The effect of distance on observed mortality, childhood pneumonia and vaccine efficacy in rural Gambia.

We investigated whether straight-line distance from residential compounds to healthcare facilities influenced mortality, the incidence of pneumonia and vaccine efficacy against pneumonia in rural Gambia. Clinical surveillance for pneumonia was conducted on 6938 children living in the catchment areas of the two largest healthcare facilities. Deaths were monitored by three-monthly home visits. Children living >5 km from the two largest healthcare facilities had a 2·78 [95% confidence interval (CI) 1·74-4·43] times higher risk of all-cause mortality compared to children living within 2 km of these facilities. The observed rate of clinical and radiological pneumonia was lower in children living >5 km from these facilities compared to those living within 2 km [rate ratios 0·65 (95% CI 0·57-0·73) and 0·74 (95% CI 0·55-0·98), respectively]. There was no association between distance and estimated pneumococcal vaccine efficacy. Geographical access to healthcare services is an important determinant of survival and pneumonia in children in rural Gambia

Isolation and characterization of glycosaminoglycans in brain of different species

The uronic acid-containing glycosaminoglycans present in the brains of rat, monkey, chicken, sheep and rabbit were isolated into various fractions by combining the cetyl pyridinium procedure and DEAE-Sephadex column chromatography. The analyses of the fractions show that hyaluronic acid, chondroitin-4-sulphate, chondroitin-6-sulphate, heparan sulphate and a testicular hyaluronidase-resistant galactosamine-containing GAG are present in the brain of all the species studied. Hyaluronic acid is the major GAG (33-41 per cent). Chondroitin-4-sulphate (19-35 per cent), and heparan sulphate (11-19 per cent), are the next prominent GAGs, in all the species except chicken. The results indicate the similarity in the pattern of GAGs in the brain of all the species

3D Co-culture of hiPSC-Derived Cardiomyocytes With Cardiac Fibroblasts Improves Tissue-Like Features of Cardiac Spheroids

Purpose: Both cardiomyocytes and cardiac fibroblasts (CF) play essential roles in cardiac development, function, and remodeling. Properties of 3D co-cultures are incompletely understood. Hence, 3D co-culture of cardiomyocytes and CF was characterized, and selected features compared with single-type and 2D culture conditions.Methods: Human cardiomyocytes derived from induced-pluripotent stem cells (hiPSC-CMs) were obtained from Cellular Dynamics or Ncardia, and primary human cardiac fibroblasts from ScienCell. Cardiac spheroids were investigated using cryosections and whole-mount confocal microscopy, video motion analysis, scanning-, and transmission-electron microscopy (SEM, TEM), action potential recording, and quantitative PCR (qPCR).Results: Spheroids formed in hanging drops or in non-adhesive wells showed spontaneous contractions for at least 1 month with frequent media changes. SEM of mechanically opened spheroids revealed a dense inner structure and no signs of blebbing. TEM of co-culture spheroids at 1 month showed myofibrils, intercalated disc-like structures and mitochondria. Ultrastructural features were comparable to fetal human myocardium. We then assessed immunostained 2D cultures, cryosections of spheroids, and whole-mount preparations by confocal microscopy. CF in co-culture spheroids assumed a small size and shape similar to the situation in ventricular tissue. Spheroids made only of CF and cultured for 3 weeks showed no stress fibers and strongly reduced amounts of alpha smooth muscle actin compared to early spheroids and 2D cultures as shown by confocal microscopy, western blotting, and qPCR. The addition of CF to cardiac spheroids did not lead to arrhythmogenic effects as measured by sharp-electrode electrophysiology. Video motion analysis showed a faster spontaneous contraction rate in co-culture spheroids compared to pure hiPSC-CMs, but similar contraction amplitudes and kinetics. Spontaneous contraction rates were not dependent on spheroid size. Applying increasing pacing frequencies resulted in decreasing contraction amplitudes without positive staircase effect. Gene expression analysis of selected cytoskeleton and myofibrillar proteins showed more tissue-like expression patterns in co-culture spheroids than with cardiomyocytes alone or in 2D culture.Conclusion: We demonstrate that the use of 3D co-culture of hiPSC-CMs and CF is superior over 2D culture conditions for co-culture models and more closely mimicking the native state of the myocardium with relevance to drug development as well as for personalized medicine.Peer reviewe

