Recurrence of carcinoma showing thymus-like differentiation (CASTLE) involving the thyroid gland.

BACKGROUND: Carcinoma showing thymus-like differentiation (CASTLE) in the thyroid gland is a rare disease with generally a favorable prognosis. Treatment with surgery and adjuvant radiotherapy has been shown to improve local control and long-term survival rates. In this report, we present a case of a recurrent thyroid gland CASTLE and review the literature on the diagnosis and treatment of this disease. CASE PRESENTATION: A 60-year-old woman, who was diagnosed with a CASTLE thyroid tumor in 2015, had a total thyroidectomy and was maintained on thyroid hormone replacement (levothyroxine). After 5 years, the patient had a recurrence, in an advanced stage unsuitable for surgery. As the patient declined to undergo radiotherapy, she was followed up without intervention and is currently stable after 15 months. CONCLUSIONS: CASTLE is a rare disease, diagnosed based on postoperative pathology and immunohistochemistry analysis, especially upon CD5 marker. In case of relapse, treatment options include surgery and radiotherapy; however conservative management without intervention is an acceptable alternative in some cases.

Over-under cartilage tympanoplasty: technique, results and a call for improved reporting.

OBJECTIVE: This study aimed to describe the microscopic over-under cartilage tympanoplasty technique, provide hearing results and detail clinically significant complications. METHOD: This was a retrospective case series chart review study of over-under cartilage tympanoplasty procedures performed by the senior author between January 2015 and January 2019 at three tertiary care centres. Cases were excluded for previous or intra-operative cholesteatoma, if a mastoidectomy was performed during the procedure or if ossiculoplasty was performed. Hearing results and complications were obtained. RESULTS: Sixty-eight tympanoplasty procedures met the inclusion criteria. The median age was 13 years (range, 3-71 years). The mean improvement in pure tone average was 6 dB (95 per cent confidence interval 4-9 dB; p < 0.0001). The overall perforation closure rate was 97 per cent (n = 66). Revision surgery was recommended for a total of 6 cases (9 per cent) including 2 post-operative perforations, 1 case of middle-ear cholesteatoma and 3 cases of external auditory canal scarring. CONCLUSION: Over-under cartilage tympanoplasty is effective at improving clinically meaningful hearing with a low rate of post-operative complications.

An unsupervised deep learning technique for susceptibility artifact correction in reversed phase-encoding EPI images.

Echo planar imaging (EPI) is a fast and non-invasive magnetic resonance imaging technique that supports data acquisition at high spatial and temporal resolutions. However, susceptibility artifacts, which cause the misalignment to the underlying structural image, are unavoidable distortions in EPI. Traditional susceptibility artifact correction (SAC) methods estimate the displacement field by optimizing an objective function that involves one or more pairs of reversed phase-encoding (PE) images. The estimated displacement field is then used to unwarp the distorted images and produce the corrected images. Since this conventional approach is time-consuming, we propose an end-to-end deep learning technique, named S-Net, to correct the susceptibility artifacts the reversed-PE image pair. The proposed S-Net consists of two components: (i) a convolutional neural network to map a reversed-PE image pair to the displacement field; and (ii) a spatial transform unit to unwarp the input images and produce the corrected images. The S-Net is trained using a set of reversed-PE image pairs and an unsupervised loss function, without ground-truth data. For a new image pair of reversed-PE images, the displacement field and corrected images are obtained simultaneously by evaluating the trained S-Net directly. Evaluations on three different datasets demonstrate that S-Net can correct the susceptibility artifacts in the reversed-PE images. Compared with two state-of-the-art SAC methods (TOPUP and TISAC), the proposed S-Net runs significantly faster: 20 times faster than TISAC and 369 times faster than TOPUP, while achieving a similar correction accuracy. Consequently, S-Net accelerates the medical image processing pipelines and makes the real-time correction for MRI scanners feasible. Our proposed technique also opens up a new direction in learning-based SAC.

Epidemiology and risk factors for extrapulmonary tuberculosis in Lebanon.

