The Influence of Natural Barriers in Shaping the Genetic Structure of Maharashtra Populations

BACKGROUND: The geographical position of Maharashtra state makes it rather essential to study the dispersal of modern humans in South Asia. Several hypotheses have been proposed to explain the cultural, linguistic and geographical affinity of the populations living in Maharashtra state with other South Asian populations. The genetic origin of populations living in this state is poorly understood and hitherto been described at low molecular resolution level. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we have analyzed the mitochondrial DNA (mtDNA) of 185 individuals and NRY (non-recombining region of Y chromosome) of 98 individuals belonging to two major tribal populations of Maharashtra, and compared their molecular variations with that of 54 South Asian contemporary populations of adjacent states. Inter and intra population comparisons reveal that the maternal gene pool of Maharashtra state populations is composed of mainly South Asian haplogroups with traces of east and west Eurasian haplogroups, while the paternal haplogroups comprise the South Asian as well as signature of near eastern specific haplogroup J2a. CONCLUSIONS/SIGNIFICANCE: Our analysis suggests that Indian populations, including Maharashtra state, are largely derived from Paleolithic ancient settlers; however, a more recent (∼10 Ky older) detectable paternal gene flow from west Asia is well reflected in the present study. These findings reveal movement of populations to Maharashtra through the western coast rather than mainland where Western Ghats-Vindhya Mountains and Narmada-Tapti rivers might have acted as a natural barrier. Comparing the Maharastrian populations with other South Asian populations reveals that they have a closer affinity with the South Indian than with the Central Indian populations

Hepatitis B virus: prevalence of precore/core promoter mutants in different clinical categories of Indian patients

To determine the association of precore (Pre-C)/basal core promoter (BCP) mutants with clinical outcome of hepatitis B in Western India, 192 hepatitis B virus (HBV) infected individuals were investigated. HBV-DNA PCR positivity among asymptomatic hepatitis B surface antigen (HBsAg) positive carriers (61/100) was lower (P < 0.0001) than chronic hepatitis B (CHB), acute (P = 0.0001), and fulminant hepatitis B patients (P=0.047). Pre-C status was based on restriction fragment length polymorphism (RFLP, n=153) and sequencing (n=118). Prevalence of Pre-C mutants was higher among carriers (23/61) than CHB (10/62, P=0.0071) or acute (3/22; P=0.037) patients. Children from carrier and CHB categories showed significantly higher circulation of Pre-C-wild than mutant HBV. Clinical manifestations were independent of BCP mutations (1762/64-T/A). Hepatitis B e antigen (HBeAg) negative CHB patients [62.5% (15/24)] were circulating wild HBV. Higher HBV-DNA levels were associated with chronic hepatitis and HBeAg positivity, whilst Pre-C mutant positives had lower levels. BCP mutations did not affect HBV-DNA levels. Multivariate regression analysis identified HBeAg (OR=4.3) and Pre-C mutants (OR=3.1) to be associated with chronic hepatitis and carriers respectively. In a separate sub-set analysis (n=59), HBV-DNA level was identified as the only variable. In conclusion, chronic or fulminant hepatitis B was not associated with Pre-C or BCP mutants and switching over to Pre-C mutant was beneficial for the infected individual in maintaining disease free status for extended periods

Effect of benzalkonium chloride-free latanoprost ophthalmic solution on ocular surface in patients with glaucoma

Tejaswini Walimbe,1 Vidya Chelerkar,2 Purvi Bhagat,3 Abhijeet Joshi,4 Atul Raut4 1Walimbe Eye Clinic, 2PBMA’s H.V. Desai Eye Hospital, Pune, 3Glaucoma Clinic, M and J Western Regional Institute of Ophthalmology, Civil Hospital, Ahmedabad, 4Clinical Research Department, Sun Pharma Advanced Research Company Ltd., Mumbai, India Introduction: Benzalkonium chloride (BAK), included as a preservative in many topical treatments for glaucoma, induces significant toxicity and alters tear breakup time (TBUT). BAK-containing latanoprost, an ester prodrug of prostaglandin F2a, can cause ocular adverse events (AEs) associated with BAK. The purpose of this study was to evaluate the efficacy and safety of BAK-free latanoprost. Patients and methods: A prospective, open-label, single-arm, multicenter, 8-week study in patients with primary open-angle glaucoma or ocular hypertension taking BAK-containing latanoprost for ≥12 months was performed. Patients were switched to BAK-free latanoprost ophthalmic solution 0.005% administered once daily, and eyes were assessed after 28 and 56 days. Primary efficacy and safety variables were TBUT and treatment-emergent AEs, respectively. Results: At day 56, 40 eyes were evaluable. Mean TBUT increased significantly from baseline (3.67±1.60 seconds) to 5.03±2.64 and 6.06±3.39 seconds after 28 and 56 days of treatment with BAK-free latanoprost (P<0.0001). Ocular Surface Disease Index© (OSDI©) score also decreased significantly to 12.06±13.40 and 7.06±10.75 at 28 and 56 days, respectively, versus baseline (18.09±18.61, P<0.0001). In addition, inferior corneal staining score decreased significantly to 0.53 from baseline (0.85, P=0.0033). A reduction in conjunctival hyperemia and intraocular pressure was observed at both time points. No treatment-related serious AEs were evident and 12 (26.08%) treatment-emergent AEs occurred in seven patients, with eye pain and irritation being the most frequent. No clinically significant changes in vital signs or slit lamp examinations were observed. Conclusion: Results indicate that switching from BAK-containing latanoprost to BAK-free latanoprost resulted in significant improvements in TBUT, OSDI© score, and inferior corneal staining score, and measurable reductions in conjunctival hyperemia score. Furthermore, BAK-free latanoprost was well tolerated with only mild-to-moderate and self-limiting AEs. BAK-free latanoprost appears to be effective in protecting ocular surface integrity in glaucoma patients but further studies are needed to confirm this beneficial effect. Keywords: tear breakup time, TBUT, Ocular Surface Disease Index, OSDI©, inferior corneal staining score, conjunctival hyperemia, intraocular pressure, glaucoma, ocular surfac

Retrospective serological analysis of hepatitis E patients: a long-term follow-up study

The aim of this study was to evaluate the persistence and protective role of antibodies to hepatitis E virus (anti-HEV) after natural hepatitis E infection. A retrospective analysis of immunoglobulin G (IgG) anti-HEV was performed in 37 patients followed-up for 5 years after epidemics of HEV. Two patients with sporadic hepatitis E (HE) were followed-up for 12 and 8 years. All patients infected during epidemics of HE were positive for IgG anti-HEV at 5 years of follow-up (geometric mean titre: 174.75). The two patients with sporadic HE were positive for IgG anti-HEV at the end of 12 and 8 years of follow-up (the IgG anti-HEV titre was 1 : 200 in each patient). This study showed protection against disease by antibodies to HEV. It was therefore concluded that hepatitis E may be preventable by an efficacious vaccine