Temporary Labour–Migration System and Long–term Residence Strategies in the United Arab Emirates

© 2019 The Authors. International Migration © 2019 IOM The United Arab Emirates’ migration system, the sponsorship–based kafala system, is defined as a temporary labour–migration regime. Although there are policies making permanent residence unattainable for virtually all migrants, it is still relevant to explore the temporality of migrations in the UAE. The purpose of this study is to investigate developments in migration, migration policies and population trends in the country, including trends that concern the duration of migrants’ stay. We also identify some of the major strategies used by migrants to prolong their sojourn in the UAE. It is maintained that the migrant stock has increased continuously in the last decades and that a large number of migrants devise strategies to continue their residence and remain in the country for years. The authors also identify and discuss migrants’ transition within and in-between regularity and irregularity, and analyse the reasons for utilizing different strategies over time

Genetic divergence of Chikungunya viruses in India (1963-2006) with special reference to the 2005-2006 explosive epidemic

Re-emergence of Chikungunya (CHIK), caused by CHIK virus, was recorded in India during 2005-2006 after a gap of 32 years, causing 1.3 million cases in 13 states. Several islands of the Indian Ocean reported similar outbreaks in the same period. These outbreaks were attributed to the African genotype of CHIK virus. To examine relatedness of the Indian isolates (IND-06) with Reunion Island isolates (RU), full-genome sequences of five CHIK virus isolates representative of different Indian states were determined. In addition, an isolate obtained from mosquitoes in the year 2000 (Yawat-2000), identified as being of the African genotype, and two older strains isolated in 1963 and 1973 (of the Asian genotype), were sequenced. The IND-06 isolates shared 99.9 % nucleotide identity with RU isolates, confirming involvement of the same strain in these outbreaks. The IND-06 isolates shared 98.2 % identity with the Yawat-2000 isolate. Of two crucial substitutions reported for RU isolates in the E1 region, M269V was noted in the Yawat-2000 and IND-06 isolates, whereas D284E was seen only in the IND-06 isolates. The A226V shift observed with the progression of the epidemic in Reunion Island, probably associated with adaptation to the mosquito vector, was absent in all of the Indian isolates. Three unique substitutions were noted in the IND-06 isolates: two (T128K and T376M) in the Nsp1 region and one (P23S) in the capsid protein. The two Asian strains showed 99.4 % nucleotide identity to each other, indicating relative stability of the virus. No evidence of recombination of the Asian and African genotypes, or of positive selection was observed. The results may help in understanding the association, if any, of the unique mutations with the explosive nature of the CHIK outbreak

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS) synthase (Cho1p) was developed based on antagonism of the toxin papuamide A (Pap-A). Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ) do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A) as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A), but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins

Breeding Biofortified Pearl Millet Varieties and Hybrids to Enhance Millet Markets for Human Nutrition

Pearl millet is an important food crop in the arid and semi-arid tropical regions of Africa and Asia. Iron and zinc deficiencies are widespread and serious public health problems worldwide, including in India and Africa. Biofortification is a cost-effective and sustainable agricultural strategy to address this problem. The aim of this review is to provide the current biofortification breeding status and future directions of the pearl millet for growing nutrition markets. Research on the pearl millet has shown that a large genetic variability (30–140 mg kg−1 Fe and 20–90 mg kg−1 Zn) available in this crop can be effectively utilized to develop high-yielding cultivars with high iron and zinc densities. Open-pollinated varieties (Dhanashakti) and hybrids (ICMH 1202, ICMH 1203 and ICMH 1301) of pearl millet with a high grain yield and high levels of iron (70–75 mg kg−1) and zinc (35–40 mg kg−1) densities have been developed and released first in India. Currently, India is growing > 70,000 ha of biofortified pearl millet, and furthermore more pipeline cultivars are under various stages of testing at the national (India) and international (west Africa) trials for a possible release. Until today, no special markets existed to promote biofortified varieties and hybrids as no incentive price to products existed to address food and nutritional insecurity simultaneously. The market demand is likely to increase only after an investment in crop breeding and the integration into the public distribution system, nutritional intervention schemes, private seed and food companies with strong mainstreaming nutritional policies. The following sections describe various aspects of breeding and market opportunity for addressing micronutrient malnutrition

The factorial structure of the supervisor’s core competencies scale

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