Browsing by Subject "Adult"

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Open Access
Aging alters the molecular dynamics of synapses in a sexually dimorphic pattern in zebrafish (Danio rerio)
(Elsevier, 2017-06) Karoglu, Elif Tugce; Halim, Dilara Ozge; Erkaya, Bahriye; Altaytas, Ferda; Arslan-Ergul, Ayca; Konu, Ozlen; Adams, Michelle M.
The zebrafish has become a popular model for studying normal brain aging due to its large fecundity, conserved genome, and available genetic tools; but little data exists about neurobiological age-related alterations. The current study tested the hypothesis of an association between brain aging and synaptic protein loss across males and females. Western blot analysis of synaptophysin (SYP), a presynaptic vesicle protein, and postsynaptic density-95 (PSD-95) and gephyrin (GEP), excitatory and inhibitory postsynaptic receptor-clustering proteins, respectively, was performed in young, middle-aged, and old male and female zebrafish (Danio rerio) brains. Univariate and multivariate analyses demonstrated that PSD-95 significantly increased in aged females and SYP significantly decreased in males, but GEP was stable. Thus, these key synaptic proteins vary across age in a sexually dimorphic manner, which has been observed in other species, and these consequences may represent selective vulnerabilities for aged males and females. These data expand our knowledge of normal aging in zebrafish, as well as further establish this model as an appropriate one for examining human brain aging.
Open Access
Analysis of skewed X-chromosome inactivation in females with rheumatoid arthritis and autoimmune thyroid diseases
(BioMed Central, 2009) Chabchoub, G.; Uz, E.; Maalej, A.; Mustafa, C. A.; Rebai, A.; Mnif, M.; Bahloul, Z.; Farid, N. R.; Ozcelik, T.; Ayadi, H.
Introduction The majority of autoimmune diseases such as rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) are characterized by a striking female predominance superimposed on a predisposing genetic background. The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of several autoimmune diseases.
Open Access
Application of the RIMARC algorithm to a large data set of action potentials and clinical parameters for risk prediction of atrial fibrillation
(Springer, 2015) Ravens, U.; Katircioglu-Öztürk, D.; Wettwer, E.; Christ, T.; Dobrev, D.; Voigt, N.; Poulet, C.; Loose, S.; Simon, J.; Stein, A.; Matschke, K.; Knaut, M.; Oto, E.; Oto, A.; Güvenir, H. A.
Ex vivo recorded action potentials (APs) in human right atrial tissue from patients in sinus rhythm (SR) or atrial fibrillation (AF) display a characteristic spike-and-dome or triangular shape, respectively, but variability is huge within each rhythm group. The aim of our study was to apply the machine-learning algorithm ranking instances by maximizing the area under the ROC curve (RIMARC) to a large data set of 480 APs combined with retrospectively collected general clinical parameters and to test whether the rules learned by the RIMARC algorithm can be used for accurately classifying the preoperative rhythm status. APs were included from 221 SR and 158 AF patients. During a learning phase, the RIMARC algorithm established a ranking order of 62 features by predictive value for SR or AF. The model was then challenged with an additional test set of features from 28 patients in whom rhythm status was blinded. The accuracy of the risk prediction for AF by the model was very good (0.93) when all features were used. Without the seven AP features, accuracy still reached 0.71. In conclusion, we have shown that training the machine-learning algorithm RIMARC with an experimental and clinical data set allows predicting a classification in a test data set with high accuracy. In a clinical setting, this approach may prove useful for finding hypothesis-generating associations between different parameters.
Open Access
Assessment of diagnostic enzyme-linked immunosorbent assay kit and serological markers in human brucellosis
(2008) Cakan G.; Bezirci F.B.; Kacka, A.; Cesur, S.; Aksaray, S.; Tezeren, D.; Saka, D.; Ahmed, K.
