Τετάρτη, 9 Ιανουαρίου 2019

Genetic, Inflammatory, and Epithelial Cell Differentiation Factors Control Expression of Human Calpain-14

Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease resulting in eosinophilic esophageal inflammation. We recently found that EoE susceptibility is associated with genetic variants in the promoter of CAPN14, a gene with reported esophagus-specific expression. CAPN14 is dynamically up-regulated as a function of EoE disease activity and after exposure of epithelial cells to interleukin-13 (IL-13). Herein, we aimed to explore molecular modulation of CAPN14 expression. We identified three putative binding sites for the IL-13-activated transcription factor STAT6 in the promoter and first intron of CAPN14. Luciferase reporter assays revealed that the two most distal STAT6 elements were required for the ~10-fold increase in promoter activity subsequent to stimulation with IL-13 or IL-4, and also for the genotype-dependent reduction in IL-13-induced promoter activity. One of the STAT6 elements in the promoter was necessary for IL-13-mediated induction of CAPN14 promoter activity while the other STAT6 promoter element was necessary for full induction. Chromatin immunoprecipitation in IL-13 stimulated esophageal epithelial cells was used to further support STAT6 binding to the promoter of CAPN14 at these STAT6 binding sites. The highest CAPN14 and calpain-14 expression occurred with IL-13 or IL-4 stimulation of esophageal epithelial cells under culture conditions that allow the cells to differentiate into a stratified epithelium. This work corroborates a candidate molecular mechanism for EoE disease etiology in which the risk variant at 2p23 dampens mediated CAPN14 expression in differentiated esophageal epithelial cells following IL-13/STAT6 induction of CAPN14 promoter activity.



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Biliary Atresia Associated Cholangitis – The Central Role and Effective Management of Bile Lakes

Objectives: Cholangitis and bile lakes are incompletely understood complications after portoenterostomy (PE). We investigated relationships between recurrent cholangitis, bile lakes and clinical outcomes as well as surgical management of bile lakes. Methods: In this retrospective observational single institution study medical records and imaging studies of all patients who had undergone PE for biliary atresia during 1987–2016 (N = 61) were reviewed. We related occurrence of cholangitis episodes with the presence of intrahepatic bile lakes, patient characteristics, and PE outcomes. Risk factors for recurrent cholangitis and bile lakes, and management of bile lakes were analysed. Results: Despite routine antibiotic prophylaxis median of 3.0 cholangitis episodes (0.75 episodes/year) occurred in 48 (79%) patients. Intrahepatic bile lakes were discovered in 8 (13%) patients by 16 months after PE. Overall, 54% had survived with their native liver at median age of 7.3 years and 28 (46%) patients had ≥1 cholangitis episodes/year. Number and frequency of cholangitis episodes were >5 times higher among patients with bile lakes (P 

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Vitamin D and Inflammatory Mediators in Preterm Infants with Late-Onset Sepsis: A Randomized Controlled Trial

Objective: To evaluate biochemical and clinical effects of two different doses of vitamin D supplementation in preterm infants with late onset sepsis (LOS). Study Design: A double blinded randomized controlled stratified trial included preterm infants with gestational age (GA) ≥28 weeks with LOS. Subjects were randomly assigned to receive 400 or 800 IU/d of vitamin D3. Serum concentrations of 25(OH)D, TNF-α and IL-6 were measured at enrollment, 7 days after vitamin D supplementation, and at 40 weeks of postmenstrual age (PMA). Short-term outcomes and growth parameters were assessed. Results: A total of 50 infants were enrolled, 25 in each group. Seventy-six percent of enrolled infants were vitamin D deficient at enrollment in both groups whereas only one infant in the 400 IU and none in the 800 IU group remained deficient at 40 week's PMA; vitamin D concentrations at 40 weeks PMA were 54.8 ± 35.1 and 67.4 ± 37.1 ng/mL, respectively, p = 0.01). None of the infants enrolled in the study had signs of vitamin D toxicity. Serum pro-inflammatory cytokines IL-6 and TNF- α concentrations decreased at one week and at discharge in both groups without differences between groups. The two groups did not differ in anthropometric measurements, duration of oxygen and respiratory support, duration of antimicrobial use, length of hospital stay, and mortality. Conclusions: A dose of 400 IU of vitamin D was adequate to treat vitamin D deficiency in the majority of premature infants with LOS. The two dosing regimens did not differ in clinical or biochemical changes. Address correspondence and reprint requests to Hany Aly, MD, Cleveland Clinic Children's, Department of Neonatology, 9500 Euclid Avenue, Suite M31-37, Cleveland, OH 44195 (e-mail: alyh@ccf.org). Received 16 July, 2018 Accepted 6 December, 2018 Conflict of Interest and Source of Funding: All authors have nothing to declare. The study was registered at clinical trials.gov (identifier: NCT02273843). Conflict of Interest: The authors declare no conflict of interest. Authors' contributions Hesham Abdel-Hady: Contributed to the concept and design of the work. He wrote the paper, approved the final version and agreed to be accountable for all aspects of the work. Sohier Yahia: Contributed to data acquisition. She wrote the first draft of the paper. She approved the final version and agreed to be accountable for all aspects of the work. Ahmed Megahed: Contributed to data acquisition. He approved the final version and agreed to be accountable for all aspects of the work. Abeer Mosbah: Performed the microbiological analysis. She approved the final version and agreed to be accountable for all aspects of the work. Basma Seif: Contributed to data acquisition. She wrote the first draft of the paper. She approved the final version and agreed to be accountable for all aspects of the work. Eman Nageh: Contributed to data acquisition. She wrote the first draft of the paper. She approved the final version and agreed to be accountable for all aspects of the work. Indrani Bhattacharjee: She contributed to the analysis and interpretation of the data. She assisted with writing the paper and the figures. She approved the final version and agreed to be accountable for all aspects of the work. Hany Aly: Contributed to the concept and design of the work. Revised the manuscript, approved the final version and agreed to be accountable for all aspects of the work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Barium Enema Revisited in the Workup for the Diagnosis of Hirschsprung's Disease

The diagnostic capacity of barium enema (BE) in the diagnostic investigation for Hirschsprung's disease (HD) was analyzed for transition zone (TZ) identification and rectosigmoid index (RSI) ≤ 1.0 determination. BE images were analyzed retrospectively by two examiners and the results were compared with the histopathology of rectal biopsies. TZ identification and RSI ≤ 1.0 were assessed separately and combined in 43 patients. Twelve (27.9%) patients had the diagnosis of HD based on rectal biopsies. TZ identification presented better diagnostic capacity for the two examiners than RSI ≤ 1.0. However, inter-examiner agreement was higher for RSI ≤ 1.0 than for TZ identification. The combination of TZ identification and RSI≤ 1.0 increased the sensitivity (83.3% to 92.3%) and the negative predictive value (90.4% to 92.3%). Therefore, the high diagnostic sensitivity of TZ identification combined to RSI ≤ 1.0 reinforces the usefulness of these BE parameters in the screening for Hirschsprung's disease. Address correspondence and reprint requests to Pedro Luiz Toledo de Arruda Lourenção, Department of Surgery, Division of Pediatric Surgery, Botucatu Medical School, Unesp - Sao Paulo State University, Botucatu-SP, Brazil – CEP 18618-687 (e-mail: plourencao@gmail.com). Received 20 June, 2018 Accepted 6 December, 2018 The study did not receive support or funding from any organization. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Author contributions Pedro Luiz Toledo de Arruda Lourencao was responsible for the study conception and design, performed the radiological analysis, the interpretation of data and drafted the manuscript. Felipe Gilberto Valerini was responsible for acquisition of data, analysis and interpretation of data and drafted the manuscript. Antonio Jose Maria Cataneo was responsible for analysis and interpretation of data.and revised the manuscript critically. Erika Veruska Paiva Ortolan was responsible for the study conception and design, performed the interpretation of data and drafted the manuscript. Guilherme Lopes da Silveira performed the radiological analysis. Mariana Floriano Luiza Piva was responsible for acquisition of data, analysis and interpretation of data. Lucas da Matta Cucco was responsible for acquisition of data, analysis and interpretation of data. Maria Aparecida Marchesan Rodrigues was responsible for analysis and interpretation of data and revised the manuscript critically. © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Correlation Between Clinical Signs and High-Resolution Manometry Data in Children

Objectives: High-resolution manometry (HRM) is the gold standard for diagnosis of esophageal motility disorders. However, clinical signs associated with these disorders are non-specific, and it is difficult to correlate clinical signs with HRM data. The main objective of our study was to assess the positive predictive value (PPV) and negative predictive value (NPV) of each clinical sign, as well as their sensitivity and specificity in the diagnosis of esophageal motility disorders. Methods: This is a bicentric retrospective cohort study based on HRM data collected between May 2012 and May 2016. The studied symptoms were weight loss, feeding difficulties, swallowing disorders, dysphagia, food blockages, vomiting, gastro-esophageal reflux disease (GERD), belching, and respiratory symptoms. HRM data were analyzed according to the Chicago Classification (3.0). Results: In total, 271 HRM data were analyzed, of which 90.4% showed abnormal results. HRM was well tolerated in 91% of the cases. The most common esophageal motility disorder was ineffective esophageal motility (38%). Weight loss was significantly associated (p = 0.003) with an abnormal HRM with a 96% PPV. Conclusions: With non-specific clinical signs suggesting an esophageal motility disorder, weight loss was a predictive sign of abnormal HRM results. HRM was well tolerated in pediatric patients, and ineffective esophageal motility appears to be the most frequent motility disorder in our cohort, as already observed in adult patient studies. Address correspondence and reprint requests to Marine Juzaud, MD, MS, Service de pédiatrie multidisciplinaire, CHU La Timone, APHM, 264 Rue Saint Pierre, 13005 Marseille 05, Provence-Alpes-Côte d'Azur, France (e-mail: marine.juzaud@hotmail.fr). Received 23 March, 2018 Accepted 3 December, 2017 Conflicts of interest statement: All authors have no conflicts of interest relevant to this article to disclose. Financial disclosure Statement: All authors have no financial relationships relevant to this article to disclose. Funding source: All authors have no sources of funding to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Endoscopic Management of Duodenal Web

