[Prediction of microvascular invasion in hepatocellular carcinoma with magnetic resonance imaging using models combining deep attention mechanism with clinical features].

OBJECTIVE: To investigate the consistency and diagnostic performance of magnetic resonance imaging (MRI) for detecting microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and the validity of deep learning attention mechanisms and clinical features for MVI grade prediction. METHODS: This retrospective study was conducted among 158 patients with HCC treated in Shunde Hospital Affiliated to Southern Medical University between January, 2017 and February, 2020. The imaging data and clinical data of the patients were collected to establish single sequence deep learning models and fusion models based on the EfficientNetB0 and attention modules. The imaging data included conventional MRI sequences (T1WI, T2WI, and DWI), enhanced MRI sequences (AP, PP, EP, and HBP) and synthesized MRI sequences (T1mapping-pre and T1mapping-20 min), and the high-risk areas of MVI were visualized using deep learning visualization techniques. RESULTS: The fusion model based on T1mapping-20min sequence and clinical features outperformed other fusion models with an accuracy of 0.8376, a sensitivity of 0.8378, a specificity of 0.8702, and an AUC of 0.8501 for detecting MVI. The deep fusion models were also capable of displaying the high-risk areas of MVI. CONCLUSION: The fusion models based on multiple MRI sequences can effectively detect MVI in patients with HCC, demonstrating the validity of deep learning algorithm that combines attention mechanism and clinical features for MVI grade prediction.

Expression analysis of transcription factors in sugarcane during cold stress / Análise de expressão de fatores de transcrição em cana-de-açúcar sob estresse por frio

Transcription factors (TF) are a wide class of genes in plants, and these can regulate the expression of other genes in response to various environmental stresses (biotic and abiotic). In the current study, transcription factor activity in sugarcane was examined during cold stress. Initially, RNA transcript reads of two sugarcane cultivars (ROC22 and GT08-1108) under cold stress were downloaded from SRA NCBI database. The reads were aligned into a reference genome and the differential expression analyses were performed with the R/Bioconductor edgeR package. Based on our analyses in the ROC22 cultivar, 963 TF genes were significantly upregulated under cold stress among a total of 5649 upregulated genes, while 293 TF genes were downregulated among a total of 3,289 downregulated genes. In the GT08-1108 cultivar, 974 TF genes were identified among 5,649 upregulated genes and 283 TF genes were found among 3,289 downregulated genes. Most transcription factors were annotated with GO categories related to protein binding, transcription factor binding, DNA-sequence-specific binding, transcription factor complex, transcription factor activity in RNA polymerase II, the activity of nucleic acid binding transcription factor, transcription corepressor activity, sequence-specific regulatory region, the activity of transcription factor of RNA polymerase II, transcription factor cofactor activity, transcription factor activity from plastid promoter, transcription factor activity from RNA polymerase I promoter, polymerase II and RNA polymerase III. The findings of above results will help to identify differentially expressed transcription factors during cold stress. It also provides a comprehensive analysis of the regulation of the transcription activity of many genes. Therefore, this study provides the molecular basis for improving cold tolerance in sugarcane and other economically important grasses.

