Pediatric Critical Care Medicine

Epidemiology of Pediatric Severe Sepsis in Main PICU Centers in Southwest China Objectives: To estimate the prevalence, management, and outcomes of pediatric severe sepsis in the main PICUs in Southwest China. Design: A prospective, observational, and multicenter study. Setting: Eight PICUs in Southwest China with 19 (13–24) beds and 1,322 (1,066–1,452) annual admissions each. Patients: A total of 10,598 patients (29 d to 18 yr old) were consecutively admitted between September 1, 2016, and August 31, 2017. All patients were screened and evaluated for severe sepsis or septic shock. Of them, 10,353 patients were excluded due to incomplete data or not meeting the consensus criteria for severe sepsis or septic shock; 245 patients were included with complete data. Interventions: None. Measurements and Main Results: Finally, 245 patients who were diagnosed with severe sepsis or septic shock were included in the study, with an incidence rate of 2.3%. Of them, 64.0% of the enrolled patients were male with 80.8% being less than 5 years old and 60.8% being from rural areas. The respiratory system was the most common organ system in which dysfunction was observed (76.7%) as well as the most frequently infected site (37.6%). The primary therapies were antibiotics (99.0%), immunoglobulin (88.3%), mechanical ventilation (78.4%), vasoactive infusions (59.6%), and corticosteroids (46.1%). Among the 188 patients who had respiratory dysfunction, 173(92%) required mechanical ventilation and 39 (20.7%) met the criteria for pediatric acute respiratory distress syndrome. Seven of the patients with pediatric acute respiratory distress syndrome died (7/39, 17.9%). The median durations for mechanical ventilation and vasoactive medications were 123.5 hours (35.25–226.00 hr) and 2 days (1–5 d), respectively. Eighty-six percent of patients had multiple organ dysfunction syndrome at the point at which severe sepsis was recognized, and 31% had underlying conditions. The hospital mortality rate was 18.8%. Conclusions: This report is the first to present the prevalence, treatment, and outcomes of pediatric severe sepsis in the main PICU centers in Southwest China. The mortality rate remains high; therefore, improved clinical management and implementation of large-scale clinical trials are necessary to improve early diagnoses and treatment. Dr. Xu received support for article research from Chongqing Science and Technology Bureau. Drs. C. Xiao, S. Wang, Fang, Xu, S. Xiao, Li, Zhang, Luo, Jiang, Huang, Y. Chen, J. Chen, Yu, D. Ren, X. Ren, and Tang disclosed government work. Dr. H. Wang has disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: xufeng9899@163.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Barriers to Communication in a PICU: A Qualitative Investigation of Family and Provider Perceptions Objectives: Family and medical provider perceptions of communication barriers within the PICU are poorly understood. We designed a qualitative study to characterize the perspective of families and medical providers of critically ill children regarding communication barriers. The identified barriers may be used to direct efforts to improve communication. Design: Semi-structured interviews were conducted from August 2017 to January 2018. Interviews were audio recorded and professionally transcribed verbatim. Setting: A PICU at a tertiary care academic center. Patients: Forty-two families whose children were admitted to the PICU (excluding patients receiving end-of-life care or with protective services involvement) and 12 PICU staff members, including nurses, residents, fellows, and attending's. Interventions: None. Measurements and Main Results: An interprofessional team of a physician, nurse manager, and medical student coded the transcripts. Interviewing continued until thematic saturation was reached. Codes were organized into common themes using a modified constant comparative method. The families interviewed represented 16 previously healthy children, and 26 children with a chronic health condition. Staff interviewed included three residents, three fellows, three attending intensivists, and three nurses. Participants' perceptions and experiences of barriers to communication included the following: 1) Communication breakdowns related to coordination of care among several services, 2) Family-centered rounds are insufficient for effective communication, 3) Undervaluing the knowledge of families of children with chronic health conditions or special needs, and 4) Communication breakdowns occur across provider hand-offs. Theme 3 was identified by families, but not by providers. Conclusions: Families and medical providers both identified several barriers to communication. However, only families identified the barrier "Undervaluing the knowledge of families with chronically ill children." Future work should explore these barriers and the discrepancy in perception between providers and families to determine if there are interventions that improve both family satisfaction and patient care. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http:/journals.lww.com/pccmjournal). Supported, in part, by grant from the Yale School of Medicine Office of Student Research and the Yale School of Medicine Department of Pediatrics, Section of Critical Care. Mr. Greenway received funding from Yale School of Medicine, Office of Student Research and Yale School of Medicine, Department of Pediatrics, Section of Critical Care. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Kevin G. Couloures, DO, MPH, Department of Pediatrics, 333 Cedar Street, New Haven, CT 06520-8064. E-mail: kevin.couloures@yale.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Sedative and Analgesic Drug Rotation Protocol in Critically Ill Children With Prolonged Sedation. Evaluation of Implementation and Efficacy to Reduce Withdrawal Syndrome Objectives: The first aim of this study was to assess the implementation of a sedative and analgesic drug rotation protocol in a PICU. The second aim was to analyze the incidence of withdrawal syndrome, drug doses, and time of sedative or analgesic drug infusion in children after the implementation of the new protocol. Design: Prospective observational study. Setting: PICU of a tertiary care hospital between June 2012 and June 2016. Patients: All patients between 1 month and 16 years old admitted to the PICU who received continuous IV infusion of sedative or analgesic drugs for more than 4 days were included in the study. Interventions: A sedative and analgesic drug rotation protocol was designed. The level of sedation, analgesia, and withdrawal syndrome were monitored with validated scales. The relationship between compliance with the protocol and the incidence of withdrawal syndrome was studied. Measurements and Main Results: One-hundred pediatric patients were included in the study. The protocol was followed properly in 35% of patients. Sixty-seven percent of the overall cohort presented with withdrawal syndrome. There was a lower incidence rate of withdrawal syndrome (34.3% vs 84.6%; p < 0.001), shorter PICU length of stay (median 16 vs 25 d; p = 0.003), less time of opioid infusion (median 5 vs 7 d for fentanyl; p = 0.004), benzodiazepines (median 5 vs 9 d; p = 0.001), and propofol (median 4 vs 8 d; p = 0.001) in the cohort of children in which the protocol was followed correctly. Conclusions: Our results show that compliance with the drug rotation protocol in critically ill children requiring prolonged sedation may reduce the appearance of withdrawal syndrome without increasing the risk of adverse effects. Furthermore, it may reduce the time of continuous IV infusions for most sedative and analgesic drugs and the length of stay in PICU. Dr. Sanavia involved in patient recruitment, data collection, analysis and interpretation of data, and writing up of the article. Dr. Mencía involved in study design, analysis and interpretation of data, and drafting the article or revising it critically for important intellectual content. Dr. Lafever involved in data collection and translation. Dr. Solana involved in patient recruitment and data collection. Dr. Garcia involved in data collection. Dr. López-Herce involved in drafting the article or revising it critically for important intellectual content and final approval of the version to be published. Supported, in part, by Dodot Scholarship from the Spanish Pediatric Association. Maternal and Child Health and Development Network. RETICS Health Research Networks financed by the R + D + I PN 2008–2011, ISCIII (Health Institute Carlos III)—General Subdirectorate for Evaluation and Promotion of Research and the European Regional Development Fund, ef. RD16/0022/0007. