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Cystic echinococcosis is a socioeconomically important parasitic disease caused by the larval stage of the canid tapeworm Echinococcus granulosus, afflicting millions of humans and animals worldwide. The development of a vaccine (called EG95) has been the most notable translational advance in the fight against this disease in animals. However, almost nothing is known about the genomic organisation/location of the family of genes encoding EG95 and related molecules, the extent of their conservation or their functions. The lack of a complete reference genome for E. granulosus genotype G1 has been a major obstacle to addressing these areas. Here, we assembled a chromosomal-scale genome for this genotype by scaffolding to a high quality genome for the congener E. multilocularis, localised Eg95 gene family members in this genome, and evaluated the conservation of the EG95 vaccine molecule. These results have marked implications for future explorations of aspects such as developmentally-regulated gene transcription/expression (using replicate samples) for all E. granulosus stages; structural and functional roles of non-coding genome regions; molecular 'cross-talk' between oncosphere and the immune system; and defining the precise function(s) of EG95. Applied aspects should include developing improved tools for the diagnosis and chemotherapy of cystic echinococcosis of humans. A high-quality genome for the parasitic tapeworm, Echinococcus granulosus, provides further insight into the EG95 vaccine target for cystic echinococcosis. [ABSTRACT FROM AUTHOR]

Some snails act as intermediate hosts (vectors) for parasitic flatworms (flukes) that cause neglected tropical diseases, such as schistosomiases. Schistosoma haematobium is a blood fluke that causes urogenital schistosomiasis and induces bladder cancer and increased risk of HIV infection. Understanding the molecular biology of the snail and its relationship with the parasite could guide development of an intervention approach that interrupts transmission. Here, we define the genome for a key intermediate host of S. haematobium—called Bulinus truncatus—and explore protein groups inferred to play an integral role in the snail's biology and its relationship with the schistosome parasite. Bu. truncatus shared many orthologous protein groups with Biomphalaria glabrata—the key snail vector for S. mansoni which causes hepatointestinal schistosomiasis in people. Conspicuous were expansions in signalling and membrane trafficking proteins, peptidases and their inhibitors as well as gene families linked to immune response regulation, such as a large repertoire of lectin-like molecules. This work provides a sound basis for further studies of snail-parasite interactions in the search for targets to block schistosomiasis transmission. The snail Bulinus truncatus is an intermediate host of the carcinogenic human blood fluke Schistosoma haematobium. Here the authors report the genome of Bu. truncatus, explore protein groups inferred to play a role in its interaction with the schistosome parasite, and identify expansions in gene families linked to immune response regulation. [ABSTRACT FROM AUTHOR]

Background: Studies investigating bladder cancer risk in pioglitazone-treated type 2 diabetes mellitus patients report conflicting results. Previous meta-analyses on this topic utilized publications prior to 2013. More long-term observational studies have been published since then. We reviewed the accumulated evidence and updated findings from previous meta-analyses.Methods: This meta-analysis was based on a systematic review of peer-reviewed observational studies published prior to September 30, 2016. Eligible studies were identified using a specified MEDLINE search. References from included studies and from previous meta-analyses were screened for additional records. Meta-analysis hazards ratios were derived using a random-effects model. Several sensitivity analyses including hierarchical Bayesian meta-analysis with country-specific effects were conducted.Results: Of 363 identified records, 23 studies were included in this review and 18 in the actual meta-analyses. For bladder cancer outcome, the estimated effect size for ever vs. never use of pioglitazone was 1.16 [95% confidence interval (CI), 1.04-1.28]. In the cumulative dose and duration analyses, highest effect was observed in the highest/longest exposure group, but substantial heterogeneity was present. In the sensitivity analysis, only studies adjusted for lifestyle-related factors were included and the frequentist effect size was 1.18 (95% CI, 1.00-1.40, p = 0.054). However, the risk was not verified in the Bayesian framework with an effect size of 1.17 [95% credible interval (CrI), 0.94-1.54].Conclusions: In line with previous meta-analyses, we observed a small but statistically significant association between ever (vs. never) use of pioglitazone and bladder cancer risk; however, causality is not established and alternative explanations cannot be ruled out. [ABSTRACT FROM AUTHOR]

