Emotional labor among Turkish nurses: A cross-sectional study.

Nurses are the closest healthcare providers to patients and emotional labor is the most invisible part of nursing work. However, the management of emotions to promote organizational goals and to ensure patient satisfaction may have both positive and negative impacts on nurses' working life. The purpose of this cross-sectional, descriptive study was to examine the emotional labor behaviors of nurses and their opinions on emotional labor. Two hundred nineteen nurses working at public hospitals in Ankara between September and December 2018 participated to this study. Data were collected using the sociodemographic characteristics form and "The Scale of Emotional Labor Behavior for Nurses." Nurses had higher scores on the deep and sincere emotional acting subdimensions of the emotional labor scale than the surface acting subdimension. Findings suggest that nurses act deeply and intimately, instead of surface acting. Most of the nurses expressed that nurses were emotionally affected when caring for patients; however, nurses had to control their feelings toward patients and behave professionally to meet the expectations of their managers, which may lead to an implicit emotional dissonance. Based on the results of this study, we suggest to support nurses emotionally and to incorporate the topic of emotional labor into educational programs.

Current molecular and therapeutic advances in liposarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, and angiosarcoma.

Sarcomas probably develop after malignant transformation of embryonic mesenchymal cells and have broad spectrum histopathologically since they can develop from striated skeletal muscle and smooth muscle, fat and fibrous tissue, bone, cartilage and other mesenchymal tissues. The most common histological subtypes of soft tissue sarcoma in adults are: liposarcoma, leiomyosarcoma, poorly differentiated pleomorphic sarcoma, and gastrointestinal stromal tumor. Molecular and genetic studies of soft tissue sarcomas, which are considered as heterogeneous groups in terms of their molecular and clinical characteristics, are still an important area of ​​interest The heterogeneity of the molecular and genetic alterations of these malignancies, which are mostly treated with surgery and chemotherapy, also offers hope to the researchers in terms of treatment targets. In this article, molecular biologic features of the soft tissue sarcomas including liposarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, and angiosarcoma are discussed in the light of recent developments in molecular biology, targeted therapies and immunotherapy.

Public perceptions about nurses communicated via Twitter in Turkey.

OBJECTIVES: Social media platforms such as Twitter allow people to openly express their views about many topics, including the nursing profession. COVID-19 is currently a frequently searched and discussed topics on Twitter. This study was performed to identify the image of nursing in the social media before and during COVID-19 pandemic in Turkey, and to review of public perceptions about nurses' communication on twitter in Turkey. DESIGN: This study was conducted using content analysis with a sample of tweets posted on Twitter before and during the COVID-19 pandemic. Codes were created, including expressions of respect, anxiety, violence, gratefulness, anger, positivity, and negativity. RESULTS: Findings showed that 35.65% of the 373 tweets posted prior to the COVID-19 pandemic were positive while 64.35% were negative. During the pandemic 91.94% of the 1006 tweets were positive and 8.06% were negative. CONCLUSION: The results of this study suggests that public opinion about nurses, as reflected on Twitter during the COVID 19 pandemic, was positive.

Determining the Spiritual Care Requirements and Death Anxiety Levels of Patients Diagnosed with COVID-19 in Turkey.

Our study was conducted to determine the spiritual care needs and death anxiety levels of individuals diagnosed with COVID-19. The population consisted of patients who were diagnosed with COVID-19 in Turkey. The mean total Spiritual Care Requirements Scale score of the participants was 67.05 ± 26.30. The mean VAS for Death Anxiety score of the participants was 8.82 ± 1.26. In our study, it was found that the patients diagnosed with COVID-19 had an increased need for spiritual care and high levels of anxiety about death.

Extracellular microRNAs: key players to explore the outcomes of in vitro fertilization.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown. METHODS: This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS. RESULTS: The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p < 0.001). Our results showed that miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 in NOR patients with a sensitivity of 80% and specificity of 71%, (AUC = [0.753 (0.651; 0.855)], p = 0.001). For clinical pregnancy outcome prediction, FF miRNA-21 exhibited high sensitivity (74.8%) and specificity (83.7%) with the AUC value of 0.774 (0.682; 0.865). CONCLUSION: Conclusively, our results provide evidence that miR-7-5p, miR-378-3p, miR-224, miR-212-3p were a differentially high expression in normo-androgenic PCOS patients than NOR patients. While miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 (p = 0.001). The expression level of FF miR-212-3p was significantly related to the probability of embryos to develop into a high-quality blastocyst in patients with normal ovarian reserve.

