Diallyl disulfide antagonizes DJ-1 mediated proliferation, epithelial-mesenchymal transition, and chemoresistance in gastric cancer cells.

Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

Molecular Mechanism of Salvia miltiorrhiza in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology.

Purpose: This study aimed to investigate the effect of Salvia miltiorrhiza on colorectal cancer, as well as the mechanisms involved. Methods: The active compounds of Salvia miltiorrhiza and the associated genes in colorectal cancer were sourced from publicly available databases. Targets associated with colorectal cancer were identified by searching the GeneCards and OMIM databases. Subsequently, the Cytoscape 3.6.0 software was employed to create a regulatory network that illustrates the relationships among active ingredients, colorectal cancer, and their corresponding targets. The String database was utilized to generate a PPI network. Molecular docking studies, conducted with AutoDock Vina, verified the binding capabilities of these active components to core targets. The findings from network pharmacology analysis were corroborated through in vitro experiments. Results: In this study, we identified 39 active components derived from Salvia miltiorrhiza that are predicted to target 544 genes associated with colorectal cancer through network pharmacology. Through a combined analysis of network pharmacology, we isolated three key targets: SRC, IL6, and INS. Molecular docking results convincingly demonstrated Salvia miltiorrhiza's strong binding affinity to these targets. Additionally, in vitro experiments confirmed that Salvia miltiorrhiza effectively inhibited the progression of colorectal cancer via regulating the INS/SRC/IL6 pathway. Conclusion: Salvia miltiorrhiza emerges as a compelling herbal intervention for colorectal cancer. This study lays the foundation for potential future clinical trials assessing the efficacy of Salvia miltiorrhiza in the management of colorectal cancer.

Circ0060467 sponges miR-6805 to promote hepatocellular carcinoma progression through regulating AIFM2 and GPX4 expression.

BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.

A high-performance liquid chromatography-tandem mass spectrometry method for quantification of perampanel in human plasma: Effect of concomitant anti-seizure medications on perampanel concentration in patients with epilepsy.

Perampanel is a first-in-class α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist and a novel anti-seizure medication. It is currently used as adjunctive treatment for partial seizures in patients over 12 years of age. With the increasing clinical application of perampanel, monitoring its concentration under certain clinical conditions is important. This study developed a rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method to quantify perampanel in human plasma. Protein precipitation with acetonitrile was performed for sample preparation. Perampanel and perampanel-d5 (internal standard) were analyzed under gradient conditions using a C18 column. The mobile phase was composed of 0.1% (v/v) formic acid in water (solvent A) and 0.1% (v/v) formic acid in acetonitrile (solvent B) at a flow rate of 0.4 mL/min. Mass detection was performed using multiple reaction monitoring in the positive ionization mode. The proposed method was validated over a range of 0.5-500 ng/mL for perampanel. The linearity (r2 value) was higher than 0.999, and the linear equation was y = 0.00116x + 0.0116. The accuracy of the low-, middle-, and high-quality control samples was between 103% and 113%, and the intra- and inter-day precisions were below 6.81%. The quality of the proposed method was evaluated in accordance with the US Food and Drug Administration Bioanalytical Method Validation Guidance for Industry. The plasma concentrations of perampanel in 25 patients were successfully determined to be 38.7-577.7 ng/mL using the validated method.

Blood Lost: A Retrospective Review of Blood Wastage from a Massive Transfusion Protocol in a Tertiary Paediatric Hospital.

