Long pepper (Piper longum) derived carbon dots as fluorescent sensing probe for sensitive detection of Sudan I.

In this piece of work, microwave-assisted conversion of a natural precursor in to high-valued nano-scale material was carried out by a completely greener method. The fluorescent carbon dots prepared, designated as long pepper derived carbon dots (LPCDs), have been thoroughly characterized to explore the physical and chemical properties. The system exhibits excitation dependent emission behavior and from the optimal studies the excitation and emission wavelength of the system was found to be 330 nm and 455 nm respectively. On account of the superior fluorescent behavior of the LPCDs, it was successfully employed as a fluorescent sensing probe to detect Sudan I with good level of selectivity and sensitivity. This carcinogenic dye extensively used as food adulterant can impart several health issues. Food product safety is of high concern, therefore a simple facile and economical analytical method was proposed based on the fluorescence of LPCDs for this dye detection with satisfactory statistical parameters. A linear relationship was maintained in the range of 0 to 27.27 µM Sudan I with limit of detection of 0.92 µM. The quenching mechanism was studied and finally attributed to Förster resonance energy transfer (FRET) mechanism. In addition, the probe was effectively implemented for Sudan I detection in commercial chili powder samples with good level of recovery parameters.

Microwave-assisted green synthesis of carbon dots derived from wild lemon (Citrus pennivesiculata) leaves as a fluorescent probe for tetracycline sensing in water.

Herein, we report an eco-friendly biomass based completely greener microwave assisted synthesis of carbon dots from wild lemon leaves having superior photo-luminescent properties with moderately good quantum yield. The carbon dots synthesized (LLCDs) were characterized by high resolution transmission electron microscopy, fluorescent, UV-vis absorption, Fourier transform infrared and Raman spectroscopic techniques. The quenching of native fluorescence of LLCDs observed with tetracycline antibiotic was made use to make it as a fluorescent probe. Tetracycline is widely used as a drug to treat various bacterial infections and as a growth promoter in variety of farming fields like aquaculture and feedstock's. The excessive usage of this antibiotic in farming fields caused severe water pollution and micro level detection of tetracycline in water system is highly demanded for the protection of health and environment. Based on the selective interaction of tetracycline with LLCDs, a simple and cost effective analytical method was proposed to detect tetracycline in water with satisfactory parameters. The limit of detection is 0.42 µM with a linear range of 0 to 27. 27 µM. The mechanism of quenching was investigated through various experiments and finally accredited to static quenching. Furthermore, the same method has been practically applied for tetracycline detection in natural water resources with acceptable recoveries ranging from 95.56 % to 101.93 %.

Cortical excitability changes as a marker of cognitive impairment in Parkinson's disease.

Cognitive impairment of different severity with eventual progression to dementia in Parkinson's disease (PD) appears during the course of the disease. In this study, transcranial magnetic stimulation (TMS) was used to assess cortical excitability changes in PD patients with varying cognitive impairment. We aimed to identify the TMS parameters that could serve as a non-invasive marker of cognitive impairment in patients with PD. Consecutive PD patients were recruited in the study. Detailed neuropsychological assessment was carried out to identify PD without cognitive impairment (PD-nC), PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD). Twenty patients of PDD (2 females and 18 males), 20 PD-MCI (4 females and 16 males), 18 PD-nC (5 females, 13 males) and 18 healthy controls (4 females, and 14 males) were included in the study. All the participants underwent TMS with recording of resting motor threshold, central motor conduction time, silent period, short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). All the groups were age matched. The SICI was present in all; however, significantly greater inhibition was noted in PDD (Mean±SD; 0.11 ± 0.08) followed by PD-MCI (0.31 ± 0.17), PD-nC (0.49 ± 0.26) and controls (0.61 ± 0.23; p < 0.001). The ICF was significantly reduced in PDD (Mean±SD; 0.15 ± 0.18), PD-MCI (0.55 ± 0.31), PD-nC (0.96 ± 0.59), when compared to healthy controls (1.81 ± 0.83; p < 0.001). Patients with PD-nC, PD-MCI and PDD had graded reduction in ICF and increasing intracortical inhibition as the disease progressed from PD-nC through PD-MCI to PDD. This suggests progressive overactivity of GABAergic transmission, glutaminergic deficiency with consequent reduction of cholinergic transmission leading to dementia.