Fatores de transcrição (FT) são uma ampla classe de genes em plantas e podem regular a expressão de outros genes em resposta a vários estresses ambientais (estresses bióticos e abióticos). No presente estudo, a atividade do fator de transcrição na cana-de-açúcar foi examinada durante o estresse pelo frio. Inicialmente, as leituras de transcrição de RNA de duas cultivares de cana-de-açúcar (ROC22 e GT08-1108) sob estresse frio foram baixadas do banco de dados SRA NCBI. As leituras foram alinhadas em um genoma de referência e as análises de expressão diferencial foram realizadas com o pacote R / Bioconductor edgeR. Com base em nossas análises no cultivar ROC22, 963 genes TF foram significativamente regulados positivamente sob estresse pelo frio entre um total de 5.649 genes regulados positivamente, enquanto 293 genes TF foram regulados negativamente entre um total de 3.289 genes regulados negativamente. No cultivar GT08-1108, 974 genes TF foram identificados entre 5.649 genes regulados positivamente e 283 genes TF foram encontrados entre 3.289 genes regulados negativamente. Os fatores de transcrição, em sua maioria, foram anotados com categorias GO relacionadas à ligação de proteína, ligação de fator de transcrição, ligação específica de sequência de DNA, complexo de fator de transcrição, atividade de fator de transcrição em RNA polimerase II, atividade de fator de transcrição de ligação de ácido nucleico, atividade de corepressor de transcrição, sequência específica da região reguladora, atividade do fator de transcrição da RNA polimerase II, atividade do cofator do fator de transcrição, atividade do fator de transcrição do promotor do plastídio, atividade do fator de transcrição do promotor da RNA polimerase I, polimerase II e RNA polimerase III. As descobertas dos resultados acima ajudarão a identificar fatores de transcrição expressos diferencialmente durante o estresse pelo frio. Ele também fornece uma análise abrangente da regulação da atividade [...].

Expression analysis of transcription factors in sugarcane during cold stress

Abstract Transcription factors (TF) are a wide class of genes in plants, and these can regulate the expression of other genes in response to various environmental stresses (biotic and abiotic). In the current study, transcription factor activity in sugarcane was examined during cold stress. Initially, RNA transcript reads of two sugarcane cultivars (ROC22 and GT08-1108) under cold stress were downloaded from SRA NCBI database. The reads were aligned into a reference genome and the differential expression analyses were performed with the R/Bioconductor edgeR package. Based on our analyses in the ROC22 cultivar, 963 TF genes were significantly upregulated under cold stress among a total of 5649 upregulated genes, while 293 TF genes were downregulated among a total of 3,289 downregulated genes. In the GT08-1108 cultivar, 974 TF genes were identified among 5,649 upregulated genes and 283 TF genes were found among 3,289 downregulated genes. Most transcription factors were annotated with GO categories related to protein binding, transcription factor binding, DNA-sequence-specific binding, transcription factor complex, transcription factor activity in RNA polymerase II, the activity of nucleic acid binding transcription factor, transcription corepressor activity, sequence-specific regulatory region, the activity of transcription factor of RNA polymerase II, transcription factor cofactor activity, transcription factor activity from plastid promoter, transcription factor activity from RNA polymerase I promoter, polymerase II and RNA polymerase III. The findings of above results will help to identify differentially expressed transcription factors during cold stress. It also provides a comprehensive analysis of the regulation of the transcription activity of many genes. Therefore, this study provides the molecular basis for improving cold tolerance in sugarcane and other economically important grasses.

Resumo Fatores de transcrição (FT) são uma ampla classe de genes em plantas e podem regular a expressão de outros genes em resposta a vários estresses ambientais (estresses bióticos e abióticos). No presente estudo, a atividade do fator de transcrição na cana-de-açúcar foi examinada durante o estresse pelo frio. Inicialmente, as leituras de transcrição de RNA de duas cultivares de cana-de-açúcar (ROC22 e GT08-1108) sob estresse frio foram baixadas do banco de dados SRA NCBI. As leituras foram alinhadas em um genoma de referência e as análises de expressão diferencial foram realizadas com o pacote R / Bioconductor edgeR. Com base em nossas análises no cultivar ROC22, 963 genes TF foram significativamente regulados positivamente sob estresse pelo frio entre um total de 5.649 genes regulados positivamente, enquanto 293 genes TF foram regulados negativamente entre um total de 3.289 genes regulados negativamente. No cultivar GT08-1108, 974 genes TF foram identificados entre 5.649 genes regulados positivamente e 283 genes TF foram encontrados entre 3.289 genes regulados negativamente. Os fatores de transcrição, em sua maioria, foram anotados com categorias GO relacionadas à ligação de proteína, ligação de fator de transcrição, ligação específica de sequência de DNA, complexo de fator de transcrição, atividade de fator de transcrição em RNA polimerase II, atividade de fator de transcrição de ligação de ácido nucleico, atividade de corepressor de transcrição, sequência específica da região reguladora, atividade do fator de transcrição da RNA polimerase II, atividade do cofator do fator de transcrição, atividade do fator de transcrição do promotor do plastídio, atividade do fator de transcrição do promotor da RNA polimerase I, polimerase II e RNA polimerase III. As descobertas dos resultados acima ajudarão a identificar fatores de transcrição expressos diferencialmente durante o estresse pelo frio. Ele também fornece uma análise abrangente da regulação da atividade de transcrição de muitos genes. Portanto, este estudo fornece base molecular para melhorar a tolerância ao frio em cana-de-açúcar e outras gramíneas economicamente importantes.