No abstract available

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Change in Prevalence of Family History During Long-term Follow-up of Pediatric-onset Inflammatory Bowel Disease Patients

Objectives: To prospectively study changes in prevalence of positive family history (FH+) in pediatric-onset inflammatory bowel disease (IBD) in contrast to previously published cross-sectional data. Methods: An observational cohort study was performed using a prospective pediatric-onset IBD database including 485 patients with disease duration ≥10yrs as of December 2016. Proband characteristics and FH+ were obtained at diagnosis and subsequently from the database, medical records and follow-up telephone interviews in 2006 and 2016. Results: Updated 2016 information was obtained from 322 (66%) patients and included in analysis with median follow-up of 18yrs (IQR 14, 26). Prevalence of FH+ increased from 13.7% at diagnosis to 26.6% at 20 years for first-degree relatives and from 38.5% to 52.2% for all relatives. At 20-year follow-up, an additional 10.0% of probands had a sibling, 6.1% had a parent, 1.9% had a grandparent, and 4.5% had a cousin diagnosed with IBD. FH+ at diagnosis was associated with greater risk for additional FH+ at 20 years (43% vs 22%, P 

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Congenital Portosystemic Shunts: Current Diagnosis and Management

Congenital porto-systemic shunts are increasingly recognized in several settings and at any age. The following are some of the most common presentations: prenatal ultrasound, neonatal cholestasis, incidental finding on abdominal imaging, or systemic complications such as unexplained cardiopulmonary or neurological disease, or the presence of liver nodules in a non-cirrhotic liver. The purpose of the present review is to summarize clinical presentation and current recommendations for management, and highlight areas of future research. Illustrative examples from the veterinary literature complement our current lack of knowledge of this rare malformation often masquerading as a multisystem disease. Address correspondence and reprint requests to Valérie A. McLin, MD, Swiss Pediatric Liver Center, Pediatric Gastroenterology, Hepatology and Nutrition Unit, University Hospitals Geneva and Geneva University, Geneva, Switzerland (e-mail: valerie.mclin@hcuge.ch). Received 12 July, 2018 Accepted 12 December, 2018 The authors report no conflicts of interest. © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Hepatic Lesions Associated with McCune Albright Syndrome

McCune Albright Syndrome (MAS) results from a GNAS gene mutation. It is associated with café-au-lait macules, fibrous dysplasia, and several endocrinopathies to include gonadotropin-independent precocious puberty, growth hormone excess, Cushing syndrome, thyroid disease, and renal phosphate wasting. It is recognised to be a rare cause of neonatal cholestasis. We describe the hepatic outcome of three children with MAS referred to a single national liver unit. All presented with high gamma-glutamyl transpeptidase cholestasis and hepatitis. Cholestasis resolved by one year; but hepatic inflammation persisted, and two children developed progressive atypical focal nodular hyperplasia and one developed hepatoblastoma. This the first reported malignant hepatic lesion associated with MAS. MAS should be considered part of the differential diagnosis of neonatal cholestasis and affected children should be closely monitored for the development of hepatic lesions with regular liver ultrasound and alpha fetoprotein level (AFP). Address correspondence and reprint requests to Lauren Johansen, MBBS (Hons), MRCPCH, Liver Unit, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, UK (e-mail: ljohansen@nhs.net). Received 20 October, 2018 Accepted 18 December, 2018 Conflicts of interest and source of funding: None declared © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Serum Calprotectin in Adolescents with Inflammatory Bowel Disease - A Pilot Investigation

Objectives: Fecal calprotectin (FC) is a well-integrated parameter in the monitoring of adolescent patients with inflammatory bowel disease (IBD). However, measurement of FC is limited by day-to-day-variation and by the feces' consistency. Furthermore, adolescents are often non-compliant to deliver fecal sampling leading to suboptimal monitoring. Consequently, we see the need of a substitute biomarker when measurement of FC fails and aimed to investigate serum calprotectin (SC) in adolescents with IBD. Methods: In cross sectional data from 19 UC patients

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Immediate Use of Continuous Positive Airway Pressure in Patients With Obstructive Sleep Apnea Following Transsphenoidal Pituitary Surgery: A Case Series

Background: Patients who undergo transsphenoidal pituitary resection have an elevated risk of obstructive sleep apnea (OSA) yet their outcomes and the safety of continuous positive airway pressure (CPAP) remains unclear. Our study objective was to determine the incidence of complications related to the use of early positive airway pressure following pituitary resection. Methods: We retrospectively identified all patients who underwent endoscopic transsphenoidal pituitary tumor resection between January 1, 2005 and March 24, 2016 at our institution, including those with diagnosed or suspected OSA. We compared characteristics and postoperative complications of OSA patients who did and did not receive CPAP postoperatively. Results: In total, 427 patients underwent transsphenoidal pituitary resection. Of these, 64 (15%) had OSA. Acromegaly was more common in patients with OSA (42% vs. 10%; P

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JNA Journal Club

No abstract available

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SNACC Is Moving and We Are Really Excited!

No abstract available

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Improving Severe Traumatic Brain Injury Observational Research: Not All Questions Need an RCT

No abstract available

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Physical Activity and Cardiovascular Risk among Kidney Transplant Patients

Purpose Research examining the relationship between physical activity and cardiovascular disease (CVD) risk factors among kidney transplant recipients (KTRs) is limited. Accordingly, we sought to: (1) describe the levels of physical activity (PA) in KTRs and (2) analyze the associations between PA levels and CVD risk factors in KTRs. Methods Baseline data from KTRs participants in a large multiethnic, multicenter trial (FAVORIT) were examined. PA was categorized in tertiles (low, moderate, high) derived from a modified PA summary score from the Yale Physical Activity Survey (YPAS). CVD risk factors were examined across levels of PA by ANOVA, Kruskal-Wallis rank test and hierarchical multiple regression. Results The 4,034 participants were 37% female; averaged 51.9 ± 9.4 years of age; 75% White, 97% with stage 2T-4T Chronic Kidney Disease and 20% with prevalent CVD. Participants in the "high" PA tertile reported more vigorous PA and walking, compared to participants in moderate and low tertiles (both p

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Women Experience the Same Ergogenic Response to Caffeine as Men

Purpose This study aimed to determine if 1) consumption of caffeine improves endurance cycling performance in women, and 2) sex differences exist in the magnitude of the ergogenic and plasma responses to caffeine supplementation. Methods Twenty-seven (11 women and 16 men) endurance-trained cyclists and triathletes participated in this randomized, double-blind, placebo-controlled, crossover study. Participants completed an incremental exercise test to exhaustion, two familiarization trials and two performance trials. Ninety minutes prior to the performance trials participants ingested opaque capsules containing either 3 mg·kg-1 body mass of anhydrous caffeine or a placebo. They then completed a set amount of work (75% of peak sustainable power output) in the fastest possible time. Plasma was sampled at baseline, pre- and post-exercise for caffeine. Strict standardization and verification of diet, hydration, training volume and intensity, and for women, contraceptive hormone phase was implemented. Results Performance time was significantly improved following caffeine administration in women (placebo: 3863±419s, caffeine: 3757±312s; p=0.03) and men (placebo: 3903±341s, caffeine: 3734±287s; p

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Quadriceps Impairment is Associated with Gait Mechanics in Young Adults with Obesity

Purpose Obesity influences gait and muscle function, which may contribute to knee osteoarthritis. The purpose of this study was to (1) compare gait biomechanics and quadriceps function between individuals with and without obesity, and (2) examine the association between quadriceps function and gait biomechanics. Methods 48 individuals with and 48 without obesity participated and were matched on age and sex. Gait biomechanics at standardized and self-selected speeds were used to assess peak vertical ground reaction force (vGRF), vertical loading rate (vLR), internal knee extension moment (KEM), peak knee flexion angle (KFA), knee flexion excursion (KFE), and knee joint stiffness. Quadriceps function was assessed using peak isometric strength (PT), early (RTD100) and late (RTD200) rate of torque development, and vastus lateralis cross sectional area (CSA) and echo intensity (EI). Results When normalized to fat-free mass, individuals with obesity had lower RTD100 (p=0.04) and RTD200 (p=0.02), but higher vastus lateralis CSA (p

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PHYSIOLOGICAL RESPONSES TO EXERCISE IN PEDIATRIC HEART TRANSPLANT RECIPIENTS

Introduction Pediatric heart transplant recipients (HTx) have reduced exercise capacity typically two-thirds of predicted values; the mechanisms of which are not fully understood. We sought to assess the cardiorespiratory responses to progressive exercise in HTx relative to controls matched for age, sex, body size, and work rate. Methods Fourteen HTx and matched controls underwent exercise stress echocardiography on a semi-supine cycle ergometer. Hemodynamics, left ventricular (LV) dimensions and volumes were obtained, and indexed to body surface area. Oxygen consumption (V[Combining Dot Above]O2) was measured and arteriovenous oxygen difference (a-vO2) was estimated using the Fick Principle. Results At rest, LV mass index (p=0.03) and volumes (p

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Exercise Training Prevents Doxorubicin-induced Mitochondrial Dysfunction of the Liver