Cost-Effectiveness of Quadrivalent Versus Trivalent Influenza Vaccination in the Dutch National Influenza Prevention Program.

OBJECTIVES: As of 2019, quadrivalent influenza vaccine (QIV) has replaced trivalent influenza vaccine (TIV) in the national immunization program in The Netherlands. Target groups are individuals of 60+ years of age and those with chronic diseases. The objective was to estimate the incremental break-even price of QIV over TIV at a threshold of €20 000 per quality-adjusted life-year (QALY). METHODS: An age-structured compartmental dynamic model was adapted for The Netherlands to assess health outcomes and associated costs of vaccinating all individuals at higher risk for influenza with QIV instead of TIV over the seasons 2010 to 2018. Influenza incidence rates were derived from a global database. Other parameters (probabilities, QALYs and costs) were extracted from the literature and applied according to Dutch guidelines. A threshold of €20 000 per QALY was applied to estimate the incremental break-even prices of QIV versus TIV. Sensitivity analyses were performed to test the robustness of the model outcomes. RESULTS: Retrospectively, vaccination with QIV instead of TIV could have prevented on average 9500 symptomatic influenza cases, 2130 outpatient visits, 84 hospitalizations, and 38 deaths per year over the seasons 2010 to 2018. This translates into 385 QALYs and 398 life-years potentially gained. On average, totals of €431 527 direct and €2 388 810 indirect costs could have been saved each year. CONCLUSION: Using QIV over TIV during the influenza seasons 2010 to 2018 would have been cost-effective at an incremental price of maximally €3.81 (95% confidence interval, €3.26-4.31). Sensitivity analysis showed consistent findings on the incremental break-even price in the same range.

Nanophotonics based label free detection mechanism for real-time monitoring of interleukin-6.

Magneto-photonic crystals/MPCs are promising candidates for devising high-fidelity embedded biosensor systems which offer facile & real time detection of diagnostic proteins. Despite extensive use of magnetic nanomaterials for theranostic applications, the idea of exploiting its photonic response when assembled as a colloid inside a matrix remains unexplored. Herein, we report a novel label free method for quantitative detection of interleukin 6 which is a widely used prognostic marker for multiple pathological conditions. Cobalt ferrite/CoF and magnetite nanoparticles with Ms of 74.8 and 77 emu g-1 were assembled inside a hydrogel matrix with the application of an external magnetic field. Through the use of click chemistry, detecting antibodies were immobilized on their surface. The interaction of interleukin 6 with the antibodies produces a blue-shift in resonant wavelength and the reflectance intensity increases up to 50% and 44% when tested with CoF & magnetite based MPC respectively at a concentration of 50 pg ml-1. The dynamic range of the sensor lies within the prognostic values of IL-6, and the integrated sensing mechanism proposed in this study provides an ideal platform for real-time management of sepsis in patients with higher degree burns.

Prospects of kefiran as a food-derived biopolymer for agri-food and biomedical applications.

There is a huge demand for food-derived polysaccharides in the field of materials research due to the increasing concerns posed by synthetic biopolymers. The scientific community is extensively searching for other natural, food-derived or bio-inspired polymers that possess promising potentials and advantageous properties that can be promptly utilized for multifarious applications. Kefiran, a food-derived microbial exopolysaccharide extracted from kefir grains has exhibited evidence of non-toxicity, anti-microbial activity, nutritional value, and other favourable characteristics. This review aims to shed light on the properties of kefiran and provide an overview of its applications in the agri-food and biomedical sectors. The present work also discusses the challenges and prospects that lie ahead for kefiran in finding its place amongst the existing spectrum of natural and biodegradable polymers.

Cd-Free Zn(O,S) as Alternative Buffer Layer for Chalcogenide and Kesterite Based Thin Films Solar Cells: A Review.