BACKGROUND: The paediatric massive transfusion protocol (MTP) is activated in the paediatric population for both trauma and non-trauma related indications. While it helps to improve the efficiency and efficacy of the delivery of blood products, it can also result in increased wastage. We aimed to evaluate the wastage rates from our paediatric MTP activations from 2013 to 2018. METHOD: As part of an audit, we retrospectively reviewed the records of the paediatric patients who had MTP activations. We collected the following data: reason for MTP activation, weight of patient, number of cycles of MTP required, blood products used, blood products wasted, deviation from our institution's recommended MTP blood product ratio, and reason for wastage. RESULT: We had 26 paediatric MTP activations within the audit period. There was an overall wastage rate of 1.5%, with wastage occurring in 3 out of 26 patients. The reason for all wastage was demise of the patient. Most patients' transfusion ratios deviated from our institution's MTP protocol. CONCLUSION: Our wastage rates are low likely because of clear MTP activation guidelines and a flexible MTP workflow.

Smart Garden Planning and Design Based on the Agricultural Internet of Things.

To improve the effect of urban agricultural garden landscape planning and design, this paper combines the agricultural Internet of Things technology to construct a smart garden planning and design system. Moreover, this paper selects the LEACH protocol that can support monitoring for a long time according to actual application needs, introduces the latest swarm intelligence optimization algorithm, the gray wolf algorithm, to optimize some of the problems in the LEACH protocol, and conducts simulation experiments on the improved algorithm. The simulation experiment results show that the improved algorithm has obvious advantages in cluster head selection, data transmission within the cluster, and route maintenance. After constructing a smart garden planning system based on the agricultural Internet of Things, the effect of the agricultural Internet of Things data processing in this paper is evaluated. Finally, this paper constructs a garden simulation system and analyzes the performance of the system. The results verify that the agricultural Internet of Things has a good effect in the planning and design of smart gardens.

White Blood Cell Counts to High-Density Lipoprotein Cholesterol Ratio, as a Novel Predictor of Long-Term Adverse Outcomes in Patients After Percutaneous Coronary Intervention: A Retrospective Cohort Study.

Background: White blood cell (WBC) counts and high-density lipoprotein cholesterol (HDL-C) are widely available in clinical practice. However, the predictive value for cardiovascular disease (CVD) is uncertain. In the present study, we firstly assessed the prognostic value of WBC to HDL-C ratio (WHR) in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). Methods: Six thousand and fifty patients with CAD after PCI from a retrospective cohort study (identifier: ChiCTR-INR-16010153) were evaluated initially. Three hundred and seventy-one patients were excluded due to HDL cholesterol data not available, malignancy, dementia, psoriasis or eczema, systemic connective tissue disorders, multiple sclerosis, chronic liver disease, and chronic obstructive pulmonary disorder. Finally, 5,679 patients were included in the study. The primary outcome was long-term mortality. Secondary endpoints were mainly major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a combination of stroke, cardiac death, stent thrombosis, recurrent myocardial infarction, and target vessel revascularization. The mean follow-up time of this study was 35.9 ± 22.5 months. We defined the best cutoff value of MHR according to the receiver operating curve (ROC), and then patients were divided into high and low WHR groups according to the cutoff value. We analyzed the data in both an acute coronary syndrome group (ACS) and a stable CAD subgroup, respectively. Results: Overall, there were 293 cases of long-term mortality during the follow-up period. According to the cutoff value (WHR = 8.25), 1,901 ACS patients were divided into high WHR group (n = 724) and low WHR group (n = 1,177). Compared to low WHR group, the incidence of all-cause mortality (ACM, 5.5 vs. 3.6%, p = 0.048) and cardiac death (4.7vs. 2.9%, p = 0.042) were significantly higher in the high WHR group. In stable CAD group, we also found the incidence of ACM and cardiac death were significantly higher in the high group compared to that in the low group. We did not find significant difference between the high and the low WHR group in the incidence of MACCEs. The multivariate Cox proportional hazards model showed that increased WHR level was independently correlated with the mortality. In the high WHR group, the risk of ACM increased two times in ACS [adjusted HR = 2.036 (1.258-3.296), p = 0.004] and 1.5 times in stable CAD [adjusted HR = 1.586 (1.178-2.136), p = 0.002]. Conclusion: The present study indicated that an increased WBC count to HDL-C ratio was independently associated with long-term mortality in CAD patients who underwent PCI.

