Because of the less adverse effects, especially for constipation,

Because of the less adverse effects, especially for constipation, transdermal fentanyl might be easier to improve QOL. In present study, 6 trials reported data on QOL and showed either transdermal fentanyl or sustained-release oral morphine improved QOL of cancer patients [9, 14, 17, 32–34]. Especially, one of trials supported more patients got better Daporinad mouse QOL after sustained-release oral morphine transferred to transdermal fentanyl [34]. Cost effectiveness was not an endpoint in the present

systematic review, but it was a valuable index to evaluate a drug for clinical use. 2 out of selected trials reported data about cost effectiveness that transdermal fentanyl had higher expenditure to control certain pain than oral morphine [35, 36]. However, we MK-1775 concentration should keep in mind that cost effectiveness was affected by many factors in fact and only 2 out of 32 trials reported data about cost effectiveness when we concluded cost effectiveness was higher in transdermal fentanyl. Similar with European and American data [4–6], our data also showed that both transdermal fentanyl and find more sustained-release oral morphine were effective in treating stable moderate-severe cancer pain in Chinese population with less

adverse effects for transdermal fentanyl. However, two differences should be pointed out. First, QOL was only analyzed in our study, and data suggested that transdermal fentanyl potentially improved QOL of cancer pain patients and resulted in better compliance compared with oral morphine. Second, more patients were included in the present systematic review and all

patients were Chinese. To explain the results reasonably, several issues should be considered as follow. First, the data source was extracted from abstracted data and not individual patient data (IPD). In general, an IPD-based meta-analysis would give a more robust estimation for the association; therefore, we should interpret the results with care, especially for a positive result. Clearly, further investigations using IPD should be conducted to examine the main end points. Second, all selected trials were cohort studies, which is not most suitable clinical trial to explore the difference of two drugs. Third, 5 FU heterogeneity existed among the trials when pooled analysis of adverse effects (constipation and nausea/vomiting), fortunately, the data was not materially changed in sensitivity analysis. Fourth, side effects seemed to be lower in our selected trials compared with clinical practice. We thought that these results might be explained in two aspects of small sample in single trial and better tolerance in Chinese population. At last, transdermal fentanyl takes 12-24 hours for serum levels to stabilize after starting the patch and dose increment was trouble in clinic practice, so it is less flexible and needs to be used with caution in patients with unstable pain.

This suggests that replicating SINV-TR339EGFP has triggered the R

This suggests that replicating SINV-TR339EGFP has triggered the RNAi pathway in the mosquito midgut. Effects of Aa-dcr2 silencing in the midgut of Carb/dcr16 females on intensity of SINV-TR339EGFP infection, infection rate, and dissemination in an initial experiment To test whether midgut-specific silencing of Aa-dcr2 affects the vector competence for SINV-TR339EGFP, infection intensities and virus infection and dissemination rates were evaluated in Carb/dcr16 mosquitoes. In see more an initial experiment (virus titer in the bloodmeal: 1.8 × 107 pfu/ml), midgut infection rate and intensity of virus infection were significantly higher in Carb/dcr16 than in HWE mosquitoes

at 7 days pbm (Fig. 3A). We observed that 21/30 Carb/dcr16 females were infected with a ~1300-fold higher mean virus titer than the HWE control. In Navitoclax contrast, only 2/30 HWE mosquitoes had measurable virus infection in their midguts. Accordingly, 53% of the remaining mosquito bodies of Carb/dcr16 females were infected with SINV at 7 days pbm, whereas no HWE carcasses showed any https://www.selleckchem.com/products/Pazopanib-Hydrochloride.html detectable infection. This indicates that midgut infection rate and intensity affect the dissemination potential of the virus to secondary tissues. However, at 14 days pbm the overall SINV infection patterns of Carb/dcr16 females were no longer significantly

different from those of the HWE control. These results suggest that SINV-TR339EGFP encountered MIB and MEB in HWE mosquitoes at 7 days pbm, whereas in the RNAi-impaired Carb/dcr16 females these barriers were not evident. Figure 3 Intensity of SINV-TR339EGFP infection in Carb/dcr16 and HWE mosquitoes. A) Raw data of a single