Aim: To identify how the electronic health record (EHR) systems and national registers can be used for research purposes. We focused on how the primary care physicians adhere to clinical guidelines.Methods: Study population included incident type 2 diabetes patients from four selected regions. Data were collected in two phases. At the first phase study cohort was identified using the prescription registers of the Social Insurance Institution (SII) and EHR systems used within the study regions. At second phase, data were collected from SII’s registers, local EHR systems, the hospital discharge and the primary care registers of National Institute for Health and Welfare.Results: Metformin was the most common choice as first drug. Among all study patients, 8375 (76.0%) started metformin monotherapy or combinations. The treatment was intensified at variable levels of HbA1c depending on the area. DPP4-inhibitors were by far the most common agent for treatment intensification. Sulphonylureas were used less often than basal insulin as the second-line agent. The use of DPP4-inhibitors increased between years 2009-2010, when first DPP4-inhibitor received reimbursement and this class became dominant drug for treatment intensification increasingly thereafter.Conclusions: The EHR systems and national registers can be used for research purposes in Finland. The realization of diabetes treatment national guidelines are followed in primary care to a large extent. However, the subsequent intensification of therapy was delayed and occurred at elevated Hba1c levels. [ABSTRACT FROM AUTHOR]

Trichuris (whipworm) infects 1 billion people worldwide and causes a disease (trichuriasis) that results in major socioeconomic losses in both humans and pigs. Trichuriasis relates to an inflammation of the large intestine manifested in bloody diarrhea, and chronic disease can cause malnourishment and stunting in children. Paradoxically, Trichuris of pigs has shown substantial promise as a treatment for human autoimmune disorders, including inflammatory bowel disease (IBD) and multiple sclerosis. Here we report whole-genome sequencing at ∼140-fold coverage of adult male and female T. suis and ∼80-Mb draft assemblies. We explore stage-, sex- and tissue-specific transcription of mRNAs and small noncoding RNAs. [ABSTRACT FROM AUTHOR]

Objective: This large nationwide study describes the prevalence and predictors of long-term antipsychotic polypharmacy among patients with schizophrenia. Methods: A register-based longitudinal study of all people in Finland, who had at least one hospitalization due to schizophrenia during the years 2000-2007 and who were alive on March 1, 2007. Entry to the cohort was defined from the first hospitalization for schizophrenia during the years 2000-2007, and the date of assessment of antipsychotic polypharmacy was March 1, 2007. We studied separately chronic ( N = 8,037) and recent onset ( N = 8,046) schizophrenia patients. Antipsychotic polypharmacy was defined as overlapping of two or more filled prescriptions of antipsychotics for over 60 days. Results: In a total 16,083 patients with schizophrenia the prevalence of antipsychotic polypharmacy was 46.2 % ( N = 7,436, mean age 47.5 years, male 55 %). The longer the duration of schizophrenia, the more common the antipsychotic polypharmacy. Long index hospitalization and being male significantly associated with antipsychotic polypharmacy among all schizophrenia patients. Especially, in chronic schizophrenia patients, the previous use of benzodiazepine like agents was associated with antipsychotic polypharmacy, but the use of antidepressants associated with less frequent antipsychotic polypharmacy. Conclusions: Antipsychotic polypharmacy was widely prevalent among patients with schizophrenia and it was associated with long hospitalizations and long duration of illness. Benzodiazepine use was associated with increased risk and antidepressant use with decreased risk of antipsychotic polypharmacy when the effect of other clinical and socioeconomic factors was adjusted. Research is needed of risks and benefits of antipsychotic polypharmacy and augmentation of antipsychotic with other psychoactive drugs. [ABSTRACT FROM AUTHOR]

