Update on the pathogenic potential and treatment options for Blastocystis sp

Although Blastocystis is one of the most common enteric parasites, there is still much controversy surrounding the pathogenicity and potential treatment options for this parasite. In this review we look at the evidence supporting Blastocystis as an intestinal pathogen as shown by numerous case studies and several in vivo studies and the evidence against. We describe the chronic nature of some infections and show the role of Blastocystis in immunocompromised patients and the relationship between irritable bowel syndrome and Blastocystis infection. There have been several studies that have suggested that pathogenicity may be subtype related. Metronidazole is the most widely accepted treatment for Blastocystis but several cases of treatment failure and resistance have been described. Other treatment options which have been suggested include paromomycin and trimethroprim- sulfamethoxazole. © 2014 Roberts et al.; licensee BioMed Central Ltd

Mechanistic Insights into Aging, Cell-Cycle Progression, and Stress Response

The longevity of an organism depends on the health of its cells. Throughout life cells are exposed to numerous intrinsic and extrinsic stresses, such as free radicals, generated through mitochondrial electron transport, and ultraviolet irradiation. The cell has evolved numerous mechanisms to scavenge free radicals and repair damage induced by these insults. One mechanism employed by the yeast Saccharomyces cerevisiae to combat stress utilizes the Anaphase Promoting Complex (APC), an essential multi-subunit ubiquitin-protein ligase structurally and functionally conserved from yeast to humans that controls progression through mitosis and G1. We have observed that yeast cells expressing compromised APC subunits are sensitive to multiple stresses and have shorter replicative and chronological lifespans. In a pathway that runs parallel to that regulated by the APC, members of the Forkhead box (Fox) transcription factor family also regulate stress responses. The yeast Fox orthologs Fkh1 and Fkh2 appear to drive the transcription of stress response factors and slow early G1 progression, while the APC seems to regulate chromatin structure, chromosome segregation, and resetting of the transcriptome in early G1. In contrast, under non-stress conditions, the Fkhs play a complex role in cell-cycle progression, partially through activation of the APC. Direct and indirect interactions between the APC and the yeast Fkhs appear to be pivotal for lifespan determination. Here we explore the potential for these interactions to be evolutionarily conserved as a mechanism to balance cell-cycle regulation with stress responses

Treatment failure in patients with chronic Blastocystis infection

This article reports long-term infection and treatment failure in 18 symptomatic individuals infected with Blastocystis spp. Patients were initially treated with either metronidazole, iodoquinol or triple combination therapy consisting of nitazoxanide, furazolidone and secnidazole. Following treatment, resolution of clinical symptoms did not occur and follow-up testing revealed ongoing infection with the same subtype. Patients then underwent secondary treatment with a variety of antimicrobial agents but remained symptomatic with Blastocystis spp. still present in faeces. Sequencing of the SSU rDNA was completed on all isolates and four subtypes were identified in this group: ST1, ST3, ST4 and ST5. This study highlights the lack of efficacy of several commonly used antimicrobial regimens in the treatment of Blastocystis and the chronic nature of some infections. It also demonstrates the need for further research into treatment options for Blastocystis infection. © 2014 SGM

In vitro antimicrobial susceptibility patterns of Blastocystis

Copyright © 2015, American Society for Microbiology. All Rights Reserved. Blastocystis is the most common human enteric protist with controversial clinical significance. Metronidazole is considered a first-line treatment for Blastocystis infection; however, there has been increasing evidence for the lack of efficacy of this treatment. Treatment failure has been reported in several clinical cases, and recent in vitro studies have suggested the occurrence of metronidazole-resistant strains. In this study, we tested 12 Blastocystis isolates from 4 common Blastocystis subtypes (ST1, ST3, ST4, and ST8) against 12 commonly used antimicrobials (metronidazole, paromomycin, ornidazole, albendazole, ivermectin, trimethoprim-sulfamethoxazole [TMP-SMX], furazolidone, nitazoxanide, secnidazole, fluconazole, nystatin, and itraconazole) at 10 different concentrations in vitro. It was found that each subtype showed little sensitivity to the commonly used metronidazole, paromomycin, and triple therapy (furazolidone, nitazoxanide, and secnidazole). This study highlights the efficacy of other potential drug treatments, including trimethoprim-sulfamethoxazole and ivermectin, and suggests that current treatment regimens be revised

Fatigue reliability method with in-service inspections

The first reliability method (FORM) has traditionally been applied in a fatigue reliability setting to one inspection interval at a time, so that the random distribution of crack lengths must be recharacterized following each inspection. The FORM presented here allow each analysis to span several inspection periods without explicit characterization of the crack length distribution upon each inspection. The method thereby preserves the attractive feature of FORM in that relatively few realizations in the random variable space need to be considered. Examples are given which show that the present methodology gives estimates which are in good agreement with Monte Carlo simulations and is efficient even for complex components

Activity of benzimidazoles against Dientamoeba fragilis (Trichomonadida, Monocercomonadidae) in vitro and correlation of beta-tubulin sequences as an indicator of resistance