This study was performed to evaluate commercial brucella immunoglobulin G and M-enzymelinked immunosorbent assay (IgG and IgM ELISA) kits for the diagnosis of human brucellosis and to suggest a candidate prognostic marker for human brucellosis. We determined the serum levels of brucella IgG, IgM, C-reactive protein (CRP), soluble CD14 (sCD 14), and neopterin in patients with brucellosis and compared them with those of normal healthy persons, patients with tuberculosis, and patients with other diseases. It was found that the sensitivity of ELISA to diagnose brucellosis was high when both IgG and IgM ELISA were used together. This study showed that serum CRP, sCD14, or neopterin levels were significantly high during the course of human brucellosis. The above markers, alone or in combination, might have the potential to evaluate treatment outcomes in human brucellosis. The markers that can predict the variability of agglutination titer was also determined. It was found that the titer value alone does not fully represent disease status.
Open Access
Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes
(2010) Akturk, M.; Altinova, A.; Mert I.; Dincel, A.; Sargin, A.; Buyukkagnici, U.; Arslan, M.; Danisman, N.
As shown in the previous studies, asymmetric dimethylarginine (ADMA) is related to endothelial dysfunction, whereas high-sensitive C-reactive protein (hCRP) is the marker of inflammation. In our study, we investigated ADMA, hCRP, and homocysteine concentrations in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) during late pregnancy. Fifty-four women with GDM and 69 women with NGT between 32 and 39 weeks of gestation were included in this study. ADMA, hCRP, homocysteine, lipid parameters, glycated hemoglobin (HbA1c) levels, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. The plasma ADMA concentrations were significantly higher in GDM patients than in NGT subjects (P = 0.03) and the hCRP levels were also significantly increased in GDM group when compared with those in the NGT group (P = 0.008). However, plasma homocysteine levels did not differ between the groups (P = 0.4), while HOMA-IR, insulin, and triglyceride levels were higher in the GDM group than in the NGT group (P = 0.001, 0.002, and 0.02, respectively). The ADMA concentrations in the third trimester were positively correlated with the glucose levels the 50-g glucose challenge test (GCT) during 24-28 weeks in the whole group (r = 0.21, P = 0.02). Our results demonstrate that ADMA and hCRP are elevated in women with GDM during late pregnancy. Further studies are needed to clarify the significance and the underlying mechanisms of the elevated ADMA and hCRP levels in women with GDM. © 2010 Springer Science+Business Media, LLC.
Open Access
Aviation risk perception: a comparison between experts and novices
(Wiley-Blackwell Publishing, 2004) Thomson, M. E.; Önkal D.; Avcioǧlu, A.; Goodwin, P.
This article describes an exploratory investigation of the risk perceptions of experts and novices in relation to helicopter operations, under conditions where the participants are matched on various characteristics previously found to affect perceptions, such as demographic, gender, and background factors. The study reports considerable evidence of perceptual differences between the two participant groups (i.e., expert pilots and candidate pilots). We find that the experts' perceptions of relative risks are more veridical, in terms of their higher correlation with the true relative frequencies. A significant positive correlation between the flight hours and the contextual risk-taking tendency is also shown, leading the experienced pilots' choices toward risky alternatives in scenarios - a potential result of their overconfidence based on superior task performance. Possible explanations are offered for the findings and potential avenues for future research are identified.
Open Access
BRAPH: A graph theory software for the analysis of brain connectivity
(Public Library of Science, 2017) Mijalkov, M.; Kakaei, E.; Pereira, J. B.; Westman, E.; Volpe, G.
The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH–BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer’s disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson’s patients with mild cognitive impairment. © 2017 Mijalkov 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.
Open Access
Characterization of a novel zebrafish (Danio rerio) gene, wdr81, associated with cerebellar ataxia, mental retardation and dysequilibrium syndrome (CAMRQ)
(BioMed Central Ltd., 2015) Doldur-Balli, F.; Ozel, M. N.; Gulsuner, S.; Tekinay, A. B.; Ozcelik, T.; Konu, O.; Adams, M. M.
