Exploring the host factors affecting asymptomatic Plasmodium falciparum infection: insights from a rural Burkina Faso study.

BACKGROUND Asymptomatic Plasmodium falciparum parasitaemia forms a reservoir for the transmission of malaria disease in West Africa. Certain haemoglobin variants are known to protect against severe malaria infection. However, data on the potential roles of haemoglobin variants and nongenetic factors in asymptomatic malaria infection is scarce and controversial. Therefore, this study investigated the associations of iron homeostasis, inflammation, nutrition, and haemoglobin mutations with parasitaemia in an asymptomatic cohort from a P. falciparum-endemic region during the high transmission season. METHODS A sub-study population of 688 asymptomatic individuals (predominantly children and adolescents under 15 years, n = 516) from rural Burkina Faso previously recruited by the NOVAC trial (NCT03176719) between June and October 2017 was analysed. Parasitaemia was quantified with conventional haemocytometry. The haemoglobin genotype was determined by reverse hybridization assays targeting a selection of 21 HBA and 22 HBB mutations. Demographics, inflammatory markers (interleukins 6 and 10, hepcidin), nutritional status (mid upper-arm circumference and body mass index), and anaemia (total haemoglobin, ferritin, soluble transferrin receptor) were assessed as potential predictors through logistic regression. RESULTS Malaria parasites were detected in 56% of subjects. Parasitaemia was associated most strongly with malnutrition. The effect size increased with malnutrition severity (OR = 6.26, CI95: 2.45-19.4, p < 0.001). Furthermore, statistically significant associations (p < 0.05) with age, cytokines, hepcidin and heterozygous haemoglobin S were observed. CONCLUSIONS According to these findings, asymptomatic parasitaemia is attenuated by haemoglobin S, but not by any of the other detected genotypes. Aside from evidence for slight iron imbalance, overall undernutrition was found to predict parasitaemia; thus, further investigations are required to elucidate causality and inform strategies for interventions

Replicated anthropogenic hybridisations reveal parallel patterns of admixture in marine mussels.

Human-mediated transport creates secondary contacts between genetically differentiated lineages, bringing new opportunities for gene exchange. When similar introductions occur in different places, they provide informally replicated experiments for studying hybridisation. We here examined 4,279 Mytilus mussels, sampled in Europe and genotyped with 77 ancestry-informative markers. We identified a type of introduced mussels, called "dock mussels," associated with port habitats and displaying a particular genetic signal of admixture between M. edulis and the Mediterranean lineage of M. galloprovincialis. These mussels exhibit similarities in their ancestry compositions, regardless of the local native genetic backgrounds and the distance separating colonised ports. We observed fine-scale genetic shifts at the port entrance, at scales below natural dispersal distance. Such sharp clines do not fit with migration-selection tension zone models, and instead suggest habitat choice and early-stage adaptation to the port environment, possibly coupled with connectivity barriers. Variations in the spread and admixture patterns of dock mussels seem to be influenced by the local native genetic backgrounds encountered. We next examined departures from the average admixture rate at different loci, and compared human-mediated admixture events, to naturally admixed populations and experimental crosses. When the same M. galloprovincialis background was involved, positive correlations in the departures of loci across locations were found; but when different backgrounds were involved, no or negative correlations were observed. While some observed positive correlations might be best explained by a shared history and saltatory colonisation, others are likely produced by parallel selective events. Altogether, genome-wide effect of admixture seems repeatable and more dependent on genetic background than environmental context. Our results pave the way towards further genomic analyses of admixture, and monitoring of the spread of dock mussels both at large and at fine spacial scales.ANR Project HySea (ANR-12-BSV7-0011); Russian Science Foundation project N°19-74-2002

Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations

Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably, an underlying mechanism has not yet been fully elucidated and no predictive factors are known to identify at-risk patients. With the aim to identify genetic susceptibility variants to metamizole-induced agranulocytosis (MIA) and neutropenia (MIN), we conducted a retrospective multi-center collaboration including cases and controls from three European populations. Association analyses were performed using genome-wide genotyping data from a Swiss cohort (45 cases, 191 controls) followed by replication in two independent European cohorts (41 cases, 273 controls) and a joint discovery meta-analysis. No genome-wide significant associations (p < 1 × 10−7) were observed in the Swiss cohort or in the joint meta-analysis, and no candidate genes suggesting an immune-mediated mechanism were identified. In the joint meta-analysis of MIA cases across all cohorts, two candidate loci on chromosome 9 were identified, rs55898176 (OR = 4.01, 95%CI: 2.41–6.68, p = 1.01 × 10−7) and rs4427239 (OR = 5.47, 95%CI: 2.81–10.65, p = 5.75 × 10−7), of which the latter is located in the SVEP1 gene previously implicated in hematopoiesis. This first genome-wide association study for MIA identified suggestive associations with biological plausibility that may be used as a stepping-stone for post-GWAS analyses to gain further insight into the mechanism underlying MIA.This research was funded by Swiss National Science Foundation, grant number 31003A_160206. The EuDAC study was funded by Carlos III Spanish Health Institute [FIS10/02632], the European Regional Development Fund FEDER, the Swedish Research Council [Medicine 521-2011-2440,521-2014-3370 and 2018-03307], the Swedish Heart and Lung Foundation [20120557,20140291 and 20170711] and a grant from the Federal Institute for Drugs and Medical Devices (Bonn, Germany). The EUDRAGENE collaboration has received support from the EC 5th Framework program [QLRI-CR-2002-02757] and the Serious Adverse Events Consortium, SAEC, a collaboration for academia and industry. M.M. is supported by the National Institute for Health Research Biomedical Research Center at Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London

