Safety of Artemether-Lumefantrine Exposure in First Trimester of Pregnancy: An Observational Cohort.

There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy. Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery. 2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]). Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.\u

Global variation in the beta diversity of lake macrophytes is driven by environmental heterogeneity rather than latitude

Aim: We studied global variation in beta diversity patterns of lake macrophytes using regional data from across the world. Specifically, we examined 1) how beta diversity of aquatic macrophytes is partitioned between species turnover and nestedness within each study region, and 2) which environmental characteristics structure variation in these beta diversity components.  Location: Global  Methods: We used presence-absence data for aquatic macrophytes from 21 regions distributed around the world. We calculated pairwise-site and multiple-site beta diversity among lakes within each region using Sørensen dissimilarity index and partitioned it into turnover and nestedness coefficients. Beta regression was used to correlate the diversity coefficients with regional environmental characteristics. Results: Aquatic macrophytes showed different levels of beta diversity within each of the 21 study regions, with species turnover typically accounting for the majority of beta diversity, especially in high-diversity regions. However, nestedness contributed 30-50% of total variation in macrophyte beta diversity in low-diversity regions. The most important environmental factor explaining the three beta diversity coefficients (total, species turnover and nestedness) was altitudinal range, followed by relative areal extent of freshwater, latitude and water alkalinity range. Main conclusions: Our findings show that global patterns in beta diversity of lake macrophytes are caused by species turnover rather than by nestedness. These patterns in beta diversity were driven by natural environmental heterogeneity, notably variability in altitudinal range (also related to temperature variation) among regions. In addition, a greater range in alkalinity within a region, likely amplified by human activities, was also correlated with increased macrophyte beta diversity. These findings suggest that efforts to conserve aquatic macrophyte diversity should primarily focus on regions with large numbers of lakes that exhibit broad environmental gradients.

Soft Ionization of Thermally Evaporated Hypergolic Ionic Liquid Aerosols

Isolated ion pairs of a conventional ionic liquid, 1-Ethyl-3-Methyl-Imidazolium Bis(trifluoromethylsulfonyl)imide ([Emim+][Tf2N?]), and a reactive hypergolic ionic liquid, 1-Butyl-3-Methyl-Imidazolium Dicyanamide ([Bmim+][Dca?]), are generated by vaporizing ionic liquid submicron aerosol particles for the first time; the vaporized species are investigated by dissociative ionization with tunable vacuum ultraviolet (VUV) light, exhibiting clear intact cations, Emim+ and Bmim+, presumably originating from intact ion pairs. Mass spectra of ion pair vapor from an effusive source of the hypergolic ionic liquid show substantial reactive decomposition due to the internal energy of the molecules emanating from the source. Photoionization efficiency curves in the near threshold ionization region of isolated ion pairs of [Emim+][Tf2N?]ionic liquid vapor are compared for an aerosol source and an effusive source, revealing changes in the appearance energy due to the amount of internal energy in the ion pairs. The aerosol source has a shift to higher threshold energy (~;;0.3 eV), attributed to reduced internal energy of the isolated ion pairs. The method of ionic liquid submicron aerosol particle vaporization, for reactive ionic liquids such as hypergolic species, is a convenient, thermally ?cooler? source of isolated intact ion pairs in the gas phase compared to effusive sources

Imipramine Is an Orally Active Drug against Both Antimony Sensitive and Resistant Leishmania donovani Clinical Isolates in Experimental Infection

Background: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. Methodology/Principal Findings: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug wasfound to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD) promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF a, IFN c and iNOS activity increased with the concomitant decrease in IL 10 and TGF b level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. Conclusions: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar

A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine.

A multinational, multicentre, randomised, double-blind, double-dummy, crossover study (368 patients treating two attacks) was conducted to compare the efficacy and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60 minutes after dosing, significantly more patients obtained headache relief (change from moderate or severe to none or mild) after treatment with sumatriptan than with DHE (53% sumatriptan, 41% DHE, p < 0.001). Significantly more patients reported relief of nausea after sumatriptan than after DHE at 60 minutes (64% sumatriptan, 49% DHE, p = 0.006). A significant difference between the two treatments was first observed at 45 minutes with respect to both headache relief (38% sumatriptan, 31% DHE, p = 0.037) and relief of nausea (55% sumatriptan, 40% DHE, p = 0.014). There were no significant differences between the two treatments for other measures of efficacy. Both treatments were well tolerated, with only 10% of patients in each group reporting one or more adverse events. The most frequently reported adverse event after sumatriptan was a bad or bitter taste, which was reported by 5% of patients. After DHE, 4% of patients reported symptoms of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse events. It is concluded that sumatriptan nasal spray is superior to DHE nasal spray in the relief of pain and nausea associated with acute migraine headache