A Novel ABC Score Predicts Mortality in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Who underwent Percutaneous Coronary Intervention.

OBJECTIVE: In the present study, we aimed to establish a novel score to predict long-term mortality of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI). METHODS: A total of 2,174 NSTE-ACS patients from the CORFCHD-ZZ study were enrolled as the derivation cohort. The validation cohort including 1,808 NSTE-ACS patients were from the CORFCHD-PCI study. Receiver operating characteristic analysis and area under the curve (AUC) evaluation were used to select the candidate variables. The model performance was validated internally and externally. The primary outcome was cardiac mortality (CM). We also explored the model performance for all-cause mortality (ACM). RESULTS: Initially, 28 risk factors were selected and ranked according to their AUC values. Finally, we selected age, N-terminal pro-B-type natriuretic peptide, and creatinine to develop a novel prediction model named "ABC" model. The ABC model had a high discriminatory ability for both CM (C-index: 0.774, p < 0.001) and ACM (C-index: 0.758, p < 0.001) in the derivation cohort. In the validation cohort, the C-index of CM was 0.802 (p < 0.001) and that of ACM was 0.797 (p < 0.001), which suggested good discrimination. In addition, this model had adequate calibration in both the derivation and validation cohorts. Furthermore, the ABC score outperformed the GRACE score to predict mortality in NSTE-ACS patients who underwent PCI. CONCLUSION: In the present study, we developed and validated a novel model to predict mortality in patients with NSTE-ACS who underwent PCI. This model can be used as a credible tool for risk assessment and management of NSTE-ACS after PCI.

Assessment of the Understanding of Concussion and Care Protocols Amongst Student Athletes and Coaches: A Qualitative Study.

Background: Pediatric sports-induced concussions have become a topic of interest and concern in the scientific community. Already, the literature is rich with studies that have identified numerous short-term and long-term consequences of childhood sports-induced concussions. However, there are very few studies that have identified how well the students who participate in concussion-prone sports and their coaches understand these consequences and how they can be avoided. This study aimed to explore student athletes' and their coaches' understanding of the concept of concussion and how it is managed both immediately after the injury occurs and during long-term recovery. Methods: This study utilized a qualitative design. The study was conducted in local and international schools in Singapore. Participants were recruited through purposive sampling. 42 student athletes aged 13-18 who participated in rugby, softball, football, cricket, volleyball, and/or water polo were recruited. Fourteen coaches who coached these same sports were also recruited. Four focus groups and three semi-structured interviews were conducted. Data collected were then analyzed with thematic analysis. Risk factors were assessed through four domains of focus: understanding of what concussion is; attitudes toward concussion; existing protocols for treating concussion; and return-to-school and return-to-play protocols. As this is a qualitative study, outcome measures were not identified. Results: Analysis of the data revealed four themes for each group. For student-athletes these included: limited understanding of concussion; non-reporting of injuries; variable supervision of athletes; and a lack of established return-to-school and return-to-play guidelines. For coaches these included: variable understanding of concussion; insufficient formal training in concussion management; limited medical support in managing injuries; and lack of understanding and adherence to return-to-school and return-to-play protocols. Conclusions: Of the themes identified, the most pressing was a lack of clearly defined return-to-play guidelines. This is an urgent issue that needs to be jointly addressed by healthcare professionals and schools with evidence-based guidelines.

Gut Microbiome-Based Diagnostic Model to Predict Coronary Artery Disease.

