Quasi-diffusion magnetic resonance imaging (QDI): A fast, high b-value diffusion imaging technique.

To enable application of non-Gaussian diffusion magnetic resonance imaging (dMRI) techniques in large-scale clinical trials and facilitate translation to clinical practice there is a requirement for fast, high contrast, techniques that are sensitive to changes in tissue structure which provide diagnostic signatures at the early stages of disease. Here we describe a new way to compress the acquisition of multi-shell b-value diffusion data, Quasi-Diffusion MRI (QDI), which provides a probe of subvoxel tissue complexity using short acquisition times (1-4 min). We also describe a coherent framework for multi-directional diffusion gradient acquisition and data processing that allows computation of rotationally invariant quasi-diffusion tensor imaging (QDTI) maps. QDI is a quantitative technique that is based on a special case of the Continuous Time Random Walk model of diffusion dynamics and assumes the presence of non-Gaussian diffusion properties within tissue microstructure. QDI parameterises the diffusion signal attenuation according to the rate of decay (i.e. diffusion coefficient, D in mm2 s-1) and the shape of the power law tail (i.e. the fractional exponent, α). QDI provides analogous tissue contrast to Diffusional Kurtosis Imaging (DKI) by calculation of normalised entropy of the parameterised diffusion signal decay curve, Hn, but does so without the limitations of a maximum b-value. We show that QDI generates images with superior tissue contrast to conventional diffusion imaging within clinically acceptable acquisition times of between 84 and 228 s. We show that QDI provides clinically meaningful images in cerebral small vessel disease and brain tumour case studies. Our initial findings suggest that QDI may be added to routine conventional dMRI acquisitions allowing simple application in clinical trials and translation to the clinical arena

A matter of words: NLP for quality evaluation of Wikipedia medical articles

Automatic quality evaluation of Web information is a task with many fields of applications and of great relevance, especially in critical domains like the medical one. We move from the intuition that the quality of content of medical Web documents is affected by features related with the specific domain. First, the usage of a specific vocabulary (Domain Informativeness); then, the adoption of specific codes (like those used in the infoboxes of Wikipedia articles) and the type of document (e.g., historical and technical ones). In this paper, we propose to leverage specific domain features to improve the results of the evaluation of Wikipedia medical articles. In particular, we evaluate the articles adopting an "actionable" model, whose features are related to the content of the articles, so that the model can also directly suggest strategies for improving a given article quality. We rely on Natural Language Processing (NLP) and dictionaries-based techniques in order to extract the bio-medical concepts in a text. We prove the effectiveness of our approach by classifying the medical articles of the Wikipedia Medicine Portal, which have been previously manually labeled by the Wiki Project team. The results of our experiments confirm that, by considering domain-oriented features, it is possible to obtain sensible improvements with respect to existing solutions, mainly for those articles that other approaches have less correctly classified. Other than being interesting by their own, the results call for further research in the area of domain specific features suitable for Web data quality assessment

Natural parasitism of the Citrus Leafminer (Lepidoptera: Gracillariidae) over eight years in seven citrus regions of São Paulo, Brazil

