4,453 research outputs found

    Does hydatid cyst fluid from Echinococcus granulosus cysts have any effect on cells involved in fibrosis in cystic echinococcosis?

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    Cystic echinococcosis is characterized by the presence of slow growing hydatid cysts, usually in the liver or lungs. Survival of the parasite is based on an interaction of the host immune system and a range of parasite immune-evasive strategies. Fibrosis in the tissues surrounding the cysts can be seen as a host protective response isolating the parasite and restricting its growth or from another perspective fibrosis may be protective for the parasite by providing a barrier to more effective immunological responses. In this study the adenocarcinomic human alveolar basal epithelial cell line (A549) was used as model system. This cell line can be involved in fibrosis as cells can transform into mesenchymal cells and differentiate later to fibroblasts and/or myofibroblasts which can ultimately secrete collagen. Cells were initially cultured in vitro in RPMI-1640 medium containing 1-10% hydatid cyst fluid (HCF). The possible effect of the parasite extracts on cell migration was investigated using a wound healing assay. The ability of HCF components to modify cell surface markers of mesenchymal transition was also investigated by fluorescence microscopy. Results showed that there was a dose-dependent increase in cell growth in the presence of cyst fluid after 5 days of culture. The migratory response of cells was also enhanced by the presence of HCF. Both the enhanced growth and migratory activity were still evident when the HCF had been boiled indicating that the components responsible were thermostable. Semi-purified extracts of a major HCF component, antigen B showed a similar high stimulatory effect similar to that of HCF. The fluorescence microscopy showed a significant expression in the fibronectin and E-cadherin cell markers in cells treated with HCF. These results indicate that components within HCF have a stimulatory effect in the possible enhancement of fibrosis

    Non-Homologous end joining induced alterations in DNA methylation: A source of permanent epigenetic change

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    In addition to genetic mutations, epigenetic revision plays a major role in the development and progression of cancer; specifically, inappropriate DNA methylation or demethylation of CpG residues may alter the expression of genes that promote tumorigenesis. We hypothesize that DNA repair, specifically the repair of DNA double strand breaks (DSB) by Non-Homologous End Joining (NHEJ) may play a role in this process. Using a GFP reporter system inserted into the genome of HeLa cells, we are able to induce targeted DNA damage that enables the cells, after successfully undergoing NHEJ repair, to express WT GFP. These GFP+ cells were segregated into two expression classes, one with robust expression (Bright) and the other with reduced expression (Dim). Using a DNA hypomethylating drug (AzadC) we demonstrated that the different GFP expression levels was due to differential methylation statuses of CpGs in regions on either side of the break site. Deep sequencing analysis of this area in sorted Bright and Dim populations revealed a collection of different epi-alleles that display patterns of DNA methylation following repair by NHEJ. These patterns differ between Bright and Dim cells which are hypo- and hypermethylated, respectively, and between the post-repair populations and the original, uncut cells. These data suggest that NHEJ repair facilitates a rewrite of the methylation landscape in repaired genes, elucidating a potential source for the altered methylation patterns seen in cancer cells, and understanding the mechanism by which this occurs could provide new therapeutic targets for preventing this process from contributing to tumorigenesis

    The Dutch version of the Oral Health Impact Profile (OHIP-NL): Translation, reliability and construct validity

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    Background The purpose of this study was to make a cross-culturally adapted, Dutch version of the Oral Health Impact Profile (OHIP), a 49-item questionnaire measuring oral health-related quality of life, and to examine its psychometric properties. Methods The original English version of the OHIP was translated into the Dutch language, following the guidelines for cross-cultural adaptation of health-related quality of life measures. The resulting OHIP-NL's psychometric properties were examined in a sample of 119 patients (68.9 % women; mean age = 57.1 ± 12.2 yrs). They were referred to the clinic of Prosthodontics and Implantology with complaints concerning their partial or full dentures or other problems with missing teeth. To establish the reliability of the OHIP-NL, internal consistency and test-retest reliability (N = 41; 1 - 2 weeks interval) were examined, using Cronbach's alpha and intraclass correlation coefficients (ICC), respectively. Further, construct validity was established by calculating ANOVA. Results Internal consistency and test-retest reliability were excellent (Cronbach's alpha = 0.82 - 0.97; ICC = 0.78 - 0.90). In addition, all associations were significant and in the expected direction. Conclusion In conclusion: the OHIP-NL can be considered a reliable and valid instrument to measure oral health-related quality of life