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: eva.sanavia@hotmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Critical Trio Exome Benefits In-Time Decision-Making for Pediatric Patients With Severe Illnesses Objectives: Critical illnesses caused by undiagnosed genetic conditions are challenging in PICUs. Whole-exome sequencing is a powerful diagnostic tool but usually costly and often fail to arrive at a final diagnosis in a short period. We assessed the feasibility of our whole-exome sequencing as a tool to improve the efficacy of rare diseases diagnosis for pediatric patients with severe illness. Design: Observational analysis. Method: We employed a fast but standard whole-exome sequencing platform together with text mining-assisted variant prioritization in PICU setting over a 1-year period. Setting: A tertiary referral Children's Hospital in Taiwan. Patients: Critically ill PICU patients suspected of having a genetic disease and newborns who were suspected of having a serious genetic disease after newborn screening were enrolled. Interventions: None. Measurements and Main Results: Around 50,000 to 100,000 variants were obtained for each of the 40 patients in 5 days after blood sampling. Eleven patients were immediately found be affected by previously reported mutations after searching mutation databases. Another seven patients had a diagnosis among the top five in a list ranked by text mining. As a whole, 21 patients (52.5%) obtained a diagnosis in 6.2 ± 1.1 working days (range, 4.3–9 d). Most of the diagnoses were first recognized in Taiwan. Specific medications were recommended for 10 patients (10/21, 47.6%), transplantation was advised for five, and hospice care was suggested for two patients. Overall, clinical management was altered in time for 81.0% of patients who had a molecular diagnosis. Conclusions: The current whole-exome sequencing algorithm, balanced in cost and speed, uncovers genetic conditions in infants and children in PICU, which helps their managements in time and promotes better utilization of PICU resources. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Supported, in part, by the Ministry of Science and Technology, R.O.C., under grant number MOST 106-3114-B-002-009. Dr. Hwu's institution received funding from Ministry of Science and Technology. Miss. Chen disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: ncleentu@ntu.edu.tw ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Epidemiology of Clinically Relevant Bleeding in Critically Ill Adolescents Objectives: The epidemiology of clinically relevant bleeding in critically ill adolescents, particularly those who are at high risk of venous thromboembolism, is unclear. In preparation for a randomized clinical trial of pharmacologic prophylaxis against venous thromboembolism, we characterized the epidemiology of clinically relevant bleeding in critically ill adolescents. Design: Post hoc analysis of data from a pediatric multicenter observational study of venous thromboembolism. Setting: Six PICUs. Patients: Adolescents 13–17 years old who received cardiac or pulmonary support for at least 48 hours were eligible. Those admitted with venous thromboembolism or receiving therapeutic anticoagulation were excluded. Interventions: None. Measurements and Main Results: Adolescents (n = 88) were followed daily for the development of any bleeding event. The severity of the event was categorized based on the definitions by the International Society on Thrombosis and Haemostasis. The frequency of clinically relevant bleeding was 29.5% (95% CI, 20.3–40.2%) or 3.7 events (95% CI, 2.5–5.4 events) per 100 patient-days. Adolescents with venous thromboembolism were more likely to develop clinically relevant bleeding (hazard ratio, 2.06; 95% CI, 1.08–3.94). Age was negatively associated with clinically relevant bleeding (hazard ratio for every 1-year increase in age: 0.68; 95% CI, 0.58–0.79). In contrast, predicted risk of mortality (hazard ratio for every 0.10 increase in risk: 1.35; 95% CI, 1.05–1.74) and admission for trauma or surgery (hazard ratio: 2.04; 95% CI, 1.21–3.44) were positively associated with clinically relevant bleeding. The association of clinically relevant bleeding with medications, interventions, or laboratory tests, including mechanical ventilation and pharmacologic prophylaxis with anticoagulation, did not reach statistical significance. Adolescents with clinically relevant bleeding stayed in the hospital longer than those without clinically relevant bleeding. Conclusions: Clinically relevant bleeding is common in critically ill adolescents who are at high risk of venous thromboembolism. Admission for trauma or surgery can be used to stratify the risk of clinically relevant bleeding in these adolescents. Supported, in part, by grant from the American Heart Association Award Number 14CRP20490002 to Dr. Faustino. It was also made possible by Clinical and Translational Science Award grant number UL1 RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research to Dr. Shabanova, and an unrestricted grant support from Layla's Dream to Dr. Polikoff. For information regarding this article, E-mail: Matthew.Pinto@wmchealth.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Functional Status Scale: Cross-Cultural Adaptation and Validation in Brazil Objective: The goal of the present study was to perform a cross-cultural adaptation and clinical validation of the Functional Status Scale for use in the Brazilian population. Design: Cross-cultural adaptation study followed by a cross-sectional validation study. Setting: Single-center PICU at a hospital in Porto Alegre, Brazil. Patients: Children and adolescents of both sexes, 1 month and under 18 years old, who had been treated at the PICU. Interventions: The cross-cultural adaptation consisted of the following stages: translation, synthesis of the translated versions, back translations, synthesis of the back translations, committee review, and pretesting. For the clinical validation stage, the Brazilian Functional Status Scale was applied within 48 hours after discharge from the PICU. The Brazilian Functional Status Scale's reliability and validity properties were tested. Measurements and Main Results: A total of 314 patients were evaluated. Median age was 24 months (7.0–105.0 mo), 54.1% were males, and their overall functional score was 9 ± 2.8. The Brazilian Functional Status Scale demonstrated excellent interobserver reliability, with an intraclass correlation coefficient of 0.98, and κ coefficients between 0.716 and 1.000 for the functional domains, which indicated good to excellent agreement. Using the Bland-Altman method, we confirmed low variability among the evaluator's responses (0.93 to –1.06 points). Regarding the Brazilian Functional Status Scale's content validity, there was a correlation between length of PICU stay (r = 0.378; p < 0.001) and time on invasive mechanical ventilation (r = 0.261; p < 0.05), and the test could discriminate between groups with different comorbidity levels (p < 0.001). Conclusions: The Functional Status Scale has been culturally adapted and validated for use in Brazil and is now available for use in the assessment of functionality in Brazilian children and adolescents. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Supported, in part, by grants from the Higher Education Improvement Coordination (CAPES). The authors have disclosed that they do not have any potential conflicts of interest. This work was performed at the Hospital da Criança Santo Antônio, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS), Brazil. For information regarding this article, E-mail: gabi.apereira@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

