Human leukocyte antigen-associated sequence polymorphisms in hepatitis C virus reveal reproducible immune responses and constraints on viral evolution

CD8(+) T cell responses play a key role in governing the outcome of hepatitis C virus (HCV) infection, and viral evolution enabling escape from these responses may contribute to the inability to resolve infection. To more comprehensively examine the extent of CD8 escape and adaptation of HCV to human leukocyte antigen (HLA) class I restricted immune pressures on a population level, we sequenced all non-structural proteins in a cohort of 70 chronic HCV genotype 1a-infected subjects (28 subjects with HCV monoinfection and 42 with HCV/human immunodeficiency virus [HIV] coinfection). Linking of sequence polymorphisms with HLA allele expression revealed numerous HLA-associated polymorphisms across the HCV proteome. Multiple associations resided within relatively conserved regions, highlighting attractive targets for vaccination. Additional mutations provided evidence of HLA-driven fixation of sequence polymorphisms, suggesting potential loss of some CD8 targets from the population. In a subgroup analysis of mono- and co-infected subjects some associations lost significance partly due to reduced power of the utilized statistics. A phylogenetic analysis of the data revealed the substantial influence of founder effects upon viral evolution and HLA associations, cautioning against simple statistical approaches to examine the influence of host genetics upon sequence evolution of highly variable pathogens. Conclusion: These data provide insight into the frequency and reproducibility of viral escape from CD8(+) T cell responses in human HCV infection, and clarify the combined influence of multiple forces shaping the sequence diversity of HCV and other highly variable pathogens.     

Coronary sinus and fossa ovalis ablation: effect on interatrial conduction and atrial fibrillation

Background: Interatrial conduction occurs via discrete pathways along the coronary sinus musculature, fossa ovalis region, and Bachman's bundle. We assessed the feasibility of altering interatrial conduction by selectively ablating two of these conduction pathways using a novel mesh electrode ablation catheter.
Methods: Circular radiofrequency energy catheter ablation lesions were created in the proximal coronary sinus in four dogs and in both the fossa ovalis and the proximal coronary sinus regions in seven pigs. Interatrial conduction was assessed by analyzing intracardiac electrogram and noncontact isopotential mapping data. Inducibility of atrial fibrillation was assessed before and after ablation (in six pigs).
Results: Ablation lesions in the proximal coronary sinus eliminated interatrial conduction along the coronary sinus musculature in four dogs and five of seven pigs. Ablation lesions in the fossa ovalis region eliminated interatrial conduction via midseptal pathways in six of seven pigs. Atrial fibrillation, inducible in five of seven pigs at baseline, was rendered noninducible in all five. There was no adverse effect on AV nodal conduction.
Conclusions: (1) Using a novel mesh electrode ablation catheter, we were able to ablate interatrial conduction pathways along the proximal coronary sinus and fossa ovalis regions. (2) This altered interatrial conduction and altered atrial fibrillation inducibility and maintenance. (3) Catheter ablation of interatrial conduction pathways may be useful in the therapy of atrial fibrillation.     

Significant increase in HBV, HCV, HIV and syphilis infections among blood donors in West Bengal, Eastern India 2004-2005： Exploratory screening reveals high frequency of occult HBV infection

AIM： To evaluate the prevalence of markers of hepatitis B virus （HBV） and hepatitis C virus （HCV） and human immunodeficiency virus （HIV） among blood donors in Kolkata, Eastern India for two consecutive years and to conduct a pilot study to explore the presence of HBV DNA among hepatitis B surface antigen （HBsAg） negative but anti-HBc positive blood donors.
METHODS： Seroprevalence of HBsAg, anti-HCV and anti-HIV was studied among 113051 and 106695 voluntary blood donors screened in 2004 and 2005, respectively. Moreover, a pilot study on 1027 HBsAg negative donors was carried out for evaluating the presence of HBV DNA by PCR on HBsAg negative/anti- HBc positive donors.
RESULTS： A statistically significant increase in the prevalence of HBV （1448 vs 1768, P 〈 0.001）, HIV （262 vs 374, P 〈 0.001）, HCV （314 vs 372, P = 0.003） and syphilis （772 vs 853, P = 0.001） infections was noted among blood donors of Kolkata West Bengal in 2005 as compared to 2004. Moreover, the exploratory study on 1027 HBsAg negative donors revealed that 188 （18.3%）of them were anti-HBc positive out of which 21% were positive for HBV DNA.
CONCLUSION： The findings of this study underscore the significantly increasing endemicity of hepatitis viruses, syphilis and HIV among the voluntary blood donors of our community. The pilot study indicates a high rate of prevalence of HBV DNA among HBsAg negative/anti-HBc positive donors and thus emphasizes the need for a more sensitive and stringent screening algorithm for blood donations.     

