Use of Comparative Genomics-Based Markers for Discrimination of Host Specificity in <i>Fusarium oxysporum</i>

The polyphyletic nature of many formae speciales of Fusarium oxysporum prevents molecular identification of newly encountered strains based on conserved, vertically inherited genes. Alternative molecular detection methods that could replace labor- and time-intensive disease assays are therefore highly desired. Effectors are functional elements in the pathogen-host interaction and have been found to show very limited sequence diversity between strains of the same forma specialis, which makes them potential markers for host-specific pathogenicity. We therefore compared candidate effector genes extracted from 60 existing and 22 newly generated genome assemblies, specifically targeting strains affecting cucurbit plant species. Based on these candidate effector genes, a total of 18 PCR primer pairs were designed to discriminate between each of the seven Cucurbitaceae-affecting formae speciales. When tested on a collection of strains encompassing different clonal lineages of these formae speciales, nonpathogenic strains, and strains of other formae speciales, they allowed clear recognition of the host range of each evaluated strain. Within Fusarium oxysporum f. sp. melonis more genetic variability exists than anticipated, resulting in three F. oxysporum f. sp. melonis marker patterns that partially overlapped with the cucurbit-infecting Fusarium oxysporum f. sp. cucumerinum, Fusarium oxysporum f. sp. niveum, Fusarium oxysporum f. sp. momordicae, and/or Fusarium oxysporum f. sp. lagenariae For F. oxysporum f. sp. niveum, a multiplex TaqMan assay was evaluated and was shown to allow quantitative and specific detection of template DNA quantities as low as 2.5 pg. These results provide ready-to-use marker sequences for the mentioned F. oxysporum pathogens. Additionally, the method can be applied to find markers distinguishing other host-specific forms of F. oxysporum IMPORTANCE Pathogenic strains of Fusarium oxysporum are differentiated into formae speciales based on their host range, which is normally restricted to only one or a few plant species. However, horizontal gene transfer between strains in the species complex has resulted in a polyphyletic origin of host specificity in many of these formae speciales. This hinders accurate and rapid pathogen detection through molecular methods. In our research, we compared the genomes of 88 strains of F. oxysporum with each other, specifically targeting virulence-related genes that are typically highly similar within each forma specialis. Using this approach, we identified marker sequences that allow the discrimination of F. oxysporum strains affecting various cucurbit plant species through different PCR-based methods

The prognostic value of the hamstring outcome score to predict the risk of hamstring injuries

OBJECTIVES: Hamstring injuries are common among soccer players. The hamstring outcome score (HaOS) might be useful to identify amateur players at risk of hamstring injury. Therefore the aims of this study were: To determine the association between the HaOS and prior and new hamstring injuries in amateur soccer players, and to determine the prognostic value of the HaOS for identifying players with or without previous hamstring injuries at risk of future injury. DESIGN: Cohort study. METHODS: HaOS scores and information about previous injuries were collected at baseline and new injuries were prospectively registered during a cluster-randomized controlled trial involving 400 amateur soccer players. Analysis of variance and t-tests were used to determine the association between the HaOS and previous and new hamstring injury, respectively. Logistic regression analysis indicated the prognostic value of the HaOS for predicting new hamstring injuries. RESULTS: Analysis of data of 356 players indicated that lower HaOS scores were associated with more previous hamstring injuries (F=17.4; p=0.000) and that players with lower HaOS scores sustained more new hamstring injuries (T=3.59, df=67.23, p=0.001). With a conventional HaOS score cut-off of 80%, logistic regression models yielded a probability of hamstring injuries of 11%, 18%, and 28% for players with 0,1, or 2 hamstring injuries in the previous season, respectively. CONCLUSIONS: The HaOS is associated with previous and future hamstring injury and might be a useful tool to provide players with insight into their risk of sustaining a new hamstring injury risk when used in combination with previous injuries

Case finding of mild cognitive impairment and dementia and subsequent care; results of a cluster RCT in primary care