Expression analysis of transcription factors in sugarcane during cold stress / Análise de expressão de fatores de transcrição em cana-de-açúcar sob estresse por frio

Abstract Transcription factors (TF) are a wide class of genes in plants, and these can regulate the expression of other genes in response to various environmental stresses (biotic and abiotic). In the current study, transcription factor activity in sugarcane was examined during cold stress. Initially, RNA transcript reads of two sugarcane cultivars (ROC22 and GT08-1108) under cold stress were downloaded from SRA NCBI database. The reads were aligned into a reference genome and the differential expression analyses were performed with the R/Bioconductor edgeR package. Based on our analyses in the ROC22 cultivar, 963 TF genes were significantly upregulated under cold stress among a total of 5649 upregulated genes, while 293 TF genes were downregulated among a total of 3,289 downregulated genes. In the GT08-1108 cultivar, 974 TF genes were identified among 5,649 upregulated genes and 283 TF genes were found among 3,289 downregulated genes. Most transcription factors were annotated with GO categories related to protein binding, transcription factor binding, DNA-sequence-specific binding, transcription factor complex, transcription factor activity in RNA polymerase II, the activity of nucleic acid binding transcription factor, transcription corepressor activity, sequence-specific regulatory region, the activity of transcription factor of RNA polymerase II, transcription factor cofactor activity, transcription factor activity from plastid promoter, transcription factor activity from RNA polymerase I promoter, polymerase II and RNA polymerase III. The findings of above results will help to identify differentially expressed transcription factors during cold stress. It also provides a comprehensive analysis of the regulation of the transcription activity of many genes. Therefore, this study provides the molecular basis for improving cold tolerance in sugarcane and other economically important grasses.

Resumo Fatores de transcrição (FT) são uma ampla classe de genes em plantas e podem regular a expressão de outros genes em resposta a vários estresses ambientais (estresses bióticos e abióticos). No presente estudo, a atividade do fator de transcrição na cana-de-açúcar foi examinada durante o estresse pelo frio. Inicialmente, as leituras de transcrição de RNA de duas cultivares de cana-de-açúcar (ROC22 e GT08-1108) sob estresse frio foram baixadas do banco de dados SRA NCBI. As leituras foram alinhadas em um genoma de referência e as análises de expressão diferencial foram realizadas com o pacote R / Bioconductor edgeR. Com base em nossas análises no cultivar ROC22, 963 genes TF foram significativamente regulados positivamente sob estresse pelo frio entre um total de 5.649 genes regulados positivamente, enquanto 293 genes TF foram regulados negativamente entre um total de 3.289 genes regulados negativamente. No cultivar GT08-1108, 974 genes TF foram identificados entre 5.649 genes regulados positivamente e 283 genes TF foram encontrados entre 3.289 genes regulados negativamente. Os fatores de transcrição, em sua maioria, foram anotados com categorias GO relacionadas à ligação de proteína, ligação de fator de transcrição, ligação específica de sequência de DNA, complexo de fator de transcrição, atividade de fator de transcrição em RNA polimerase II, atividade de fator de transcrição de ligação de ácido nucleico, atividade de corepressor de transcrição, sequência específica da região reguladora, atividade do fator de transcrição da RNA polimerase II, atividade do cofator do fator de transcrição, atividade do fator de transcrição do promotor do plastídio, atividade do fator de transcrição do promotor da RNA polimerase I, polimerase II e RNA polimerase III. As descobertas dos resultados acima ajudarão a identificar fatores de transcrição expressos diferencialmente durante o estresse pelo frio. Ele também fornece uma análise abrangente da regulação da atividade de transcrição de muitos genes. Portanto, este estudo fornece base molecular para melhorar a tolerância ao frio em cana-de-açúcar e outras gramíneas economicamente importantes.