experiment in which Carb/dcr16 females were orally challenged with SINV. Each data point represents the virus titer (pfu/ml) in midgut or carcass of an individual mosquito. P-values for intensities of virus infection are shown in the table. B) Mean intensities of SINV infection in midguts and carcasses of Carb/dcr 16 and HWE females at 7 and 14 days pbm. Mean values of three experiments are shown. (N = sample size; * = statistically significantly Org 27569 different (α = 0.05); error bars = SEM). Effects of Aa-dcr2 silencing in the midgut of Carb/dcr16 females on mean intensities of SINV-TR339EGFP infection, infection and dissemination rates To confirm this observation, we repeated the experiment three more times and assessed mean intensity of SINV infection and midgut infection rates. To reveal mean midgut dissemination rates for the virus, two additional replicates of the experiment were analyzed. SINV-TR339EGFP titers in the bloodmeals ranged from 1.7-2.7 × 107 pfu/ml. The mean intensity of virus infection in midguts of Carb/dcr16 females (14,000 pfu/ml) was >8-fold higher than in the control at 7 days pbm, which was highly significant (Fig. 3B). Similarly, in the remaining mosquito bodies the difference between HWE and Carb/dcr16 females was statistically significant.

Figure 4 ZR-ATMi cells are more sensitive than ZR-ctr cells

Figure 4 ZR-ATMi cells are more sensitive than ZR-ctr cells

to click here olaparib but not to iniparib. (A) ZR-75-1 cells were transfected with shATM-carrying vector (ZR-ATMi) and its siR5 negative control (ZR-ctr). ATM protein levels in ZR-ATMi and ZR-ctr cells were analyzed by Western blot. α-tubulin was used as an internal control. B-C ZR-ATMi and ZR-ctr cells were exposed to increased concentrations of olaparib (B) or iniparib for 72 hrs (C). Data are represented as mean ± SD. (D) Flow cytometry analysis of cell-cycle distribution of ZR-ATMi and ZR-ctr cells treated with the indicated concentrations with olaparib or iniparib for 72 hrs. E-F Quantitative analyses of colony formation. The numbers of DMSO-resistant colonies in ZR-ATMi and ZR-ctr cells were set to 100, while olaparib (E) or iniparib (F) treated cel1s were presented as mean ± SD. Asterisks Tideglusib manufacturer indicate statistical significant difference (*P < 0.1; **P < 0.05). In contrast with the sensitivity induced by ATM-depletion in MCF-7 cells, when treated with iniparib, both ZR-ATMi and ZR-ctr cells showed a substantial loss of viability that was independent of ATM, as indicated by the similarity of

their survival curves (Figure 4C) and cell cycle distribution (Figure 4D). These results were confirmed by the complete inhibition of colony formation induced by iniparib in ZR-75-1 cells, independent of their ATM status (Figure 4F). In addition, the different response between MCF-7 and ZR-75-1 cells to this drug suggests that ER expression and the wild-type status of BRCA1/2 and TP53 are not involved in the sensitivity to iniparib. These results might be explained by the recent observations indicating that the primary mechanism of action for iniparib is a nonselective modification of cysteine-containing proteins, rather then inhibition of PARP activity [32]. Conclusions In a few hematological malignancies, ATM-deficiency was shown to confer sensitivity to PARP inhibitors, indicating that ATM might be included in the DDR factors whose mutation or loss of expression confer sensitivity to this class of drugs. Based on these observations, we asked whether

ATM deficiency plays a similar role in Oligomycin A price breast cancer, the solid tumor linked to ATM germline mutations. For this study, we employed two breast-cancer cell lines selected of among those showing the molecular feature we recently observed in the breast tumors arising in A-T heterozygotes. In addition, we selected two compounds, olaparib and iniparib, originally described as PARP inhibitors. We show that ATM-depletion confers sensitivity to olaparib in both cell lines and a mild sensitivity to iniparib in the MCF-7 cells indicating that ATM mutation/inactivation might be consider in the selection of breast cancers responsive to PARP inhibition. Acknowledgements We thank Dr. Tania Merlino for the proof reading of the manuscript and Dr. Lidia Strigari for statistical support.