Background: WDR81 (WD repeat-containing protein 81) is associated with cerebellar ataxia, mental retardation and disequilibrium syndrome (CAMRQ2, [MIM 610185]). Human and mouse studies suggest that it might be a gene of importance during neurodevelopment. This study aimed at fully characterizing the structure of the wdr81 transcript, detecting the possible transcript variants and revealing its expression profile in zebrafish, a powerful model organism for studying development and disease. Results: As expected in human and mouse orthologous proteins, zebrafish wdr81 is predicted to possess a BEACH (Beige and Chediak-Higashi) domain, a major facilitator superfamily domain and WD40-repeats, which indicates a conserved function in these species. We observed that zebrafish wdr81 encodes one open reading frame while the transcript has one 5' untranslated region (UTR) and the prediction of the 3' UTR was mainly confirmed along with a detected insertion site in the embryo and adult brain. This insertion site was also found in testis, heart, liver, eye, tail and muscle, however, there was no amplicon in kidney, intestine and gills, which might be the result of possible alternative polyadenylation processes among tissues. The 5 and 18 hpf were critical timepoints of development regarding wdr81 expression. Furthermore, the signal of the RNA probe was stronger in the eye and brain at 18 and 48 hpf, then decreased at 72 hpf. Finally, expression of wdr81 was detected in the adult brain and eye tissues, including but not restricted to photoreceptors of the retina, presumptive Purkinje cells and some neurogenic brains regions. Conclusions: Taken together these data emphasize the importance of this gene during neurodevelopment and a possible role for neuronal proliferation. Our data provide a basis for further studies to fully understand the function of wdr81.
Open Access
Coagulation factor V gene mutation increases the risk of venous thrombosis in Behcet's disease
(Oxford University Press, 1996) Gül, A.; Özbek, U.; Öztürk, C.; Inanç, M.; Koniçe, M.; Özçelik, T.
We investigated the prevalence of the coagulation factor V gene G1691A mutation in 64 patients with Behcet's disease (BD) and in 107 apparently healthy individuals. The mutation was present in the heterozygous state in 37.5% of the patients with a history of deep vein thrombosis (12/32) and in 9.4% of the patients without any thrombotic event (3/32). Eleven healthy individuals were also heterozygous for the mutation (10.3%). The prevalence of the mutation in BD patients with and without thrombosis was significantly different (P = 0.0079). We conclude that the factor V gene mutation may play a major role in the development of venous thrombosis in BD.
Open Access
Cognitive and emotional representations of terror attacks: a cross-cultural exploration
(Wiley-Blackwell Publishing, 2007) Shiloh, S.; Güvenç, G.; Önkal D.
A questionnaire measuring cognitive and affective representations of terror risk was developed and tested in Turkey and Israel. Participants in the study were university students from the two countries (n = 351). Four equivalent factors explained terror risk cognitions in each sample: costs, vulnerability, trust, and control. A single negative emotionality factor explained the affective component of terror risk representations in both samples. All factors except control could be measured reliably. Results supported the validity of the questionnaire by showing expected associations between cognitions and emotions, as well as indicating gender differences and cultural variations. Current findings are discussed in relation to previous results, theoretical approaches, and practical implications.
Open Access
Colon cancer associated transcript-1 (CCAT1) expression in adenocarcinoma of the stomach
(Ivyspring International Publisher, 2015) Mizrahi, I.; Mazeh, H.; Grinbaum, R.; Beglaibter, N.; Wilschanski, M.; Pavlov, V.; Adileh, M.; Stojadinovic, A.; Avital, I.; Gure, A. O.; Halle, D.; Nissan, A.
Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Methods: Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Results: Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). Conclusion: CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance.
Open Access
A combined ULBP2 and SEMA5A expression signature as a prognostic and predictive biomarker for colon cancer
(Ivyspring International Publisher, 2017) Demirkol, S.; Gomceli, I.; Isbilen, M.; Dayanc, B. E.; Tez, M.; Bostanci, E. B.; Turhan, N.; Akoglu, M.; Ozyerli, E.; Durdu, S.; Konu, O.; Nissan, A.; Gonen, M.; Gure, A. O.
