393 results on '"Xie, Jianling"'
Search Results
152. Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada.
- Author
-
Sumner, Madeleine W., Xie, Jianling, Zemek, Roger, Winston, Kathleen, Freire, Gabrielle, Burstein, Brett, Kam, April, Emsley, Jason, Gravel, Jocelyn, Porter, Robert, Sabhaney, Vikram, Mater, Ahmed, Salvadori, Marina I., Berthelot, Simon, Beer, Darcy, Poonai, Naveen, Moffatt, Anne, Wright, Bruce, and Freedman, Stephen B.
- Published
- 2023
- Full Text
- View/download PDF
153. Exendin-4 stimulates islet cell replication via the IGF1 receptor activation of mTORC1/S6K1
- Author
-
Xie, Jianling, primary, El Sayed, Norhan M, additional, Qi, Cheng, additional, Zhao, Xuechan, additional, Moore, Claire E, additional, and Herbert, Terence P, additional
- Published
- 2014
- Full Text
- View/download PDF
154. Signaling crosstalk between the mTOR complexes
- Author
-
Xie, Jianling, primary and Proud, Chris G, additional
- Published
- 2014
- Full Text
- View/download PDF
155. Crosstalk between mTOR complexes
- Author
-
Xie, Jianling, primary and Proud, Christopher G., additional
- Published
- 2013
- Full Text
- View/download PDF
156. Cellular signalling of the receptor for advanced glycation end products (RAGE)
- Author
-
Xie, Jianling, primary, Méndez, José D., additional, Méndez-Valenzuela, Verna, additional, and Aguilar-Hernández, María Montserrat, additional
- Published
- 2013
- Full Text
- View/download PDF
157. Factors Associated With Prolonged Stay in a Pediatric Emergency Observation Unit of an Urban Tertiary Children’s Hospital in China
- Author
-
Xie, Jianling, primary, Lin, Yiqun, additional, and Kissoon, Niranjan, additional
- Published
- 2013
- Full Text
- View/download PDF
158. Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin–Producing Escherichia coli: A Systematic Review and Meta-analysis
- Author
-
Grisaru, Silviu, Xie, Jianling, Samuel, Susan, Hartling, Lisa, Tarr, Phillip I., Schnadower, David, and Freedman, Stephen B.
- Abstract
IMPORTANCE: The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin–producing Escherichia coli (STEC) remain unclear. OBJECTIVE: To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. STUDY SELECTION: Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. MAIN OUTCOMES AND MEASURES: Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). RESULTS: Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]). CONCLUSIONS AND RELEVANCE: Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.
- Published
- 2017
- Full Text
- View/download PDF
159. cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity
- Author
-
Xie, Jianling, primary, Ponuwei, Godwin A., additional, Moore, Claire E., additional, Willars, Gary B., additional, Tee, Andrew R., additional, and Herbert, Terence P., additional
- Published
- 2011
- Full Text
- View/download PDF
160. The role of mammalian target of rapamycin (mTOR) in the regulation of pancreatic β-cell mass: implications in the development of type-2 diabetes
- Author
-
Xie, Jianling, primary and Herbert, Terence P., additional
- Published
- 2011
- Full Text
- View/download PDF
161. Less Protein, Longer Life?
- Author
-
BENSALEM, JULIEN, XIE, JIANLING, SARGEANT, TIM, and PROUD, CHRIS
- Abstract
Highlights from the article: In particular, the ratio of proteins to carbohydrates and fats appears to drive food intake. In a process called "protein leveraging", populations consuming low-protein diets may consume more total energy than those eating more protein as they try to make up for the low protein content by eating more in total (https://bit.ly/2GwgnB6). According to the protein leverage theory, we tend to keep eating until we've reached a specific amount of protein in our diet.
- Published
- 2019
162. Risk factors on length of stay in pediatric emergency observation unit of a tertiary children's hospital in Guangzhou city
- Author
-
Xie, Jianling, primary
- Full Text
- View/download PDF
163. Supporting mechanism of non‐toxic chromium (III) acetate on silica for preparation of Phillips ethylene polymerization catalysts
- Author
-
Qiu, Pengyuan, primary, Li, Xiaofang, additional, Zhang, Shiliang, additional, Cheng, Ruihua, additional, Dong, Qi, additional, Liu, Boping, additional, Li, Liuzhong, additional, Yu, Yongling, additional, Tang, Yan, additional, Xie, JianLing, additional, and Wang, Wenqing, additional
- Published
- 2009
- Full Text
- View/download PDF
164. Identification of cAMP-Dependent Kinase as a Third in Vivo Ribosomal Protein S6 Kinase in Pancreatic β-Cells
- Author
-
Moore, Claire E.J., primary, Xie, Jianling, additional, Gomez, Edith, additional, and Herbert, Terence P., additional
- Published
- 2009
- Full Text
- View/download PDF
165. Regulated stability of eukaryotic elongation factor 2 kinase requires intrinsic but not ongoing activity.
- Author
-
Xuemin Wang, Xie, Jianling, da Mota, Sergio Regufe, Moore, Claire E., and Proud, Christopher G.
- Subjects
- *
EUKARYOTES , *ELONGATION factors (Biochemistry) , *PROTEIN kinases , *PROTEIN synthesis , *CYTOPROTECTION , *CANCER cells - Abstract
Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical protein kinase which negatively regulates protein synthesis, is activated under stress conditions and plays a role in cytoprotection, e.g. in cancer cells. It is regarded as a possible target for therapeutic intervention in solid tumours. Earlier studies showed that eEF2K is degraded by a proteasome-dependent pathway in response to genotoxic stress and that this requires a phosphodegron that includes an autophosphorylation site. Thus, application of eEF2K inhibitors would stabilize eEF2K, partially negating the effects of inhibiting its activity. In the present study, we show that under a range of other stress conditions, including acidosis or treatment of cells with 2-deoxyglucose, eEF2K is also degraded. However, in these settings, the previously identified phosphodegron is not required for its degradation. Nevertheless, kinase-dead and other activity-deficient mutants of eEF2K are stabilized, as is a mutant lacking a critical autophosphorylation site (Thr348 in eEF2K), which is thought to be required for eEF2K and other a-kinases to achieve their active conformations. In contrast, application of small-molecule eEF2K inhibitors does not stabilize the protein. Our data suggest that achieving an active conformation, rather than eEF2K activity per se, is required for its susceptibility to degradation. Additional degrons and E3 ligases beyond those already identified are probably involved in regulating eEF2K levels. Our findings have significant implications for therapeutic targeting of eEF2K, e.g. in oncology. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
166. Growth of large birefringent YVO4 crystal
- Author
-
Wu, Shaofan, primary, Wang, Guofu, additional, Xie, Jianling, additional, Wu, Xiquan, additional, and Li, Gangshen, additional
- Published
- 2003
- Full Text
- View/download PDF
167. 112 Characterizing Pain in Children with Acute Gastroenteritis in the Emergency Department.
- Author
-
Ali, Samina, Maki, Claudia, Xie, Jianling, Lee, Bonita, Graham, Timothy, Vanderkooi, Otto, MacDonald, Shannon, Poonai, Naveen, Thull-Freedman, Jennifer, Rajagopal, Manasi, Dow, Nadia, Sivakumar, Mithra, Freedman, Stephen, and TEam), Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE
- Subjects
ANALGESICS ,PAIN risk factors ,CONFERENCES & conventions ,GASTROENTERITIS ,HOSPITAL emergency services ,PAIN ,DISCHARGE planning ,ACUTE diseases ,DISEASE complications ,CHILDREN - Published
- 2019
- Full Text
- View/download PDF
168. Oral Ondansetron Administration to Nondehydrated Children With Diarrhea and Associated Vomiting in Emergency Departments in Pakistan: A Randomized Controlled Trial.
