Clinical Interpretation of Detection of IgM Anti-Brucella Antibody in the Absence of IgG and Vice Versa; a Diagnostic Challenge for Clinicians.

Non-specific and often misleading clinical presentation of active brucellosis has made it a diagnostic puzzle for treating physicians. Clinicians rely greatly on the detection of IgG and IgM anti-Brucella antibodies by ELISA. Different patterns of positivity have been observed for IgG and IgM anti-Brucella antibodies in different cases, which further increases the risk of an erroneous diagnosis. Detailed herein is our two-years data with varied Brucella serology patterns and their clinical interpretation. Between January 2015 to December 2017, 1102 samples were processed in the Immunology Laboratory of KFHU for Brucella serology. 68 samples were positive for both IgG and IgM, 28 samples were positive for IgG and negative for IgM while 15 samples were positive for IgM and negative for IgG antibodies against Brucella. Electronic medical records, history of exposure, signs, symptoms, laboratory data, and the final diagnosis were recorded for all these patients. None of the patients with only positive IgM antibodies was finally diagnosed with brucellosis, while a diagnosis of brucellosis was established for only one patient with IgG antibodies positive in his serum. All the double-positive (IgG- and IgM-positive) serology patterns were diagnosed as having brucellosis. We concluded that determination of single IgM or IgG anti-Brucella-antibodies by ELISA could both be considered as definite and should ideally be interpreted in the context of appropriate clinical scenario and confirmation by other laboratory assays.Non-specific and often misleading clinical presentation of active brucellosis has made it a diagnostic puzzle for treating physicians. Clinicians rely greatly on the detection of IgG and IgM anti-Brucella antibodies by ELISA. Different patterns of positivity have been observed for IgG and IgM anti-Brucella antibodies in different cases, which further increases the risk of an erroneous diagnosis. Detailed herein is our two-years data with varied Brucella serology patterns and their clinical interpretation. Between January 2015 to December 2017, 1102 samples were processed in the Immunology Laboratory of KFHU for Brucella serology. 68 samples were positive for both IgG and IgM, 28 samples were positive for IgG and negative for IgM while 15 samples were positive for IgM and negative for IgG antibodies against Brucella. Electronic medical records, history of exposure, signs, symptoms, laboratory data, and the final diagnosis were recorded for all these patients. None of the patients with only positive IgM antibodies was finally diagnosed with brucellosis, while a diagnosis of brucellosis was established for only one patient with IgG antibodies positive in his serum. All the double-positive (IgG- and IgM-positive) serology patterns were diagnosed as having brucellosis. We concluded that determination of single IgM or IgG anti-Brucella-antibodies by ELISA could both be considered as definite and should ideally be interpreted in the context of appropriate clinical scenario and confirmation by other laboratory assays.

Parameter estimation of qualitative biological regulatory networks on high performance computing hardware.

BACKGROUND: Biological Regulatory Networks (BRNs) are responsible for developmental and maintenance related functions in organisms. These functions are implemented by the dynamics of BRNs and are sensitive to regulations enforced by specific activators and inhibitors. The logical modeling formalism by René Thomas incorporates this sensitivity with a set of logical parameters modulated by available regulators, varying with time. With the increase in complexity of BRNs in terms of number of entities and their interactions, the task of parameters estimation becomes computationally expensive with existing sequential SMBioNET tool. We extend the existing sequential implementation of SMBioNET by using a data decomposition approach using a Java messaging library called MPJ Express. The approach divides the parameters space into different regions and each region is then explored in parallel on High Performance Computing (HPC) hardware. RESULTS: The performance of the parallel approach is evaluated on BRNs of different sizes, and experimental results on multicore and cluster computers showed almost linear speed-up. This parallel code can be executed on a wide range of concurrent hardware including laptops equipped with multicore processors, and specialized distributed memory computer systems. To demonstrate the application of parallel implementation, we selected a case study of Hexosamine Biosynthetic Pathway (HBP) in cancer progression to identify potential therapeutic targets against cancer. A set of logical parameters were computed for HBP model that directs the biological system to a state of recovery. Furthermore, the parameters also suggest a potential therapeutic intervention that restores homeostasis. Additionally, the performance of parallel application was also evaluated on a network (comprising of 23 entities) of Fibroblast Growth Factor Signalling in Drosophila melanogaster. CONCLUSIONS: Qualitative modeling framework is widely used for investigating dynamics of biological regulatory networks. However, computation of model parameters in qualitative modeling is computationally intensive. In this work, we presented results of our Java based parallel implementation that provides almost linear speed-up on both multicore and cluster platforms. The parallel implementation is available at https://psmbionet.github.io .

Skin Prick Test Reactivity to Common Aeroallergens among Allergic Rhinitis Patients.

OBJECTIVE: To identify the common aeroallergens causing allergy symptoms among the allergic rhinitis patients. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January to July 2016. METHODOLOGY: Patients with a clinical diagnosis of allergic rhinitis were enrolled. Skin Prick Test (SPT) was performed on these patients using 12 common aeroallergens along with positive (histamine hydrochloride, 10 mg/ml) and negative (glycerin saline) controls. Results were recorded after 15 minutes, considering a wheal diameter >3 mm as positive. Chi-square test was used to compare frequencies; and p-value of less than 0.05 was considered significant. RESULTS: Out of 130 patients, 78 (60%) were males and 52 (40%) were females. The rate of sensitization to any allergen was 90%. One hundred and two (78%) were poly-sensitized to more than two allergens and 20% were sensitized to more than six allergens. Most common outdoor and indoor allergens were Broussonetia papyrifera (50.7%) and Dermatophagoides farina (42.3%), respectively. Dog epithelia and aspergillus were the least prevalent allergens (13.8% each). CONCLUSION: This study highlighted an increased overall frequency of sensitization to any allergen and significance of tree and weed allergens; especially, Broussonetia papyrifera and Cannabis sativa. It also emphasized increased prevalence of skin reactivity to indoor allergen, Dermatophagoides farina in the city.

Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression.

The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. We compute delay constraints to reveal important associations between the production and degradation rates of proteins. O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer.