Adaptation of 2016 European Society of Cardiology/European Atherosclerosis Society guideline for lipid management to Indian patients - A consensus document.

In the year 2016, European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines provided recommendations on dyslipidemia management. The recommendation from these guidelines are restricted to European subcontinent. To adapt the updated recommendations for Indian subset of dyslipidemia, a panel of experts in management of dyslipidemia provided their expert opinions. This document provides expert consensus on adapting 2016 ESC dyslipidemia guidelines recommendations in Indian setting. The document also discussed India-specific relevant literature to support the consensus opinions provided in management of dyslipidemia.

Co-factor-independent phosphoglycerate mutase of Leishmania donovani modulates macrophage signalling and promotes T-cell repertoires bearing epitopes for both MHC-I and MHC-II.

Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1ß (IL-1ß) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-ß. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design.

Aflatoxin B1 contamination in wheat grain samples collected from different geographical regions of India: A multicenter study.

In a multicenter study conducted by the Indian Council of Medical Research, 1,646 samples of wheat grain collected from rural and urban areas of 10 states representing different geographical regions of India were analyzed for aflatoxin B1 (AFB1). AFB1 concentrations of > or = 5 microg kg(-1) were recorded in 40.3% of the samples, and concentrations above the Indian permissible regulatory limit of 30 microg kg(-1) were found in 16% of the samples. The proportion of samples with AFB1 concentrations above the Indian regulatory limit ranged from 1.7 to 55.8% in different states, with the minimum in Haryana and the maximum in Orissa. The variation in wheat contamination among states seems to be mainly the result of unsatisfactory storage conditions. Median AFB1 concentrations of 11, 18, and 32 microg kg(-1) were observed in samples from Uttar Pradesh, Assam, and Orissa, respectively; concentrations in other states were <5 microg kg(-1). The maximum AFB1 concentration of 606 microg kg(-1) was observed in a sample from the state of Uttar Pradesh. The calculated probable daily intakes of AFB1 through consumption of contaminated wheat for the population in some states were much higher than the suggested provisional maximum tolerable daily intake. Human health hazards associated with such AFB1 exposure over time cannot be ruled out.

Aflatoxin B(1) contamination of parboiled rice samples collected from different states of India: A multi-centre study.

Under a multi-centre study conducted by the Indian Council of Medical Research, 1,511 samples of parboiled rice were collected from rural and urban areas of 11 states representing different geographical regions of India. These samples were analysed for contamination with aflatoxin B(1.) The presence of aflatoxin B(1) at levels=5 microg g(-1) was found in 38.5% of the total number of samples of the parboiled rice. About 17% of the total samples showed the presence of aflatoxin B(1) above the Indian regulatory limit of 30 microg kg(-1). No statistically significant difference in percentage of samples contaminated with >30 microg kg(-1) was observed between pooled rural (19.4%) and urban (14.5%) data. A median value of 15 microg kg(-1) of aflatoxin B(1) was observed in samples from Assam, Bihar and Tripura. In all other states surveyed the median value was <5 microg?kg(-1).

Molecular analysis of GAA repeats and four linked bi-allelic markers in and around the frataxin gene in patients and normal populations from India.

Friedreich ataxia (FRDA), the most common type of ataxia worldwide, is an autosomal recessive disease. Homozygous expansion of GAA repeats in the first intron of the frataxin gene constitute the major type of mutation that causes the disease. The prevalence of FRDA in diverse ethnic populations of India has not been widely studied. We have studied the distribution of polymorphic GAA repeats in the frataxin gene among 6 clinically diagnosed patients and 160 ethnically matched normal individuals, to gather information on the prevalence of FRDA in the eastern part of India. Homozygous expansion in the range of 250-730 GAA repeats was detected among the patients. Among normal individuals, we observed a unimodal distribution of GAA repeats, consisting of 10 different alleles ranging from 7 to 16 GAA repeats, where the 9 repeat allele had maximal frequency. Only 5.9% of all chromosomes were found to harbour >12 GAA repeats. Haplotype analysis using closely linked four bi-allelic markers in and around the frataxin gene indicated that 66.7% of the expanded alleles harbour the ATCC haplotype that has been reported worldwide. This haplotype was present in 53.3% of the chromosomes with >12 GAA repeats, and accounted for only 3.8% of chromosomes with 7 to 12 GAA repeats. We found one novel haplotype, ACCT, among the expanded alleles as well as among normal individuals, though at low frequency; this haplotype may be characteristic of Indian populations.