- Author
-
Freedman, Stephen B, Soofi, Sajid B, Willan, Andrew R, Williamson-Urquhart, Sarah, Ali, Noshad, Xie, Jianling, Dawoud, Fady, and Bhutta, Zulfiqar A
- Abstract
Study Objective: We determine whether single-dose oral ondansetron administration to children with vomiting as a result of acute gastroenteritis without dehydration reduces administration of intravenous fluid rehydration.Methods: In this 2-hospital, double-blind, placebo-controlled, emergency department-based, randomized trial conducted in Karachi Pakistan, we recruited children aged 0.5 to 5.0 years, without dehydration, who had diarrhea and greater than or equal to 1 episode of vomiting within 4 hours of arrival. Patients were randomly assigned (1:1), through an Internet-based randomization service using a stratified variable-block randomization scheme, to single-dose oral ondansetron or placebo. The primary endpoint was intravenous rehydration (administration of ≥20 mL/kg of an isotonic fluid during 4 hours) within 72 hours of randomization.Results: Participant median age was 15 months (interquartile range 10 to 26) and 59.4% (372/626) were male patients. Intravenous rehydration use was 12.1% (38/314) and 11.9% (37/312) in the placebo and ondansetron groups, respectively (odds ratio 0.98; 95% confidence interval [CI] 0.60 to 1.61; difference 0.2%; 95% CI of the difference -4.9% to 5.4%). Bolus fluid administration occurred within 72 hours of randomization in 10.8% (34/314) and 10.3% (27/312) of children administered placebo and ondansetron, respectively (odds ratio 0.95; 95% CI 0.56 to 1.59). A multivariable regression model fitted with treatment group and adjusted for antiemetic administration, antibiotics, zinc prerandomization, and vomiting frequency prerandomization yielded similar results (odds ratio 0.91; 95% CI 0.55 to 1.53). There was no interaction between treatment group and age, greater than or equal to 3 stools in the preceding 24 hours, or greater than or equal to 3 vomiting episodes in the preceding 24 hours.Conclusion: Oral administration of a single dose of ondansetron did not result in a reduction in intravenous rehydration use. In children without dehydration, ondansetron does not improve clinical outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
169. Growth of large birefringent YVO 4 crystal
- Author
-
Wu, Shaofan, Wang, Guofu, Xie, Jianling, Wu, Xiquan, and Li, Gangshen
- Abstract
This paper reports the growth of large sized birefringent YVO 4 crystal with perfect appearance and dimension φ 42×42 mm.
- Published
- 2002
- Full Text
- View/download PDF
170. Eukaryotic elongation factor 2 kinase regulates foam cell formation via translation of CD36.
- Author
-
Fernando, Sanuja, Salagaras, Thalia, Schwarz, Nisha, Sandeman, Lauren, Tan, Joanne T. M., Xie, Jianling, Zareh, Jonar, Jensen, Kirk, Williamson, Anna, Dimasi, Catherine, Chhay, Pich, Toledo‐Flores, Deborah, Long, Aaron, Manavis, Jim, Worthington, Michael, Fitridge, Robert, Di Bartolo, Belinda A., Bursill, Christina A., Nicholls, Stephen J., and Proud, Christopher G.
- Abstract
Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical protein kinase that controls protein synthesis in cells under stress. Although well studied in cancer, less is known about its roles in chronic inflammatory diseases. Here, we examined its regulation of macrophage cholesterol handling in the context of atherosclerosis. eEF2K mRNA expression and protein activity were upregulated in murine bone marrow‐derived macrophages (BMDMs) exposed to oxidized low‐density lipoprotein cholesterol (oxLDL). When incubated with oxLDL, BMDMs from eEF2K knockout (Eef2k−/−) mice formed fewer Oil Red O+ foam cells than Eef2k+/+ BMDMs (12.5% ± 2.3% vs. 32.3% ± 2.0%, p < .01). Treatment with a selective eEF2K inhibitor, JAN‐384, also decreased foam cell formation for C57BL/6J BMDMs and human monocyte‐derived macrophages. Disabling eEF2K selectively decreased protein expression of the CD36 cholesterol uptake receptor, mediated by a reduction in the proportion of translationally active Cd36 mRNA. Eef2k−/− mice bred onto the Ldlr−/− background developed aortic sinus atherosclerotic plaques that were 30% smaller than Eef2k+/+‐Ldlr−/− mice after 16 weeks of high cholesterol diet (p < .05). Although accompanied by a reduction in plaque CD36+ staining (p < .05) and lower CD36 expression in circulating monocytes (p < .01), this was not associated with reduced lipid content in plaques as measured by oil red O staining. Finally, EEF2K and CD36 mRNA levels were higher in blood mononuclear cells from patients with coronary artery disease and recent myocardial infarction compared to healthy controls without coronary artery disease. These results reveal a new role for eEF2K in translationally regulating CD36 expression and foam cell formation in macrophages. Further studies are required to explore therapeutic targeting of eEF2K in atherosclerosis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
171. Design, synthesis and activity of Mnk1 and Mnk2 selective inhibitors containing thieno[2,3-d]pyrimidine scaffold.
- Author
-
Jin, Xin, Merrett, James, Tong, Sheng, Flower, Bartholomew, Xie, Jianling, Yu, Rilei, Tian, Shuye, Gao, Ling, Zhao, Jiajun, Wang, Xuemin, Jiang, Tao, and Proud, Christopher G.
- Subjects
- *
PYRIMIDINES , *MITOGEN-activated protein kinases , *THIAMIN pyrophosphate , *ANTINEOPLASTIC agents , *SUBSTITUTION reactions , *BINDING sites - Abstract
Abstract The mitogen-activated protein kinase-interacting kinases 1 and 2 (MNK1 and MNK2) phosphorylate eukaryotic initiation factor 4E (eIF4E) and play important roles in promoting tumorigenesis and metabolic disease. Thus, inhibiting these enzymes might be valuable in the treatment of such conditions. We designed and synthesized a series of 4-((4-fluoro-2-isopropoxyphenyl)amino)-5-methylthieno[2,3- d ]pyrimidine derivatives, and evaluated their inhibitory activity against the MNKs. We found 15 compounds that were active as MNK inhibitors and that one in particular, designated MNK-7g , which was potent against MNK1 and substantially more potent against MNK2. The compound MNK-7g did not affect other signaling pathways tested and had no adverse effects on cell viability. As expected from earlier studies, MNK-7g also inhibited cell migration. Therefore, the compound MNK-7g , which forms an ionic bond with Asp226 in MNK2 and possesses a substituted aniline in a thieno[2,3-d] pyrimidine structure, is a promising starting point for the future development of novel drugs for treating or managing cancer and metabolic disease. Graphical abstract Image 1 Highlights • The MNK protein kinases (MNK1/2) play roles in cancer and metabolic disease. • From a set of 28 thienopyrimidines, 15 MNK inhibitors were identified. • One compound in particular, termed 7g, shows selectivity for MNK2 compared to MNK1. • Molecular docking revealed two H-bonds that are important for binding to MNKs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
172. Liver transaminase concentrations in children with acute SARS-CoV-2 infection.
- Author
-
Sumner, Madeleine W., Florin, Todd A., Kuppermann, Nathan, Xie, Jianling, Tancredi, Daniel J., and Freedman, Stephen B.
- Subjects
- *
ASPARTATE aminotransferase , *SARS-CoV-2 , *RESPIRATORY syncytial virus , *PEDIATRIC emergency services , *ALANINE aminotransferase , *PEDIATRIC emergencies - Abstract
• We studied 2462 children who had SARS-CoV-2 and transaminase testing performed. • Transaminase concentrations were elevated in 26% with isolated SARS-CoV-2 detection. • Isolated SARS-CoV-2 detection was not associated with elevated transaminases. • 90-day follow-up revealed no cases of new-onset liver disease. To evaluate the relationship between SARS-CoV-2 infection and liver injury by comparing transaminase concentrations among children tested for SARS-CoV-2 and other respiratory viruses in pediatric emergency departments. Eligible children were <18 years with suspected SARS-CoV-2, tested using molecular approaches in emergency departments between March 7, 2020, and June 15, 2021 (Pediatric Emergency Research Network), and between August 6, 2020, and February 22, 2022 (Pediatric Emergency Research Canada). We compared aspartate (AST) and alanine aminotransferase (ALT) concentrations at presentation for SARS-CoV-2 and other respiratory viruses through a multivariate linear regression model, with the natural log of serum transaminase concentrations as dependent variables. Of 16,892 enrolled children, 2,462 (14.6%) had transaminase concentrations measured; 4318 (25.6%) were SARS-CoV-2 positive, and 3932 (23.3%) were tested for additional respiratory viruses. Among study participants who had additional respiratory virus testing performed, the most frequently identified viruses were enterovirus/rhinovirus [8.7% (343/3,932)], respiratory syncytial virus [4.6% (181/3,932)], and adenovirus [2.6% (103/3,932)]. Transaminase concentrations were elevated in 25.6% (54/211) of children with isolated SARS-CoV-2 detection and 21.6% (117/541) of those with no virus isolated; P = 0.25. In the multivariable model, isolated SARS-CoV-2 detection was not associated with elevated ALT (adjusted geometric mean ratio (IU/L): 0.96; 95%Confidence Interval (CI): 0.84, 1.08) or AST (adjusted geometric mean ratio (IU/L): 1.03; 95%CI: 0.92, 1.16) concentrations, with negative respiratory panel as the referent group. Ninety-day follow-up was completed in 82.2% (3,550/4,318) of SARS-CoV-2 positive children; no cases of new-onset liver disease were reported. Among those tested, transaminase concentrations did not vary between SARS-CoV-2-positive children and those with a negative respiratory viral panel. In multivariate analysis, SARS-CoV-2 infection was not associated with increased initial transaminase concentrations compared to other respiratory viruses. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
173. Bicuculline regulated protein synthesis is dependent on Homer1 and promotes its interaction with eEF2K through mTORC1‐dependent phosphorylation
- Author
-
Marcelo Cossenza, Roberto Paes-de-Carvalho, Makoto Kamei, Christopher G. Proud, Jianling Xie, Kirk B. Jensen, Luis F. H. Gladulich, Gladulich, Luis FH, Xie, Jianling, Jensen, Kirk B, Kamei, Makoto, Paes-de-Carvalho, Roberto, Cossenza, Marcelo, and Proud, Christopher G
- Subjects
Elongation Factor 2 Kinase ,0301 basic medicine ,Scaffold protein ,protein synthesis ,Homer1 ,mTORC1 ,Mechanistic Target of Rapamycin Complex 1 ,Bicuculline ,EEF2 ,Biochemistry ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Homer Scaffolding Proteins ,synapse ,Protein biosynthesis ,Animals ,Humans ,GABA-A Receptor Antagonists ,Phosphorylation ,Cells, Cultured ,Neurons ,Kinase ,Chemistry ,eEF2K ,Cell biology ,Elongation factor ,030104 developmental biology ,Protein Biosynthesis ,Signal transduction ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
The regulation of protein synthesis is a vital and finely tuned process in cellular physiology. In neurons, this process is very precisely regulated, as which mRNAs undergo translation is highly dependent on context. One of the most prominent regulators of protein synthesis is the enzyme eukaryotic elongation factor kinase 2 (eEF2K) that regulates the elongation stage of protein synthesis. This kinase and its substrate, eukaryotic elongation factor 2 (eEF2) are important in processes such as neuronal development and synaptic plasticity. eEF2K is regulated by multiple mechanisms including Ca2+-ions and the mTORC1 signaling pathway, both of which play key roles in neurological processes such as learning and memory. In such settings, the localized control of protein synthesis is of crucial importance. In this work, we sought to investigate how the localization of eEF2K is controlled and the impact of this on protein synthesis in neuronal cells. In this study, we used both SH-SY5Y neuroblastoma cells and mouse cortical neurons, and pharmacologically and/or genetic approaches to modify eEF2K function. We show that eEF2K activity and localization can be regulated by its binding partner Homer1b/c, a scaffolding protein known for its participation in calcium-regulated signaling pathways. Furthermore, our results indicate that this interaction is regulated by the mTORC1 pathway, through a known phosphorylation site in eEF2K (S396), and that it affects rates of localized protein synthesis at synapses depending on the presence or absence of this scaffolding protein. (Figure presented.). Refereed/Peer-reviewed
- Published
- 2020
174. Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis
- Author
-
Stuart P. De Poi, Makoto Kamei, Ming Hong Shen, Roman V. Lenchine, Shuye Tian, Andrew C.W. Zannettino, Xuemin Wang, Sally Martin, Christopher G. Proud, Swati Irani, Ashley T. Jones, Derick Wong, Lisa M. Butler, Marten F. Snel, Kirk B. Jensen, Jianling Xie, James E. Merrett, Stephen Fitter, Andrew R. Tee, Paul J. Trim, Kaikai Shen, Jian Yang, Mengyuan Yu, Xie, Jianling, Shen, Kaikai, Jones, Ashley T, Yang, Jian, Kamei, Makoto, and Proud, Christopher G
- Subjects
Male ,mRNA translation ,protein synthesis ,Morpholines ,Regulator ,P70-S6 Kinase 1 ,Mice, Transgenic ,mTORC1 ,Mechanistic Target of Rapamycin Complex 1 ,Protein Serine-Threonine Kinases ,environment and public health ,Cell Line ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Mice ,Tuberous Sclerosis Complex 2 Protein ,Animals ,Humans ,Phosphorylation ,Molecular Biology ,Protein Kinase Inhibitors ,Cell Proliferation ,Pharmacology ,Mice, Inbred BALB C ,Kinase ,Cell growth ,Chemistry ,EIF4G ,rapamycin ,EIF4E ,Intracellular Signaling Peptides and Proteins ,Prostatic Neoplasms ,Cell Biology ,Cell Cycle Checkpoints ,prostate cancer ,Cell biology ,Eukaryotic Initiation Factor-4E ,eIF4E ,Mutagenesis, Site-Directed ,Molecular Medicine ,Protein Binding ,Signal Transduction - Abstract
eIF4E plays key roles in protein synthesis and tumorigenesis. It is phosphorylated by the kinases MNK1 and MNK2. Binding of MNKs to eIF4G enhances their ability to phosphorylate eIF4E. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G. These effects provide a novel mechanism by which mTORC1 signaling impairs the function of MNK2 and thereby decreases eIF4E phosphorylation. MNK2[S74A] knock-in cells show enhanced phosphorylation of eIF4E and S6K1 (i.e., increased mTORC1 signaling), enlarged cell size, and increased invasive and transformative capacities. MNK2[Ser74] phosphorylation was inversely correlated with disease progression in human prostate tumors. MNK inhibition exerted anti-proliferative effects in prostate cancer cells in vitro. These findings define a novel feedback loop whereby mTORC1 represses MNK2 activity and oncogenic signaling through eIF4E phosphorylation, allowing reciprocal regulation of these two oncogenic pathways. Refereed/Peer-reviewed
- Published
- 2019
175. Intrinsic motivation, favorability, time management, and achievement: A cross-lagged panel analysis.
- Author
-
Xu, Jianzhong, Du, Jianxia, Wang, Chuang, Liu, Fangtong, Huang, Bosu, Zhang, Meng, and Xie, Jianling
- Subjects
- *
INTRINSIC motivation , *TIME management , *PANEL analysis , *ACHIEVEMENT , *MOTIVATION (Psychology) - Abstract
• There are positive relations between intrinsic motivation and favorability. • Cross-lagged effects indicate that these relations are reciprocal. • Prior time management positively affects intrinsic motivation, favorability, and achievement. • Measuring favorability could be a complementary approach to study motivational conflicts. Informed by theoretical frameworks and related literature concerning intrinsic motivation, favorability, motivational interference, and time management, the current study uses cross-lagged panel models to investigate the longitudinal relations among homework intrinsic motivation, favorability, time management, and math achievement, using data from 1450 Chinese 8th graders over two time points. Results indicated there were positive reciprocal influences of intrinsic motivation and favorability; higher prior intrinsic motivation led to higher subsequent favorability, and higher prior favorability led to higher subsequent intrinsic motivation. Additionally, higher prior time management resulted in higher subsequent intrinsic motivation, favorability, and math achievement. Finally, our study suggests that measuring favorability could be a complementary approach to investigate motivational conflicts in the field of motivational interference. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
176. Social Behaviors Associated with SARS-CoV-2 Test Positivity Among Children Evaluated in Canadian Emergency Departments, 2020 to 2022: A Cross-Sectional Survey Study.
- Author
-
Sumner M, Tarr G, Xie J, Mater A, Winston K, Gravel J, Poonai N, Burstein B, Berthelot S, Zemek R, Porter R, Wright B, Kam A, Emsley J, Sabhaney V, Beer D, Freire G, Moffatt A, and Freedman SB
- Abstract
Objective: To evaluate how social behaviors relate to SARS-CoV-2 test positivity across pediatric age groups., Methods: Multicenter, cross-sectional study recruiting children <18 years old tested for SARS-CoV-2 infection in emergency departments between 2020 and 2022. We used multivariate logistic regression to assess how self-reported social behaviors affect SARS-CoV-2 test positivity across four age groups. Causal mediation analysis quantified how mask-wearing and presence of an infected close contact mediated the SARS-CoV-2 risk of given behaviors., Results: 7272 children were enrolled and 1457 (20.0%) tested positive for SARS-CoV-2. Attending a social gathering was associated with increased odds (aOR 1.64, 95%CI: 1.05, 2.57) of SARS-CoV-2 positivity among children aged 5-<12 years. Those attending in-person school/daycare were less likely to test positive for SARS-CoV-2 across all age categories. Attending childcare was associated with 16.3% (95%CI: -21.0%, -11.2%) and 9.0% (95%CI: -11.6%, -6.5%) reductions in the probability of testing positive for SARS-CoV-2 infection, with 53.5% (95%CI: 39.2%, 73.9%) and 22.8% (95%CI: 9.7%, 36.2%) of the effects being mediated by the presence of a close contact among <1 year and 1-<5 year age groups, respectively. Masking in public mediated the association between childcare attendance and SARS-CoV-2 positivity in children aged <1 year., Conclusions: Attending social gatherings increased the risk of SARS-CoV-2 test positivity in 5-<12-year-old children, but in-person daycare/school was associated with a reduced odds of testing positive across all ages. Settings with high public health adherence (i.e., schools) reduced the risk of testing positive for SARS-CoV-2, possibly from reduced close contact with SARS-CoV-2 positive individuals., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
177. CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer.
- Author
-
Rahman R, Rahaman MH, Hanson AR, Choo N, Xie J, Townley SL, Shrestha R, Hassankhani R, Islam S, Ramm S, Simpson KJ, Risbridger GP, Best G, Centenera MM, Balk SP, Kichenadasse G, Taylor RA, Butler LM, Tilley WD, Conn SJ, Lawrence MG, Wang S, and Selth LA
- Abstract
Background: Cyclin-dependent kinase 9 (CDK9) stimulates oncogenic transcriptional pathways in cancer and CDK9 inhibitors have emerged as promising therapeutic candidates., Methods: The activity of an orally bioavailable CDK9 inhibitor, CDKI-73, was evaluated in prostate cancer cell lines, a xenograft mouse model, and patient-derived tumor explants and organoids. Expression of CDK9 was evaluated in clinical specimens by mining public datasets and immunohistochemistry. Effects of CDKI-73 on prostate cancer cells were determined by cell-based assays, molecular profiling and transcriptomic/epigenomic approaches., Results: CDKI-73 inhibited proliferation and enhanced cell death in diverse in vitro and in vivo models of androgen receptor (AR)-driven and AR-independent models. Mechanistically, CDKI-73-mediated inhibition of RNA polymerase II serine 2 phosphorylation resulted in reduced expression of BCL-2 anti-apoptotic factors and transcriptional defects. Transcriptomic and epigenomic approaches revealed that CDKI-73 suppressed signaling pathways regulated by AR, MYC, and BRD4, key drivers of dysregulated transcription in prostate cancer, and reprogrammed cancer-associated super-enhancers. These latter findings prompted the evaluation of CDKI-73 with the BRD4 inhibitor AZD5153, a combination that was synergistic in patient-derived organoids and in vivo., Conclusion: Our work demonstrates that CDK9 inhibition disrupts multiple oncogenic pathways and positions CDKI-73 as a promising therapeutic agent for prostate cancer, particularly aggressive, therapy-resistant subtypes., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
178. No Association between SARS-CoV-2 Infection and Quality of Life 6- and 12-Months After Infection.
- Author
-
Dun-Dery F, Xie J, Winston K, Burstein B, Emsley J, Sabhaney V, Gravel J, Zemek R, Kam A, Mater A, Beer D, Freire G, Poonai N, Berthelot S, Porter R, Moffatt A, Salvadori M, Dixon A, and Freedman SB
- Abstract
Objective: To assess the association between SARS-CoV-2 infection and long-term quality of life (QoL)., Methods: Prospective cohort study with 6- and 12-month follow-up conducted in 14 Canadian institutions. Children tested for SARS-CoV-2 between August 2020 and February 2022 were eligible. QoL was measured using PedsQL
TM -4.0, overall health status scores 6- and 12-months after testing., Results: Among SARS-CoV-2 positive and negative participants eligible for long-term follow-up, 74.8% (505/675) and 71.8% (1106/1541) at 6- and 59.0% (727/1233) and 68.1% (2520/3699) at 12-months, completed follow-up, respectively. Mean ± SD PedsQL™ scores did not differ between positive and negative groups; difference: -0.86 (95%CI: -2.33, 0.61) at 6- and -0.48 (95%CI: -1.6, 0.64) at 12-months, respectively. SARS-CoV-2 test-positivity was associated with higher social subscale scores. Although in bivariate analysis, overall health status at 6-month was higher among SARS-CoV-2 cases [difference: 2.16 (95%CI: 0.80, 3.53)], after adjustment for co-variates, SARS-CoV-2 infection was not independently associated with total PedsQL™ or overall health status at either time point. Parental perception of recovery did not differ based on SARS-CoV-2 test-status at either time point., Conclusions: SARS-CoV-2 infection was not associated with QoL, overall health status, or parental perception of recovery 6- and 12-months following infection., Clinical Trial Registration (if Any): N/A., Competing Interests: Declaration of Competing Interest This work was supported by the Public Health Agency of Canada’s Immunization Partnership Fund (Emerging Issues Fund) and their Emerging Issues Fund (Enhanced Surveillance), and the Canadian Institute of Health Research (Operating Grant: Emerging COVID 19 Research Gaps and Priorities Funding Opportunity). SF is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness. FD is supported by the University of Calgary, Eyes High Post-Doctoral Fellowship., (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2024
- Full Text
- View/download PDF
179. Features Associated With Radiographic Pneumonia in Children with SARS-CoV-2.
- Author
-
Florin TA, Freedman SB, Xie J, Funk AL, Tancredi DJ, Kim K, Neuman MI, Yock-Corrales A, Bergmann KR, Breslin KA, Finkelstein Y, Ahmad FA, Avva UR, Lunoe MM, Chaudhari PP, Shah NP, Plint AC, Sabhaney VJ, Sethuraman U, Gardiner MA, Sartori LF, Wright B, Navanandan N, Mintegi S, Gangoiti I, Borland ML, Chong SL, Kwok MY, Eckerle M, Poonai N, Romero CMA, Waseem M, Nebhrajani JR, Bhatt M, Caperell K, Campos C, Becker SM, Morris CR, Rogers AJ, Kam AJ, Pavlicich V, Palumbo L, Dalziel SR, Morrison AK, Rino PB, Cherry JC, Salvadori MI, Ambroggio L, Klassen TP, Payne DC, Malley R, Simon NJ, and Kuppermann N
- Subjects
- Humans, Child, Male, Female, Child, Preschool, Adolescent, Infant, Lung diagnostic imaging, Tomography, X-Ray Computed, Pneumonia, Viral diagnostic imaging, Pneumonia, Viral complications, COVID-19 diagnostic imaging, COVID-19 complications, SARS-CoV-2
- Published
- 2024
- Full Text
- View/download PDF
180. Presentations and Outcomes Among Infants ≤90 Days With and Without SARS-CoV-2.
- Author
-
Burstein B, Sabhaney V, Florin TA, Xie J, Kuppermann N, and Freedman SB
- Subjects
- Child, Humans, COVID-19 Testing, Critical Care, Lethargy, SARS-CoV-2, COVID-19 diagnosis
- Abstract
Objectives: To compare symptoms and outcomes among infants aged ≤90 days tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a broad, international sample of emergency departments (EDs)., Methods: This was a secondary analysis of infants aged 0 to 90 days with suspected SARS-CoV-2 infections tested using molecular approaches and with 14-day follow-up. The parent studies were conducted at 41 EDs in 10 countries (the global Pediatric Emergency Research Network; March 2020-June 2021) and 14 EDs across Canada (Pediatric Emergency Research Canada network; August 2020-February 2022). Symptom profiles included presence and number of presenting symptoms. Clinical outcomes included hospitalization, ICU admission, and severe outcomes (a composite of intensive interventions, severe organ impairment, or death)., Results: Among 1048 infants tested for SARS-CoV-2, 1007 (96.1%) were symptomatic at presentation and 432 (41.2%) were SARS-CoV-2-positive. A systemic symptom (any of the following: Apnea, drowsiness, irritability, or lethargy) was most common and present in 646 (61.6%) infants, regardless of SARS-CoV-2 status. Although fever and upper respiratory symptoms were more common among SARS-CoV-2-positive infants, dehydration, gastrointestinal, skin, and oral symptoms, and the overall number of presenting symptoms did not differ between groups. Infants with SARS-CoV-2 infections were less likely to be hospitalized (32.9% vs 44.8%; difference -11.9% [95% confidence interval (CI) -17.9% to -6.0%]), require intensive care (1.4% vs 5.0%; difference -3.6% [95% CI -5.7% to -1.6%]), and experience severe outcomes (1.4% vs 5.4%; difference -4.0% [95% CI -6.1% to -1.9%])., Conclusions: SARS-CoV-2 infections may be difficult to differentiate from similar illnesses among the youngest infants but are generally milder. SARS-CoV-2 testing can help inform clinical management., (Copyright © 2024 by the American Academy of Pediatrics.)
