Nucleic Acid Preservation Card Surveillance Is Effective for Monitoring Arbovirus Transmission on Crocodile Farms and Provides a One Health Benefit to Northern Australia

The Kunjin strain of West Nile virus (WNV_KUN) is a mosquito-transmitted flavivirus that can infect farmed saltwater crocodiles in Australia and cause skin lesions that devalue the hides of harvested animals. We implemented a surveillance system using honey-baited nucleic acid preservation cards to monitor WNV_KUN and another endemic flavivirus pathogen, Murray Valley encephalitis virus (MVEV), on crocodile farms in northern Australia. The traps were set between February 2018 and July 2020 on three crocodile farms in Darwin (Northern Territory) and one in Cairns (North Queensland) at fortnightly intervals with reduced trapping during the winter months. WNV_KUN RNA was detected on all three crocodile farms near Darwin, predominantly between March and May of each year. Two of the NT crocodile farms also yielded the detection of MVE viral RNA sporadically spread between April and November in 2018 and 2020. In contrast, no viral RNA was detected on crocodile farms in Cairns during the entire trapping period. The detection of WNV_KUN and MVEV transmission by FTA^TM cards on farms in the Northern Territory generally correlated with the detection of their transmission to sentinel chicken flocks in nearby localities around Darwin as part of a separate public health surveillance program. While no isolates of WNV_KUN or MVEV were obtained from mosquitoes collected on Darwin crocodile farms immediately following the FTA^TM card detections, we did isolate another flavivirus, Kokobera virus (KOKV), from Culex annulirostris mosquitoes. Our studies support the use of the FTA^TM card system as a sensitive and accurate method to monitor the transmission of WNV_KUN and other arboviruses on crocodile farms to enable the timely implementation of mosquito control measures. Our detection of MVEV transmission and isolation of KOKV from mosquitoes also warrants further investigation of their potential role in causing diseases in crocodiles and highlights a “One Health” issue concerning arbovirus transmission to crocodile farm workers. In this context, the introduction of FTA^TM cards onto crocodile farms appears to provide an additional surveillance tool to detect arbovirus transmission in the Darwin region, allowing for a more timely intervention of vector control by relevant authorities.     

Analysis of the HNF4A isoform-regulated transcriptome identifies CCL15 as a downstream target in gastric carcinogenesis

Objective:Hepatocyte nuclear factor 4α (HNF4A) has been demonstrated to be an oncogene in gastric cancer (GC). However, the roles of different HNF4A isoforms derived from the 2 different promoters (P1 and P2) and the underlying mechanisms remain obscure.Methods:The expression and prognostic values of P1- and P2-HNF4A were evaluated in The Cancer Genome Atlas (TCGA) databases and GC tissues. Then, functional assays of P1- and P2-HNF4A were conducted both in vivo and in vitro. High-throughput RNA-seq was employed to profile downstream pathways in P1- and P2-HNF4A-overexpressing GC cells. The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays.Results:HNF4A amplification was a key characteristic of GC in TCGA databases, especially for the intestinal type and early stage. Moreover, P1-HNF4A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues (P < 0.05), but no significant differences were found in P2-HNF4A expression (P > 0.05). High P1-HNF4A expression indicated poor prognoses in GC patients (P < 0.01). Furthermore, P1-HNF4A overexpression significantly promoted SGC7901 and BGC823 cell proliferation, invasion and migration in vitro (P < 0.01). Murine xenograft experiments showed that P1-HNF4A overexpression promoted tumor growth (P < 0.05). Mechanistically, RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4A-overexpressing GC cells. Finally, chemokine (C-C motif) ligand 15 was identified as a direct target of P1-HNF4A in GC tissues.Conclusions:P1-HNF4A was the main oncogene during GC progression. The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.     