Osseointegrated Implants for Orbito-Facial Prostheses: Common Complications and Solutions.

PURPOSE: To evaluate anatomical and functional results of osseointegration with magnetic coupling for oculofacial prosthetic rehabilitation after exenteration. METHODS: This retrospective study included 11 consecutive patients who received orbital reconstruction and oculofacial prosthetic rehabilitation between September 2015 and October 2019. Patient demographics, surgical indications, previous treatment procedures, histopathologic features, and reconstructive procedures were recorded. RESULTS: The mean age was 37.81 ±â€Š23 years (range 5-78 years). The mean follow-up was 23.81 ±â€Š12 months (range 10-48 months). The principal diagnoses were squamous cell carcinoma of the eyelids (n = 2/11), mucoepidermoid carcinoma of the maxillary sinus (n = 2/11), rhabdomyosarcoma (n = 1/11), mucormycosis (n = 1/11), neurofibromatosis (n = 1/11), basosquamous carcinoma (n = 1/11), malign melanoma (n = 1/11), primitive neuroectodermal tumor (n = 1/11), and retinoblastoma (n = 1/11). Six of the patients were repaired by primary closure. Procedures performed to reconstruct the orbital cavity included split-thickness skin graft (n = 2/11), temporalis muscle flap (n = 2/11), and frontalis muscle flap (n = 1/11). Nine of the 11 patients who received orbital implants were successfully rehabilitated by epithesis. Postoperative complications included implant loss (n = 4/11), periprosthetic local infection (n = 3/11), and soft tissue overgrowth around the orbital prosthesis (n = 2/11). All patients had Straumann bone level implant (Basel, Switzerland) osseointegrated titanium implants (3.5 mm) placed in a 2-stage procedure over a span of 3 to 4 months with subsequent successful prosthesis fitting. CONCLUSION: The reconstructive methods following orbital exenteration, should be customized according to the patients' characteristics such as extension of the orbital defect, bone quality, and expectations to achieve satisfactory results.

Association Between Anterior Cingulate Cortex Neurochemical Profile and Clinical Remission After Electroconvulsive Treatment in Major Depressive Disorder: A Longitudinal 1H Magnetic Resonance Spectroscopy Study.

BACKGROUND: The aim of the study was to assess anterior cingulate cortex (ACC) neurochemical profile of patients with unipolar major depressive disorder (MDD) before and after electroconvulsive therapy (ECT) by using 1H magnetic resonance spectroscopy (1H-MRS). METHOD: Using 1H-MRS, the metabolite levels of choline, glutamate + glutamine (Glx), myo-inositol, N-acetylaspartate, and total creatine were measured in ACC before and after 4-week ECT. The Montgomery-Åsberg Depression Rating Scale (MADRS) was implemented by blind raters to evaluate the efficacy of the treatment. Electroconvulsive therapy-remitter (ER) and nonremitter groups were compared using the 1-way repeated measures analysis of variance. RESULTS: Thirty patients with unipolar MDD (aged 41.3 ± 10.0 years, 66.7% female) were included in the study. The ER group (n = 16, 53.3%) and NR group did not differ regarding baseline Global Assessment of Functioning and MADRS scores. At the end of 4-week ECT treatment, results did not suggest any significant difference for metabolite levels in ACC. When compared with the NR group, the ER group had higher baseline levels of Glx (8.8 ± 1.8 vs 6.3 ± 2.0, P = 0.005) and total creatine (5.3 ± 0.6 vs 4.7 ± 0.5, P = 0.010). In addition, elevated baseline Glx (r = -0.68, P = 0.002) was associated with lower MADRS scores at the end treatment. Finally, the change in Glx levels was correlated with change in MADRS scores after ECT (r = 0.47, P = 0.049). LIMITATIONS: Modest sample size and 1H-MRS at 1.5 Tesla are limitations of the study. CONCLUSIONS: Results suggested that Glx levels could be a predictor of remission. Studies with larger samples should explore neurochemical correlates of ECT in unipolar MDD.