The Base Deficit, International Normalized Ratio, and Glasgow Coma Scale (BIG) Score, and Functional Outcome at Hospital Discharge in Children With Traumatic Brain Injury Objectives: To examine the association of the base deficit, international normalized ratio, and Glasgow Coma Scale (BIG) score on emergency department arrival with functional dependence at hospital discharge (Pediatric Cerebral Performance Category ≥ 4) in pediatric multiple trauma patients with traumatic brain injury. Design: A retrospective cohort study of a pediatric trauma database from 2001 to 2018. Setting: Level 1 trauma program at a university-affiliated pediatric institution. Patients: Two to 17 years old children sustaining major blunt trauma including a traumatic brain injury and meeting trauma team activation criteria. Interventions: None. Measurements and Main Results: Two investigators, blinded to the BIG score, determined discharge Pediatric Cerebral Performance Category scores. The BIG score was measured on emergency department arrival. The 609 study patients were 9.7 ± 4.4 years old with a median Injury Severity Score 22 (interquartile range, 12). One-hundred seventy-one of 609 (28%) had Pediatric Cerebral Performance Category greater than or equal to 4 (primary outcome). The BIG constituted a multivariable predictor of Pediatric Cerebral Performance Category greater than or equal to 4 (odds ratio, 2.39; 95% CI, 1.81–3.15) after adjustment for neurosurgery requirement (odds ratio, 2.83; 95% CI, 1.69–4.74), pupils fixed and dilated (odds ratio, 3.1; 95% CI, 1.49–6.38), and intubation at the scene or referral hospital (odds ratio, 2.82; 95% CI, 1.35–5.87) and other postulated predictors of poor outcome. The area under the BIG receiver operating characteristic curve was 0.87 (0.84–0.90). Using an optimal BIG cutoff less than or equal to 8, sensitivity and negative predictive value for functional dependence at discharge were 93% and 96%, respectively, compared with a sensitivity of 79% and negative predictive value of 91% with Glasgow Coma Scale less than or equal to 8. In children with Glasgow Coma Scale 3, the BIG score was associated with brain death (odds ratio, 2.13; 95% CI, 1.58–2.36). The BIG also predicted disposition to inpatient rehabilitation (odds ratio, 2.26; 95% CI, 2.17–2.35). Conclusions: The BIG score is a simple, rapidly obtainable severity of illness score that constitutes an independent predictor of functional dependence at hospital discharge in pediatric trauma patients with traumatic brain injury. The base deficit, international normalized ratio, and Glasgow Coma Scale score may benefit Trauma and Neurocritical care programs in identifying ideal candidates for traumatic brain injury trials within the therapeutic window of treatment. Presented, in part, as oral presentations at the: 1) Trauma Association of Canada meeting, Toronto, ON, Canada, February 23, 2018; and 2) Pediatric Academic Societies meeting, Toronto, ON, Canada, May 6, 2018. Drs. Davis, Hochstadter, and Schuh conceived the study and wrote the protocol. Dr. Davis supervised data collection by Drs. Hochstadter and Daya. Mr. Stephens performed the data analysis. Drs. Davis, Hochstadter, and Schuh drafted the article and Drs. Davis, Hochstadter, Daya, Kulkarni, Wales, and Schuh contributed substantially to its revision. All authors take responsibility for the article as a whole. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Adrienne Davis, MD, MSc, FRCPC, Division of Pediatric Emergency Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. E-mail: adrienne.davis@sickkids.ca ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass Objectives: Cardiopulmonary bypass–induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants. Design: Single-center prospective observational cohort pilot study. Setting: Pediatric cardiac ICU at a tertiary children's hospital. Patients: Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion. Intervention: None. Measurements and Main Results: Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2–4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2–4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R2 = 0.43; p = 0.008). Conclusions: Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes. The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government. Dr. Krispinsky is a military service member. This work was prepared as part of his official duties. Title 17 U.S.C. 105 provides that "Copyright protection under this title is not available for any work of the U.S. Government." Title 17 U.S.C. 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Supported, in part, by grants from Vanderbilt University Medical Center. Dr. Stark is supported by a grant from the National Institute of General Medical Sciences (K08 GM117367). Dr. Krispinsky disclosed government work. Dr. Stark's institution received funding from the National Institutes of Health (NIH), and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: luke.t.krispinsky.mil@mail.mil Address requests for reprints to: Fred S. Lamb, MD, PhD, Pediatric Critical Care, Vanderbilt Children's Hospital, 2200 Children's Way, 5111 Doctors' Office Tower, Nashville, TN 37232. E-mail: fred.s.lamb@vanderbilt.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Current Epidemiology of Vocal Cord Dysfunction After Congenital Heart Surgery in Young Infants Objectives: Surgery of the aortic arch poses risk of recurrent laryngeal nerve injury due to the anatomic proximity and can manifest as vocal cord dysfunction after surgery. We assessed risk factors for vocal cord dysfunction and calculated surgical procedure associated rates in young infants after congenital heart surgery. Design: Cross section analysis. Setting: Forty-four children's hospitals reporting administrative data to Pediatric Health Information System. Participants: Cardiac surgical patients less than or equal to 90 days old and discharged between January 2004 and June 2014. Interventions: None. Measurements and Main Results: Overall, 2,319 of 46,567 subjects (5%) had vocal cord dysfunction, increasing from 4% to 7% over the study period. Of those with vocal cord dysfunction, 75% had unilateral partial paralysis. Vocal cord dysfunction was significantly more common in newborn infants (74%), those with aortic arch procedures (77%) and with greater surgical complexity. Rates of vocal cord dysfunction ranged from 0.7% to 22.4% across surgical procedure groups. Vocal cord dysfunction was significantly associated with greater use of: prolonged mechanical ventilation (53% vs 40%), diaphragmatic plication (3% vs 1%), feeding tube use (32% vs 8%), surgical airways (4% vs 2%), and prolonged length of stay (44 vs 21 d). Vocal cord dysfunction testing increased significantly over the study (6–14 %), and vocal cord dysfunction diagnosis increased almost two-fold (odds ratio, 1.9; 95% CI, 1.7–2.1) comparing the last to first study quarters with the increase in vocal cord dysfunction diagnosis occurring predominately in surgeries to the aortic arch supported by cardiopulmonary bypass. However, aortic procedures without cardiopulmonary bypass and nonaortic arch procedures were common surgeries accounting for 27% and 23% of vocal cord dysfunction cases despite low overall vocal cord dysfunction rates (3.7% and 2.6%). Conclusions: Vocal cord dysfunction complicated all cardiac surgical procedures among infants including those without aortic arch involvement. Increased efforts to determine appropriate indications for prevention, screening and treatment of vocal cord dysfunction among young infants after congenital heart surgery are needed. This work was performed at the University of Utah. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http:/journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Susan.Bratton@hsc.utah.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Anemia at Discharge From PICU: A Bicenter Descriptive Study Objective: To determine the prevalence and risk markers of anemia at PICU discharge. Design: Bicenter retrospective cohort study. Setting: Two multidisciplinary French PICUs. Patients: All children admitted during a 5-year period, staying in the PICU for at least 2 days, and for whom a hemoglobin was available at PICU discharge. Interventions: None. Measurements and Main Results: Patient, admission, and PICU stay characteristics were retrospectively collected in the electronic medical records of each participating PICU. Anemia was defined according to the World Health Organization criteria. Among the 3,170 patients included for analysis, 1,868 (58.9%) were anemic at discharge from PICU. The proportion of anemic children differed between age categories, whereas the median hemoglobin level did not exhibit significant variations according to age. After multivariate adjustment, anemia at PICU admission was the strongest predictor of anemia at PICU discharge, and the strength of this association varied according to age (interaction). Children anemic at PICU admission had a reduced risk of anemia at PICU discharge if transfused with RBCs during the PICU stay, if less than 6 months old, or if creatinine level at PICU admission was low. Children not anemic at PICU admission had an increased risk of anemia at PICU discharge if they were thrombocytopenic at PICU admission, if they had higher C-reactive protein levels, and if they received plasma transfusion, inotropic/vasopressor support, or mechanical ventilation during the PICU stay. Conclusions: Anemia is frequent after pediatric critical illness. Anemia status at PICU admission defines different subgroups of critically ill children with specific prevalence and risk markers of anemia at PICU discharge. Further studies are required to confirm our results, to better define anemia during pediatric critical illness, and to highlight the causes of post-PICU stay anemia, its course, and its association with post-PICU outcomes. This work was performed at the Hôpital Universitaire Jeanne de Flandre, Service de Réanimation Pédiatrique 2, Avenue Eugène Avinée, 59037 Lille Cedex, France, and Hôpital Universitaire Femme Mère Enfant, Hospices Civils de Lyon, Service de Réanimation Pédiatrique, 59, Boulevard Pinel, 69677 Lyon-Bron, France. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: pierre.demaret@chc.be ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Environmental Research

