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   Table of Contents - Current issue
Coverpage
August 2018
Volume 148 | Issue 2
Page Nos. 123-246

Online since Friday, October 19, 2018

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EDITORIAL  

Eliminating malaria in India by 2027: The countdown begins! Highly accessed article p. 123
Jai Prakash Narain, Lalit M Nath
DOI:10.4103/ijmr.IJMR_1175_18  
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COMMENTARY Top

Mediators of insulin resistance & cardiometabolic risk: Newer insights p. 127
Dhanasekaran Bodhini, Viswanathan Mohan
DOI:10.4103/ijmr.IJMR_969_18  
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VIEWPOINT Top

Violence against doctors: A wake-up call Highly accessed article p. 130
Kanjaksha Ghosh
DOI:10.4103/ijmr.IJMR_1299_17  
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REVIEW ARTICLES Top

New genetic players in late-onset Alzheimer's disease: Findings of genome-wide association studies Highly accessed article p. 135
Anamika Misra, Sankha Shubhra Chakrabarti, Indrajeet Singh Gambhir
DOI:10.4103/ijmr.IJMR_473_17  
Late-onset Alzheimer's disease (LOAD) or sporadic AD is the most common form of AD. The precise pathogenetic changes that trigger the development of AD remain largely unknown. Large-scale genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms in multiple genes which are associated with AD; most notably, these are ABCA7, bridging integrator 1 (B1N1), triggering receptor expressed on myeloid cells 2 (TREM2), CD33, clusterin (CLU), complement receptor 1 (CRI), ephrin type-A receptor 1 (EPHA1), membrane-spanning 4-domains, subfamily A (MS4A) and phosphatidylinositol binding clathrin assembly protein (PICALM) genes. The proteins coded by the candidate genes participate in a variety of cellular processes such as oxidative balance, protein metabolism, cholesterol metabolism and synaptic function. This review summarizes the major gene loci affecting LOAD identified by large GWASs. Tentative mechanisms have also been elaborated in various studies by which the proteins coded by these genes may exert a role in AD pathogenesis have also been elaborated. The review suggests that these may together affect LOAD pathogenesis in a complementary fashion.
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Clinical & epidemiological significance of Kyasanur forest disease p. 145
Ashok Munivenkatappa, Rima Rakesh Sahay, Pragya D Yadav, Rajalakshmi Viswanathan, Devendra T Mourya
DOI:10.4103/ijmr.IJMR_688_17  
Kyasanur forest disease (KFD) is a known viral haemorrhagic fever in India, for the last 60 years. However, in recent years, the change in epidemiological profile of the disease has suggested that it is now time to consider KFD as an emerging tropical disease in India. The preference should be to educate not only the villagers where it is being reported or detected but also to public health experts, veterinarians, forest officials and medical professionals to pay attention while seeing a patient overlapping with endemic diseases such as Japanese encephalitis, West Nile, dengue, chikungunya, malaria and tuberculosis. Although the existence of KFD is known for a long time, updated understanding of its clinical profile in humans is still limited. This article describes in detail the clinical presentation of KFD reported till date. It also highlights geographical distribution of the disease, risk factors for virus transmission, biochemical/haematological findings and control measures. There is an urgent need for research on KFD, particularly for understanding biphasic nature of illness, development of cost-effective diagnostic tools, utility of non-invasive samples for diagnosis and development of new vaccines.
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ORIGINAL ARTICLES Top

Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity p. 151
Jagadeeswaran Indumathy, Gopal Krushna Pal, Pravati Pal, Palakkad Hariharan Ananthanarayanan, Subash Chandra Parija, Jayaraman Balachander, Tarun Kumar Dutta
DOI:10.4103/ijmr.IJMR_1751_16  
Background & objectives: Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals. Methods: Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis. Results: Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group. Interpretation & conclusions: Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.
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Association of increased risk of asthma with elevated arginase & interleukin-13 levels in serum & rs2781666 G/T genotype of arginase I p. 159
Suhasini Donthi, Venkata Sanjeev Kumar Neela, Sumanlatha Gaddam, Hidayath Hussain Mohammed, Soheb Sadath Ansari, Vijaya Lakshmi Valluri, Krovvidi S. R. Sivasai
DOI:10.4103/ijmr.IJMR_379_16  
Background & objectives: High expression of arginase gene and its elevated level in serum and bronchial lavage reported in animal models indicated an association with the pathogenesis of asthma. This study was undertaken to assess the serum arginase activity in symptomatic asthma patients and healthy controls and to correlate it with cytokine levels [interleukin (IL)-4 and IL-13] and arginase I (ARG1) gene polymorphism. Methods: Asthma was confirmed by lung function test according to the GINA guidelines in patients attending Allergy and Pulmonology Clinic, Bhagwan Mahavir Hospital and Research Centre, Hyderabad, India, a tertiary care centre, during 2013-2015. Serum arginase was analyzed using a biochemical assay, total IgE and cytokine levels by enzyme-linked immunosorbent assay and genotyping of ARG1 for single-nucleotide polymorphisms (SNPs) rs2781666 and rs60389358 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: There was a significant two-fold elevation in the arginase activity in asthmatics as compared to healthy controls which correlated with disease severity. Non-atopic asthmatics showed elevated activity of arginase compared to atopics, indicating its possible role in intrinsic asthma. Levels of serum IL-13 and IL-4 were significantly high in asthma group which correlated with disease severity that was assessed by spirometry. A positive correlation was observed between arginase activity and IL-13 concentration. Genetic analysis of ARG1 SNPs revealed that rs2781666 G/T genotype, T allele and C-T haplotype (rs60389358 and rs2781666) were associated with susceptibility to asthma. Interpretation & conclusions: This study indicated that high arginase activity and IL-13 concentration in the serum and ARG1 rs2781666 G/T genotype might increase the risk of asthma in susceptible population. Further studies need to be done with a large sample to confirm these findings.
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Candidate gene polymorphisms related to lipid metabolism in Asian Indians living in Durban, South Africa p. 169
Tanya Maistry, Michelle Gordon, Benn Sartorius, Datshana P Naidoo
DOI:10.4103/ijmr.IJMR_1150_16  
Background & objectives: Asian Indians have been shown to have a high prevalence of metabolic syndrome (MetS), related to insulin resistance and possibly genetic factors. The aim of this study was to determine the genetic patterns associated with MetS in Asian Indians living in Durban, South Africa. Methods: Nine hundred and ninety nine participants from the Phoenix Lifestyle Project underwent clinical, biochemical and genetic assessment. MetS was diagnosed according to the harmonized definition. The apolipoprotein A5 Q139X, lipoprotein lipase (LPL) Hinf I, human paraoxonase 1 (PON1) 192Arg/Gln, cholesteryl ester transfer protein (CETP) Taq1B, adiponectin 45T>G and leptin (LEP) 25CAG were genotyped by real-time polymerase chain reaction in participants with and without MetS. Univariate-unadjusted and multivariate-adjusted relations were conducted for all analyses. Results: The prevalence of MetS was high (49.0%). More females had MetS than males (51.0 vs 42.8%). There was no significant difference in the distribution of genotypes between participants with MetS and those without. Males with the MetS who had the adiponectin TG genotype and human paraoxonase 1 AA genotype were more likely to have reduced high-density lipoprotein cholesterol (HDL-C) (P=0.001) and higher systolic blood pressure (P=0.018), respectively. Interpretation & conclusions: About half of the Asian Indians living in Phoenix had MetS. No association between the polymorphisms studied and the risk for MetS was observed. The adiponectin TG genotype may be associated with reduced HDL-C and the human paraoxonase 1 AA genotype with hypertension in males. This suggested that lifestyle factors were the major determinant for MetS in this ethnic group and the genetic risk might be related to its component risk factors than to MetS as an entity.
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Inequity & burden of out-of-pocket health spending: District level evidences from India p. 180
Samik Chowdhury, Indrani Gupta, Mayur Trivedi, Shankar Prinja
DOI:10.4103/ijmr.IJMR_90_17  
Background & objectives: Numerous studies have highlighted the regressive and immiserating impact of out-of-pocket (OOP) health spending in India. However, most of these studies have explored this issue at the national or up to the State level, with an associated risk of overlooking intra-State diversities in the health system and health-seeking behaviour and their implication on the financial burden of healthcare. This study was aimed to address this issue by analyzing district level diversities in inequity, financial burden and impoverishing impact of OOP health spending. Methods: A household survey of 62,335 individuals from 12,134 households, covering eight districts across three States, namely Gujarat, Haryana and Rajasthan was conducted during 2014-2015. Other than general household characteristics, the survey collected information on household OOP [sum total of expenditure on doctor consultation, drugs, diagnostic tests etc. on inpatient depatment (IPD), outpatient depatment (OPD) or chronic ailments] and household monthly consumption expenditure [sum total of monthly expenditure on food, clothing, education, healthcare (OOP) and others]. Gini index of consumption expenditure, concentration index and Kakwani index (KI) of progressivity of OOP, catastrophic burden (at 20% threshold) and poverty impact (using district-level poverty thresholds) were computed, for these eight districts using the survey data. The concentration curve (of OOP expenditure) and Lorenz curve (of consumption expenditure) for the eight districts were also drawn. Results: The distribution of OOP was found to be regressive in all the districts, with significant inter-district variations in equity parameters within a State (KI ranges from −0.062 to −0.353). Chhota Udepur, the only tribal district within the sample was found to have the most regressive distribution (KI of −0.353) of OOP. Furthermore, the economic burden of OOP was more pronounced among the rural sample (CB of 19.2% and IM of 8.9%) compared to the urban sample (CB of 9.4% and IM of 3.7%). Interpretation & conclusions: The results indicate that greater decentralized planning taking into account district-level health financing patterns could be an effective way to tackle inequity and financial vulnerability emerging out of OOP expenses on healthcare.