PURPOSE Doxorubicin (DOX) is a highly effective chemotherapeutic agent used in the treatment of a broad spectrum of cancers. However, clinical use of DOX is limited by irreversible and dose-dependent hepatotoxicity. The liver is the primary organ responsible for the clearance of antineoplastic agents, and evidence indicates that hepatotoxicity occurs as a result of impaired mitochondrial efficiency during DOX metabolism. In this regard, exercise training is sufficient to improve mitochondrial function and protect against DOX-induced cytotoxicity. Therefore, the purpose of this study was to determine if short-term exercise preconditioning is sufficient to protect against DOX-induced liver mitochondrionopathy. METHODS Female Sprague-Dawley rats (4-6 months old) were randomly assigned to one of four groups: 1) sedentary, treated with saline; 2) sedentary, treated with DOX; 3) exercise trained, treated with saline; 4) exercise trained, treated with DOX. Exercise trained animals underwent 5 days of treadmill running habituation followed by 10 days of running for 60 min/day (30 m/min; 0% grade). Following the last training bout, exercise-trained and sedentary animals were injected with either DOX (20 mg/kg; i.p.) or saline. Two days following drug treatment the liver was removed and mitochondria were isolated. RESULTS DOX treatment induced mitochondrial dysfunction of the liver in sedentary animals, due to alterations in mitochondrial oxidative capacity, biogenesis, degradation, and protein acetylation. Furthermore, exercise preconditioning protected against DOX-mediated liver mitochondrionopathy, which was associated with maintenance of mitochondrial oxidative capacity and protein acetylation. CONCLUSION These findings demonstrate that endurance exercise training protects against DOX-induced liver mitochondrial dysfunction, which was attributed to modifications in organelle oxidative capacity and mitochondrial protein acetylation. Corresponding author: Ashley J. Smuder, Department of Exercise Science, University of South Carolina, Public Health Research Center, Room 227, 921 Assembly Street, Columbia, SC 29208. Email: smuder@mailbox.sc.edu J. Matthew Hinkley Present Address: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. ABM was supported by NIH T32 HD043730. CONFLICT OF INTEREST: No conflicts of interest, financial or otherwise, are declared by the authors. The results of the present study do not constitute endorsement by ACSM, and are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for publication: 30 December 2018. © 2019 American College of Sports Medicine

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Lack of consensus on the peri-operative management of patients with diabetes mellitus

imageNo abstract available

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Thromboprophylaxis in the obese surgical patient

No abstract available

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Intra-operative heart rate and postoperative outcomes – rowing against the tide?

No abstract available

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Noninvasive continuous arterial pressure monitoring with Clearsight during awake carotid endarterectomy: A prospective observational study

imageBACKGROUND Continuous noninvasive blood pressure (CNBP) measurement using the volume-clamp method is a less invasive alternative compared with invasive intra-arterial monitoring for awake patients during carotid endarterectomy (CEA) under regional anaesthesia. OBJECTIVE We investigated the agreement of blood pressure (BP) recorded with invasive and CNBP methods during awake CEA. DESIGN A prospective observational study for assessing agreement with Bland–Altman plots, agreement-tolerability indices (ATI), concordance and interchangeability. SETTING Azienda Ospedaliera Universitaria G. Martino, Messina, a University tertiary referral centre in Italy. PATIENTS In 30 consecutive patients, we recorded continuously ipsilateral invasive and noninvasive BPs, from 3 min before carotid cross-clamping to 5 min after unclamping. MAIN OUTCOME MEASURES Primary outcome was bias, 95% limits of agreement, ATI, concordance and interchangeability for mean arterial pressure (MAP). Secondary outcomes were agreements for systolic arterial pressure and diastolic arterial pressure. Tracking of changes was assessed with four-quadrant polar plots and the trend interchangeability method. Optimal bias was defined as 5 mmHg or less. RESULTS A total of 2672 invasive and CNBP paired measurements (93% of overall data) were analysed, with a median of 92 readings per patient [IQR 76 to 100]. Mean (SD) bias for MAP, systolic arterial pressure and DAP were −6.8 (6.7), −3.0 (9.7) and −9.0 (5.4) mmHg, respectively. The ATIs were 0.88, 0.95 and 0.71, respectively, where ATI of 1.0 or less and at least 2.0 defined acceptable, marginal and unacceptable agreements. The four-quadrant plot analysis for beat-to-beat differences showed concordance rates of 97.3%, 99.98% and 96.4%, respectively. Polar plot analysis showed 95% limits of agreement of −3 to 3, −2 to 2 and −2 to 2 mmHg respectively. Trend interchangeability method showed an interchangeability rate of 95% for MAP. CONCLUSION During CEA performed under regional anaesthesia, CNBP offers a less invasive approach for BP monitoring. We found acceptable agreement for MAP defined by an ATI of 0.88 and an excellent 95% global interchangeability rate. A suboptimal bias of 7 mmHg was found with CNBP for MAP.

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Development of a prediction model for postoperative pneumonia: A multicentre prospective observational study

imageBACKGROUND Postoperative pneumonia is associated with increased morbidity, mortality and costs. Prediction models of pneumonia that are currently available are based on retrospectively collected data and administrative coding systems. OBJECTIVE To identify independent variables associated with the occurrence of postoperative pneumonia. DESIGN A prospective observational study of a multicentre cohort (Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe database). SETTING Sixty-three hospitals in Europe. PATIENTS Patients undergoing surgery under general and/or regional anaesthesia during a 7-day recruitment period. MAIN OUTCOME MEASURE The primary outcome was postoperative pneumonia. Definition: the need for treatment with antibiotics for a respiratory infection and at least one of the following criteria: new or changed sputum; new or changed lung opacities on a clinically indicated chest radiograph; temperature more than 38.3 °C; leucocyte count more than 12 000 μl−1. RESULTS Postoperative pneumonia occurred in 120 out of 5094 patients (2.4%). Eighty-two of the 120 (68.3%) patients with pneumonia required ICU admission, compared with 399 of the 4974 (8.0%) without pneumonia (P 

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Six-minute walk test in pre-operative evaluation of patients for upper abdominal surgery

imageNo abstract available

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Intra-operative tachycardia is not associated with a composite of myocardial injury and mortality after noncardiac surgery: A retrospective cohort analysis

imageBACKGROUND Myocardial injury after noncardiac surgery (MINS) is a major contributor to peri-operative morbidity and mortality with a reported incidence of about 8%. Tachycardia increases myocardial oxygen demand, and decreases oxygen supply, and is therefore a potential cause of MINS. OBJECTIVE We tested the hypothesis that there is an association between intra-operative area above a heart rate (HR) of 90 bpm and a composite of MINS and in-hospital all-cause mortality. DESIGN Retrospective analyses. SETTING Major tertiary care hospital, Cleveland, USA. PATIENTS Adults having elective or nonelective noncardiac surgery and scheduled troponin monitoring during the first 3 postoperative days between 2010 and 2015. MAIN OUTCOME MEASURES All-or-none composite of myocardial injury (MINS), defined by a peak postoperative generation 4 troponin T concentration at least 0.03 ng ml−1, and in-hospital all-cause mortality. RESULTS Among 2652 eligible patients, 123 (4.6%) experienced MINS within 7 days after surgery and 6 (0.2%) died before discharge. Intra-operative area above HR more than 90 bpm was not associated with the all-or-none composite of MINS and in-hospital mortality, with an estimated odds ratio (95% confidence interval) of 0.99 (0.97 to 1.01) per 1 h bpm increase in area above HR more than 90 bpm. Secondary outcomes were also unrelated to the composite, with estimated odds ratios (98.3% confidence interval) of 0.99 (0.98 to 1.00) for area above HR more than 80, 0.98 (0.92 to 1.04) for area above HR more than 100 bpm, and 0.96 (0.88 to 1.05) for maximum HR. CONCLUSION There was no apparent association between various measures of tachycardia and a composite of MINS and death, a result that contradicts previously reported associations between other measures of intra-operative tachycardia and MINS/mortality.

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Postoperative pneumonia: Can this important complication be predicted and anticipated?

imageNo abstract available

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Relevance of peripheral cholinesterase activity on postoperative delirium in adult surgical patients (CESARO): A prospective observational cohort study

imageBACKGROUND The cholinergic system is considered to play a key role in the development of postoperative delirium (POD), which is a common complication after surgery. OBJECTIVES To determine whether peri-operative acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities are associated with the development of POD in in-hospital surgical patients, and raise hypotheses on cholinergic regulatory mechanisms in POD. DESIGN A prospective multicentre observational study by the Peripheral Cholinesterase-activity on Neurocognitive Dysfunctions in Surgical Patients (CESARO) study group. SETTING Nine German hospitals. PATIENTS Patients of at least 18 years of age scheduled for inpatient elective surgery for a variety of surgical procedures. A total of 650 patients (mean age 61.5 years, 52.8% male) were included. METHODS Clinical variables, and peripheral AChE and BuChE activities, were assessed throughout the peri-operative period using bedside point-of-care measurements (one pre-operative and two postoperative measurements). POD screening was conducted postoperatively for at least 24 h and up to the third postoperative day using a validated screening tool (nursing delirium screening scale). RESULTS In all, 179 patients (27.5%) developed POD within the early postoperative phase. There was a lower BuChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.07, P = 0.091), on postoperative day 1 (Cohen's r = 0.12, P = 0.003) and on postoperative day 2 (Cohen's r = 0.12, P = 0.002). In contrast, there was a significantly higher AChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.10, P = 0.012), on postoperative day 1 (Cohen's r = 0.11, P = 0.004) and on postoperative day 2 (Cohen's r = 0.13, P = 0.002). After adjusting for covariates in multiple logistic regression, a significant association between both BuChE and AChE activities and POD was not found. However, in the multivariable analysis using the Generalized Estimating Equation, cholinesterase activities showed that a decrease of BuChE activity by 100 U L−1 increased the risk of a delirium by approximately 2.1% (95% CI 1.6 to 2.8%) and for each 1 U g−1 of haemoglobin increase in AChE activity, there was a 1.4% (95% CI 0.6 to 2.2%) increased risk of POD. CONCLUSION Peri-operative peripheral cholinesterase activities may be related to the development of POD, but the clinical implications remain unclear. Further studies, in homogeneous patient groups with a strict protocol for measurement time points, are needed to investigate the relationship between cholinesterase activities and POD. TRIAL REGISTRATION www.clinicaltrials.gov. Identifier NCT01964274.