Similarly to Figure 4, the plots present values averaged from sev

Similarly to Figure 4, the plots present values averaged from several measurements made on three Niraparib in vivo different samples evaporated at each temperature. Surprisingly, in 10-nm-thick films in the whole range of temperatures 200 to 350 K, adhesive forces between Ag adatoms and Ge wetting layer dominate over cohesive forces in silver. Thus, the temperature-dependent mobility of Ag adatoms does not deteriorate significantly the surface smoothness. RMS roughness values from tapping-mode AFM measurements of 10-nm Ag films are in agreement with those obtained using

XRR. An example of XRR data obtained for the 10-nm-thick Ag film deposited on 1-nm Ge interlayer and a fitted model are shown in Figure 7. The average film thickness measured learn more using XRR is 10.9 ± 1.1 nm and differs up to 10% from the SN-38 purchase values controlled with calibrated quartz weight installed in the vicinity of substrates in the vacuum chamber of the e-beam evaporator. In single-layer structures, e.g., plasmonic silver lenses [28, 29], such fabrication

inaccuracies should less deteriorate performance than in the case of metal-dielectric-layered flat lenses [30–32]. Figure 6 Ten-point and average height values measured on 3 × 3 μm 2 area on 10-nm Ag films. Thin films were deposited at temperatures in the range 200 to 350 K, and RMS values were measured using both AFM and XRR. Figure 7 XRR data and fitted model for 10-nm Ag and 1-nm Ge film on sapphire substrate. At the end, we investigated the interior structure of 10-nm-thick samples using one-dimensional XRD. The dependency between grain size and the substrate temperature is presented in Figure 8. Again, the samples evaporated at temperatures close to RT have the best uniformity. Figure 8 Grain sizes measured using one-dimensional XRD. Ag films of 10-nm thickness were deposited at temperatures in the range 200 to 350 K. Conclusions A new sublimation-pressure empirical equation valid in the range from 50 K to T t = 273.16 K of the triple point helps Nutlin-3 nmr select the optimum temperature in high-vacuum physical vapor deposition systems. We have demonstrated the possibility

to fabricate ultrasmooth metal nanolayers deposited onto epi-polished substrates at the lowest achievable pressure and at such a temperature that the whole dynamic range of both parameters is located on the gas side of the phase-boundary curve of water in a p-T diagram. The temperature range 230 to 350 K is established as the optimum for deposition of Ag nanolayers using e-beam evaporators. For the 10-nm Ag film on 1-nm Ge interlayer deposited at RT on sapphire substrate, a surface roughness with RMS = 0.22 nm has been achieved. For 30-nm-thick Ag films on sapphire substrate with 1-nm Ge wetting layer, RMS increases up to 0.49 nm. The ten-point height parameter given by extreme local surface features, which reflects scattering properties, has its minimum at 295 K.

(see Figure 6) Eight

(see Figure 6). Eight this website of the 10 terms have their own child and lower level offspring terms, and each of those “”response”" terms has a child term such as “”maintenance of symbiont tolerance to host …”" (see details in Figure 6). The term “”GO ID 0075147 regulation of signal selleckchem transduction in response to host”" has five children to describe different types of signal transduction, similar to the five child terms of “”GO ID 0052470 modulation by host of symbiont signal transduction pathway”" in the first set. Each of the five terms has child terms for positive regulation and negative regulation. The three sets of new GO terms can be used

to explicitly describe genes of signal transduction pathways involved in host recognition. For instance, the PMK1 gene of the rice blast fungus Magnaporthe oryzae encodes a mitogen-activated protein kinase (MAPK), which is a key component in the MAPK signaling cascade and is involved in appressorium formation and infectious growth [32]. Thus, the PMK1 protein can be annotated with the term “”GO ID 0075171 regulation of MAP kinase-mediated signal

transduction in response to host”". Note that this gene product would not be annotated with “”GO ID 0052435 modulation by host of symbiont MAP kinase-mediated signal transduction selleck kinase inhibitor pathway”" since this latter GO term is reserved to annotate host gene products. Similarly, this protein should not be annotated with “”GO ID 0052080 modulation by symbiont of host MAP kinase-mediated signal transduction pathway”" since PMK1 belongs to the symbiont’s and not the host’s signaling transduction pathway. In addition, the modulation terms have children

that describe more specific kinds of signal transduction. For example, “”GO ID 0075168 regulation of protein kinase-mediated signal transduction in response to host”" has a child “”GO ID 0075171 regulation of MAP kinase-mediated signal transduction in response to host”" (see details in Figure 6). Penetration into the host Pathogens have evolved several mechanisms that include structural and/or enzymatic components in order to enter into their plant hosts [5]. Many fungi, such many as Alternaria alternata, Colletotrichum graminicola, M. oryzae, Pyrenophora teres, and many oomycetes, such as P. infestans and Phytophthora cinnamomi, develop appressoria to directly penetrate plant cuticles [13, 33–38]. An appressorium is a highly specialized structure that differentiates from the end of a symbiont germ tube. It is a swollen, dome-shaped or cylindrical organ, from which a narrow penetration peg emerges to rupture the plant cuticle and cell wall [33]. The penetration peg extends and forms a penetration hypha to penetrate through the epidermal cells and emerge into the underlying tissue [34, 35]. In some instances, penetration is driven by astoundingly high turgor pressures within the appressoria [36, 38].