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Imaging & neuropsychological changes in brain with spiritual practice: A pilot study p. 190
Santosh S Gupta, Shailendra M Maheshwari, Urvashi R Shah, Rose Dawn Bharath, Natasha Singh Dawra, Madhuri Shimpi Mahajan, Aishani Desai, Arvind Prajapati, Mangesh Ghodke
DOI:10.4103/ijmr.IJMR_194_17  
Background & objectives: Some studies have systematically assessed the effects of spiritual practice (SP) on the brain using combined neuropsychological testing and functional imaging. The objective of the present study was to compare imaging and neuropsychological changes in healthy individuals after SP and those with only physical exercise. Methods: Healthy adult male volunteers, aged 25-45 yr were randomized into two groups. Group 1 (SP group) underwent the SP and group 2 (controls) did brisk walk for 30 min daily. Detailed neuropsychological evaluation, resting-state functional magnetic resonance imaging (fMRI) and brain 99mTc ethyl cysteinate dimer single-photon emission computed tomography (SPECT) were carried out for both groups before and three months after intervention. Results: Post-intervention, resting state fMRI showed increased connections of left precuneus (in the posterior cingulate cortex area of default mode network) in group 1 and increased left frontal connections in group 2. The neuropsychological tests showed significant improvement in 'Speed of Processing' (Digit Symbol Test) in group 1 and in Focused Attention (Trail Making A) in group 2. The SPECT data in group 1 showed significant improvement in perfusion of the frontal areas, with relatively lesser improvement in parietal areas. Group 2 showed significant improvement in perfusion predominantly in parietal areas, as compared to frontal areas. In addition, significantly improved mood was reported by group 1 and not by group 2. Interpretation & conclusions: This pilot study shows important functional imaging and neuropsychological changes in the brain with SP.
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Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India p. 200
Manas Kumar Behera, Sunit Kumar Shukla, Vinod Kumar Dixit, Preetam Nath, VB Abhilash, Pankaj Kumar Asati, Ashok Kumar Jain
DOI:10.4103/ijmr.IJMR_1295_15  
Background & objectives: The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection. Methods: Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon α-2a 180 μg per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients). Results: There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74). Interpretation & conclusions: The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.
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Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients p. 207
Dhakshinamoorthy Subashini, Thongadi Ramesh Dinesha, Rao B Srirama, Jayaseelan Boobalan, Selvamuthu Poongulali, Devaraj A Chitra, Sarvode N Mothi, Sunil Suhas Solomon, Shanmugam Saravanan, Suniti Solomon, Pachamuthu Balakrishnan
DOI:10.4103/ijmr.IJMR_1144_16  
Background & objectives: Nucleoside reverse transcriptase inhibitors (NRTIs) are known to cause mitochondrial toxicity. This study was done to estimate mitochondrial DNA (mtDNA) content of peripheral blood mononuclear cells (PBMCs) among human immunodeficiency virus (HIV) infected, NRTI treated and antiretroviral therapy (ART)-naïve patients and evaluate the utility of mtDNA content as a biomarker of mitochondrial toxicity. Methods: mtDNA content in PBMCs of 57 HIV-infected ART untreated and 30 ART treated with stavudine (d4T) or zidovudine (AZT) containing regimen were compared against 24 low-risk healthy controls (LoRHC). Results: There was a significant (P=0.01) reduction in mtDNA content among HIV-infected (104; 80-135) compared to LoRHC (127; 110-167), and it was the same in both the treated (104.8; 88-130) and untreated patients (104.7; 78-142). mtDNA significantly (P=0.014) declined in ART treated patients symptomatic for toxicity (97; 74-111) than the asymptomatic patients (128; 103- 153). Interpretation & conclusions: mtDNA depletion in PBMCs was evident among HIV-infected individuals on ART. Moreover, as mtDNA content was reduced among the patients symptomatic for toxicity than the asymptomatic in both the HIV-infected groups, the current study supports mtDNA content of PBMCs to serve as a biomarker of mitochondrial dysfunction induced by NRTI and HIV. Longitudinal studies with a large sample need to be done to confirm these findings.
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A surface antigen of Orientia tsutsugamushi activates human monocyte-derived dendritic cells via nuclear factor-kB & p38 mitogen-activated protein kinase pathways p. 215
Rong-Hwa Jan, Chia-Jung Chen, Yi-Ren Hong, Yu-Li Lin, Li-Kuang Chen
DOI:10.4103/ijmr.IJMR_1417_16  
Background & objectives: Scrub typhus is a chigger-borne disease caused by Orientia tsutsugamushi. The immunological reactions to O. tsutsugamushi infection are not completely understood. In this study, we investigated the response of dendritic cells (DCs) to a major 56-kDa scrub typhus antigen Sta56. Methods: Monocyte-derived human DCs were incubated with different concentrations of recombinant Sta56 and analyzed for maturation based on phagocytic capacity, the ability to induce T-cell proliferation, expression of surface markers, cytokine secretion and activation of toll-like receptor (TLR)-dependent signalling pathways. Results: Treatment of DCs with Sta56 induced cell surface expression of CD80, CD83, CD86 and MHC Class II increased the production of interleukin-12 (IL-12) p40, IL-12 p70 and IL-10 and decreased DC phagocytic capacity. Furthermore, Sta56 increased the ability of DCs to activate T-cell proliferation and interferon-γ secretion. TLR4-specific antibodies neutralized Sta56-elicited effects on DC maturation, suggesting direct interaction between Sta56 and TLR4. Moreover, Sta56 activated nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) signalling as evidenced by decrease in Sta56-induced cytokine production and surface marker expression by specific inhibitors helenalin and SB203580, respectively, and increase in IκBα and p38 phosphorylation and NF-κB-DNA binding. Interpretation & conclusions: Our results showed that the surface antigen of O. tsutsugamushi activated DCs through interaction with TLR4 and activation of MAPK and NF-κB signalling, suggesting Sta56 as a potential candidate molecule for the development of vaccine against scrub typhus.
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Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia p. 225
Prasanna Subramaniam, Kartini Abdul Jabar, Boon Pin Kee, Chun Wie Chong, Anna Marie Nathan, Jessie de Bruyne, Surendran Thavagnanam, Kek Heng Chua, Mohd Yasim Md Yusof, Cindy Shuan Ju Teh
DOI:10.4103/ijmr.IJMR_1987_16  
Background & objectives: Streptococcus pneumoniae (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia. Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated. Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F. Interpretation & conclusions: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.
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CORRESPONDENCES Top