Cd is categorized as a toxic material with restricted use in electronics as there are inherent problems of treating waste and convincing consumers that it is properly sealed inside without any threat of precarious leaks. Apart from toxicity, band-gap of CdS is about 2.40-2.50 eV, which results significant photon loss in short-wavelength range which restricts the overall performance of solar cells. Thin film of Zn(O,S) is a favorable contender to substitute CdS thin film as buffer layer for CuInGaSe2 (CIGS), CuInGa(S,Se)2 (CIGSSe), Cu2ZnSn(S,Se)4 (CZTSSe) Cu2ZnSnSe4 (CZTSe), Cu2ZnSnS4 (CZTS) thin film absorber material based photovoltaic due to it made from earth abundant, low cost, non-toxic materials and its ability to improve the efficiency of chalcogenide and kesterite based photovoltaic due to wider band-gap which results in reduction of absorption loss compared to CdS. In this review, apart from mentioning various deposition technique for Zn(O,S) thin films, changes in various properties i.e., optical, morphological, and opto-electrical properties of Zn(O,S) thin film deposited using various methods utilized for fabricating solar cell based on CIGS, CIGSSe, CZTS, CZTSe and CZTSSe thin films, the material has been evaluated for all the properties of buffer layer (high transparency for incident light, good conduction band lineup with absorber material, low interface recombination, high resistivity and good device stability).

The usefulness of trained field workers in diagnosis of post-kala-azar dermal leishmaniasis (PKDL) and clinico-epidemiological profile in highly endemic areas of Bihar.

BACKGROUND: Surveillance of post-kala-azar dermal leishmaniasis (PKDL) is critical to the elimination of visceral leishmaniasis (VL). In this study we assessed the feasibility of using trained field workers for detecting suspected PKDL cases. METHODS: A cross-sectional study using a multistage sampling technique was conducted in the Araria district of Bihar. Trained field workers were utilized for identification of suspected PKDL case. RESULTS: We investigated 57 099 individuals from 11 300 households. The trained field workers were useful in identifying 107 (18%) probable PKDL cases. The calculated PKDL prevalences were 18.7/10 000 and 9.7/10 000 for probable and confirmed PKDL cases, respectively. The median duration of onset of PKDL was 23 months (interquartile range 16.5-56.5). The younger age group developed PKDL significantly more often compared with the older age group (p=0.007). Of the 107 patients, 25 (55.5%) were positive by microscopy of slit skin smear and 42 (93.3%) by polymerase chain reaction. Of 45 patients, 33 (73%) PKDL cases were cured after full treatment. The risk of not being cured with incomplete treatment was three times higher than with complete treatment (relative risk 3.12 [95% confidence interval 1.23 to 8.67], p=0.004). CONCLUSIONS: We conclude that the prevalence of PKDL is high and the use of trained field workers may be feasible to actively detect PKDL cases in VL-endemic areas of Bihar, India.

Cytokines and chemokines differentially regulate innate immune cell trafficking during post kala-azar dermal leishmaniasis.

Post kala-azar dermal leishmaniasis (PKDL) is often considered to be the anthroponotic reservoir of visceral leishmaniasis (VL) in India. A better understanding of the host immune-response in dermal lesions of PKDL patients is therefore of utmost significance to minimize such patients and to restrict VL transmission. Although the innate immune response is known to play an important role in parasite clearance from dermal lesions, the actual contribution of innate cells to the pathogenicity of PKDL is poorly understood. The present study explored the immune-pathogenesis of PKDL patients to understand the expression of CD62L, CD11b, CXCL8/IL-8, and MIP1-α and their contribution in signaling during innate cell trafficking. Twenty-five individuals were enrolled, who comprised eight active and untreated macular cases, seven active and untreated cases with papulo-nodular PKDL manifestations, five successfully treated post PKDL cases and five healthy individuals from a non-endemic region of Bihar, India. The immunological investigation was performed on biopsy specimens prepared with a disaggregation technique and blood samples. We observed that the PMNs in nodular patients displayed decreased L-selectin (CD62L) levels and increased integrin (CD11b) expression compared with those in macular patients. Further analysis showed that lower PMN extravasation in macular patients occurred because of inadequate CXCL8/ IL-8 release. In summary, Leishmania donovani (L. donovani) infection in macular PKDL patients decreased leucocyte rolling (L-selectin shedding) and induced up-regulation of the cellular signaling factors involved in pathogenesis (ERK1/2) as well as down regulated the signaling elements (p38 MAPK) involved in the Th1 response, especially in PMNs.

