•Largest study to date on the effect of malaria on fetal growth using ultrasound.•First to assess fetal growth after sexually transmitted/reproductive tract infection.•Dual burden of the infections ...negatively impact fetal growth.•First- and second-time mothers are especially vulnerable to the infections.•Integrated antenatal care is needed to reduce the burden.
Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi.
This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine vs dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and bacterial vaginosis at enrollment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression.
In total, 1435 pregnant women had fetal/birth weight assessed 3950 times. Compared to women without malaria or STIs/RTIs (n = 399), malaria-only (n = 267), STIs/RTIs only (n = 410) or both (n = 353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score 95% confidence interval: malaria = -0.18 -0.31,-0.04, P = 0.01; STIs/RTIs = -0.14 -0.26,-0.03, P = 0.01; both = -0.20 -0.33,-0.07, P = 0.003). Paucigravidae experienced the greatest impact.
Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs.
Metabolic reprogramming in breast cancer is depicted as a crucial change in the tumor microenvironment. Besides the molecular understanding of metabolic heterogeneity, appreciable attention is drawn ...to characterizing metabolite profiles in tumor tissue and derived biological fluids and tissue materials. Several findings reported on the metabolic alterations of free aromatic amino acids (FAAAs) and other metabolites in biological fluids. Furthermore, there is a significant gap in the development of a suitable method for the purification and analysis of metabolite biomarkers in nails of cancer patients.
To address the metabolite alterations, specifically FAAA levels in nails, fingernail clippings of breast cancer patients (
= 10) and healthy subjects (N-12) were used for extraction and purification of metabolites. Here, we reported a novel and specifically designed vertical tube gel electrophoresis (VTGE) system that helped in the purification of metabolites in the range of 100-1,000 Da from nail materials. Here, the VTGE system uses 15% polyacrylamide under non-denaturing and non-reducing conditions, which makes eluted metabolites directly compatible with LC-HRMS and other analytical techniques. Qualitative and quantitative determination of FAAAs in nail lysates was done in positive ESI mode of the Agilent LC-HRMS platform.
The analysis on collected data of nail metabolites clearly suggested that FAAAs including tryptophan, tyrosine, phenylalanine, and histidine were undetectable in nail lysates of breast cancer over healthy subjects. This is a first report that showed highly reduced levels of FAAAs in nails of breast cancer patients. Furthermore, the present observation is in consonance with previous findings that showed cancer cachexia and high amino acid catabolism in breast cancer patients that drive metabolite-led cancer growth and proliferation.
This paper provides a proof of concept for a novel and specifically developed VTGE process that showed first evidence on the undetectable level of FAAAs in nails of breast cancer patients as metabolite biomarkers. Here, the authors propose the potential use of a VTGE-assisted process to achieve metabolomic discovery in nails of breast cancer and other tumor types.
Poor health worker performance is a well-documented obstacle to quality service provision. Due to the increasingly widespread availability of mobile devices, mobile health (mHealth) has received ...growing attention as a service improvement tool. This pilot study explored feasibility, acceptability and outcomes of an mHealth intervention designed to increase coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) in two districts of West Nile, Uganda. In both districts, selected health workers (N = 48) received classroom training on malaria in pregnancy. All health workers in one district (N = 49) subsequently received 24 text messages reinforcing the training content. The intervention was evaluated using a mixed-methods approach, including four focus group discussions with health workers and three in-depth interviews with district health officials, health worker knowledge assessments one month (N = 90) and six months (N = 89) after the classroom training, and calculation of IPTp coverage from participating health facilities' (N = 16) antenatal care registers covering six months pre- and post-intervention. Complementing classroom training with text messaging was found to be a feasible, acceptable and inexpensive approach to improving health worker performance. The messages served as reminders to those who had attended the classroom training and helped spread information to those who had not. Health workers in the district where text messages were sent had significantly better knowledge of IPTp, achieving an increased composite knowledge score of 6.00 points (maximum score: 40) compared with those in the district where only classroom training was provided. Average facility coverage of three doses of IPTp was also significantly higher where text messages were sent (85.8%) compared with the district where only classroom training was provided (54.1%). This intervention shows promise for the improvement of health worker performance for delivery of IPTp, and could have significant broader application.
The aims of this study were to quantify and describe the variations in respiratory symptoms and diagnosis prevalence across regions of the world according to national income. In 2002 and 2003, the ...World Health Organization implemented the World Health Survey (WHS), which used a standardised survey instrument to compile comprehensive baseline information on health and healthcare expenditure. We analysed the WHS data to assess the global patterns of self-reported wheeze and doctor-diagnosed asthma, two commonly reported measures of respiratory health. In total there were 308,218 participants with complete records, from 64 countries. The weighted mean age of the survey population was 43 yrs. Global prevalence of current wheezing symptoms ranged from 2.4% in Vietnam to 24% in Brazil; the prevalence of diagnosed asthma ranged from 1.8% in Vietnam to 32.8% in Australia. Overall, the prevalence of symptoms and diagnosis showed a U-shaped pattern with the largest prevalence reported in low- and high-income countries. The smallest prevalence was consistently found in middle-income countries. These WHS analyses have provided global prevalence estimates of wheeze and doctor-diagnosed asthma using data gathered simultaneously and consistently across six continents. These findings support the need for continued global respiratory illness surveillance for disease prevention, health policy and management.
Herein, we report the synthesis of 4′-C-aminomethyl-2′-deoxy-2′-fluorouridine, a therapeutically appealing RNA modification. Conformational analysis by DFT calculations and molecular dynamics ...simulations using trinucleotide model systems revealed that modified sugar adopts C3′-endo conformation. In this conformer, a weak intramolecular C–H···F H-bond between the hydrogen atom of the 4′-C-CH2 group and the F atom at the 2′ position is observed. Comparative studies with unmodified, 2′-fluoro-, 2′-O-methyl-, and 4′-C-aminomethyl-2′-O-methyluridine showed the chemical nature of 2′-substituent dictates the sugar puckering of 2′,4′-modified nucleotides.
The capacitance of the polycrystalline gold electrode–ionic liquid BMIMTf 1-butyl-3- methyl imidazolium trifluoromethanesulfonate (triflate) interface has been studied using ac voltammetry and ...electrochemical impedance spectroscopy (EIS). Slow potential scanning reveals a massive hysteresis between potential scans toward negative or positive directions and provides a distorted
C(
E) curve. Kinetic studies indicate that 10
min wait times are required after each potential step for system relaxation. EIS resolves the overall series capacitance into contributions from ion adsorption and double-layer capacitance,
C
DL
. Isolation of
C
DL
reveals that even 10 min of equilibration time is insufficient to completely remove the hysteresis. The shape of the negative-going
C
DL
(
E) curve is camel-shaped whereas the shape of the positive-going curve is bell-shaped.
Atrial Fibrillation (AF), the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. ...Genome-wide association studies (GWAS) have identified that the single nucleotide polymorphisms (SNPs) most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.
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