A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell-Mediated Cytotoxicity

Benralizumab is a humanized anti-IL5 receptor α (IL5Rα) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function. An ADCC reporter cell-based neutralizing antibody (NAb) assay was developed and characterized to detect NAb against benralizumab in human serum to support the clinical development of benralizumab. The optimal ratio of target cells to effector cells was 3:1. Neither parental benralizumab (fucosylated) nor benralizumab Fab resulted in ADCC activity, confirming the requirement for ADCC activity in the NAb assay. The serum tolerance of the cells was determined to be 2.5%. The cut point derived from normal and asthma serum samples was comparable. The effective range of benralizumab was determined, and 35 ng/mL [80% maximal effective concentration (EC₈₀)] was chosen as the standard concentration to run in the assessment of NAb. An affinity purified goat anti-benralizumab polyclonal idiotype antibody preparation was shown to have NAb since it inhibited ADCC activity in a dose-dependent fashion. The low endogenous concentrations of IL5 and soluble IL5 receptor (sIL5R) did not demonstrate to interfere with the assay. The estimated assay sensitivities at the cut point were 1.02 and 1.10 μg/mL as determined by the surrogate neutralizing goat polyclonal and mouse monoclonal anti-drug antibody (ADA) controls, respectively. The assay can detect NAb (at 2.5 μg/mL) in the presence of 0.78 μg/mL benralizumab. The assay was not susceptible to non-specific matrix effects. This study provides an approach and feasibility of developing an ADCC cell-based NAb assay to support biopharmaceuticals with an ADCC function.KEY WORDS: ADCC, benralizumab, cell-based assay, mechanism of action, neutralizing antibody     

Inpatient Management of Pulmonary Embolism: Clinical Characteristics and Mortality in a High-Volume Tertiary Care Center

Journal of Thrombosis and Thrombolysis - The optimal management strategy for submassive or intermediate risk pulmonary embolism (IRPE)—anticoagulation alone versus anticoagulation plus...     

Automatic Computation of Left Ventricular Volume Changes Over a Cardiac Cycle from Echocardiography Images by Nonlinear Dimensionality Reduction

Curve of left ventricular (LV) volume changes throughout the cardiac cycle is a fundamental parameter for clinical evaluation of various cardiovascular diseases. Currently, this evaluation is often performed manually which is tedious and time consuming and suffers from significant interobserver and intraobserver variability. This paper introduces a new automatic method, based on nonlinear dimensionality reduction (NLDR) for extracting the curve of the LV volume changes over a cardiac cycle from two-dimensional (2-D) echocardiography images. Isometric feature mapping (Isomap) is one of the most popular NLDR algorithms. In this study, a modified version of Isomap algorithm, where image to image distance metric is computed using nonrigid registration, is applied on 2-D echocardiography images of one cycle of heart. Using this approach, the nonlinear information of these images is embedded in a 2-D manifold and each image is characterized by a symbol on the constructed manifold. This new representation visualizes the relationship between these images based on LV volume changes and allows extracting the curve of the LV volume changes automatically. Our method in comparison to the traditional segmentation algorithms does not need any LV myocardial segmentation and tracking, particularly difficult in the echocardiography images. Moreover, a large data set under various diseases for training is not required. The results obtained by our method are quantitatively evaluated to those obtained manually by the highly experienced echocardiographer on ten healthy volunteers and six patients which depict the usefulness of the presented method.     

Outcomes of Second Look Exploration in Testicular Torsion of Children

Background:

Testicular torsion (TT), or twisting of the testicle resulting in a strangulation of the blood supply, occurs in men whose tissue surrounding the testicle is not well attached to the scrotum. It is important to emphasize that testicular torsion is a medical emergency.

Objectives:

The aim of this study is to evaluate the second look exploration and outcomes in TT.