Endovascular Stent Treatment for Symptomatic Benign Iliofemoral Venous Occlusive Disease: Long-Term Results 1987–2009

Venous stenting has been shown to effectively treat iliofemoral venous obstruction with good short- and mid-term results. The aim of this study was to investigate long-term clinical outcome and stent patency. Twenty patients were treated with venous stenting for benign disease at our institution between 1987 and 2005. Fifteen of 20 patients (15 female, mean age at time of stent implantation 38 years [range 18–66]) returned for a clinical visit, a plain X-ray of the stent, and a Duplex ultrasound. Four patients were lost to follow-up, and one patient died 277 months after stent placement although a good clinical result was documented 267 months after stent placement. Mean follow-up after stent placement was 167.8 months (13.9 years) (range 71 (6 years) to 267 months [22 years]). No patient needed an additional venous intervention after stent implantation. No significant difference between the circumference of the thigh on the stented side (mean 55.1 cm [range 47.0–70.0]) compared with the contralateral thigh (mean 54.9 cm [range 47.0–70.0]) (p = 0.684) was seen. There was a nonsignificant trend toward higher flow velocities within the stent (mean 30.8 cm/s [range 10.0–48.0]) and the corresponding vein segment on the contralateral side (mean 25.2 cm/s [range 12.0–47.0]) (p = 0.065). Stent integrity was confirmed in 14 of 15 cases. Only one stent showed a fracture, as documented on x-ray, without any impairment of flow. Venous stenting using Wallstents showed excellent long-term clinical outcome and primary patency rate

Evidence of multiple paternity and cooperative parental care in the so called monogamous silver arowana Osteoglossum bicirrhosum (Osteoglossiformes: Osteoglossidae)

Monogamy is rare in fishes and is usually associated with elaborate parental care. When parental care is present in fishes, it is usually the male that is responsible, and it is believed that there is a relationship between the high energetic investment and the certainty of paternity (except in the case of sneaker males). Osteoglossum bicirrhosum is considered a monogamous fish, and has particular behavioral traits that permit the study of mating systems and parental care, such as male mouthbrooding. We investigated the genetic relationships of males with the broods found in their oral cavities in Osteoglossum samples collected in a natural environment in the lower Purus river basin, Amazonas, Brazil. Fourteen broods were analyzed for parentage (268 young and 14 adult males) using eight microsatellite loci. The results indicate that eleven broods show a monogamous system. In one brood, however, approximately 50% of the young were genetically compatible with being offspring of another male, and in another two broods, none of the subsampled young were compatible with the genotypes of the brooding male. The result of this first brood may be explained by the extra-parental contribution of a sneaker male, whereas cooperative parental care may explain the result in the other two broods

Morphological variation in a secondary contact between divergent lineages of brown trout (Salmo trutta) from the Iberian Peninsula

The aim of this study was to analyze the morphological variation of brown trout (Salmo trutta) in the Duero basin, an Atlantic river basin in the Iberian Peninsula, where a spatial segregation of two divergent lineages was previously reported, based on isozyme, microsatellite and mtDNA data. In these studies, two divergent pure regions (Pisuerga and Lower-course) and several hybrid populations between them were identified. Morphological variation was evaluated in 11 populations representative of the genetic differentiation previously observed in the Duero basin, using multivariate analysis on 12 morphometric and 4 meristic traits. A large differentiation between populations was observed (interpopulation component of variance: 41.8%), similar to that previously detected with allozymes and microsatellites. Morphometric differentiation was also reflected by the high classification success of pure and hybrid individuals to their respective populations, using multivariate discriminant functions (94.1% and 79.0%, respectively). All multivariate and clustering analyses performed demonstrated a strong differentiation between the pure regions. The hybrid populations, though showing large differentiation among them, evidenced an intermediate position between the pure samples. Head and body shape traits were the most discriminant among the morphometric characters, while pectoral rays and gillrakers were the most discriminant among the meristic traits. These results confirmed the high divergence of the brown trout from the Duero basin and suggest some traits on which selection could be acting to explain the spatial segregation observed

