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Aim: Coronavirus disease 2019 (COVID-19, 2019-nCoV) which first appeared in Wuhan, China in December 2019 is a disease causing acute respiratory failure. Home isolation methods are used to control the disease all around the world and also in our country. In this study we planned to explain the relationship between some mental symptoms, diet compliance, frequency of blood glucose measurement and blood glucose levels in diabetic patients during home isolation. Material and Method: In this study some questions about the frequency of blood glucose measurement, blood glucose levels, dietary compliance and mental states of the patients were asked on the phone and the patients were asked to give a score to the symptom severity. The notes were retrospectively screened. Results: It is known that social isolation triggers the anxiety and depression. Anxiety and depression can increase the secretion of some hormones which leads high blood glucose levels (respectively 54.4% of those with 200-300 mg/dl, 91.7% of those with >300 mg/dl don't follow their diets) in diabetic patients. These symptoms can reduce dietary compliance and frequency of the blood sugar measurement, therefore can make metabolic control of the diabetes difficult. Conclusion: In this study, we found that blood glucose levels were very high and the frequency of blood glucose measurements were very low in the patients who had some mood changes and we saw that the patients did not follow on their diets. It is important to support patients mentally during this process. Training and following up should be used with some various methods.

Telomere repeats at the ends of human chromosomes protect chromosomes from degradation, and telomerase has a prominent role in telomere maintenance. Telomerase also affects cell proliferation, DNA replication, differentiation, and tumourigenesis. TERT (telomerase reverse transcriptase enzyme) is the catalytic subunit of telomerase and is critical for enzyme activity. TERT promoter mutations and promoter methylation are strongly associated with increased telomerase activation in cancer cells. Notably, TERT and telomerase are downregulated in stem cells during their differentiation. Therefore, the link between differentiation and telomerase provides a valuable tool for studying the epigenetic regulation of TERT enzyme. Oxygen tension affects several cellular behaviours including proliferation, metabolic activity, stemness, and differentiation. The role of oxygen tension in driving promoter modifications of the TERT gene in embryonic stem cells (ESCs) is poorly understood either in vitro or in vivo. We adopted a monolayer ESCs differentiation model to explore the role of low, physiological, oxygen (physoxia) in the epigenetic regulation of telomerase and associated genes, including TERT, DNMTs, and HDACs. Cells were cultured in either air, a 2% O2 incubator, or a 2% O2 oxygen workstation to provide a fully defined 2% O2 environment. Pre-gassed media (pre-conditioned to 2% O2 in a HypoxyCool unit) was used in all 2% O2 experimentation. As anticipated, physoxia culture increased the proliferation rate and stemness of ESCs and a slower onset of differentiation in physoxia was evident. Further, downregulated TERT expression was correlated to reduced telomerase activity during differentiation. TERT expression and telomerase activity remained significantly elevated in physoxia during differentiation. A substantial increase in TERT promoter methylation levels was noted during differentiation. Chemical inhibition of DNMT3B reduced TERT promoter methylation and was associated with increased TERT gene and telomerase activity during differentiation. DNMT3B CHiP demonstrated that downregulated TERT expression and increased proximal promoter methylation were associated with DNMT3B binding to the promoter. In conclusion, we have demonstrated that DNMT3B can directly bind TERT promoter, change its methylation levels, and contribute to regulation of telomerase activity.

The epigenetic nature of telomeres is still controversial and different human cell lines might show diverse histone marks at telomeres. Epigenetic modifications regulate telomere length and telomerase activity that influence telomere structure and maintenance. Telomerase is responsible for telomere elongation and maintenance and is minimally composed of the catalytic protein component, telomerase reverse transcriptase (TERT) and template forming RNA component, telomerase RNA (TERC). TERT promoter mutations may underpin some telomerase activation but regulation of the gene is not completely understood due to the complex interplay of epigenetic, transcriptional, and posttranscriptional modifications. Pluripotent stem cells (PSCs) can maintain an indefinite, immortal, proliferation potential through their endogenous telomerase activity, maintenance of telomere length, and a bypass of replicative senescence in vitro. Differentiation of PSCs results in silencing of the TERT gene and an overall reversion to a mortal, somatic cell phenotype. The precise mechanisms for this controlled transcriptional silencing are complex. Promoter methylation has been suggested to be associated with epigenetic control of telomerase regulation which presents an important prospect for understanding cancer and stem cell biology. Control of down-regulation of telomerase during differentiation of PSCs provides a convenient model for the study of its endogenous regulation. Telomerase reactivation has the potential to reverse tissue degeneration, drive repair, and form a component of future tissue engineering strategies. Taken together it becomes clear that PSCs provide a unique system to understand telomerase regulation fully and drive this knowledge forward into aging and therapeutic application.

The purpose of this study is to examine the perceptions of fourth-grade elementary school students and their teachers regarding students’ asking-question in order to develop a model of students’ as...