Autosomal dominant cerebellar ataxia: SCA2 is the most frequent mutation in eastern India.

OBJECTIVE: Spinocerebellar ataxia type 2 (SCA2) has been reported as the commonest dominant hereditary ataxia in India. However, India is an ethnically and religiously diverse population. Previous studies have not clearly indicated exact ethnic and religious origins, and must therefore be interpreted with caution. The purpose of this study was to determine the prevalence of different SCA mutations in a relatively homogeneous population from eastern India. METHODS: We identified 28 families with autosomal dominant cerebellar ataxia from eastern India. Each underwent full clinical evaluation and were analysed for the presence of SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, and SCA17 mutations. In addition, haplotype analysis was carried out in seven of the 16 families with SCA2. RESULTS: Seven patients from four (14%) families were positive for an expansion in SCA1 and 26 patients from 16 (57%) families were positive for an expansion in SCA2. No mutations were detected in the remaining eight families (29%). Most of the SCA1 and SCA2 families were Hindu from the state of Bihar. Five out of 26 SCA2 patients in this study did not have slow saccades. In addition, four of seven SCA1 patients had slow saccades. We found an association between the SCA2 CAG repeat expansion and the 285 base pair (bp) allele of microsatellite marker D12S1672, and also data supportive of the association between the expansion and the 225 bp allele of D12S1333, which has been previously described. CONCLUSIONS: We conclude that (1) although slow ocular saccades are highly suggestive of SCA2, that they are not universal, nor are they exclusive to this disorder and (2) SCA2 is likely to be the commonest dominant ataxia in eastern India, with further evidence for a founder effect.

Variation of CAG repeats and two intragenic polymorphisms at SCA3 locus among Machado-Joseph disease/SCA3 patients and diverse normal populations from eastern India.

OBJECTIVES: MJD1/SCA3 is the most common type of spinocerebellar ataxia (SCA) worldwide. To explain the low prevalence of the disease among SCA patients from eastern India, we analysed CAG repeats and two bi-allelic intragenic markers at SCA3 locus among 412 normal individuals and 10 patients. MATERIALS AND METHODS: For CAG repeat analysis, PCR amplified fragments were run on polyacrylamide gel, transferred to a membrane, probed with (CAG)10 and detected on an autoradiograph. Bi-allelic markers were analysed using allele specific PCR amplification. RESULTS: Large normal alleles (>33 CAG repeats) were 0.015 in pooled populations. All the patients had the common haplotype C-A as observed worldwide. Frequency of C-A haplotype among large normal alleles was 0.75. CONCLUSIONS: Observed low prevalence of SCA3 could be because of the low prevalence of large normal alleles that might act as the reservoir for the expanded alleles. SCA3 mutation in Indian populations had the same origin as found worldwide.

Wilson's disease in Eastern India.