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Goal-directed therapy during transthoracic oesophageal resection does not improve outcome: Randomised controlled trial

imageBACKGROUND Goal-directed therapy (GDT) is expected to be of highest benefit in high-risk surgery. Therefore, GDT is recommended during oesophageal resection, which carries a high risk of postoperative complications. OBJECTIVES The aim of this study was to confirm the hypothesis that GDT during oesophageal resection improves outcome compared with standard care. DESIGN A randomised controlled study. SETTING Two Swedish university hospitals, between October 2011 and October 2015. PATIENTS Sixty-four patients scheduled for elective transthoracic oesophageal resection were randomised. Exclusion criteria included colonic interposition and significant aortic or mitral valve insufficiency. INTERVENTION A three-step GDT protocol included stroke volume optimisation using colloid boluses as assessed by pulse-contour analysis, dobutamine infusion if cardiac index was below 2.5 l min−1 m−2 and norepinephrine infusion if mean arterial blood pressure was below 65 mmHg. MAIN OUTCOME MEASURE The incidence of complications per patient at 5 and 30 days postoperatively as assessed using a predefined list. RESULTS Fifty-nine patients were available for analysis. Patients in the intervention group received more colloid fluid (2190 ± 875 vs. 1596 ± 759 ml, P 

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Orthostatic intolerance following hip arthroplasty: incidence, risk factors and effect on length of stay: A prospective cohort study

imageBACKGROUND Early postoperative mobilisation is important for enhanced recovery, but can be hindered by orthostatic intolerance, characterised by dizziness, nausea, vomiting, feeling of heat, blurred vision and ultimately syncope. Although the incidence of orthostatic intolerance following total hip arthroplasty has been identified, few studies have yet investigated potential risk factors for developing orthostatic intolerance after hip arthroplasty. OBJECTIVES The aim of this study was to assess the incidence of orthostatic intolerance on the first postoperative day after total hip arthroplasty, potential predisposing risk factors for developing orthostatic intolerance and its effect on length of stay. DESIGN A prospective observational study. SETTING Tertiary hospital, Auckland, New Zealand, May to September 2015. PATIENTS One hundred and seventeen consecutive patients undergoing unilateral total hip arthroplasty. Patients were excluded if they had revision surgery. MAIN OUTCOME MEASURES Incidence of orthostatic intolerance during mobilisation on the first postoperative day. Significant peri-operative risk factors for developing orthostatic intolerance were identified using logistic regression. Length of stay was compared between orthostatic intolerant and orthostatic tolerant patients using the Mann–Whitney U-test. RESULTS On the first postoperative day, 22% of patients failed mobilisation due to orthostatic intolerance. Factors independently associated with orthostatic intolerance were female sex; OR (95% CI), 3.11 (1.01 to 9.57), postoperative use of gabapentin; OR 3.55 (1.24 to 10.15) and high peak pain levels (≥5/10) during mobilisation; OR 4.05 (1.30 to 12.61). Overall, 78% of patients were correctly identified. The model was more accurate at predicting those who would not get orthostatic intolerance (89% correct), compared with those who did have orthostatic intolerance (39% correct). Length of stay was longer in patients with orthostatic intolerance (P = 0.019). CONCLUSION Orthostatic intolerance is common after total hip arthroplasty. Optimising pain control prior to mobilisation and limiting gabapentin use may modify the risk of developing postoperative orthostatic intolerance. Although personalised recovery pathways appear attractive, at present, the ability to predict at-risk individuals is still limited.

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Reply to: thromboprophylaxis in the obese surgical patient

No abstract available

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Peri-operative endothelial dysfunction in patients undergoing minor abdominal surgery: An observational study

imageBACKGROUND Myocardial injury after noncardiac surgery is common and associated with major adverse cardiac events. Surgery induces acute endothelial dysfunction, which might be central in the pathophysiology of myocardial injury; however, the relationship between surgical stress and endothelial function remains incompletely understood. OBJECTIVES This study aimed to assess the acute peri-operative changes in endothelial function after minor elective abdominal surgery. DESIGN A prospective, observational, single-centre study. SETTING A university hospital from February 2016 to January 2017. PATIENTS Sixty patients undergoing elective minor abdominal surgery. MAIN OUTCOME MEASURES The change in endothelial function, expressed as the reactive hyperaemia index (RHI), was assessed by non-invasive digital pulse tonometry. RHI, biomarkers of nitric oxide bioavailability and oxidative stress were assessed prior to and 4 h after surgery. RESULTS RHI decreased significantly from 1.93 [95% confidence interval (95% CI 1.78 to 2.09)] before surgery to 1.76 (95% CI 1.64 to 1.90), P = 0.03, after surgery. The nitric oxide production, L-arginine/asymmetric dimethylarginine, decreased significantly from a ratio of 213.39 (95% CI 188.76 to 241.2) to a ratio of 193.3 (95% CI 171.82 to 217.54), P = 0.03. Plasma biopterins increased significantly after surgery, while the ratio between tetrahydrobiopterin and dihydrobiopterin was unchanged. Total ascorbic acid decreased significantly after surgery (P 

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Anaesthesiology residents have no significant effect on anaesthesia or procedure times

imageNo abstract available

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Monitoring haemodynamic response to fluid-challenge in ICU: comparison of pressure recording analytical method and oesophageal Doppler: A prospective observational study

imageBACKGROUND The ability of the pressure recording analytical method (PRAM) in tracking change in cardiac output (ΔCO) after a fluid challenge in ICU needs to be evaluated with the most contemporary comparison methods recommended by experts. OBJECTIVE Our objective was to report the trending ability of PRAM in tracking ΔCO after a fluid challenge in ICU and to compare this with oesophageal Doppler monitoring (ODM). DESIGN Prospective, observational study. SETTING Hôpital Lariboisière and Hôpital Européen George Pompidou, Paris, France, from April 2016 to December 2017. PATIENTS Critically ill patients admitted to ICU with monitoring of CO monitored by ODM and invasive arterial pressure. INTERVENTION ΔCO after fluid challenge was simultaneously registered with ODM and PRAM connected to the arterial line. MAIN OUTCOME MEASURE Polar statistics (mean angular bias, radial limits of agreement and polar concordance rate) and clinical concordance evaluation (error grid and clinical concordance rate). Predictors of bias were determined. RESULTS Sixty-eight fluid challenge were administered in 49 patients. At the time of fluid challenge, almost all were mechanically ventilated (99%), with 85% receiving norepinephrine. Admission diagnosis was septic shock in 70% of patients. Patients had a Sequential Organ Failure Assessment score of 10 [7 to 12] and a median Simplified Acute Physiology Score II of 61 [49 to 69]. Relative ΔCO bias was 7.8° (6.3°) with radial limits of agreement of ±41.7°, polar concordance rate 80% and clinical concordance rate 74%. ΔCO bias was associated with baseline bias (P = 0.007). Baseline bias was associated with radial location of the arterial line (P = 0.03). CONCLUSION When compared with ODM, PRAM has insufficient performance to track ΔCO induced by fluid challenge in ICU patients. Baseline bias is an independent predictor of trending bias. TRIAL REGISTRATION IRB 00010254-2016-033.

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European paediatric anaesthesia e-learning platform pearls and challenges

No abstract available

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An analysis of results in a single-blinded, prospective randomized controlled trial comparing non-fixating versus self-fixating mesh for laparoscopic inguinal hernia repair

Abstract

Background

It remains unclear whether use of self-fixating mesh during laparoscopic inguinal hernia repair (LIHR) impacts postoperative quality of life (QoL). We hypothesize patients receiving self-fixating mesh during totally extraperitoneal (TEP) LIHR will report less pain and improved QoL compared to those receiving non-fixating mesh.

Methods

An IRB-approved, single-blinded randomized controlled trial was conducted. Patients with primary, unilateral inguinal hernias were randomized to receive either non-fixating (control) or self-fixating mesh. Clinical visits were conducted 3 weeks and 1 year after LIHR. A validated Surgical Outcomes Measurement System (SOMS) instrument was used to assess patients' QoL preoperatively and postoperatively along with Carolinas Comfort Scale (CCS) at 3 weeks and 1 year after surgery. Comparisons between self-fixating and non-fixating mesh groups were made using Chi-square, Wilcoxon rank-sum or independent samples t tests.

Results

Two hundred and seventy patients were enrolled (137 non-fixating vs 133 self-fixating). Preoperatively, there was no difference in mean age, BMI, or median hernia duration between groups (57.9 vs 56.6 years, p = 0.550; 26.1 vs 26.8, p = 0.534; 3.0 vs 3.0 months, p = 0.846). Median operative times (34 vs 34 min, p = 0.545) and LOS were similar. More patients in the non-fixating group received tacks (43 vs 19, p = 0.001). Patients receiving non-fixating mesh recorded better mean SOMS scores for the first 3 days following surgery (Day 1: p = 0.005; Day 2: p = 0.002; Day 3: p = 0.024, Table 1) indicating less pain. No differences in pain were seen 3 weeks or 1 year postoperatively. There were zero recurrences found during clinical follow-up in either of the groups.