In terms of PI, co-formulations of COBI/ATV and COBI/DRV are in d

In terms of PI, co-formulations of COBI/ATV and COBI/DRV are in development. The low incidence of neuro-psychiatric side

effects with COBI/EVG compared with EFV, and the lower prevalence of diarrhoea with COBI/ATV compared with RTV/ATV, makes it a potentially attractive alternative to these commonly prescribed agents. The reduced pill burden and once-daily administration distinguish COBI/EVG www.selleckchem.com/products/Lapatinib-Ditosylate.html from RTG, the only other II currently licensed. However, a single-tablet regimen based on the investigational integrase, dolutegravir, co-formulated with abacavir and lamivudine is expected to be licensed within the next 12 months and is currently under review by the FDA. Stribild’s lack of interaction with acid-reducing agents distinguishes it from ATV and RPV. There remain several data gaps, and widespread uptake of Stribild and COBI may be hampered by these. The male predominance and high median CD4 cell count of the phase III trial participants limit data in women and YAP-TEAD Inhibitor 1 patients with low CD4 cell counts, opportunistic infections, malignancy or other serious co-morbidities, although the WAVES study, comparing Stribild

to Truvada® (Gilead Inc., Foster City, CA, USA) plus RTV/ATV in women, is currently recruiting. COBI is associated with drug–drug interactions, few of which have been studied to date. Although virological failure with Stribild was uncommon, patients that did fail commonly enough did so with dual-class resistance, and it remains unclear whether these viral isolates remain susceptible to dolutegravir. Also, Stribild selleck is only licensed for use in patients

with creatinine clearance ≥70 mL/min thus is not suitable for patients with renal impairment. The inclusion of TDF in Stribild makes it a less attractive option for patients with, or at risk of, osteoporosis, although the renal and bone concerns are likely to be less if TAF becomes the preferred tenofovir formulation of COBI-based single-tablet regimens. Finally, in an increasingly cost-conscious environment, the relative benefits of Stribild and COBI will have to be weighed against any incremental cost relative to current proprietary medications as well as forthcoming generic formulations. Acknowledgments No funding or sponsorship was received for this study or publication of this article. Frank A. Post is the guarantor for this article, and takes responsibility for the integrity of the work as a whole. Prior to peer review Gilead were offered the opportunity to review the article solely to ensure scientific accuracy of the details. Minor changes were made to the content as a result, at the discretion of the authors. No writing assistance or other editorial involvement was provided by the manufacturer.

This phase III study was designed to test the non-inferiority (ba

This phase III study was designed to test the non-inferiority (based on the percent change in lumbar spine BMD from baseline NVP-LDE225 cost after 1 year) of the risedronate 35 mg DR weekly formulation taken before or after breakfast compared

to the 5 mg daily IR dose taken per label. Comparison to the 5 mg daily dose of risedronate IR instead of the 35 mg weekly dose was performed to meet regulatory guidelines for the approval of new formulations of a previously approved drug. The efficacy and safety results for the first year of the study are reported here. Methods and materials Study design This randomized, double-blind, active-controlled, parallel-group study was conducted at 43 study centers in North America, South America, and the European Union. The first subject was screened in November 2007,

and the last subject observation for the first year of the study took place in April 2009. The study was performed Poziotinib cost in accordance with good clinical practice and the ethical principles that have their origin in the Declaration of Helsinki. The protocol was approved by the appropriate institutional review boards or ethics committees, and the subjects gave written, informed consent to participate. Subjects Women were eligible to enroll in the study if they were at least 50 years of age, ambulatory, in generally good health, postmenopausal (at least 5 years since last menses), had at least three vertebral bodies in the lumbar spine (L1 to L4) evaluable by densitometry (i.e., without fracture or degenerative disease), and had a lumbar spine or total hip BMD corresponding to a T-score of −2.5 or lower or a T-score of −2.0 or lower with at least one prevalent vertebral fracture (T4 to L4). Exclusion criteria included contraindications to oral bisphosphonate therapy, lumbar spine BMD corresponding to a T-score of −5 or lower, use of medications that could interfere with the study evaluations, conditions that would interfere with the BMD measurements,