Correction to: Bioaccumulation of Zinc and Copper in Tissues of Chicken Fed Corn Grain Irrigated with Different Water Regimes The article listed above was initially published with incorrect first author name and incomplete acknowledgments.

Which Water Sources Do People Revert to in Times of War? Evidence from the Sana'a Basin, Yemen Abstract Current war in Yemen affects the lives of Yemenis, their properties, and basic needs through several impacts and damages on fuel, electricity, and water systems. This paper investigates how this war has affected the people's main water sources. The war impact framework developed in this study is the combination of difference-in-difference (DID) and Human Rights to Water and Sanitation (HRWS) framework, as so far there are no tools to gage the impact of wars on people's choices of water sources. The availability, accessibility, and prices of water keep unstable. Decentralized systems of water and energy showed more stability than public-centralized systems. The majority of families relied on the public water and electricity systems before the war. Now, while the war is ongoing the public water networks and electricity grids serve not more than 10% of families. Solar energy has become the first energy source. Rainwater started to be collected as secondary water source. Getting water and energy through renewable sources is accepted and supported by locals. Many people are willing to continue using these new sources. This study verifies the importance of renewable resources transition to achieve secure sustainable water management.

Effects of Co-occurring Species Present in Swine Lagoons on Adsorption of Copper on Eggshell Abstract There is a significant interest in mitigating copper from swine lagoons. Adsorptive removal of copper using eggshells was proposed to be an effective approach. Most of the previous research on the adsorption of copper was focused on single and binary metals. However, in swine lagoons, copper always co-occurs with acetate, ammonia, and zinc. Hence, in this research, adsorption of copper (0–150 mg L−1) on eggshells was studied in the presence of different concentrations (low, medium, and high) of acetate (250, 500, and 1000 mg L−1) ammonia (250, 500, and 1000 mg L−1), and zinc (25, 50, and 100 mg L−1), for the first time. Results indicated that at highest concentrations, adsorption was negatively affected (< 20%) by acetate and zinc. Ammonia, however, was found to enhance copper adsorption (30%) presumably by formation of ternary complexes. Considering their easy availability, eggshells appear to be promising and a practical solution for copper abatement in lagoons. Graphical Abstract

A Comparison of Some Interpolation Techniques for Determining Spatial Distribution of Nitrogen Compounds in Groundwater Abstract The aim of the study was to analyse spatial variability of selected parameters of subsurface waters in the area of approximately 10 ha, located in the valley of the Ciemięga River in the village of Snopków, near Lublin, Poland. For the purpose of this study, nine sections were delimited, each with four points of collecting groundwater. In the groundwater samples, there were measured \({\text{NH}}_{4}^{ + }\) , \({\text{NO}}_{3}^{-} ,\) and \({\text{NO}}_{2}^{-}\) . Due to the small number of samples, the analysis was limited to deterministic interpolation methods. The following methods were compared using leave-one-out cross-validation procedure: triangulation, inverse distance weighting, radial base function, and modified Shepard's method. The methods which proved to be optimal were used to create spatial variability maps of the analysed parameters. Spatial interpolation and visualization of the results were performed in Surfer ver.16, and other calculations were conducted using R software.

Assessment of the Petroleum Oil Degradation Capacity of Indigenous Bacterial Species Isolated from Petroleum Oil-Contaminated Soil Abstract Petroleum hydrocarbons are highly toxic to plants, animals, and humans and are carcinogenic effects to plants, animals, and humans. The present study is focused to enhance the degradation of petroleum hydrocarbons using potential indigenous bacterial isolates. Bacteria were isolated from different petroleum oil-contaminated sites and characterized. Bacterial growth was evaluated under different physico-chemical parameters. The petroleum hydrocarbon degradation potentiality was assessed using GC–MS analysis. Forty-nine bacterial isolates were screened; only three isolates (ALK-14, ALK-16, and ALK-23) have good potential to degrade petroleum hydrocarbons and were identified as Alcaligenes species ALK-14, Bacillus methylotrophicus ALK-16, and Enterobacter species ALK-23, respectively, on the basis of morphology, biochemical characterization, and 16S rRNA sequencing. Optimum growth of Alcaligenes species ALK-14, Bacillus methylotrophicus ALK-16, and Enterobacter species ALK-23 occurred at pH 7, 6, and 6, respectively. Petroleum oil concentration found suitable for growth of selected bacterial isolates Alcaligenes species ALK-14, Bacillus methylotrophicus ALK-16, and Enterobacter species ALK-23 were 4%, 8%, and 4% (v/v), respectively. Among different nitrogen sources, ammonium nitrate was found suitable source for the maximum growth of Alcaligenes species ALK-14, Bacillus methylotrophicus ALK-16 at the concentration of 0.15 and 0.2%, respectively, and sodium nitrate for Enterobacter species ALK-23 at the concentration of 0.2%. All bacterial isolates showed maximum growth at 30 °C temperature. Synergistic effect on the growth of bacterial isolates under favourable conditions increased up to 11–28%. GC–MS analysis indicated that the hydrocarbon compounds in the range of C20–C44 were present in petrol. Maximum hydrocarbon degradation by Alcaligenes species ALK-14, Bacillus methylotrophicus ALK-16, and Enterobacter species ALK-23 was 11.65%, 8.11%, and 5.59%, respectively. The degradation of docosane 11-decyl, hexatriacontane, and eicosane by Alcaligenes species ALK-14 was 100%, 60%, and 48.8%, respectively. The degradation of docosane 11-decyl by, Bacillus methylotrophicus ALK-16, was 80%. Degradation of hexatriacontane by Enterobacter species ALK-23 was 31%. Further understanding of the metabolic processes of these organisms on crude oil hydrocarbons degradation will increase possibilities to develop strategies for removing crude oil pollutants from oil-impacted environments.

The Potential Impact of Underwater Exhausted CO 2 from Innovative Ships on Invertebrate Communities Abstract Liquefied natural gas (LNG) powered ships equipped with an underwater exhaust system to reduce the ship's water resistance could form a future generation of energy-efficient ships. The potential consequences of the underwater exhaust gas to the local ecosystems are still unknown. Especially, the CO2 levels may locally exceed estimated future global levels. The present study exposes marine communities to a wide range of CO2dosages, resulting in pH 8.6–5.8 that was remained for 49 days. We found that the zooplankton and benthic community were adversely affected by high CO2 exposure levels. In detail, (1) between pH 6.6 and 7.1 polychaete worms became the dominating group of the benthic community and their larvae dominated the zooplankton group. (2) Due to the reduced grazing pressure and the flux of nutrients from decaying organic material planktonic microalgae (phytoplankton) stared blooming at the highest exposure level. The periphyton (fouling microalgae) community was not able to take advantage under these conditions. (3) Marine snails' (periwinkle) shell damage and high mortality were observed at pH < 6.6. However, the growth of the surviving periwinkles was not directly related to pH, but was positively correlated with the availability of periphyton and negatively correlated with the polychaete worm density that most likely also used the periphyton as food source. Our result indicates that the impact of underwater exhaust gasses depends on various factors including local biological and abiotic conditions, which will be included in future research.

Assessment of the Potential of Indole-3-Acetic Acid Producing Bacteria to manage Chemical Fertilizers Application Abstract Indole-3-acetic acid (IAA) has a vital role in stimulation of root growth and nutrients acquisition from soil. The study was conducted to isolate rhizospheric (R) and endophytic (E) IAA producer bacteria from the rhizosphere soil and surface sterilized root of wheat, and evaluate the effects of isolates to managing of chemical fertilizers application. For this, we examined the influence of different chemical fertilizer application rates (40, 60, 80 and 100%) coupled with R (Bacillus toyonensis) and E (Pseudomonas mosselii) IAA producer bacteria on wheat growth. Results indicated that supplementing 80% of the recommended chemical fertilizers rate with E isolates resulted in increase of wheat growth indices, which were similar to 100%-fertilizer need without bacterial inoculant. It seems that application of reduced chemical fertilizers integrated with IAA producer bacteria can positively affect the plant growth and led to decrease of chemical fertilizers application. Then optimal condition for IAA release was determined by P. mosselii and B. toyonensis. Results revealed that optimal growth medium conditions for isolates defined to be at l-tryptophan concentration of 3.0 mg mL−1 at 96 h of incubation and 32 °C by spectrophotometry. Increase in l-tryptophan concentration (> 3.0 mg m−1) significantly decreased the IAA production. These results could be attributed to a possible inhibition towards the indigenous (and/or exogenous) soil microbial population by the higher concentrations of l-tryptophan. Glucose used as carbon source, gave the most IAA production (22.9 μg mL−1) in E isolate. About R isolate use of sucrose in the medium culture stimulates IAA production.