Evaluating the association of bone morphogenetic protein 4-V152A and SIX homeobox 6-H141N polymorphisms with congenital cataract and microphthalmia in Western Indian population.

Background: Congenital cataract and microphthalmia are highly heterogeneous congenital eye disorders that affect normal vision. Although mutation in several genes has been shown to cause congenital cataract and microphthalmia, genetic studies associating single-nucleotide polymorphisms with these conditions is scarce. Hence, the present study aims to investigate the association of bone morphogenetic protein 4 (BMP4)-V152A (rs17563), and SIX homeobox 6 (SIX6)-H141N (rs33912345) polymorphisms with congenital cataract and microphthalmia in Western Indian cohorts. Materials and Methods: BMP4-V152A and SIX6-H141N were genotyped in 561 participants comprising of 242 congenital cataracts, 52 microphthalmia, and 267 controls using polymerase chain reaction (PCR) and allele specific oligonucleotide (ASO)-PCR method, respectively. Results: The frequency of BMP4- 152A was found to be significantly different between the cases and controls (Odds ratio (OR) 95% confidence interval [CI] = 1.4 [1.03-1.76], P = 0.0275). The frequency of BMP4- 152AA genotype was found to be significantly higher in congenital cataract cases as compared to controls (OR [95% CI] = 2.1 [1.14-3.67], P = 0.0154. The V-N haplotype of BMP4-V152A and SIX6-H141N was found to have a protective effect toward congenital cataract (OR [95% CI] = 0.72 [0.56-0.94], P = 0.0163) and microphthalmia (OR [95% CI] = 0.63 [0.40-1.01, P = 0.0541). Conclusions: The BMP4- 152AA genotype might play role in the causation of congenital cataract, whereas BMP4-SIX6 V-N haplotype might play a protective role toward the development of congenital cataract and microphthalmia.

Multidrug-eluting bi-layered microparticle-mesh scaffolds for musculoskeletal tissue regeneration.

Stem cell-based tissue engineering necessitates the development of a biocompatible scaffold, as a structural support, that provides a continuous supply of bioactive molecules for specific lineage differentiation. While incorporating bioactive molecules within a scaffold to improve stem cell differentiation has been reported in the literature, there is minimal evidence of any scaffold that can deliver a customized concoction of both hydrophobic and hydrophilic bioactive molecules to induce in situ lineage differentiation without any external supplements. In this study, we established a bioactive, drug-eluting bi-layered microparticle-mesh scaffold (BMMS) using the electrospinning technique. This BMMS was co-encapsulated with hydrophobic dexamethasone (in the mesh), hydrophilic ascorbic acid and ß-glycerophosphate or proline (in the microparticles). We hypothesized that a sustained-releasing BMMS can direct in situ specific lineage differentiation of MSCs (e.g. osteogenic and chondrogenic) in a minimally supplemented culture environment into musculoskeletal tissues. The characterization of this BMMS revealed good encapsulation efficiencies of the bioactive molecules with sustained-releasing capabilities. The release kinetics of each drug was further analyzed using mathematical drug-releasing models. These scaffolds were subsequently shown to have potential for osteogenic or chondrogenic lineage differentiation from mesenchymal stem cells (MSCs) in a minimally supplemented culture medium.

Sustained releasing sponge-like 3D scaffolds for bone tissue engineering applications.

Tissue engineering (TE) is envisaged to play a vital role in improving quality of life by restoring, maintaining or enhancing tissue and organ functions. TE scaffolds that are two-dimensional in structure suffer from undesirable issues, such as pore blockage, and do not closely mimic the native extra-cellular matrix in tissues. Significant efforts have therefore been channeled to fabricate three-dimensional (3D) scaffolds using various techniques, especially electrospinning. In this study, we propose a modified one-step electrospinning process to arrive at a 3D scaffold with highly interconnected pores. Using a blend of poly (L-lactide)/polycaprolactone/poly (ethylene oxide), this mechanically viable, sponge-like 3D scaffold exhibited sufficiently large pores and enabled cell penetration beyond 500 µm. Dexamethasone (Dex) was loaded into the fibers and a sustained drug release was achieved. Further, the potential of this Dex-loaded 3D scaffold was evaluated for upregulation of osteogenic genes with mesenchymal stem cells. The as-produced Dex-loaded 3D scaffold possesses a unique intertwined sub-micron fibrous morphology that can be tailored for use in bone tissue engineering and beyond.

