Recent advances in biological nanopores for nanopore sequencing, sensing and comparison of functional variations in MspA mutants.

Biological nanopores are revolutionizing human health by the great myriad of detection and diagnostic skills. Their nano-confined area and ingenious shape are suitable to investigate a diverse range of molecules that were difficult to identify with the previous techniques. Additionally, high throughput and label-free detection of target analytes instigated the exploration of new bacterial channel proteins such as Fragaceatoxin C (FraC), Cytolysin A (ClyA), Ferric hydroxamate uptake component A (FhuA) and Curli specific gene G (CsgG) along with the former ones, like α-hemolysin (αHL), Mycobacterium smegmatis porin A (MspA), aerolysin, bacteriophage phi 29 and Outer membrane porin G (OmpG). Herein, we discuss some well-known biological nanopores but emphasize on MspA and compare the effects of site-directed mutagenesis on the detection ability of its mutants in view of the surface charge distribution, voltage threshold and pore-analyte interaction. We also discuss illustrious and latest advances in biological nanopores for past 2-3 years due to limited space. Last but not the least, we elucidate our perspective for selecting a biological nanopore and propose some future directions to design a customized nanopore that would be suitable for DNA sequencing and sensing of other nontrivial molecules in question.

CORRIGENDUM to: Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population.

Due to oversight of an author, in the manuscript entitled "Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population" one author's name in the authors' list was erroneously published in the Journal "Current HIV Research" 2018; 16(4): 297-301.

Predictive value of IL-28B rs12979860 variants for peg-IFN, sofosbuvir plus ribavirin treatment of HCV infection in Pakistani population.

AIM: The correlation of IL28-B genetic variants (rs12979860) with combinational therapy (peg-interferon, sofosbuvir plus ribavirin) of hepatitis C virus infection were studied in 154 chronic hepatitis C patients. METHODS & RESULTS: The sustained virological response for efficient antiviral regimen was achieved in 75.32% treated individuals. Three genotypes of rs12979860 (CC, CT and TT) were compared both in sustained virological response and nonresponders groups (p = 0.25, p ≤ 0.001, p = 0.10, respectively). CT genotype demonstrated a significant correlation (p ≤ 0.001) in both groups with higher positive predictive value (81.55%). CONCLUSION: IL28 polymorphism and positive predictive value may be considered as the markers for the evaluation of the effectiveness of the treatment regimen. Further clinical trials are recommended to verify the role of IL28-B in hepatitis C virus treatment.

Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population.

BACKGROUND: Human immunodeficiency virus (HIV) infection is a global health burden which ultimately results in acquired immune deficiency syndrome (AIDS). There are multiple host factors which are capable of limiting HIV-1 replication. One of the most important host factors which inhibit HIV-1 DNA synthesis is the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide- like 3G (APOBEC3G). Any genetic variation of this important host factor may influence the host susceptibility to viral infection. OBJECTIVE: The aim of the current study was to evaluate any correlation of APOBEC3G genetic variation rs8177832 with HIV-1 infection. METHODS: The study involved 142 healthy control and 100 HIV-1 infected subjects. The genetic variation rs8177832 of all studied subjects was determined by allele-specific polymerase chain reaction (AS-PCR). RESULTS: The results showed that the distribution of rs8177832 genotypes AA, AG and GG in healthy subjects and HIV-1 subjects was; 42.253%, 42.957%, 14.788% and 66%, 27%, 7% respectively. Statistical analyses of data showed that there was a significant variation in rs8177832 genotype AA in healthy control and HIV-1 infected subjects (42.257% vs 66%; p-value<0.001). CONCLUSION: Thus it was concluded that APOBEC3G rs8177832 AA genotype contributes in genetic predisposition to HIV-1 infection in Pakistani population.

Clinical profile in arrhythmogenic cardiomyopathy and a recessive plakophilin-2 gene mutation.

OBJECTIVE: Arrhythmogenic cardiomyopathy (ACM) is not an uncommon cause of cardiac morbidity in Kashmir valley. This study was designed to document various clinical features and to sequence exons 11 and 12 of plakophilin 2 (PKP2) gene in these patients. METHODS: ACM patients who attended cardiology outpatient department of our institute from January 2014 to April 2015 were included in the study. Their records were reviewed. Controls were randomly selected, who had no history or family history of cardiac illness and had a normal cardiac examination. A blood sample was also taken from both the groups for sequencing of exon 11 and 12 of PKP2 gene. ACM patients were followed up until July 2016. RESULTS: Eleven ACM patients and seven controls were included in the study. Most common mode of presentation was ventricular tachycardia (VT). Two patients had left ventricular (LV) systolic dysfunction. One patient had a splice site mutation in exon 12 of PKP2 gene and one patient died during follow-up. One of the controls had an intronic variation that has no pathogenic significance vis-à-vis ACM. CONCLUSION: Our study describes various clinical parameters in ACM patients and a recessive plakophilin 2 mutation after a limited PKP2 gene sequencing.