Alkaline Sustained-Release Material Based on In Situ Manganese Removal Technique of Groundwater Abstract To improve the pH of groundwater for in situ manganese removal, we prepared high-performance and long-life alkali sustained-release materials (ASRMs) from calcium oxide (CaO) and cement (CEM) by a physical mixing method. The ASRMs were tested by alkali-releasing experiments under dynamic conditions and filtration experiments. Surface microstructures were characterized using scanning electron microscopy and energy-dispersive spectrometry. ASRMs exhibited high alkali-releasing performance and effective pH controllability. The optimal matching conditions were flow rate of 5.0 ml/min, solid–liquid ratio of 13.5 g/l, and CaO:CEM weight ratio of 1:20. Under the influence of flow velocity, initial dosage and raw material ratio, the Elovich equation well fitted alkali release with correlation coefficients above 0.982476. The release kinetic equation of ASRMs was determined on MATLAB. In these conditions, the ASRMs could release well and maintain the aqueous pH over 9.5, with a long releasing life of 10 days. This study can be referred to for practical application of this technology into groundwater restoration.

Release of Nutrients and Trace Elements from Wood-, Agricultural Residue- and Manure-Based Biochars Abstract Biochar has been used in many applications as a remediation material, but less attention has been paid to the potential release of various soluble components that may alter the effectiveness of the remediation process. Here, we report the release of nutrients, trace elements, anions and cations from 36 types of biochars. A batch-style experiment was performed by mixing biochar and water at a mass ratio of 1:75. Elevated concentrations of these components were observed in the majority of the solutions mixed with the biochars. No significant differences were observed between low-temperature (low-T, 300 °C) and high-temperature (high-T, 600 °C) biochars in terms of NO3−, Cl−, Na+, Ca2+, Fe, Cu, PO4-P, NH3-N, and K+ concentrations (P < 0.05). Agricultural residue biochars released significantly less Cl−, Na+, Mn, Ca2+, and K+ than manure-based biochars. The observation of nutrients and metal ions in solution was supported by the results of scanning electron microscope/energy-dispersive X-ray (SEM/EDX) analysis. The release of elevated concentrations of anions, cations, trace elements, and nutrients may affect receiving water bodies after the application of biochar.

Bioaccumulation of Zinc and Copper in Tissues of Chicken Fed Corn Grain Irrigated with Different Water Regimes Abstract Water scarcity in agriculture sector enforces farmers to apply urban waste water without considering its pollutant effects on the environment. The aim of present research was to observe the effect of sewage, canal and ground water on accumulation of zinc (Zn) and copper (Cu) in different parts of corn plants and also in tissues of chicken that were reared on grains of corn crop in two growing seasons, spring and autumn during 2016. Representative samples of water, soil, grains and different chicken parts were assayed for Zn and Cu contents. There were higher concentrations of Zn (8.97–11.47 mg/kg) and Cu (14.73–15.45 mg/kg) in sewage water irrigated soil compared with other sources of water. In spring season, the highest concentration of zinc (5.28 mg/kg) and copper (2.65 mg/kg) was found in grains of Sadaf variety at sewage water treatment. In autumn season, maximum level of zinc (0.38 mg/kg) was found in grains of Sadaf variety at sewage water treatment and copper (3.60 mg/kg) was found in grains of MMRI variety at sewage water treatment. Similarly the group of chickens that consumed the grains raised with sewage water showed higher concentrations of Zn and Cu in their all body parts. However, Cu in contrast to Zn was found above the permissible limits in selected chicken parts due to irrigation with sewage water showing the transferability of this metal threatening the health issues. The values of transfer factor for Zn were greater than Cu. Target hazard quotient (THQ) was also calculated to estimate the potential consumer health risk of Zn and Cu contamination from consumption of selected chicken parts (liver, breast meat and gizzard) and the THQ values for both Cu and Zn were < 1 indicating that the consumption of these chicken edibles was safe for human. However, this study can only be regarded as preliminary since there is a dire need for more comprehensive study for the public awareness to combat health issues.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Otolaryngology

Hypermethylation of DcR1, DcR2, DR4, DR5 gene promoters and clinical significance in tongue carcinoma  Available Online 02 July 2019  Yong Zhou, ShuCan Zheng, QingHua Luo, XuYao Huang, Yong Zhou, ZhaoHui Li

  

Elsevier
American Journal of Otolaryngology
Available online 2 July 2019
In Press, Accepted ManuscriptWhat are Accepted Manuscript articles?
American Journal of Otolaryngology
Hypermethylation of DcR1, DcR2, DR4, DR5 gene promoters and clinical significance in tongue carcinoma
Author links open overlay panelYongZhouaShuCanZhengaQingHuaLuobXuYaoHuangaYongZhoucZhaoHuiLia
a
Department of stomatology, Affiliated Guangzhou Huadu Hospital of Guangdong Medical University, China
b
Department of medical imaging, Affiliated Guangzhou Huadu Hospital of Guangdong Medical University, China
c
Department of surgery, Affiliated Guangzhou Huadu Hospital of Guangdong Medical University, China
Received 9 March 2019, Available online 2 July 2019.

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https://doi.org/10.1016/j.amjoto.2019.07.002Get rights and content
Abstract
Objective
Tongue squamous cell carcinoma (TSCC) is one of the most common malignancies in the oral cavity, and its incidence and mortality have been constantly increasing these years. A large number of tumor suppressor genes are involved in the development of the TSCC and it has been reported that the aberrant hypermethylation of tumor suppressor genes may play a key role in the process of the TSCC. In this study, we sought to analyze the association of methylation of DcR1, DcR2, DR4 and DR5 gene promoters and clinical significance in the TSCC to evaluate association between methylation of DcR1, DcR2, DR4 and DR5 gene and Clinical Significance in tongue squamous cell carcinoma.

Methods
Methylation-specific PCR(MSP) was used to analyze the methylation of the promoters of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptors in 45 TSCC cases. Real-Time PCR was used to detect the expression of the DcR1, DcR2, DR4 and DR5 gene.

Results
All the four genes (DcR1, DcR2, DR4 and DR5) showed different methylation of promoters in TSCC, while methylation of these promoters in paired adjacent normal tissues were almost undetectable. Patients with high methylation index were diagnosed at younger age when compared with the ones with low methylation index. DcR1 and DR4 hypermethylation was correlated significantly with patients' TNM stage.

Conclusions
Methylation of DcR1, DcR2,DR4 and DR5 promoters are found in TSCC and may associate with its occurrence and development. Taking the reversibility of methylation into account，methylation is a potential targeted therapy of TSCC.