Films of Reduced Graphene Oxide with Metal Oxide Nanoparticles Formed at a Liquid/Liquid Interface as Reusable Surface Enhanced Raman Scattering Substrates for Dyes.

Free standing, thin films of reduced graphene oxide (rGO) with ZnO, CuO and SnO(2) nanostructures are prepared at a water/toluene interface utilizing simple interfacial reaction and self-assembly. rGO-ZnO, rGO-CuO and rGO-SnO(2) films exhibit unique morphologies such as hexagonal cylinders, elongated splinters, and balls, respectively, wrapped by rGO layers. The hybrid films exhibit surface enhanced Raman scattering (SERS) of rhodamine 6G dye with enhancement factors one order higher than bare metal oxide caused by a synergic effect of charge transfer between the dye, metal oxide and rGO. Doping with Ag+ ions improves SERS enhancement in rGO-Ag­ZnO hybrid films, exploiting the electromagnetic effect of metal surface plasmons. Detection sensitivity up to 10 µM dye with an enhancement factor of 104 is shown. The enhanced photodegradation rate by the hybrid films is utilized for UV induced regeneration of the used SERS substrate and is demonstrated for successive use of different analytes.

Snowball Vs. House-to-House Technique for Measuring Annual Incidence of Kala-azar in the Higher Endemic Blocks of Bihar, India: A Comparison.

BACKGROUND: Visceral Leishmaniasis, commonly known as kala-azar, is widely prevalent in Bihar. The National Kala-azar Control Program has applied house-to-house survey approach several times for estimating Kala-azar incidence in the past. However, this approach includes huge logistics and operational cost, as occurrence of kala-azar is clustered in nature. The present study aims to compare efficiency, cost and feasibility of snowball sampling approach to house-to-house survey approach in capturing kala-azar cases in two endemic districts of Bihar, India. METHODOLOGY/PRINCIPAL FINDINGS: A community based cross-sectional study was conducted in two highly endemic Primary Health Centre (PHC) areas, each from two endemic districts of Bihar, India. Snowball technique (used to locate potential subjects with help of key informants where subjects are hard to locate) and house-to-house survey technique were applied to detect all the new cases of Kala-azar during a defined reference period of one year i.e. June, 2010 to May, 2011. The study covered a total of 105,035 households with 537,153 populations. Out of total 561 cases and 17 deaths probably due to kala-azar, identified by the study, snowball sampling approach captured only 221 cases and 13 deaths, whereas 489 cases and 17 deaths were detected by house-to-house survey approach. Higher value of McNemar's χ² statistics (64; p<0.0001) for house-to-house survey approach than snowball sampling and relative difference (>1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to-house approach with 13% of omission. CONCLUSION/SIGNIFICANCE: Snowball sampling was not found sensitive enough as it captured only about 50% of VL cases. However, it captured about 77% of the deaths probably due to kala-azar and was found more cost-effective than house-to-house approach. Standardization of snowball approach with improved procedure, training and logistics may enhance the sensitivity of snowball sampling and its application in national Kala-azar elimination programme as cost-effective approach for estimation of kala-azar burden.

Hybrid materials of ZnO nanostructures with reduced graphene oxide and gold nanoparticles: enhanced photodegradation rates in relation to their composition and morphology.

