Circular frame fixation for calcaneal fractures risks injury to the medial neurovascular structures: a cadaveric description

Aim: There is a risk of iatrogenic injury to the soft tissues of the calcaneus and this study assesses the risk of injury to these structures in circular frame calcaneal fracture fixation. Materials and Methods: After olive tip wires were inserted, an L-shaped incision on the lateral and medial aspects of 5 formalin fixed cadaveric feet was performed to expose the underlying soft tissues. The calcaneus was divided into zones corresponding to high, medium and low risk using a grading system. Results: Structures at high risk included the posterior tibial artery, posterior tibial vein and posterior tibial nerve on the medial aspect. Soft tissue structures on the lateral side that were shown to be at lower risk of injury were the small saphenous vein and the sural nerve and the tendons of fibularis longus and fibularis brevis. Conclusion: The lateral surface of the calcaneus provides a lower risk area for external fixation. The risk of injury to significant soft tissues using a circular frame fixation approach has been shown to be greater on the medial aspect. Clinical Relevance: This study highlights the relevant anatomical relations in circular frame fixation for calcaneal fractures to minimize damage to these structures

High Grade B-Cell Non-Hodgkin’s Lymphoma Masquerading as Thyroid Carcinoma; a Case Report

Introduction: High grade B-cell lymphoma and diffuse large B cell exhibiting myelocytoma (MYC) translocation with B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) re-arrangements, also known as double and triple hit lymphomas, are aggressive entities. World Health Organization update 2017 includes this cytogenetically defined category of “High grade B cell lymphoma with myelocytoma MYC and BCL2 and/or BCL6 rearrangements” as a distinct entity on their own. We present an interesting case of an obese patient presenting with a neck mass, suspected to be an aggressive thyroid carcinoma, which eventually turned out to be a high grade B-cell lymphoma. Case description: A 64 years-old male presented with complaints of neck pain for 10 weeks and a huge swelling in front of neck for 4 weeks. Respiratory system evaluation revealed cough, pleuritic pain and expectoration. Rest of the systemic review was unremarkable. Baseline reports showed hypothyroid status. Ultrasonography (USG) thyroid showed right upper pole Thyroid Imaging Reporting and Data Systems - 4 (TIRADS-4) nodule with bilateral cervical lymphadenopathy for which correlation with fine needle aspiration cytology (FNAC) was advised. Magnetic resonance imaging (MRI) films were submitted for review which showed overall features of locally invasive primary thyroid malignancy. Case was discussed in a multi-disciplinary team (MDT) meeting and suspicion arose of non-thyroidal origin of tumor. Patient underwent Positron emission tomography/computed tomography (PET/CT) as per MDT recommendations. PET/CT findings were highly suggestive of lymphomatous disease as opposed to thyroidal malignancy suspicion early on, which was confirmed on histopathology of cervical nodes. Practical implications: High grade B-cell lymphoma is an aggressive entity and can be very deceptive in its presentation, as evident from this case report. Functional imaging modalities such as Fluorodeoxyglucose (F-18 FDG) PET/CT can provide crucial assistance in unmasking a deceptive disease entity masquerading as some other, thus changing the management plan completely

APOBEC3G Variant (rs6001417) CG and GG Genotypes and their protective feature against HIV-1 Infection in Pakistani Dwelled Community

Background: APOBEC3G (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) gene is one of the genetic host factors, have been linked with HIV-1 AIDS predisposing and protection in different residence populations. The investigation of genetic marker (APOBEC3G) variant (rs6001417) CC, CG and GG genotypes in Pakistan.Methods: The extraction of DNA, the DNA Rapid Salting-out method was used. Then the observed DNA with electrophoresis technique referred for quantitative real-time PCR to identify the APOBEC3G variant rs6001417 genotypes and Taq Man genotyping.  Results: Three genotypes of rs6001417 (CC, CG and GG) were compared both in HIV-1 infected patients and healthy control groups (p=0.73, p=0.007, p=0.01 respectively). The rs6001417 CG and GG genotype demonstrated a significant involvement in both the healthy and infected individuals and portraying possible protective effect against HIV-1 infection with predictive value of 36.43% and 13.57% respectively.Conclusion: APOBEC3G (rs6001417) CG and GG genotypes may have a protective feature in the progression of HIV-1 infection and we may use this as a preliminary predictive marker in the country for HIV-1 infected individuals as well.Keywords: HIV-1; APOBEC3G; Predictive marker; Predictive value; Real-time PC