- Published
- 2024
- Full Text
- View/download PDF
181. Inflammatory Markers in Febrile Young Infants With and Without SARS-CoV-2 Infections.
- Author
-
Burstein B, Florin TA, Sabhaney V, Xie J, Freedman SB, and Kuppermann N
- Subjects
- Infant, Humans, SARS-CoV-2, Fever etiology, COVID-19
- Published
- 2024
- Full Text
- View/download PDF
182. Biocompatibility and antibacterial activity of MgO/Ca3(PO4)2 composite ceramic scaffold based on vat photopolymerization technology.
- Author
-
Ge M, Xie D, Yang Y, Liang H, Gu J, Zhang Q, Xie J, and Tian Z
- Subjects
- Escherichia coli, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Calcium Phosphates pharmacology, Calcium Phosphates chemistry, Ceramics pharmacology, Technology, Magnesium Oxide pharmacology, Magnesium Oxide chemistry, Staphylococcus aureus
- Abstract
Recent advancements in medical technology and increased interdisciplinary research have facilitated the development of the field of medical engineering. Specifically, in bone repair, researchers and potential users have placed greater demands on orthopedic implants regarding their biocompatibility, degradation rates, antibacterial properties, and other aspects. In response, our team developed composite ceramic samples using degradable materials calcium phosphate and magnesium oxide through the vat photopolymerization (VP) technique. The calcium phosphate content in each sample was, respectively, 80 %, 60 %, 40 %, and 20 %. To explore the relationship between the biocompatibility, antibacterial activity, and MgO content of the samples, we cultured them with osteoblasts (MC3T3-E1), Escherichia coli (a gram-negative bacterium), and Staphylococcus aureus (a gram-positive bacterium). Our results demonstrate that as the MgO content of the sample increases, its biocompatibility improves but its antibacterial activity decreases. Regarding the composite material samples, the 20 % calcium phosphate content group exhibited the best biocompatibility. However, after 0.5 h of co-cultivation, the antibacterial rates of all groups except the 20 % calcium phosphate content group co-cultured with S. aureus exceed 80 %. Furthermore, after 3 h, the antibacterial rates against E. coli exceed 95 % in all groups. This is because higher levels of MgO correspond to lower pH values and Mg
2+ concentrations in the cell and bacterial culture solutions, which ultimately promote cell and bacterial proliferation. This elevates the biocompatibility of the samples, albeit at the expense of their antimicrobial efficacy. Thus, modulating the MgO content in the composite ceramic samples provides a strategy to develop gradient composite scaffolds for better control of their biocompatibility and antibacterial performance during different stages of bone regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
183. Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.
- Author
-
Xie J, Kuppermann N, Florin TA, Tancredi DJ, Funk AL, Kim K, Salvadori MI, Yock-Corrales A, Shah NP, Breslin KA, Chaudhari PP, Bergmann KR, Ahmad FA, Nebhrajani JR, Mintegi S, Gangoiti I, Plint AC, Avva UR, Gardiner MA, Malley R, Finkelstein Y, Dalziel SR, Bhatt M, Kannikeswaran N, Caperell K, Campos C, Sabhaney VJ, Chong SL, Lunoe MM, Rogers AJ, Becker SM, Borland ML, Sartori LF, Pavlicich V, Rino PB, Morrison AK, Neuman MI, Poonai N, Simon NE, Kam AJ, Kwok MY, Morris CR, Palumbo L, Ambroggio L, Navanandan N, Eckerle M, Klassen TP, Payne DC, Cherry JC, Waseem M, Dixon AC, Ferre IB, and Freedman SB
- Abstract
Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations., Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations., Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 10
9 /L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109 /L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts., Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)- Published
- 2023
- Full Text
- View/download PDF
184. Molecular epidemiology of rotavirus among children in Western Canada: Dynamic changes in genotype prevalence in four consecutive seasons.
- Author
-
Zhuo R, Freedman SB, Xie J, Charlton C, Plitt S, Croxen MA, Li V, Tarr GAM, Lee B, Ali S, Chui L, Luong J, and Pang X
- Subjects
- Child, Child, Preschool, Female, Male, Alberta, Epidemiological Monitoring, Incidence, Patient Acuity, Rotavirus Vaccines administration & dosage, Humans, Gastroenteritis epidemiology, Gastroenteritis virology, Rotavirus classification, Rotavirus genetics, Rotavirus isolation & purification, Rotavirus Infections epidemiology, Rotavirus Infections virology
- Abstract
Rotavirus molecular surveillance remains important in the postvaccine era to monitor the changes in transmission patterns, identify vaccine-induced antigenic changes and discover potentially pathogenic vaccine-related strains. The Canadian province of Alberta introduced rotavirus vaccination into its provincial vaccination schedule in June 2015. To evaluate the impact of this program on stool rotavirus positivity rate, strain diversity, and seasonal trends, we analyzed a prospective cohort of children with acute gastroenteritis recruited between December 2014 and August 2018. We identified dynamic changes in rotavirus positivity and genotype trends during pre- and post-rotavirus vaccine introduction periods. Genotypes G9P[8], G1P[8], G2P[4], and G12P[8] predominated consecutively each season with overall lower rotavirus incidence rates in 2016 and 2017. The demographic and clinical features of rotavirus gastroenteritis were comparable among wild-type rotaviruses; however, children with G12P[8] infections were older (p < 0.001). Continued efforts to monitor changes in the molecular epidemiology of rotavirus using whole genome sequence characterization are needed to further understand the impact of the selection pressure of vaccination on rotavirus evolution., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
185. Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.
- Author
-
Qiu Y, Freedman SB, Williamson-Urquhart S, Farion KJ, Gouin S, Poonai N, Schuh S, Finkelstein Y, Xie J, Lee BE, Chui L, Pang X, and On Behalf Of The Pediatric Emergency Research Canada Probiotic Regimen For Outpatient Gastroenteritis Utility Of Treatment Progut Trial Group
- Subjects
- Child, Humans, Infant, Child, Preschool, Adenoviridae, Prospective Studies, Feces, Rotavirus, Norovirus, Gastroenteritis, Adenoviridae Infections epidemiology, Rotavirus Infections, Caliciviridae Infections
- Abstract
Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus ( p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus ( p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children ( p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.
- Published
- 2023
- Full Text
- View/download PDF
186. Visits to Alberta Emergency Departments for Child Mental Health Concerns During the COVID-19 Pandemic: An Examination of Visit Trends in Relation to School Closures and Reopenings.
- Author
-
Newton AS, Xie J, Wright B, Lategan C, Winston K, and Freedman SB
- Subjects
- Humans, Child, Pandemics, Alberta epidemiology, Mental Health, Emergency Service, Hospital, COVID-19 epidemiology
- Abstract
Objective: We examined emergency department (ED) mental health visit trends by children in relation to periods of school closure and reopening during the COVID-19 pandemic in Alberta, Canada., Methods: Mental health visits by school-aged children (5 to <18 years) were extracted from the Emergency Department Information System, a province-wide database, from March 11, 2020, to November 30, 2021 (pandemic period; n = 18,997) and March 1, 2019, to March 10, 2020 (1-year, prepandemic comparator period; n = 11,540). We calculated age-specific visit rates and compared rate differences between periods of school closure (March 15-June 30, 2020; November 30, 2020-January 10, 2021; April 22-June 30, 2021) and reopening (September 4-November 29, 2020; January 11-April 21, 2021; September 3-November 30, 2021) to matched prepandemic periods. We used a ratio of relative risk to examine the risk of a visit during closures versus reopenings., Results: The cohort included 11,540 prepandemic visits and 18,997 pandemic visits. Compared with prepandemic periods, ED visit rates increased across all ages during the first (+85.53%; 95% confidence interval [CI], 73.68% to 100.41%) and third (+19.92%; 95% CI, 13.28% to 26.95%) school closures, and decreased during the second closure (-15.37%; 95% CI, -22.22% to -7.92%). During school reopenings, visit rates decreased across all ages during the first reopening (-9.30%; 95% CI, -13.94% to -4.41%) and increased during the third reopening (+13.59%; 95% CI, 8.13% to 19.34%); rates did not change significantly during the second reopening (2.54%; 95% CI, -3.45% to 8.90%). The risk of a visit during school closure versus reopening was only higher for the first closure with 2.06 times the risk (95% CI, 1.88 to 2.25)., Conclusions: Emergency department mental health visit rates were highest during the first school closure of the COVID-19 pandemic, and the risk of a visit during this closure period was twice compared with when schools first reopened., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
187. Comparison of a Rapid Multiplex Gastrointestinal Panel with Standard Laboratory Testing in the Management of Children with Hematochezia in a Pediatric Emergency Department: Randomized Controlled Trial.
