Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal individuals

Accumulation of Heavy Metal Ions by Eichhornia Crassipes from Battery Industry Effluent under the Influence of Cattle Manure

Phytoremediation, an emerging technology which uses plants to remove contaminants of concern (COC) such as organic and inorganic compounds especially heavy metals (HM). The present study focuses on assessing the toxicity of heavy metals available in effluents discharged from industries and the accumulation ability of an aquatic plant, Eichhornia crassipes (water hyacinth). Phytoremedial potential of E. Crassipes and HM interaction between soil and water were evaluated in the present study under the presence of cow dung manure as an enhancer. Heterogenous accumulation of metal ions were found in the plant. Heavy metal concentration in plant parts were varied for roots and shoots. The concentration of HM ions in the plant parts were varied from root to shoot. Value of translocation factor (TF) was found to be in the region 0.5 – 0.8, with Fe has low (0.51) and Pb has high (0.77), bioconcentration factor (BCF) were in the order of Ar > Ca > Zn > Fe > Pb at both roots and shoots. Transposition factor (TrF) of all HM ions were >1.5 except for Zn (1.21). E. Crassipes was found to accumulate a large amount of HM ions and could be used for efficient treatment of contaminated water

“A Study on Occurrence, Risk Factors and Cardiovascular Event Associated with Qt Interval Prolongation and Increased Dispersion in Newly Diagnosed Hypertension Patients”

Background: Systemic hypertension is a widely prevalent non-communicable disease in India, impacting approximately 21–25% of the population. It is commonly linked to cardiovascular complications and target organ damage. Notably, changes in cardiac electrical activity, such as QT interval prolongation and increased dispersion, serve as important indicators associated with arrhythmias and sudden cardiac death. However, there is limited data on these parameters in patients newly diagnosed with hypertension. Aim: This study aimed to determine the occurrence and risk factors associated with QT interval prolongation and increased dispersion in newly diagnosed hypertensive patients. Materials and Methods: An observational cross-sectional study was conducted at Aarupadi Veedu Medical College, Puducherry, over an 18-month period. A total of 140 consecutive patients, newly diagnosed with hypertension based on JNC 8 guidelines (mean age 49.2 years; 58.6% male; 22.1% smokers), were enrolled. Comprehensive demographic, anthropometric, and biochemical data were collected. Electrocardiograms (ECGs) were performed, and the QT interval was measured using Bazett’s formula. Cardiovascular risk was further evaluated using the Framingham Risk Score (FRS). Results: QT prolongation was present in 65.7% of cases, with 65% of patients exhibiting an FRS >1%. Notably, male patients showed a significantly higher incidence of both QT prolongation (73.2% vs. 55.2%) and elevated FRS (76.8% vs. 48.3%) compared to females (p<0.05). In patients with QTc prolongation, an FRS >1% was found in 85% of males and 68.8% of females, while among smokers, a significantly higher association was observed in males (52.9% vs. 18.2%, p<0.05). Conclusion: The study demonstrates a high occurrence of QT interval prolongation in newly diagnosed hypertensive patients, particularly among males and smokers. Early risk stratification and targeted interventions are recommended to mitigate future cardiovascular events

Molecular Diversity Studies and Core Development in Sesame Germplasm (Sesamum indicum L.) Using SSR Markers

Sesame (Sesamum indicum L.), an ancient oilseed crop being cultivated across geographical locations in the tropics, is known for its high-quality oil with a longer shelf life. India, being the center of diversity for this crop, understanding the genetic variability of sesame germplasm being conserved in the national Genebank (NGB) of ICAR-NBPGR, will help identify genotypes for its potential use in broadening the genetic base of the cultivars for sesame crop improvement. We report here the molecular diversity analysis performed using SSR markers on a set of 2,496 sesame germplasm. Hence, the derived data was also subjected to population structure analysis, and a molecular core was generated to assess its phenotypic variability. Parallelly, they were phenotypically characterized for important qualitative and quantitative traits as per the standard descriptor developed by IPGRI, and accessions exhibiting desirable traits were identified. The sesame germplasm used in our study represents collections from 17 countries across the globe and 26 states in India. A total of 140 alleles were obtained using seven polymorphic SSR markers selected from an initial screening comprising 43 SSR markers. The observed heterozygosity was less than the expected heterozygosity since it is a self-pollinated crop (up to 35% outcrossing is reported, categorized as often cross-pollinated). The molecular diversity analysis grouped 2496 accessions into six clusters, while the population structure analysis grouped them into three major clusters or populations. A molecular core developed using the PowerCore software identified 196 accessions, representing all the alleles from the entire 2496 accessions, that can be utilized in breeding programs after phenotypic validation. This study contributes to genetic diversity assessment for sesame germplasm, identifying genetically diverse accessions, and establishing a core set that encapsulates the genetic variability of the sesame germplasm collection. These findings hold relevance for addressing agricultural challenges and enhancing the resilience and productivity of sesame crops in various environmental conditions

Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden

INTRODUCTION: Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. MATERIALS AND METHOD: We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. RESULTS: Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p2 zones, were 3.05 (95% CI: 1.12–8.23) and 1.92 (95% CI: 0.72–5.08) respectively. Patients without cavitation, zonal involvement 2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting “minimal disease”, had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens

Enhancement of cadmium removal by oxygen-doped carbon nitride with molybdenum and sulphur hybridization

Graphitic carbon nitride, as a popular material in the field of environmental remediation, still suffers from unsatisfactory performance for heavy metals adsorption owing to lack of specific adsorption sites. In this study, molybdenum (Mo) and sulphur (S) were simultaneously introduced onto the surface of oxygen-doped graphitic carbon nitride (OCN) for the enhancement of Cd2+ adsorption. The synthesized MOS/OCN-1 exhibited substantially increased maximum adsorption capacity of 293.8 mg/g, calculated from Sips isotherm model, which was 8.7 times higher than that for pristine OCN (33.9 mg/g). The adsorption efficiency of MOS/OCN-1 was >94% even under high concentration of coexisting ions (ie. Ca2+, Mg2+ and Zn2+). MoO3 and MoS2 on the surface of OCN were proven to interact with Cd2+ by forming CdMoO4 and CdS species. OCN provided a stable matrix with a large surface area making more active sites exposed, which greatly facilitated Mo(IV) oxidation and Cd2+ precipitation. Our findings revealed that as well as the well-known Cd-S interaction, Mo atoms in the hybrid composites also played an important role in Cd2+ removal, which opened up the application possibility of OCN with Mo and S hybridization for in-situ Cd2+ remediation