Speedy/RINGO protein interacts with ERK/MAPK and PI3K/AKT pathways in SH-SY5Y neuroblastoma cells.

Abnormal activity of ERK/MAPK and PI3K/AKT pathways is one of the most important factors for the development of many cancer types including neuroblastoma cancer. Apart from these two pathways, some cell cycle regulators such as Speedy/RINGO also contribute to neuroblastoma development. There is data reinforcing the possible communication of the components of ERK/MAPK and PI3K/AKT pathways in carcinogenic process. In addition to this, there are studies about the direct/indirect interaction of Speedy/RINGO with these pathways in different cell types other than neuroblastoma. However, there is not any study available showing the interaction of Speedy/RINGO with both pathways in neuroblastoma cells. Therefore, the aim of this study is to determine the possible effect of Speedy/RINGO on PI3K/AKT and ERK/MAPK pathways in SH-SY5Y neuroblastoma cells. For this aim, Speedy/RINGO was silenced by siRNA technique to analyze the effects of direct inhibition of Speedy/RINGO on these pathways. Results showed that Speedy/RINGO silencing caused a significant decrease in MEK1/2 expression and AKT phosphorylation. Afterward, MEK1/2 was inhibited using a specific inhibitor U0126. Data reveal a corresponding decrease in the Speedy/RINGO expression and AKT phosphorylation indicating a reciprocal interaction between ERK/MAPK and Speedy/RINGO. In addition, MTS analysis showed that both ERK/MAPK inhibition and Speedy/RINGO silencing significantly reduced the viability of SH-SY5Y cells. This study provides information about a possible interaction of Speedy/RINGO with PI3K/AKT and ERK/MAPK pathways in SH-SY5Y cells for the first time. It will not only help to better understand the cancer-prone interactions of these pathways but also enable us to identify the appropriate molecular targets for developing efficient treatment strategies.

p60-katanin: a novel interacting partner for p53.

Katanin, one of the best-characterized microtubule (MT) severing proteins, is composed of two subunits: catalytic p60-katanin, and regulatory p80-katanin. p60-katanin triggers MT reorganization by severing them. MT reorganization is essential for both mitotic cells and post-mitotic neurons in numerous vital processes such as intracellular transport, mitosis, cellular differentiation and apoptosis. Due to the deleterious effect of continuous severing for cells, p60-katanin requires a strategic regulation. However, there are only a few known regulators of p60-katanin. p53 functions in similar cellular processes as katanin such as cell cycle, differentiation, and apoptosis depending on its interacting partners. Considering this similarity, in this study we investigated p53 as a potential regulatory candidate of p60-katanin, and examined their interaction. Co-immunoprecipitation analyses revealed that p60-katanin interacts with p53. We were able to locate a potential interaction site for the two proteins by deleting different candidate regions We showed for the first time that p53 and p60-katanin interact. This interaction appears to occur via p53's DNA binding domain and p60-katanin's C-terminal. This study will pave the way for future studies regarding the functional outcomes of this interaction which is vital for understanding the regulation of cellular events such as cell cycle, differentiation, and apoptosis in disease and in health.

Evaluation of Lacrimal Drainage Function in the Anophthalmic Socket by Dacryoscintigraphy.

