Neutrophil-to-Lymphocyte Ratio as an Early Predictor of Complication and Mortality Outcomes in Individuals With Acute Pancreatitis at a UK District General Hospital: A Retrospective Analysis.

Aim The purpose of this study was to evaluate the predictive usefulness of the neutrophil-to-lymphocyte ratio (NLR) in patients with acute pancreatitis (AP) and establish a threshold for the prediction of poor outcomes. Methods For this investigation, we looked back at all cases of acute pancreatitis treated at Torbay Hospital in Torquay, UK, between January 1st, 2019, and December 31st, 2020. Those who were found to have chronic pancreatitis or whose baseline laboratory values could not be obtained were not included. Each patient's entire hospital stay was analyzed, including up to 72 hours of medical and laboratory data. Results According to the Glasgow Coma Scale scoring system, 28 of the 314 included patients had severe acute pancreatitis, and 81 patients had pancreatitis with complications. Those with complications had a substantially higher NLR on day 1 (9.43 ± 7.57) than patients who recovered without complications (7.37 ± 5.88) (P-value = 0.028). The NLR on day 0 (>18.71) exhibited a sensitivity of 80%, a specificity of 90.2%, and an accuracy of 83.9% in forecasting the death of patients with pancreatitis. Conclusion Elevated baseline NLR corresponds with pancreatitis with complications and can predict mortality.

Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model.

Variants in cardiac myosin-binding protein C (cMyBP-C) are the leading cause of inherited hypertrophic cardiomyopathy (HCM), demonstrating the key role that cMyBP-C plays in the heart's contractile machinery. To investigate the c-MYBPC3 HCM-related cardiac impairment, we generated a zebrafish mypbc3-knockout model. These knockout zebrafish displayed significant morphological heart alterations related to a significant decrease in ventricular and atrial diameters at systolic and diastolic states at the larval stages. Immunofluorescence staining revealed significant hyperplasia in the mutant's total cardiac and ventricular cardiomyocytes. Although cardiac contractility was similar to the wild-type control, the ejection fraction was significantly increased in the mypbc3 mutants. At later stages of larval development, the mutants demonstrated an early cardiac phenotype of myocardium remodeling, concurrent cardiomyocyte hyperplasia, and increased ejection fraction as critical processes in HCM initiation to counteract the increased ventricular myocardial wall stress. The examination of zebrafish adults showed a thickened ventricular cardiac wall with reduced heart rate, swimming speed, and endurance ability in both the mypbc3 heterozygous and homozygous groups. Furthermore, heart transcriptome profiling showed a significant downregulation of the actin-filament-based process, indicating an impaired actin cytoskeleton organization as the main dysregulating factor associated with the early ventricular cardiac hypertrophy in the zebrafish mypbc3 HCM model.

Arrhythmogenic calmodulin E105A mutation alters cardiac RyR2 regulation leading to cardiac dysfunction in zebrafish.

Calmodulin (CaM) is a universal calcium (Ca2+ )-binding messenger that regulates many vital cellular events. In cardiac muscle, CaM associates with ryanodine receptor 2 (RyR2) and regulates excitation-contraction coupling. Mutations in human genes CALM1, CALM2, and CALM3 have been associated with life-threatening heart disorders, such as long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia. A novel de novo LQTS-associated missense CaM mutation (E105A) was recently identified in a 6-year-old boy, who experienced an aborted first episode of cardiac arrest. Herein, we report the first molecular characterization of the CaM E105A mutation. Expression of the CaM E105A mutant in zebrafish embryos resulted in cardiac arrhythmia and increased heart rate, suggestive of ventricular tachycardia. In vitro biophysical and biochemical analysis revealed that E105A confers a deleterious effect on protein stability and a reduced Ca2+ -binding affinity due to loss of cooperativity. Finally, the CaM E105A mutation resulted in reduced CaM-RyR2 interaction and defective modulation of ryanodine binding. Our findings suggest that the CaM E105A mutation dysregulates normal cardiac function by a complex mechanism involving alterations in both CaM-Ca2+ and CaM-RyR2 interactions.

Biocompatibility and toxicity of novel iron chelator Starch-Deferoxamine (S-DFO) compared to zinc oxide nanoparticles to zebrafish embryo: An oxidative stress based apoptosis, physicochemical and neurological study profile.

OBJECTIVES: Clinically approved iron chelators are effective in decreasing significant transfusional iron accumulation. Starch-Deferoxamine (S-DFO), a novel high molecular weight iron chelator, was produced to increase binding capacity to iron and reduce toxicity. Although its efficacy was established in one small cohort clinical trial, its potential adverse effect was not adequately addressed. METHODS: We utilized zebrafish model to assess S-DFO toxicity using following assays: mortality, teratogenicity, hatching rate, tail flicking, Acridine Orange staining for apoptosis detection, o-dianisidine staining for hemoglobin synthesis, and the level of Hsp70 as a general stress indicator. Embryos were exposed to different concentrations of S-DFO, Zinc Oxide nanoparticle (ZnO) (positive control), along with untreated control (UC). RESULTS: S-DFO showed no significant mortality nor deformities at all tested concentrations (0.0-1000 µM). Thus, the LC50 is expected to >1000 µM. 100 µM S-DFO treatment did not affect embryo development (as judged by hatching rate); neuromuscular activity (as judged by tail flicking); and hemoglobin synthesis. Neither apoptosis, nor increase in Hsp70 level was noticed upon S-DFO treatment. CONCLUSION: Our assays demonstrate that S-DFO does not induce cellular or biochemical stress and has no adverse effect on organ development of zebrafish embryos, suggesting its safe use as an iron chelator.

Toxicity evaluation of selected ionic liquid compounds on embryonic development of Zebrafish.

Hydrate formation in seafloor pipelines is considered an economic and flow assurance issue for the oil and gas industries. Ionic liquids (ILs) have been recently used as potential hydrate inhibitors. Although branded as green compounds, their ecotoxicity in case of leakage from pipelines onto the aquatic environment needs more deep evaluations. Here, we investigate the impacts of three ILs previously used as successful thermodynamic hydrate inhibitors namely choline chloride (ChC1), 1-methyl-1-propyl pyrrolidinium triflate (PMPy [triflate]) and tetra-methyl ammonium acetate (TMAA). Mortality (including LC50), teratogenicity, locomotion and neurotoxicity, and hatching rate were utilized to investigate any potential acute toxicity of these ILs on embryonic development of zebrafish. No significant mortality or teratogenic effects were found for all tested compounds in a concentration range between 50 and 200 mg/L. The LC50 was significantly higher than the tested dose >200 mg/L. While, up to 200 mg/L all compound had no impact on the survival rate, ChCl showed a significant effect on neuromuscular development as judged by the increase of spontaneous tail coiling activity (25 VS 4 burst/ minutes of the negative control-treated embryos). Further, apart from PMPy [triflate], ChC1 and TMAA had a significant adverse effect on the hatching rate of the treated embryos at concentrations of 200 mg/L. However, this effect was very mild at lower concentrations (≤100 mg/L). Our data indicate that within the tested concentrations both TMAA and PMPy [triflate] had no or little potential harmful effect on embryonic development of aquatic fauna "green", while ChC1 should be used with caution.