Male predominant association with Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G variants (rs6001417, rs35228531, rs8177832) predict protection against HIV-1 infection

Background: Human immunodeficiency virus (HIV) infection, it is a global health concern mainly lead to acquired immune deficiency syndrome (AIDS). There are numerous limitations of this infection particularly in the form of host factors which may limit and interfere HIV-1 replication. The most notable host factors which hinder HIV-1 DNA propagation is the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide- like 3G (APOBEC3G). Any genetic polymorphism of this substantial host factor may impact the host susceptibility pattern to HIV viral infection in different part of the world. The aim of this study to examine genetic variants (rs6001417, rs35228531, rs8177832) effecting HIV-1 infection.Method: Three variants of APOBEC3G gene polymorphism were genotyped while using RT-PCR method. Frequency distribution of these genotypes was evaluated in both the HIV-1 and healthy group.Results: The rs6001417 CG (p = 0.03) and rs35228531 CT (p = 0.01) genotypes were found as protective elements, while rs35228531 TT (p = 0.02) and rs8177832 AA (p = 0.03) genotypes had shown susceptibility against the HIV-1 infection. Our data suggest, rs35228531 CT (p = 0.003) and rs8177832 AA (P = <0.001) genotypes have predominant incidences in HIV-1 male population than healthy control.Conclusion: We predict rs6001417 CG, rs35228531 CT as protective and rs35228531 TT, rs8177832 AA genotypes as a predisposing tool, against the HIV-1 infection in a section of Pakistani population. In addition, male gender was found predominantly high in both protective genotype rs35228531 CT (p = 0.003) and predisposing genotype rs8177832 AA (p = <0.001). The predominant contribution may help the patient to be predict about the status of HIV infection, however, extra efforts are required to study larger cohort of patients to better elucidate the association

Association of anti C1q and ds-DNA levels with the pathogenesis of Lupus Nephritis among SLE patients

Background: Lupus nephritis (LN) is the most common and serious complication associated with SLE and it results in significant morbidity and mortality. It is known by several studies that patients of LN have higher levels of anti-dsDNA and anti-C1q compared with SLE patients without renal involvement. The current study was designed to determine and compare the level of anti-dsDNA and anti-C1q in patients of SLE with and without lupus nephritis in the Pakistani population. This current study was also aimed at providing proof that anti-C1q levels are more prominent in LN/non-LN SLE as compared to anti-dsDNA. This project may help in the determination of results in Pakistan and contribute to the further confirmation of the sensitivity of anti-C1q.Method: The patient samples were collected from Sheikh Zayed hospital, Lahore. These patients were clinically diagnosed by the Rheumatologists as SLE and LN positive on the basis of ACR and SLEDAI scoring criteria. This study was performed and samples were analyzed in the Department of Medical and Laboratory Sciences, Imperial College of Business Study, Lahore on the patient’s serum by ELISA technique.Result: About 38% (12) patients with LN were positive for anti-dsDNA and 31% (9) SLE patients without LN were positive whereas about 38.7% (12) were anti-dsDNA negative in LN cases and 58.6% (17) in SLE without LN. In case of anti-C1q 100% (31) of these LN patients were positive and 93.1% (27) patients SLE without LN showed positive anti C1q results. Only 6.9% (2) patients showed negative results for anti-C1q in LN negative patientsConclusion: The higher levels of anti-C1q suggest that it may be a better diagnostic marker for LN than that of anti-dsDNA and that it can be helpful in the prognosis of SLE patients

Expression level of serum Interleukin-37 in Rheumatoid Arthritis patients and its correlation with Disease Activity Score