Background: Prognostic biomarkers for cancer have the power to change the course of disease if they add value beyond known prognostic factors, if they can help shape treatment protocols, and if they are reliable. The aim of this study was to identify such biomarkers for colon cancer and to understand the molecular mechanisms leading to prognostic stratifications based on these biomarkers. Methods and Findings: We used an in house R based script (SSAT) for the in silico discovery of stage-independent prognostic biomarkers using two cohorts, GSE17536 and GSE17537, that include 177 and 55 colon cancer patients, respectively. This identified 2 genes, ULBP2 and SEMA5A, which when used jointly, could distinguish patients with distinct prognosis. We validated our findings using a third cohort of 48 patients ex vivo. We find that in all cohorts, a combined ULBP2/SEMA5A classification (SU-GIB) can stratify distinct prognostic sub-groups with hazard ratios that range from 2.4 to 4.5 (p=0.01) when overall- or cancer-specific survival is used as an end-measure, independent of confounding prognostic parameters. In addition, our preliminary analyses suggest SU-GIB is comparable to Oncotype DX colon(®) in predicting recurrence in two different cohorts (HR: 1.5-2; p=0.02). SU-GIB has potential as a companion diagnostic for several drugs including the PI3K/mTOR inhibitor BEZ235, which are suitable for the treatment of patients within the bad prognosis group. We show that tumors from patients with worse prognosis have low EGFR autophosphorylation rates, but high caspase 7 activity, and show upregulation of pro-inflammatory cytokines that relate to a relatively mesenchymal phenotype. Conclusions: We describe two novel genes that can be used to prognosticate colon cancer and suggest approaches by which such tumors can be treated. We also describe molecular characteristics of tumors stratified by the SU-GIB signature.
Open Access
Contact guidance enhances the quality of a tissue engineered corneal stroma
(John Wiley & Sons, Inc., 2008) Vrana, E.; Builles, N.; Hindie, M.; Damour O.; Aydınlı, Atilla; Hasirci, V.
Corneal stroma is a very complex structure, composed of 200 lamellae of oriented collagen fibers. This highly complex nature of cornea is known to be important for its transparency and mechanical integrity. Thus, an artificial cornea design has to take into account this complex structure. In this study, behavior of human corneal keratocytes on collagen films patterned with parallel channels was investigated. Keratocytes proliferated well on films and reached confluency after 7 days in the incubation medium. Nearly all of the cells responded to the patterns and were aligned in contrast to the cells on unpatterned surfaces. Collagen type I and keratan sulfate secreted by keratocytes on patterned films appeared to be aligned in the direction of the patterns. The films showed an intermediate degradation over the course of a month. On the whole, transparency of the films increased with degradation and decreased by the presence of the cells. The decrease was, however, low and transparency level was maintained on the patterned films while on the unpatterned films a sharp decrease in transparency was followed by an improvement. This was due to the more organized distribution of cells and the oriented secretion of extracellular matrix molecules on patterned collagen films. Thus, these results suggest that application of contact guidance in cornea tissue engineering may facilitate the remodeling process, hence decrease the rehabilitation period.
Open Access
Determinants of choosing withdrawal over modern contraceptive methods in Turkey
(Taylor & Francis, 2008) Cindoglu, D.; Sirkeci, I.; Sirkeci, R. F.
Objectives The determinants of the use of withdrawal in Turkey are examined using a multinomial logistic model. Methods Data were drawn from a nation-wide population-based cross-sectional study, the Turkish Demographic Health Surveys that took place in 1998 and 2003. Detailed interviews were conducted with 8576 women aged 15-49 and analysed using SPSS. Results Contextual, cultural and demographic characteristics define women's choice of withdrawal over modern methods. Socio-economic status, education, employment status, and past fertility behaviour are among key determinants. First-ever used contraception method has a very strong impact on later choices. Urban women, the more educated, those with better socioeconomic status, and those living in less crowded households resort less to withdrawal. Experience and empowerment positively linked to modern contraceptive use among women in Turkey. Conclusions The use of contraceptive methods in Turkey differs greatly. Empowerment of women in terms of better socioeconomic status, better education, modern and liberal attitudes towards women and family planning seem to reduce withdrawal use as the main method of contraception. The results suggest the need for education (particularly targeting young women and couples), information and provision of modern contraceptive services particularly for disadvantaged groups.
