Acibadem University Repository
Not a member yet
2603 research outputs found
Sort by
Computational analysis of missense filamin-A variants, including the novel p.Arg484Gln variant of two brothers with periventricular nodular heterotopia
No full textBackground Periventricular nodular heterotopia (PNH) is a cell migration disorder associated with mutations in Filamin-A (FLNA) gene on chromosome X. Majority of the individuals with PNHassociated FLNA mutations are female whereas liveborn males with FLNA mutations are very rare. Fetal viability of the males seems to depend on the severity of the variant. Splicing or severe truncations presumed loss of function of the protein product, lead to male lethality and only partial-loss-of-function variants are reported in surviving males. Those variants mostly manifest milder clinical phenotypes in females and thus avoid detection of the disease in females. Methods We describe a novel p.Arg484Gln variant in the FLNA gene by performing whole exome analysis on the index case, his one affected brother and his healthy non-consanguineous parents. The transmission of PNH from a clinically asymptomatic mother to two sons is reported in a fully penetrant classical X-linked dominant mode. The variant was verified via Sanger sequencing. Additionally, we investigated the impact of missense mutations reported in affected males on the FLNa protein structure, dynamics and interactions by performing molecular dynamics (MD) simulations to examine the disease etiology and possible compensative mechanisms allowing survival of the males. Results We observed that p.Arg484Gln disrupts the FLNa by altering its structural and dynamical properties including the flexibility of certain regions, interactions within the protein, and conformational landscape of FLNa. However, these impacts existed for only a part the MD trajectories and highly similar patterns observed in the other 12 mutations reported in the liveborn males validated this mechanism. Conclusion It is concluded that the variants seen in the liveborn males result in transient pathogenic effects, rather than persistent impairments. By this way, the protein could retain its function occasionally and results in the survival of the males besides causing the disease.5MAY 251
The Attitude of Turkish Physicians Toward COVID-19 Vaccination and the Effects of Vaccination on Their Mental Health
No full textBackground: The study aims to investigate the willingness of physicians for the coronavirus disease 2019 vaccination, factors contributing to their attitude, and the effects of vaccination on their mental health. It is conducted online with physicians between February 17 and March 17, 2021, corresponding to a period of at least 1 month after the first dosage. Methods: Sociodemographic and professional characteristics are investigated along with coronavirus disease 2019 experiences. The Fear of Coronavirus Disease 2019 Scale, Attitudes Toward the Coronavirus Disease 2019 Vaccine, The Hospital Anxiety and Depression Scale, and Beck Hopelessness Scale are given to evaluate the effects on mental health. Results: Among 578 participants, the total vaccination rate was 91.5\% and the main reason for non-vaccination is being already infected by coronavirus disease 2019. Vaccination affected mental health positively in more than half of the participants (59.2\% in the vaccinated group). Advanced age (odds ratio= 0.985, P < .05), positive attitude toward vaccination (odds ratio=0.918, P < .001), and high fear of coronavirus disease 2019 (odds ratio=0.937, P= .001) were among the predictors of being positively affected by the vaccination. Fear of coronavirus disease 2019 was positively correlated with hopelessness (r = .239, P < .001), depression (r = 0.387, P < .001), and anxiety (r = 0.531, P < .001). The negative thoughts about the vaccination were found to be correlated with hopelessness levels (r=-0.093, P < .05). Conclusions: Physicians have positive attitudes toward vaccination and vaccination has positive effects on their mental health. As vaccination is a key point during the fight against the coronavirus disease 2019 pandemic, studies on vaccination and its effects on mental health gained importance. The role of physicians in this regard is inevitable.2JUN149-1583
Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology
No full textThe blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK-STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK-STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK-STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs.9SEP1
Microcirculatory Response to Blood vs. Crystalloid Cardioplegia During Coronary Artery BypassGrafting With Cardiopulmonary Bypass
No full textBackground: Blood cardioplegia attenuates cardiopulmonary bypass (CPB)-induced systemic inflammatory response in patients undergoing cardiac surgery, which may favorably influence the microvascular system in this cohort. The aim of this study was to investigate whether blood cardioplegia would offer advantages over crystalloid cardioplegia in the preservation of microcirculation in patients undergoing coronary artery bypass grafting (CABG) with CPB.Methods: In this prospective observational cohort study, 20 patients who received crystalloid (n = 10) or blood cardioplegia (n = 10) were analyzed. The microcirculatory measurements were obtained sublingually using incident dark-field imaging at five time points ranging from the induction of anesthesia (T-0) to discontinuation of CPB (T-5).Results: In the both crystalloid {[}crystalloid cardioplegia group (CCG)] and blood cardioplegia {[}blood cardioplegia group (BCG)] groups, perfused vessel density (PVD), total vessel density (TVD), and proportion of perfused vessels (PPV) were reduced after the beginning of CPB. The observed reduction in microcirculatory parameters during CPB was only restored in patients who received blood cardioplegia and increased to baseline levels as demonstrated by the percentage changes from T-0 to T-5 (\%Delta)(T0-T5) in all the functional microcirculatory parameters {[}\%Delta TVDT0-T5(CCG): -10.86 +/- 2.323 vs. \%Delta TVDT0-T5(BCG): 0.0804 +/- 1.107, p < 0.001\%Delta PVDT0-T5(CCG): -12.91 +/- 2.884 vs. \%Delta PVDT0-T5(BCG): 1.528 +/- 1.144, p < 0.001\%Delta PPVT0-T5(CCG): -2.345 +/- 1.049 vs. \%Delta PPVT0-T5(BCG): 1.482 +/- 0.576, p < 0.01].Conclusion: Blood cardioplegia ameliorates CPB-induced microcirculatory alterations better than crystalloid cardioplegia in patients undergoing CABG, which may reflect attenuation of the systemic inflammatory response. Future investigations are needed to identify the underlying mechanisms of the beneficial effects of blood cardioplegia on microcirculation.JAN 13
Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation
No full textMany multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identifiedhowever, approximately half of MS heritability remains unexplained. We studied seven multiplex MS families, six of which with parental consanguinity, to identify genetic factors that increase MS risk. Candidate genomic regions were identified through linkage analysis and homozygosity mapping, and fully penetrant, rare, and low-frequency variants were detected by exome sequencing. Weighted sum score and polygenic risk score (PRS) analyses were conducted in MS families (24 affected, 17 unaffected), 23 sporadic MS cases, 63 individuals in 19 non-MS control families, and 1272 independent, ancestry-matched controls. We found that familial MS cases had a significantly higher common risk variation burden compared with population controls and control families. Sporadic MS cases tended to have a higher PRS compared with familial MS cases, suggesting the presence of a higher rare risk variation burden in the families. In line with this, score distributions among affected and unaffected family members within individual families showed that known susceptibility alleles can explain disease development in some high-risk multiplex families, while in others, additional genetic contributors increase MS risk.1OCT 101
COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information
No full textBackground: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.111-141
Personalized reference intervals - statistical approaches and considerations
No full textFor many measurands, physicians depend on population-based reference intervals (popRI), when assessing laboratory test results. The availability of personalized reference intervals (prRI) may provide a means to improve the interpretation of laboratory test results for an individual. prRI can be calculated using estimates of biological and analytical variation and previous test results obtained in a steady-state situation. In this study, we aim to outline statistical approaches and considerations required when establishing and implementing prRI in clinical practice. Data quality assessment, including analysis for outliers and trends, is required prior to using previous test results to estimate the homeostatic set point. To calculate the prRI limits, two different statistical models based on `prediction intervals' can be applied. The first model utilizes estimates of `within-person biological variation' which are based on an individual's own data. This model requires a minimum of five previous test results to generate the prRI. The second model is based on estimates of `within-subject biological variation', which represents an average estimate for a population and can be found, for most measurands, in the EFLM Biological Variation Database. This model can be applied also when there are lower numbers of previous test results available. The prRI offers physicians the opportunity to improve interpretation of individuals' test results, though studies are required to demonstrate if using prRI leads to better clinical outcomes. We recommend that both popRIs and prRIs are included in laboratory reports to aid in evaluating laboratory test results in the follow-up of patients.4MAR 28629-6356
Sclerosing stromal tumor: a rare ovarian neoplasm
No full textSclerosing stromal tumor (SST) is an extremely rare and distinctive sex cord stromal tumor, which occurs predominantly in the second and third decades of life. SSTs make up 2-6\% of ovarian sex-cord stromal tumors. Due to the solid and distinct vascular structure of the tumor, it can be mistaken as a number of malignant ovarian tumors. As this specific neoplasm is very rare, it is not always possible to diagnose the tumor preoperatively with clinical and ultrasonographic findings. Furthermore, histopathological and immunohistochemical analysis does not always confirm the diagnosis. In this case report, clinical findings, histopathological features, and macroscopic appearance during laparoscopy of an SST are presented in a 20-year-old woman with pelvic pain. SST should be considered among the differential diagnosis of women with adnexal masses.1MAR68-702
Online peer observation: Reflections on a process-based job-embedded professional development activity through video recordings
No full textGuided by the sociocultural approach to teacher learning, this collective case study describes in-depth online peer observation experiences of six English language teachers and how they reflected on the scheme carried out for a semester at a university. Data were collected via an interest analysis form, 24 reflective diaries, 24 video recordings of pre- and post-observation meetings, and two experience sharing day colloquiums. Thematic analysis was conducted to reveal emerging themes and codes. OLPO led the participants to telecollaborate, scrutinize their online classes, offer solutions for improved teaching, test these solutions in their practices, and reflect on the whole process. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).DEC12
Leukocyte telomere length as a compensatory mechanism in vitamin D metabolism
No full textVitamin D deficiency is common among postmenopausal women. Telomere length can be a potential protective mechanism for age-related diseases. The objective of our study is to examine the association of vitamin D supplementation on leukocyte telomere length (LTL) in healthy postmenopausal women with vitamin D deficiency. The study was designed as a placebo-controlled study to investigate the short-term effects of vitamin D supplementation and seasonal changes on vitamin D related parameters, including 25(OH)D, 1,25(OH)(2)D parathormone (PTH), Vitamin D binding protein (VDBP), vitamin D receptor (VDR), and telomere length in a cohort of postmenopausal women (n = 102). The group was divided as supplementation (n = 52) and placebo groups (n = 50). All parameters were measured before and after treatment. Serum VDBP levels were measured by ELISA method and VDR, GC (VDBP) gene expressions and relative telomere lengths were measured in peripheral blood mononuclear cells (PBMC) using a quantitative real-time PCR method. The results demonstrate that baseline levels were similar between the groups. After vitamin D supplementation 25(OH)D, 1,25(OH)(2)D, PTH and VDBP levels were changed significantly compared to the placebo group. At the end of the study period, LTL levels were significantly increased in both groups and this change was more prominent in placebo group. The change in GC expression was significant between treatment and placebo groups but VDR expression remained unchanged. Even though the study was designed to solely assess the effects of vitamin D supplementation, LTL was significantly increased in the whole study group in summer months suggesting that LTL levels are affected by sun exposure and seasonal changes rather than supplementation. The study displayed the short-term effect of Vitamin D supplementation on vitamin D, PTH levels, LTL and vitamin D associated gene expressions. The relation between Vitamin D and LTL is not linear and could be confounded by several factors such as the population differences, regional and seasonal changes in sun exposure.2FEB 241