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Many freshwater snails of the genus Bulinus act as intermediate hosts in the life cycles of schistosomes in Africa and adjacent regions. Currently, 37 species of Bulinus representing four groups are recognised. The mitochondrial cytochrome c oxidase subunit 1 (cox1) gene has shown utility for identifying and differentiating Bulinus species and groups, but taxonomic relationships based on genetic data are not entirely consistent with those inferred using morphological and biological features. To underpin future systematic studies of members of the genus, we characterised here the mitochondrial genome of Bulinus truncatus (from a defined laboratory strain) using a combined second- and third-generation sequencing and informatics approach, enabling taxonomic comparisons with other planorbid snails for which mt genomes were available. Analyses showed consistency in gene order and length among mitochondrial genomes of representative planorbid snails, with the lowest and highest nucleotide diversities being in the cytochrome c oxidase and nicotinamide dehydrogenase subunit genes, respectively. This first mt genome for a representative of the genus Bulinus should provide a useful resource for future investigations of the systematics, population genetics, epidemiology and/or ecology of Bulinus and related snails. The sequencing and informatic workflow employed here should find broad applicability to a range of other snail vectors of parasitic trematodes.

Review history.

Supplemental material, ER-9430_MS_Preg_manuscript_FINAL_supplementary_material_TAND_2020-06-10_FINAL_revised_clean for Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden by Katja Marja Hakkarainen, Rosa Juuti, Sarah Burkill, Yvonne Geissbühler, Meritxell Sabidó, Catrinel Popescu, Kiliana Suzart-Woischnik, Jan Hillert, Miia Artama, Auli Verkkoniemi-Ahola, Kjell-Morten Myhr, Juha Mehtälä, Shahram Bahmanyar, Scott Montgomery and Pasi Korhonen in Therapeutic Advances in Neurological Disorders

Supplementary Text and Supplementary Figures: Figures S1 – S34.

As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mito-ribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans) nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation.—Preston, S., Korhonen, P. K., Mouchiroud, L., Cornaglia, M., McGee, S. L., Young, N. D., Davis, R. A., Crawford, S., Nowell, C., Ansell, B. R. E., Fisher, G. M., Andrews, K. T., Chang, B. C. H., Gijs, M. A. M., Sternberg, P. W., Auwerx, J., Baell, J., Hofmann, A., Jabbar, A., Gasser, R. B. Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain.

Alignment of sequences of the variable D8 domain of the large subunit of nuclear ribosomal RNA gene (LSU) representing Cryptosporidium and closely related apicomplexans, alveolates and dinoflagellates. Oligonucleotide primers (LSU2040F, LSU3020R; LSU2065F and LSU2557R) designed specifically to regions flanking the variable D8 domain are indicated in green. Nucleotide differences from the majority consensus of the alignment are highlighted. Figure S2. Alignment of sequences of the variable D8 domain of the large subunit of nuclear ribosomal RNA gene (LSU) representing Cryptosporidium derived from 45 faecal DNA samples. Nucleotide differences from the majority consensus of the alignment are highlighted. Colpodella angusta was included as an outgroup. (PDF 222 kb)

To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes) of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts’ immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes., Author Summary Despite the clinical importance of Trichobilharzia regenti in bird hosts and as a cause of cercarial dermatitis in humans, almost nothing is known about the molecular aspects of this fluke and its interactions with its hosts. Here, we sequenced, assembled and annotated the transcriptome representing two life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the bird host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for related flukes. Detailed analyses showed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during invasion and in growth and development, as well as cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during migration in neural tissues. These molecular insights into T. regenti biology should support future genomic and proteomic investigations of T. regenti, and comparative studies of flatworms.

Figure S1. The number of conserved domains common to >75 % of the sequences in each ion channel subfamily within the training dataset. The proportion of the sequences in the subfamilies that share the number of domains is given in the graph. The number of conserved domains is grouped according to the ion channel families. Figure S2. The range of transmembrane domains predicted in training dataset ion channel proteins. Range of transmembrane domains per subfamily, grouped according to each ion channel family. Figure S3. Receiver operating characteristic (ROC) curves for each probabilistic classification method. Figure S4. Probability values of each ion channel subfamilies computed during classification of sequences in the test dataset. Figure A shows the relation between the probability values and classifications made by SVM classifier. Figure B shows average probability values for individual ion channel subfamilies. The average values were grouped according to the ion channel families. Figure S5. Characteristics of putative ion channels identified and classified from the test dataset (human and C. elegans proteins). Panel A: Test sequences ordered by their SVM probability value, with their identification grouping presented on the second y-axis. Most of the sequences classified using high probability values were classified in Groups 1 and 2. Panel B: Confidence in test data ion channel classifications by group and classification category. (DOCX 1083 kb)