Patients and Methods:

Seventy boys out of 124 patients underwent early exploration and 48 hours later second look exploration due to TT. All patients were checked with preoperative color-doppler ultrasonography (CDU) and intraoperative bleeding test. Data included age at admission, side of pathology, relation of TT with season of year, duration of preoperative history, degree of testicular torsion, CDU findings, and degree of bleeding; results of second look exploration, follow-up, and outcomes were analyzed.

Results:

Totally 70 patients were included in this study within five years, of which mean age was 28.6 ± 32.9 months (range 1 to 144), 48% of our patients had nausea and vomiting. Preoperative CDU showed absent/weak flow in 50 (71%) cases. Winter showed most frequently (44%) referred cases of testicular torsion. Orchidopexy was performed in 44 (63%) and orchidectomy in 26 (37%) cases after second look exploration. Mean follow-up duration was 3.1 ± 1.4 years. 4 (9%) cases in orchidopexy group developed testicular atrophy during follow-up, all four cases had a history of longer than 12 hours and grade II testicular bleeding test intra-operatively. Other orchidopexy patients salvaged. 26 patients, who were in grade III, underwent orchidectomy in second look exploration.

Conclusions:

TT requires emergency attention. The ischemia time of the testis is traditionally after 6 hours, and imaging or other diagnostic modality should not be a cause of delay. Early surgical exploration is modality of choice, and second look exploration after 48 hours can be more effective and salvageable in these patients.     

Persistent Truncus Arteriosus With Intact Ventricular Septum: Clinical,Hemodynamic and Short-term Surgical Outcome

Introduction:

Truncus arteriosus with intact ventricular septum is a rare and unique variant of persistent truncus arteriosus (PTA) which usually presents with central cyanosis and congestive heart failure in neonate and early infancy. Associated cardiac and non-cardiac anomalies may affect morbidity and mortality of these patients.

Case Presentation:

We describe clinical presentation, echocardiography and angiographic features of a 7-month old boy with PTA and intact ventricular septum who underwent surgical repair of the anomaly at our institution. Operative findings, surgical procedure and short-term outcome are reported.

Conclusions:

While our patient had systemic pulmonary arterial pressure at the time of complete surgical repair, it was improved after surgery.     

Ex Situ Conservation Strategies for <Emphasis Type="Italic">Fritillaria cirrhosa</Emphasis> D. Don (Liliaceae): A Critically Endangered Medicinal Herb of Kashmir Himalaya

Fritillaria cirrhosa D. Don (Liliaceae), a valuable and critically endangered medicinal herb of northwest India, including Jammu and Kashmir, grows in temperate to alpine regions of the Himalaya. The bulbs of the plant are very valuable and are used to cure asthma, tuberculosis, haematemesis and many other health complications. The species faces threat due to multiple factors including habitat loss, over-exploitation for medicine, domestic and commercial trade. The present study was therefore undertaken to develop ex situ conservation strategies and domestication protocols for Fritillaria cirrhosa. The experimental treatments utilized to enhance the regeneration potential, growth and development of Fritillaria cirrhosa include soil texture variation, fertilizer treatment and farmyard manure treatment. The highest values of phenotypic attributes of the plants were recorded in soil: sand combination of 3:1. The plants prefer to grow in low sandy soils. Maximum plant height was attained in a combination of urea (nitrogen), diammonium phosphate (phosphorous) and potash (potassium) fertilizers. The plants depicted an admirably increased height and flower length in 1:1:2 combination and highest flower and leaf numbers in 2:1:1 combination of soil: sand: farmyard manure. Thus, low sandy soil with high organic matter was found to be favourable for better growth and development of the plants of Fritillaria cirrhosa.     

The psychometric properties of the mindful attention awareness scale among Arab parents of children with autism spectrum disorder

Aim

The purpose of this study was to examine the psychometric properties and the theoretical structure of the mindful attention awareness scale (MAAS) with parents of children with autism spectrum disorder (ASD) in Jordan.