Time series analysis of malaria in Afghanistan: using ARIMA models to predict future trends in incidence

Additional file 6: Annex 1. Right side: Autocorrelation (ACF) and partial autocorrelation (PACF) functions of the residuals from ARIMA model (1, 0, 1) × (1, 0, 1)12 on log-transformed, differenced data. Left side: ACF and PACF of the residuals from ARIMA model (4, 0, 1) × (1, 0, 1)12 on log-transformed, differenced data

Isolation and Characterization of Bacterial Endophytes from Lycopersicon esculentum Plant and their Plant Growth Promoting Characteristics

The study was designed to isolate and characterize bacterial endophytes from root and stem of Lycopersicon esculentum plant which was collected form different region of Gujarat. Total 18 isolates of endophytic bacteria were selected in which, all the endophytic bacteria produced one or the other different characteristics involved in plant growth promotion. They either produced phytohormones like indole acetic acid, siderophore, protease, pectinase, organic acid showed antifungal activity, chromium tolerance and solubilized phosphate. Four of the strains among the 18 showed maximum positive results of plant growth promoting regulators (PGPR) test and among them best probable isolate was selected and thus its 16SrDNA was amplified and sequenced. Only HR7 endophyte of tomato turned out to be Pseudomonas aeruginosa. It’s a gram negative coccobacili, sporeforming motile bacilli and show maximum PGPR activity. The results of our present studies indicated that above strains might be endophytic and therefore, were associated with the plant growth. Keywords: Lycopersicon esculentum; endophytic bacteria; PGPR; IAA; 16SrDNA DOI: http://dx.doi.org/10.3126/njb.v2i1.5679   Nepal Journal of Biotechnology Jan.2012, Vol.2(1): 37-5

Structure of N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) from Mycobacterium tuberculosis in a cubic space group

The structure of M. tuberculosis N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) was determined by the molecular-replacement method to 3.4 Å resolution in space group I432 and was refined to a final R work and R free of 0.285 and 0.321, respectively

Retrospective Study of Clinical and Epidemiological Parameters of Patients Undergoing Percutaneous Coronary Intervention with Their Follow-Up

AIM: To study clinical and epidemiological parameters of patients undergoing percutaneous coronary intervention (PCI) and to follow them up for understanding the outcomes of the procedure. MATERIAL AND METHODS: This is a retrospective data analysis of 862 patients who underwent PCI from January 2016 to November 2017 RESULTS: Out of 862 patients, 611 (70.88%) were male & 251 (29.12%) were female, with the mean age being 55. 243 (28.19%) were diabetic, 470 (54.52%) were hypertensive, 158 (18.32%) patients were tobacco chewer, 215 (24.92%) were smokers and 111 (12.87%) were alcoholic. 636 (73.78%) patients had STEMI, 153 (17.74%) had NSTE-ACS, 61 (7.07%) had CSA.578 (67.05%) were SVD, 262 (30.39%) were DVD and 19 (2.20%) were TVD. Out of SVD, 350 (60.55%) patients had LAD involvement and among DVD patients, LAD and RCA were most commonly involved in 107 (40.83%) patients. On follow-up of mean 604.42 days (minimum 236 days, maximum 909 days), 2 (0.23%) episodes of subacute stent thrombosis occurred and 11 (1.27%) patients had ISR but no mortality was reported. CONCLUSION: The study shows affection of young population predominately and genders inequality, suggesting primarily male disease. PCI is often sought in ACS and CSA is predominately treated medically. Thrombolysis remains the first treatment received by STEMI patients. SVD is the most common angiographic diagnosis with LAD predominately affected vessel. This real world-data on clopidogrel with aspirin as dual antiplatelet therapy and second-generation stent shows negligible event of stent thrombosis and ISR. LIMITATION: Due to non-invasive follow-up, the exact amount of stent restenosis cannot be calculated. IMPACT ON DAILY PRACTICE: This real world-data on clopidogrel with aspirin as dual antiplatelet therapy and second-generation stent shows negligible event of stent thrombosis and ISR. This can help reduce the cost burden on society and help better distribution of health budget

Modelling the impact of antimalarial quality on the transmission of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum

Background: The use of poor quality antimalarial medicines, including the use of non-recommended medicines for treatment such as sulfadoxine-pyrimethamine (SP) monotherapy, undermines malaria control and elimination efforts. Furthermore, the use of subtherapeutic doses of the active ingredient(s) can theoretically promote the emergence and transmission of drug resistant parasites. Methods: We developed a deterministic compartmental model to quantify the impact of antimalarial medicine quality on the transmission of SP resistance, and validated it using sensitivity analysis and a comparison with data from Kenya collected in 2006. We modelled human and mosquito population dynamics, incorporating two Plasmodium falciparum subtypes (SP-sensitive and SP-resistant) and both poor quality and good quality (artemether-lumefantrine) antimalarial use. Findings: The model predicted that an increase in human malaria cases, and among these, an increase in the proportion of SP-resistant infections, resulted from an increase in poor quality SP antimalarial use, whether it was full- or half-dose SP monotherapy. Interpretation: Our findings suggest that an increase in poor quality antimalarial use predicts an increase in the transmission of resistance. This highlights the need for stricter control and regulation on the availability and use of poor quality antimalarial medicines, in order to offer safe and effective treatments, and work towards the eradication of malaria

Substrate Suppression of Thermal Roughness in Stacked Supported Bilayers

We have fabricated a stack of five 1,2-dipalmitoyl-sn-3-phosphatidylethanolamine (DPPE) bilayers supported on a polished silicon substrate in excess water. The density profile of these stacks normal to the substrate was obtained through analysis of x-ray reflectivity. Near the substrate, we find the layer roughness and repeat spacing are both significantly smaller than values found in bulk multilayer systems. The reduced spacing and roughness result from suppression of lateral fluctuations due to the flat substrate boundary. The layer spacing decrease then occurs due to reduced Helfrich repulsion.This work was partially supported by NSF Grants No. DMR-0706369 and No. DMR-0706665. Use of the Advanced Photon Sourcewas supported by theUSDepartment of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. SKS and ANP wish to acknowledge support from the Office of Basic Energy Sciences, US Department of Energy, via Grant No. DE-FG02- 04ER46173. We would also like to thank Suresh Narayanan for his support of the experimental work at Sector 8-ID

Super-mini percutaneous nephrolithotomy (SMP) vs retrograde intrarenal surgery (RIRS) in the management of renal calculi <= 2 cm: A propensity matched study

Objective: To compare the effectiveness and safety of Super-Mini PCNL (SMP) and Retrograde Intrarenal Surgery (RIRS) in the management of renal calculi ≤ 2 cm. Patients and methods: A prospective, inter-institutional, observational study of patients presenting with renal calculi ≤ 2 cm. Patients underwent either SMP (Group 1) or RIRS (Group 2) and were performed by 2 experienced high-volume surgeons. Results: Between September 2018 and April 2019, 593 patients underwent PCNL and 239 patients had RIRS in two tertiary centers. Among them, 149 patients were included for the final analysis after propensity-score matching out of which 75 patients underwent SMP in one center and 74 patients underwent RIRS in the other. The stone-free rate (SFR) was statistically significantly higher in Group 1 on POD-1 (98.66% vs. 89.19%; p = 0.015), and was still higher in Group 1 on POD-30 (98.66% vs. 93.24%, p = 0.092) SFR on both POD-1 and POD-30 for lower pole calculi was higher in Group 1 (100 vs. 82.61%, p = 0.047 and 100 vs 92.61% p = 0.171). The mean (SD) operative time was significantly shorter in Group 1 at 36.43 min (14.07) vs 51.15 (17.95) mins (p < 0.0001). The mean hemoglobin drop was significantly less in Group 1 (0.31 vs 0.53 gm%; p = 0.020). There were more Clavien–Dindo complications in Group 2 (p = 0.021). The mean VAS pain score was significantly less in Group 2 at 6 and 12 h postoperatively (2.52 vs 3.67, 1.85 vs 2.40, respectively: p < 0.0001), whereas the mean VAS pain score was significantly less in Group 1 at 24 h postoperatively (0.31 vs 1.01, p < 0.0001). The mean hospital stay was significantly shorter in Group 1 (28.37 vs 45.70 h; p < 0.0001). Conclusion: SMP has significantly lower operative times, complication rates, shorter hospital stay, with higher stone-free rates compared to RIRS. SMP is associated with more early post-operative pain though.Manipal Academy of Higher Education, Manipa

Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children.