Purpose Despite a call for earlier diagnosis of dementia, the diagnostic yield of case finding and its impact on the mental health of patients and relatives are unclear. This study assessed the effect of a two-component intervention of case finding and subsequent care on these outcomes. Methods In a cluster RCT we assessed whether education of family physicians (FPs; trial stage 1) resulted in more mild cognitive impairment (MCI) and dementia diagnoses among older persons in whom FPs suspected cognitive decline and whether case finding by a practice nurse and the FP (trial stage 2) added to this number of diagnoses. In addition, we assessed mental health effects of case finding and subsequent care (trial stage 2). FPs of 15 primary care practices (PCPs = clusters) judged the cognitive status of all persons ≤ 65 years. The primary outcome, new MCI and dementia diagnoses by FPs after 12 months as indicated on a list, was assessed among all persons in whom FPs suspected cognitive impairment but without a formal diagnosis of dementia. The secondary outcome, mental health of patients and their relatives, was assessed among persons consenting to participate in trial stage 2. Trial stage 1 consisted of either intervention component 1: training FPs to diagnose MCI and dementia, or control: no training. Trial stage 2 consisted of either intervention component 2: case finding of MCI and dementia and care by a trained nurse and the FP, or control: care as usual. Results Seven PCPs were randomized to the intervention; eight to the control condition. MCI or dementia was diagnosed in 42.3 (138/326) of persons in the intervention, and in 30.5 (98/321) in the control group (estimated difference GEE: 10.8, OR: 1.51, 95-CI 0.60-3.76). Among patients and relatives who consented to stage 2 of the trial (n = 145; 25), there were no differences in mental health between the intervention and control group. Conclusions We found a non-significant increase in the number of new MCI diagnoses. As we cannot exclude a clinically relevant effect, a larger study is warranted to replicate ours. Trial Registration Nederlands Trial Register NTR3389 © 2016 van den Dungen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The effect of metformin on cardiovascular risk profile in patients without diabetes presenting with acute myocardial infarction:data from the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) trial

Objective: In patients with diabetes mellitus, metformin treatment is associated with reduced mortality and attenuation of cardiovascular risk. As a subanalysis of the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) study, we evaluated whether metformin treatment in patients with ST-segment elevation myocardial infarction (STEMI) without diabetes improves the cardiovascular risk profile. Methods: A total of 379 patients, without known diabetes, presenting with STEMI were randomly allocated to receive metformin 500 mg twice daily or placebo for 4 months. Results: After 4 months, the cardiovascular risk profile of patients receiving metformin (n= 172) was improved compared with placebo (n= 174); glycated hemoglobin (5.83% (95% CI 5.79% to 5.87%) vs 5.89% (95% CI 5.85% to 5.92%); 40.2 mmol/mol (95% CI 39.8 to 40.6) vs 40.9 mmol/mol (40.4 to 41.2), p= 0.049); total cholesterol (3.85 mmol/L (95% CI 3.73 to 3.97) vs 4.02 mmol/L (95% CI 3.90 to 4.14), p= 0.045); low-density lipoprotein cholesterol (2.10 mmol/L (95% CI 1.99 to 2.20) vs 2.3 mmol/L (95% CI 2.20 to 2.40), p= 0.007); body weight (83.8 kg (95% CI 83.0 to 84.7) vs 85.2 kg (95% CI 84.4 to 86.1), p= 0.024); body mass index (26.8 kg/m(2) (95% CI 26.5 to 27.0) vs 27.2 kg/m(2) (95% CI 27.0 to 27.5), p= 0.014). Levels of fasting glucose, postchallenge glucose, insulin, high-density lipoprotein cholesterol, and blood pressure were similar in both groups. Conclusions: Among patients with STEMI without diabetes, treatment with metformin for 4 months resulted in a modest improvement of the cardiovascular risk profile compared with placebo

Asymptomatic lipofibroadenoma in a 17-year-old male:a case report and literature review of a rare entity

Background: The most common thymic tumours, thymomas, are derived from thymic epithelium and are generally low-grade neoplasm. Frankly malignant tumours, thymic carcinomas are rarer still. Exceedingly rare thymic tumours contain a mesenchymal tissue component such as fibrous connective tissue and/or mature fat. Lipofibroadenoma (LFA) is a very rare mixed epithelial-mesenchymal thymic tumour, included in the category of thymic epithelial tumors. LFA in addition to a mature adipocytic component, contains variable epithelial and mesenchymal tissue components. Owing to the presence of an epithelial component in LFA, this entity, in contrast to thymolipoma, is included in the World Health Organization (WHO) category of thymic epithelial neoplasm. Currently only 12 LFA cases have been described. The 12 previously reported cases all behaved in a benign fashion, although four cases were associated with a conventional type of thymoma. We here present a new, 13th, case of LFA. Case Description: The LFA was discovered incidentally in a previously healthy 17-year-old male after investigations for suspected pneumonia. On imaging a mass was discovered in the anterior mediastinum which was subsequently surgically removed. The resected tumour was extensively investigated, including the first instance of full molecular analysis of this rare entity and all available literature on LFA was sourced to provide a comprehensive overview. The histology of this LFA was similar to previously described cases. No gene mutations or rearrangements were identified. The patient made an uneventful recovery and after 13 months of follow-up remained well. Conclusions: An additional, 13th case of LFA is presented. Based on the available literature it appears that LFA may be considered a benign composite thymic tumour, although the combination of an additional conventional thymoma component may warrant closer follow-up.</p