Lymphoma presenting as severe left ventricular systolic dysfunction: a case report.

Lymphoma involving the heart is rare. This is a case report on non-Hodgkin lymphoma where the patient presented for the first time with heart failure and severe left ventricular systolic dysfunction due to lymphoma infiltrating the heart muscle and had simultaneous bilateral involvement of kidneys. This type of presentation has never been described in world literature and is the first reported case.

Combined severe valvular aortic and valvular pulmonary stenosis and its management - A case report and literature review.

Isolated congenital valvular stenosis of either aortic or pulmonary valve is commonly seen yet the presence of both these lesions in the same patient is rare. This combination presents unusual diagnostic as well as management problems. Apart from a few case reports, there is little in the literature on the combined stenosis of both semilunar valves. We present here a case report of a three and half year old boy diagnosed as a combined congenital severe valvular aortic stenosis with valvular pulmonary stenosis. The patient underwent successful balloon dilatation of both these valves in the same sitting.

Clinico-radiological profile of arrhythmogenic right ventricular dysplasia at a tertiary care center: Two year experience.

BACKGROUND: Arrythmogenic right ventricular dysplasia (ARVD/C) refers to fibro fatty infiltration replacement of ventricular myocardium especially that of right ventricle. The clinical presentation varies from asymptomatic state to ventricular tachycardia, heart failure and even sudden death. Diagnosis is established using modified ARVD/C taskforce criteria. Among all the various modalities of diagnosis, magnetic resonance imaging (MRI) gives most comprehensive evaluation of both morphological and functional abnormalities in this disease. MRI may not only obviate need for myocardial biopsy but also give insights into the nature of disease like presence of left ventricular myocardial involvement. We present our 2 years experience of ARVD/C patents who were admitted in our center and in whom diagnosis of ARVD/C was supported by excellent MR imaging. MATERIALS AND METHODS: This study was conducted by Department of Radiology and Cardiology SKIMS, a tertiary care center for a period of 2 years. Patients with suspected ARVD/C based on clinical, electrophysiological and echocardiographic findings were subjected to MR imaging. Patients were excluded if they had history metallic implants, claustrophobia or were uncooperative. In this study stress was laid on diagnostic role of MRI in ARVD/C. RESULTS: The median age at presentation was 31 years (range 21-43 years). 80% of patients were males. Most common clinical presentation was palpatations (40%). Syncope was present in 27% and heart failure in 13%. EKG suggestive of ARVD was seen in 87%. Echocardiographic features suggestive of ARVD/C was seen in all 15 patients. Family history of premature sudden death less than 35 years old was present in one patient only. MRI evidence classical for ARVD/C was seen in 80%. CONCLUSION: Demographic features and mode of presentation of our patients is consistent with what has been rest of the world. We performed MRI in all patients to increase the specificity of our diagnosis. MR imaging allows a three-dimensional evaluation of the right ventricle and provides the most important anatomic, functional, and morphologic criteria for diagnosis of ARVD/C within one single study. MR imaging appears to be the optimal imaging technique for detection and follow-up of clinically suspected ARVD/C.

Low Voltage Electric Injury induced Atrial Fibrillation as a Presenting Feature of Wolff-Parkinson-White Syndrome: A Case Report.

Electric injury can cause a variety of cardiac arrhythmias. Atrial fibrillation as a result of such injury is very rare. We present a case of a young asymptomatic patient who developed acute atrial fibrillation with antegrade conduction over the atrioventricular bypass tract and very high ventricular rate after accidental low voltage electric injury, which was reverted successfully by DC shock.

Mitral annuloplasty using a cardiac resynchronization device.

Percutaneous Transvenous Mitral Annuloplasty for mitral regurgitation is in early stages of development and involves a complex intervention which can not be done in patients with left ventricular leads. Since functional mitral regurgitation is common in low ejection fraction states, we propose a device which can serve for annuloplasty in addition to cardiac resynchronization therapy and simplifying the intervention.

A novel way of repair of insulation breaks during pacemaker generator replacement.

Minor abrasions can occur while mobilising old lead during pacemaker generator replacement necesittating placement of additional lead adding to the financial burden and junk in heart. We describe a novel way of repair of old pacemaker lead preventing additional lead placement.