BACKGROUND: The optimal treatment of malaria in human immunodeficiency virus (HIV)-infected children requires consideration of critical drug-drug interactions in coinfected children, as these may significantly impact drug exposure and clinical outcomes. METHODS: We conducted an intensive and sparse pharmacokinetic/pharmacodynamic study in Uganda of the most widely adopted artemisinin-based combination therapy, artemether-lumefantrine. HIV-infected children on 3 different first-line antiretroviral therapy (ART) regimens were compared to HIV-uninfected children not on ART, all of whom required treatment for Plasmodium falciparum malaria. Pharmacokinetic sampling for artemether, dihydroartemisinin, and lumefantrine exposure was conducted through day 21, and associations between drug exposure and outcomes through day 42 were investigated. RESULTS: One hundred forty-five and 225 children were included in the intensive and sparse pharmacokinetic analyses, respectively. Compared with no ART, efavirenz (EFV) reduced exposure to all antimalarial components by 2.1- to 3.4-fold; lopinavir/ritonavir (LPV/r) increased lumefantrine exposure by 2.1-fold; and nevirapine reduced artemether exposure only. Day 7 concentrations of lumefantrine were 10-fold lower in children on EFV vs LPV/r-based ART, changes that were associated with an approximate 4-fold higher odds of recurrent malaria by day 28 in those on EFV vs LPV/r-based ART. CONCLUSIONS: The choice of ART in children living in a malaria-endemic region has highly significant impacts on the pharmacokinetics and pharmacodynamics of artemether-lumefantrine treatment. EFV-based ART reduces all antimalarial components and is associated with the highest risk of recurrent malaria following treatment. For those on EFV, close clinical follow-up for recurrent malaria following artemether-lumefantrine treatment, along with the study of modified dosing regimens that provide higher exposure, is warranted

Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria.

Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant women compared to nonpregnant adults; however, the results are inconclusive. We conducted a study in rural Uganda to compare the pharmacokinetics of artemether-lumefantrine and the treatment responses between 30 pregnant women and 30 nonpregnant adults with uncomplicated Plasmodium falciparum malaria. All participants were uninfected with HIV, treated with a six-dose regimen of artemether-lumefantrine, and monitored clinically for 42 days. The pharmacokinetics of artemether, its metabolite dihydroartemisinin, and lumefantrine were evaluated for 21 days following treatment. We found no significant differences in the overall pharmacokinetics of artemether, dihydroartemisinin, or lumefantrine in a direct comparison of pregnant women to nonpregnant adults, except for a statistically significant but small difference in the terminal elimination half-lives of both dihydroartemisinin and lumefantrine. There were seven PCR-confirmed reinfections (5 pregnant and 2 nonpregnant participants). The observation of a shorter terminal half-life for lumefantrine may have contributed to a higher frequency of reinfection or a shorter posttreatment prophylactic period in pregnant women than in nonpregnant adults. While the comparable overall pharmacokinetic exposure is reassuring, studies are needed to further optimize antimalarial efficacy in pregnant women, particularly in high-transmission settings and because of emerging drug resistance. (This study is registered at ClinicalTrials.gov under registration no. NCT01717885.)

Population Pharmacokinetic Properties of Piperaquine in Falciparum Malaria: An Individual Participant Data Meta-Analysis.

BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children (<5 y) with malaria are under-dosed. This study utilised a population-based pharmacokinetic approach to optimise the antimalarial treatment regimen for piperaquine. METHODS AND FINDINGS: Published pharmacokinetic studies on piperaquine were identified through a systematic literature review of articles published between 1 January 1960 and 15 February 2013. Individual plasma piperaquine concentration-time data from 11 clinical studies (8,776 samples from 728 individuals) in adults and children with uncomplicated malaria and healthy volunteers were collated and standardised by the WorldWide Antimalarial Resistance Network. Data were pooled and analysed using nonlinear mixed-effects modelling. Piperaquine pharmacokinetics were described successfully by a three-compartment disposition model with flexible absorption. Body weight influenced clearance and volume parameters significantly, resulting in lower piperaquine exposures in small children (<25 kg) compared to larger children and adults (≥25 kg) after administration of the manufacturers' currently recommended dose regimens. Simulated median (interquartile range) day 7 plasma concentration was 29.4 (19.3-44.3) ng/ml in small children compared to 38.1 (25.8-56.3) ng/ml in larger children and adults, with the recommended dose regimen. The final model identified a mean (95% confidence interval) increase of 23.7% (15.8%-32.5%) in piperaquine bioavailability between each piperaquine dose occasion. The model also described an enzyme maturation function in very young children, resulting in 50% maturation at 0.575 (0.413-0.711) y of age. An evidence-based optimised dose regimen was constructed that would provide piperaquine exposures across all ages comparable to the exposure currently seen in a typical adult with standard treatment, without exceeding the concentration range observed with the manufacturers' recommended regimen. Limited data were available in infants and pregnant women with malaria as well as in healthy individuals. CONCLUSIONS: The derived population pharmacokinetic model was used to develop a revised dose regimen of dihydroartemisinin-piperaquine that is expected to provide equivalent piperaquine exposures safely in all patients, including in small children with malaria. Use of this dose regimen is expected to prolong the useful therapeutic life of dihydroartemisinin-piperaquine by increasing cure rates and thereby slowing resistance development. This work was part of the evidence that informed the World Health Organization technical guidelines development group in the development of the recently published treatment guidelines (2015)