Genome-wide SNP and microsatellite variation illuminate population-level epidemiology in the Leishmania donovani species complex

The species of the Leishmania donovani species complex cause visceral leishmaniasis, a debilitating infectious disease transmitted by sandflies. Understanding molecular changes associated with population structure in these parasites can help unravel their epidemiology and spread in humans. In this study, we used a panel of standard microsatellite loci and genome-wide SNPs to investigate population-level diversity in L. donovani strains recently isolated from a small geographic area spanning India, Bihar and Nepal, and compared their variation to that found in diverse strains of the L. donovani complex isolates from Europe, Africa and Asia. Microsatellites and SNPs could clearly resolve the phylogenetic relationships of the strains between continents, and microsatellite phylogenies indicated that certain older Indian strains were closely related to African strains. In the context of the anti-malaria spraying campaigns in the 1960s, this was consistent with a pattern of episodic population size contractions and clonal expansions in these parasites that was supported by population history simulations. In sharp contrast to the low resolution provided by microsatellites, SNPs retained a much more fine-scale resolution of population-level variability to the extent that they identified four different lineages from the same region one of which was more closely related to African and European strains than to Indian or Nepalese ones. Joining results of in vitro testing the antimonial drug sensitivity with the phylogenetic signals from the SNP data highlighted protein-level mutations revealing a distinct drug-resistant group of Nepalese and Indian L. donovani. This study demonstrates the power of genomic data for exploring parasite population structure. Furthermore, markers defining different genetic groups have been discovered that could potentially be applied to investigate drug resistance in clinical Leishmania strains.     

Patterns of globalized reproduction: Egg cells regulation in Israel and Austria

ABSTRACT: Since the successful introduction of in vitro fertilization in 1978, medically assisted reproduction (MAR) has proliferated in multiple clinical innovations. Consequently, egg cells have become an object of demand for both infertility treatment and stem cell research, and this raises complex legal, ethical, social and economic issues.In this paper we compare how the procurement and use of human egg cells is regulated in two countries: Israel and Austria. Israel is known for its scientific leadership, generous public funding, high utilization and liberal regulation of assisted reproductive technology (ART). Austria lies at the other extreme of the regulatory spectrum in terms of restrictions on reproductive interventions.In both countries, however, there is a constant increase in the use of the technology, and recent legal developments make egg cells more accessible. Also, in both countries the scarcity of egg cells in concert with the rising demand for donations has led to the emergence of cross-border markets and global 'reproductive tourism' practices. In Israel, in particular, a scandal known as the 'eggs affair' was followed by regulation that allowed egg cell donations from outside the country under certain conditions.Cross-border markets are developed by medical entrepreneurs, driven by global economic gaps, made possible by trans-national regulatory lacunae and find expression as consumer demand. The transnational practice of egg cell donations indicates the emergence of a global public health issue, but there is a general lack of medical and epidemiological data on its efficacy and safety. We conclude that there is need for harmonisation of domestic laws and formulation of new instruments for international governance.     

Effects of increased white blood cell count on endothelin-induced vasoconstriction in healthy subjects

It is known that administration of granulocyte-colony stimulating factor is followed by an increase of white blood cell count. There is evidence from other vascular beds that an increase in white blood cell count impairs blood flow regulation especially in the microcirculation. Whether this also holds true for the ocular circulation is unknown. In the following study we investigated whether an increase in white blood cell count alters the endothelin-1 induced vasoconstriction in humans. Neither granulocyte-colony stimulating factor nor endothelin-1 had any consistent effect on blood pressure, pulse rate or intraocular pressure. Administration of granulocyte-colony stimulating factor induced a pronounced increase in retinal white blood cell density (p < 0.01). Administration of endothelin-1 decreased choroidal (p < 0.01) and retinal blood flow (p < 0.01). The change in choroidal blood flow in response to endothelin-1 was not altered by pre-treatment with granulocyte-colony stimulating factor. By contrast, the decrease in retinal blood flow was more pronounced during an increase in white blood cell count (p = 0.02) when compared to placebo. Our data indicates that during pronounced vasoconstriction, as induced by administration of endothelin-1, vascular regulation can be altered by the number of circulating white blood cells. Whether this effect is caused by an interaction of red and white blood cells in the microcirculation or a yet unknown mechanism needs further investigation.     

Low‐amplitude high frequency vibration down‐regulates myostatin and atrogin‐1 expression,two components of the atrophy pathway in muscle cells

Whole body vibration (WBV) is a very widespread mechanical stimulus used in physical therapy, rehabilitation and fitness centres. It has been demonstrated that vibration induces improvements in muscular strength and performance and increases bone density. We investigated the effects of low‐amplitude, high frequency vibration (HFV) at the cellular and tissue levels in muscle. We developed a system to produce vibrations adapted to test several parameters in vitro and in vivo. For in vivo experiments, we used newborn CD1 wild‐type mice, for in vitro experiments, we isolated satellite cells from 6‐day‐old CD1 mice, while for proliferation studies, we used murine cell lines. Animals and cells were treated with high frequency vibration at 30 Hz. We analyzed the effects of mechanical stimulation on muscle hypertrophy/atrophy pathways, fusion enhancement of myoblast cells and modifications in the proliferation rate of cells. Results demonstrated that mechanical vibration strongly down‐regulates atrophy genes both in vivo and in vitro. The in vitro experiments indicated that mechanical stimulation promotes fusion of satellite cells treated directly in culture compared to controls. Finally, proliferation experiments indicated that stimulated cells had a decreased growth rate compared to controls. We concluded that vibration treatment at 30 Hz is effective in suppressing the atrophy pathway both in vivo and in vitro and enhances fusion of satellite muscle cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Mycobacterium chimaera causes tuberculosis-like infection in a male patient with anorexia nervosa