Patulin Detoxification by Recombinant Manganese Peroxidase from Moniliophthora roreri Expressed by Pichia pastoris

The fungal secondary metabolite patulin is a mycotoxin widespread in foods and beverages which poses a serious threat to human health. However, no enzyme was known to be able to degrade this mycotoxin. For the first time, we discovered that a manganese peroxidase (MrMnP) from Moniliophthora roreri can efficiently degrade patulin. The MrMnP gene was cloned into pPICZα(A) and then the recombinant plasmid was transformed into Pichia pastoris X-33. The recombinant strain produced extracellular manganese peroxidase with an activity of up to 3659.5 U/L. The manganese peroxidase MrMnP was able to rapidly degrade patulin, with hydroascladiol appearing as a main degradation product. Five mg/L of pure patulin were completely degraded within 5 h. Moreover, up to 95% of the toxin was eliminated in a simulated patulin-contaminated apple juice after 24 h. Using Escherichia coli as a model, it was demonstrated that the deconstruction of patulin led to detoxification. Collectively, these traits make MrMnP an intriguing candidate useful in enzymatic detoxification of patulin in foods and beverages.     

Acute myeloid leukemia: negative prognostic impact of early blast persistence can be in part overcome by a later remission prior to post-induction therapy

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, event-free survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases.     

Combined first-pass perfusion and viability study at MR imaging in patients with non-ST segment-elevation acute coronary syndromes: feasibility study

PURPOSE: To assess the feasibility of combined perfusion and viability testing by using magnetic resonance (MR) imaging in one setting in patients with non-ST segment-elevation acute coronary syndromes. MATERIALS AND METHODS: The data of 13 patients (mean age, 68 years; range, 40-85 years) at high risk for myocardial infarction who underwent MR imaging at 1.5 T were reviewed. Risk factors were increased troponin T levels in seven, reversible ST depression on an electrocardiogram in four, history of myocardial infarction in two, and presence of heart failure in four. Cine imaging of the left ventricle was performed with a true-fast imaging with steady-state precession (FISP) sequence to assess the regional myocardial contraction and ejection fraction. After injection of 0.1 mmol per kilogram of body weight of gadopentetate dimeglumine, first-pass MR images were obtained by using an inversion-recovery true-FISP sequence at rest and during infusion of adenosine (140 microg/kg/min). Resting and stress images were assessed qualitatively for abnormal regional perfusion (hypoenhancement). The myocardium was divided into three radial segments corresponding to the three coronary artery territories. Delayed (after 15 minutes) contrast material-enhanced images were acquired with use of a segmented inversion-recovery fast low-angle shot sequence. Conventional coronary angiograms were compared with the first-pass images. A more than 50% stenosis in diameter in any coronary artery was considered substantial. Mann-Whitney test was used to assess any significant difference between the left ventricular ejection fraction (LVEF) in patients with and those without myocardial infarct. RESULTS: Mean LVEF was 51.5% (range, 30%-77%). First-pass stress perfusion studies depicted 25 segments of hypoenhancement in 11 patients. Comparison of first-pass perfusion defects with findings on coronary angiograms indicated an overall sensitivity of 92% (24 of 26) and specificity of 92% (12 of 13) in detection of substantial coronary artery disease. Infarcts detected from hyperenhancement on delayed contrast-enhanced images were present in eight segments (four were transmural) in five patients. No significant difference was noted in the LVEF between patients with and those without infarct (P =.724). CONCLUSION: Combined stress perfusion and viability MR imaging was feasible in patients with acute coronary syndromes. First-pass MR perfusion defects compare well with the presence of substantial coronary artery stenosis on conventional angiograms.     

神经外科护士参与质量管理的实践

目的探讨病区护士参与质量管理对神经外科护理质量的影响。方法2012年(实施前)单纯由护士长和质控员实施病区护理质量管理;2013年(实施后)全体护士参与病区护理质量管理,质控问题及时反馈整改,将质控结果纳入护士当月绩效考核。结果全体护士参与病区护理质量管理后,病区护理质量指标检查评分较实施前显著提升(均P0.01)。结论全体护士参与质量管理能提高护理质量,提高护士满意度。