and peripheral blood mononuclear cells from 9 HCV vertically infected children, 32 uninfected children born to HCV infected mothers, and 15 HCV chronically infected mothers, were analyzed. HCV-RNA-negative adults and children were used as controls. HCV-specific T cell responses were analyzed by interferon gamma using an enzyme-linked immunospot assay and 3H-thymidine incorporation assay. HCV antibodies were also analyzed. Results: An HCV-specific T cell response was detected in 73% (11/15) of the HCV-infected mothers, 67% (6/9) of the vertically infected children, 56% (18/32) of the exposed but uninfected children and in 10% and 20% of the control groups, respectively. The 2 groups of HCV-exposed children both had a significantly higher proportion of HCV-specific T cell responders compared to pediatric controls (P = 0.01 and P = 0.02). Conclusions: HCV-specific immune responses were more common in children born to HCV-infected mothers, regardless of the presence of HCV RNA. We conclude that noninfected children born to HCV-infected mothers may have been exposed to HCV antigens.

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Probiotics for the Prevention of Nosocomial Diarrhea in Children

imageThis document provides recommendations developed by the ESPGHAN Working Group on Probiotics and Prebiotics on the role of probiotics in the prevention of nosocomial diarrhea in children based on a systematic review of previously completed systematic reviews and of subsequently published randomized controlled trials. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation guidelines. Recommendations were given only if at least 2 randomized controlled trials examined the same probiotic strain. Based on currently available evidence the Working Group recommends using Lactobacillus rhamnosus GG if the use of probiotics for preventing nosocomial diarrhea in children is considered.

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Neuropathic Pain as Potential Source of Feed-induced Dystonia in Children With Severe Central Nervous System Disorders

No abstract available

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Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial

imageABSTRACTObjective:The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350 + E) compared to PEG4000 without electrolytes (PEG4000).Methods:In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of

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Variceal Hemorrhage and Adverse Liver Outcomes in Patients With Cystic Fibrosis Cirrhosis

imageABSTRACTObjectives:Cirrhosis occurs in 5% to 10% of cystic fibrosis (CF) patients, often accompanied by portal hypertension. We analyzed 3 adverse liver outcomes, variceal bleeding (VB), liver transplant (LT), and liver-related death (LD), and risk factors for these in CF Foundation Patient Registry subjects with reported cirrhosis.Methods:We determined 10-year incidence rates for VB, LT, LD, and all-cause mortality (ACM), and examined risk factors using competing risk models and Cox-proportional hazard regression.Results:From 2003 to 2012, 943 participants (41% females, mean age 18.1 years) had newly reported cirrhosis; 24.7% required insulin, 85% had previous pseudomonas. Seventy-three subjects had reported VB: 38 with first VB and new cirrhosis reported simultaneously and 35 with VB after cirrhosis report. Ten-year cumulative VB, LT, and LD rates were 6.6% (95% confidence interval [CI]: 4.0, 9.1%), 9.9% (95% CI: 6.6%, 13.2%), and 6.9% (95% CI: 4.0%, 9.8%), respectively, with an ACM of 39.2% (95% CI: 30.8, 36.6%). ACM was not increased in subjects with VB compared to those without (hazard ratio [HR] 1.10, 95% CI: 0.59, 2.08). CF-related diabetes (HR: 3.141, 95% CI:1.56, 6.34) and VB (HR: 4.837, 95% CI: 2.33, 10.0) were associated with higher LT risk, whereas only worse lung function was associated with increased LD in multivariate analysis. Death rate among subjects with VB was 24% with LT and 20.4% with native liver.Conclusions:VB is an uncommon complication of CF cirrhosis and can herald the diagnosis, but does not affect ACM. Adverse liver outcomes and ACM are frequent by 10 years after cirrhosis report. Objectives: Cirrhosis occurs in 5% to 10% of cystic fibrosis (CF) patients, often accompanied by portal hypertension. We analyzed 3 adverse liver outcomes, variceal bleeding (VB), liver transplant (LT), and liver-related death (LD), and risk factors for these in CF Foundation Patient Registry subjects with reported cirrhosis. Methods: We determined 10-year incidence rates for VB, LT, LD, and all-cause mortality (ACM), and examined risk factors using competing risk models and Cox-proportional hazard regression. Results: From 2003 to 2012, 943 participants (41% females, mean age 18.1 years) had newly reported cirrhosis; 24.7% required insulin, 85% had previous pseudomonas. Seventy-three subjects had reported VB: 38 with first VB and new cirrhosis reported simultaneously and 35 with VB after cirrhosis report. Ten-year cumulative VB, LT, and LD rates were 6.6% (95% confidence interval [CI]: 4.0, 9.1%), 9.9% (95% CI: 6.6%, 13.2%), and 6.9% (95% CI: 4.0%, 9.8%), respectively, with an ACM of 39.2% (95% CI: 30.8, 36.6%). ACM was not increased in subjects with VB compared to those without (hazard ratio [HR] 1.10, 95% CI: 0.59, 2.08). CF-related diabetes (HR: 3.141, 95% CI:1.56, 6.34) and VB (HR: 4.837, 95% CI: 2.33, 10.0) were associated with higher LT risk, whereas only worse lung function was associated with increased LD in multivariate analysis. Death rate among subjects with VB was 24% with LT and 20.4% with native liver. Conclusions: VB is an uncommon complication of CF cirrhosis and can herald the diagnosis, but does not affect ACM. Adverse liver outcomes and ACM are frequent by 10 years after cirrhosis report.