Microbial architecture of pregnant women: A culture independent pilot study p. 232
Utpala Devi, Suman Kalyan Paine, Kanwar Narain, Nabanita Barman, Jagadish Mahanta
DOI:10.4103/ijmr.IJMR_604_17  
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Do medical college students living in hostel in India need hepatitis A vaccine? p. 235
Rahul Karna, Rajesh Ruttala, Premashis Kar
DOI:10.4103/ijmr.IJMR_636_17  
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CLINICAL IMAGES Top

An unusual case of guide wire fracture during percutaneous transluminal coronary angioplasty p. 238
Sezen Baglan Uzunget, Celal Kervancioğlu
DOI:10.4103/ijmr.IJMR_1951_16  
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Detection of amalgam tattoo in oral mucosa by wide-field optical fluorescence p. 240
Sérgio Araújo Andrade, Fernando de Pilla Varotti
DOI:10.4103/ijmr.IJMR_699_17  
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OBITUARY Top

Prof. Denis A. Mitchison (1919-2018) p. 242
S Radhakrishna
DOI:10.4103/ijmr.IJMR_1463_18  
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BOOK REVIEWS Top

Evaluation of certain veterinary drug residues in food p. 245
B Dinesh Kumar
DOI:10.4103/ijmr.IJMR_624_17  
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Evaluation of certain food additives and contaminants p. 245
Arun Sharma
DOI:10.4103/ijmr.IJMR_85_17  
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