In this study, an instrument assessing elementary education students’ attitudes towards asking questions in the classroom was developed. Items were determined based on interviews with students and teachers and scaled according to five-point Likert scale, “Never”, Rarely”, “Sometimes”, “Usually”, “Always”. Validity and reliability analyses of the instrument were conducted with two different study groups. Firstly, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were done with Study Groups 1 (203 fourth-grade students). Then, CFA was repeated with data obtained from Study Group 2 (334 fourth-grade students). According to EFA results, two constructs were determined and these constructs including 24 items were named as Openness towards asking question and Anxiety towards asking question . CFA goodness of fit indices obtained from both groups showed that the scale with two constructs was acceptable. Cronbach’s α reliability coefficients for each construct were respectively .78 and .80 for Study Group 1 and .76 and .77 for Study Group 2. As a result of analyses, reliability and validity of the developed instrument was ensured.

Amaç- Bu çalışmada bir devlet üniversitesi bünyesindeki meslek yüksekokulunda öğrenim gören öğrencilerin sunulan hizmet kalitesini değerlendirmeleri istenmiş ve hizmet kalitesine ilişkin algılarının öğrenci memnuniyetleri üzerindeki etkisinin ölçülmesi amaçlanmıştır. Ayrıca öğrencilerin demografik özelliklerine (cinsiyet, yaş, öğrenim gördükleri bölüm gibi) bağlı olarak hizmet kalitesine ve memnuniyet düzeylerine ilişkin algılarında bir farklılığın olup olmadığı belirlenmek istenmiştir.Yöntem- Çalışmanın verileri Kahramanmaraş Sütçü İmam Üniversitesi’ne bağlı Türkoğlu Meslek Yüksekokulu öğrencilerinden anket tekniği ile elde edilmiştir. Öğrencilerin hizmet kalitesi algısı fiziksel özellikler, güvenilirlik, heveslilik, güven ve empati olmak üzere çok boyutlu bir yapıda ele alınmıştır. Verilerin analizi için SPSS programından faydalanılmıştır. Çalışmada frekans analizi, Bağımsız t-Testi, ANOVA, korelasyon ve regresyon analizleri kullanılmıştır.Bulgular- Çalışmanın amacı doğrultusunda geliştirilen hipotezlerin test edilmesi sonucunda hizmet kalitesinin tüm boyutları ile öğrencilerin memnuniyetleri üzerinde etkili olduğu bulunmuştur. Hizmet kalitesi boyutları açısından ayrı ayrı incelendiğinde empati boyutunun öğrencilerin memnuniyetleri üzerinde diğer boyutlara göre daha etkili; heveslilik boyutunun da daha az etkili olduğu bulgusuna ulaşılmıştır. Ayrıca kadın ve erkek öğrencilerin hizmet kalitesi algılarının ve memnuniyet düzeylerinin birbirinden farklı olduğu bulgusu elde edilmiştir. Yine öğrencilerin öğrenim gördükleri bölümlere göre hizmet kalitesine ilişkin algılarının ve memnuniyet düzeylerinin birbirinden farklı olduğu sonucuna ulaşılmıştır.Sonuç- Yapılan analizler sonucunda değişkenler arasında anlamlı ilişkiler olduğu ve hizmet kalitesinin öğrencilerin memnuniyet düzeyleri üzerinde pozitif etkiye sahip olduğu sonucuna ulaşılmıştır., Purpose- The purpose of this study is to evaluate the service quality of students studying at a vocational high school within a state university and to measure the effect of their perceptions about service quality on student satisfaction. In addition, it is aimed to determine whether there is a difference in students' perceptions of service quality and satisfaction depending on their demographic characteristics (gender, age, department where they study).Methodology- The data of the study were obtained from the students of Türkoğlu Vocational School of Kahramanmaraş Sütçü İmam University using a survey method. Students' perception of service quality is handled in a multidimensional structure including tangibles, reliability, responsiveness, assurance and empathy. SPSS program was used for data analysis. Frequency analysis, Independent t-Test, ANOVA, correlation and regression analysis were used.Findings- As a result of testing the hypotheses developed in line with the purpose of the study, it was found that the quality of service was effective on satisfaction of the students. When examined separately in terms of service quality dimensions, empathy dimension is more effective on students' satisfaction than other dimensions; it was found that the responsiveness dimension was also less effective. In addition, it was found that female and male students' perceptions of service quality and satisfaction differ from each other. Also it was concluded that students' perceptions of service quality and satisfaction differ from each other according to their departments. Conclusion- Based upon the analysis showed that there were significant relationships between the variables.

Restoring stability after total knee arthroplasty (TKA) and improving joint function using a cemented rotating hinge system. Ligament instability and/or osseous defects (including Anderson Orthopaedic Research Institute [AORI] classification type II defects) after primary TKA or TKA revision surgery. Distal femoral or proximal tibial bowing requiring implant systems that provide femoral or tibial offset stems. Persistent periprosthetic infection. Poor therapeutic compliance. AORI type III defects. Medial arthrotomy. Femoral and tibial component removal with small saw blades and chisels. Intramedullary alignment for the tibial and femoral cuts. Debridement and removal of membranes and cement remnants. Reconstruction of joint line and correct TKA alignment. Trial reduction. Cement fixation. Unrestricted range of motion, partial weight bearing for 4 weeks. Between 2012 and 2013, 18 patients suffering from ligament insufficiency after TKA were revised using the described system and included in a prospective study protocol. The mean follow-up was 37 months (range 30–46 months). There was a significant improvement of the Oxford Knee Score (OKS) from 19 (range 7–29) preoperatively to 29 (range 10–45) postoperatively (p = 0.004). The Knee Society Score (KSS) knee assessment subscore improved from 35 (range 9–70) to 67 (range 35–97) (p = 0.002) and the pain score from 7 (range 0–50) to 24 (range 0–50) (p = 0.008).