Primers used to isolate Hc-pdk-1 of Haemonchus contortus and to make constructs for green fluorescent protein (GFP) localization in Caenorhabditis elegans . (DOC 32Â kb)

Cloning strategy for reporter constructs. The constructs containing the Caenorhabditis elegans Ce-pdk-1 and the Haemonchus contortus Hc-pdk-1 promoters (pL-Cepdk and pL-Hcpdk) were made in the vector pPV199 [34]. Briefly, the Ce-pdk-1 promoter region was cloned into pPV199 (BamH1 and Age1 sites). The Hc-pdk-1 promoter region was cloned into pPV199 by homologous recombination. (DOC 127Â kb)

Transcription profiles for kinase genes in all key developmental stages (egg, L1, L2, L3, L4 and adult) and both sexes (L4 and adult) of Haemonchus contortus for eleven individual kinase groups. Figure S2. All clusters of transcription profiles for Haemonchus contortus kinase genes based on the Ward-clustering method (kâ =â 15). (DOCX 222 kb)

Transcription profiles for kinase genes in all key developmental stages (egg, L1, L2, L3, L4 and adult) and both sexes (L4 and adult) of Haemonchus contortus for eleven individual kinase groups. Figure S2. All clusters of transcription profiles for Haemonchus contortus kinase genes based on the Ward-clustering method (kâ =â 15). (DOCX 222 kb)

The occurrence of pressure ulcers was examined in a cross-sectional study in 23 health care facilities and in home care involving 548 patients. The screening of pressure ulcer risk was assessed simultaneously using the Braden Scale and the new Shape Risk Scale (SRS), and the results were compared. The overall prevalence of pressure ulcers in the study population was 15·5% (85/548). The Braden Scale was performed as described in the literature. The direct concordance of the Braden and SRS scales was 46%. In more than 90% of cases, the SRS classified patients as well as or better than the Braden Scale. The SRS allocates patients significantly different from the Braden Scale into the risk categories, especially the difference is significant between the low and medium-risk categories. The greatest advantage of SRS to Braden Scale is that it correctly identifies patients with low risk of pressure ulcers. It is interesting that the two risk scores, taking into consideration the basically different pathophysiological factors, can still give rather similar results. The users considered that both scales are easy to use.

Sukupolvien maisema. Porvoonjokilaakson kansallismaiseman syhtyvaiheita, Hannu Poutiainen (toim.), Lahti (2002)

Rakennusperintömme: kulttuuriympäristön lukukirja, Irma Lounatvirta & Lauri Putkonen (toim.), Helsinki (2001)

Generalized Estimating Equations (GEE), developed by (Zeger & Liang 1986), is a method of estimation that accounts for correlations among repeated measurements and is widely used in longitudinal analysis. The purpose of this master’s thesis is to provide an overview of GEE and use this approach on a cluster-randomized study called IndiMed. The data are from the Estonian Genome Center of University of Tartu. The clusters are doctors who were randomized to intervention or control group and subjects are patients with high blood pressure. All subjects in one cluster are either in intervention (received genetic risk information on the 2nd visit) or control group (received risk information on the 4th visit). Systolic and diastolic blood pressures were measured on all 5 visits for all patients and compared for the two study groups, taking into account the correlation among the repeated measurements.

The aim of this Bachelor’s Thesis is to explain what missing data means and give some ways to deal with it in clinical trials. Firstly, an overview of different types of missing data is given and the reasons for their occurrence. Second part of the thesis explains which analytical approaches can be used to conduct an unbiased analysis. Further, missing data are simulated for a data set to show how the approaches described are used in practice with SAS software.

The aim of this thesis is to give an overview of calculating sample size in clinical trials. First, a brief introduction to clinical trials and factors affecting sample size is given. This is followed by chapters on sample size calculations for three main trial types. Every design is then illustrated by a practical example and instructions for calculations in SAS and R software.