In the present study, we aimed to characterize gut microbiome and develop a gut microbiome-based diagnostic model in patients with coronary artery disease (CAD). Prospectively, we collected 309 fecal samples from Central China and Northwest China and carried out the sequencing of the V3-V4 regions of the 16S rRNA gene. The gut microbiome was characterized, and microbial biomarkers were identified in 152 CAD patients and 105 healthy controls (Xinjiang cohort, n = 257). Using the biomarkers, we constructed a diagnostic model and validated it externally in 34 CAD patients and 18 healthy controls (Zhengzhou cohort, n = 52). Fecal microbial diversity was increased in CAD patients compared to that in healthy controls (P = 0.021). Phylum Bacteroidetes was increased in CAD patients versus healthy controls (P = 0.001). Correspondingly, 48 microbial markers were identified through a 10-fold cross-validation on a random forest model, and an area under the curve (AUC) of 87.7% (95% CI: 0.832 to 0.916, P < 0.001) was achieved in the Xinjiang cohort (development cohort, n = 257). Notably, an AUC of 90.4% (95% CI: 0.848 to 0.928, P < 0.001) was achieved using combined analysis of gut microbial markers and clinical variables. This model provided a robust tool for the prediction of CAD. It could be widely employed to complement the clinical assessment and prevention of CAD.

Parental knowledge and beliefs on the use of child car restraints in Singapore: a qualitative study.

INTRODUCTION: Road traffic injuries and fatalities represent a significant public health problem. In Singapore, compliance with appropriate child car restraints (CCRs) is poor. We aimed to understand parental knowledge, beliefs and barriers regarding the use of CCRs. METHODS: In this qualitative study, we conducted five focus group discussions with parents who drive with their children in private cars. Participants were recruited using the KK Women's and Children's Hospital's social media page. Guiding questions were derived by consensus following literature review and adaptation to the Singapore context, exploring parental perceptions of CCR use. Focus group interviews were then transcribed and analysed. RESULTS: 33 participants were recruited, with an age range of 28‒46 (mean age 35.5) years. They had a total of 46 children with ages ranging from 2.5 months to 14 years (mean age 4.2 years). Three key themes were identified: parental knowledge regarding CCRs, barriers to CCR use, and suggestions to increase CCR compliance. Barriers to compliance included lack of knowledge, difficult child behaviour and cultural norms. A multipronged approach was proposed to increase CCR use, including educating the public, reinforcing positive behaviour, legal enforcement as a deterrent to non-compliance, increasing CCR installation services, providing CCRs for taxi users and offering financial incentives. CONCLUSION: Non-compliance to CCR use is multidimensional, including multiple potentially modifiable factors. This study could inform ongoing collaborative injury prevention efforts among healthcare professionals, industry partners and the traffic police, using public education and outreach to reduce the burden of road traffic injuries.

[The neural encoding of continuous speech - recent advances in EEG and MEG studies].

Speech comprehension is a central cognitive function of the human brain. In cognitive neuroscience, a fundamental question is to understand how neural activity encodes the acoustic properties of a continuous speech stream and resolves multiple levels of linguistic structures at the same time. This paper reviews the recently developed research paradigms that employ electroencephalography (EEG) or magnetoencephalography (MEG) to capture neural tracking of acoustic features or linguistic structures of continuous speech. This review focuses on two questions in speech processing: (1) The encoding of continuously changing acoustic properties of speech; (2) The representation of hierarchical linguistic units, including syllables, words, phrases and sentences. Studies have found that the low-frequency cortical activity tracks the speech envelope. In addition, the cortical activities on different time scales track multiple levels of linguistic units and constitute a representation of hierarchically organized linguistic units. The article reviewed these studies, which provided new insights into the processes of continuous speech in the human brain.

Synthesis and Biological Evaluation of Lipophilic Nucleoside Analogues as Inhibitors of Aminoacyl-tRNA Synthetases.