- Author
-
Xie J, Kim K, Berenger BM, Chui L, Vanderkooi OG, Grisaru S, and Freedman SB
- Subjects
- Humans, Child, Diarrhea diagnosis, Diarrhea microbiology, Emergency Service, Hospital, Gastrointestinal Hemorrhage diagnosis, Gastrointestinal Hemorrhage therapy, Gastroenteritis microbiology
- Abstract
Advances in diagnostic microbiology allow for the rapid identification of a broad range of enteropathogens; such knowledge can inform care and reduce testing. We conducted a randomized, unblinded trial in a tertiary-care pediatric emergency department. Participants had stool (and rectal swabs if stool was not immediately available) tested using routine microbiologic approaches or by use of a device (BioFire FilmArray gastrointestinal panel), which identifies 22 pathogens with a 1-h instrument turnaround time. Participants were 6 months to <18.0 years and had acute bloody diarrhea. Primary outcome was performance of blood tests within 72 h. From 15 June 2018 through 7 May 2022, 60 children were randomized. Patients in the BioFire FilmArray arm had a reduced time to test result (median 3.0 h with interquartile range [IQR] of 3.0 to 4.0 h, versus 42.0 h (IQR 23.5 to 47.3 h); difference of -38.0 h, 95% confidence interval [CI] of -41.0 to -22.0 h). Sixty-five percent (20/31) of participants in the BioFire FilmArray group had a pathogen detected-most frequently enteropathogenic Escherichia coli (19%), Campylobacter (16%), and Salmonella (13%). Blood tests were performed in 52% of children in the BioFire FilmArray group and 62% in the standard-of-care group (difference of -10.5%, 95% CI of -35.4% to 14.5%). There were no between-group differences in the proportions of children administered intravenous fluids, antibiotics, hospitalized, or who had diagnostic imaging performed. Testing with the BioFire FilmArray reduced the time to result availability by 38 h. Although statistical significance was limited by study power, BioFire FilmArray use was not associated with clinically meaningful reductions in health care utilization or improved outcomes. IMPORTANCE Advances in diagnostic microbiology now allow for the faster and more accurate detection of an increasing number of pathogens. We determined, however, that in children with acute bloody diarrhea, these advances did not necessarily translate into improved clinical outcomes. While a greater number of pathogens was identified using a rapid turnaround multiplex stool diagnostic panel, with a reduction in the time to stool test result of over 1.5 days, this did not alter the practice of pediatric emergency medicine physicians, who continued to perform blood tests on a large proportion of children. While our conclusions may be limited by the relatively small sample size, targeted approaches that educate clinicians on the implementation of such technology into clinical care will be needed to optimize usage and maximize benefits., Competing Interests: The authors declare a conflict of interest. A BioFire FilmArray Gastrointestinal Panel device was initially provided free of charge by bioMérieux. During the study period, a device was purchased for research purposes by the Alberta Children's Hospital Research Institute. All study test kits were purchased for usage.
- Published
- 2023
- Full Text
- View/download PDF
188. Predictors of Adherence to Short-Course Probiotics Among Children with Gastroenteritis who are Enrolled in a Clinical Trial.
- Author
-
Hurley KF, Fitzpatrick EA, Xie J, Urquhart S, Farion KJ, Gouin S, Schuh S, Poonai N, and Freedman S
- Subjects
- Child, Humans, Infant, Dehydration complications, Diarrhea drug therapy, Diarrhea complications, Vomiting complications, Vomiting therapy, Gastroenteritis drug therapy, Gastroenteritis complications, Probiotics therapeutic use
- Abstract
Background: To improve our understanding of adherence to discharge medications in the ED and within research trials, we sought to quantify medication adherence and identify predictors thereof in children with acute gastroenteritis (AGE)., Methods: We conducted a secondary analysis of a randomized trial of twice daily probiotic for 5 days. The population included previously healthy children aged 3-47 months with AGE. The primary outcome was patient-reported adherence to the treatment regimen, defined a priori as having received >70% of the prescribed doses. Secondary outcomes included predictors of treatment adherence and concordance between patient-reported adherence and the returned medication sachet counts., Results: After excluding participants with missing data on adherence, 760 participants were included in this analysis: 383 in the probiotic arm (50.4%); and 377 in the placebo arm (49.6%). Self-reported adherence was similar in both groups (77.0% in probiotic versus 80.3% in placebo). There was good agreement between self-reported adherence and sachet counts (87% within limits of agreement (-2.9 to 3.5 sachets) on the Bland-Altman plots). In the multivariable regression model, covariates associated with adherence were greater number of days of diarrhea post-emergency department visit, and the study site; covariates negatively associated with adherence were age 12-23 months, severe dehydration and greater total number of vomiting and diarrhea episodes after enrolment., Conclusions: Longer duration of diarrhea and study site were associated with higher probiotic adherence. Age 12-23 months, severe dehydration and greater number of vomiting and diarrhea episodes post enrolment negatively predicted treatment adherence.
- Published
- 2023
- Full Text
- View/download PDF
189. Correction to "Using Imidazo[2,1- b ][1,3,4]thiadiazol Skeleton to Design and Synthesize Novel MNK Inhibitors".
- Author
-
Jin X, Qiu T, Xie J, Wei X, Wang X, Yu R, Proud C, and Jiang T
- Abstract
[This corrects the article DOI: 10.1021/acsmedchemlett.2c00442.]., (© 2023 American Chemical Society.)
- Published
- 2023
- Full Text
- View/download PDF
190. Characterizing the Pain Experience of Children With Acute Gastroenteritis Based on Identified Pathogens.
- Author
-
Ma K, Ali S, Xie J, Maki C, Lee B, Chui L, Pang XL, Zhuo R, Parsons B, Vanderkooi O, Poonai N, MacDonald SE, Tarr P, and Freedman SB
- Subjects
- Female, Child, Humans, Infant, Diarrhea etiology, Vomiting etiology, Vomiting diagnosis, Pain etiology, Alberta epidemiology, Emergency Service, Hospital, Gastroenteritis complications, Gastroenteritis diagnosis, Viruses
- Abstract
Objectives: Pain is common with acute gastroenteritis (AGE) yet little is known about the severity associated with specific enteropathogens. We sought to explore the correlation of pain severity with specific enteropathogens in children with AGE., Methods: Participants were prospectively recruited by the Alberta Provincial Pediatric EnTeric Infection TEam at 2 pediatric emergency departments (EDs) (December 2014-August 2018). Pain was measured (by child and/or caregiver) using the 11-point Verbal Numerical Rating Scale., Results: We recruited 2686 participants; 46.8% (n = 1256) females, with median age 20.1 months (interquartile range 10.3, 45.3). The mean highest pain scores were 5.5 [standard deviation (SD) 3.0] and 4.2 (SD 2.9) in the 24 hours preceding the ED visit, and in the ED, respectively. Prior to ED visit, the mean highest pain scores with bacterial detection were 6.6 (SD 2.5), compared to 5.5 (SD 2.9) for single virus and 5.5 (SD 3.1) for negative stool tests. In the ED, the mean highest pain scores with bacterial detection were 5.5 (SD 2.7), compared to 4.1 (SD 2.9) for single virus and 4.2 (SD 3.0) for negative stool tests. Using multivariable modeling, factors associated with greater pain severity prior to ED visit included older age, fever, illness duration, number of diarrheal or vomiting episodes in the preceding 24 hours, and respiratory symptoms, but not enteropathogen type., Conclusion: Children with AGE experience significant pain, particularly when the episode is associated with the presence of a bacterial enteric pathogen. However, older age and fever appear to influence children's pain experiences more than etiologic pathogens., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2023
- Full Text
- View/download PDF
191. Using Imidazo[2,1- b ][1,3,4]thiadiazol Skeleton to Design and Synthesize Novel MNK Inhibitors.
- Author
-
Jin X, Qiu T, Xie J, Wei X, Wang X, Yu R, Proud C, and Jiang T
- Abstract
Mitogen-activated protein kinase-interacting protein kinases (MNKs) phosphorylate eukaryotic initiation factor 4E (eIF4E) and regulate the processes of cell proliferation, cell cycle, and migration and invasion of cancer cells. Selectively inhibiting the activity of MNKs could be effective in treating cancers. In this study, we report a series of novel MNK inhibitors with an imidazo[2,1- b ][1,3,4]thiadiazol scaffold, from which, compound 18 inhibited the phosphorylation of eIF4E in various cancer cell lines potently. Compound 18 was more potent against MNK2 than MNK1, and decreased the levels of cyclin-B1, cyclin-D3, and MMP-3 in A549 and MDA-MB-231 cells, impaired cell growth and colony formation, arrested the cell cycle in the G0/G1 phase, and inhibited cell migration and the secretion of TNF-α, MCP-1, and IL-8 from A549 cells. It represents a starting compound to design further inhibitors that selectively target MNKs and apply in other diseases., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)
- Published
- 2022
- Full Text
- View/download PDF
192. Comparative Evaluation of Luminex xTAG ® Gastrointestinal Pathogen Panel and Direct-From-Stool Real-Time PCR for Detection of C. difficile Toxin tcdB in Stool Samples from a Pediatric Population.