Open Access
Determining the origin of synchronous multifocal bladder cancer by exome sequencing
(BioMed Central Ltd., 2015) Acar, Ö.; Özkurt, E.; Demir, G.; Saraç, H.; Alkan C.; Esen, T.; Somel, M.; Lack, N. A.
Background: Synchronous multifocal tumours are commonly observed in urothelial carcinomas of the bladder. The origin of these physically independent tumours has been proposed to occur by either intraluminal migration (clonal) or spontaneous transformation of multiple cells by carcinogens (field effect). It is unclear which model is correct, with several studies supporting both hypotheses. A potential cause of this uncertainty may be the small number of genetic mutations previously used to quantify the relationship between these tumours. Methods: To better understand the genetic lineage of these tumours we conducted exome sequencing of synchronous multifocal pTa urothelial bladder cancers at a high depth, using multiple samples from three patients. Results: Phylogenetic analysis of high confidence single nucleotide variants (SNV) demonstrated that the sequenced multifocal bladder cancers arose from a clonal origin in all three patients (bootstrap value 100 %). Interestingly, in two patients the most common type of tumour-associated SNVs were cytosine mutations of TpC*dinucleotides (Fisher's exact test p < 10-41), likely caused by APOBEC-mediated deamination. Incorporating these results into our clonal model, we found that TpC*type mutations occurred 2-5× more often among SNVs on the ancestral branches than in the more recent private branches (p < 10-4) suggesting that TpC*mutations largely occurred early in the development of the tumour. Conclusions: These results demonstrate that synchronous multifocal bladder cancers frequently arise from a clonal origin. Our data also suggests that APOBEC-mediated mutations occur early in the development of the tumour and may be a driver of tumourigenesis in non-muscle invasive urothelial bladder cancer.
Open Access
Developing empathy towards older adults in design
(Routledge, 2017-02-06) Altay, Burçak
In design disciplines, an affective understanding of users’ everyday lives can increase designer sensitivity and awareness, leading to higher-quality design outcomes. Developing students’ empathic understanding within design education is required to accomplish this goal. This article discusses learning strategies that enhance students’ empathic horizons, and specifically analyzes an assignment conducted in an Interior Architecture and Environmental Design course, “The Grandparent Experience.” Here, exposure through observation and interviewing, and art-based methods are employed to develop students’ empathy towards older adults. We conducted a survey with students who completed the exercise and the course, exploring their perspectives on their learning. The results reveal that students had positive views on the assignment’s effectiveness regarding the learning outcome and learning process. Implications for empathic design education and educational gerontology are discussed.
Open Access
Diagnosis of gastric carcinoma by classification on feature projections
(Elsevier, 2004) Güvenir, H. A.; Emeksiz, N.; İkizler, N.; Örmeci, N.
A new classification algorithm, called benefit maximizing classifier on feature projections (BCFP), is developed and applied to the problem of diagnosis of gastric carcinoma. The domain contains records of patients with known diagnosis through gastroscopy results. Given a training set of such records, the BCFP classifier learns how to differentiate a new case in the domain. BCFP represents a concept in the form of feature projections on each feature dimension separately. Classification in the BCFP algorithm is based on a voting among the individual predictions made on each feature. In the gastric carcinoma domain, a lesion can be an indicator of one of nine different levels of gastric carcinoma, from early to late stages. The benefit of correct classification of early levels is much more than that of late cases. Also, the costs of wrong classifications are not symmetric. In the training phase, the BCFP algorithm learns classification rules that maximize the benefit of classification. In the querying phase, using these rules, the BCFP algorithm tries to make a prediction maximizing the benefit. A genetic algorithm is applied to select the relevant features. The performance of the BCFP algorithm is evaluated in terms of accuracy and running time. The rules induced are verified by experts of the domain. © 2004 Elsevier B.V. All rights reserved.
Open Access
DNA repair gene polymorphisms and bladder cancer susceptibility in a Turkish population
(International Institute of Anticancer Research, 2006) Karahalil, B.; Kocabas, N. A.; Özçelik, T.