Medium-term prospects for portuguese agriculture under health check Proposals: a quantitative analysis with the CAPRI modelling system

The challenges of Common Agricultural Policy are driven by internal and external factors, such as the budgetary constraints, the budget reform, the globalization and the world financial crisis. According to this work results, CAP will continue its evolution from a sectorial to a territorial approach, with a slow re-balance of its two pillars. The Portuguese agriculture will slowly adjust itself to the disappearance of prices and markets policy and the reinforcement of rural development policy. As in the past, agriculture will accommodate the reform effects and adjust to a new framework without sudden brakes or disclosers

Chitosan polymer electrolytes doped with a dysprosium ionic liquid

In this work, we studied polymer electrolytes (PEs) that had the natural polymer chitosan as their matrix host. Different quantities of an ionic liquid that contains the lanthanide dysprosium as part of the anion, were incorporated in the chitosan matrix through the solvent casting method. The thermal, morphological and electrochemical properties of the membranes were accessed. The results, obtained by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), force microscopy (AFM), and complex impedance spectroscopy, revealed a minimum thermal stability of about 139 degrees C; a predominantly amorphous morphology combined with the presence of small crystalline domains and a satisfactory ionic conductivity. The sample with the highest ionic conductivity was the chitosan(1)[C(2)mim][Dy(SCN)(4)], (where 1 corresponds to the quotient between the mass of the polymer and the mass of the IL) which attained 6.76 x 10(-6) S(.)cm(-1) at 30 degrees C and 5.62 x 10(-4) S(.)cm(-1) at 100 degrees C. The results presented here suggest that these materials are promising and may find application in practical electrochemical devices.- The financial support of the Brazilian agencies Capes and CNPq is gratefully acknowledged as well as the support by Fundacao para a Ciencia e a Tecnologia (FCT/MCTES) in the Strategic Funding grant UID/QUI/0686/2019 and in the framework of the Research unit Associate Laboratory for Green Chemistry- LAQV which is financed by national funds (UID/QUI/50006/2019), grant SRFH/BD/90366/2012 (R.L.), and two contracts under Investigador FCT program (IF/00355/2012 - J.M.S.S.E. and IF/00621/2015 - P.M.R.)

Accounting for the unique, doubly dual nature of ionic liquids from a molecular thermodynamic, and modeling standpoint

The fascinating, complex behavior of ionic liquids is analyzed using a molecular perspective that emphasizes the doubly dual nature of ionic liquids underlying the existence of cations and anions forming high- and low-charge-density regions. Our work bridges the liquid, gas, and solid phases spanning 5 years of research on themes as diverse as the vaporization, liquid-liquid demixing, solidification, and thermophysical behavior of ionic liquids and their mixtures and solutions

A detailed thermodynamic analysis of [C(4)mim][BF4] plus water as a case study to model ionic liquid aqueous solutions

Since determining experimentally a wide variety of thermophysical properties - even for a very small portion of the already known room temperature ionic liquids ( and their mixtures and solutions) - is an impossible goal, it is imperative that reliable predictive methods be developed. In turn, these methods might offer us clues to understanding the underlying ion - ion and ion - molecule interactions. 1-Butyl-3-methylimidazolium tetrafluoroborate, one of the most thoroughly investigated ionic liquids, together with water, the greenest of the solvents, have been chosen in this work in order to use their mixtures as a case study to model other, greener, ionic liquid aqueous solutions. We focus our attention both on very simple methodologies that permit one to calculate accurately the mixture's molar volumes and heat capacities as well as more sophisticated theories to predict excess properties, pressure and isotope effects in the phase diagrams, and anomalies in some response functions to criticality, with a minimum of information. In regard to experimental work, we have determined: ( a) densities as a function of temperature (278.15 <T/ K <333.15), pressure ( 1 <p/bar <600), and composition (0 <x(IL) <1), thus also excess molar volumes; (b) heat capacities and excess molar enthalpies as a function of temperature ( 278.15 <T/ K <333.15) and composition ( 0 <xIL <1); and ( c) liquid - liquid phase diagrams and their pressure ( 1 <p/ bar <700) and isotopic (H2O/D2O) dependences. The evolution of some of the aforementioned properties in their approach to the critical region has deserved particular attention