[Fetal ECG extraction using temporal convolutional encoder-decoder network].

OBJECTIVE: To extract weak fetal ECG signals from mixed ECG signals recorded from maternal abdominal wall for accurate analysis of fetal heart rate and fetal ECG patterns. METHODS: By exploiting the superior nonlinear mapping ability of deep convolutional network, we developed a nonlinear adaptive noise cancelling (nonlinear ANC) extraction framework based on a temporal convolutional encoder-decoder network for extracting fetal ECG signals. We first constructed a deep temporal convolutional network (TCED-Net) model for fetal ECG signal extraction, and with the maternal chest ECG signal as the reference signal, the maternal ECG component in the abdominal mixed signal was estimated using this model. The estimated maternal ECG component was subtracted from the mixed abdominal ECG signals to obtain the fetal ECG component. Experimental analyses were performed using synthetic ECG signals (FECGSYNDB) and clinical ECG signals (NIFECGDB, PCDB) to test the performance of the propose method. RESULTS: The results of experiments on the FECGSYNDB dataset showed that the proposed approach achieved good performance in F1-score (98.89%), mean-square-error (MSE; 0.20) and quality signalto-noise ratio (qSNR; 7.84). The F1- score reached 99.1% on the NIFECGDB dataset and 98.61% on the PCDB dataset. The R peak detection accuracy index of the proposed method was higher than the existing best-performing algorithms such as EKF (F1=93.84%), ES-RNN (F1=97.20%) and AECG-DecompNet (F1=95.43%) by 5.05%, 1.9% and 3.18%, respectively. CONCLUSION: The fetal ECG signals extracted using the proposed method are clearer than those by the existing algorithms, suggesting the potential value this method for effective fetal health monitoring during pregnancy.

Expression analysis of transcription factors in sugarcane during cold stress.

Transcription factors (TF) are a wide class of genes in plants, and these can regulate the expression of other genes in response to various environmental stresses (biotic and abiotic). In the current study, transcription factor activity in sugarcane was examined during cold stress. Initially, RNA transcript reads of two sugarcane cultivars (ROC22 and GT08-1108) under cold stress were downloaded from SRA NCBI database. The reads were aligned into a reference genome and the differential expression analyses were performed with the R/Bioconductor edgeR package. Based on our analyses in the ROC22 cultivar, 963 TF genes were significantly upregulated under cold stress among a total of 5649 upregulated genes, while 293 TF genes were downregulated among a total of 3,289 downregulated genes. In the GT08-1108 cultivar, 974 TF genes were identified among 5,649 upregulated genes and 283 TF genes were found among 3,289 downregulated genes. Most transcription factors were annotated with GO categories related to protein binding, transcription factor binding, DNA-sequence-specific binding, transcription factor complex, transcription factor activity in RNA polymerase II, the activity of nucleic acid binding transcription factor, transcription corepressor activity, sequence-specific regulatory region, the activity of transcription factor of RNA polymerase II, transcription factor cofactor activity, transcription factor activity from plastid promoter, transcription factor activity from RNA polymerase I promoter, polymerase II and RNA polymerase III. The findings of above results will help to identify differentially expressed transcription factors during cold stress. It also provides a comprehensive analysis of the regulation of the transcription activity of many genes. Therefore, this study provides the molecular basis for improving cold tolerance in sugarcane and other economically important grasses.

[Synergistic effect of polysaccharide from Trichoderma pseudokoningii and oxaliplatin on colorectal cancer cells in vitro].