Swift Observations of MAXI J1659-152: A Compact Binary with a Black Hole Accretor

We report on the detection and follow-up high cadence monitoring observations of MAXI J1659-152, a bright Galactic X-ray binary transient with a likely black-hole accretor, by Swift over a 27 day period after its initial outburst detection. MAXI J1659-152 was discovered almost simultaneously by Swift and MAXI on 2010 Sept 25, and was monitored intensively from the early stages of the outburst through the rise to a brightness of ~0.5 Crab by the Swift XRT, UVOT, and BAT. We present temporal and spectral analysis of the Swift observations. The broadband light-curves show variability characteristic of black-hole candidate transients. We present the evolution of thermal and non-thermal components of the 0.5-150 keV combined X-ray spectra during the outburst. MAXI J1659-152 displays accretion state changes typically associated with black-hole binaries, transitioning from its initial detection in the Hard State, to the Steep Power-Law State, followed by a slow evolution towards the Thermal State, signified by an increasingly dominant thermal component associated with the accretion disk, although this state change did not complete before Swift observations ended. We observe an anti-correlation between the increasing temperature and decreasing radius of the inner edge of the accretion disk, suggesting that the inner edge of the accretion disk in-falls towards the black-hole as the disk temperature increases. We observed significant evolution in the absorption column during the initial rise of the outburst, with the absorption almost doubling, suggestive of the presence of an evolving wind from the accretion disk. We detect quasi- periodic oscillations that evolve with the outburst, as well as irregular shaped dips that recur with a period of 2.42\pm0.09 hours, strongly suggesting an orbital period that would make MAXI J1659-152 the shortest period black-hole binary yet known.Comment: Accepted for publication in ApJ. 9 pages, 7 figure

Early X-ray and optical observations of the soft gamma-ray repeater SGR 0418+5729

Emission of two short hard X-ray bursts on 2009 June 5 disclosed the existence of a new soft gamma-ray repeater, now catalogued as SGR 0418+5729. After a few days, X-ray pulsations at a period of 9.1 s were discovered in its persistent emission. SGR 0418+5729 was monitored almost since its discovery with the Rossi X-ray Timing Explorer (2-10 keV energy range) and observed many times with Swift (0.2-10 keV). The source persistent X-ray emission faded by a factor 10 in about 160 days, with a steepening in the decay about 19 days after the activation. The X-ray spectrum is well described by a simple absorbed blackbody, with a temperature decreasing in time. A phase-coherent timing solution over the 160 day time span yielded no evidence for any significant evolution of the spin period, implying a 3-sigma upper limit of 1.1E-13 s/s on the period derivative and of 3E+13 G on the surface dipole magnetic field. Phase-resolved spectroscopy provided evidence for a significant variation of the spectrum as a function of the stellar rotation, pointing to the presence of two emitting caps, one of which became hotter during the outburst. Finally, a deep observation of the field of SGR 0418+5729 with the new Gran Telescopio Canarias 10.4-m telescope allowed us to set an upper limit on the source optical flux of i'>25.1 mag, corresponding to an X-ray-to-optical flux ratio exceeding 10000, consistent with the characteristics of other magnetars.Comment: The paper (10 pages) contains 6 colour figures and 2 tables; accepted for publication in MNRA

MAXI J1659-152: the shortest orbital period black-hole binary

Following the detection of a bright new X-ray source, MAXI J1659-152, a series of observations was triggered with almost all currently flying high-energy missions. We report here on XMM-Newton, INTEGRAL and RXTE observations during the early phase of the X-ray outburst of this transient black-hole candidate. We confirm the dipping nature in the X-ray light curves. We find that the dips recur on a period of 2.4139+/-0.0005 hrs, and interpret this as the orbital period of the system. It is thus the shortest period black-hole X-ray binary known to date. Using the various observables, we derive the properties of the source. The inclination of the accretion disk with respect to the line of sight is estimated to be 60-75 degrees. The companion star to the black hole is possibly a M5 dwarf star, with a mass and radius of about 0.15 M_sun and 0.23 R_sun, respectively. The system is rather compact (orbital separation is about 1.35 R_sun) and is located at a distance of roughly 7 kpc. In quiescence, MAXI J1659-152 is expected to be optically faint, about 28 mag in the V-band.Comment: 5 pages, 4 figures, to be published in the proceedings of the 4th International MAXI Workshop `The First Year of MAXI: Monitoring variable X-ray sources', 2010 Nov 30 - Dec 2, Tokyo, Japa