1,059 research outputs found

    The Primary Pretenders

    Full text link
    We call a composite number q such that there exists a positive integer b with b^p == b (mod q) a prime pretender to base b. The least prime pretender to base b is the primary pretender q_b. It is shown that there are only 132 distinct primary pretenders, and that q_b is a periodic function of b whose period is the 122-digit number 19568584333460072587245340037736278982017213829337604336734362- 294738647777395483196097971852999259921329236506842360439300.Comment: 7 page

    Development and application of -omics and bioinformatics approaches for a deeper understanding of infectious diseases systems

    Get PDF
    Background: Research in infectious diseases underwent a revolution with the uprising of Omics approaches, including, but not limited to, genomics, metagenomics and metatranscriptomics. In fact, there are several examples where Omics approaches showed their potential to tackle different challenges related to the versatile nature of infectious diseases by promoting “studies of one” to “system-wide studies”. In the frame of this PhD programme, we focused on the development and validation of Omics approaches and bioinformatics workflow aiming at tackling mainly diagnostics but also to some extents the treatment of infectious diseases. The four applications presented in this thesis had following specific objectives; (i) to develop and validate a bioinformatics approach aiming at selecting high quality markers among a large amount of complete genomic sequences; (ii) to characterise the viral metagenome of a plant to determine aetiology of a disease that could not be identified and/or fully characterised with other tools; (iii) to assess the potential of metagenomics in the field of personalised medicine and compare its diagnostics accuracy with validated diagnostics tools; and (iv) to make a system-wide survey of microbial populations and estimate its potential to cause harm to humans. Methods: Methodology was specific for each application but as a general rule, we only used published bioinformatics tools that have been used and validated in other studies. This includes, but is not limited to, the BLAST algorithm for the comparison of sequences to various databases and the MIRA assembler to assemble the metagenomics datasets obtained within the different projects. Results: For clarity, the results are summarised by project, corresponding to the different applications investigated during this PhD. Project (i): The developed bioinformatics workflow allowed the selection of highly conserved and specific molecular markers among various viral species with inputs of up to several hundred complete genomic sequences. The quality of the selected markers was successfully validated using several types of molecular assays including real-time PCR, LAMP and Sanger sequencing. Project (ii): We were able to find the aetiology of a grapevine plant presenting leafroll symptoms. A new virus, named Grapevine Leafroll-associated virus 4 Ob, with a thirteen kilobases genome was found in the viral metagenome. Other viruses that were co-identified in the virome were known to be asymptomatic viruses for grapevine, and with the help of additional serological experiences, we were able to confirm that this GLRaV-4 Ob was the causative agent of the Leafroll symptoms. Project (iii): The gut pathobiomes from four patients presenting persistent digestive disorders were fully characterised using a metagenomics approach. Comparison of validated diagnostics tools with this approach showed that the diagnostics rate was in favour of the latter for the detection of bacterial and helminths pathogens and in favour of the validated tools for the detection of viruses and protozoa. Using the same datasets, but compared to a different database, we were also able to screen the stool samples for antimicrobial resistance genes and retrieve potential resistance genes that might interfere with the treatment of these patients. Project (iv): In this project, a system-wide assessment of the microbial communities of the wastewater treatment system was done using a metagenomics approach. We were able to demonstrate how closely the genetic diversity of Escherichia coli and the overall genetic diversity were linked in this environment. We were also able to map the repartition of different pathogenic classes, including bacteria, helminths, intestinal protozoa and viruses as well as to show if and how human waterborne pathogens spread throughout this ecosystem. Conclusion: Omics offer new strategies of how challenges, mainly related to the vast diversity within the research area of infectious diseases, can be tackled. Meta-analyses, like metagenomics or metatranscriptomics are the applications that benefited most from the use of Next-Generation Sequencing technologies, and they now allow system-wide studies where previous studies were only focusing on one parameter (one microbe or one specific gene for instance). However, these Omics approaches have their limitations, mainly due to the bioinformatics challenges they give rise to. As a general conclusion, it is foreseeable that, because of the increased amount of results they generate, Omics approaches, once matured, will be more widely used and will replace standard approaches in the field of infectious diseases

    Outcome of renal grafts after simultaneous kidney/ pancreas transplantation

    Get PDF
    Nineteen patients with endstage renal failure due to Type 1 (insulin-dependent) diabetes mellitus received simultaneous pancreas/kidney transplants using bladder drainage technique. Another group of 25 Type 1 diabetic patients received pancreas/kidney transplants by the duct occlusion technique. We observed a higher incidence of rejection episodes in the patients of the bladder drainage group than those in the duct occlusion group, 14 of 19 patients (74%) vs 7 of 25 (28%) respectively. Anti CD3 antibodies (Orthoclone, OKT3) as a part of induction treatment was used more often in the bladder drainage group (58%) than in the control group (20%)