17-DMAG (Alvespimycin) HCl bilateral hip prostheses, body mass index greater than 32 kg/m2, allergy to bisphosphonates, history of click here cancer in the last 5 years (excluding basal or squamous skin cancers or successfully treated cervical cancer in situ), drug or alcohol abuse, abnormal clinical laboratory measurements, creatinine clearance less than 30 mL/min, hypo- or hypercalcemia, history of hyperparathyroidism or hyperthyroidism (unless corrected), osteomalacia, and any previous or ongoing condition that the investigator judged could prevent the subject from being able to complete the study. Eligible subjects who gave consent were stratified by anti-coagulant use (since fecal occult blood testing was performed during the study) and randomly assigned in a 1:1:1 ratio to the three treatment groups.

Comparing Figure 3a (6 h annealed)

and Figure 3b (9 h ann

Comparing Figure 3a (6 h annealed)

and Figure 3b (9 h annealed), the atomic ratio of Si to Al of the microparticle formed through 9 h annealing (50.5%) PXD101 is much larger than that of the microparticle which underwent 6 h annealing (10.5%). Taking into account that the annealing SYN-117 in vitro temperature (550°C) of the present study is lower than the eutectic temperature (577°C) of Al-Si systems and the Si solubility in Al crystal is only about 1.4 at. % at 550°C [22], the measured large Si concentrations reflect solid-state interdiffusion of Al and Si atoms facilitated by compressive stress that is developed by larger expansion of Al film than Si substrate during annealing (see the middle panel of Figure 1) [23, 24]. It is speculated that more mobile Al atoms move first over the surface or through grain boundaries to agglomerate, leaving behind a lot of vacancies. These vacancies in Al film may accelerate outward diffusion

of Si atoms and direct Si atomic flow to Al granules to finally form Al-Si alloys. In addition, since the surface energy of Si (100) plane is relatively high (2.13 J/m2) [25], Si atoms are prone to diffuse into a foreign material at elevated temperatures to reduce the surface energy. This hypoeutectic interdiffusion progresses further as the annealing time is made longer. The atomic ratio of Si/Al rises to 82% for selleck kinase inhibitor a microparticle from the 90-nm-thick film, as shown in Figure 3c. This may be because a larger volume of Al vacancies in Al film absorbs more Si atoms from the substrate. As a consequence of Al-Si microparticle formation, the majority of the original Al film is exhausted as seen in Figure 3b,c. Interestingly, it is found from Figure 3c that the residual Al film resembles the network structures of narrow channels. Figure 3 SEM images of microparticles. SEM images of microparticles transformed through (a) 6 h annealing and (b) 9 h annealing of a 40-nm-thick Al film and (c) 9 h annealing of a 90-nm-thick Al film on Si substrate. Annealing temperature was set at 550°C. Scale bars 2.5 μm. Histone demethylase EDX element analysis results are also presented

for the particle area (notated as ‘1’) and the rest (notated as ‘2’), respectively. The composition and the crystal structure of both untreated and heat-treated Al films on the Si substrate were further analyzed using XRD. Figure 4 shows XRD patterns of 90-nm-thick Al films before and after annealing. For both samples, three major peaks are sharp, representing the samples are crystalline irrespective of heat treatment. The overwhelming peak of 68° to 69° is assigned to Si (400). Al (220) peak that usually appears around 66° is presumed to be superposed with the Si (400) peak. The other two peaks observed at approximately 33° and 62° are related to Al2O3 or Al-Si oxide. The peak intensities of a 9-h annealed sample are far larger than those of the untreated sample at those 2θ angles, particularly at approximately 33°.

Our result suggested that PPARα agonist could sensitize the effec

Our result suggested that PPARα agonist could sensitize the effect of NAC on cell growth inhibition and also implied that NAC may act as a potential PPARα ligand. Consistent with this, one report demonstrated a synergistic effect of PPARα agonist and NAC in control of brain tumor cells [18]. Note that no report showed a link between PPARα ligand and PDK1 although PDK1 was reported to be a target gene of PPARσ/β [19], another isoforms of PPAR family, which strongly expressed in the majority of lung cancers,

