In the Indian subcontinent, Visceral leishmaniasis is endemic in a geographical area coinciding with the Lower Gangetic Plain, at low altitude. VL occurring in residents of hill districts is ...therefore often considered the result of Leishmania donovani infection during travel. Early 2014 we conducted an outbreak investigation in Okhaldhunga and Bhojpur districts in the Nepal hills where increasing number of VL cases have been reported.
A house-to-house survey in six villages documented retrospectively 35 cases of Visceral Leishmaniasis (VL). Anti-Leishmania antibodies were found in 22/23 past-VL cases, in 40/416 (9.6%) persons without VL and in 12/155 (7.7%) domestic animals. An age- and sex- matched case-control study showed that exposure to known VL-endemic regions was no risk factor for VL, but having a VL case in the neighbourhood was. SSU-rDNA PCR for Leishmania sp. was positive in 24 (5%) of the human, in 18 (12%) of the animal samples and in 16 (14%) bloodfed female Phlebotomus argentipes sand flies. L. donovani was confirmed in two asymptomatic individuals and in one sand fly through hsp70-based sequencing.
This is epidemiological and entomological evidence for ongoing local transmission of L. donovani in villages at an altitude above 600 meters in Nepal, in districts considered hitherto non-endemic for VL. The VL Elimination Initiative in Nepal should therefore consider extending its surveillance and control activities in order to assure VL elimination, and the risk map for VL should be redesigned.
e19037
Background: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. tAML demonstrates high ...risk characteristics and poorer outcomes compared with de novo AML. We aimed to quantify the risk of tAML in NHL, determine factors associated with overall survival (OS) in tAML, and compare them with de novo AML. Methods: Patients with a histologic diagnosis of NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) 18 database. AML that developed at least 1 year after the diagnosis of NHL was classified as tAML. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software (version 8.3.9) were used to calculate SIR and absolute excess risk (AER) of tAML based on - age, sex, race, year of diagnosis, chemotherapy, radiotherapy, and interval from NHL diagnosis. The 95% confidence intervals (CI) and p-values were generated using multivariate Poisson regression model. OS of both tAML and de novo AML was assessed using Kaplan Meier curves and then compared using log rank test. The roles of various factors on OS in tAML and de novo AML were evaluated using multivariate cox proportional hazard regression. Results: A total of 373 patients with tAML (N for NHL = 301,903) and 23,360 patients with de novo AML were included in the analysis. More de novo AML cases were ≥70 years compared to tAML (41.1% vs 32.7%, p < 0.001). The risk of development of tAML was significantly higher in ages < 60 years compared to 60-69 years and ≥70 years (SIR 14.0, 95% confidence interval CI 11.79-16.51 vs SIR 4.87, 95% CI 4.00-5.86 vs SIR 2.80, 95% CI 2.32-3.34, p < 0.0001). Patients who received chemotherapy were more likely to develop tAML than the non- recipients (SIR 8.44, 95% CI 7.51-9.44 vs SIR 1.75, 95% CI 1.37-2.21, p < 0.0001). The risk of tAML was higher within 5 years of NHL diagnosis (SIR 5.05, 95% CI 4.49-5.67 vs SIR 4.39, 95% CI 3.49-5.45, p < 0.001). There was no statistically significant difference in SIR based on sex, race, receipt of radiotherapy, and year of diagnosis. The median OS and 5-year OS were- 8 months and 13.1% for tAML and 10 months and 27.6% for de novo AML. On multivariate analysis, tAML was not found to be an independent predictor of OS (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years (age 60-69 years: HR 1.53, 95% CI 1.08-2.15, p = 0.01, age ≥70 years: HR 1.93, 95% CI 1.40-2.66, p < 0.001) and no chemotherapy (HR 1.82, 95% CI 1.40-2.35, p < 0.001) were associated with poor OS in tAML subcategory. Conclusions: Our large population-based study shows increased risk of tAML within the first 5 years of NHL diagnosis, younger NHL survivors, and chemotherapy recipients. Older age and no chemotherapy predispose to dismal OS in tAML.
We designed a straightforward method for discriminating circulating Leishmania populations in the Indian subcontinent (ISC). Research on transmission dynamics of visceral leishmaniasis (VL, or ...Kala-azar) was recently identified as one of the key research priorities for elimination of the disease in the ISC. VL in Bangladesh, India, and Nepal is caused by genetically homogeneous populations of Leishmania donovani parasites, transmitted by female sandflies. Classical methods to study diversity of these protozoa in other regions of the world, such as microsatellite typing, have proven of little use in the area, as they are not able to discriminate most genotypes. Recently, whole genome sequencing (WGS) so far identified 10 different populations termed ISC001-ISC010.