    Detailing the effects of polypharmacy in psychiatry: longitudinal study of 320 patients hospitalized for depression or schizophrenia

    Get PDF
    Current treatment standards in psychiatry are oriented towards polypharmacy, that is, patients receive combinations of several antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, antihistamines, and anticholinergics, along with other somatic treatments. In tandem with the beneficial effects of psychopharmacological drug treatment, patients experience significant adverse reactions which appear to have become more frequent and more severe with the rise of ubiquitous polypharmacy. In this study, we aimed to assess today's acute inpatient treatment of depressive and schizophrenic disorders with focus on therapeutic strategies, medications, adverse side effects, time course of recovery, and efficacy of treatments. Of particular interest was the weighing of the benefits and drawbacks of polypharmacy regimens. We recruited a total of 320 patients hospitalized at three residential mental health treatment centers with a diagnosis of either schizophrenic (ICD-10: "F2x.x"; n = 94; "F2 patients") or depressive disorders (ICD-10: "F3x.x"; n = 226; "F3 patients"). The study protocol included (1) assessment of previous history by means of the SADS Syndrome Check List SSCL-16 (lifetime version); (2) repeated measurements over 5 weeks assessing the time course of improvement by the Hamilton Depression Scale HAM-D and the Positive and Negative Syndrome Scale PANSS, along with medications and adverse side effects through the Medication and Side Effects Inventory MEDIS; and (3) the collection of blood samples from which DNA and serum were extracted. Polypharmacy was by far the most common treatment regimen (85%) in this study. On average, patients received 4.50 ± 2.68 medications, consisting of 3.30 ± 1.84 psychotropic drugs, plus 0.79 ± 1.13 medications that alleviate adverse side effects, plus 0.41 ± 0.89 other somatic medications. The treating psychiatrists appeared to be the main determining factor in this context, while «previous history» and «severity at baseline» played a minor role, if at all. Adverse drug reactions were found to be an inherent component of polypharmacy and tended to have a 2-3 times higher incidence compared to monotherapy. Severe adverse reactions could not be attributed to a particular drug or drug combination. Rather, the empirical data suggested that severe side effects can be triggered by virtually all combinations of drugs, provided patients have a respective vulnerability. In terms of efficacy, there were no advantages of polypharmacy over monotherapy. The results of this study underlined the fact that polypharmacy regimens are not equally suited for every patient. Specifically, such regimens appeared to have a negative impact on treatment outcome and to obfuscate the "natural" time course of recovery through a multitude of interfering factors. Evidence clearly speaks against starting just every therapeutic intervention in psychiatry with a combination of psychopharmaceuticals. We think that it is time for psychiatry to reconsider its treatment strategies, which are far too one-sidedly fixated on psychopharmacology and pay far too little attention to alternative approaches, especially in mild cases where psychotherapy without concurrent medication should still be an option. Also, regular exercises and sports can definitely be an effective therapeutic means in a considerable number of cases. General practitioners (GPs) are particularly in demand here

    Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome

    Get PDF
    Schistosomiasis is a neglected tropical disease burdening millions of people. One drug, praziquantel, is currently used for treatment and control. Clinically relevant drug resistance has not yet been described, but there is considerable heterogeneity in treatment outcomes, ranging from cure to only moderate egg reduction rates. The objectives of this study are to investigate potential worm-induced dysbacteriosis of the gut microbiota and to assess whether a specific microbiome profile could influence praziquantel response.; Using V3 and V4 regions of 16S rRNA genes, we screened the gut microbiota of 34 Schistosoma mansoni infected and uninfected children from CĂ´te d'Ivoire. From each infected child one pre-treatment, one 24-hour and one 21-day follow-up sample after administering 60 mg/kg praziquantel or placebo, were collected.; Overall taxonomic profiling and diversity indicators were found to be close to a "healthy" gut structure in all children. Slight overall compositional changes were observed between S. mansoni-infected and non-infected children. Praziquantel treatment was not linked to a major shift in the gut taxonomic profiles, thus reinforcing the good safety profile of the drug by ruling out off-targets effects on the gut microbes.16S rRNA gene of the Fusobacteriales order was significantly more abundant in cured individuals, both at baseline and 24 hours post-treatment. A real-time qPCR confirmed the over-abundance of Fusobacterium spp. in cured children. Fusobacterium spp. abundance could also be correlated with treatment induced S. mansoni egg-reduction.; Our study suggests that neither a S. mansoni infection nor praziquantel administration triggers a significant effect on the microbial composition and that a higher abundance of Fusobacterium spp., before treatment, is associated with higher efficacy of praziquantel in the treatment of S. mansoni infections.; International Standard Randomised Controlled Trial, number ISRCTN15280205
    • …
    corecore