- Author
-
Tyrrell H, Morin SBN, Lloyd CD, Parsons B, Stokowski T, Xie J, Zhuo R, Lee BE, Pang XL, Freedman SB, and Chui L
- Abstract
Detection of Clostridioides difficile toxins in patients with gastroenteritis has increasingly been accomplished through the use of enteric multiplex syndromic panels. Comparisons of the performance of these panels to both direct-from-stool (DFS) and culture-enriched stools followed by polymerase chain reaction (PCR) methods in pediatric populations are limited. Here, we compare the performance of the Luminex xTAG
® Gastrointestinal Pathogen Panel (GPP) to our DFS in-house real-time PCR (DFS RT-PCR) assay for the detection of C. difficile toxin gene, tcdB , using 2641 stool specimens collected from children enrolled in the Alberta Provincial Pediatric EnTeric Infection Team (APPETITE) study in Alberta, Canada. We used culture enrichment followed by in-house RT-PCR to resolve discordant results between the two assays. We found excellent agreement ( k = 0.89) between the GPP and our DFS RT-PCR assay: the positive percent agreement between the two assays was 97%, and the negative percent agreement was 99%. GPP, a multi-analyte platform can easily be implemented into a routine diagnostic laboratory for detecting enteric pathogens including C. difficile .- Published
- 2022
- Full Text
- View/download PDF
193. Corticosteroids and Other Treatments Administered to Children Tested for SARS-CoV-2 Infection in Emergency Departments.
- Author
-
Freedman SB, Kuppermann N, Funk AL, Kim K, Xie J, Tancredi D, Dalziel SR, Neuman MI, Mintegi S, Plint AC, Gómez-Vargas J, Finkelstein Y, Ambroggio L, Klassen TP, Salvadori M, Malley R, Payne DC, and Florin TA
- Subjects
- Adolescent, Adrenal Cortex Hormones therapeutic use, Child, Cross-Sectional Studies, Emergency Service, Hospital, Humans, SARS-CoV-2, Nucleic Acids, COVID-19 Drug Treatment
- Abstract
Objective: We sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children., Methods: We collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were <18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed. To determine if SARS-CoV-2 test status was independently associated with corticosteroid administration, we used a multivariable conditional logistic regression model matched by study site to compare treatments administered based on SARS-CoV-2 test and disposition status. This analysis was repeated for the subgroup of study participants who were hospitalized., Results: 30.3% (3,121/10,315) of participants were SARS-CoV-2-positive. Although remdesivir was more commonly administered to SARS-CoV-2-positive children, use was infrequent (25/3120 [0.8%] vs 1/7188 [0.01%]; P = .001). Corticosteroid use was less common among SARS-CoV-2-positive children (219/3120 [7.0%] vs 759/7190 [10.6%]; P < .001). Among hospitalized children, there were no differences in provision of inotropes, respiratory support, chest drainage or extracorporeal membrane oxygenation between groups. Corticosteroid administration was associated with age, history of asthma, wheezing, study month, hospitalization and intensive care unit admission; it was not associated with a positive SARS-CoV-2 test result overall (aOR: 0.91; 95%CI: 0.74, 1.12) or among the subgroup of those hospitalized (aOR: 1.04; 95%CI: 0.75, 1.44)., Conclusions: Few disease-specific treatments are provided to SARS-CoV-2-positive children; clinical trials evaluating therapies in children are urgently needed., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
194. Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.
- Author
-
Funk AL, Kuppermann N, Florin TA, Tancredi DJ, Xie J, Kim K, Finkelstein Y, Neuman MI, Salvadori MI, Yock-Corrales A, Breslin KA, Ambroggio L, Chaudhari PP, Bergmann KR, Gardiner MA, Nebhrajani JR, Campos C, Ahmad FA, Sartori LF, Navanandan N, Kannikeswaran N, Caperell K, Morris CR, Mintegi S, Gangoiti I, Sabhaney VJ, Plint AC, Klassen TP, Avva UR, Shah NP, Dixon AC, Lunoe MM, Becker SM, Rogers AJ, Pavlicich V, Dalziel SR, Payne DC, Malley R, Borland ML, Morrison AK, Bhatt M, Rino PB, Beneyto Ferre I, Eckerle M, Kam AJ, Chong SL, Palumbo L, Kwok MY, Cherry JC, Poonai N, Waseem M, Simon NJ, and Freedman SB
- Subjects
- Acute Disease, Child, Child, Preschool, Cohort Studies, Fatigue, Female, Humans, Infant, Infant, Newborn, Male, Prospective Studies, SARS-CoV-2, COVID-19 epidemiology
- Abstract
Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children., Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs., Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls., Exposure: SARS-CoV-2 detected via nucleic acid testing., Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey., Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00])., Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.
- Published
- 2022
- Full Text
- View/download PDF
195. SARS-CoV-2 Viral Load Quantification, Clinical Findings and Outcomes in Children Seeking Emergency Department Care: Prospective Cohort Study.
- Author
-
Freedman SB, Oberding LK, Kim K, Xie J, Berenger BM, Goulden R, Weisbeck S, and Pillai DR
- Subjects
- Child, Emergency Service, Hospital, Humans, Prospective Studies, RNA, Viral analysis, RNA, Viral genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, Viral Load, COVID-19 diagnosis, COVID-19 epidemiology, SARS-CoV-2 genetics
- Abstract
We compared the perfomance of SARS-CoV-2 reverse transcriptase real-time polymerase chain reaction (RT-PCR) to droplet digital PCR (ddPCR). 95% and 40% of positive and negative RT-PCR specimens, respectively, were positive on ddPCR yielding sensitivities of 84% (95% CI: 74, 91) and 97% (95% CI: 89, 99), for RT-PCR and ddPCR, respectively. We found that SARS-CoV-2 RT-PCR testing in children has a concerning false-negative rate at lower nucleocapsid gene copy numbers., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
196. Intestinal Microbial Composition of Children in a Randomized Controlled Trial of Probiotics to Treat Acute Gastroenteritis.
- Author
-
Horne RG, Freedman SB, Johnson-Henry KC, Pang XL, Lee BE, Farion KJ, Gouin S, Schuh S, Poonai N, Hurley KF, Finkelstein Y, Xie J, Williamson-Urquhart S, Chui L, Rossi L, Surette MG, and Sherman PM
- Subjects
- Child, Child, Preschool, Feces microbiology, Humans, Intestines, RNA, Ribosomal, 16S genetics, Gastroenteritis drug therapy, Gastrointestinal Microbiome, Microbiota, Probiotics therapeutic use
- Abstract
Compositional analysis of the intestinal microbiome in pre-schoolers is understudied. Effects of probiotics on the gut microbiota were evaluated in children under 4-years-old presenting to an emergency department with acute gastroenteritis. Included were 70 study participants (n=32 placebo, n=38 probiotics) with stool specimens at baseline (day 0), day 5, and after a washout period (day 28). Microbiota composition and deduced functions were profiled using 16S ribosomal RNA sequencing and predictive metagenomics, respectively. Probiotics were detected at day 5 of administration but otherwise had no discernable effects, whereas detection of bacterial infection (P<0.001) and participant age (P<0.001) had the largest effects on microbiota composition, microbial diversity, and deduced bacterial functions. Participants under 1 year had lower bacterial diversity than older aged pre-schoolers; compositional changes of individual bacterial taxa were associated with maturation of the gut microbiota. Advances in age were associated with differences in gut microbiota composition and deduced microbial functions, which have the potential to impact health later in life., Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01853124., Competing Interests: SF is supported by the Alberta Children’s Hospital Professorship in Child Health and Wellness. MS is the recipient of a Canadian Research Chair in Interdisciplinary Microbiome Research. YF is the recipient of the Canada Research Chair in Pediatric Drug Safety and Efficacy. PS is the recipient of a Canadian Research Chair in Gastrointestinal Disease and research funded by the Canadian Institutes of Health Research (MOP-89894 and IOP-92890) and received honoraria from Abbott Nutrition, Mead Johnson Nutritionals and Nestlé Nutrition. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Horne, Freedman, Johnson-Henry, Pang, Lee, Farion, Gouin, Schuh, Poonai, Hurley, Finkelstein, Xie, Williamson-Urquhart, Chui, Rossi, Surette and Sherman.)