OBJECTIVE: To explore the synergistic inhibitory effect of polysaccharide from Trichoderma pseudokoningii (EPS) and oxaliplatin (Oxa) on colorectal cancer (CRC) HCT116 cells. OBJECTIVE: HCT116 cells were treated with 8 µg/mL Oxa and 100 µg/mL EPS alone or in combination, and the changes in cell viability was assessed with CCK-8 assay. CompuSyn software was used for fitting the Fa-CI curve to evaluate the combined effect of the two agents. Flow cytometry was performed to analyze cell apoptosis and cell cycle changes, and wound healing assay and Transwell assay were used to examine the migration ability of the treated cells. Oxa- and EPS-related genes and CRC-related genes were intersected for protein-protein interaction (PPI) analysis and GO and KEGG enrichment analyses. OBJECTIVE: Treatment with Oxa alone or in combination with EPS significantly inhibited the viability of HCT116 cells in a dose- and time-dependent manner, and the two agents exhibited a significant synergistic effect (CI < 1). The combined treatment with Oxa and EPS resulted in a significantly higher total cell apoptosis rate and a higher percentage of cells in S phase than Oxa alone and the control treatment (P < 0.05). EPS and Oxa alone both inhibited the migration of HCT116 cells, and their combination produced a stronger inhibitory effect. GO enrichment analysis of the key genes related with Oxa, EPS and CRC suggested that these genes were involved mainly in such biological processes as exogenous apoptosis signaling, cell response to chemical stress, and reactive oxygen metabolism; KEGG analysis showed that these genes were involved in the pathways of drug resistance, apoptosis and angiogenesis. OBJECTIVE: EPS and Oxa can synergistically inhibit the proliferation of HCT116 cells possibly through the PI3K-Akt, MAPK, VEGF, and p53 signaling pathways.

[A new lossy compression method for fetal heart rate signals-Convolutional Codec Network].

In order to reduce the energy loss during data transmission and storage in the Internet of Things system and improve the transmission efficiency of fetal heart rate data to allow real-time monitoring of the fetus, we used a convolutional codec network (CC-Net) to compress the data. The network has two modules: the encoding and decoding modules. The original data are compressed in the encoding module and reconstructed in the decoding module. The internal parameters are continuously updated using the mean square error of the original and the reconstructed signals to minimize the error to obtain effectively compressed data in the encoding module. In this study, the compression ratio of fetal heart rate signals using this method reached 12.07%, and the error between the reconstructed and original signals was 0.03. The proposed CC-Net can achieve a very low compression ratio for fetal heart rate compression while ensuring a high similarity between the reconstructed and the original signals to retain important information in fetal heart rate signals.

Neuroprotective effect of DUSP14 overexpression against isoflurane-induced inflammatory response, pyroptosis and cognitive impairment in aged rats through inhibiting the NLRP3 inflammasome.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a common complication after general anesthesia in the elderly people. Dual-specificity phosphatase 14 (DUSP14, also known as MKP6) has been implicated in the pathogenesis of various inflammatory diseases. However, the exact role and mechanism of DUSP14 in POCD remains unclear. MATERIALS AND METHODS: An isoflurane exposure induced POCD aged rat model was successfully constructed. The pathological changes of hippocampal tissues of aged rats were detected by Nissl staining. Evaluation of learning and memory abilities in aged rats was measured using Morris water maze task test. The DUSP14 level was detected by immunohistochemistry (IHC) assay, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Levels of brain injury markers [S-100ß and neuron specific enolase (NSE)] and inflammatory cytokines [interleukin (IL)-1ß (tumor necrosis factor (TNF)-α and IL-6] were detected using Enzyme Linked Immunosorbent Assay (ELISA) or qRT-PCR. The apoptosis of hippocampal nerve cells was assessed by Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Western blot assay was used to measure the expression of proteins related to apoptosis, pyroptosis and NOD-like receptor family pyrin domain-containing 3 (NLRP3)-Caspase-1 pathway. RESULTS: Isoflurane exposure led to brain injury, inflammatory response, cognitive dysfunction in aged rats and decreased the expression of DUSP14. Overexpression of DUSP14 could inhibit apoptosis, inflammation, pyroptosis, brain tissue damage, and improve cognitive dysfunction of aged rats after isoflurane anesthesia. Further mechanism studies revealed that DUSP14 may play a neuroprotective effect on POCD by regulating NLRP3 inflammasome-mediated pyroptosis. CONCLUSIONS: DUSP14 may effectively protect against isoflurane-induced neuro-inflammation, brain damage and cognitive dysfunction, indicating that DUSP14 may be a potential predictor and therapeutic target for POCD.