Objective: To study the associations between the intake of flavonols and flavones and the risk of cancer. Methods: The study cohort consisted of 27,110 male smokers, aged 50–69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases of cancers were identified through national registers. During an average 6.1-year follow-up, 791 lung cancers, 226 prostate cancers, 156 urothelial cancers, 133 colorectal cancers, 111 stomach cancers, and 92 renal cell cancers were diagnosed. Results: Intake of flavonols and flavones was inversely associated with the risk of lung cancer; multivariate relative risk in the highest vs. the lowest quartile 0.56, 95% confidence interval 0.45–0.69, p for trend 0.0001. The risk was similar in all histological types of lung cancer. No association was found between flavonol and flavone intake and the risk of other cancers. Conclusions: Intake of flavonols and flavones seemed to be inversely associated with the risk of lung cancer, but not with that of other cancers. [ABSTRACT FROM AUTHOR]

This paper investigates the effect of one dose of vitamin A on subsequent 4 month mortality in children under 6 months of age in a randomized, double-blind placebo-controlled community trial in Nepal. An earlier published intention-to-treat analysis showed no benefit, but ignored the information on actual receipt of treatment. Structural failure time models (Robins and Tsiatis, '91) use randomization based inference and incorporate compliance information which is possibly selective. The data presented here offer some new challenges for this approach: ward-based randomization induces correlation between survival outcomes; and the actual receipt of vitamin A dose is not always recorded. To tackle the problem of the clustered survival data we consider a robust version of the structural parameter vector estimator. A sensitivity analysis captures boundaries for the estimated structural parameters reflecting a range of potential values of children whose true receipt of treatment is unknown. The analysis suggests that the effect of vitamin A was beneficial in the beginning of the trial but towards the end of the trial there was a reversal of this effect. [ABSTRACT FROM AUTHOR]

We validated diagnoses of acute myocardial infarction (AMI) and death from coronary heart disease (CHD) found in the Finnish National Hospital Discharge Register and the Register of Causes of Death from a sample of the 29,133 men participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cases were traced to hospitals and institutes performing medico-legal death cause examinations and all relevant information was collected. The cardiac events were re-evaluated according to the diagnostic criteria of the Finnish contribution to the WHO MONICA project, i.e. the FINMONICA criteria. Altogether 408 cases of non-fatal AMI (n = 217) and death from CHD (n = 191) were reviewed. In the re-evaluation 94% of them (95% confidence interval 92--96%) were diagnosed as either definite (57%) or possible (37%) AMI. Non-fatal cases were more often classified definite AMI in the review, whereas fatal cases were more often classified possible AMI. Age or trial supplementation group did not affect classification, and no secular trend was observed. In conclusion, the diagnoses of AMI and death from CHD in the registers were highly predictive of a true major coronary event defined by strict criteria, thus their use in endpoint assessment in epidemiological studies and clinical trials is justified. [ABSTRACT FROM AUTHOR]

Trichobilharzia species are parasitic flatworms (called schistosomes or flukes) that cause important diseases in birds and humans, but very little is known about their molecular biology. Here, using a transcriptomics-bioinformatics-based approach, we explored molecular aspects pertaining to the nutritional requirements of Trichobilharzia szidati ('visceral fluke') and T. regenti ('neurotropic fluke') in their avian host. We studied the larvae of each species before they enter (cercariae) and as they migrate (schistosomules) through distinct tissues in their avian (duck) host. Cercariae of both species were enriched for pathways or molecules associated predominantly with carbohydrate metabolism, oxidative phosphorylation and translation of proteins linked to ribosome biogenesis, exosome production and/or lipid biogenesis. Schistosomules of both species were enriched for pathways or molecules associated with processes including signal transduction, cell turnover and motility, DNA replication and repair, molecular transport and/or catabolism. Comparative informatic analyses identified molecular repertoires (within, e.g., peptidases and secretory proteins) in schistosomules that can broadly degrade macromolecules in both T. szidati and T. regenti, and others that are tailored to each species to selectively acquire nutrients from particular tissues through which it migrates. Thus, this study provides molecular evidence for distinct modes of nutrient acquisition between the visceral and neurotropic flukes of birds. [ABSTRACT FROM AUTHOR]