As an alternative to WGS for epidemiological or clinical studies, we designed assays based on PCR amplification followed by dideoxynucleotide sequencing for identification of the non-recombinant genotypes ISC001 up to ISC007. These assays were applied on 106 parasite isolates collected in Nepal between 2011 and 2014. Combined with data from WGS on strains collected in the period 2002-2011, we provide a proof-of-principle for the application of genotyping to study treatment outcome, and differential geographic distribution.
Our method can aid in epidemiological follow-up of visceral leishmaniasis in the Indian subcontinent, a necessity in the frame of the Kala-azar elimination initiative in the region.
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•This is one of the very few studies of this kind in the Nepal Himalaya.•Six indicators representing various aspects of groundwater potential were selected.•A simplistic two-step ...validation strategy using spring-discharge & ERT was applied.•Lithology and lineament density were found to be the most influencing indicators.
Eastern Nepal, The Himalayas.
This research is aimed at delineating groundwater potential zones in a hard-rock aquifer Himalayan watershed integrating geo-spatial and field exploration techniques. A customized indicator-based weighting method, consisting of six indicators, was developed and applied in the study watershed. Spatially-distributed maps for the indicators were produced based on information from primary as well as secondary sources. The indicators were further aggregated and groundwater potential map was prepared using relative weights derived from Analytical Hierarchy Process with inputs from key hydrogeology experts. The map was then validated using observed data of springs as well as results from Electrical Resistivity Tomography (ERT).
The novelty of this study lies in the application of two-step validation (using springs data from the field and ERT) of the groundwater potential mapping approach which demonstrates the robustness of the overall methodology for data scarce regions and paves way for its wider applicability in decision support for groundwater exploration activities. Further, this is one of the very few groundwater potential studies in the Nepal Himalaya hydrogeological setting.
e19079
Background: Primary myelofibrosis (PMF) carries a poorer prognosis compared to other BCR-ABL-negative myeloproliferative diseases (MPD), and there is increased risk of early mortality due to ...blast transformation, thrombosis, bleeding complications, and progression of disease. Prior studies report greater incidence of second primary malignancy (SPM) among MPD patients, although the true risk in PMF has not been elucidated. We performed a large database study to evaluate the risk of SPM in PMF patients and analyzed the effects of sociodemographic factors on the risk of SPM. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients with a histologic diagnosis of PMF from 2009 to 2018. SPM was defined as any subsequent malignancy that developed at least 1 year after the diagnosis of PMF. Using multiple primary standardized incidence ratio (SIR) session of the SEER*Stat software (version 8.3.9), we calculated SIR and absolute excess risk (AER) of SPM for the entire cohort of PMF and also stratified based on age, sex, race, marital status, receipt of chemotherapy, follow-up duration, and year of diagnosis. We generated the 95% confidence intervals (CI) and p-values assuming Poisson distribution of the observed incidences of SPM. Results: A total of 5,273 patients with PMF were included in the analysis, of which 342 patients (6.4%) developed SPM. SPM occurred at SIR of 1.97 (95% CI 1.77-2.18, p<0.05) and AER of 151.87 per 10,000 population. A significantly higher incidence of melanoma (SIR 1.96, 95% CI 1.14-3.14, p<0.05), lymphoma (SIR 3.45, 95% CI 2.31-4.96, p<0.05), and leukemia (SIR 26.87, 95% CI 22.69-31.59, p<0.05) was observed. There was no statistically significant difference in SIR based on sex, race, marital status, follow-up duration, and receipt of chemotherapy. The risk was significantly higher in patients ≤60 years vs patients >60 years (SIR 2.34, 95% CI 1.89-2.86 vs SIR 1.86, 95% CI 1.65-2.10, p 0.01) and for PMF diagnosed after 2009 vs ≤2009 (SIR 2.64, 95% CI 2.26-3.07 vs SIR 1.61, 95% CI 1.40-1.85, p<0.001). Conclusions: Patients with PMF are at a high risk of developing SPM, especially leukemia and lymphoma. Data suggests higher incidence of SPM in patients aged ≤60 years and in the decade after 2009. The impact of ruxolitinib, which was approved in 2011, on the incidence of SPM deserves further study. Table: see text
Background. Recent reports indicated high miltefosine treatment failure rates for visceral leishmaniasis (VL) on the Indian subcontinent. To further explore the pharmacological factors associated ...with these treatment failures, a population pharmacokinetic-pharmacodynamic study was performed to examine the relationship between miltefosine drug exposure and treatment failure in a cohort of Nepalese patients with VL. Methods. Miltefosine steady-state blood concentrations at the end of treatment were analyzed using liquid chromatography tandem mass spectrometry. A population pharmacokinetic-pharmacodynamic analysis was performed using nonlinear mixed-effects modeling and a logistic regression model. Individual estimates of miltefosine exposure were explored for their relationship with treatment failure. Results. The overall probability of treatment failure was 21%. The time that the blood concentration was > 10 times the half maximal effective concentration of miltefosine (median, 30.2 days) was significantly associated with treatment failure: each 1-day decrease in miltefosine exposure was associated with a 1.08-fold (95% confidence interval, 1.01-1.17) increased odds of treatment failure. Conclusions. Achieving a sufficient exposure to miltefosine is a significant and critical factor for VL treatment success, suggesting an urgent need to evaluate the recently proposed optimal allometric miltefosine dosing regimen. This study establishes the first evidence for a drug exposure-effect relationship for miltefosine in the treatment of VL.