Cefepime neurotoxicity: thresholds and risk factors. A retrospective cohort study.

OBJECTIVES: Toxic serum cefepime trough concentrations are not well defined in the current literature. We aimed to define a more precise plasma trough concentration threshold for this antibiotic's neurological toxicity and to identify individuals at risk for developing neurotoxic side effects. METHODS: Retrospective study including all individuals who underwent cefepime therapeutic drug monitoring (TDM) between 2013 and 2017. Individuals with cefepime concentrations other than trough were excluded. The primary outcome was to assess the incidence of neurotoxicity and its relationship with cefepime plasma trough concentrations. Secondary outcomes were the relationship of renal function, cefepime daily dose, age, and cerebral and general co-morbidities with the occurrence of neurotoxicity. We also compared the mortality rate during hospitalization in individuals with and without neurotoxicity, and the possible impact of neuroprotective co-medications on outcomes. RESULTS: Cefepime concentrations were determined in 584 individuals. Among 319 individuals with available trough concentrations included, the overall incidence of neurotoxicity was 23.2% (74 of 319 individuals). Higher cefepime plasma trough concentrations were significantly associated with risk of neurotoxicity (no neurotoxicity 6.3 mg/L (interquartile range (IQR) 4.1-8.6) versus with neurotoxicity 21.6 mg/L (IQR 17.0-28.6), p <0.001). Individuals with presumed cefepime neurotoxicity had a significantly lower renal function (estimated glomerular filtration rate 82.0 mL/min/1.73 m2 (IQR 45.0-105.0) versus 35.0 mL/min/1.73 m2 (IQR 23.3-53.3], p <0.001), and significantly higher in-hospital mortality (19 (7.8%) versus 26 (35.1%) individuals, p <0.001). No neurotoxic side effects were seen below a trough concentration of 7.7 mg/L. Levels ≥38.1 mg/L always led to neurological side effects. CONCLUSION: In individuals with risk factors for cefepime neurotoxicity, such as renal insufficiency, TDM should be systematically performed, aiming at trough concentrations <7.5 mg/L.

The changing landscape of phase II/III metastatic sarcoma clinical trials-analysis of ClinicalTrials.gov.

BACKGROUND: Well-designed clinical trials are of great importance in validating novel treatments and ensuring an evidence-based approach for sarcoma. This study aimed to provide a comprehensive landscape of the characteristics of metastatic or advanced sarcoma clinical trials using the substantial resource of the ClincialTrials.gov database. METHODS: We identified 260,755 trials registered with ClinicalTrials.gov in the last 20 years, and 277 of them were eligible for inclusion. The baseline characteristics were ascertained for each trial. The trials were systematically reviewed to validate their classification into 96 trials registered before 2008 and 181 trials registered between 2008 and 2017. RESULTS: We found that in the last decade, metastatic and advanced sarcoma trials were predominantly phase II-III studies (p = 0.048), were more likely to be ≥2 arms (17.7% vs 35.3%, respectively; p = 0.007), and were more likely to use randomized (13.5% vs 30.4%; p = 0.002) and double-blinded (2.1% vs 9.4%; p = 0.024) assignment than trials registered before 2008. Furthermore, in the last 10-year period, metastatic sarcoma trials were more likely to be conducted in Asia. Treatment involving target therapy and immunotherapy were more common (71.8% vs 37.5%; p < 0.001) than in previous years. CONCLUSIONS: Our data showed provocative changes in the sarcoma landscape and demonstrated that the incidence of clinical trials with target therapy and immunotherapy is increasing. These findings emphasize the desperate need for novel strategies, including target therapy and immunotherapy, to improve the outcomes for patients with advanced sarcoma.

Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit.

As pharmacokinetics after burn trauma are difficult to predict, we conducted a 3-year prospective, monocentric, randomized, controlled trial to determine the extent of under- and overdosing of antibiotics and further evaluate the impact of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adaptation to reach and maintain antibiotic concentrations within the therapeutic range. Forty-five consecutive burn patients treated with antibiotics were prospectively screened. Forty fulfilled the inclusion criteria; after one patient refused to participate and one withdrew consent, 19 were randomly assigned to an intervention group (patients with real-time antibiotic concentration determination and subsequent adaptations) and 19 were randomly assigned to a standard-of-care group (patients with antibiotic administration at the physician's discretion without real-time TDM). Seventy-three infection episodes were analyzed. Before the intervention, only 46/82 (56%) initial trough concentrations fell within the range. There was no difference between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% confidence interval {CI}, 0.81 to 2.39], P = 0.227) or the time to reach the target. However, thanks to real-time dose adjustments, the trough concentrations of the intervention group remained more within the predefined range (57/77 [74.0%] versus 48/85 [56.5%]; adjusted odd ratio [OR] = 2.34 [95% CI, 1.17 to 4.81], P = 0.018), more days were spent within the target range (193 days/297 days on antibiotics [65.0%] versus 171 days/311 days in antibiotics [55.0%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32], P = 0.005), and fewer results were below the target trough concentrations (25/118 [21.2%] versus 44/126 [34.9%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87], P = 0.015). No difference in infection outcomes was observed between the study groups. Systematic TDM with same-day real-time dose adaptation was effective in reaching and maintaining therapeutic antibiotic concentrations in infected burn patients, which prevented both over- and underdosing. A larger multicentric study is needed to further evaluate the impact of this strategy on infection outcomes and the emergence of antibiotic resistance during long-term burn treatment. (This study was registered with the ClinicalTrials.gov platform under registration no. NCT01965340 on 27 September 2013.).

Staphylococcus aureus carriage at admission predicts early-onset pneumonia after burn trauma.

Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital's computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156 S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p < 0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.

New genotyping method discovers sustained nosocomial Pseudomonas aeruginosa outbreak in an intensive care burn unit.

BACKGROUND: Pseudomonas aeruginosa is a leading cause of healthcare-associated infections in the intensive care unit (ICU). AIM: To investigate an unexplained increase in the incidence of P. aeruginosa recovered from clinical samples in the ICU over a two-year period. METHODS: After unsuccessful epidemiological investigation by conventional tools, P. aeruginosa clinical isolates of all patients hospitalized between January 2010 and July 2012 were typed by a novel double-locus sequence typing (DLST) method and compared to environmental isolates recovered during the investigation period. FINDINGS: In total, 509 clinical isolates from 218 patients and 91 environmental isolates were typed. Thirty-five different genotypic clusters were found in 154 out of 218 patients (71%). The largest cluster, DLST 1-18, included 23 patients who were mostly hospitalized during overlapping periods in the burn unit. Genotype DLST 1-18 was also recovered from floor traps, shower trolleys and the shower mattress in the hydrotherapy rooms, suggesting environmental contamination of the burn unit as the source of the outbreak. After implementation of appropriate infection control measures, this genotype was recovered only once in a clinical sample from a burned patient and twice in the environment, but never thereafter during a 12-month follow-up period. CONCLUSION: The use of a novel DLST method allowed the genotyping of a large number of clinical and environmental isolates, leading to the identification of the environmental source of a large unrecognized outbreak in the burn unit. Eradication of the outbreak was confirmed after implementation of a continuous epidemiological surveillance of P. aeruginosa clones in the ICU.

Changes in blood monocyte Toll-like receptor and serum surfactant protein A reveal a pathophysiological mechanism for community-acquired pneumonia in patients with type 2 diabetes.