The citrus leafminer (CLM) Phyllocnists citrella Stainton (Lepidoptera: Gracillariidae) was frst recorded in Brazil in 1996. In 1998, the parasitoid Ageniaspis citricola Logvinovskaya (Hymenoptera: Encyrtdae) was introduced and established in many regions of the country. In this study, 130 onehour-samplings of sweet orange leaves (Citrus sinensis [L.] Osbeck) hostng CLM pupal chambers were carried out to estmate the CLM parasitsm rate (%) by its parasitoids in 7 regions of São Paulo State between 2000 and 2008. The sample sizes varied from 10 to 275 leaves (mean = 65). The most abundant parasitoid was the encyrtd A. citricola (found in 91.8% of the samplings). The highest level of CLM parasitsm by A. citricola was recorded in the southern region (Botucatu), 70.2 ± 6.6 (mean ± SEM), and the lowest level was recorded in the northern region (Barretos), 12.8 ± 5.7%. CLM parasitsm by A. citricola and by natve parasitoids (Galeopsomyia fausta LaSalle, Cirrospilus spp. and Elasmus sp.) did not differ between seasons. The 6-fold increase in the use of insectcides in citrus groves, afer 2004 when the Huanglongbing (HLB) disease was found in São Paulo State, did not reduce the level of CLM parasitsm. The level of parasitsm was 50.8 ± 4.2% before the advent of HLB (2000–2004) and 56.0 ± 4.4% thereafer (2005–2008), indicatng adaptaton of A. citricola in a disturbed agroecosystem.A minadora das folhas dos citros (MFC), Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae), foi encontrada pela primeira vez no Brasil em 1996. Em 1998, o parasitoide Ageniaspis citricola Logvinovskaya (Hymenoptera: Encyrtidae) foi introduzido e se estabeleceu em várias regiões do país. Nesse estudo, foram feitas130 amostragens, de uma hora, de folhas de laranjeiras doces [Citrus sinensis (L.) Osbeck] com câmaras pupais da MFC, para se estimar o parasitismo da MFC em 7 regiões do estado de São Paulo, entre 2000 e 2008. O tamanho das amostras variou de 10 a 275 folhas (média = 65). O parasitoide mais abundante foi o encirtídeo A. citricola (encontrado em 91.8% das amostragens). O maior parasitismo da MFC por A. citricola foi observado na região sul do estado (Botucatu), 70,2 ± 6,6 (média ± EPM), e o menor parasitismo na região norte (Barretos), 12,8 ± 5,7%. O parasitismo da MFC por A. citricola e seus parasitoides nativos (Galeopsomyia fausta LaSalle, Cirrospilus spp. and Elasmus sp.) não diferiram entre as estações do ano. O aumento de seis vezes no uso de inseticidas nos pomares de citros, após 2004, quando o Huanglongbing (HLB) foi encontrado no estado de São Paulo, não reduziu o nível de parasitismo da MFC. O nível médio de parasitismo foi de 50,8 ± 4,2%, antes do HLB (2000-2004), e 56,0 ± 4,4%, após o HLB (2005-2008), indicando a adaptação de A. citricola a um agroecossistema perturbado.info:eu-repo/semantics/publishedVersio

An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Whole-body fasciculation detection in amyotrophic lateral sclerosis using motor unit MRI (MUMRI)

\ua9 2024 International Federation of Clinical NeurophysiologyObjective: Compare fasciculation rates between amyotrophic lateral sclerosis (ALS) patients and healthy controls in body regions relevant for diagnosing ALS using motor unit MRI (MUMRI) at baseline and 6 months follow-up, and relate this to single-channel surface EMG (SEMG). Methods: Tongue, biceps brachii, paraspinals and lower legs were assessed with MUMRI and biceps brachii and soleus with SEMG in 10 healthy controls and 10 patients (9 typical ALS, 1 primary lateral sclerosis [PLS]). Results: MUMRI-detected fasciculation rates in typical ALS patients were higher compared to healthy controls for biceps brachii (2.40 \ub1 1.90 cm-3min−1 vs. 0.04 \ub1 0.10 cm-3min−1, p = 0.004), paraspinals (1.14 \ub1 1.61 cm-3min−1 vs. 0.02 \ub1 0.02 cm-3min−1, p = 0.016) and lower legs (1.42 \ub1 1.27 cm-3min−1 vs. 0.13 \ub1 0.10 cm-3min−1, p = 0.004), but not tongue (1.41 \ub1 1.94 cm-3min−1 vs. 0.18 \ub1 0.18 cm-3min−1, p = 0.556). The PLS patient showed no fasciculation. At baseline, 6/9 ALS patients had increased fasciculation rates compared to healthy controls in at least 2 body regions. At follow-up every patient had increased fasciculation rates in at least 2 body regions. The MUMRI-detected fasciculation rate correlated with SEMG-detected fasciculation rates (τ = 0.475, p = 0.006). Conclusion: MUMRI can non-invasively image fasciculation in multiple body regions and appears sensitive to disease progression in individual patients. Significance: MUMRI has potential as diagnostic tool for ALS

PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins

Neurodegenerative diseases are an enormous public health problem, affecting tens of millions of people worldwide. Nearly all of these diseases are characterized by oligomerization and fibrillization of neuronal proteins, and there is great interest in therapeutic targeting of these aggregates. Here, we show that soluble aggregates of α-synuclein and tau bind to plate-immobilized PrP in vitro and on mouse cortical neurons, and that this binding requires at least one of the same N-terminal sites at which soluble Aβ aggregates bind. Moreover, soluble aggregates of tau, α-synuclein and Aβ cause both functional (impairment of LTP) and structural (neuritic dystrophy) compromise and these deficits are absent when PrP is ablated, knocked-down, or when neurons are pre-treated with anti-PrP blocking antibodies. Using an all-human experimental paradigm involving: (1) isogenic iPSC-derived neurons expressing or lacking PRNP, and (2) aqueous extracts from brains of individuals who died with Alzheimer's disease, dementia with Lewy bodies, and Pick's disease, we demonstrate that Aβ, α-synuclein and tau are toxic to neurons in a manner that requires PrPC. These results indicate that PrP is likely to play an important role in a variety of late-life neurodegenerative diseases and that therapeutic targeting of PrP, rather than individual disease proteins, may have more benefit for conditions which involve the aggregation of more than one protein

Effect of formant frequency spacing on perceived gender in pre-pubertal children's voices

<div><p>Background</p><p>It is usually possible to identify the sex of a pre-pubertal child from their voice, despite the absence of sex differences in fundamental frequency at these ages. While it has been suggested that the overall spacing between formants (formant frequency spacing - ΔF) is a key component of the expression and perception of sex in children's voices, the effect of its continuous variation on sex and gender attribution has not yet been investigated.</p><p>Methodology/Principal findings</p><p>In the present study we manipulated voice ΔF of eight year olds (two boys and two girls) along continua covering the observed variation of this parameter in pre-pubertal voices, and assessed the effect of this variation on adult ratings of speakers' sex and gender in two separate experiments. In the first experiment (sex identification) adults were asked to categorise the voice as either male or female. The resulting identification function exhibited a gradual slope from male to female voice categories. In the second experiment (gender rating), adults rated the voices on a continuum from “masculine boy” to “feminine girl”, gradually decreasing their masculinity ratings as ΔF increased.</p><p>Conclusions/Significance</p><p>These results indicate that the role of ΔF in voice gender perception, which has been reported in adult voices, extends to pre-pubertal children's voices: variation in ΔF not only affects the perceived sex, but also the perceived masculinity or femininity of the speaker. We discuss the implications of these observations for the expression and perception of gender in children's voices given the absence of anatomical dimorphism in overall vocal tract length before puberty.</p></div

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

Coherent spinor dynamics in a spin-1 Bose condensate

Collisions in a thermal gas are perceived as random or incoherent as a consequence of the large numbers of initial and final quantum states accessible to the system. In a quantum gas, e.g. a Bose-Einstein condensate or a degenerate Fermi gas, the phase space accessible to low energy collisions is so restricted that collisions be-come coherent and reversible. Here, we report the observation of coherent spin-changing collisions in a gas of spin-1 bosons. Starting with condensates occupying two spin states, a condensate in the third spin state is coherently and reversibly created by atomic collisions. The observed dynamics are analogous to Josephson oscillations in weakly connected superconductors and represent a type of matter-wave four-wave mixing. The spin-dependent scattering length is determined from these oscillations to be -1.45(18) Bohr. Finally, we demonstrate coherent control of the evolution of the system by applying differential phase shifts to the spin states using magnetic fields.Comment: 19 pages, 3 figure