Technologies bringing young Zebrafish from a niche field to the limelight

Fundamental life science and pharmaceutical research are continually striving to provide physiologically relevant context for their biological studies. Zebrafish present an opportunity for high-content screening (HCS) to bring a true in vivo model system to screening studies. Zebrafish embryos and young larvae are an economical, human-relevant model organism that are amenable to both genetic engineering and modification, and direct inspection via microscopy. The use of these organisms entails unique challenges that new technologies are overcoming, including artificial intelligence (AI). In this perspective article, we describe the state-of-the-art in terms of automated sample handling, imaging, and data analysis with zebrafish during early developmental stages. We highlight advances in orienting the embryos, including the use of robots, microfluidics, and creative multi-well plate solutions. Analyzing the micrographs in a fast, reliable fashion that maintains the anatomical context of the fluorescently labeled cells is a crucial step. Existing software solutions range from AI-driven commercial solutions to bespoke analysis algorithms. Deep learning appears to be a critical tool that researchers are only beginning to apply, but already facilitates many automated steps in the experimental workflow. Currently, such work has permitted the cellular quantification of multiple cell types in vivo, including stem cell responses to stress and drugs, neuronal myelination and macrophage behavior during inflammation and infection. We evaluate pro and cons of proprietary versus open-source methodologies for combining technologies into fully automated workflows of zebrafish studies. Zebrafish are poised to charge into HCS with ever-greater presence, bringing a new level of physiological context

C-reactive protein serum levels as an early predictor of outcome in patients with pandemic H1N1 influenza A virus infection

<p>Abstract</p> <p>Background</p> <p>Data for predicting which patients with pandemic influenza A (H1N1) infection are likely to run a complicated course are sparse. We retrospectively studied whether the admission serum C-reactive protein (CRP) levels can serve as a predictor of illness severity.</p> <p>Methods</p> <p>Included were all consecutive adult patients who presented to the emergency department (ED) between May-December, 2009 with a flu-like illness, a confirmed diagnosis of pandemic influenza A (H1N1) infection and a serum CRP level measured within 24 hours of presentation. Patients with a proven additional concurrent acute illness (e.g., bacteremia) were excluded. We used the ROC curve analysis, Kaplan-Meier curves and the Cox proportional hazard model to evaluate the predictive ability of CRP as a prognostic factor.</p> <p>Results</p> <p>Seventeen (9%) of the 191 enrolled patients were admitted to the intensive care unit (ICU), of whom eight (4%) required mechanical ventilation and three (2%) died. The median admission serum CRP levels were significantly higher among patients who required subsequent ICU care and mechanical ventilation than among patients who did not (123 mg/L and 112 mg/L vs. 40 mg/L, <it>p </it>< .001 and 43 mg/L, <it>p </it>= .017, respectively). A Cox proportional hazard model identified admission serum CRP levels and auscultatory findings over the lungs as independent prognostic factors for ICU admission. Admission serum CRP levels were the only independent prognostic factor for mechanical ventilation. Thirty days after presenting to the ED, none of the patients with admission serum CRP level <28 mg/L (lower tertile) required either ICU admission or mechanical ventilation. At the same time point, 19% of the patients with admission serum CRP level ≥70 mg/L (upper tertile) needed to be admitted to the ICU and 8% of the same upper tertile group required mechanical ventilation. The differences in the rates between the lower vs. upper tertile groups were significant (Log-Rank <it>p </it>< .001 for ICU and <it>p </it>< .024 for mechanical ventilation).</p> <p>Conclusions</p> <p>In our study group, serum CRP levels obtained in the early ED admission stage from patients presenting with pandemic H1N1 influenza A infection were found to serve as a useful gauge for predicting disease course and assisting in patient management.</p

Community standards for open cell migration data

Cell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited owing to the diversity of experimental protocols and non-standardized output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardized data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardization efforts by the Cell Migration Standardisation Organisation (CMSO), an open community-driven organization to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration

Travel-Related Tick-Borne Encephalitis, Israel, 2006–2014

During 2006–2014, four tick-borne encephalitis (TBE) cases occurred among Israeli travelers. We calculated TBE incidence at 321.0, 45.0, 13.2, and 7.5 cases/100,000 travelers/year of travel to Sweden, Switzerland, Austria, and Germany, respectively. TBE incidence among travelers to these destinations appears to justify TBE vaccination in accordance with World Health Organization recommendations

Original Investigation Orijinal Araflt›rma Drug-induced Torsades de Pointes in patients aged 80 years or more Seksen yafl ve üstü hastalarda ilaçlara ba¤l› Torsades de Pointes