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Development of the Aim to Decrease Anxiety and Pain Treatment for Pediatric Functional Abdominal Pain Disorders

imageABSTRACTObjectives:To evaluate the feasibility and acceptability of the Aim to Decrease Anxiety and Pain Treatment (ADAPT), a brief, on-line and in-person behavioral intervention targeting pain and anxiety in youth with functional abdominal pain disorders (FAPDs).Methods:Patients were recruited from several outpatient pediatric gastroenterology clinics. Nine participants (ages 9–13) completed the full protocol. Thematic analysis of detailed qualitative feedback was obtained via semistructured patient and caregiver interviews after treatment was conducted. Feasibility and preliminary outcomes were examined using nonparametric tests.Results:Preliminary results indicate that the ADAPT treatment is feasible, acceptable, and potentially effective for youth with FAPD. Treatment completers reported that they enjoyed the program and used the skills to manage their pain and worry. Results also indicated that the majority of participants experienced a reduction in anxiety and several reported reductions in pain and functional disability levels.Conclusions:Findings from this study suggest that targeting both pain and anxiety may positively impact outcomes in youth with FAPD. The ADAPT intervention has the potential to provide a cost effective and practical application of cognitive behavioral therapy using an innovative combination of in-person and technology-based platforms. Overall, the ADAPT intervention is a promising and innovative intervention to improve the outcomes of youth with FAPD. Objectives: To evaluate the feasibility and acceptability of the Aim to Decrease Anxiety and Pain Treatment (ADAPT), a brief, on-line and in-person behavioral intervention targeting pain and anxiety in youth with functional abdominal pain disorders (FAPDs). Methods: Patients were recruited from several outpatient pediatric gastroenterology clinics. Nine participants (ages 9–13) completed the full protocol. Thematic analysis of detailed qualitative feedback was obtained via semistructured patient and caregiver interviews after treatment was conducted. Feasibility and preliminary outcomes were examined using nonparametric tests. Results: Preliminary results indicate that the ADAPT treatment is feasible, acceptable, and potentially effective for youth with FAPD. Treatment completers reported that they enjoyed the program and used the skills to manage their pain and worry. Results also indicated that the majority of participants experienced a reduction in anxiety and several reported reductions in pain and functional disability levels. Conclusions: Findings from this study suggest that targeting both pain and anxiety may positively impact outcomes in youth with FAPD. The ADAPT intervention has the potential to provide a cost effective and practical application of cognitive behavioral therapy using an innovative combination of in-person and technology-based platforms. Overall, the ADAPT intervention is a promising and innovative intervention to improve the outcomes of youth with FAPD.