Conclusions

Patients receiving self-fixating mesh report worse postoperative pain in the first 2–3 days than those receiving non-fixating mesh. The groups showed no differences across QoL metrics (SOMS and CCS) at 3 weeks or 1 year postoperatively. Self-fixating mesh does not appear to positively impact QoL after TEP LIHR.



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Using Infant Mortality Data to Improve Maternal and Child Health Programs: An Application of Statistical Process Control Techniques for Rare Events

Abstract

Introduction The infant mortality rate (IMR) in the United States remains higher than most developed countries. To understand this public health issue and support state public health departments in displaying and analyzing data in ways that support learning, states participating in the Collaborative Improvement and Innovation Network to Reduce Infant Mortality (IM CoIIN) created statistical process control (SPC) charts for rare events. Methods State vital records data on live births and infant deaths was used to create U, T and G charts for Kansas and Alaska, two states participating in the IM CoIIN who sought methods to more effectively analyze IMR for subsets of their populations with infrequent number of deaths. The IMR and the number of days and number of births between infant deaths was charted for Kansas Non-Hispanic black population and six Alaska regions for the time periods 2013–2016 and 2011–2016, respectively. Established empirical patterns indicated points of special cause variation. Results The T and G charts for Kansas and G charts for Alaska depict points outside the upper control limit. These points indicate special cause variation and an increased number of days and/or births between deaths at these time periods. Discussion T and G charts offer value in examining rare events, and indicate special causes not detectable by U charts or other more traditional analytic methods. When small numbers make traditional analysis challenging, SPC has potential in the MCH field to better understand potential drivers of improvements in rare outcomes, inform decision making and take interventions to scale.



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Downregulation of genes outside the deleted region in individuals with 22q11.2 deletion syndrome

Abstract

The 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent hemizygous deletions of chromosome 22q11.2. The phenotype of the syndrome is complex and varies widely among individuals. Little is known about the role of the different genes located in 22q11.2, and we hypothesized that genetic risk factors lying elsewhere in the genome might contribute to the phenotype. Here, we present the whole-genome gene expression data of 11 patients with approximately 3 Mb deletions. Apart from the hemizygous genes mapped to the 22q11.2 region, the TUBA8 and GNAZ genes, neighboring the deleted interval but in normal copy number, showed altered expression. When genes mapped to other chromosomes were considered in the gene expression analysis, a genome-wide dysregulation was observed, with increased or decreased expression levels. The enriched pathways of these genes were related to immune response, a deficiency that is frequently observed in 22q11.2DS patients. We also used the hypothesis-free weighted gene co-expression network analysis (WGCNA), which revealed the co-expression gene network modules with clear connection to mechanisms associated with 22q11.2DS such as immune response and schizophrenia. These findings, combined with the traditional gene expression profile, can be used for the identification of potential pathways and genes not previously considered to be related to the 22q11.2 deletion syndrome.



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The Transcriptional Regulator Hbx1 Affects the Expression of Thousands of Genes in the Aflatoxin-Producing Fungus Aspergillus flavus

In filamentous fungi, homeobox proteins are conserved transcriptional regulators described to control conidiogenesis and fruiting body formation. Eight homeobox (hbx) genes are found in the genome of the aflatoxin-producing ascomycete, Aspergillus flavus. While loss-of-function of seven of the eight genes had little to no effect on fungal growth and development, disruption of hbx1, resulted in aconidial colonies and lack of sclerotial production. Furthermore, the hbx1 mutant was unable to produce aflatoxins B1 and B2, cyclopiazonic acid and aflatrem. In the present study, hbx1 transcriptome analysis revealed that hbx1 has a broad effect on A. flavus gene expression, and the effect of hbx1 increases overtime, impacting more than five thousand protein-coding genes. Among the affected genes, those in the category of secondary metabolism (SM), followed by that of cellular transport, were the most affected. Specifically, regarding the effect of hbx1 on SM, we found that genes in 44 SM gene clusters where upregulated while 49 were downregulated in the absence of hbx1, including genes in the SM clusters responsible for the synthesis of asparasone, piperazine and aflavarin, all known to be associated with sclerotia. In addition, our study revealed that hbx1 affects the expression of other transcription factor genes involved in development, including the conidiation central regulatory pathway and flb genes.



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OCMA: Fast, Memory-Efficient Factorization of Prohibitively Large Relationship Matrices

Matrices representing genetic relatedness among individuals (i.e., Genomic Relationship Matrices, GRMs) play a central role in genetic analysis. The eigen-decomposition of GRMs (or its alternative that generates fewer top singular values using genotype matrices) is a necessary step for many analyses including estimation of SNP-heritability, Principal Component Analysis (PCA), and genomic prediction. However, the GRMs and genotype matrices provided by modern biobanks are too large to be stored in active memory. To accommodate the current and future "bigger-data", we develop a disk-based tool, Out-of-Core Matrices Analyzer (OCMA), using state-of-the-art computational techniques that can nimbly perform eigen and Singular Value Decomposition (SVD) analyses. By integrating memory mapping (mmap) and the latest matrix factorization libraries, our tool is fast and memory-efficient. To demonstrate the impressive performance of OCMA, we test it on a personal computer. For full eigen-decomposition, it solves an ordinary GRM (N = 10,000) in 55 sec. For SVD, a commonly used faster alternative of full eigen-decomposition in genomic analyses, OCMA solves the top 200 singular values (SVs) in half an hour, top 2,000 SVs in 0.95 hr, and all 5,000 SVs in 1.77 hr based on a very large genotype matrix (N = 1,000,000, M = 5,000) on the same personal computer. OCMA also supports multi-threading when running in a desktop or HPC cluster. Our OCMA tool can thus alleviate the computing bottleneck of classical analyses on large genomic matrices, and make it possible to scale up current and emerging analytical methods to big genomics data using lightweight computing resources.



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Suppressor Analysis Uncovers That MAPs and Microtubule Dynamics Balance with the Cut7/Kinesin-5 Motor for Mitotic Spindle Assembly in Schizosaccharomyces pombe

The Kinesin-5 motor Cut7 in Schizosaccharomyces pombe plays essential roles in spindle pole separation, leading to the assembly of bipolar spindle. In many organisms, simultaneous inactivation of Kinesin-14s neutralizes Kinesin-5 deficiency. To uncover the molecular network that counteracts Kinesin-5, we have conducted a genetic screening for suppressors that rescue the cut7-22 temperature sensitive mutation, and identified 10 loci. Next generation sequencing analysis reveals that causative mutations are mapped in genes encoding α-, β-tubulins and the microtubule plus-end tracking protein Mal3/EB1, in addition to the components of the Pkl1/Kinesin-14 complex. Moreover, the deletion of various genes required for microtubule nucleation/polymerization also suppresses the cut7 mutant. Intriguingly, Klp2/Kinesin-14 levels on the spindles are significantly increased in cut7 mutants, whereas these increases are negated by suppressors, which may explain the suppression by these mutations/deletions. Consistent with this notion, mild overproduction of Klp2 in these double mutant cells confers temperature sensitivity. Surprisingly, treatment with a microtubule-destabilizing drug not only suppresses cut7 temperature sensitivity but also rescues the lethality resulting from the deletion of cut7, though a single klp2 deletion per se cannot compensate for the loss of Cut7. We propose that microtubule assembly and/or dynamics antagonize Cut7 functions, and that the orchestration between these two factors is crucial for bipolar spindle assembly.



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Deciphering Hybrid Larch Reaction Norms Using Random Regression

The link between phenotypic plasticity and heterosis is a broad fundamental question, with stakes in breeding. We report a case-study evaluating temporal series of wood ring traits of hybrid larch (Larix decidua x L. kaempferi and reciprocal) in relation to soil water availability. Growth rings record the tree plastic responses to past environmental conditions, and we used random regressions to estimate the reaction norms of ring width and wood density with respect to water availability. We investigated the role of phenotypic plasticity on the construction of hybrid larch heterosis and on the expression of its quantitative genetic parameters. The data came from an intra-/interspecific diallel mating design between both parental species. Progenies were grown in two environmentally contrasted sites, in France. Ring width plasticity with respect to water availability was confirmed, as all three taxa produced narrower rings under the lowest water availability. Hybrid larch appeared to be the most plastic taxon as its superiority over its parental species increased with increasing water availability. Despite the low heritabilities of the investigated traits, we found that the expression of a reliable negative correlation between them was conditional to the water availability environment. Finally, by means of a complementary simulation, we demonstrated that random regression can be applied to model the reaction norms of non-repeated records of phenotypic plasticity bound by a family structure. Random regression is a powerful tool for the modeling of reaction norms in various contexts, especially perennial species.



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Medaka Population Genome Structure and Demographic History Described via Genotyping-by-Sequencing

Medaka is a model organism in medicine, genetics, developmental biology and population genetics. Lab stocks composed of more than 100 local wild populations are available for research in these fields. Thus, medaka represents a potentially excellent bioresource for screening disease-risk- and adaptation-related genes in genome-wide association studies. Although the genetic population structure should be known before performing such an analysis, a comprehensive study on the genome-wide diversity of wild medaka populations has not been performed. Here, we performed genotyping-by-sequencing (GBS) for 81 and 12 medakas captured from a bioresource and the wild, respectively. Based on the GBS data, we evaluated the genetic population structure and estimated the demographic parameters using an approximate Bayesian computation (ABC) framework. The genome-wide data confirmed that there were substantial differences between local populations and supported our previously proposed hypothesis on medaka dispersal based on mitochondrial genome (mtDNA) data. A new finding was that a local group that was thought to be a hybrid between the northern and the southern Japanese groups was actually an origin of the northern Japanese group. Thus, this paper presents the first population-genomic study of medaka and reveals its population structure and history based on chromosomal genetic diversity.