SETTING: Lebanon is a relatively low TB-burden country, but has a high proportion of extrapulmonary tuberculosis (EPTB). Concern has been expressed that Syrian-born refugees could add to the TB burden and rates of EPTB: since 2011, >1 000 000 Syrian refugees have entered Lebanon.OBJECTIVE: The Lebanese National Tuberculosis Programme (NTP) sought to identify factors for the high proportion of EPTB and to assess the potential impact of Syrian refugees.DESIGN: NTP line-listed data from 2014-2015 were analyzed with logistic regression identified risk factors for EPTB. A trend analysis for 2011-2015 assessed TB burden by nationality and site of TB.RESULTS: Of 1347 reported TB cases from 2014 to 2015, 507 (38%) were EPTB and 46% were Lebanese. In analysis limited to Lebanese-born, the proportion of EPTB cases was relatively stable, 47% in 2011 and 52% in 2015. Modeling identified risk factors for EPTB as being female (aOR 1.79, 95%CI 1.39-2.32) and 5-15 years old (aOR 3.31, 95%CI 1.47-7.45) compared with children aged <5 years. Between 2011 and 2015, the proportion of TB cases among Syrian-born increased from 3% in 2011 to 21% in 2015 (P < 0.001); however, the proportion of EPTB versus PTB cases among Syrians remained stable (P = 0.264).CONCLUSION: Syrian TB cases increased almost 10-fold in five years (2011-2015) but their contribution to EPTB did not change. The high proportion of EPTB in Lebanon and those aged 5-15 years merits further investigation.

Do central vestibular findings predict abnormal findings on magnetic resonance imaging?

OBJECTIVE: To determine whether central findings from vestibular tests predict abnormal findings on magnetic resonance imaging. METHOD: This study was a retrospective case series at a tertiary referral centre. The main outcome measure of this diagnostic intervention study was the positive predictive value of central vestibular findings in relation to magnetic resonance imaging abnormalities. RESULTS: Central vestibular findings had a 50.9 per cent positive predictive value for magnetic resonance imaging abnormalities across all age groups although they varied according to age group. Optokinetic nystagmus (p < 0.05) and abnormal findings on videonystagmography tests (p < 0.05) were the main predictors of magnetic resonance imaging abnormalities. White matter lesions constituted the bulk of the central lesions on magnetic resonance imaging followed by cortical and cerebellar atrophy. CONCLUSION: Central vestibular findings had a 50.9 per cent positive predictive value for magnetic resonance imaging abnormalities across all age groups. Magnetic resonance imaging is medically justified to further evaluate patients with central findings on vestibular studies. Therefore, it is reasonable to request magnetic resonance imaging in these patients.

Dynamics of Inter-Molecular Interactions Between Single Aß42 Oligomeric and Aggregate Species by High-Speed Atomic Force Microscopy.

Within the amyloid hypothesis in Alzheimer's disease, current focus has shifted to earlier stages of amyloid beta (Aß) peptide assembly, involving soluble oligomers and smaller aggregates, which are more toxic to cells compared to their morphological distinct fibril forms. Critical to the Aß field is unlocking the molecular-level kinetic pathways of oligomerization, leading to the culprit subset or specific species of Aß oligomer populations responsible for the disease etiology. Here, we apply high-speed atomic force microscopy to enable direct visualization of dynamic interactions between single Aß42 oligomers and aggregate forms, with combined nanometre structural and millisecond temporal resolution in liquid. Analysis of dimensions revealed up to three main Aß42 species distributions, in addition to the appearance of monomers that showed fast surface diffusion compared to the larger Aß42 species. Significantly, we devised a new single-molecule analysis based on image contrast in high-speed atomic force microscopy movies to quantify rate determining kinetic constants for interactions between the different Aß42 species. The findings revealed that smaller Aß42 species show an exponential decay of lifetime distribution, indicating that all molecules undergo the same process with a single well-defined energy barrier. In contrast, larger aggregates show randomized lifetimes, indicating a distribution of interactions energies/barriers that must be overcome in order to dissociate. We interpret the latter as being due to "permissive" binding, arising from different conformation states of the aggregates, along with a variety of accessible interacting groups. Inevitably, this may lead to the formation of different complexes or alloforms, which is known to contribute to difficulties in identifying Aß oligomer toxicity and has implications for mechanisms underlying neuronal death accompanying Alzheimer's disease.

Identification and characterisation of conserved epitopes of E. ruminantium that activate Th1 CD4+ T cells: Towards the development of a multi-epitope vaccine.