BACKGROUND: The lung is one of the target organs of microangiopathy in diabetes mellitus (DM); patients with type 2 diabetes mellitus (T2DM) are vulnerable to pneumonia, and a variety of pathophysiological mechanisms has been described. AIM: This study aimed to determine the pathophysiological mechanism of community-acquired pneumonia (CAP) in T2DM patients. METHODS: A total of 90 individuals was included in this study comprised of three groups (n = 30): healthy control, T2DM and T2DM+ CAP groups. Toll-like receptor (TLR)2 and 4 protein and messenger RNA expression in peripheral blood monocytes(PBMC) was assessed by western blot and reverse transcription-polymerase chain reaction, respectively, and surfactant protein A (SP-A) levels were examined in serum samples by enzyme-linked immunosorbent assay. RESULTS: In T2DM and T2DM+CAP groups, levels of both TLR2/4 protein and mRNA in PBMC were decreased compared with controls (P <0.05), with lower levels observed in the T2DM+CAP group in comparison with T2DM patients (P <0.05). The serum SP-A levels in T2DM+CAP individuals were significantly higher than the values obtained for T2DM patients (P <0.05). It also showed apparent increases when compared with that in controls although no statistical significance was detected. CONCLUSION: In T2DM patients with pneumonia, TLR2/4 levels in PBMC and serum SP-A were altered, maybe playing an important role in the susceptibility to pneumonia in T2DM patients.

Molecular variation of Sporisorium scitamineum in Mainland China revealed by internal transcribed spacers.

Sugarcane smut caused by the fungus Sporisorium scitamineum is a worldwide disease and also one of the most prevalent diseases in sugarcane production in mainland China. To study molecular variation in S. scitamineum, 23 S. scitamineum isolates from the 6 primary sugar-cane production areas in mainland, China (Guangxi, Yunnan, Guangdong, Hainan, Fujian, and Jiangxi Provinces), were assessed using internal transcribed spacer (ITS) methods. The results of ITS sequence analysis showed that the organisms can be defined at the genus level, including Ustilago and Sporisorium, and can also differentiate between closely related species. This method was not suitable for phylogenetic relationship analysis of different S. scitamineum isolates and could not provide support regarding their race ascription at the molecular level. The results of the present study will be useful for studies examining the molecular diversity of S. scitamineum and for establishing a genetic foundation for their pathogenicity differentiation and new race detection. In addition, our results can provide useful information for the pathogen selection principle in sugarcane smut resistance breeding and variety distribution.

Identification of smut-responsive genes in sugarcane using cDNA-SRAP.

Sugarcane smut, caused by the fungus Sporisorium scitamineum, is one of the main diseases that affect sugarcane worldwide. In the present study, the cDNA-SRAP technique was used to identify genes that are likely to be involved in the response of sugarcane to S. scitamineum infection. In total, 21 bands with significant differential expression during cDNA-SRAP analysis were cloned and sequenced. Real-time qPCR confirmation demonstrated that expression of 19 of these 21 differential bands was consistent with the expression observed during cDNA-SRAP analysis, with a deduced false positive rate of 9.5%. Sequence alignment indicated that 18 of 19 differentially expressed genes showed homologies from 19% to 100% to certain genes in GenBank, including the following genes: topoisomerase (EU048780), ethylene insensitive (EU048778), and tetraspanin (EU048770). A real-time qPCR assay showed that during 0-72 h after pathogen infection, expression of the topoisomerase and the ethylene insensitive genes was upregulated, whereas expression of the tetraspanin gene was downregulated, identical to the expression patterns observed under salicylic acid treatment. Therefore, all three genes are thought to play a role during S. scitamineum challenge, but with different functions. To our knowledge, this is the first report on the application of cDNA-SRAP in differential gene expression analysis of sugarcane during a sugarcane-S. scitamineum interaction. The results obtained also contribute to a better understanding of the molecular mechanisms associated with sugarcane-S. scitamineum interactions.