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© 2019 Published by Elsevier Inc.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Prostaglandins & Other Lipid Mediators

A novel mPGES-1 inhibitor alleviates inflammatory responses by downregulating PGE2 in experimental models Publication date: October 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 144 Author(s): Hwi-Ho Lee, YoonHyoung Moon, Ji-Sun Shin, Jeong-Hun Lee, Tae-Woo Kim, Changyoung Jang, Changmin Park, Juhee Lee, Younghoon Kim, Younggwan Kim, Oliver Werz, Boyoung Y. Park, Jae Yeol Lee, Kyung-Tae Lee Abstract We previously reported the strong inhibitory potency of N-phenyl-N'-(4- benzyloxyphenoxycarbonyl)-4-chlorophenylsulfonyl hydrazide (PBCH) on lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) production in macrophages. Herein, we characterized PBCH as a microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor and evaluated its anti-inflammatory effects using in vivo experimental models. PBCH inhibited PGE2production in various activated cells in addition to inhibiting the mPGES-1 activity. In the ear edema and paw edema rat models, PBCH significantly reduced ear thickness and paw swelling, respectively. Besides, in adjuvant-induced arthritis (AIA) rat model, PBCH decreased paw swelling, plasma rheumatoid factor (RF), and receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. Furthermore, while PBCH reduced the plasma prostaglandin E metabolite (PGEM) levels, it did not affect the plasma levels of prostacyclin (PGI2) and thromboxane A2 (TXA2). Our data suggest that PBCH downregulates PGE2 production by interfering with the mPGES-1 activity, thus reducing edema and arthritis in rat models. Graphical abstract

Prostaglandin E2 and an EP4 receptor agonist inhibit LPS-Induced monocyte chemotactic protein 5 production and secretion in mouse cardiac fibroblasts via Akt and NF-κB signaling Publication date: October 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 144 Author(s): Timothy D. Bryson, Jacob Ross, Edward Peterson, Pamela Harding Abstract Background Prostaglandin E2 (PGE2) signals through 4 separate G-protein coupled receptor sub-types to elicit a variety of physiologic and pathophysiological effects. We have previously reported that mice lacking the EP4 receptor in the cardiomyocytes develop heart failure with a phenotype of dilated cardiomyopathy. Also, these mice have increased levels of chemokines, like MCP-5, in their left ventricles. We have recently reported that overexpression of the EP4 receptor could improve cardiac function in the myocardial infarction model. Furthermore, we showed that overexpression of EP4 had an anti-inflammatory effect in the whole left ventricle. It has also been shown that PGE2 can antagonize lipopolysaccharide-induced secretion of chemokines/cytokines in various cell types. We therefore hypothesized that PGE2 inhibits lipopolysaccharide (LPS)-induced MCP-5 secretion in adult mouse cardiac fibroblasts via its EP4 receptor. Methods and results Our hypothesis was tested using isolated mouse adult ventricular fibroblasts (AVF) treated with LPS. Pre-treatment of the cells with PGE2 and the EP4 agonist CAY10598 resulted in reductions of the pro-inflammatory response induced by LPS. Specifically, we observed reductions in MCP-5 secretion. Western blot analysis showed reductions in phosphorylated Akt and IκBα indicating reduced NF-κB activation. The anti-inflammatory effects of PGE2 and EP4 agonist signaling appeared to be independent of cAMP, p-44/42, or p38 pathways. Conclusion Exogenous treatment of PGE2 and the EP4 receptor agonist blocked the pro-inflammatory actions of LPS. Mechanistically, this was mediated via reduced Akt phosphorylation and inhibition of NF-κB.

Enhancement by HSP90 inhibitor of PGD2-stimulated HSP27 induction in osteoblasts: Suppression of SAPK/JNK and p38 MAP kinase Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): Woo Kim, Haruhiko Tokuda, Tetsu Kawabata, Kazuhiko Fujita, Go Sakai, Daiki Nakashima, Junko Tachi, Gen Kuroyanagi, Rie Matsushima-Nishiwaki, Kumiko Tanabe, Takanobu Otsuka, Hiroki Iida, Osamu Kozawa Abstract Heat shock protein (HSP) 90 that is ubiquitously expressed in various tissues is a major molecular chaperone. We have previously demonstrated that prostaglandin D2 (PGD2), a bone remodeling factor, elicits the expression of HSP27, a small HSP, through stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of HSP90 in the PGD2-stimulated HSP27 induction and the underlying mechanism in MC3T3-E1 cells. Onalespib, an inhibitor of HSP90, significantly enhanced the PGD2-stimulated HSP27 induction. In addition, geldanamycin, another HSP90 inhibitor, potentiated the HSP27 induction. Both onalespib and geldanamycin markedly amplified the PGD2-induced phosphorylation of SAPK/JNK and p38 MAP kinase. SP600125, an inhibitor of SAPK/JNK, and SB203580, an inhibitor of p38 MAP kinase, suppressed the amplification by onalespib of the PGD2-stimulated HSP27 induction. These results strongly suggest that HSP90 plays a negative role in the HSP27 induction stimulated by PGD2 in osteoblasts, and that the inhibitory effect of HSP90 is mediated through the regulation of SAPK/JNK and p38 MAP kinase.

mPGES-1 as a new target to overcome acquired resistance to gefitinib in non-small cell lung cancer cell lines Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): Erika Terzuoli, Filomena Costanza, Valerio Ciccone, Marina Ziche, Lucia Morbidelli, Sandra Donnini Abstract Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as gefitinib are standard treatment of non-small cell lung cancer (NSCLC), but resistance often occurs. This study demonstrates that NSCLC cells resistant to gefitinib (GR cells) displayed a significantly higher microsomal prostaglandin E synthase-1 (mPGES-1) expression and activity than parental cells. Overexpression of mPGES-1/prostaglandin E-2 (PGE-2) signaling in GR cells was associated with acquisition of mesenchymal and stem-like cell properties, nuclear EGFR translocation and tolerance to cisplatin. mPGES-1 inhibition reduced mesenchymal and stem-like properties, and nuclear EGFR translocation in GR cells. Consistently, inhibition of mPGES-1 activity enhanced sensitivity to cisplatin and responsiveness to gefitinib in GR cells. We propose the mPGES-1/PGE-2 signaling as a potential target for treating aggressive and resistant lung cancers.

Seasonal expressions of COX-1, COX-2 and EP4 in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus) Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): Yu Wang, Yuchen Yao, Chunjiao Zhang, Yuanyuan Guo, Haolin Zhang, Yingying Han, Zhengrong Yuan, Qiang Weng Abstract Prostaglandins (PGs) play a pivotal role in uterine reproductive process including maternal recognition of pregnancy, cell proliferation, and myometrium contractions in mammals. In this study, we investigated the immunolocalizations and expression levels of Prostaglandin E2 synthases cyclo-oxygenase (COX)-1 and COX-2, as well as one of PGE2 receptor subtypes 4 (EP4) in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus) during the breeding and non-breeding seasons. Histologically, the thickness of endometrium: myometrium ratio in the uteri of the breeding season was higher than that of the non-breeding season. The immunostainings of COX-1, COX-2 and EP4 were observed in stromal cells, glandular cells and myometrium cells in the breeding and non-breeding seasons. The protein and mRNA expression levels of COX-1, COX-2 and EP4 were higher in the uteri of the breeding season than those of in the non-breeding season. The mean mRNA levels of COX-1, COX-2 and EP4 were positively correlated with uterine weights. In addition, the PGE2 concentration of uterine tissues as well as plasma PGE2, 17β-estradiol, progesterone, LH and FSH levels were also significantly higher in the breeding season compared to those of the non-breeding season. These results suggested that PGE2 might play an important autocrine or paracrine role in the regulation of seasonal changes in the uterine functions of the wild Daurian ground squirrels during the breeding and non-breeding seasons.

Formyl-peptide receptor 2 suppresses proliferation, migration and invasion in human extravillous trophoblastic cells Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): Shenzhi Zhao, Tingting Liao, Tong Zhou, Xianping Huang, Huiqiu Xiang, Jiajia Chen, Zhangye Xu Abstract Although FPR2 receptor is distributed in the endometrium and placenta, its function in human extravillous trophoblastic (TEV-1) cells still remains enigmatic. In this study, overexpression of FPR2 was performed in TEV-1 cells. Then, CCK8 transwell and wound healing assays were used to assess the cell proliferation, migration and invasion, respectively. The results showed that FPR2 overexpression significantly inhibited proliferation, invasion and migration in TEV-1 cells. In addition, FPR2 overexpression significantly decreased mRNA and protein levels of integrin-linked kinase (ILK), nuclear factor-kappa B (NF--κB), matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF) in TEV-1 cells. These findings indicated that FPR2 overexpression alters proliferation, migration and invasion in human extravillous trophoblastic cellsthrough the ILK/NF-κB signaling pathway; ideal FPR2 levels are important for TEV-1 cells functions.