© 2022 IEEE.Communication of things is one of the important research topics open to development today. The emergence of the concept of the Internet of Things (IoT) has accelerated with the needs of things; to operate on remotely, to collect data from objects, to transmit collected data to servers or applications, and to process data. Wi-Fi and cellular network technologies are currently used for the IoT but they consume high power. Bluetooth, Zigbee and Z-Wave wireless technologies consume low power and are effective at short-range. However, Low Power Wireless Access Network (LPWAN) has become a good research area as low power consuming technologies in long distance for the communication of objects. LoRa is a long range and low power LPWAN technology develop by Semtech. In this paper, the principle of LoRa is explained and the results of the communication test with two LoRa modules carried out in a rainy weather of Ankara city are presented. In the test, the first LoRa module is placed inside the car and then the car travels around the city on certain routes according to the building densities. The first LoRa module in the vehicle sends data to the second LoRa module placed in the home environment. For each sending data the received signal strength indicator (RSSI) value is measured. The results show that data transmission with LoRa devices varies according to the density of buildings in the city and LoRa modules can communicate with each other at a distance of up to 1 km. Overall, as the distance and the number of buildings between the locations of the receiver and transmitter LoRa modules increase, data transmission rate decreases and data loss occurs.

This is an open, prospective, comparative parallel-arm medical device clinical study of Dermalix (Dx) in diabetic foot wounds. Dx is a 3-dimensional collagen-laminin porous-structured dermal matrix prepared and additionally impregnated with resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine-based microparticles. the aim was to evaluate the efficacy and safety of Dx, an investigational medical device, in Wagner 1 and 2 wounds in comparison to a standard wound care (SWC) that consists of irrigation and cleaning with sterile saline solution. Forty-eight patients were randomized to receive either SWC or SWC + Dx. A 4-week treatment period was followed by a 2-month follow-up without treatment. the wound area measurement, total collagen, vascular epidermal growth factor, tumor necrosis factor, interleukin 1, caspase 3, glutathione, reduced/oxidized glutathione, and lipid peroxidation levels were evaluated. At the end of 4 weeks, the percentage closures of wounds were determined as 57.82% for Dx, and 26.63% for SWC groups. Dx had a significant effect on tumor necrosis factor, caspase 3, and reduced/oxidized glutathione levels. Dx provided 2 times faster wound healing and decreased oxidative stress. Application of Dx in the first phase of wound would help the wound area heal faster with a safe profile., Abdi Ibrahim Ilac San. ve Tic. A.S., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Abdi Ibrahim Ilac San. ve Tic. A.S.

Applicability of multilingual education, which is applied in many countries, has increasingly proficiency and learning been a question of debate in Turkey because of the inclusion of living languages and dialects lessons into educational institutions. The purpose of this study is to develop a valid and reliable Likert-type scale to determine the perception of multilingual education of teachers with the inclusion of living languages and dialects lesson into curricula. For this purpose, a study was conducted with teachers in Turkey. After the instrument was constructed based on the literature, field experts evaluated it, and revisions were made to clarify the language and the design. Following this process, a pilot study was conducted among 150 teachers, resulting in a scale comprising 28 items after the alterations were made. Then, the instrument was sent to 898 teachers utilizing a snowball technique. Exploratory factor analysis was applied to determine the validity of the scale. Factor analysis showed that the scale had a single factor explaining 72.4% of the total variance. The scale’s KMO (Kaiser-Meyer-Olkin) was .974; and the Barlett test was 21828.8. For the sake of validity and reliability, the Cronbach’s alpha internal consistency coefficient for the scale (content validity, construct validity, distinctiveness validity, internal consistency and reliability) was determined as 0.97. Thus, the conclusion can be made that the scale is applicable and reliable enough for future development.

Mesenchymal stem cells (MSCs), as multipotent stem cells, can be obtained from many tissues/organs including bone marrow, adipose tissue, dental pulp, and amniotic or synovial fluids1. MSCs are unique cells that can support functions of many tissues and organs by releasing soluble factors such as growth factors, anti-apoptotic and anti-inflammation factors, and they can synthesize extracellular matrix (ECM) mainly composed of collagen fibrils, a key component of tissues. In damaged tissues, MSCs can help the formation of new blood vessels by secreting angiogenic factors. Therefore, MSCs are very helpful for reducing the inflammation2, decreasing the progress of autoimmune diseases3 and preventing rejection of transplant4. Our objective in this study is to use MSCs as supportive /feeder cells for the maintenance of liver cells including cell adhesion, cell growth and proliferation other biological activity in microfluidic chip by benefitting from such protective and regenerative properties of MSCs for tissues. To accomplish this aim, as part of a liver-on-a-chip study, we investigate the behavior of MSCs in microfluidic (MF) culture by monitoring cell viability, proliferation, cell numbers, and the expression of MSC-specific genes. Moreover, we will investigate the effect of MSCs on the viability and maintenance of liver cells within the MF-chip conducted by co-culture of MSCs with liver cells. &nbsp

Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To promote muscle repair and regeneration, various strategies for skeletal muscle tissue engineering have been developed in the last decades. However, there is still a high demand for the development of new methods and materials that promote skeletal muscle repair and functional regeneration to bring approaches closer to therapies in the clinic that structurally and functionally repair muscle. The combination of stem cells, biomaterials, and biomolecules is used to induce skeletal muscle regeneration. In this review, we provide an overview of different cell types used to treat skeletal muscle injury, highlight current strategies in biomaterial-based approaches, the importance of topography for the successful creation of functional striated muscle fibers, and discuss novel methods for muscle regeneration and challenges for their future clinical implementation.