Here we present a 27-year-old male patient--with a known prolonged history of anorexia nervosa (AN)--suffering from tuberculosis like infection. At the time he was admitted to clinical treatment, he had developed fever up to 40°C and survived on a body mass index of 11.8. In this case, Mycobacterium chimaera, generally recognized for low pathogenicity, was identified as the causative agent. Remission from lung infection was achieved after antibiotic treatment according to laboratory susceptibility testing while earlier antituberculosis therapies had failed. Because of a large cavity in the upper left lung, surgical excision was necessary to prevent recurrence of lung infection. Moreover, stabilization of the patient general health problem needs to be supported by a lasting psychotherapy.     

Early respiratory morbidity in a multicultural birth cohort: the Generation R Study

Ethnic disparities in the prevalence of asthma symptoms in children have been described. We evaluated to what extent the association between ethnic background and respiratory symptoms during the first 2 years of life could be explained by the mediating effect of risk factors for respiratory morbidity. The Generation R Study is a multiethnic, population-based birth cohort study. Pre and postnatal risk factors for respiratory morbidity were prospectively assessed by questionnaires. Information about ethnicity was available for 5,684 infants. The associations between ethnic background and lower respiratory symptoms at 12 and 24 months were evaluated with log-binomial regression models. Relative risks and 95 % confidence intervals (RR [95 % CI]) were computed for Cape Verdean, Moroccan, Antillean, Surinamese and Turkish ethnicity with Dutch ethnicity as the reference category. We found an increased risk of lower respiratory symptoms at 24 months in Antillean infants (1.32 [95 % CI 1.12-1.57]) that was mediated by early postnatal exposures (pets keeping, siblings, breastfeeding, daycare attendance, smoke exposure). Turkish infants also had an increased risk of lower respiratory symptoms at 12 and 24 months (1.14 [95 % CI 1.02-1.27] and 1.21 [95 % CI 1.07-1.38], respectively), partly explained by previous morbidity (eczema, infections and upper respiratory symptoms). There were no differences for Cape Verdean, Moroccan or Surinamese, as compared to Dutch infants. Hence, ethnic background was associated with respiratory symptoms during the first 2 years of life and this association was largely explained by mediating effects of known pre and postnatal risk factors for respiratory morbidity.     

Television habits in relation to overweight, diet and taste preferences in European children: the IDEFICS study

Early television exposure has been associated with various health outcomes including childhood obesity. This paper describes associations between patterns of television viewing, on one hand, and diet, taste preference and weight status, on the other, in European preschoolers and schoolchildren. The IDEFICS baseline survey was conducted at examination centers in Italy, Estonia, Cyprus, Belgium, Sweden, Germany, Hungary, and Spain. 15,144 children aged 2–9 completed the basic protocol, including anthropometry and parental questionnaires on their diets and television habits. A subsample of 1,696 schoolchildren underwent further sensory testing for fat and sweet taste preferences. Three dichotomous indicators described: children’s habitual television exposure time; television viewing during meals; and having televisions in their bedrooms. Based on these variables we investigated television habits in relation to overweight (IOTF) and usual consumption of foods high in fat and sugar. A possible role of taste preference in the latter association was tested in the sensory subgroup. All television indicators were significantly associated with increased risk of overweight, with odds ratios ranging from 1.21 to 1.30, in fully adjusted models. Children’s propensities to consume high-fat and high-sugar foods were positively and, in most analyses, monotonically associated with high-risk television behaviors. The associations between television and diet propensities were not explained by preference for added fat or sugar in test foods. To summarize, in addition to being more overweight, children with high-risk television behaviors may, independent of objectively measured taste preferences for fat and sugar, passively overconsume higher-fat and particularly higher-sugar diets.     

Reproducibility of the Carpet View system: a novel technical solution for display and off line analysis of OCT images

The optical coherence tomography (OCT) evaluation of the stent anatomy requires the inspection of sequential cross section (CS). However stent coils cannot be appreciated in the conventional format as the OCT CS simply display stent struts, that are poorly representative of the stent architecture. The aim of the present study was to validate a new software (Carpet View), which unfolds the stented segment, reconstructing it as an open structure and displaying the stent meshwork. 21 patients were studied with frequency domain OCT after the deployment of different stents: seven bio-absorbable scaffolds (Dream), seven bare metal stent (Vision/Multilink8), seven drug eluting stent (Cre8). Conventional CS reconstructions were post-processed with the Carpet View software and analyzed by the same reader twice (intra-observer variability) and by two different readers (inter-observer variability). A small average difference in the number of all struts was obtained with the two methods (conventional vs carpet view reconstruction). Using the carpet view, high intra-observer and inter-observer correlations were found for the number of struts obtained in each coil. The Pearson correlation values were 0.98 (p = 0.0001) and 0.96 (p = 0.0001) respectively. The same number of coils was found when analyses were repeated by the same reader or by a different reader whilst mild differences in the count of stent junctions were reported. The Carpet View can be used to address the stent geometry with high reproducibility. This approach enables the matching of the same stent portion during serial time points and promises to improve the stent assessment.