INTRODUCTION: Wilson's disease is an inherited autosomal recessive (AR) disorder of copper metabolism transmitted by a mutant gene on chromosome 13q14-21 and results in abnormal accumulation of copper giving rise to protean manifestations. AIM: The aim is to study the clinical features, biochemical and radiological abnormalities of this disorder in Eastern India and the effect of treatment. RESULTS: Forty nine (n = 49) cases were studied over a period of 10 years. Majority of patients were male with mean age of onset being 11.13 years. They commonly presented with dysarthria, dystonia or drooling. The clinical features were dystonia (96%), silly smile (92%), dysarthria (80%), cognitive decline (71%), tremors (47%), bradykinesia (45%), etc. Family history suggested an autosomal recessive pattern. Sibling screening revealed that 4/8 (50%) were presymptomatic. All but one had presence of Keyser Fleischer (KF) ring in their cornea. Serum copper was reduced in 77% while ceruloplasmin was less in 94% of cases. The commonest abnormality seen in CT/MRI were in basal ganglia (74%) followed by white matter changes (59%) and brain stem changes (20.5%). The response to treatment was not as good and there was an initial deterioration in 50% of cases. Only five patients could go back to their school. CONCLUSION: Wilson's disease have protean manifestations. All children with slowly progressive extrapyramidal syndrome should be investigated for it. Screening of all asymptomatic siblings for Wilson's disease must be carried out. Early institution of proper treatment and life long continuation is indicated in all. In the present series, an earlier age of onset of neurological signs and symptoms were seen; there was initial deterioration in 50% of cases and the response to treatment was not as good.

Molecular anatomy of CTG expansion in myotonin protein kinase gene among myotonic dystrophy patients from eastern India.

We have studied the CTG repeat sizes in the DMPK gene and six biallelic markers which are in complete linkage disequlibrium with Caucasian DM patients, to identify any common founder haplotype in 30 clinically diagnosed unrelated DM patients from eastern India. Our results revealed that in 27 patients (90%), CTG expansion took place on a DraIII(-) - HhaI(-) - Alu(+) - HinfI(+) - Fnu4H I(-) - TaqI(+) haplotype (haplotype I), similar to what have been published for Caucasoid and other DM patients. However, in three patients (10%), the expansion of CTG repeat was on DraIII(+) - HhaI(+) - Alu(+) - HinfI(-) - Fnu4H I(+) - TaqI(-) background (haplotype II), indicating a new haplotype. The distribution of haplotypes in 52 normal individuals of eastern India revealed that percentage of haplotypes I and II were 23.1% and 7.7% respectively in normal chromosomes. Haplotype II is absent among Caucasian DM patients as well as normal individuals indicating that this particular haplotype may be characteristic of the Indian population. Hum Mutat 16:372, 2000.

Analysis of CAG and CCG repeats in Huntingtin gene among HD patients and normal populations of India.

We have analysed the distribution of CAG and adjacent polymorphic CCG repeats in the Huntingtin gene in 28 clinically diagnosed unrelated Huntington's disease (HD) patients and in normal individuals belonging to different ethnic groups of India. The range of expanded CAG repeats in HD patients varied from 41 to 56 repeats, whereas in normal individuals this number varied between 11 and 31 repeats. We identified six CCG alleles from a total of 380 normal chromosomes that were pooled across different ethnic populations of India. There were two predominant alleles: (CCG)7 (72.6%) and (CCG)10 (20%). We report here for the first time one four-repeat CCG allele which has not been found in any population so far. We found 30 haplotypes (two loci CAG-CCG) for 380 normal chromosomes. In the present study, no statistically significant preponderance of expanded HD alleles was found on either (CCG)7 or (CCG)10 backgrounds. Our studies suggest that the overall prevalence of HD in Indian populations may not be as high as in Western populations. Further studies are necessary to identify the origin of HD mutation in these populations.

Analysis of CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci in spinocerebellar ataxia patients and distribution of CAG repeats at the SCA1, SCA2 and SCA6 loci in nine ethnic populations of eastern India.