In this study, we aim to develop an antibiotic-based biosensor platform ‘Antibiotsensor’ for the specific detection of gram-positive bacteria using vancomycin modified Screen Printed Gold Electrodes (SPGEs). Through this pathway, vancomycin molecules were first functionalized with thiol groups and characterized with quadrupole time of flight (q-TOF) mass spectroscopy analysis. Immobilization of thiolated vancomycin molecules (HS-Van) onto SPGEs was carried out based on self-assembled monolayer (SAM) phenomenon. Electrochemical impedance spectroscopy (EIS) was employed to test the detection and showed a considerable change in impedance value upon the binding of HS-Van molecules onto the electrode surface. Atomic Force Microscopy analysis indicated that SPGE was successfully modified upon the treatment with HS-Van molecules based on the shift in surface roughness from 173 ± 2 nm to 301 ± 3 nm. Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy proved the EIS and AFM results as well by showing characteristic peaks of immobilized HS-Van molecule. As a proof-of-concept, EIS-based susceptibility testing was performed using Escherichia coli, Staphylococcus aureus and Mycobacterium smegmatis bacteria to prove the specificity of obtained SPGE-Van. EIS data showed that the charge transfer resistance (Rct) values changed from 1.08, 1.18 to 26.5, respectively, indicating that vancomycin susceptible S. aureus was successfully attached onto SPGE-Van surface strongly, while vancomycin resistance E. coli and M. smegmatis did not show any significant attachment properties. In addition, different concentration (108-10 CFU/mL) of S. aureus was performed to investigate sensitivity of proposed sensor platform. Limit of detection and limit of quantitation was calculated as 101.58 and 104.81 CFU/mL, respectively. Scanning electron microscopy (SEM) analysis also confirmed that only S. aureus bacteria was attached to the surface in a dense monolayer distribution. We believe that the proposed approach is selective and sensitive towards the whole-cell detection of vancomycin-susceptible bacteria and can be modified for different purposes in the future.

Free standing artificial lipid bilayers are widely used in the study of biological pores. In these types of studies, the free standing planar lipid bilayer is formed over a micron-sized aperture consisting of either polymer such as Polytetrafluoroethylene (PTFE, Teflon) or glass. Teflon is chemically inert, has a low dielectric constant, and has a high electrical resistance which combined allow for obtaining low noise recordings. This study investigates the reproducible generation of micropores in the range of 50–100 microns in diameter in a Teflon film using a high energy discharge set-up. The discharger set-up consists of a microprocessor, a transformer, a voltage regulator, and is controlled by a computer. We compared two approaches for pore creation: single and multi-pulse methods. The results showed that the multi-pulse method produced narrower aperture size distributions and is more convenient for lipid bilayer formation, and thus would have a higher success rate than the single-pulse method. The bilayer stability experiments showed that the lipid bilayer lasts for more than 33 h. Finally, as a proof-of-concept, we show that the single and multi-channel electrophysiology experiments were successfully performed with the apertures created by using the mentioned discharger. In conclusion, the described discharger provides reproducible Teflon-pores in a cheap and easy-to-operate manner. Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK) – SOBAG – Proje No - 117S114. The Scientific and Technological Research Council of Turkey - (TUBITAK) – SOBAG - 117S114. WOS:000622719400001 PMID: 33638734 Q3

Biosensors are analytical tools used for the analysis of biomaterial samples and provide an understanding about the biocomposition, structure, and function of biomolecules and/or biomechanisms by converting the biological response into an electrical and/or optical signal. In particular, with the rise in antibiotic resistance amongst pathogenic bacteria, the study of antibiotic activity and transport across cell membranes in the field of biosensors has been gaining widespread importance. Herein, for the rapid and label‐free detection of antibiotic permeation across a membrane, a microelectrode integrated microfluidic device is presented. The integrated chip consists of polydimethylsiloxane based microfluidic channels bonded onto microelectrodes on‐glass and enables us to recognize the antibiotic permeation across a membrane into the model membranes based on electrical impedance measurement, while also allowing optical monitoring. Impedance testing is label free and therefore allows the detection of both fluorescent and non‐fluorescent antibiotics. As a model membrane, Giant Unilamellar Vesicles (GUVs) are used and impedance mea- surements were performed by a precision inductance, capacitance, and resistance metre. The measured signal recorded from the device was used to determine the change in concentration inside and outside of the GUVs. We have found that permeation of antibiotic molecules can be easily monitored over time using the proposed integrated device. The results also show a clear difference between bilayer permeation that occurs through the lipidic bilayer and porin‐mediated permeation through the porin channels inserted in the lipid bilayer. Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK) - 217M151. The Scientific and Technological Research Council of Turkey - (TUBITAK) - 217M151. WOS:000614875900001 PMID: 34694729 Q4 Q3