    Speech Features for Discriminating Stress Using Branch and Bound Wrapper Search

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    Stress detection from speech is a less explored field than Automatic Emotion Recognition and it is still not clear which features are better stress discriminants. VOCE aims at doing speech classification as stressed or not-stressed in real-time, using acoustic-prosodic features only. We therefore look for the best discriminating feature subsets from a set of 6285 features – 6125 features extracted with openSMILE toolkit and 160 Teager Energy Operator (TEO) features. We use a mutual information filter and a branch and bound wrapper heuristic with an SVM classifier to perform feature selection. Since many feature sets are selected, we analyse them in terms of chosen features and classifier performance concerning also true positive and false positive rates. The results show that the best feature types for our application case are Audio Spectral, MFCC, PCM and TEO. We reached results as high as 70.36% for generalisation accuracyinfo:eu-repo/semantics/publishedVersio

    Snapping hip caused by a venous hemangioma of the gluteus maximus muscle: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Snapping hip, or coxa saltans, is defined as a clinical condition where a usually painful, audible snap occurs during hip flexion and extension. Its causes can be divided into external, internal or intra-articular origin. Accurate diagnosis is a prerequisite to successful treatment. We report a rare cause of snapping hip which is different from any previously reported cases.</p> <p>Case presentation</p> <p>A 23-year-old man presented to us with right hip pain of more than 10 years duration. Atrophy of the right gluteus maximus with snapping and tenderness were also noted. The imaging study revealed a focal intramuscular lesion in the lateral portion of the right gluteus maximus muscle. Surgery was performed and pathological examination concluded this mass to be a venous hemangioma.</p> <p>Conclusion</p> <p>Intramuscular hemangioma, though rare, should be considered in the differential diagnosis of a snapping hip even though muscle fibrosis is most frequently encountered.</p

    Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene.

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    We report that homology-directed repair of a DNA double-strand break within a single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1, DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are recruited to the site of repair and are responsible for selective methylation of the promoter-distal segment of the repaired DNA. The initial methylation pattern of the locus is modified in a transcription-dependent fashion during the 15\u201320 days following repair, at which time no further changes in the methylation pattern occur. The variation in DNA modification generates stable clones with wide ranges of GFP expression. Collectively, our data indicate that somatic DNA methylation follows homologous repair and is subjected to remodeling by local transcription in a discrete time window during and after the damage. We propose that DNA methylation of repaired genes represents a DNA damage code and is source of variation of gene expression

    Spanish version of the Oral Health Impact Profile (OHIP-Sp)

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    BACKGROUND: The need for appraisal of oral health-related quality of life has been increasingly recognized over the last decades. The aims of this study were to develop a Spanish version (OHIP-Sp) of the Oral Health Impact Profile and to evaluate its convergent and discriminative validity, and its internal consistency. METHODS: The original 49-items OHIP was translated to Spanish, revised for understanding and semantics by two independent dentists, and then translated back to English by an independent bilingual dentist. The data originated in a cross sectional study conducted among high school students from the Province of Santiago, Chile. The study group was sampled using a multistage random cluster procedure yielding 9,203 students aged 12–21 years. All selected students were invited to participate and all filled a questionnaire with information on socio-demographic factors; oral health related behaviors; and self-reported oral health status (good, fair or poor). From this group, 9,163 students also accepted to fill a detailed questionnaire on socio-economic indicators and to receive a clinical examination comprising direct recordings of clinical attachment levels (CAL) in molars and incisors, tooth loss, and the presence of necrotizing ulcerative gingival lesions. RESULTS: The participation rate and the questionnaire completeness were high with OHIP-Sp total scores being computed for 9,133 subjects. Self-perceived oral health status was associated with the total OHIP-Sp score and all its domains (Spearman rank correlation). The OHIP-Sp total score was also directly associated with the 4 dental outcomes investigated (Mann-Whitney test) and the largest impact was found for the outcomes, 'tooth loss' with a mean OHIP-Sp score = 13.5 and 'CAL >= 3 mm' with a mean OHIP-Sp score = 13.0. CONCLUSION: The OHIP-Sp revealed suitable convergent and discriminative validity and appropriate internal consistency (Cronbach's α). Further studies on OHIP-Sp warrant the inclusion of populations with a higher disease burden; and the use of test-retest reliability exercises to evaluate the stability of the test

    Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample

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    PURPOSE: The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. METHODS: A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters. RESULTS: A total of 392 men (65.4 +/- 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 +/- 0.1 ng/ml) than in those with the CC-genotype (1.7 +/- 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 +/- 2.0 vs. 32 +/- 0.8 ml, P = 0.02) and lower PSA levels (1.6 +/- 0.3 vs. 1.9 +/- 0.1 ng/ml). CONCLUSIONS: The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameter

    A telephone survey of cancer awareness among frontline staff: informing training needs

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    Background: Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff. Methods: A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England. Results: A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276). Conclusion: Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors
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