ABSTRACT Objective: We studied all English-written peer-reviewed reports on drug-induced Torsades de Pointes (TdP) in patients aged 80 years or more in order to characterize the clinical circumstances leading to this serious complication. Methods: Our literature search yielded 24 reports on 25 patients aged 80-95 years with drug-induced TdP. We systematically reviewed each report and recorded the non-modifiable risk factors for drug-induced TdP (i.e., female sex and structural heart disease) as well as preventable clinical circumstances, which might have been associated with drug-induced TdP. Results: The most prevalent risk factors for drug-induced TdP were non-modifiable risk factors: 22 (88%) patients were female patients and 19 (76%) patients had structural heart disease. Overall, 16 (64%) patients were female patients with structural heart disease. The literature did not report any elderly male patients without structural heart disease. Among the preventable clinical circumstances, which might have been associated with drug-induced TdP, the most prevalent were: administrating QT prolonging agents despite long QT interval (n=11; 44%) and co-administration of two or more QT prolonging agents (n=9; 36%). The most prevalent QT prolonging agents found to trigger TdP were macrolides and quinolones (n=9; 36%). All but three patients had at least one or more preventable clinical circumstances, which might have been associated with drug-induced TdP. Conclusion: Physicians should be more aware of the risk for drug-induced TdP in patients aged 80 years or more while administrating QT prolonging agents despite long QT interval and co-administrating two or more QT prolonging agents, specifically in elderly female patients with structural heart disease

Acute Kidney Injury Recovery Patterns in ST-Segment Elevation Myocardial Infarction Patients

Background: Acute kidney injury (AKI) is a frequent complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Identification of different AKI recovery patterns may improve patient prognostic stratification. We investigated the clinical relevance of AKI recovery patterns among STEMI patients undergoing PCI. Methods: A retrospective study of 2943 STEMI patients undergoing PCI. The incidence of renal impairment, in-hospital complications, short and long-term mortality, were compared between patients without AKI, with early recovery defined as a return to baseline creatinine within 72 h, and no AKI recovery/delayed recovery defined as all other AKI cases. Results: A total of 255 (8.7%) patients developed AKI, of whom 124/255 (49%) patients had an early recovery, whereas 131/255 (51%) had no AKI recovery/delayed recovery. Patients without recovery were more likely to have in-hospital complications and higher long-term mortality (36.64% vs. 7.25%%; p &lt; 0.001). In a multivariable regression model, the mortality hazard ratio (HR) for long term mortality remained significant for patients with no/delayed recovery AKI (HR 7.76, 95% CI 4.69 to 12.86, p &lt; 0.001), and a strong trend among patients with resolving AKI (HR 2.09, 95% CI 0.933&ndash;4.687, p = 0.071). Conclusions: Among STEMI patients undergoing PCI, the recovery pattern of AKI is a valuable prognostic marker

Antibiotic Use during the COVID-19 Pandemic in a Tertiary Hospital with an Ongoing Antibiotic Stewardship Program

During the recent pandemic, the fact that the clinical manifestation of COVID-19 may be indistinguishable from bacterial infection, as well as concerns of bacterial co-infection, have been associated with an increased use of antibiotics. The objective of this study was to assess the effect of targeted antibiotic stewardship programs (ASP) on the use of antibiotics in designated COVID-19 departments and to compare it to the antibiotic use in the equivalent departments in the same periods of 2018 and 2019. Antibiotic consumption was assessed as days of treatment (DOT) per 1000 patient days (PDs). The COVID-19 pandemic was divided into three periods (waves) according to the pandemic dynamics. The proportion of patients who received at least one antibiotic was significantly lower in COVID-19 departments compared to equivalent departments in 2018 and 2019 (Wave 2: 30.2% vs. 45.6% and 44.9%, respectively; Wave 3: 30.5% vs. 47.8% and 50.1%, respectively, p &lt; 0.001). The DOT/1000PDs in every COVID-19 wave was lower than during similar periods in 2018 and 2019 (179-282 DOT/1000PDs vs. 452-470 DOT/1000PDs vs. 426-479 DOT/1000PDs, respectively). Moreover, antibiotic consumption decreased over time during the pandemic. In conclusion, a strong ASP is effective in restricting antibiotic consumption, particularly for COVID-19 which is a viral disease that may mimic bacterial sepsis but has a low rate of concurrent bacterial infection

Empirical Anthelmintic Therapy for Patients with Eosinophilia in Nepal: A Prospective Cohort Study

Eosinophilia is common in low-resource countries and usually implies helminthiasis. Since helminthiasis is a common cause of eosinophilia and its diagnosis is cumbersome, we hypothesized that broad-spectrum anthelmintic therapy may decrease the eosinophil count and eventually cure helminthiasis, whether microbiologic diagnosis is established or not. We recruited patients with eosinophilia aged 5 years and older who presented to Dhulikhel hospital, Nepal. Patients were treated with albendazole and ivermectin. A stool sample for microscopy was obtained. Of a total of 113 patients, 106 had a follow-up visit and 56 were classified as responders to treatment (defined as a decrease in eosinophil count to below 500 cells/µL, or an absolute decrease of more than 1000 cells/µL). For all patients, we found an absolute decrease in the eosinophil count and for the responding group (more than 50% of the whole cohort), the eosinophil count decreased substantially. All stool samples were negative. The reason for a lack of response in the remaining patients is unclear. In order to ascertain whether eosinophilia should be an indication for anthelmintic treatment, a randomized controlled study of empirical treatment after a thorough microbiologic workup is needed