Multilocus Genotyping of Human Giardia Isolates Suggests Limited Zoonotic Transmission and Association between Assemblage B and Flatulence in Children

Giardia intestinalis is a protozoan parasite found world-wide and it is a major cause of diarrhea in humans and other mammals. The genetic variability within G. intestinalis is high with eight distinct genotypes or assemblages (A-H). Here we performed sequence-based multilocus genotyping of around 200 human Giardia isolates. We found evidence of limited zoonotic transmission of certain A subtypes and an association between flatulence and assemblage B infection in children. This shows that it is important to investigate different assemblages and sub-assemblages of G. intestinalis in human infections in order to understand the clinical significance, zoonotic potential, sequence divergence, and transmission pathways of this parasite

The requirements and challenges in preventing of road traffic injury in Iran. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Road traffic injuries (RTIs) are a major public health problem, especially in low- and middle-income countries. Among middle-income countries, Iran has one of the highest mortality rates from RTIs. Action is critical to combat this major public health problem. Stakeholders involved in RTI control are of key importance and their perceptions of barriers and facilitators are a vital source of knowledge. The aim of this study was to explore barriers to the prevention of RTIs and provide appropriate suggestions for prevention, based on the perceptions of stakeholders, victims and road-users as regards RTIs.</p> <p>Methods</p> <p>Thirty-eight semi-structured interviews were conducted with informants in the field of RTI prevention including: police officers; public health professionals; experts from the road administrators; representatives from the General Governor, the car industry, firefighters; experts from Emergency Medical Service and the Red Crescent; and some motorcyclists and car drivers as well as victims of RTIs. A qualitative approach using grounded theory method was employed to analyze the material gathered.</p> <p>Results</p> <p>The core variable was identified as "The lack of a system approach to road-user safety". The following barriers in relation to RTI prevention were identified as: human factors; transportation system; and organizational coordination. Suggestions for improvement included education (for the general public and targeted group training), more effective legislation, more rigorous law enforcement, improved engineering in road infrastructure, and an integrated organization to supervise and coordinate preventive activities.</p> <p>Conclusion</p> <p>The major barriers identified in this study were human factors and efforts to change human behaviour were suggested by means of public education campaigns and stricter law enforcement. However, the lack of a system approach to RTI prevention was also an important concern. There is an urgent need for both an integrated system to coordinate RTI activities and prevention and a major change in stakeholders' attitudes towards RTI prevention. The focus of all activities should take place on road users' safety.</p

Widespread Horizontal Gene Transfer from Circular Single-stranded DNA Viruses to Eukaryotic Genomes

<p>Abstract</p> <p>Background</p> <p>In addition to vertical transmission, organisms can also acquire genes from other distantly related species or from their extra-chromosomal elements (plasmids and viruses) via horizontal gene transfer (HGT). It has been suggested that phages represent substantial forces in prokaryotic evolution. In eukaryotes, retroviruses, which can integrate into host genome as an obligate step in their replication strategy, comprise approximately 8% of the human genome. Unlike retroviruses, few members of other virus families are known to transfer genes to host genomes.</p> <p>Results</p> <p>Here we performed a systematic search for sequences related to circular single-stranded DNA (ssDNA) viruses in publicly available eukaryotic genome databases followed by comprehensive phylogenetic analysis. We conclude that the replication initiation protein (Rep)-related sequences of geminiviruses, nanoviruses and circoviruses have been frequently transferred to a broad range of eukaryotic species, including plants, fungi, animals and protists. Some of the transferred viral genes were conserved and expressed, suggesting that these genes have been coopted to assume cellular functions in the host genomes. We also identified geminivirus-like and parvovirus-like transposable elements in genomes of fungi and lower animals, respectively, and thereby provide direct evidence that eukaryotic transposons could derive from ssDNA viruses.</p> <p>Conclusions</p> <p>Our discovery extends the host range of circular ssDNA viruses and sheds light on the origin and evolution of these viruses. It also suggests that ssDNA viruses act as an unforeseen source of genetic innovation in their hosts.</p