Diagnostic utility of adenosine deaminase (ADA) activity in pleural fluid and serum of tuberculous and non-tuberculous respiratory disease patients

Adenosine deaminase activity (ADA) was assayed in pleural fluid and serum of 42 subjects with pleural effusion. Twenty-nine of them had TB pleural effusion and the remaining 13 had pleural effusion due to non-TB respiratory diseases. Serum adenosine deaminase activity were also measured in 32 pulmonary tuberculosis patients without pleural effusion and equal numbers of healthy controls without systemic diseases for comparative analysis. The patients attending the medicine out-patient department (MOPD) of the B. P. Koirala Institute of Health Sciences, Dharan, Nepal were taken as study subjects. Serum and pleural fluid ADA activities were assayed spectrophotometrically by the method of Guisti and Gallanti. The mean serum ADA activity was significantly increased in patients with tubercular pleural effusion (34.53 +/- 10.27 IU/l) compared to pulmonary tuberculosis patients without pleural effusion (26.54 +/- 4.76 IU/l), (p = 0.004), those with non-TB respiratory disease (16.71 +/- 5.16 IU/l), (p = 0.0001) and healthy controls (15.53 +/- 4.4 IU/l) (p = 0.0001). The mean ADA in the pleural fluid of tubercular pleural effusion patients (90.29 +/- 54.80 IU/l) was significantly higher compared to those with non-TB respiratory disease (24.43 +/- 9.28 IU/l) (p = 0.0001). Using the lowest cutoff value for enzyme activity in the serum of patients with TB pleural effusion (25 IU/l), a test sensitivity of 72.41% and specificity of 81.53% were obtained. Using the lowest cutoff value for enzyme activity in pleural fluid of patients with TB pleural effusion (45 IU/l) the sensitivity and specificity for diagnosis were 76.10% and 100%, respectively. Therefore, the measurement of ADA in tubercular pleural effusion has a utility in the diagnosis of tuberculosis when other clinical and laboratory tests are negative.     

Prevalence of Ischemic Heart Disease Among Urban Population of Siliguri, West Bengal

Objectives:

To determine the prevalence of ischemic heart disease and the associated risk factors among the urban population of Siliguri.

Materials and Methods:

A cross-sectional survey of a random sample of the population aged ≥40 years old in the Municipal Corporation area of Siliguri. Study variables were age, sex, occupation, addiction, food habit, physical activity, body mass index, blood pressure, and electrocardiogram change.

Results:

Out of 250 individuals who took part in this study, 29 (11.6%) had ischemic heart disease (IHD) and 118 (47.2%) had hypertension. Males had a higher (13.5%) prevalence of IHD than females (9.4%). About 5% of the patients had asymptomatic IHD. IHD among the study population is significantly associated with hypertension and smoking.     

Diagnostic accuracy,reliability and validity of Childhood Autism Rating Scale in India

Background  

Since there is no established measure for autism in India, we evaluated the diagnostic accuracy, reliability and validity of Childhood Autism Rating Scale (CARS).     

EYS is a major gene for rod‐cone dystrophies in France

Autosomal‐recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well‐characterized cohort of 239 sporadic and arRP French cases. Direct sequencing of EYS was performed in 186 subjects for whom known mutations had previously been excluded by applying microarray technology. We mostly identified novel mutations in EYS in a total of 29 patients: Fifteen of the mutations were predicted to create premature stop codons and two represent exonic deletions. In addition, twenty missense, silent or splice‐site mutations were detected. Patients revealed homozygous or compound heterozygous mutations and in some cases, only a single mutation. Most patients showed classical signs of RP with relatively preserved central vision and visual field until late in the course of the disorder. One patient showed predominance of the disease in the inferior part of the retina suggesting potential phenotypic variability. With a prevalence of 12% or more we provide evidence that EYS is a major gene for RP in France and probably elsewhere. © 2010 Wiley‐Liss, Inc.