Successful lysis of cells/microorganisms is a key step in the sample preparation in fields like molecular biology, bioengineering, and biomedical engineering. This study therefore aims to investigate the lysis of bacteria on-chip and its dependence on both microfluidic channel structure and flow rate. Effects of temperature on lysis on-chip were also investigated. To perform these investigations, three different microfluidic chips were designed and produced (straight, zigzag and circular configurations), while the length of the channels were kept constant. As an exemplary case, Mycobacterium smegmatis was chosen to represent the acid-fast bacteria. Bacterial suspensions of 1.5 McFarland were injected into the chips at various flow rates (0.6- $8~\mu \text{l}$ /min) either at room temperature or 50° C. In order to understand the on-chip lysis performance fully, off-chip experiments were carried out at durations which are equal to those bacteria spent in the channel from inlet to the outlet at different flow rates. We also performed COMSOL multiphysics program simulations to evaluate further the effect of the applied parameters. As a result, we found that the structure and the flow rate do not affect lysis over all in all investigated channel types, however on-chip experiments at room temperature produced more effective lysis compared to the on-chip and the off-chip samples performed at higher temperatures. Interestingly on-chip experiments at higher tempratures do not result in effective lysis.

Today, the emergence of antibiotic resistance in pathogenic bacteria is considered an important problem for society. Excessive consumption of antibiotics, long-term treatments, and inappropriate prescriptions continually increase the severity of the problem. Improving antibiotic stewardship requires improved diagnostic testing, and, therefore, in vitro antibiotic susceptibility testing is becoming increasingly important. This research details the development of an antibiotic susceptibility test for Mycobacterium smegmatis using streptomycin as antibiotics. This strain was selected because it is a member of the slow growing Mycobacterium genus and serves as a useful surrogate organism for M. tuberculosis. A commercially available and low-cost screen-printed gold electrode in combination with a specifically developed nucleic acid probe sequence for the 16SrRNA region of the mycobacterial genome was employed to monitor M. smegmatis nucleic acid sequences using the techniques of square-wave voltammetry and electrochemical impedance spectroscopy. The results show that it was possible to detect M. smegmatis sequences and distinguish antibiotic-treated cells from untreated cells with a label-free molecular detection. As a result, the in vitro antibiotic susceptibility test revealed that M. smegmatis showed sensitivity to streptomycin after a 24-H incubation, with the developed protocol representing a potential approach to determining antibiotic susceptibility more quickly and economically than current methods.

Antibiotic resistance in Gram-negative bacteria causes serious health issues worldwide. Bacteria employ several resistance mechanisms to cope with antimicrobials. One of their strategies is to reduce the permeability of antibiotics either through general diffusion porins or substrate-specific channels. In this study, one of the substrate-specific channels from Pseudomonas aeruginosa, OccK8 (also known as OprE), was investigated using single-channel electrophysiology. The study also includes the investigation of permeability properties of several amino acids with different charged groups (i.e. arginine, glycine and glutamic acid) through OccK8. We observed four different conformations of the same OccK8 channel when inserted in lipid bilayers. This is in contrast to previous studies where heterologous expressed OccK8 in E. coli showed only one conformation. We hypothesized that the difference in our study was due to the expression and purification of the native channel from P. aeruginosa. The single-channel uptake characteristics of the porin showed that negatively charged glutamic acid preferentially interacted with the channel while the positively charged arginine molecule showed infrequent interaction with OccK8. The neutral amino acid glycine did not show any interaction at the physiological conditions.

Digoxin is a cardiac glycoside that is used for the treatment of heart failure and atrial fibrillation. Besides its careful close follow-up, toxicity affects nearly 1% of congestive heart failure patients. Cessation of the drug, appropriate electrolyte and rhythm control and digoxin-Fab antibody are the mainstay for toxicity treatment in these patients. As known, hemodialysis and peritoneal dialysis are not effective by the means of digoxin removal. We present a 66-year-old patient who admitted to hospital with digoxin toxicity and severe acute kidney injury. The patient was treated with continuous venovenous hemodialysis because of her hypervolemia, hyperkalemia, cardiac instability, and the thought of probable decrease in digoxin levels concerning the continuous nature of solute clearance. Without the treatment using digoxin-specific Fab antibodies, the patient's digoxin level was decreased successfully with continuous venovenous hemodialysis. In conclusion, continuous venovenous hemodialysis may be a treatment option in digoxin toxicity especially those who suffer from severe renal dysfunction and cannot access digoxin antidote.

Body membranes are thin sheets/layers of cells or tissues which cover the surface of internal organs, the outside of the body and lines various body cavities. These membranes are separated into two main groups which are epithelial membranes and connective tissue membranes. Decellularized forms of inner body membranes in the groups of epithelial membranes (amniotic membrane, mesentery, omentum, pericardium, peritoneum, pleura) and connective tissue membranes (fascia, periosteum, synovial membrane) have been used in tissue engineering studies for preparation and regeneration of various tissues such as bone, tendon, cartilage, skin, cornea, ocular surface, uterine, periodontium, vascular and cardiovascular structures. Decellularized inner body membranes have high biocompatibility and support cell attachment, cell growth and angiogenesis which are desired properties for using as versatile tools in tissue engineering applications. Even though, decellularized forms of these membranes have been used in many studies, it is necessary to develop new decellularization methods for more effective cell removal and less destructive properties on tissue structures. Moreover, development of decellularization agents which target removal of antigens of donor tissues is also essential because these antigens are one of the main reasons for tissue-organ rejections in allogeneic and xenogeneic tissue-organ implantations. This review provides comprehensive information and analysis about the current state of the art in the literature on decellularized inner body membranes and applications of these membranes in tissue engineering.