Postglacial recolonizations, watershed crossings and human translocations shape the distribution of chub lineages around the Swiss Alps

Background: Distributions of European fish species were shaped by glaciations and the geological history of river networks until human activities partially abrogated the restrictions of biogeographical regions. The nearby origins of the Rhine, Rhone, Danube and Po rivers in the Swiss Alps allow the examination of historical and human-influenced patterns in fish genetic structure over a small geographic scale. We investigated these patterns in the widespread European chub (Squalius cephalus) from the Rhone, Rhine and Danube catchments and its proposed southern sister species Italian chub (Squalius squalus) from the Po catchment. Results: A phylogenetic tree constructed from mitochondrial Cytochrome b and COI sequences was consistent with earlier work in that it showed a separation of European chub and Italian chub, which was also reflected in microsatellite allele frequencies, morphological traits and shape differences quantified by geometric morphometrics. A new finding was that the predominant mitochondrial haplotype of European chub from the Rhine and Rhone catchments was also discovered in some individuals from Swiss populations of the Italian chub, presumably as a result of human translocation. Consistent with postglacial recolonizations from multiple refugia along the major rivers, the nuclear genetic structure of the European chub largely reflected drainage structure, but it was modified by watershed crossings between Rhine and Rhone near Lake Geneva as well as between Danube and Rhine near Lake Constance. Conclusion: Our study adds new insights into the cyprinid colonization history of central Europe by showing that multiple processes shaped the distribution of different chub lineages around the Swiss Alps. Interestingly, we find evidence that cross-catchment migration has been mediated by unusual geological events such as drainage captures or watershed crossings facilitated by retreating glaciers, as well as evidence that human transport has interfered with the historical distribution of these fish (European chub haplotypes present in the Italian chub). The desirable preservation of evolutionarily distinct lineages will thus require the prevention of further translocations

[Chronic anterior tibial syndrome]

In two young athletic men we made the diagnosis of chronic tibialis anterior syndrome. Pain during strenuous exercise was localized in the anterolateral aspect of both calves. After stopping exercise the complaints disappeared within 15-20 minutes and not in 2-3 minutes as it would be typical for patients with atherosclerotic peripheral arterial occlusive disease. Diagnosis is based on patient history, normal clinical examination (systolic ankle pressure determined by Doppler-Sonography, electronic segmental oscillography) and increased intramuscular pressure at rest (> 10 mmHg) and after exercise (42 and 35 mmHg). Bilateral fasciotomy was performed in both patients. They are free of pain after 3 respectively 6 months postoperatively

Sequence capture and next-generation resequencing of multiple tagged nucleic acid samples for mutation screening of urea cycle disorders

BACKGROUND: Molecular genetic testing is commonly used to confirm clinical diagnoses of inherited urea cycle disorders (UCDs); however, conventional mutation screenings encompassing only the coding regions of genes may not detect disease-causing mutations occurring in regulatory elements and introns. Microarray-based target enrichment and next-generation sequencing now allow more-comprehensive genetic screening. We applied this approach to UCDs and combined it with the use of DNA bar codes for more cost-effective, parallel analyses of multiple samples. METHODS: We used sectored 2240-feature medium-density oligonucleotide arrays to capture and enrich a 199-kb genomic target encompassing the complete genomic regions of 3 urea cycle genes, OTC (ornithine carbamoyltransferase), CPS1 (carbamoyl-phosphate synthetase 1, mitochondrial), and NAGS (N-acetylglutamate synthase). We used the Genome Sequencer FLX System (454 Life Sciences) to jointly analyze 4 samples individually tagged with a 6-bp DNA bar code and compared the results with those for an individually sequenced sample. RESULTS: Using a low tiling density of only 1 probe per 91 bp, we obtained strong enrichment of the targeted loci to achieve ≥90% coverage with up to 64% of the sequences covered at a sequencing depth ≥10-fold. We observed a very homogeneous sequence representation of the bar-coded samples, which yielded a >30% increase in the sequence data generated per sample, compared with an individually processed sample. Heterozygous and homozygous disease-associated mutations were correctly detected in all samples. CONCLUSIONS: The use of DNA bar codes and the use of sectored oligonucleotide arrays for target enrichment enable parallel, large-scale analysis of complete genomic regions for multiple genes of a disease pathway and for multiple samples simultaneously. This approach thus may provide an efficient tool for comprehensive diagnostic screening of mutations