Several studies have shown that cytotoxic T lymphocytes (CTL) require CD4 + Th1 epitopes to generate strong immune responses to intracellular pathogens. However, not much is known about Ehrlichia ruminantium epitopes, particularly those that can be considered potential candidates for inclusion in a multi-epitope vaccine. In order to identify CD4+ Th1 epitopes that induce IFNγ, a number of proteins previously identified as immunogenic were first screened to determine if they induce cellular immunity in tick infected immune sheep PBMC. Significant IFN-γ production and other Th1 cytokines were evident for 10 recombinant proteins in all sheep tested. Secondly, peptides (n = 246) derived from the top 10 E. ruminantium vaccine candidate proteins were assayed using enzyme linked immunospot (ELISPOT) assay, quantitative real-time PCR and flow cytometry. Of the 246 peptides, 23 peptides, Erum0660 (p0660-42), Erum1150 (p1150-18, p1150-19), Erum2540 (p2540-6, p2540-16, p2540-19, p2540-20, p2540-21), Erum5420 (p5420-13, p5420-14), Erum7140 (p7140-6, p7140-7, p7140-12, p7140-13, p7140-20), Erum7320 (p7320-8, p7320-9, p7320-21), Erum7350 (p7350-9), Erum7360 (p7360-8), Erum7620 (p7620-2, p7620-12) and Erum8010 (p8010-8) were identified that stimulate the best and different cell mediated immune responses. Amino acid sequences of these peptides except for p7140-12, p7140-13, p7140-20, and p7350-9 were conserved between 13 different local strains. These peptides could efficiently induce memory CD4+ T cells to rapidly proliferate and significantly increase IFN-γ production in immune sheep PBMC. The upregulation of pro-inflammatory cytokines, which include, IL-1α, IL-2, IL-12p40, TNF-α, IFN-γ, inducible nitric oxide synthase (iNOS) and granulocyte-macrophage colony stimulating factor (GM-CSF) was also detected. Our results show that these peptides could serve as promising candidates for a multi-epitope vaccine against E. ruminantium.

Ehrlichia ruminantium antigens and peptides induce cytotoxic T cell responses in vitro.

Since CD8+ T cells play an important role in resistance to infection with heartwater, effective vaccines against this disease will likely require identification of antigens that contain CD8+ T cell epitopes responsible for cytotoxic T lymphocyte (CTL) responses. With the use of the fluorescent antigen-transfected target cell (FATT)-CTL assay, IFN-γ ELISPOT and flow cytometry, peptides that induce CTL, proliferation of CD8 + T cells and IFN-γ production were identified as possible target antigens for vaccine development. Of particular relevance was the finding that different peptides from different antigens were able to elicit varied cytotoxic activities by immune peripheral blood mononuclear cells (PBMC) from heartwater immune tick-infected sheep. Several peptides derived from Erum0660, Erum2330, Erum2540, Erum2580 and Erum5000 induced CTL in immune sheep PBMC. Peptide Erum2540-6 was the only peptide that induced significant CTL, CD8+CD45RO+ and CD8+IFN-γ+ by PBMC from all three sheep, and Erum2540 and p2540-20 induced the highest % CTL response in all three outbred sheep. These results suggest that these epitopes may be of major importance in heartwater recombinant vaccine development.

Non-contrast magnetic resonance imaging for monitoring patients with acoustic neuroma.

OBJECTIVE: To assess the feasibility of non-contrast T2-weighted magnetic resonance imaging as compared to T1-weighted post-contrast magnetic resonance imaging for detecting acoustic neuroma growth. METHODS: Adult patients with acoustic neuroma who underwent at least three magnetic resonance imaging scans of the internal auditory canals with and without contrast in the past nine years were identified. T1- and T2-weighted images were reviewed by three neuroradiologists, and tumour size was measured. Accuracy of the measurements on T2-weighted images was defined as a difference of less than or equal to 2 mm from the measurement on T1-weighted images. RESULTS: A total of 107 magnetic resonance imaging scans of 26 patients were reviewed. Measurements on T2-weighted magnetic resonance imaging scans were 88 per cent accurate. Measurements on T2-weighted images differed from measurements on T1-weighted images by an average of 1.27 mm, or 10.4 per cent of the total size. The specificity of T2-weighted images was 88.2 per cent and the sensitivity was 77.8 per cent. CONCLUSION: The T2-weighted sequences are fairly accurate in measuring acoustic neuroma size and identifying growth if one keeps in mind the caveats associated with the tumour characteristics or location.

