Standard atlas space for C57BL/6J neonatal mouse brain

A standard atlas space with stereotaxic co-ordinates for the postnatal day 0 (P0) C57BL/6J mouse brain was constructed from the average of eight individual co-registered MR image volumes. Accuracy of registration and morphometric variations in structures between subjects were analyzed statistically. We also applied this atlas coordinate system to data acquired using different imaging protocols as well as to a high-resolution histological atlas obtained from separate animals. Mapping accuracy in the atlas space was examined to determine the applicability of this atlas framework. The results show that the atlas space defined here provides a stable framework for image registration for P0 normal mouse brains. With an appropriate feature-based co-registration strategy, the probability atlas can also provide an accurate anatomical map for images acquired using invasive imaging methods. The atlas templates and the probability map of the anatomical labels are available at .     

A Novel Bayesian Method for Efficacy Assessment in Animal Oncology Studies

In pre-clinical oncology studies, the investigator often compares efficacy of two or more treatments on tumor-bearing animals over a period of time. This is accomplished either through comparison of tumor volumes at various time points or overall survival. Due to ethical concerns, animals are euthanized before the end of the study whenever their tumor volumes reach a prespecified limit, the loss of bodyweight is beyond 20% or severely ulcerated tumors are observed. The traditional cross time-point tumor-size comparisons should not be performed when animals leave the study in a nonrandom nature. Survival analysis may alternatively be carried out to compare the time-to-euthanasia or natural death across treatment groups. As a result of government regulations, however, animal survival studies are hampered by small-sample sizes, often making statistical inference of survival data difficult. For example, it may be impossible to estimate median survival for an efficacious treatment group in which the majority of animals survive to the end of the study. Such cases create challenges to investigators who wish to rank-order the treatment effects, in effect picking the “winners” for further investigation. In this aricle, we list the benefits and shortcomings of popular methods and then propose a novel hypothesis test based directly on the survival probability to rank order the efficacy of treatments. The performance of the method is illustrated using a real-life example.     

A meta-summary of case reports of non-vitamin K antagonist oral anticoagulant use in patients with left ventricular thrombus

Left ventricular (LV) thrombus is commonly seen in patients with extensive anterior ST-elevation myocardial infarction. The standard of care for LV thrombus is anticoagulation with warfarin. However, there has been an increasing trend of case reports using non-vitamin K antagonist oral anticoagulants (NOAC) for the treatment of LV thrombus. This study aimed to perform a meta-summary of the literature to characterise and evaluate the safety and feasibility of using NOAC in patients with LV thrombus. We searched for articles published in four electronic databases: PubMed, EMBASE, Scopus and Google Scholar using an appropriate keyword/MeSH term search strategy. Twenty-four studies comprising 36 patients were included in the analysis. Rivaroxaban was used in majority of patients (47.2%), whilst Apixaban and Dabigatran were prescribed in 25.0% and 27.8% of patients respectively. The most commonly associated risk factor found was post-acute myocardial infarction in 15 patients (41.7%). LV thrombus resolution was met by most patients (87.9%), and the median duration of treatment to resolution was 30.0 days (IQR?=?22.5–47.0). One non-fatal bleeding event (3.0%) and no embolic events were reported. The use of NOAC may have a role in the treatment of LV thrombus in selected patients. Further randomized controlled trials are needed to evaluate this treatment strategy.     

Evaluation of smear layer removal by bicarbonate soda,ethylenediamine tetraacetic acid with cetrimide and sodium hypochlorite with a new model

Various methods are used to evaluate irrigants. The primary aim was to develop a model for preliminary testing of potential irrigants. The second aim was to investigate the effect of bicarbonate soda on smear layer by comparing it with ethylenediamine tetraacetic acid with cetrimide (EDTAC) and sodium hypochlorite (NaOCl). Extracted human single‐canal teeth were halved, and a uniform filing method was used to create smear layer. The following solutions were then applied – distilled water (control), 1% NaOCl, 17% EDTAC and bicarbonate soda at concentrations of 1%, 5%, 10% and 15%. Some samples had multiple solutions in different sequences. Samples were examined by scanning electron microscopy. Representative images were scored based on the degree of smear layer remaining. Results were analysed with the SAS system, using the GENMOD procedure. Complete smear layer was found in samples treated with all solutions except EDTAC used alone. There were no significant differences between the sequences, EDTAC/NaOCl/EDTAC and NaOCl/EDTAC/NaOCl. There were no significant differences between groups with and without bicarbonate soda. In conclusion, the model was effective for testing chemical effects on solutions on smear layer. Bicarbonate soda did not remove smear layer and provided no additional cleaning effects after EDTAC and NaOCl.     

Development of decellularized conjunctiva as a substrate for the ex vivo expansion of conjunctival epithelium

This study was performed to develop a method to decellularize human conjunctiva and to characterize the tissue in terms of its deoxyribose nucleic acid (DNA) content, tensile strength, collagen denaturation, basement membrane, extracellular matrix components and its potential to support conjunctival epithelial growth. Human conjunctival tissues were subjected to a decellularization process involving hypotonic detergent and nuclease buffers. Variations in sodium dodecyl sulfate concentration (0.05–0.5%, w/v) were tested to determine the appropriate concentration of detergent buffer. DNA quantification, collagen denaturation, cytotoxicity and tensile strength were investigated. Human conjunctival cell growth by explant culture on the decellularized tissue substrate was assessed after 28 days in culture. Samples were fixed and paraffin embedded for immunohistochemistry including conjunctival epithelial cell markers and extracellular matrix proteins. Conjunctival tissue from 20 eyes of 10 donors (age range 65–92 years) was used. Decellularization of human conjunctiva was achieved to 99% or greater DNA removal (p < 0.001) with absence of nuclear staining. This was reproducible at the lowest concentration of sodium dodecyl sulfate (0.05% w/v). No collagen denaturation (p = 0.74) and no difference in tensile strength parameters was demonstrated following decellularization. No significant difference was noted in the immunolocalization of collagen IV, laminin and fibronectin, or in the appearance of periodic acid–Schiff‐stained basement membranes following decellularization. The decellularized tissue did not exhibit any cytotoxicity and explant culture resulted in the growth of stratified conjunctival epithelium. Allogeneic decellularized human conjunctiva can be successfully decellularized using the described protocol. It represents a novel substrate to support the expansion of conjunctival epithelium for ocular surface cellular replacement therapies. Copyright © 2017 John Wiley & Sons, Ltd.     

Massive pulmonary embolism in a patient with nephrotic syndrome and single lung

Journal of Thrombosis and Thrombolysis - We present a novel case of a patient with nephrotic syndrome and previous left pneumonectomy who had a massive pulmonary embolism of his remnant right...