Background: Interleukin-37 (IL-37) is a member of IL-1 cytokine family. IL-37 immunosuppresses the pathogenesis of rheumatoid arthritis via down-regulating pro-inflammatory cytokines. The aim of the current study was to evaluate the expression level of IL-37 in rheumatoid arthritis (RA) patients and its correlation with the disease activity score in 28 joints (DAS-28).Methods: In the current study, forty-six RA patients, having a ratio of 19 males and 27 females, and twenty healthy controls (11 males and 9 females) were included. DAS-28 was measured on the basis of patients’ clinical observations of the tender and swollen joints, physical examination and erythrocyte sedimentation rate (ESR). ESR was measured according to the Westergren method. Serum IL-37 level was measured by ELISA. Depending upon the DAS28 calculations the patients were divided in four groups as; 19 in remission, 6 had mild disease activity, 6 were in moderate state and 15 patients were found with severe disease activity.Results: Serum IL-37 levels were found markedly raised in RA patients (mean = 862.6) than in healthy individuals (mean ± SD = 4.4 ± 1.74 pg/ml). Further, our results suggest that level of IL-37 increased significantly from mild (mean ± SD = 829.17 ± 61.40 pg/ml) to moderate (mean ± SD = 1307.5 ± 165.1 pg/ml) and severe (mean ± SD = 1607 ± 86.8 pg/ml) disease prognosis.Conclusion: Thus we conclude, IL-37 has a positive correlation with DAS28 and thus has a potential role in RA pathogenesis. Keywords: Interleukin 37, rheumatoid arthritis, autoimmune disorder, inflammation, disease activity scor

Impact of IL28B gene variants (rs12979860) in peg-IFN therapy against Chronic Hepatitis B Pakistani patients

Background: Genome wide association studies elucidate that IL28B rs12979860 genetic polymorphism has a substantial role as a pretreatment predictor during PEG-IFN therapy in Hepatitis C virus (HCV) infection, however its role in chronic hepatitis B (CHB) is ambiguous.Methods: In this study, we have investigated the role of IL28B variant rs12979860 for chronic hepatitis B (CHB) infection. 200 CHB patients were treated for 24 weeks, then we carried out our study on these patients. Moreover, all patients were investigated for IL28B rs12979860 genotypes CC, CT, TT through RT-PCR. Based on our preliminary results we categorized these patients into two groups i.e. Responder ¢R (n = 104) and Non-responder¢NR (n = 96).Results: The proportion of IL28B CC, CT, TT genotypes were in both responder and non-responder groups as (72.1%, 25.0%, 2.9% vs 53.1%, 40.6%, 6.2% respectively; P = 0.02). In this study CC was the most frequent genotype, which has significant outcome in PEG-IFN therapy in both R and NR groups (72.1% vs 53.1%) (P = 0.03), while CT and TT were found as (25.0% vs 40.6%) (P = 0.1, 2.09% vs 6.2%) (P = 0.3) respectively.Conclusion: Current study clearly demonstrates that IL28B rs12979860 polymorphism is a pretreatment predictor during PEG-IFN therapy in CHB infection, and patients with favorable genotype of rs12979860 (CC) may clear the virus than the non-favorable genotypes (CT, TT) in Pakistani population.

Molecular Basis of Binding Interactions of NSAIDs and Computer-Aided Drug Design Approaches in the Pursuit of the Development of Cyclooxygenase-2 (COX-2) Selective Inhibitors

The nonsteroidal anti-inflammatory drugs (NSAIDs) are important class of therapeutic agents used for the treatment of pain, inflammation and fever. Nonselective inhibition of cyclooxygenase (COX-1 and COX-2) isoenzymes by classical NSAIDs is associated with undesirable side effects such as gastrointestinal (GI) and renal toxicities due to COX-1 inhibition. To circumvent this problem, several COX-2 selective inhibitors were developed with superior GI safety profile. However, the voluntary market withdrawal of potent COX-2 selective inhibitors (rofecoxib and valdecoxib) due to their severe cardiovascular toxicity which is also found to be associated with some of the traditional NSAIDs suggesting the need to relook into the entire class of NSAIDs rather than exclusively victimizing the COX-2 selective inhibitors. Furthermore, the recent evidences for the involvement of COX-2 selective inhibitors in the aetiology of many diseases, such as Alzheimer’s disease, Parkinson’s disease, diabetes, various cancers and so on, have gained much attention for researchers to design and develop novel COX-2 selective inhibitors with improved pharmacodynamics and pharmacokinetic profile. This chapter is focused on the detailed analysis of molecular basis of binding interactions of various NSAIDs by highlighting the role of crucial amino acid residues at the binding site of cyclooxygenase enzymes (COXs) to be considered for selective inhibition of COX-2 enzyme while emphasising the impact of significant CADD strategies employed for designing new potent COX-2 inhibitors with tuned selectivity