Binary and ternary hybrid systems of ZnO possessing nanoparticle and nanorod morphologies on reduced graphene oxide (rGO) and rGO with Au nanoparticles are explored as photocatalysts and a comparative study of their photodegradation performance is presented. Various preparation methods such as solution phase and hydrothermal routes have been employed to produce rGO-ZnO hybrids and rGO-Au-ZnO hybrids to impart different morphologies and defect states in ZnO. All the hybrids exhibit faster photodegradation kinetics and the rGO-Au-ZnO system exhibits the highest rate, five times faster than bare ZnO, followed by the binary systems, rGO-ZnO nanoparticles and nanorods. Various factors such as structure, morphology, charge transfer and adsorption are considered to explain the observed kinetics. Excited state electron transfer from ZnO to both rGO and Au levels facilitates faster dye degradation for rGO-Au-ZnO and is reflected as highly quenched band edge and defect state photoluminescence. Intimate physical interfaces formed between rGO, Au and ZnO in the hybrid material during in situ reactions favour charge transfer across the components. The charge transfer contribution even dominates the adsorption factor and the rGO-Au-ZnO system with a slightly lower adsorption capacity than the rGO-ZnO system exhibits a higher degradation rate. A power law dependence of the photodegradation rate on light intensity is also expressed.

Understanding the virulence of the entero-aggregative E. coli O104:H4.

O104:H4 is a new strain of E. coli that has caused an outbreak in Germany. It was isolated from patients with bloody diarrhoea and Haemolytic Uremic Syndrome (HUS). BGI (www.genomics.cn) sequenced and assembled this new strain. It was reported to show resistance to a number of drugs that are toxic to other E. coli and causes serious complications during infections, which ultimately lead to death. Multi-drug resistance and high virulence of this strain is thought to be acquired from different sources, by horizontal gene transfer. A total of 38 prophage elements were detected from the new strain by using three computational tools viz., DRAD, Prophage Finder and PHAST. Analysis on these prophage elements shows a number of virulence proteins like Shiga toxin and multi-drug resistance protein encoding genes. The high virulence of the strain could be attributed by the prophage elements acquired from its micro environment.

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. METHODS: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. RESULTS: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥ 40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. CONCLUSIONS: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.

Effectiveness of miltefosine treatment in targeting anti-leishmanial HO-1/Nrf-2-mediated oxidative responses in visceral leishmaniasis patients.

OBJECTIVES: Miltefosine, an alkylphosphocholine anti-cancer drug, exhibits direct activity against Leishmania donovani and also promotes anti-leishmanial host immunomodulatory functions. Nuclear factor-erythroid 2-related factor 2 (Nrf-2), a redox-sensitive transcription factor, regulates the host stress responses leading to effective microbial clearance by a positive effect on haem oxygenase-1 (HO-1) enzyme expression/activity. We aimed to investigate the role of miltefosine in regulating HO-1/Nrf-2-mediated oxidative responses in visceral leishmaniasis (VL) patients in vivo and in vitro. METHODS: Splenic aspirate and bone marrow aspirate cells of VL patients (n = 23) were used in the study. RT-PCR of HO-1, Nrf-2 translocation analysis and HO-1 ELISA were used to investigate the HO-1/Nrf-2-mediated modulation of oxidative responses by miltefosine in vivo. Fluorometric measurement of reactive oxygen species (ROS) was performed, determination of glutathione peroxidase (GPx) activity was performed, and bilirubin and superoxide dismutase (SOD) levels were determined. The in vitro HO-1/Nrf-2-dependent anti-leishmanial effect of miltefosine was assessed by the use of specific inhibitors/inducers and subsequent microscopic measurement of parasite killing and Th1/Th2 cytokine regulation by ELISA. RESULTS: Increased levels of transcript and serum HO-1, Nrf-2 nuclear translocation, serum bilirubin, GPx and SOD activity in untreated VL patients were reversed after miltefosine chemotherapy. The effectiveness of miltefosine for positive induction of ROS via NADPH correlated with a decrease in HO-1/ERK/Nrf-2-dependent parasite load. Furthermore, HO-1 blockade by miltefosine led to suppression of interleukin-10 and transforming growth factor-ß, but enhanced interleukin-12 and tumour necrosis factor-α production, in VL patients. CONCLUSIONS: The antioxidant promoting property of L. donovani is crucial for protection against the mounting redox threat in the host. Therefore, these findings provide direct evidence for targeting HO-1/Nrf-2 as an anti-leishmanial approach for chemotherapy in human VL.

Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: There is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually. METHODS: We cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected. RESULTS: The total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18-98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively. CONCLUSION: The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies.It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India.