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The Regulation of Cbf1 by PAS Kinase Is a Pivotal Control Point for Lipogenesis vs. Respiration in Saccharomyces cerevisiae

PAS kinase 1 (Psk1) is a key regulator of respiration in Saccharomyces cerevisiae. Herein the molecular mechanisms of this regulation are explored through the characterization of its substrate, Centromere binding factor 1 (Cbf1). CBF1-deficient yeast displayed a significant decrease in cellular respiration, while PAS kinase-deficient yeast, or yeast harboring a Cbf1 phosphosite mutant (T211A) displayed a significant increase. Transmission electron micrographs showed an increased number of mitochondria in PAS kinase-deficient yeast consistent with the increase in respiration. Although the CBF1-deficient yeast did not appear to have an altered number of mitochondria, a mitochondrial proteomics study revealed significant differences in the mitochondrial composition of CBF1-deficient yeast including altered Atp3 levels, a subunit of the mitochondrial F1-ATP synthase complex. Both beta-galactosidase reporter assays and western blot analysis confirmed direct transcriptional control of ATP3 by Cbf1. In addition, we confirmed the regulation of yeast lipid genes LAC1 and LAG1 by Cbf1. The human homolog of Cbf1, Upstream transcription factor 1 (USF1), is also known to be involved in lipid biogenesis. Herein, we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro. Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose toward respiration and away from lipid biogenesis, while PAS kinase inhibits respiration in part through the inhibition of Cbf1/USF1.



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Dosage Compensation and Gene Expression of the X Chromosome in Sheep

Ohno's hypothesis predicts that the expression of the single X chromosome in males needs compensatory upregulation to balance its dosage with that of the diploid autosomes. Additionally, X chromosome inactivation ensures that quadruple expression of the two X chromosomes is avoided in females. These mechanisms have been actively studied in mice and humans but lag behind in domestic species. Using RNA sequencing data, we analyzed the X chromosome upregulation in sheep fetal tissues from day 135 of gestation under control, over or restricted maternal diets (100%, 140% and 60% of National Research Council Total Digestible Nutrients), and in conceptuses, juvenile, and adult somatic tissues. By computing the mean expression ratio of all X-linked genes to all autosomal genes (X:A), we found that all samples displayed some levels of X chromosome upregulation. The degrees of X upregulation were not significant (P-value = 0.74) between ovine females and males in the same somatic tissues. Brain, however, displayed complete X upregulation. Interestingly, the male and female reproduction-related tissues exhibited divergent X dosage upregulation. Moreover, expression upregulation of the X chromosome in fetal tissues was not affected by maternal diets. Maternal nutrition, however, did change expression levels of several X-linked genes, such as sex determination genes SOX3 and NR0B1. In summary, our results showed that X chromosome upregulation occurred in nearly all sheep somatic tissues analyzed, thus support Ohno's hypothesis in a new species. However, the levels of upregulation differed by different subgroups of genes such as those that are house-keeping and "dosage-sensitive".



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A Gene Expression Screen in Drosophila melanogaster Identifies Novel JAK/STAT and EGFR Targets During Oogenesis

The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) and epidermal growth factor receptor (EGFR) signaling pathways are conserved regulators of tissue patterning, morphogenesis, and other cell biological processes. During Drosophila oogenesis, these pathways determine the fates of epithelial follicle cells (FCs). JAK/STAT and EGFR together specify a population of cells called the posterior follicle cells (PFCs), which signal to the oocyte to establish the embryonic axes. In this study, whole genome expression analysis was performed to identify genes activated by JAK/STAT and/or EGFR. We observed that 317 genes were transcriptionally upregulated in egg chambers with ectopic JAK/STAT and EGFR activity in the FCs. The list was enriched for genes encoding extracellular matrix (ECM) components and ECM-associated proteins. We tested 69 candidates for a role in axis establishment using RNAi knockdown in the FCs. We report that the signaling protein Semaphorin 1b becomes enriched in the PFCs in response to JAK/STAT and EGFR. We also identified ADAM metallopeptidase with thrombospondin type 1 motif A (AdamTS-A) as a novel target of JAK/STAT in the FCs that regulates egg chamber shape. AdamTS-A mRNA becomes enriched at the anterior and posterior poles of the egg chamber at stages 6 to 7 and is regulated by JAK/STAT. Altering AdamTS-A expression in the poles or middle of the egg chamber produces rounder egg chambers. We propose that AdamTS-A regulates egg shape by remodeling the basement membrane.



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Using Maize Chromosome Segment Substitution Line Populations for the Identification of Loci Associated with Multiple Disease Resistance

Southern Leaf Blight (SLB), Northern Leaf Blight (NLB), and Gray Leaf Spot (GLS) caused by Cochliobolus heterostrophus, Setosphaeria turcica, and Cercospora zeae-maydis respectively, are among the most important diseases of corn worldwide. Previously, moderately high and significantly positive genetic correlations between resistance levels to each of these diseases were identified in a panel of 253 diverse maize inbred lines. The goal of this study was to identify loci underlying disease resistance in some of the most multiple disease resistant (MDR) lines by the creation of chromosome segment substitution line (CSSL) populations in multiple disease susceptible (MDS) backgrounds. Four MDR lines (NC304, NC344, Ki3, NC262) were used as donor parents and two MDS lines (Oh7B, H100) were used as recurrent parents to produce eight BC3F4:5 CSSL populations comprising 1,611 lines in total. Each population was genotyped and assessed for each disease in replicated trials in two environments. Moderate to high heritabilities on an entry mean basis were observed (0.32 to 0.83). Several lines in each population were significantly more resistant than the MDS parental lines for each disease. Multiple quantitative trait loci (QTL) for disease resistance were detected for each disease in most of the populations. Seventeen QTL were associated with variation in resistance to more than one disease (SLB/NLB: 2; SLB/GLS: 7; NLB/GLS: 2 and 6 to all three diseases). For most populations and most disease combinations, significant correlations were observed between disease scores and also between marker effects for each disease. The number of lines that were resistant to more than one disease was significantly higher than would be expected by chance. Using the results from individual QTL analyses, a composite statistic based on Mahalanobis distance (Md) was used to identify joint marker associations with multiple diseases. Across all populations and diseases, 246 markers had significant Md values. However further analysis revealed that most of these associations were due to strong QTL effects on a single disease. Together, these findings reinforce our previous conclusions that loci associated with resistance to different diseases are clustered in the genome more often than would be expected by chance. Nevertheless true MDR loci which have significant effects on more than one disease are still much rarer than loci with single disease effects.



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Fitness and Genomic Consequences of Chronic Exposure to Low Levels of Copper and Nickel in Daphnia pulex Mutation Accumulation Lines

In at least some unicellular organisms, mutation rates are temporarily raised upon exposure to environmental stress, potentially contributing to the evolutionary response to stress. Whether this is true for multicellular organisms, however, has received little attention. This study investigated the effects of chronic mild stress, in the form of low-level copper and nickel exposure, on mutational processes in Daphnia pulex using a combination of mutation accumulation, whole genome sequencing and life-history assays. After over 100 generations of mutation accumulation, we found no effects of metal exposure on the rates of single nucleotide mutations and of loss of heterozygosity events, the two mutation classes that occurred in sufficient numbers to allow statistical analysis. Similarly, rates of decline in fitness, as measured by intrinsic rate of population increase and of body size at first reproduction, were negligibly affected by metal exposure. We can reject the possibility that Daphnia were insufficiently stressed to invoke genetic responses as we have previously shown rates of large-scale deletions and duplications are elevated under metal exposure in this experiment. Overall, the mutation accumulation lines did not significantly depart from initial values for phenotypic traits measured, indicating the lineage used was broadly mutationally robust. Taken together, these results indicate that the mutagenic effects of chronic low-level exposure to these metals are restricted to certain mutation classes and that fitness consequences are likely minor and therefore unlikely to be relevant in determining the evolutionary responses of populations exposed to these stressors.



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Perturbations of Transcription and Gene Expression-Associated Processes Alter Distribution of Cell Size Values in Saccharomyces cerevisiae

The question of what determines whether cells are big or small has been the focus of many studies because it is thought that such determinants underpin the coupling of cell growth with cell division. In contrast, what determines the overall pattern of how cell size is distributed within a population of wild type or mutant cells has received little attention. Knowing how cell size varies around a characteristic pattern could shed light on the processes that generate such a pattern and provide a criterion to identify its genetic basis. Here, we show that cell size values of wild type Saccharomyces cerevisiae cells fit a gamma distribution, in haploid and diploid cells, and under different growth conditions. To identify genes that influence this pattern, we analyzed the cell size distributions of all single-gene deletion strains in Saccharomyces cerevisiae. We found that yeast strains which deviate the most from the gamma distribution are enriched for those lacking gene products functioning in gene expression, especially those in transcription or transcription-linked processes. We also show that cell size is increased in mutants carrying altered activity substitutions in Rpo21p/Rpb1, the largest subunit of RNA polymerase II (Pol II). Lastly, the size distribution of cells carrying extreme altered activity Pol II substitutions deviated from the expected gamma distribution. Our results are consistent with the idea that genetic defects in widely acting transcription factors or Pol II itself compromise both cell size homeostasis and how the size of individual cells is distributed in a population.



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Functional Analysis of a Putative Target of Spatially Varying Selection in the Menin1 Gene of Drosophila melanogaster

While significant effort has been devoted to investigating the potential influence of spatially varying selection on genomic variation, relatively little effort has been devoted to experimental analysis of putative variants or genes experiencing such selection. Previous population genetic work identified an amino acid polymorphism in the Mnn1 gene as one of the most strongly latitudinally differentiated SNPs in the genome of Drosophila melanogaster in the United States and Australia. Here we report the results of our transgenic analysis of this amino acid polymorphism. Genotypes carrying alternative Mnn1 alleles differed in multiple phenotypes in a direction generally consistent with phenotypic differences previously observed along latitudinal clines. These results support inferences from earlier population genomic work that this variant influences fitness, and support the idea that the alleles exhibiting clines may be likely to have pleiotropic effects that are correlated along the axes favored by natural selection.