Si3N4ceramics show excellent characteristics of mechanical and chemical resistance in combination with good biocompatibility, antibacterial property and radiolucency. Therefore, they are intensively studied as structural materials in skeletal implant applications. Despite their attractive properties, there are limited data in the field about in vitro studies of cellular growth on ceramic implant materials. In this study, the growth of bone cells was investigated on porous silicon nitride (Si3N4) ceramic implant by using electrochemical impedance spectroscopy (EIS). Partial sintering was performed at 1700 °C with limited amount of sintering additive for the production of porous Si3N4scaffolds. All samples were then sterilized by using ethylene oxide followed by culturing MG-63 osteosarcoma cells on the substrates for in vitro assays. At 20 and 36 h, EIS was performed and results demonstrated that magnitude of the impedance as a result of the changes in the culture medium increased after incubation with osteosarcoma cells. The changes are attributed to the cellular uptake of charged molecules from the medium. Si3N4samples appear to show large impedance magnitude changes, especially between 100 and 1 Hz. Impedance changes were also correlated with WST-1 measurements (36 h) and DAPI results.

Pluripotent stem cells (PSC) possess unlimited proliferation, self-renewal, and a differentiation capacity spanning all germ layers. Appropriate culture conditions are important for the maintenance of self-renewal, pluripotency, proliferation, differentiation, and epigenetic states. Oxygen concentrations vary across different human tissues depending on precise cell location and proximity to vascularisation. The bulk of PSC culture-based research is performed in a physiologically hyperoxic, air oxygen (21% O2) environment, with numerous reports now detailing the impact of a physiologic normoxia (physoxia), low oxygen culture in the maintenance of stemness, survival, morphology, proliferation, differentiation potential, and epigenetic profiles. Epigenetic mechanisms affect multiple cellular characteristics including gene expression during development and cell-fate determination in differentiated cells. We hypothesized that epigenetic marks are responsive to a reduced oxygen microenvironment in PSCs and their differentiation progeny. Here, we evaluated the role of physoxia in PSC culture, the regulation of DNA methylation (5mC (5-methylcytosine) and 5hmC (5-hydroxymethylcytosine)), and the expression of regulatory enzyme DNMTs and TETs. Physoxia enhanced the functional profile of PSC including proliferation, metabolic activity, and stemness attributes. PSCs cultured in physoxia revealed the significant downregulation of DNMT3B, DNMT3L, TET1, and TET3 vs. air oxygen, accompanied by significantly reduced 5mC and 5hmC levels. The downregulation of DNMT3B was associated with an increase in its promoter methylation. Coupled with the above, we also noted decreased HIF1A but increased HIF2A expression in physoxia-cultured PSCs versus air oxygen. In conclusion, PSCs display oxygen-sensitive methylation patterns that correlate with the transcriptional and translational regulation of the de novo methylase DNMT3B.

Nanopore biosensors have attracted attention due to their label-free single molecule detection capability. To date, different materials and applications have been shown in the field, varying from Si3N4 to graphene and biomolecule sensing to DNA sequencing. Classical nanopore devices are composed of Si3N4 material supported on a Si wafer and the detection is largely based on electrochemical sensing using chambers of ml volumes on both sides of the nanopore device. In this study, in-flow label-free electrochemical detection of DNA molecules at single molecule level is shown using a classical Si3N4 nanopore device integrated into a microfluidic device. The layout of the device given here set the basics for future works and discussions regarding future microfluidic integrated solid-state nanopores and the behaviour of the molecule under the influence of hydrodynamic flow.

The effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of β-catenin responsive transcription (ICRT-3) blocks the Wnt signaling pathway by binding to β-catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT-3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer. The effect of this compound on cytotoxicity and cell viability in FaDu and HNCSC line was assessed by using the water-soluble tetrazolium salt-1 method. The effect of ICRT-3 on apoptosis was detected by using Annexin V and caspase-3, caspase-9 kit, on cell cycle progression by cycle test plus DNA reagent kit, on gene expression by dual luciferase reporter assay, and on migration activity by wound healing assay in both cell lines. ICRT-3 was determined to have cytotoxic and apoptotic effect in both cell lines. In addition, it was also found that the administration of ICRT-3 caused cell cycle arrest and significant decrease in gene expression level and migration ability of the cells.