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Unusual Presentation of Giant Omental Cystic Lymphangioma Mimicking Hemorrhagic Ascites in a Child

imageNo abstract available

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Long-term Follow-up of Adolescents Treated for Rumination Syndrome in an Inpatient Setting

imageABSTRACTObjectives:Although several studies have demonstrated the short-term benefit of the behavioral treatment of rumination syndrome, few have investigated the long-term outcomes. Studies reporting long-term benefit have involved combined pediatric and adult samples or have examined outcomes of patients involved in various types of treatment. The purpose of the present study was to examine several aspects of long-term outcome in adolescent patients who took part in the same intensive, interdisciplinary, inpatient behavioral treatment approach.Methods:Self-report measures were completed by 47 adolescent patients (mean age = 15.9) around 1 year or more from discharge from our inpatient program. Measures indexed changes in rumination, medical outcomes (eg, use of supplemental nutrition), somatic symptoms, and quality of life.Results:Most patients reported continued improvement in their rumination over time, with 20% reporting cessation of rumination for at least 6 months. The majority of patients no longer required supplemental nutrition and reported improvements in somatic symptoms and quality of life. Patients who reported greater improvement in rumination also reported more significant improvements in their somatic symptoms and quality of life.Conclusions:Intensive behavioral treatment of rumination syndrome leads to long-term improvement in rumination as well as other related factors, including somatic symptoms and quality of life. Objectives: Although several studies have demonstrated the short-term benefit of the behavioral treatment of rumination syndrome, few have investigated the long-term outcomes. Studies reporting long-term benefit have involved combined pediatric and adult samples or have examined outcomes of patients involved in various types of treatment. The purpose of the present study was to examine several aspects of long-term outcome in adolescent patients who took part in the same intensive, interdisciplinary, inpatient behavioral treatment approach. Methods: Self-report measures were completed by 47 adolescent patients (mean age = 15.9) around 1 year or more from discharge from our inpatient program. Measures indexed changes in rumination, medical outcomes (eg, use of supplemental nutrition), somatic symptoms, and quality of life. Results: Most patients reported continued improvement in their rumination over time, with 20% reporting cessation of rumination for at least 6 months. The majority of patients no longer required supplemental nutrition and reported improvements in somatic symptoms and quality of life. Patients who reported greater improvement in rumination also reported more significant improvements in their somatic symptoms and quality of life. Conclusions: Intensive behavioral treatment of rumination syndrome leads to long-term improvement in rumination as well as other related factors, including somatic symptoms and quality of life.

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Mimicking Own Mother's Milk for Preterms: Are We Getting Closer?

No abstract available

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Retrospective Comparison of Fluticasone Propionate and Oral Viscous Budesonide in Children With Eosinophilic Esophagitis

imageABSTRACTBackground:Eosinophilic esophagitis (EoE) is treated with dietary modification and/or pharmacologic management with swallowed topical steroids. Swallowed fluticasone propionate (FP) and oral viscous budesonide (OVB) have proven to be effective in resolving symptoms and reversing histologic changes in children and adults with EoE. There are minimal comparative studies between the 2 agents.Objective:The aim of the study was to retrospectively compare endoscopic and histologic outcomes after FP versus OVB therapy in children with EoE in our center.Methods:We performed a retrospective chart review of subjects diagnosed with EoE at a tertiary care center between 2010 and 2015. Inclusion criteria were FP or OVB therapy for ≥8 weeks along with pre- and post-treatment endoscopic evaluation. Demographic and clinical features and endoscopic and histologic assessment were recorded for comparative analysis. Histologic response was defined as

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Cholangiocarcinoma Among Children and Adolescents: A Review of the Literature and Surveillance, Epidemiology, and End Results Program Database Analysis

imageABSTRACTObjective:Cholangiocarcinoma (CCA) is a biliary malignancy found primarily in adults. The incidence of CCA in children is unknown. The aim of this study was to describe characteristics of CCA in children and adolescents.Methods:Using the Surveillance, Epidemiology, and End Results Program (SEER 18) database, we identified incident cases of CCA diagnosed at

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Unsedated In-office Transgastrostomy Esophagoscopy to Monitor Therapy in Pediatric Esophageal Disease

imageMonitoring therapy in esophageal inflammatory disorders such as eosinophilic esophagitis and reflux esophagitis often requires frequent endoscopic evaluation. We recently reported the effective use of unsedated in-office transnasal esophagoscopy that significantly decreased costs and anesthetic exposure associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we report a series of pediatric patients with esophagitis with gastrostomy tubes who underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting. Nine patients (ages 16 months–21 years) tolerated TGE without significant adverse events. Biopsy specimens were adequate for evaluation. This series confirms that unsedated in-office TGE can be used to successfully obtain mucosal biopsies to monitor esophageal inflammatory conditions in children without the use of sedation.