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High Efficiency Targeting of Non-coding Sequences Using CRISPR/Cas9 System in Tilapia

The CRISPR/Cas9 has been successfully applied for disruption of protein coding sequences in a variety of organisms. The majority of the animal genome is actually non-coding sequences, which are key regulators associated with various biological processes. In this study, to understand the biological significance of these sequences, we used one or dual gRNA guided Cas9 nuclease to achieve specific deletion of non-coding sequences including microRNA and 3' untranslated region (UTR) in tilapia, which is an important fish for studying sex determination and evolution. Co-injection of fertilized eggs with single gRNA targeting seed region of miRNA and Cas9 mRNA resulted in indel mutations. Further, co-injection of fertilized eggs with dual gRNAs and Cas9 mRNA led to the removal of the fragment between the two target loci, yielding maximum efficiency of 11%. This highest genomic deletion efficiency was further improved up to 19% using short ssDNA as a donor. The deletions can be transmitted through the germline to the next generation at average efficiency of 8.7%. Cas9-vasa 3'-UTR was used to increase the efficiency of germline transmission of non-coding sequence deletion up to 14.9%. In addition, the 3'-UTR of the vasa gene was successfully deleted by dual gRNAs. Deletion of vasa 3'-UTR resulted in low expression level of vasa mRNA in the gonad when compared with the control. To summarize, the improved CRISPR/Cas9 system provided a powerful platform that can assist to easily generate desirable non-coding sequences mutants in non-model fish tilapia to discovery their functions.



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Nuclear Transcriptomes of the Seven Neuronal Cell Types That Constitute the Drosophila Mushroom Bodies

The insect mushroom body (MB) is a conserved brain structure that plays key roles in a diverse array of behaviors. The Drosophila melanogaster MB is the primary invertebrate model of neural circuits related to memory formation and storage, and its development, morphology, wiring, and function has been extensively studied. MBs consist of intrinsic Kenyon Cells that are divided into three major neuron classes (, α'/β' and α/β) and 7 cell subtypes (d, m, α'/β'ap, α'/β'm, α/βp, α/βs and α/βc) based on their birth order, morphology, and connectivity. These subtypes play distinct roles in memory processing, however the underlying transcriptional differences are unknown. Here, we used RNA sequencing (RNA-seq) to profile the nuclear transcriptomes of each MB neuronal cell subtypes. We identified 350 MB class- or subtype-specific genes, including the widely used α/β class marker Fas2 and the α'/β' class marker trio. Immunostaining corroborates the RNA-seq measurements at the protein level for several cases. Importantly, our data provide a full accounting of the neurotransmitter receptors, transporters, neurotransmitter biosynthetic enzymes, neuropeptides, and neuropeptide receptors expressed within each of these cell types. This high-quality, cell type-level transcriptome catalog for the Drosophila MB provides a valuable resource for the fly neuroscience community.



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iProteinDB: An Integrative Database of Drosophila Post-translational Modifications

Post-translational modification (PTM) serves as a regulatory mechanism for protein function, influencing their stability, interactions, activity and localization, and is critical in many signaling pathways. The best characterized PTM is phosphorylation, whereby a phosphate is added to an acceptor residue, most commonly serine, threonine and tyrosine in metazoans. As proteins are often phosphorylated at multiple sites, identifying those sites that are important for function is a challenging problem. Considering that any given phosphorylation site might be non-functional, prioritizing evolutionarily conserved phosphosites provides a general strategy to identify the putative functional sites. To facilitate the identification of conserved phosphosites, we generated a large-scale phosphoproteomics dataset from Drosophila embryos collected from six closely-related species. We built iProteinDB (https://www.flyrnai.org/tools/iproteindb/), a resource integrating these data with other high-throughput PTM datasets, including vertebrates, and manually curated information for Drosophila. At iProteinDB, scientists can view the PTM landscape for any Drosophila protein and identify predicted functional phosphosites based on a comparative analysis of data from closely-related Drosophila species. Further, iProteinDB enables comparison of PTM data from Drosophila to that of orthologous proteins from other model organisms, including human, mouse, rat, Xenopus tropicalis, Danio rerio, and Caenorhabditis elegans.



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A de Novo EDA-Variant in a Litter of Shorthaired Standard Dachshunds with X-Linked Hypohidrotic Ectodermal Dysplasia

In this study, we present a detailed phenotype description and genetic elucidation of the first case of X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund. This condition is characterized by partial congenital hypotrichosis, missing and malformed teeth and a lack of eccrine sweat glands. Clinical signs including dental radiographs and histopathological findings were consistent with ectodermal dysplasia. Pedigree analysis supported an X-recessive mode of inheritance. Whole-genome sequencing of one affected puppy and his dam identified a 1-basepair deletion within the ectodysplasin-A (EDA) gene (CM000039.3:g.54509504delT, c.458delT). Sanger sequencing of further family members confirmed the EDA:c.458delT-variant. Validation in all available family members, 37 unrelated shorthaired standard Dachshunds, 128 further Dachshunds from all other coat and size varieties and samples from 34 dog breeds revealed the EDA:c.458delT-variant to be private for this family. Two heterozygous females showed very mild congenital hypotrichosis but normal dentition. Since the dam is demonstrably the only heterozygous animal in the ancestry of the affected animals, we assume that the EDA:c.458delT-variant arose in the germline of the granddam or in an early embryonic stage of the dam. In conclusion, we detected a very recent de-novo EDA mutation causing X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund.



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Genetic Basis of Variation in Heat and Ethanol Tolerance in Saccharomyces cerevisiae

Saccharomyces cerevisiae has the capability of fermenting sugar to produce concentrations of ethanol that are toxic to most organisms. Other Saccharomyces species also have a strong fermentative capacity, but some are specialized to low temperatures, whereas S. cerevisiae is the most thermotolerant. Although S. cerevisiae has been extensively used to study the genetic basis of ethanol tolerance, much less is known about temperature dependent ethanol tolerance. In this study, we examined the genetic basis of ethanol tolerance at high temperature among strains of S. cerevisiae. We identified two amino acid polymorphisms in SEC24 that cause strong sensitivity to ethanol at high temperature and more limited sensitivity to temperature in the absence of ethanol. We also identified a single amino acid polymorphism in PSD1 that causes sensitivity to high temperature in a strain dependent fashion. The genes we identified provide further insight into genetic variation in ethanol and temperature tolerance and the interdependent nature of these two traits in S. cerevisiae.



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Domestication and Temperature Modulate Gene Expression Signatures and Growth in the Australasian Snapper Chrysophrys auratus

Identifying genes and pathways involved in domestication is critical to understand how species change in response to human-induced selection pressures, such as increased temperatures. Given the profound influence of temperature on fish metabolism and organismal performance, a comparison of how temperature affects wild and domestic strains of snapper is an important question to address. We experimentally manipulated temperature conditions for F1-hatchery and wild Australasian snapper (Chrysophrys auratus) for 18 days to mimic seasonal extremes and measured differences in growth, white muscle RNA transcription and hematological parameters. Over 2.2 Gb paired-end reads were assembled de novo for a total set of 33,017 transcripts (N50 = 2,804). We found pronounced growth and gene expression differences between wild and domesticated individuals related to global developmental and immune pathways. Temperature-modulated growth responses were linked to major pathways affecting metabolism, cell regulation and signaling. This study is the first step toward gaining an understanding of the changes occurring in the early stages of domestication, and the mechanisms underlying thermal adaptation and associated growth in poikilothermic vertebrates. Our study further provides the first transcriptome resources for studying biological questions in this non-model fish species.



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A Strategy To Exploit Surrogate Sire Technology in Livestock Breeding Programs

In this work, we performed simulations to develop and test a strategy for exploiting surrogate sire technology in animal breeding programs. Surrogate sire technology allows the creation of males that lack their own germline cells, but have transplanted spermatogonial stem cells from donor males. With this technology, a single elite male donor could give rise to huge numbers of progeny, potentially as much as all the production animals in a particular time period. One hundred replicates of various scenarios were performed. Scenarios followed a common overall structure but differed in the strategy used to identify elite donors and how these donors were used in the product development part. The results of this study showed that using surrogate sire technology would significantly increase the genetic merit of commercial sires, by as much as 6.5 to 9.2 years' worth of genetic gain compared to a conventional breeding program. The simulations suggested that a strategy involving three stages (an initial genomic test followed by two subsequent progeny tests) was the most effective of all the strategies tested. The use of one or a handful of elite donors to generate the production animals would be very different to current practice. While the results demonstrate the great potential of surrogate sire technology there are considerable risks but also other opportunities. Practical implementation of surrogate sire technology would need to account for these.



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Development of peak oxygen uptake from 11–16 years determined using both treadmill and cycle ergometry

Abstract

Purposes

To investigate the development of peak oxygen uptake ( \(\dot{\text{O}}_{2}\) ) assessed on both a treadmill and a cycle ergometer in relation with sex and concurrent changes in age, body mass, fat-free mass (FFM), and maturity status and to evaluate currently proposed 'clinical red flags' or health-related cut-points for peak \(\dot{\text{O}}_{2}\) .

Methods

Multiplicative multilevel modelling, which enables the effects of variables to be partitioned concurrently within an allometric framework, was used to analyze the peak \(\dot{\text{O}}_{2}\) s of 138 (72 boys) students initially aged 11–14 years and tested on three annual occasions. Models were founded on 640 (340 from boys) determinations of peak \(\dot{\text{O}}_{2}\) , supported by anthropometric measures and maturity status.