NO Dioxygenase Activity in Hemoglobins Is Ubiquitous In Vitro, but Limited by Reduction In Vivo

Genomics has produced hundreds of new hemoglobin sequences with examples in nearly every living organism. Structural and biochemical characterizations of many recombinant proteins reveal reactions, like oxygen binding and NO dioxygenation, that appear general to the hemoglobin superfamily regardless of whether they are related to physiological function. Despite considerable attention to “hexacoordinate” hemoglobins, which are found in nearly every plant and animal, no clear physiological role(s) has been assigned to them in any species. One popular and relevant hypothesis for their function is protection against NO. Here we have tested a comprehensive representation of hexacoordinate hemoglobins from plants (rice hemoglobin), animals (neuroglobin and cytoglobin), and bacteria (Synechocystis hemoglobin) for their abilities to scavenge NO compared to myoglobin. Our experiments include in vitro comparisons of NO dioxygenation, ferric NO binding, NO-induced reduction, NO scavenging with an artificial reduction system, and the ability to substitute for a known NO scavenger (flavohemoglobin) in E. coli. We conclude that none of these tests reveal any distinguishing predisposition toward a role in NO scavenging for the hxHbs, but that any hemoglobin could likely serve this role in the presence of a mechanism for heme iron re-reduction. Hence, future research to test the role of Hbs in NO scavenging would benefit more from the identification of cognate reductases than from in vitro analysis of NO and O2 binding

A two-dimensional gel electrophoretic study of proteins in tumours of the lung and breast

Defining differences in gene expression between benign and malignant cells is an important aspectof cancer research, and has been the object of a large number of studies. Such studies are aimed atdefining tumour markers to be used in prognostic studies, and to understand mechanisms leading touncontrolled growth and tumour metastasis. In this thesis two-dimensional polyacrylamide gelelectrophoresis (2-DE) of polypeptides was used to document patterns of gene expression in humanbreast and lung carcinomas. Applying 2-DE to the analysis of human material is not trivial, sinceserum proteins and extracellular matrix components frequently obscure the patterns and impair gelquality. Techniques therefore had to be established for the preparation of clinical tumour material for2-De. These methods allowed the characterisation of polypeptide expression in breast and lungtumours. The levels of a number of polypeptides with known identity were determined in carcinomas. Wefound that the expression of high molecular weight tropomyosin polypeptides (TMI-3) were down-regulated in both lung and breast tumours. The expression of cytokeratins 8 and 18 were lower inbreast carcinomas compared to fibroadenomas. This result should be considered when interpretingexperiments where cytokeratins are used as markers for breast cancer cells (gating cells for flowcytometry, staining for carcinoma cells in bone marrow). The levels of some members of the heatshock protein family were found to be elevated in high malignant carcinomas. A number of potential polypeptide markers were detected in lung carcinomas. One of thesemarkers (TA02) was studied in some detail. The overall pattern of polypeptide expression was studiedwith the aid of the 2-DE PDQUEST software. By pairwise comparisons of 2-DE patterns derivedfrom different tumours, we concluded that malignant breast carcinomas are highly heterogeneouswith respect to their patterns of gene expression. In contrast, polypeptide profiles from different partsof a tumour or from a tumour and its metastasis showed large similarities. These studies that 2-DEoffers an alternative to nucleic acid based techniques in studies show gene expression in humantumours .Key Words:Two-dimensional gel electrophoresis, protein analysis, sample preparation, mammary tumour, lungcarcinomas, heterogeneity, diagnostic markers

Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours

Background: Midgut carcinoid tumours often present with widespread disease making curative surgery impossible. Medical treatment therefore plays a major role in the treatment of these patients. Methods: In this prospective randomized study, the effect of interferon (IFN) alpha on survival and risk of tumour progression was evaluated in 68 patients with midgut carcinoid tumours metastatic to the liver. All patients had undergone primary surgical treatment and hepatic arterial embolization of liver metastases before randomization. Patients were randomized to treatment with either octreotide alone (n = 35) or octreotide in combination with IFN-alpha (n = 33). Results: Forty-one of the 68 patients died during a follow-up period of 33-120 months, equivalent to a 5-year survival rate of 46.5 per cent. There was no significant difference in survival between patients treated with octreotide alone (5-year survival rate 36.6 per cent) and those given octreotide in combination with IFN-alpha (56.8 per cent). However, patients treated with IFN-alpha had a significantly reduced risk of tumour progression during follow-up (P = 0.008). Conclusion: Addition of IFN-alpha to octreotide may retard tumour growth in patients with midgut carcinoid tumours

Super-resolution microscopy can identify specific protein distribution patterns in platelets incubated with cancer cells

Protein contents in platelets are frequently changed upon tumor development and metastasis. However, how cancer cells can influence protein-selective redistribution and release within platelets, thereby promoting tumor development, remains largely elusive. With fluorescence-based super-resolution stimulated emission depletion (STED) imaging we reveal how specific proteins, implicated in tumor progression and metastasis, re-distribute within platelets, when subject to soluble activators (thrombin, adenosine diphosphate and thromboxane A2), and when incubated with cancer (MCF-7, MDA-MB-231, EFO21) or non-cancer cells (184A1, MCF10A). Upon cancer cell incubation, the cell-adhesion protein P-selectin was found to re-distribute into circular nano-structures, consistent with accumulation into the membrane of protein-storing alpha-granules within the platelets. These changes were to a significantly lesser extent, if at all, found in platelets incubated with normal cells, or in platelets subject to soluble platelet activators. From these patterns, we developed a classification procedure, whereby platelets exposed to cancer cells, to non-cancer cells, soluble activators, as well as non-activated platelets all could be identified in an automatic, objective manner. We demonstrate that STED imaging, in contrast to electron and confocal microscopy, has the necessary spatial resolution and labelling efficiency to identify protein distribution patterns in platelets and can resolve how they specifically change upon different activations. Combined with image analyses of specific protein distribution patterns within the platelets, STED imaging can thus have a role in future platelet-based cancer diagnostics and therapeutic monitoring. The presented approach can also bring further clarity into fundamental mechanisms for cancer cell-platelet interactions, and into non-contact cell-to-cell interactions in general

PCI Versus CABG in Patients With Type 1 Diabetes and Multivessel Disease

BACKGROUND It is unknown if coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) may offer a survival benefit in patients with type 1 diabetes (T1D) in need of multivessel revascularization. OBJECTIVES This study sought to determine if patients with T1D and multivessel disease may benefit from CABG compared with PCI. METHODS In an observational cohort study, the authors included all patients with T1D who underwent a first multivessel revascularization in Sweden from 1995 to 2013. The authors used the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) register, the Swedish National Diabetes Register, and the Swedish National Patient Register to retrieve information about patient characteristics and outcomes. They estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) for all-cause and coronary heart disease mortality, myocardial infarction, repeat revascularization, stroke, and heart failure using inverse probability of treatment weighting based on propensity scores. RESULTS In total, 683 patients whounderwent CABGand 1,863 patientswho underwent PCI were included. During a mean follow-up of 10.6 years, 53% of patients in the CABG group and 45% in the PCI group died. PCI, compared with CABG, was associated with a similar risk of all-cause mortality (HR: 1.14; 95% CI: 0.99 to 1.32), but higher risks of death from coronary heart disease (HR: 1.45; 95% CI: 1.21 to 1.74), myocardial infarction (HR: 1.47; 95% CI: 1.23 to 1.78), and repeat revascularization (HR: 5.64; 95% CI: 4.67 to 6.82). No differences in risks of stroke or heart failure were found. CONCLUSIONS Notwithstanding the inclusion of patients with T1D who might not have been able to undergo CABG in the PCI group we found that PCI, compared with CABG, was associated with higher rates and risks of coronary heart disease mortality, myocardial infarction, and repeat revascularizations. Our findings indicate that CABG may be the preferred strategy in patients with T1D in need of multivessel revascularization. (J Am Coll Cardiol 2017; 70: 1441-51