Respective contribution of cytosolic phospholipase A2α and secreted phospholipase A2 IIA to inflammation and eicosanoid production in arthritis Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): Anne-Claire Duchez, Luc H. Boudreau, Gajendra S. Naika, Matthieu Rousseau, Nathalie Cloutier, Tania Levesque, Michael H. Gelb, Eric Boilard Abstract Phospholipase A2s (PLA2) play a key role in generation of eicosanoids. Cytosolic PLA2α (cPLA2α) is constitutively expressed in most cells, whereas IIA secreted PLA2 (sPLA2-IIA) is induced during inflammation and is present at high levels in the synovial fluid of rheumatoid arthritis patients. In mice, both cPLA2α and sPLA2-IIA have been implicated in autoimmune arthritis; however, the respective contribution of these two enzymes to the pathogenesis and production of eicosanoids is unknown. We evaluated the respective role of cPLA2α and sPLA2-IIA with regard to arthritis and eicosanoid profile in an in vivo model of arthritis. While arthritis was most severe in mice expressing both enzymes, it was abolished when both cPLA2α and sPLA2-IIA were lacking. cPLA2α played a dominant role in the severity of arthritis, although sPLA2-IIA sufficed to significantly contribute to the disease. Several eicosanoids were modulated during the course of arthritis and numerous species involved sPLA2-IIA expression. This study confirms the critical role of PLA2s in arthritis and unveils the distinct contribution of cPLA2α and sPLA2-IIA to the eicosanoid profile in arthritis.

Do arachidonic acid metabolites affect apoptosis in bovine endometrial cells with silenced PPAR genes? Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): A.A. Szczepańska, M. Łupicka, A.J. Korzekwa Abstract Peroxisome proliferator-activated receptors (PPARs) are expressed in bovine uterus, and their agonists are arachidonic acid (AA) metabolites. We hypothesised that silencing of PPAR genes in bovine endometrial stromal cells (ESC) would change the intracellular signalling through PPAR and affect apoptosis after cell treatment with different AA metabolites. The study's aims are detection of apoptosis and examining the influence of prostaglandins and leukotrienes on apoptosis occurring in physiological ESC and cells with silenced PPAR (α, δ, and γ) genes. Silencing the PPARα and PPARδ genes in cells resulted in increased DNA fragmentation and mRNA and protein expression of caspase (CASP) -3 and -8 (P < 0.05). Neither DNA fragmentation nor the mRNA and protein expression of CASP3 and -8 in cells with silenced PPARγ gene were changed compared to physiological cells (P > 0.05). Among PPARs, PPARα and PPARδ appear to inhibit apoptosis, and AA metabolites, as PPAR agonists, modify this process in bovine ESC.

Emerging class of omega-3 fatty acid endocannabinoids & their derivatives Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): Josephine E. Watson, Justin S. Kim, Aditi Das Abstract Cannabinoid receptor activation is involved in homeostatic regulation of the body. These receptors are activated by cannabinoids, that include the active constituents of Cannabis sativa, as well as endocannabinoids (eCBs). The eCBs are endogenously synthesized from the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). The consumption of omega-3 fatty acids shifts the balance towards a higher proportion of omega-3 eCBs, whose physiological functions warrants further investigation. Herein, we review the discovery of omega-3 fatty acid derived eCBs that are generated from long chain omega-3 PUFAs - docosahexaenoyl ethanolamide (DHA-EA or synaptamide), docosahexanoyl-glycerol (DHG), eicosapentaenoyl ethanolamide (EPA-EA) and eicosapentanoylglycerol (EPG). Furthermore, we outline the lesser known omega-3 eCB-like molecules that arise from the conjugation of omega-3 fatty acids with neurotransmitters serotonin and dopamine - DHA-serotonin (DHA-5HT), DHA-dopamine (DHA-DA), EPA-serotonin (EPA-5HT) and EPA-dopamine (EPA-DA). Additionally, we describe the role of omega-3 eCBs and their derivatives in different disease states, such as pain, inflammation and cancer. Moreover, we detail the formation and potential physiological roles of the oxidative metabolites that arise from the metabolism of omega-3 eCBs by eicosanoid synthesizing enzymes - cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 epoxygenase (CYP450). In summary, we outline the novel findings regarding a growing class of signaling molecules that can control the physiological and pathophysiological processes in the body.

PGE2 in fibrosis and cancer: Insights into fibroblast activation Publication date: August 2019 Source: Prostaglandins & Other Lipid Mediators, Volume 143 Author(s): Eiman Elwakeel, Bernhard Brüne, Andreas Weigert Abstract Fibroblasts are the essential cellular architects of connective tissue and as such are crucial cells in contributing to organ homeostasis. While fulfilling important repair functions during tissue regeneration upon wounding, chronic fibroblast activation provokes pathological organ fibrosis and promotes neoplastic disease progression. Identifying targets that may serve to therapeutically terminate fibroblast activation is therefore desirable. Among the mediators that may be relevant in this context is the prostanoid prostaglandin E2 (PGE2) that is produced during inflammatory settings, where pathological fibrosis occurs. Here, we summarize current, in part controversial, concepts on the impact of PGE2 on fibroblast activation in fibrotic diseases including cancer, and discuss these findings in the context of the evolving concept of fibroblast heterogeneity.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Environmental Science and Pollution Research

The influence of human activity and morphological characteristics of beaches on plastic debris distribution along the Caspian Sea as a closed water body Abstract The Caspian Sea is the largest land-locked lake in the world that includes numerous endemic species. Because of its enclosed nature, the pollutants entering this water body become entrapped. The present paper examines the influence of human activity and beach morphology on the abundance and distribution of stranded plastic debris along the Caspian Sea coastlines. It would be possible by relating some characteristics of these beaches (population, urbanization, substrate type, and slope of beaches) with the abundance of plastic debris through a PCo analysis. The results showed that in our study area, the most effective factors on plastic debris distribution were urbanization and population followed by the slope and substrate of beaches. Three size classes of plastic debris were defined as "large microplastic" (1 to < 5 mm), "mesoplastic" (5 to < 25 mm), and "macroplastic" (> 25 mm). The density of the large microplastic, mesoplastic, and macroplastic materials on the Caspian Sea coastline was 8.43 ± 0.54, 8.74 ± 0.42, and 7.53 ± 0.30 particles/m2, respectively. Foam was the most abundant microplastic debris along the study area (47.58%), followed by resin pellets (33.93%) and fragments (16.30%), respectively. We also selected the Boujagh National Park with limited accessibility as an appropriate area for the study of marine debris as one sampling station. Cigarette butts and film pieces displayed a different distribution pattern compared to other debris types in the Boujagh National Park station likely due to their distinct buoyancy specification.

Correction to: Ecological risk assessment of metals in sediments and selective plants of Uchalli Wetland Complex (UWC)—a Ramsar site The correct image of Figure 4 is shown in this paper. The original article has been corrected. Fig. 4: Scree plot of heavy metals in sediments. The graph shown in upper right corner shows the concentration of principle components variables in a loading plot.