Recently, Dientamoeba fragilis has emerged as a significant and common enteropathogen. The majority of patients with dientamoebiasis present with gastrointestinal complaints and chronic symptoms are common. Numerous studies have successfully demonstrated parasite clearance, coupled with complete resolution of clinical symptoms following treatment with various antiparasitic compounds. Despite this, there is very little in vitro susceptibility data available for the organism. Benzimidazoles are a class of antiparasitic drugs that are commonly used for the treatment of protozoan and helminthic infections. Susceptibility testing was undertaken on four D. fragilis clinical isolates against the following benzimidazoles: albendazole, flubendazole, mebendazole, nocodazole, triclabendazole and thiabendazole. The activities of the antiprotozoal compounds at concentrations ranging from 2 μg/mL to 500 μg/mL were determined via cell counts of D. fragilis grown in xenic culture. All tested drugs showed no efficacy. The beta-tubulin transcript was sequenced from two of the D. fragilis isolates and amino acid sequences predicted a susceptibility to benzimidazoles. This is the first study to report susceptibility profiles for benzimidazoles against D. fragilis, all of which were not active against the organism. This study also found that beta-tubulin sequences cannot be used as a reliable marker for resistance of benzimidazoles in D. fragilis. © D. Stark et al., published by EDP Sciences, 2014

Why We Read Wikipedia

Wikipedia is one of the most popular sites on the Web, with millions of users relying on it to satisfy a broad range of information needs every day. Although it is crucial to understand what exactly these needs are in order to be able to meet them, little is currently known about why users visit Wikipedia. The goal of this paper is to fill this gap by combining a survey of Wikipedia readers with a log-based analysis of user activity. Based on an initial series of user surveys, we build a taxonomy of Wikipedia use cases along several dimensions, capturing users' motivations to visit Wikipedia, the depth of knowledge they are seeking, and their knowledge of the topic of interest prior to visiting Wikipedia. Then, we quantify the prevalence of these use cases via a large-scale user survey conducted on live Wikipedia with almost 30,000 responses. Our analyses highlight the variety of factors driving users to Wikipedia, such as current events, media coverage of a topic, personal curiosity, work or school assignments, or boredom. Finally, we match survey responses to the respondents' digital traces in Wikipedia's server logs, enabling the discovery of behavioral patterns associated with specific use cases. For instance, we observe long and fast-paced page sequences across topics for users who are bored or exploring randomly, whereas those using Wikipedia for work or school spend more time on individual articles focused on topics such as science. Our findings advance our understanding of reader motivations and behavior on Wikipedia and can have implications for developers aiming to improve Wikipedia's user experience, editors striving to cater to their readers' needs, third-party services (such as search engines) providing access to Wikipedia content, and researchers aiming to build tools such as recommendation engines.Comment: Published in WWW'17; v2 fixes caption of Table

An avatar-based system for identifying individuals likely to develop dementia

This paper presents work on developing an automatic dementia screening test based on patients’ ability to interact and communicate — a highly cognitively demanding process where early signs of dementia can often be detected. Such a test would help general practitioners, with no specialist knowledge, make better diagnostic decisions as current tests lack specificity and sensitivity. We investigate the feasibility of basing the test on conversations between a ‘talking head’ (avatar) and a patient and we present a system for analysing such conversations for signs of dementia in the patient’s speech and language. Previously we proposed a semi-automatic system that transcribed conversations between patients and neurologists and extracted conversation analysis style features in order to differentiate between patients with progressive neurodegenerative dementia (ND) and functional memory disorders (FMD). Determining who talks when in the conversations was performed manually. In this study, we investigate a fully automatic system including speaker diarisation, and the use of additional acoustic and lexical features. Initial results from a pilot study are presented which shows that the avatar conversations can successfully classify ND/FMD with around 91% accuracy, which is in line with previous results for conversations that were led by a neurologist

Toward the Automation of Diagnostic Conversation Analysis in Patients with Memory Complaints.

BACKGROUND: The early diagnosis of dementia is of great clinical and social importance. A recent study using the qualitative methodology of conversation analysis (CA) demonstrated that language and communication problems are evident during interactions between patients and neurologists, and that interactional observations can be used to differentiate between cognitive difficulties due to neurodegenerative disorders (ND) or functional memory disorders (FMD). OBJECTIVE: This study explores whether the differential diagnostic analysis of doctor-patient interactions in a memory clinic can be automated. METHODS: Verbatim transcripts of conversations between neurologists and patients initially presenting with memory problems to a specialist clinic were produced manually (15 with FMD, and 15 with ND). A range of automatically detectable features focusing on acoustic, lexical, semantic, and visual information contained in the transcripts were defined aiming to replicate the diagnostic qualitative observations. The features were used to train a set of five machine learning classifiers to distinguish between ND and FMD. RESULTS: The mean rate of correct classification between ND and FMD was 93% ranging from 97% by the Perceptron classifier to 90% by the Random Forest classifier.Using only the ten best features, the mean correct classification score increased to 95%. CONCLUSION: This pilot study provides proof-of-principle that a machine learning approach to analyzing transcripts of interactions between neurologists and patients describing memory problems can distinguish people with neurodegenerative dementia from people with FMD

A new technique for elucidating β\beta-decay schemes which involve daughter nuclei with very low energy excited states

A new technique of elucidating $\beta$-decay schemes of isotopes with large density of states at low excitation energies has been developed, in which a Broad Energy Germanium (BEGe) detector is used in conjunction with coaxial hyper-pure germanium detectors. The power of this technique has been demonstrated on the example of 183Hg decay. Mass-separated samples of 183Hg were produced by a deposition of the low-energy radioactive-ion beam delivered by the ISOLDE facility at CERN. The excellent energy resolution of the BEGe detector allowed $\gamma$ rays energies to be determined with a precision of a few tens of electronvolts, which was sufficient for the analysis of the Rydberg-Ritz combinations in the level scheme. The timestamped structure of the data was used for unambiguous separation of $\gamma$ rays arising from the decay of 183Hg from those due to the daughter decays