Background: Occupational exposure and life style preferences, such as smoking are the main known environmental susceptibility factors for bladder cancer. A growing list of chemicals has been shown to induce oxidative DNA damage. Base excision repair (BER) genes (X-ray repair cross complementing 1, XRCC1 and human 8-oxoguanine DNA glycosylase 1, OGG1) may play a key role in maintaining genome integrity and preventing cancer development. Materials and Methods: We tested whether polymorphisms in XRCC1 and OGG1 are associated with bladder cancer risk by using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. In addition, the possible modifying affect of cigarette smoking was evaluated. Results: No studies, to date, have examined the association between genetic polymorphisms in DNA repair genes and bladder cancer susceptibility, in the Turkish population. We found the OGG1 Cys326Cys genotype to be more frequent among bladder cancer patients (odds ratio (OR): 2.41 (95% CI, 1.36-4.25)). However, in the case of XRCC1, there was no significant difference in susceptibility to bladder cancer development between patients with the Arg399 and these with the Gln399 allele (OR: 0.72 (95% CI, 0.41-1.26)). Conclusion: Our data showed that OGG1 genetic polymorphisms might be useful as prognostic genetic markers for bladder cancer in the clinical setting.
Open Access
Early outcomes after transoral CO2 laser resection of laryngeal and hypopharyngeal squamous cell carcinoma: One centre's experience
(Cambridge University Press, 2010) Leong, S. C.; Kathan, C.; Mortimore, S.
Objectives: To review early oncological outcomes following transoral CO2 laser resection of laryngeal and hypopharyngeal squamous cell carcinoma. Design: Retrospective review of hospital electronic database. Setting: Large district general hospital in England, UK.Main outcome measures: Patients' three-year disease-specific survival and disease-free survival were evaluated, including post-operative complications, voice quality and swallowing status. Results: Seventy-seven patients (16 women and 61 men) were identified. Transoral laser excision of squamous cell carcinoma of the larynx was undergone by 65 patients, and the same procedure in the hypopharynx by 12. Patients with laryngeal cancer had statistically better disease-specific survival than those with hypopharyngeal cancer (p=0.021), although the cumulative disease-free survival probability was 0.71 for both larynx and hypopharynx groups. Patients who underwent laryngectomy following failed laser treatment or as a salvage procedure had poorer outcomes.Conclusions: The overall results of this study were comparable with those of other, larger studies. At three-year follow up, cumulative disease-specific survival probabilities were 0.92 and 0.71 for laryngeal and hypopharyngeal squamous cell carcinoma, respectively. Copyright © JLO (1984) Limited 2009.
Open Access
Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair
(B M J Group, 2014) Dal, G. M.; Ergüner, B.; Saǧıroǧlu, M. S.; Yüksel, B.; Onat, O. E.; Alkan C.; Özçelik, T.
Background: Human de novo single-nucleotide variation (SNV) rate is estimated to range between 0.82-1.70×10-8 mutations per base per generation. However, contribution of early postzygotic mutations to the overall human de novo SNV rate is unknown. Methods: We performed deep whole-genome sequencing (more than 30-fold coverage per individual) of the whole-blood-derived DNA samples of a healthy monozygotic twin pair and their parents. We examined the genotypes of each individual simultaneously for each of the SNVs and discovered de novo SNVs regarding the timing of mutagenesis. Putative de novo SNVs were validated using Sanger-based capillary sequencing. Results: We conservatively characterised 23 de novo SNVs shared by the twin pair, 8 de novo SNVs specific to twin I and 1 de novo SNV specific to twin II. Based on the number of de novo SNVs validated by Sanger sequencing and the number of callable bases of each twin, we calculated the overall de novo SNV rate of 1.31×10-8 and 1.01×10-8 for twin I and twin II, respectively. Of these, rates of the early postzygotic de novo SNVs were estimated to be 0.34×10-8 for twin I and 0.04×10-8 for twin II. Conclusions: Early postzygotic mutations constitute a substantial proportion of de novo mutations in humans. Therefore, genome mosaicism resulting from early mitotic events during embryogenesis is common and could substantially contribute to the development of diseases.