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Randomized Trial of a Yogurt-type Amino Acid−based Formula in Infants and Children With Severe Cow's Milk Allergy

imageABSTRACTObjectives:Evaluation of a spoon-fed amino acid−based formula (AAF) with a yogurt-type texture compared to the reference oral liquid formula (Neocate).Methods:Phase III/IV, prospective, randomized (1:1), open-label, multicenter study in infants/young children (6–36 months) with severe cow's milk protein allergy (CMA) who had consumed AAF for ≥1 month before the study. Patients received reference+test formula (Neocate with a yogurt-type texture for spoon-feeding: group 1) or reference formula (group 2) for 28 days. The study formulae were integrated into the patients' usual daily diet. Efficacy on Day 0, 14, and 28 was assessed primarily in terms of symptoms associated with CMA. The evolution of symptoms, amount of formula consumed, nutritional and energy intake, anthropometric data, and tolerability were also assessed.Results:The incidence of CMA symptoms was similar in each group (P > 0.05) on day 0, 14, and 28. For specific symptoms, there was little change from day 0 and no significant difference between groups for incidence on day 0 or evolution at day 14 or 28. There was no difference in formula consumption (day 0–day 28) between groups (P = 0.90), but nutritional value was generally higher for group 1 and calcium intake was statistically higher for group 1 (P  0.05) on day 0, 14, and 28. For specific symptoms, there was little change from day 0 and no significant difference between groups for incidence on day 0 or evolution at day 14 or 28. There was no difference in formula consumption (day 0–day 28) between groups (P = 0.90), but nutritional value was generally higher for group 1 and calcium intake was statistically higher for group 1 (P 

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Novel Pressure-Impedance Parameters for Evaluating Esophageal Function in Pediatric Achalasia

imageABSTRACTObjective:In achalasia, absent peristalsis and reduced esophagogastric junction (EGJ) relaxation and compliance underlie dysphagia symptoms. Novel high-resolution impedance manometry variables, that is, bolus presence time (BPT) and trans-EGJ-bolus flow time (BFT) have been developed to estimate the duration of EGJ opening and trans-EGJ bolus flow. The aim of this study was to evaluate esophageal motor function and bolus flow in children diagnosed with achalasia using these variables.Methods:High-resolution impedance manometry recordings from 20 children who fulfilled the Chicago Classification (V3) criteria for achalasia were compared with recordings of 15 children with normal esophageal high-resolution manometry findings and no other evidence suggestive of achalasia. Matlab-based analysis software was used to calculate BPT and BFT.Results:Both BPT and BFT were significantly reduced in achalasia patients compared with children with normal esophageal motility (BPT 3.3 s vs 5.1 s P 

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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

imageABSTRACTBackground:Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed.Methods:The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation.Results:The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP.Conclusions:This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP. Background: Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. Methods: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. Results: The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. Conclusions: This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.

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Peroral Endoscopic Myotomy in Children: First Experience With a New Triangular Knife

imageABSTRACTObjectives:Peroral endoscopic myotomy (POEM) is a novel treatment modality for achalasia cardia. The procedure is technically challenging and time consuming. Recently, a new triangle tip knife (TTJ) has been introduced, which is equipped with water jet facility. In the present study, we analyzed the feasibility, safety, and efficacy of POEM in children with new triangle tip knife.Methods:We retrospectively evaluated the data of children (18 years or younger) who underwent POEM using TTJ knife at our institution. All POEM procedures were performed under general anesthesia in an endoscopy suite. Technical feasibility, safety, efficacy, and procedure duration were assessed.Results:Ten children (4 boys, 6 girls) with mean age of 14.2 ± 2.74 (9–18) years, underwent POEM with TTJ knife. The subtypes of achalasia cardia were type I (4), type II (5), and type III (1). Two children had prior treatment with pneumatic balloon dilatation. POEM was performed via anterior route in majority of children (70%). Mean operating time was 47.6 ± 19.74 (30–98) minutes with no significant difference between anterior and posterior approaches to POEM (48.57 ± 24.01 vs 45.3 ± 3.51; P 