Health assessment instruments for people with intellectual disabilities-A systematic review.

BACKGROUND: People with intellectual disabilities (ID) experience health disparities and are less likely to undergo recommended age- and gender-specific screening and health promotion. New diagnoses are frequently missed. Assessments with the aid of health assessment instruments are a way to address these problems. AIM: The aim of this review is to find the available health assessment instruments for people with ID used in primary care and evaluate their quality. METHODS: We conducted an electronic literature search of papers published between January 2000 and May 2016. After a two-phase selection process (kappa: 0.81 and 0.77) we collected data from the 29 included peer-reviewed articles on the following four domains; development, clinimetric properties (i.e. validity, reliability, feasibility, acceptability), content (i.e. ID-related health problems, prevention and health promotion topics) and effectiveness of the instruments. RESULTS/CONCLUSIONS: We distinguished 20 different health assessment instruments. Limited information was found on the development of the instruments as well as on their clinimetric properties. The content of the instruments was rather diverse. The included papers agreed that health assessment instruments are effective. However, only three instruments evaluated effectiveness in a randomised controlled trial. Patients with ID, carers and general practitioners (GPs) generally appreciated the health assessment instruments. IMPLICATION: Two instruments, "Stay well and healthy -Health risk appraisal (SWH-HRA)"and the "Comprehensive Health Assessment Programme (CHAP)", appeared to have the highest quality. These instruments can be used to construct a health assessment instrument for people with ID that meets scientific standards.

Determination of PCDD/Fs in breast milk of women living in the vicinities of Da Nang Agent Orange hot spot (Vietnam) and estimation of the infant's daily intake.

Seventeen toxic congeners of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were determined in breast milks using the high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) method. Twenty seven breast milk samples were collected from primiparae who have lived over 5 years in wards namely Chinh Gian, An Khe, Khue Trung, and Hoa Thuan Tay which are located near the Da Nang Agent Orange hot spot (the AO/Dioxin hot spot). The samples were then analyzed for PCDD/F residues in order to assess the human exposure to dioxins from the AO/Dioxin hot spot, especially health risk to the breast-fed infants. The average TEQ levels in the four studied cohorts ranged from 8.1 to 26 pg/g lipid, with the highest level up to 51 pg TEQ/g lipid found in the An Khe ward. The TEQ level was correlated with geographical position and ranking in the order of Khue Trung, Hoa Thuan Tay, Chinh Gian and An Khe. The mean estimated PCDD/Fs infant's daily intake in the cohort of Khue Trung, Hoa Thuan Tay, Chinh Gian and An Khe was about 41, 122, 124, and 134 pg TEQ/kg bw/day, respectively, which are much higher than the tolerable daily intake proposed by the World Health Organization (4 pg TEQ/kg bw/day).

[Molecular-genetic characterization of canine and rangiferine brucella isolates from different regions of Russia].

GOAL: Comparative molecular-genetic characterization of Brucella isolates from dogs and reindeers in Russia by molecular-genetic typing methods. MATERIALS AND METHODS: 19 canine and 2 rangiferine Brucella isolates were studied by molecular typing methods based on PCR for differential species and biovar specific molecular targets and MLVA (multiple locus variable number tandem repeats analysis) using primers to 12 known variable loci. RESULTS: Using PCR for differential molecular targets, canine Brucella isolates were characterized as B. canis and rangiferine isolates as B. suis biovar 4. MLVA revealed 5 identical and 7 variable MLVA loci. Using the dendrogram. all the isolates on the data of 12 loci were classified into the close related cluster. On the other hand, high discrimination power of MLVA with a resulting Hunter and Gaston discriminatory index (HGDI) of 0.9842 was shown to reveal genetic diversity for the isolates of 17 MLVA genotypes. CONCLUSION: B. canis and B. suis isolates from different geographical regions in Russia were genetically close related, thereby confirming known genetic relationship between these species. Related MLVA genotypes of isolates were connected to certain regions of preliminary isolation in Russia. To improve the system ofbrucellosis surveillance in Russia MLVA typing of more canine and rangiferine Brucella isolates having epidemiological danger for humans is required to be studied.