Recent advances on advanced oxidation process for sustainable water management

Environment-health link in a context of urban agricultures: studies of oral exposure to pollutants in order promote the human health

Photocatalytic oxidation of toluene and isopropanol by LaFeO 3 /black-TiO 2 Abstract Large amount of volatile organic compounds (VOCs) are emitted from industrial, mobile, and domestic sources, causing adverse effects on human health and environment. Among VOCs, toluene and isopropanol (IPA) are commonly used as solvent, soldering flux, and spray paint and their emissions need to be reduced. Several VOCs abatement technologies are available to reduce VOC emission and photocatalytic oxidation of VOC is regarded as a viable technique due to its advantage of utilizing solar energy. TiO2 has been investigated for its oxidation capability toward VOCs because of its good photocatalytic activity. However the utilization is limited to UV due to its wider bandgap; furthermore, its fast recombination rate of electron-hole pair reduces the oxidation rate of VOCs. Black-TiO2 and perovskite-type photocatalyst such as LaFeO3 can be applied to enhance photocatalytic activity due to narrower bandgap and longer electron-hole pair lifetime. In this study, black-TiO2 and LaFeO3 are prepared and investigated for their photocatalytic oxidation rates toward toluene and IPA. Results show that toluene removals achieved with black-TiO2 and LaFeO3 are 89% and 98% while IPA removals are 90% and 94%, respectively. Both photocatalysts show better photocatalytic activity than TiO2 and good absorption capability toward visible light. Graphical abstract

Regulating nitrate excess in lettuce-planted greenhouse soil with available carbon addition through irrigation Abstract Nitrate excess is common in greenhouse soils, imposing environmental risks and degrading vegetable quality. In this study, the effectiveness of adding sucrose as available carbon through irrigation to cut nitrate excess in lettuce-planted soil was investigated under impacts of soil texture and irrigation type. In the pot experiment using two loam soils of same origin with different clay to sand ratios (50.2% and 39.8%) and nitrate excess (116.1 and 417.7 mg/kg N), three-time sucrose addition through flood irrigation was more effective in lowering net formation of nitrate-based inorganic N and increasing lettuce yield in the soil with the higher clay to sand ratio, and sucrose addition at 150–450 mg/kg reduced nitrate accumulation and leaching, and nitrate content of lettuce at harvest by 62.5–89.6%, 19.3–36.1%, and 11.4–76.0%, respectively. In the micro-plot field experiment with two-time sucrose addition at 0.6–1.2 g/L through furrow irrigation (42 mm) into two other soils of same origin with different clay to sand ratios (56.9%, 48.4%), nitrate accumulation at 0–30-cm depth at the prone-leaching furrow location at harvest decreased by 30.9–36.0% under the higher clay to sand ratio but increased by about 35% under the lower clay to sand ratio. The nitrate content and yield of ridge-planted lettuce was less affected in either soil. Hence, carbon addition rate, irrigation type, and clay to sand ratio all affected the effect of available carbon addition on nitrate accumulation in vegetable-planted soil, and their joint impacts need better quantification for cutting nitrate excess in soil and improving vegetable quality and even yield.

Effects of vermicomposting on the main chemical properties and bioavailability of Cd/Zn in pure sludge Abstract To study the effects of vermicomposting on the chemical properties and bioavailability of Cd/Zn in sludge, earthworms (Eisenia foetida) at different densities were inoculated into pure sludge, and sludge and earthworms were collected regularly to determine the earthworm biomass, the main chemical indexes, the structure of the functional groups, and the Cd/Zn content in the sludge. The results showed that the growth curve of earthworms in pure sludge could be well fitted by the logistic model. Earthworm activity eventually reduced the total organic carbon (TOC), fulvic acid (FA), and C/N ratio and increased the electrical conductivity (EC), total nitrogen (TN), humic acid (HA), and HA/FA ratio in the sludge. TOC, TN, and pH inhibited the bioavailability of Cd/Zn, while HA and EC promoted the bioavailability of Cd/Zn. Earthworm activity ultimately increased the content of Cd/Zn in the sludge. The bioavailability of Cd/Zn was reduced during the rapid growth period of the earthworms but increased during the stable growth period of the earthworms. A suitable vermicomposting time should be determined to ensure the activation or passivation of Cd/Zn.

Metal content in the liver, kidney, and feathers of Northern gannets, Morus bassanus , sampled on the Spanish coast Abstract The value of birds as bioindicators for monitoring the environmental inorganic elements has been globally recognized. In this context, due to its well-known ecology and population stability, the Northern gannet (Morus bassanus) could be particularly useful. Dead Northern gannets (n = 30) were collected and samples from the liver, kidney, and feathers were taken, dried, mineralized, and finally analyzed via ICP-MS. Metals and metalloids, namely As, Cd, Hg, Pb, and Zn, associated with environmental pollution and toxicity on living organisms, were evaluated. The mean highest concentrations of As, Hg, and Zn were found in the liver (0.916, 7.026, and 89.81 mg/kg dry weight, respectively). For Cd, the kidney showed the highest mean concentration (17.51 mg/kg dry weight), whereas for Pb, this value corresponded to the feathers (0.399 mg/kg dry weight). Significant differences were found between the age classes in terms of contaminant concentrations, with the adults exhibiting higher metal levels. This difference was significantly relevant for Pb and Hg, where the effect of age was observed for all the considered tissues. When considering the effect of gender, no significant differences were observed, in agreement with similar studies performed in other geographical regions. Finally, positive correlations between the concentrations of Hg and Pb in the feathers and in the liver (r = 0.688, p < 0.001 and r = 0.566, p < 0.001, respectively) were observed, as well as between the feather and kidney concentrations (r= 0.685, p < 0.001) indicating the possibility to use feathers, a non-invasive biomonitoring tissue, for better understanding Hg and Pb exposure in seabirds.

Evaluation of the association between urinary cadmium levels below threshold limits and the risk of diabetes mellitus: a dose-response meta-analysis Abstract As cadmium levels are increasing in the environment, the adverse effects of cadmium exposure specifically associated with chronic diseases are receiving increasing attention. Several population–based studies have been conducted on the association between cadmium and diabetes mellitus (DM) but have reported controversial results. Here, we aimed to evaluate the association between cadmium exposure and DM. In this meta-analysis, a random effects model was used because there was evidence of heterogeneity among studies. A dose-response relationship was assessed through a restricted cubic spline model with three knots. The results showed a positive association between cadmium levels in the body and DM (OR = 1.27; 95% CI, 1.07–1.52). The cadmium levels in the body were defined on the basis of combined urinary and blood cadmium. Subgroup analysis further indicated a positive association between urinary cadmium levels and DM (OR = 1.31; 95% CI, 1.02–1.69). The dose-response analysis results showed a positive association between levels of urinary cadmium above 2.43 μg/g creatinine and DM, and the risk of DM increased by 16% for each l μg/g creatinine increase in urinary cadmium levels. The results from our meta-analysis indicate that cadmium levels in the body are positively associated with DM, and urinary cadmium levels above 2.43 μg/g creatinine are associated with an increased risk of DM.

Performance of desulfurization ash for the preparation of grouting fire prevention material Abstract The accumulation of desulfurization ash from coal-fired power plants can lead to serious waste of land resources and environmental safety problems. This work presents an experimental study on the feasibility of recycling original desulfurization ash as the main raw materials, and a new green grouting material was prepared. The results indicate that a desulfurization ash–based grouting fire prevention material which was prepared according to the following ingredient design (a water-to-solid ratio of 1.0:1 and a hydroxyethyl cellulose content of 0.09% desulfurization ash, 12% quicklime, 0.6% Na2SO4, and 0.05% triethanolamine, 80 °C curing). The slurry's viscosity meets requirements, and its suspension, liquidity, and consolidation strength are better than those of clay under the same conditions. In addition, the grouting material's inhibitor ratio is increased with temperature increase, which means it has good flame retardancy. Environmental performance tests concluded that when desulfurization ash as-recycled admixture is used for the preparation of grouting fire prevention material, from the technique point of view, the environmental safety of them is very good.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com