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Fatal Central Nervous System Post-Transplant Lymphoproliferative Disease in a Patient Who Underwent Liver Transplantation for Hepatoblastoma

imageNo abstract available

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Safety and Efficacy of the Push Endoscopic Technique in the Management of Esophageal Food Bolus Impactions in Children

imageABSTRACTObjectives:Adult-based guidelines support the use of the pull (extraction) endoscopic technique in managing esophageal food bolus impactions (FBIs) but allow the consideration of the push (advancement) technique with caution based on available published literature. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines mention the use of gentle endoscopic pushing for disimpaction but elaborate that this technique has not been studied in children. Our study aimed at assessing the safety and efficacy of the push technique in managing pediatric esophageal FBIs.Methods:This was a retrospective cohort study of all pediatric patients presenting with esophageal FBIs to a pediatric tertiary care center from 2003 to 2016.Results:Two hundred forty-two procedures for esophageal foreign body removal were reviewed. Thirty-nine procedures for managing esophageal FBIs were included in a total of 23 patients (1–4 procedures per patient). The most common underlying diagnoses were eosinophilic esophagitis and repaired tracheoesophageal fistula. The cohort had a median age of 8 years and median weight of 34.4 kg. Initial endoscopic disimpaction methods included 20 push and 19 pull technique attempts with success rates of 65% and 68%, respectively (P = 1.0). Unsuccessful attempts using 1 technique were successfully accomplished using the other technique. Patients initially managed by either of the 2 disimpaction techniques did not differ in age, weight, sex, or underlying diagnoses. No procedure-related complications were reported at our center.Conclusion:The present study shows that the push technique is as safe and effective as the pull technique in managing esophageal FBIs in pediatric patients. Objectives: Adult-based guidelines support the use of the pull (extraction) endoscopic technique in managing esophageal food bolus impactions (FBIs) but allow the consideration of the push (advancement) technique with caution based on available published literature. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines mention the use of gentle endoscopic pushing for disimpaction but elaborate that this technique has not been studied in children. Our study aimed at assessing the safety and efficacy of the push technique in managing pediatric esophageal FBIs. Methods: This was a retrospective cohort study of all pediatric patients presenting with esophageal FBIs to a pediatric tertiary care center from 2003 to 2016. Results: Two hundred forty-two procedures for esophageal foreign body removal were reviewed. Thirty-nine procedures for managing esophageal FBIs were included in a total of 23 patients (1–4 procedures per patient). The most common underlying diagnoses were eosinophilic esophagitis and repaired tracheoesophageal fistula. The cohort had a median age of 8 years and median weight of 34.4 kg. Initial endoscopic disimpaction methods included 20 push and 19 pull technique attempts with success rates of 65% and 68%, respectively (P = 1.0). Unsuccessful attempts using 1 technique were successfully accomplished using the other technique. Patients initially managed by either of the 2 disimpaction techniques did not differ in age, weight, sex, or underlying diagnoses. No procedure-related complications were reported at our center. Conclusion: The present study shows that the push technique is as safe and effective as the pull technique in managing esophageal FBIs in pediatric patients.

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Proton Pump Inhibitors May Not Be the First Line of Treatment for GERD in Infants

No abstract available

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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)

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Publication date: March 2018
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.

Thumbnail image of graphical abstract

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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.

Thumbnail image of graphical abstract

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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

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Publication date: Available online 29 December 2017
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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Editorial Board



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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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Murphy’s law and Murphy eyes



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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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The future of evidence-based medicine: is the frog still boiling?



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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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The SEP-1 quality mandate may be harmful: How to drown a patient with 30 mL per kg fluid!



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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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