Population Pharmacokinetics of Lumefantrine in Pregnant and Nonpregnant Women With Uncomplicated Plasmodium falciparum Malaria in Uganda

Pregnancy alters the pharmacokinetic properties of many antimalarial compounds. The objective of this study was to evaluate the pharmacokinetic properties of lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Uganda after a standard fixed oral artemether-lumefantrine treatment. Dense venous (n = 26) and sparse capillary (n = 90) lumefantrine samples were drawn from pregnant patients. A total of 17 nonpregnant women contributed with dense venous lumefantrine samples. Lumefantrine pharmacokinetics was best described by a flexible absorption model with multiphasic disposition. Pregnancy and body temperature had a significant impact on the pharmacokinetic properties of lumefantrine. Simulations from the final model indicated 27% lower day 7 concentrations in pregnant women compared with nonpregnant women and a decreased median time of 0.92 and 0.42 days above previously defined critical concentration cutoff values (280 and 175 ng/ml, respectively). The standard artemether-lumefantrine dose regimen in P. falciparum malaria may need reevaluation in nonimmune pregnant women.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e83; doi:10.1038/psp.2013.59; advance online publication 13 November 2013

Amino acid derangements in adults with severe falciparum malaria

Amino acid derangements are common in severe falciparum malaria and have been associated with endothelial dysfunction (L-arginine), metabolic acidosis (alanine and lactate), and disease severity (phenylalanine and tryptophan metabolites). Whether these amino acid perturbations reflect isolated pathogenic mechanisms or if they are part of overall changes in amino acid metabolism is unclear. To investigate this, we prospectively simultaneously quantified a broad range of plasma free amino acids (PFAA) using HPLC-MRM-Mass spectrometry in relation to presenting symptoms in adults with severe malaria (n = 88), septicaemia (n = 88), uncomplicated malaria (n = 71), and healthy controls (n = 48) from Bangladesh. The total plasma concentration of measured amino acids was significantly reduced in each of the patient groups when compared to normal levels observed in healthy local controls: uncomplicated malaria -54%, severe malaria -23%, and sepsis -32%, (p = <0.001). Inspection of amino acid profiles revealed that in each group the majority of amino acids were below normal levels, except for phenylalanine. Among patients with severe malaria, L-lactate was strongly associated with an increase of the total amino acid concentration, likely because this reflects tissue hypoxia. Our data confirm previously described amino acid abnormalities, likely resulting from overall changes in the concentration of PFAA

Amino acid derangements in adults with severe falciparum malaria

Amino acid derangements are common in severe falciparum malaria and have been associated with endothelial dysfunction (L-arginine), metabolic acidosis (alanine and lactate), and disease severity (phenylalanine and tryptophan metabolites). Whether these amino acid perturbations reflect isolated pathogenic mechanisms or if they are part of overall changes in amino acid metabolism is unclear. To investigate this, we prospectively simultaneously quantified a broad range of plasma free amino acids (PFAA) using HPLC-MRM-Mass spectrometry in relation to presenting symptoms in adults with severe malaria (n = 88), septicaemia (n = 88), uncomplicated malaria (n = 71), and healthy controls (n = 48) from Bangladesh. The total plasma concentration of measured amino acids was significantly reduced in each of the patient groups when compared to normal levels observed in healthy local controls: uncomplicated malaria -54%, severe malaria -23%, and sepsis -32%, (p = &lt;0.001). Inspection of amino acid profiles revealed that in each group the majority of amino acids were below normal levels, except for phenylalanine. Among patients with severe malaria, L-lactate was strongly associated with an increase of the total amino acid concentration, likely because this reflects tissue hypoxia. Our data confirm previously described amino acid abnormalities, likely resulting from overall changes in the concentration of PFAA

A Simplified Liquid Chromatography-Mass Spectrometry Assay for Artesunate and Dihydroartemisinin, Its Metabolite, in Human Plasma

molecule

The INTERSPEECH 2021 Computational Paralinguistics Challenge: COVID-19 cough, COVID-19 speech, escalation & primates

The INTERSPEECH 2021 Computational Paralinguistics Challenge addresses four different problems for the first time in a research competition under well-defined conditions: In the COVID-19 Cough and COVID-19 Speech Sub-Challenges, a binary classification on COVID-19 infection has to be made based on coughing sounds and speech; in the Escalation Sub- Challenge, a three-way assessment of the level of escalation in a dialogue is featured; and in the Primates Sub-Challenge, four species vs background need to be classified. We describe the Sub-Challenges, baseline feature extraction, and classifiers based on the 'usual' COMPARE and BoAW features as well as deep unsupervised representation learning using the AUDEEP toolkit, and deep feature extraction from pre-trained CNNs using the DEEP SPECTRUM toolkit; in addition, we add deep end-to-end sequential modelling, and partially linguistic analysis

The influence of iron stores on cadmium body burden in a Thai population

Cadmium is a toxin of increasing public health concern due to its presence in most human foodstuffs and in cigarette smoke. Exposure to cadmium leads to tissue bioaccumulation and, in particular, has nephrotoxic effects. The aim of the present study was to investigate the association between cadmium body burden and iron stores in a Thai population. A total of 182 healthy adult Thai subjects of both genders (89 males, 93 females) aged between 18 and 57 years and weighing 40-95 kg were included in this study. The total amounts of cadmium excreted in urine over 2 h (μg/g creatinine) were used as an index of long-term cadmium exposure. Quantitation of cadmium was performed using electrothermal (graphite furnace) atomic absorption spectrometry. The urinary cadmium excreted displayed a normal frequency distribution. The average urinary cadmium level did not exceed the WHO maximum tolerable internal dose for the non-exposed population (2 μg/g creatinine). Body iron stores reflected by serum ferritin levels did not show any correlation with cadmium burden in both males and females, although a relatively stronger influence of body iron store status on cadmium burden was shown in females. When the levels of serum ferritin were stratified into five levels (300 μg/l), a significant difference in total cadmium body burden was observed between females and males only in the group with a low level of serum ferritin o

The INTERSPEECH 2021 Computational Paralinguistics Challenge: COVID-19 Cough, COVID-19 Speech, Escalation & Primates

The INTERSPEECH 2021 Computational Paralinguistics Challenge addresses four different problems for the first time in a research competition under well-defined conditions: In the COVID-19 Cough and COVID-19 Speech Sub-Challenges, a binary classification on COVID-19 infection has to be made based on coughing sounds and speech; in the Escalation Sub- Challenge, a three-way assessment of the level of escalation in a dialogue is featured; and in the Primates Sub-Challenge, four species vs background need to be classified. We describe the Sub-Challenges, baseline feature extraction, and classifiers based on the 'usual' COMPARE and BoAW features as well as deep unsupervised representation learning using the AUDEEP toolkit, and deep feature extraction from pre-trained CNNs using the DEEP SPECTRUM toolkit; in addition, we add deep end-to-end sequential modelling, and partially linguistic analysis