Results

Mean peak \(\dot{\text{O}}_{2}\) s were 11–14% higher on a treadmill. The data did not meet the statistical assumptions underpinning ratio scaling of peak \(\dot{\text{O}}_{2}\) with body mass. With body mass appropriately controlled for boys' peak \(\dot{\text{O}}_{2}\) s were higher than girls' values and the difference increased with age. The development of peak \(\dot{\text{O}}_{2}\) was sex-specific, but within sex models were similar on both ergometers with FFM the dominant anthropometric factor.

Conclusions

Data should not be pooled for analysis but data from either ergometer can be used independently to interpret the development of peak \(\dot{\text{O}}_{2}\) in youth. On both ergometers and in both sexes, FFM is the most powerful morphological influence on the development of peak \(\dot{\text{O}}_{2}\) . 'Clinical red flags' or health-related cut-points proposed without consideration of exercise mode and founded on peak \(\dot{\text{O}}_{2}\) in ratio with body mass are fallacious.



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The histone H4K20 methyltransferase PR-Set7 fine-tunes the transcriptional activation of Wingless signaling in Drosophila

Publication date: Available online 8 January 2019

Source: Journal of Genetics and Genomics

Author(s): Yun Yu, Long Liu, Xiaojiao Li, Xingjie Hu, Haiyun Song



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Open-and-Shut Case: An Uncommon Cause of GI Bleeding



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Sessile Serrated Polyps with Synchronous Conventional Adenomas Increase Risk of Future Advanced Neoplasia

Abstract

Background

Surveillance colonoscopy guidelines following adenomas or sessile serrated adenomas/polyps (SSPs) are based on pathology features known to be associated with risk of future colorectal cancer. A synchronous conventional adenoma may increase the malignant potential of SSP, but current guidelines do not address this combination of pathologies.

Aims

The aim was to assess the risk of advanced neoplasia after SSP with or without synchronous adenoma compared to that following a conventional adenoma.

Methods

An audit was conducted on colonoscopies performed between 2000 and 2014 as part of a surveillance program. Index colonoscopy findings were classified as: low-risk SSP and high-risk SSP (size ≥ 10 mm or with cytological dysplasia) with and without synchronous adenoma; high-risk adenoma and low-risk adenoma. Risk of advanced neoplasia was determined at subsequent surveillance colonoscopies.

Results

In total, 2157 patients had adenoma or SSP found at index colonoscopy—low-risk adenoma (40%), high-risk adenoma (54%) and SSP (4%). Synchronous adenomas were seen with 47% of SSP. The median follow-up was 50.3 months (interquartile range 28.1–79.3). Compared to an index finding of low-risk adenoma, index findings of high-risk adenoma, as well as SSP with synchronous adenoma, were independent predictors of future advanced neoplasia (high-risk adenoma: hazard ratio (HR) = 2.04 (95% CI 1.70–2.45); high-risk SSP + adenoma HR = 3.20 (95% CI 1.31–7.82); low-risk SSP + adenoma: HR = 2.20 (95% CI 1.03–4.68)).

Conclusions

Synchronous adenoma increases the risk of advanced neoplasia for SSP equivalent to that seen following high-risk adenoma. Guidelines for surveillance should take into account concurrent pathologies with SSP.



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Hepatic miR-181b-5p Contributes to Glycogen Synthesis Through Targeting EGR1

Abstract

Background/Aim

The miR-181 family plays an important role in the regulation of various cellular functions. However, whether miR-181b-5p mediates hepatic insulin resistance remains unknown. In this study, we investigated the effect of miR-181b-5p on the regulation of hepatic glycogen synthesis.

Methods

The miR-181b-5p levels in the livers of diabetic mice were detected by real-time PCR. The glycogen levels and AKT/GSK pathway activation were examined in human hepatic L02 cells and HepG2 cells transfected with miR-181b-5p mimic or inhibitor. The potential target genes of miR-181b-5p were evaluated using a luciferase reporter assay and Western blot analysis. EGR1-specific siRNA and pCMV-EGR1 were used to further determine the role of miR-181b-5p in hepatic glycogen synthesis in vitro. Hepatic inhibition of miR-181b-5p in mice was performed using adeno-associated virus 8 (AAV8) vectors by tail intravenous injection.

Results

The miR-181b-5p levels were significantly decreased in the serum and livers of diabetic mice as well as the serum of type 2 diabetes patients. Importantly, inhibition of miR-181b-5p expression impaired the AKT/GSK pathway and reduced glycogenesis in hepatocytes. Moreover, upregulation of miR-181b-5p reversed high-glucose-induced suppression of glycogenesis. Further analysis revealed that early growth response 1 (EGR1) was a downstream target of miR-181b-5p. Silencing of EGR1 expression rescued miR-181b-5p inhibition-reduced AKT/GSK pathway activation and glycogenesis in hepatocytes. Hepatic inhibition of miR-181b-5p led to insulin resistance in C57BL/6 J mice.

Conclusion

We demonstrated that miR-181b-5p contributes to glycogen synthesis by targeting EGR1, thereby regulating PTEN expression to mediate hepatic insulin resistance.



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Risk Factors for Postpartum Emergency Department Visits in an Urban Population

Abstract

Objectives To identify risk factors associated with urban postpartum emergency department utilization. Methods This case–control study included 100 matched pairs of postpartum women who had delivered at a large, integrated urban medical system in Bronx, New York, in 2012–2013, with the cases having had an emergency department visit within 42 days of delivery. The cases, identified utilizing administrative and billing data, were matched 1:1 with controls by labor unit, delivery mode and date, excluding nonviable pregnancies. The controls did not have a known postpartum emergency department visit. Variables were abstracted from administrative data and chart review, and included demographics, antenatal/intrapartum/postpartum complications and neonatal intensive care unit admission. Factors associated with puerperal emergency department use were identified via univariate and multivariable analyses. Results Following conditional logistic regression, primiparity [54% vs. 32%, aOR 5.91, 95% CI 2.34–14.91], public insurance [70% vs. 56%, aOR 4.22, 95% CI 1.60–11.12], weekend delivery [30% vs. 26%, aOR 7.61, 95% CI 1.15–52.43] and delivery-related complications [47% vs. 28%, aOR 2.95, 95% CI 1.16–7.51] were associated with an increased risk of postpartum emergency department use, while women of younger ages (17–24 years old) were less likely to have postpartum emergency department use [aOR 0.23, 95% CI 0.07–0.74]. Univariate analysis of individual events within the composite variables showed an association between gestational hypertension/pre-eclampsia and postpartum emergency department use [28% vs. 13% OR 2.60, 95% CI 1.26–5.39]. Psychiatric history, social instability, preterm delivery/neonatal intensive care unit admission, pre-existing medical/antepartum conditions and prolonged postpartum stay were not associated. Conclusions for Practice Delivery-related complications, delivery timing, and certain sociodemographic factors are identifiable risk factors for increased postpartum emergency department utilization. These may be targeted for development of interventions improving puerperal care and potentially preventing emergency department visits, which are costly to the health system and disruptive to the lives of women and their families.



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Comparison of the scavenging intensity, remineralization and residence time of 210Po and 210Pb at key zones (biotic, sediment-water and hydrothermal) along the East Pacific GEOTRACES transect

Publication date: March 2019

Source: Journal of Environmental Radioactivity, Volume 198

Author(s): John Niedermiller, Mark Baskaran

Abstract

The contrasting geochemical behavior of two long-lived progeny of 222Rn (daughter product of 226Ra), 210Po and 210Pb, provide valuable insights on the extent of recycling of biogenic particulate matter and their preferential removal from the water column. We collected and analyzed 135 water samples from six vertical profiles for 210Po and 210Pb as well as a suite of aerosol samples for 210Pb along the US GEOTRACES East Pacific Zonal Transect (GP16). Calculated atmospheric depositional flux of 210Pb from the measured 210Pb activity in aerosols exhibits an overall decrease from east to west along the cruise track. The inventories of 210Po and 210Pb and residence times in key zones that include biotic (upper 60 and 300 m), sediment-water (bottom 300 m) and volcanogenic (bottom 300 m at the East Pacific Rise (EPR) station) were calculated and compared. A comparison of inventories of 210Po and 210Pb in 500-m layers (maximum penetration depth of atmospherically-delivered 210Pb was reported to be upper < 500 m) for all stations indicates clearly discernable disequilibrium between total (= particulate + dissolved) 210Po and total 210Pb, with 210Po/210Pb activity ratios less than 0.95 or greater than 1.05, in 63% (26 out of 41) of the 500-m layers. The observed large variations in the 210Po/210Pb activity ratio (AR) in 500 m layers (range: 0.79–1.32) of the whole water column is by far the largest disequilibrium in open ocean water reported when integrated over 500 m depths. However, the whole water-column 210Po/210Pb AR, calculated from the inventory of total 210Po and total 210Pb, varied between 0.97 ± 0.02 and 1.06 ± 0.02 (except in the EPR site, with 1.09 ± 0.02), indicating at or near-equilibrium for the whole water column in all five deep water stations. This contrasts with earlier claims of gross disequilibrium between 210Po and 210Pb in water depths >1000 m and we contend that most of these observations do not take in to account the variable extent of redistribution of 210Po and 210Pb in the water column due to remineralization of biogenic particulate matter and preferential scavenging of 210Po over 210Pb. We observed intense scavenging of 210Po and 210Pb in the bottom 300 m of the EPR site (attributed to discharge of high amounts of dissolved and colloidal Fe and Mn from the hydrothermal vent) and lower scavenging in the upper and bottom 300 m at the most oligotrophic station (ST-36), indicating that the scavenging intensities in bottom waters are likely coupled to the surface waters.



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