PURPOSE: To investigate whether impaired lacrimal pump function is a possible cause of discharge in patients wearing an artificial eye compared with the remaining healthy eye. METHODS: Consecutive patients wearing unilateral ocular prosthesis for ≥6 months were included in this retrospective study. Excluded were any deformities of eyelids or nasal passage, socket complications such as entropion, ectropion, ptosis, infection, pyogenic granuloma, contracted socket, obstruction of nasolacrimal duct diagnosed with lacrimal irrigation and a difference greater than 2 mm in terms of protrusion between two eyes detected by Hertel exophthalmometry. Patients were asked to score the levels of tearing and mucopurulent discharge between 0 and 5 to assess lacrimal drainage function subjectively. Furthermore, dacryoscintigraphy was performed to assess the functional status of the lacrimal system objectively. RESULTS: Included were 32 subjects (12 females, 20 males; aged 32.94 ±â€Š17.62, range 13-78). Mean duration of prosthetic wearing 26.41 ±â€Š21.30 (6-72) months. The mean subjective scores of tearing and mucopurulent discharge were 1.56 ±â€Š1.67 and 1.94 ±â€Š1.63, respectively. The rate of functional stenosis was significantly higher in the anophthalmic socket side as compared to the healthy side (P = 0.002). The rates of a presac, preduct, and intraduct obstruction was notes as n = 9, n = 10, n = 1 and n = 0, n = 6, n = 2 in the anophthalmic side and the companion eye, respectively (P = 0.021). CONCLUSION: Compared to paired healthy eyes, the ocular prosthesis exhibited significantly higher rates of functional lacrimal duct obstruction, especially at the presac level. The alterations in orbital volume and tear film composition in addition to reduced corneal reflex blinking may lead to the failure of lacrimal pump function in artificial eyes.

The Effect of Two Different Frontalis Sling Approaches on Postoperative Eyelid Contour: A Comparative Study.

PURPOSE: To compare two different frontalis sling approaches, tarsal fixation and orbicular muscle fixation, using silicone rod (FCI Ophthalmics, Marshfield Hills, MA, USA) in terms of postoperative upper eyelid contour in patients with poor levator muscle function. DESIGN: Retrospective, comparative, case series. METHODS: Ten eyes of seven patients who received frontalis sling surgery with orbicularis muscle fixation (group 1), eight eyes of seven patients who received frontalis sling surgery with tarsal fixation (group 2) and 30 eyes of 15 age and sex-matched healthy controls (control group) were included. Postoperative photographs of all the participants were taken in the primary gaze, and each photograph was viewed on a computer. The distance between the upper lid margin and pupillary center (MCD), nasal limbus (MND), and temporal limbus (MTD) was measured, respectively, using the ruler in Microsoft Paint Software and compared with each other for each participant. RESULTS: Both nasal, central and temporal margin distance values in group 1 and group 2 were significantly lower than those of the control group (p < 0.05 for all values). The ratio of MTD/MCD in the control group was significantly higher than group 1 (p = 0.04) besides the ratio of MND/MTD in the control group was significantly lower than group 1 (p = 0.01). DISCUSSION: Frontalis sling approach with tarsal fixation using silicone rod might provide improved cosmetic results including more symmetrical upper eyelid contour compared with orbicularis muscle fixation approach. Moreover, the novel measuring technique presented in the current study provides a simple and effective assessment of the upper lid contour in daily practice setting. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Foveal avascular zone and vessel density in children with attention deficit hyperactivity disorder.

PURPOSE: To compare the retinal and choroidal microvasculature quantitatively via optical coherence angiography (OCTA) in children with attention deficit hyperactivity disorder (ADHD) who were under methylphenidate (MFD) treatment or newly diagnosed as ADHD and were not taking any medication. METHODS: This was a cross-sectional, comparative, and observational study. The children who were between 6 and 17 years old and previously diagnosed as ADHD and were under MFD treatment or who were newly diagnosed as ADHD were included in the study. Optical coherence tomography angiography imaging was performed via OCT RT XR Avanti with AngioVue software (Optivue Inc, Freemont, CA). The main outcome measure of the study was OCTA parameters of the children with ADHD. RESULTS: A total of 186 eyes of 186 patients were included in the study. There were 80 eyes in the control group (newly diagnosed) and 106 eyes in the treatment group (under MFD treatment). The mean duration of methylphenidate use in the treatment group was 33.9 ± 20.1 months (between 6 and 84 months). The choriocapillary flow area (p = 0.03), superficial parafoveal thickness (p = 0.01), and deep parafoveal thickness (p = 0.01) were statistically greater in the treatment group than the control group. CONCLUSION: Most of the important OCTA parameters especially foveal avascular zone (FAZ) area and FAZ perimeter were similar in the two groups. There was a significant difference between the two groups in parafoveal thickness values which might point to a slight effect of MFD on retinal circulation.