Thermoplastic elastomers (TPE) offers wide design opportunities because of its rapid prototyping that provides researchers with the acquisition of many different material properties from softness and jelly-like properties to hardness and rigidity. In this regard, poly(styrene-b-(ethylene-cobutylene)-b-styrene) (SEBS) triblock copolymer has many positive aspects and is very promising when the design and requirements of devices for different applications are considered. The combination of thermoplastic and elastomeric properties of SEBS triblock copolymer makes it one of the potential materials in the production of large-scale materials. In this study, highly elastic and functional nanofibers from SEBS triblock copolymer with the diameters of 286±93 nm were produced successfully by electrospinning for the first time, to the best of our knowledge. We believe that SEBS-based functional electrospun nanofibers will find widespread applications in medicine and water purification in the near future

Single molecule detection using nanopores has proven to be a powerful way of identifying biomolecules. There-fore, a variety of materials and methods have been developed by the nanopore community to generate credible outcomes. Here we report as the first time a novel polyimide nanopore platform for single DNA sensing. Novelty of the platform arises both from the ultra-thin structure of the polyimide membrane and also the technique used in the nanopore fabrication on a polymer membrane. Furthermore, the ultra-thin nature of the membrane eliminates the involvement of highly demanding fabrication steps often employed in the solid-state nanopore membrane production. Herein we present the fabrication of nanopores in such an ultrathin polymer membrane and its successful application in sensing DNA molecules at single molecule level, holding a promise as a potential single-molecule analytical device unlike its common use in research.

Electrophysiology is the method of choice to characterize membrane channels. In this paper, we demonstrate a patch pipette based simple miniaturization that allows performing conductance measurements on a planar lipid bilayer in a microfluidic channel. Membrane proteins were reconstituted into Giant Unilamellar Vesicles (GUVs) by electroswelling, and GUVs with a single channel insertion were patched at the tip of pipette. We applied this approach to investigate the interactions of porins from E.coli with single antibiotics, and this will potentially provide information on the permeability rates. The results of this paper suggest that this approach can be extended to the integration of several pipettes into the microfluidic channel from different positions, allowing the multiplexed recordings and also reducing the substrate consumption below $\mu \text{L}$ volumes.

Membranous nephropathy is one of the most common causes of nephrotic syndrome in the adult population. According to the underlying etiology, membranous nephropathy is classified as either primary or secondary. Systemic lupus erythematosus is an autoimmune disease that can affect the kidneys in 50% of patients in the course of the disease. Renal disease may be the first manifestation of systemic lupus erythematosus and the development of systemic findings may be delayed for about 1–5 years following the diagnosis of lupus nephritis. We present a 59-year-old male patient who had a diagnosis of idiopathic membranous nephropathy since 2007 and developed membranous lupus nephritis during the 12-year follow-up without any extrarenal systemic lupus erythematosus findings.

The purpose of this study is to examine the attitudes of teacher toward heritage (mother tongue) languages based multilingual education and based on these findings to determine how teachers within public school settings perceive multilingual education. The sample comprised 150 teachers employed in public schools in Turkey. The survey method was used in this study, which used a 5-point Likert-type scale based on the multilingual education attitudes. The scale included 25 items and was prepared through the SurveyMonkey database. The survey was designed to determine the attitudes of teachers on heritage-language–based multilingual education and was conducted through the snowball sampling technique on teachers working in public schools in Turkey. A Cronbach’s alpha reliability analysis on the data was conducted, and the reliability coefficient of the scale was .968. The results showed the positive attitudes of teachers concerning multilingual education policies.

Simple Summary Maintenance of telomeres is a fundamental step in human carcinogenesis and is primarily regulated by telomerase and the human telomerase reverse transcriptase gene (TERT). Improved understanding of the transcriptional control of this gene may provide potential therapeutic targets. Epigenetic modifications are a prominent mechanism to control telomerase activity and regulation of the TERT gene. TERT-targeting miRNAs have been widely studied and their function explained through pre-clinical in vivo model-based validation studies. Further, histone deacetylase inhibitors are now in pre and early clinical trials with significant clinical success. Importantly, TERT downregulation through epigenetic modifications including TERT promoter methylation, histone deacetylase inhibitors, and miRNA activity might contribute to clinical study design. This review provides an overview of the epigenetic mechanisms involved in the regulation of TERT expression and telomerase activity. Abstract Telomerase was first described by Greider and Blackburn in 1984, a discovery ultimately recognized by the Nobel Prize committee in 2009. The three decades following on from its discovery have been accompanied by an increased understanding of the fundamental mechanisms of telomerase activity, and its role in telomere biology. Telomerase has a clearly defined role in telomere length maintenance and an established influence on DNA replication, differentiation, survival, development, apoptosis, tumorigenesis, and a further role in therapeutic resistance in human stem and cancer cells including those of breast and cervical origin. TERT encodes the catalytic subunit and rate-limiting factor for telomerase enzyme activity. The mechanisms of activation or silencing of TERT remain open to debate across somatic, cancer, and stem cells. Promoter mutations upstream of TERT may promote dysregulated telomerase activation in tumour cells but additional factors including epigenetic, transcriptional and posttranscriptional modifications also have a role to play. Previous systematic analysis indicated methylation and mutation of the TERT promoter in 53% and 31%, respectively, of TERT expressing cancer cell lines supporting the concept of a key role for epigenetic alteration associated with TERT dysregulation and cellular transformation. Epigenetic regulators including DNA methylation, histone modification, and non-coding RNAs are now emerging as drivers in the regulation of telomeres and telomerase activity. Epigenetic regulation may be responsible for reversible silencing of TERT in several biological processes including development and differentiation, and increased TERT expression in cancers. Understanding the epigenetic mechanisms behind telomerase regulation holds important prospects for cancer treatment, diagnosis and prognosis. This review will focus on the role of epigenetics in telomerase regulation.