Epidemiology chapter.

This chapter outlines the epidemiology of brucellosis in the Russian Federation and in five countries bordering Russia. Since the Soviet Union's dissolution, Russia and the newly formed independent republics have failed to maintain policies to control brucellosis and other zoonotic diseases. Many of these republics, due to weak animal control and prevention systems and dangerous food preparation practices, are still burdened with the human cost of brucellosis. The final summary of this section provides an example of the successful transboundary cooperative efforts between Arizona and Mexico, which could be applied to the situation between Russia and the bordering independent republics.

[Mathematical modelling in physiology].

The article illustrates the method of mathematical modelling in physiology as a unique tool to study physiological processes. A number of demonstrated examples appear as a result of long-term experience in mathematical modelling of electrical and mechanical phenomena in the heart muscle. These examples are presented here to show that the modelling provides insight into mechanisms underlying these phenomena and is capable to predict new ones that were previously unknown. While potentialities of the mathematical modelling are analyzed with regard to the myocardium, they are quite universal to deal with any physiological processes.

[Contribution of cooperative mechanisms of the thin filament activation to the myocardium contractile function. Assessment by a mathematical model].

We applied a mathematical model to compare the contributions to the myocardium mechanical activity of two a priori feasible variants of the cooperative effect of myosin cross-bridges on the calcium activation of sarcomere thin filaments. One of these variants implies that cross-bridge cooperative influence on the troponin C affinity to calcium is localized within the same functional cluster A7TmTn where the cross-bridge is attached. The second variant is based on the assumption that cross-bridges may affect the affinity of troponin C to calcium in other functional clusters A7TmTn as well (so that the nearer to the cross-bridge a cluster lies, the stronger the cross-bridge affects the affinity of CaTnC complex in this cluster). Each of these two variants and its contribution to the active mechanical performance of the heart muscle during the contraction-relaxation cycle were alternatively assessed in the model. It was found that only the second variant correctly simulates the mechanical activity of the muscle. Thus, the modeling suggests that just this variant of the cooperativity seems to be more feasible.

Liquid-liquid phase transitions: analytical approaches.

We consider liquid-liquid phase transitions as an indication of the local structure of condensed substances and investigate their statistics and thermodynamics. In this area there are two analytical approaches which describe the transitions: the first is purely phenomenological, while the second deals with intermolecular couplings. In the present work, we discuss the features of the above approaches and their applicability to metallic liquids.

The Wills-Harrison approach to the thermodynamics of binary liquid transition-metal alloys.

In the present study, the Wills-Harrison approach in conjunction with the Bretonnet-Silbert local model pseudopotential is applied to the thermodynamics of binary transition-metal liquid alloys. The calculation is performed in the framework of the variational method of thermodynamic perturbation theory with a hard-sphere reference system. The Vashishta-Singwi exchange-correlation function and the Nozières-Pines exchange-correlation energy are used. The free energy of mixing for liquid Fe-Co alloy is calculated at different compositions near the melting temperature. The agreement with the experimental data is quite satisfactory.

[Assessment of the mechanical activity of cardiac isomyosins V1 and V3 by an in vitro motility assay with regulated thin filaments].

A series of experiments in an in vitro motility assay with reconstructed thin filaments has been performed to determine the dependence of the velocity of thin filament movement on the concentration of calcium in solution (in the pCa range from 5 to 8) for rabbit cardiac isomyosins V1 and V3. The "pCa-velocity" curves had the sigmoid form. It was found for each isoform that sliding velocities of regulated thin filaments (at the saturating calcium concentration (pCa 5)) and actin filaments did not differ from each other. The Hill coefficient was 1.04 and 0.75 for isomyosins V1 and V3, respectively. The calcium sensitivity of V3 was found to be higher than that of V1. In the framework of the same method, the relationship between the velocity of thin filament sliding and the concentration of the actin-binding protein a-actinin (analog of the "force-velocity" relationship) has been estimated for each isoform V1 and V3 at the saturating calcium concentration. The results obtained suggest that the calcium regulation of the contractile activity of isomyosins V1 and V3 occurs by different mechanisms.

Uso de levetiracetam en el manejo de las mioclonías postanóxicas. Informe de dos casos / No disponible

No disponible