- Published
- 2022
- Full Text
- View/download PDF
197. Da-Chai-Hu-Tang Protects From Acute Intrahepatic Cholestasis by Inhibiting Hepatic Inflammation and Bile Accumulation via Activation of PPARα.
- Author
-
Xu S, Qiao X, Peng P, Zhu Z, Li Y, Yu M, Chen L, Cai Y, Xu J, Shi X, Proud CG, Xie J, and Shen K
- Abstract
Cholestasis is caused by intrahepatic retention of excessive toxic bile acids and ultimately results in hepatic failure. Da-Chai-Hu-Tang (DCHT) has been used in China to treat liver and gallbladder diseases for over 1800 years. Here, we demonstrated that DCHT treatment prevented acute intrahepatic cholestasis with liver injury in response to α-naphthylisothiocyanate (ANIT) not to bile duct ligation (BDL) induced-extrahepatic cholestasis. ANIT (80 mg/kg) increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBiL), total bilirubin (TBiL), and total bile acids (TBA) which was attenuated by DCHT treatment in a dose-dependent manner. DCHT treatment at high dose of 1.875 g/kg restored bile acid homeostasis, as evidenced by the recovery of the transcription of genes implicated in bile acid biosynthesis, uptake and efflux. DCHT treatment (1.875 g/kg) reversed ANIT-evoked disordered glutathione homeostasis (as determined by GSH/GSSG ratio) and increased in the mRNA levels for Il6 , Il1b and Tnfa associated with liver inflammation. Using network pharmacology-based approaches, we identified 22 putative targets involved in DCHT treatment for intrahepatic cholestasis not extrahepatic cholestasis. In addition, as evidenced by dual-luciferase reporter assays, compounds from DCHT with high affinity of PPARα increased luciferase levels from a PPARα-driven reporter. PPARα agonist fenofibrate was able to mimic the cytoprotective effect of DCHT on intrahepatic cholestasis, which was abolished by the PPARα antagonist GW6471. KEGG enrichment and western blot analyses showed that signaling axes of JNK/IL-6/NF-κB/STAT3 related to PPARα might be the principal pathway DCHT affects intrahepatic cholestasis. Taken together, the present study provides compelling evidence that DCHT is a promising formula against acute intrahepatic cholestasis with hepatotoxicity which works via PPARα activation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CL declared a shared affiliation with several of the authors, KS, SX, XQ, PP, YL, ZZ, LC, JX, XS, to the handling editor at time of review., (Copyright © 2022 Xu, Qiao, Peng, Zhu, Li, Yu, Chen, Cai, Xu, Shi, Proud, Xie and Shen.)
- Published
- 2022
- Full Text
- View/download PDF
198. Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.
- Author
-
Funk AL, Florin TA, Kuppermann N, Tancredi DJ, Xie J, Kim K, Neuman MI, Ambroggio L, Plint AC, Mintegi S, Klassen TP, Salvadori MI, Malley R, Payne DC, Simon NJ, Yock-Corrales A, Nebhrajani JR, Chaudhari PP, Breslin KA, Finkelstein Y, Campos C, Bergmann KR, Bhatt M, Ahmad FA, Gardiner MA, Avva UR, Shah NP, Sartori LF, Sabhaney VJ, Caperell K, Navanandan N, Borland ML, Morris CR, Gangoiti I, Pavlicich V, Kannikeswaran N, Lunoe MM, Rino PB, Kam AJ, Cherry JC, Rogers AJ, Chong SL, Palumbo L, Angelats CM, Morrison AK, Kwok MY, Becker SM, Dixon AC, Poonai N, Eckerle M, Wassem M, Dalziel SR, and Freedman SB
- Subjects
- Adolescent, COVID-19 pathology, COVID-19 Testing, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Male, Odds Ratio, Prospective Studies, Risk Factors, COVID-19 epidemiology, Emergency Service, Hospital statistics & numerical data, Hospitalization statistics & numerical data, SARS-CoV-2, Severity of Illness Index
- Abstract
Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized., Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED)., Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021., Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing., Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death., Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%)., Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.
- Published
- 2022
- Full Text
- View/download PDF
199. Microbial Etiologies and Clinical Characteristics of Children Seeking Emergency Department Care Due to Vomiting in the Absence of Diarrhea.
- Author
-
Freedman SB, Xie J, Lee BE, Ali S, Pang XL, Chui L, Zhuo R, Vanderkooi OG, Tellier R, Funk AL, and Tarr PI
- Subjects
- Adolescent, Alberta epidemiology, Child, Emergency Service, Hospital, Humans, Vomiting epidemiology, Vomiting etiology, Diarrhea epidemiology, Gastroenteritis complications, Gastroenteritis epidemiology
- Abstract
Background: As children with isolated vomiting are rarely able to provide a specimen suitable for routine pathogen testing, we have limited knowledge about their infecting pathogens., Methods: Between December 2014 and August 2018, children <18 years old with presumed acute gastroenteritis who presented to 2 emergency departments (EDs) in Alberta, Canada, were recruited. Eligible participants had ≥3 episodes of vomiting and/or diarrhea in a 24-hour period, <7 days of symptoms, and provided a rectal swab or stool specimen. We quantified the proportion of children with isolated vomiting in whom an enteropathogen was identified, and analyzed clinical characteristics, types of enteropathogens, resources used, and alternative diagnoses., Results: Of the 2695 participants, at the ED visit, 295 (10.9%), 1321 (49.0%), and 1079 (40.0%) reported having isolated diarrhea, vomiting and diarrhea, or isolated vomiting, respectively. An enteropathogen was detected most commonly in those with vomiting and diarrhea (1067/1321; 80.8%); detection did not differ between those with isolated diarrhea (170/295; 57.6%) and isolated vomiting (589/1079; 54.6%) (95% confidence interval of the difference: -3.4%, 9.3%). Children with isolated vomiting most often had a virus (557/1077; 51.7%), most commonly norovirus (321/1077; 29.8%); 5.7% (62/1079) had a bacterial pathogen. X-rays, ultrasounds, and urine tests were most commonly performed in children with isolated vomiting. Alternate etiologies were most common in those with isolated vomiting (5.7%; 61/1079)., Conclusions: The rate of enteropathogen identification in children with isolated vomiting using molecular diagnostic tests and rectal swabs is substantial. Molecular diagnostics offer an emerging diagnostic strategy in children with isolated vomiting., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
200. Detection and Clinical Implications of Monovalent Rotavirus Vaccine-Derived Virus Strains in Children with Gastroenteritis in Alberta, Canada.
- Author
-
Zhuo R, Tarr GAM, Xie J, Freedman SB, Payne DC, Lee BE, McWilliams C, Chui L, Ali S, and Pang X
- Subjects
- Alberta epidemiology, Child, Humans, Infant, Vaccines, Attenuated, Gastroenteritis epidemiology, Rotavirus genetics, Rotavirus Infections epidemiology, Rotavirus Vaccines
- Abstract
While rotavirus vaccine programs effectively protect against severe rotavirus gastroenteritis, rotavirus vaccine strains have been identified in the stool of vaccinated children and their close contacts suffering from acute gastroenteritis. The prevalence of vaccine strains, the emergence of vaccine-derived strains, and their role in acute gastroenteritis are not well studied. We developed a locked nucleic acid reverse transcription real-time PCR assay (LNA-RTqPCR) to detect the monovalent rotavirus vaccine (RV1) Rotarix nonstructural protein 2 (NSP2) in children with acute gastroenteritis and healthy controls, and validated it using sequence-confirmed RV1 strains. The association between RV1-derived strains and gastroenteritis was determined using logistic regression. The new assay exhibited 100% (95% CI 91.7%, 100%) diagnostic sensitivity and 99.4% (95% CI 96.2%, 100%) diagnostic specificity, with a detection limit of 9.86 copies/reaction and qPCR efficiency of 99.7%. Using this assay, we identified the presence of RV1-derived NSP2 sequences in 7.7% of rotavirus gastroenteritis cases and 98.6% of rotavirus-positive healthy children (94.4% had previously received the RV1). Among gastroenteritis cases, those whose stool contained RV1-derived strains had milder gastroenteritis symptoms compared to that of natural rotavirus infections. We observed no significant association between RV1-derived strains and gastroenteritis (odds ratio [OR] 0.98; 95% CI 0.60, 1.72). Our study demonstrated that the new assay is suitable for monitoring RV1-derived rotavirus strain circulation and that the RV1-derived strains are not associated with development of gastroenteritis symptoms.
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.