To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting. The data of 104 patients diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months. A total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16–0.54, p

Telomerase has a critical role in cell proliferation, tumor maintaining, and therapy resistance, which act by modifying many signaling pathways. 2-[(E)-3-Naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532) is one of the most studied telomerase inhibitors, and it targets telomerase components TERC and TERT. In this novel study, we aimed to investigate the epigenetic effects of BIBR1532 on both hematologic malignancies and solid tumors. K-562 human chronic myeloid leukemia cell line and U87MG glioblastoma cell line were compared with control groups without BIBR1532 treatment. Cytotoxic effects of BIBR1532 were determined by using WST-1 assay. Apoptotic effects of BIBR1532 were detected by using annexin V method. To assess expression changes in the human epigenetic chromatin modification enzyme genes, total RNA was isolated from K-562 and U87MG cells treated with BIBR1532 and untreated control cells. BIBR1532 induced 2.41-fold apoptotic cell death in U87MG cell lines compared with control groups. Apoptosis was slightly induced in K-562 cells with BIBR1532 treatment compared with control cells. We observed that BIBR1532 also regulates similar genes in both cell lines, and it is useful on epigenetic mechanisms. As a result, telomerase inhibitor BIBR1532 has a significant effect on both hematological malignancies and solid tumors.

It is emphasized that cancer stem cells (CSCs) forming the subpopulation of tumour cells are responsible for tumour growth, metastasis, and cancer drug resistance. Inadequate response to conventional therapy in breast cancer leads researchers to find new treatment methods and literature surveys that support CSC studies. A selective anticancer agent BIBR1532 inhibits the telomerase enzyme. Many of the chemotherapeutic drugs used in clinical trials have harmful effects, but the advantage of telomerase-based inhibitors is that they are less toxic to healthy tissues. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mammalian target of rapamycin (mTOR) pathway is common in breast cancer, and the interaction between the mTOR pathway and human telomerase reverse transcriptase (hTERT) is essential for the survival of cancer cells. In our study, we treated MCF-7, breast cancer stem cell (BCSC) and normal breast epithelial cell MCF10A with the BIBR1532 inhibitor. The IC 50 doses for the 48th hour of BIBR1532 treatment were detected as 34.59 μM in MCF-7, 29.91 μM in BCSCs, and 29.07 μM in MCF10A. It has been observed that this agent induces apoptosis in the BCSC and MCF-7 cell lines. According to the results of cell cycle analysis, G 2 /M phase accumulation was observed in BCSC and MCF-7 cell lines. It has also been shown that BIBR1532 suppresses telomerase activity in BCSC and MCF-7. The effect of BIBR1532 on the mTOR signalling pathway has been investigated for the first time in this study. It is thought that the telomerase inhibitor may bring a new approach to the treatment and it may be useful in the treatment of CSCs.

Cancer stem cells (CSCs), which are defined as a subset of tumor cells, are able to self-renew, proliferate, differentiate similar to normal stem cells. Therefore, targeting CSCs has been considered as a new approach in cancer therapy. The mammalian target of rapamycin (mTOR) is a receptor tyrosine kinase which plays an important role in regulating cell proliferation, differentiation, cell growth, self-renewal in CSCs. On the other hand, hTERT overactivation provides replicative feature and immortality to CSCs, so the stemness and replicative properties of CSCs depend on telomerase activity. Therefore hTERT/telomerase activity may become a universal biomarker for anticancer therapy and it is an attractive therapeutic target for CSCs. It is known that mTOR regulates telomerase activity at the translational and post-translational level. Researchers show that mTOR inhibitor rapamycin reduces telomerase activity without changing hTERT mRNA activity. Correlation between mTOR and hTERT is important for survival and immortality of cancer cells. In addition, the PI3K/AKT/mTOR signaling pathway and hTERT up-regulation are related with cancer stemness features and drug resistance. mTOR inhibitor and TERT inhibitor combination may construct a novel strategy in cancer stem cells and it can make a double effect on telomerase enzyme. Consequently, inhibition of PI3K/AKT/mTOR signaling pathway components and hTERT activation may prohibit CSC self-renewal and surpass CSC-mediated resistance in order to develop new cancer therapeutics.

With the view of enhancing the functionality of label-free single molecule nanopore-based detection, we have designed and developed a highly robust, mechanically stable, integrated nanopipette-microfluidic device which combines the recognized advantages of microfluidic systems and the unique properties/advantages of nanopipettes. Unlike more typical planar solid-state nanopores, which have inherent geometrical constraints, nanopipettes can be easily positioned at any point within a microfluidic channel. This is highly advantageous, especially when taking into account fluid flow properties. We show that we are able to detect and discriminate between DNA molecules of varying lengths when motivated through a microfluidic channel, upon the application of appropriate voltage bias across the nanopipette. The effects of applied voltage and volumetric flow rates have been studied to ascertain translocation event frequency and capture rate. Additionally, by exploiting the advantages associated with microfluidic systems (such as flow control and concomitant control over analyte concentration/presence), we show that the technology offers a new opportunity for single molecule detection and recognition in microfluidic devices.