Emerging antibiotic resistance in pathogenic bacteria and reduction of compounds in the existing antibiotics discovery pipeline is the most critical concern for healthcare professionals. A potential solution aims to explore new or existing targets/compounds. Inhibition of bacterial aminoacyl-tRNA synthetase (aaRSs) could be one such target for the development of antibiotics. The aaRSs are a group of enzymes that catalyze the transfer of an amino acid to their cognate tRNA and therefore play a pivotal role in translation. Thus, selective inhibition of these enzymes could be detrimental to microbes. The 5'-O-(N-(L-aminoacyl)) sulfamoyladenosines (aaSAs) are potent inhibitors of the respective aaRSs, however due to their polarity and charged nature they cannot cross the bacterial membranes. In this work, we increased the lipophilicity of these existing aaSAs in an effort to promote their penetration through the bacterial membrane. Two strategies were followed, either attaching a (permanent) alkyl moiety at the adenine ring via alkylation of the N6-position or introducing a lipophilic biodegradable prodrug moiety at the alpha-terminal amine, totaling eight new aaSA analogues. All synthesized compounds were evaluated in vitro using either a purified Escherichia coli aaRS enzyme or in presence of total cellular extract obtained from E. coli. The prodrugs showed comparable inhibitory activity to the parent aaSA analogues, indicating metabolic activation in cellular extracts, but had little effect on bacteria. During evaluation of the N6-alkylated compounds against different microbes, the N6-octyl containing congener 6b showed minimum inhibitory concentration (MIC) of 12.5 µM against Sarcina lutea while the dodecyl analogue 6c displayed MIC of 6.25 µM against Candida albicans.

Evaluation of the criteria for trauma activation in the paediatric emergency department.

BACKGROUND: Trauma team activation criteria have a variable performance in the paediatric population. We aimed to identify predictors for high-level resource utilisation during trauma resuscitation in the ED. METHODS: A retrospective study was conducted in the ED of a tertiary paediatric hospital. Patient data were collected from trauma surveillance registry and analysis was performed to identify significant predictors. We then assessed the sensitivity and specificity of proposed models with respect to observed patient outcomes. RESULTS: Among 11 282 cases, the mean age was 6.1±4.9 (SD) years old. Fall was the most common mechanism of injury in 7364 (65.3%) patients. Eighty-eight (0.8%) patients required at least one high-level resource. Significant predictors for high-resource utilisation were overall GCS of <14 (relative risk (RR) 38.841, 95% CI 21.328 to 70.739, p<0.001), high-risk mechanisms of fall from height and motor vehicle collision (RR 7.863, 95% CI 4.687 to 13.192, p<0.001), as well as age-specific tachycardia (RR 1.796, 95% CI 1.145 to 2.817, p=0.0108). A model consisting of GCS and high-risk mechanism would under-triage 21 (0.2%) patients and over-triage 681 (6.0%) patients. When age-specific tachycardia was added, 8 (0.1%) less patients would be under-triaged but an additional 3251 (28.9%) patients would be over-triaged. CONCLUSION: As utilisation of high-level resources in paediatric trauma was rare, it was difficult to find an appropriate balance between under-triage and over-triage. Between the two, minimising the proportion of under-triage is more important as patient safety is paramount in paediatric trauma care.

miR-4732-5p promotes breast cancer progression by targeting TSPAN13.

MiR-4732-5p was previously found to be dysregulated in nipple discharge of breast cancer. However, the expression and function of miR-4732-5p in breast cancer remain largely unknown. Here, the expression of miR-4732-5p was detected using quantitative real-time PCR in breast cancer tissues and cell lines. Cell proliferation, apoptosis, migration and invasion assays were performed to examine the effects of miR-4732-5p in breast cancer. In addition, mRNA sequencing, bioinformatics analysis, Western blot and luciferase assays were performed to identify the target of miR-4732-5p. Overall, miR-4732-5p was significantly down-regulated in breast cancer tissues, especially in lymph node metastasis (LNM)-negative tissues, compared with adjacent normal tissues. However, it was more highly expressed in LNM-positive breast cancer tissues, compared with LNM-negative ones. Expression of miR-4732-5p was positively correlated with lymph node metastasis, larger tumour size, advanced clinical stage, high Ki-67 levels and poor prognosis. MiR-4732-5p promoted cell proliferation, migration and invasion in breast cancer. MiR-4732-5p directly targeted the 3'-UTR of tetraspanin 13 (TSPAN13) and suppressed TSPAN13 expression at the mRNA and protein levels. These results suggested that miR-4732-5p may serve as a tumour suppressor in the initiation of breast cancer, but as a tumour promoter in breast cancer progression by targeting TSPAN13.

miR-590-3p is a novel microRNA which suppresses osteosarcoma progression by targeting SOX9.