To identify various subtypes of spinocerebellar ataxias (SCAs) among 57 unrelated individuals clinically diagnosed as ataxia patients we analysed the SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci for expansion of CAG repeats. We detected CAG repeat expansion in 6 patients (10.5%) at the SCA1 locus. Ten of the 57 patients (17.5%) had CAG repeat expansion at the SCA2 locus, while four had CAG expansion at the SCA3/MJD locus (7%). At the SCA6 locus there was a single patient (1.8%) with 21 CAG repeats. We have not detected any patient with expansion in the SCA7 and DRPLA loci. To test whether the frequencies of the large normal alleles in SCA1, SCA2 and SCA6 loci can reflect some light on prevalence of the subtypes of SCAs we studied the CAG repeat variation in these loci in nine ethnic sub-populations of eastern India from which the patients originated. We report here that the frequency of large normal alleles (>31 CAG repeats) in SCA1 locus to be 0.211 of 394 chromosomes studied. We also report that the frequency of large normal alleles (>22 CAG repeats) at the SCA2 locus is 0.038 while at the SCA6 locus frequency of large normal alleles (>13 repeats) is 0.032. We discussed our data in light of the distribution of normal alleles and prevalence of SCAs in the Japanese and white populations.

Expansion of CTG repeat in myotonin protein kinase gene on Alu(ins)-HinfI-I background in a myotonic dystrophy patient from India. Mutations in brief no. 210. Online.

To determine the founder of Indian myotonic dystrophy mutation, we have studied the expansion of CTG repeats in myotonin protein kinase gene and two intragenic linked loci Alu(ins) / Alu(del) and G/T intron 9 HinfI polymorphism in ten unrelated DM patients from eastern India. Out of these ten patients, reconstruction of haplotype was possible for five patients unambiguously. In the other five cases, haplotype for the normal allele was assumed to be the most common haplotype found in normal individuals from Indian populations. Such analysis showed that in nine cases, the expansion of CTG repeats took place on Alu(ins)-HinfI-2 background indicating common founder with other DM mutation published. However, in one case we observed a different haplotype [Alu(ins)-HinfI-1] which could be a new mutation or due to admixture.

Phaeohyphomycosis caused by Phaeoacremonium inflatipes.

Phaeoacremonium inflatipes, one of three species previously classified as strains of Phialophora parasitica, was identified as the causal agent of a subcutaneous infection of the left foot of an 83-year-old woman from South Carolina. The patient had a granulomatous growth over the anteromedial aspect of her left foot. It was surgically excised, which led to complete healing without complications. Tissue sections of the excised mass stained with hematoxylin and eosin and Gomori's methenamine silver strains showed many septate hyphal elements of various lengths, some exhibiting brownish pigment in the cell walls of the hyphae. Portions of the tissue, when cultured, yielded many colonies which were initially glabrous, off white becoming velvety, greyish brown on aging. Microscopically, their hyphae were septate, branched, and phaeoid and bore lateral and terminal, erect, septate conidiophores. The conidiogenous cells (phialides) were terminal or lateral, mostly monophialidic, subcylindrical to spinelike in shape, and constricted at their bases and bore funnel-shaped, inconspicuous collarettes at their tips. The conidia were subhyaline, oblong, and ellipsoid to allantoid.

Mycotoxin production by some IndianAlternaria species.

A total of seven species ofAlternaria: A. alternata (Fr.) Keissler;A. capsici-annui Savul & Sandu;A. citri Ellis & Pierce;A. porri (Ellis) Clfferi;A. radicina Meler, Drechsler & Eddy;A. tenuissima (Kunze: Pers) Wiltshire andA. tomato (Cooke) Jones were screened on rice culture medium for their ability to elaborate five majorAlternaria mycotoxins viz. tenuazonlc acid (TA), alternariol (AOH), alternariol methyl ether (AME), altenuene (ALT) and altertoxin-l (ATX-I). All the species produced mycotoxins in varying concentrations. A.capsici-annul was recorded as the mycotoxin producer for the first time. ALT byA. citri andA. tomato; ALT, and ATX-I byA. tenuissima; ALT, TA and AME byA. porri and TA byA. radicina are the new additions to the list of mycotoxins produced by the respective species ofAlternaria.