and IBET762 activation of this isoform induced proliferation of lung cancer through pathways including activation of Akt phosphorylation correlated with up-regulation of PDK1 [20]. Note that the PDK1 promoter contains peroxisome proliferator responsive element (PPRE) [19], our data showed that PPARα ligand inhibited PDK1 promoter activity suggesting a distinct function of PPARα activation as compared to that of PPARσ/β. More studies are required to elucidate this. Furthermore, our results indicated that NAC–mediated downregulation of PDK1 reflected inhibition of transactivation of the PDK1 gene and also demonstrated that NAC, through activation of PPARα, increased tumor suppressor, p53 and reduced p65, a subunit of NF-κB, which played important roles in mediating the effect of NAC on inhibition of PDK1 expression. This again suggested the characteristic

of NAC acted as PPARα ligand. Silencing of p53 and overexprerssion of p65 blocked the effects of NAC on PDK1 expression further Methocarbamol confirm the key roles of p53 and p65 in this process. P53 plays a critical role in tumor suppression mainly by inducing growth arrest, blocking

angiogenesis CFTRinh-172 and conferring the cancer cell sensitivity to chemoradiation [21]. Transcription factor NF-κB has been shown to regulate the expression of a number of genes that involve in many cellular processes such as inflammation and tumor growth [22]. Interestingly, the link of p53 in the regulation of glycolysis-dependent activation of NF-κB signaling in cancer has been reported [23]. However, the role of p53 and NF-κB in the direct regulation of PDK1 expression remains unknown. On the contrary, one study showed that overexpression of PDK1 resisted the apoptotic cell death caused by hypoxic injury and increased the expression of survival proteins, such as p53, in cultured rat cardiomyocytes [24]. Also, reports found that PDK1 plays a critical role by nucleating the T cell receptor-induced NF-κB activation pathway, which is important for T cell proliferation and activation during the adaptive immune response [25]. Together, these findings indicated that PDK1 was a critical PRT062607 mouse regulator of tumor cell survival by modulating the p53 and NF-κB signaling pathways. NAC also had a direct or indirect effect on the regulation of p53 and NF-κB [26, 27]. The activation of p53 has been shown to mediate the effects of NAC on prostate cancer cell growth [28].

The molecular metagenome based approach has been taken into accou

The molecular metagenome based approach has been taken into account for our ongoing studies to overcome the limitation. (ii) Limiting landscape to a small geographic region due to financial constrains; consequently the most upstream location in the landscape does not hold the merit of pristine location to be considered for absolute estimation of background

level or pool of resistance or virulence-determinants, only relative estimation of background level of resistance is the feasible option. GW786034 nmr More collaboration between the national and international labs is needed for the purpose. (iii) Lack of exact data on usage pattern of antimicrobials in human and veterinary medicine which further limits the study as the quantitative nature of cause-effect relationship remains partially explored. Strict rule

codes needed to be set and maintained by the regulatory agency for local counterparts to keep the track record of supply as well as nature and mode of consumption. However, the intricacies in retrieving specific antimicrobial usage data based on individual consumption continue to be a global challenge for environmental health researchers in the absence of national and or state regulations that require consumers to report their consumption to the local authority as earlier mentioned by Sapkota et al [22]. Conclusion In the present study, the spread of potential pathogenic enterococci ARN-509 appears to be the manifestation of NCT-501 mw complex network of ecological processes and associated factors in the landscape of river Ganga. Enterococci recognized as hardy and rogue microbe may cause very serious infections with limited options of treatment. Surface waters with emerging VRE and background pool of multiple-antimicrobial-resistant and multi-virulent enterococci can contribute to the dissemination of resistance and virulence-determinants in the diverse Enterococcus spp. and other bacteria. Therefore,

the presence of antimicrobial-resistant pathogenic enterococci in surface waters of populous PD184352 (CI-1040) nations demand improved surveillance for risk assessment and pre-emptive strategies for protection of public health. Methods Study site The study was performed along 30 km landscape in and around Kanpur city (geographic coordinates: 26.4670° North and 80.3500° east, area: 1600 km2, estimated population: 4,864,674) located on the banks of river Ganga in up-to-down-gradient fashion (Figure 1). The most upstream Site 1 is Bithoor, a rural area with agricultural farms located 20 km upstream of the city. Site 2 is Bhairon ghat, it receives municipal waste from the locality. Site 3 is Parmat ghat, receives contamination through urban sewage, hospital and one tannery located upstream to it. Site 4 is Sattichaura ghat and two watersheds of river Ganga confluence just upstream of this site. Site 5 is Jajmau, the most downstream site, hub for tanneries and receives municipal waste from whole city.