Osteosarcoma is the most common primary bone malignancy and arises primarily in the metaphyseal ends of long bones in children and adolescents. m iR-590 has been found to have anti-tumor effects in many other cancers. However, the role of miR-590-3p in osteosarcoma is poorly understood. In this study, we show that miR-590-3p was significantly decreased both in osteosarcoma tissues and cell lines, suggesting a potential role of miR-590-3p in osteosarcoma. Over-expression of miR-590-3p inhibited U2OS cell viability as shown by the CCK-8 assay and clonogenic assay. Ki-67 immunofluorescence staining and cell cycle analysis revealed that up-regulation of miR-590-3p inhibited U2OS cell proliferation. Transfection with miR-590-3p mimics suppressed PCNA, Cyclin D1 and CDK4 expression and increased p53 and p21 expression. In addition, U2OS cells transfected with miR-590-3p mimics exhibited reduced cell invasion and migration, characterized by the wound healing assay and transwell assay. Furthermore, bioinformatics analysis demonstrated that SOX9 was a potential target of miR-590-3p. SOX9 was up-regulated in osteosarcoma tissues. Transfection with miR-590-3p mimics markedly suppressed SOX9 expression both at the mRNA level and protein level. Dual luciferase assay validated the direct binding site of miR-590-3p on SOX9. Exogenous SOX9 expression in U2OS cells at least partially reversed the effects of miR-590-3p in U2OS cells. Enforced SOX9 expression restored cell viability in osteosarcoma cells transfected with miR-590-3p mimics. In addition, over-expression of SOX9 restored decreased cell metastasis properties caused by transfection with miR-590-3p mimics in osteosarcoma cells. In summary, these results indicated that miR-590-3p is an anti-cancer miRNA that can inhibit proliferation and metastasis in osteosarcoma cells. Our findings provide a novel insight into the biological function of miR-590-3p in osteosarcoma and SOX9 may be a potential therapeutic target for osteosarcoma.

Road traffic injuries among children and adolescents in Singapore - Who is at greatest risk?

INTRODUCTION: Pediatric road traffic injuries remain a significant cause of death and disability in many countries in Asia, despite the implementation of road traffic safety laws. We aim to describe the injuries, the use of restraints among road users, and risk factors associated with severe injuries for children in Singapore. METHODS: We performed a retrospective chart review of road traffic injuries presenting to the only two pediatric tertiary care hospitals in Singapore, from January 2012 to April 2016. We included children <16years old presenting to the emergency departments within 24h after injury (pedestrian, bicycle, motorcycle, motor vehicle). We calculated the frequencies for specific injury mechanisms, injury severity scores (ISS), and in-hospital outcomes of severe injuries (death, urgent resuscitation and emergent surgery). We performed a multivariate logistic regression to determine risk factors associated with severe injury. RESULTS: There were 2468 patients during the study period. The mean age was 7.9 years (SD 4.7); 60.1% of road injuries involved motor vehicle occupants (1483/2468). Most bicyclist/motorcyclists were not wearing helmets (70.0%, 245/350) and 51.1% of motor vehicle passengers (758/1483) were not restrained. Compared to motor vehicle passengers, pedestrians (adjusted OR 2.38, 95% CI 1.41-3.99), bicyclists (adjusted OR 2.12, 95% CI 1.04-4.32) and motorcyclists (adjusted OR 6.09, 95% CI 2.04-18.24) were more likely to sustain severe injuries. CONCLUSION: Child pedestrians, bicyclists and motorcyclists are especially vulnerable for severe injures. Further injury prevention efforts must focus on the enforcement of legislation to protect these high-risk groups.