Coatings made from chemicals: A review Chowdhury, Suman; Nepal, Sadiksha; Bhattarai, Ajaya ...
Vietnam journal of chemistry,
December 2023, 2023-12-00, Volume:
61, Issue:
6
Journal Article
Peer reviewed
Open access
In the ongoing process of civilization, surface modification has become almost an indispensable route to enjoy the optimum benefit from any material in the materialistic world. Especially, active ...metals require the modification maximum to escape the natural corrosion or passivation. The retention of sound performance of the metals as well as extension of their lifetime can be achieved by surface modification of coating formation. Chemical coating is one of the simple and low‐cost methods of coating with great versatility including pre‐treatment and post‐treatment. This paper includes the most widely used inorganic and organic chemical coating methods and their fewer details and their future outlooks.
Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector-borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and ...over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment.
Biogas has long been used as a household cooking fuel in many tropical counties, and it has the potential to be a significant energy source beyond household cooking fuel. In this study, we describe ...the use of low electrical energy input in an anaerobic digestion process using a microbial electrochemical cell (MEC) to promote methane content in biogas at 18, 28, and 37 °C. Although the maximum amount of biogas production was at 37 °C (25 cm3), biogas could be effectively produced at lower temperatures, i.e., 18 (13 cm3) and 28 °C (19 cm3), with an external 2 V power input. The biogas production of 13 cm3 obtained at 18 °C was ~65-fold higher than the biogas produced without an external power supply (0.2 cm3). This was further enhanced by 23% using carbon-nanotubes-treated (CNT) graphite electrodes. This suggests that the MEC can be operated at as low as 18 °C and still produce significant amounts of biogas. The share of CH4 in biogas produced in the controls was 30%, whereas the biogas produced in an MEC had 80% CH4. The MEC effectively reduced COD to 42%, whereas it consumed 98% of reducing sugars. Accordingly, it is a suitable method for waste/manure treatment. Molecular characterization using 16s rRNA sequencing confirmed the presence of methanogenic bacteria, viz., Serratia liquefaciens and Zoballella taiwanensis, in the inoculum used for the fermentation. Consistent with recent studies, we believe that electromethanogenesis will play a significant role in the production of value-added products and improve the management of waste by converting it to energy.
Leishmania donovani is the etiological agent of visceral leishmaniasis (VL) in the Indian subcontinent. However, it is also known to cause cutaneous leishmaniasis (CL) in Sri Lanka. Sri Lankan L. ...donovani differs from other L. donovani strains, both at the molecular and biochemical level. To investigate the different species or strain-specific differences of L. donovani in Sri Lanka we evaluated sequence variation of the kinetoplastid DNA (kDNA).
Parasites isolated from skin lesions of 34 CL patients and bone marrow aspirates from 4 VL patients were genotyped using the kDNA minicircle PCR analysis. A total of 301 minicircle sequences that included sequences from Sri Lanka, India, Nepal and six reference species of Leishmania were analyzed.
Haplotype diversity of Sri Lankan isolates were high (H
= 0.757) with strong inter-geographical genetic differentiation (F
> 0.25). In this study, L. donovani isolates clustered according to their geographic origin, while Sri Lankan isolates formed a separate cluster and were clearly distinct from other Leishmania species. Within the Sri Lankan group, there were three distinct sub-clusters formed, from CL patients who responded to standard antimony therapy, CL patients who responded poorly to antimony therapy and from VL patients. There was no specific clustering of sequences based on geographical origin within Sri Lanka.
This study reveals high levels of haplotype diversity of L. donovani in Sri Lanka with a distinct genetic association with clinically relevant phenotypic characteristics. The use of genetic tools to identify clinically relevant features of Leishmania parasites has important therapeutic implications for leishmaniasis.
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