A review of stroller-related and pram-related injuries to children in Singapore.

Prams and strollers are commonly used in daily childcare. We aim to study the type and severity of injuries associated with prams and strollers in an Asian population. We performed a retrospective review of children below the age of 6 who presented to a tertiary paediatric hospital in Singapore, from January 2012 to June 2015, with such injuries. There were 248 pram-related and stroller-related injuries. The median age was 12.5 months old. 69 (27.8%) sustained open wounds, 17 (6.9%) suffered fractures or dislocations and 2 children had significant head injuries. 29 patients (11.7%) sustained injuries while on stairs or escalators. Most of the injuries (197 cases, 79.4%) occurred despite adult supervision. The need for intervention was associated with older age and entrapment injuries (p<0.001). Only appropriately sized prams and strollers without exposed hinges should be used. These should not be deployed on stairs and escalators.

Prehospital Transport for Pediatric Trauma: A Comparison of Private Transport and Emergency Medical Services.

OBJECTIVES: We describe the demographics of pediatric patients with trauma transferred using private transport (PT) versus emergency medical services (EMS) and evaluate the potential impact on their treatment and outcome. METHODS: We accessed data from our national trauma registry, a prospectively collected database. Data were extracted on all patients with trauma admitted to our institution between January 2011 and June 2013, with injury severity score (ISS) higher than 8. We categorized unstable injuries as head injuries, spinal injuries, or proximal long bone fractures. Major trauma was defined as the presence of any of the following: ISS of 16 or higher, intensive care unit (ICU) admission or death. RESULTS: Ninety children were studied, including 27 major trauma and 66 unstable injuries; 69 patients (77%) used PT. Most patients with major trauma (17/27, 63%) and unstable injuries (50/66, 76%) used PT. Compared with EMS patients, PT patients were younger, smaller, took longer for emergency department physician review and stayed longer in the emergency department. Rates of ICU admission were similar in both groups, but length of stay in ICU and total hospital stay were shorter in the PT group despite similar proportions of major trauma and unstable injuries as well as median ISS. Each group had 1 mortality. CONCLUSIONS: Most children with major trauma and unstable injuries were brought by PT, risking deterioration en route. Nevertheless, this does not seem to translate to worse outcomes overall.

Increased Activity of Src Homology 2 Domain Containing Phosphotyrosine Phosphatase 2 (Shp2) Regulates Activity-dependent AMPA Receptor Trafficking.

Long term synaptic plasticity, such as long term potentiation (LTP), has been widely accepted as a cellular mechanism underlying memory. Recently, it has been unraveled that Shp2 plays a role in synaptic plasticity and memory in Drosophila and mice, revealing significant and conserved effects of Shp2 in cognitive function. However, the exact mechanism underlying this function of Shp2 in synaptic plasticity and memory still remains elusive. Here, we examine the regulation of Shp2 in hippocampal LTP and contextual fear conditioning. We find that Shp2 is rapidly recruited into spines after LTP induction. Furthermore, the phosphorylation level of Shp2 at Tyr-542 is elevated after LTP stimuli either in cultured hippocampal neurons or acute slices. Notably, contextual fear conditioning also regulates the phosphorylation level of Shp2 at Tyr-542, suggesting fine-tuned regulation of Shp2 in LTP and memory formation. By using a Shp2-specific inhibitor and adeno-associated virus-Cre mediated Shp2 knock-out in cultured neurons, we provide evidence that the phosphatase activity of Shp2 is critical for activity-dependent AMPA receptor surface trafficking. Collectively, our results have revealed a regulatory mechanism of Shp2 underlying LTP and memory, broadening our understanding of Shp2 in cognitive function.