Comparison of Three Different Techniques on the Movement of Implants After Evisceration.

PURPOSE: To compare the results of 3 evisceration techniques involving placement of an acrylic implant within the scleral shell without posterior sclerotomy (Group 1), posterior sclerotomy with placement of a porous implant within the intraconal space (Group 2) and posterior sclerotomy with placement of a acrylic implant within the intraconal space (Group 3) with respect to ocular mobility, implant complications and patient satisfaction. METHODS: Single-center, retrospective, interventional case series. A chart review of 72 patients undergoing evisceration between February 2013 and January 2018 was carried out. Thirty-five patients met the inclusion criteria having a normal or near normal size eye and at least 6 months follow-up. The horizontal movements of the implant and the artificial eye was measured by using a ruler. Data analyses were conducted using the Mann-Whitney U test for 2 independent samples. RESULTS: Neither infection nor prolapse of the implant had occurred in any of the patients. The mean implant sizes were 18 mm in Group 1, 20 mm in Group 2 and 20 mm in Group 3. Statistically, a significant difference was assessed between Group 1 and Group 2 in both nasal and temporal movement of the socket; nasal and temporal movement of the prosthesis. Statistically, a significant difference was assessed between Group 1 and Group 3 in both nasal and temporal movement of the socket; nasal and temporal movement of the prosthesis. However, there was no statistically significant difference between Group 2 and Group 3 in neither nasal and temporal movement of the socket nor nasal and temporal movement of the artificial eye. CONCLUSION: Group 1 showed the significantly better movement of both prosthesis and socket in adduction and abduction than Group 2 and 3. The likely explanation for this may be that preserving the scleral shell integrity allows more efficient transmission of muscle contraction to the socket and prosthesis.

Development and characterization of rapid dissolving ornidazole loaded PVP electrospun fibers.

Gingivitis is a common and mild form of periodontal disease and can be described as a limited inflammation of the gingiva. This study aims to develop and characterize rapid releasing mucoadhesive fibers containing ornidazole with electrospinning process for the treatment of gingivitis. Polyvinylpyrrolidone (PVP) was chosen as a polymer and used at different concentrations of 10%, 12.5%, and 15%. Scanning electron microscopy images showed that fiber diameters increased with increasing polymer concentrations. Tensile strength and elongation at break values of fibers increased with increasing PVP amount, whereas the loading of ornidazole into the fibers decreased these parameters. The contact angle values of all fibers were found to be 0° due to the hydrophilic nature of PVP. Ornidazole was released within 5 min and diffused from all of the fibers faster than that of gel and solution formulations. Electrospun ornidazole fibers were found efficient against Porphyromonas gingivalis in antimicrobial activity studies. The results demonstrated that ornidazole loaded fibers could be a potential drug delivery system for the treatment of gingivitis.

The Role of Speedy/RINGO Protein in Breast Cancer as a Future Biomarker.

Background/Aim: Cyclin-dependent kinases (CDKs) are proteins that require the binding of regulatory subunits called cyclins and play a key role in cell cycle progression and activation. CDKs play a key role in carcinogenesis of many solid malignancies, and inhibition of these proteins has produced anti-cancer effects demonstrated in preclinical studies. This narrative review was conducted to develop a hypothetical approach to determine whether Speedy/RINGO, a protein associated with CDK2, could be a possible predictive factor in breast cancer patients treated with a CDK4/6 inhibitor. Materials and Methods: A literature search was conducted in PubMed, Web of Science, Medline, and Google Scholars search engines to match the following words: "Speedy/RINGO" or "Spy1" and "CDKs" or "Cyclin-dependent kinases (CDKs)" and "CDK4/6 inhibitors" and "Regulation" and "Molecular" and "Breast cancer" and "Carcinogenesis". Only articles investigating the relationship between the Speedy/RINGO protein and CDKs at the molecular level were included. Literature information was compiled by trying to establish a relationship with our hypothesis question. Results: Speedy/RINGO is a tightly regulated proto-oncogenic mammalian protein playing important roles in the somatic cell cycle. Studies have emphasized that although it does not have amino acid sequence homology with cyclins, it can activate CDK2. In addition, results showing molecular compensation of CDK4/6 inhibition through CDK2 activation, also showed that CDK2 can predict drug resistance. Another important finding was that overexpressed Speedy/RINGO, during CDK4/6 inhibitor treatment, could strongly activate CDK2, resulting in a negative response to treatment. Conclusion: Although many predictive factors have been investigated to indicate response to CDK4/6 inhibitors or determine drug resistance, a consensus biomarker has yet to be established. In light of the information obtained from our review, it can be concluded that the Speedy/RINGO protein may have an important role as a predictive biomarker in terms of response to treatment, continuity of treatment and drug resistance in patients treated with CDK4/6 inhibitors.

Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines.

Replicating RNA, including self-amplifying RNA (saRNA) and trans-amplifying RNA (taRNA), holds great potential for advancing the next generation of RNA-based vaccines. Unlike in vitro transcribed mRNA found in most current RNA vaccines, saRNA or taRNA can be massively replicated within cells in the presence of RNA-amplifying enzymes known as replicases. We recently demonstrated that this property could enhance immune responses with minimal injected RNA amounts. In saRNA-based vaccines, replicase and antigens are encoded on the same mRNA molecule, resulting in very long RNA sequences, which poses significant challenges in production, delivery, and stability. In taRNA-based vaccines, these challenges can be overcome by splitting the replication system into two parts: one that encodes replicase and the other that encodes a short antigen-encoding RNA called transreplicon. Here, we review the identification and use of transreplicon RNA in alphavirus research, with a focus on the development of novel taRNA technology as a state-of-the art vaccine platform. Additionally, we discuss remaining challenges essential to the clinical application and highlight the potential benefits related to the unique properties of this future vaccine platform.

Total aflatoxin and ochratoxin A levels, dietary exposure and cancer risk assessment in dried fruits in Türkiye.

This study aimed to measure total aflatoxin (AF) (AFB1, AFB2, AFG1, and AFG2) and ochratoxin A (OTA) levels in dried fruit samples and to evaluate the potential dietary exposure and cancer risk to these mycotoxins in Kayseri/Türkiye. Dried fruit samples were collected between April-May 2021. A total of 11 dried grapes and apricot samples, 7 dried fig and plum samples were collected. Total aflatoxins and OTA in dried fruits were determined by ELISA method. Then, the margin of exposure (MOE) and cancer risk were calculated. Total AF was detected in dried fruit samples between 42.86%, and 100%. Between 18.18% and 57.14% of samples exceeded the European Commission (EC) limits for total AF. Moreover, OTA was detected in all samples. Between 71.43% and 100% of samples exceeded the EC limits for OTA. Cancer risk due to OTA exposure was higher than total AF and it was determined that OTA exposure could pose a risk for public health (MOE < 10,000). Although mycotoxin exposure seems to be low due to the low consumption of dried fruit in Türkiye, the risk of exposure and cancer may increase because of complying with the recommendations of the dietary guidelines. The findings provide new insights into exposure to total AF and OTA through the consumption of dried fruit.

Trans-amplifying RNA expressing functional miRNA mediates target gene suppression and simultaneous transgene expression.

The co-delivery of microRNAs (miRNAs) and protein-coding RNA presents an opportunity for a combined approach to gene expression and gene regulation for therapeutic applications. Protein delivery is established using long mRNA, self-, and trans-amplifying RNA (taRNA), whereas miRNA delivery typically uses short synthetic oligonucleotides rather than incorporating it as a precursor into long RNA. Although miRNA delivery into the cell cytoplasm using long genomes of RNA viruses has been described, concerns have remained regarding low processing efficiency. However, miRNA precursors can be released from long cytoplasmic alphaviral RNA by a cytoplasmic fraction of Drosha. taRNA, a promising vector platform for infectious disease vaccination, uses a nonreplicating mRNA expressing an alphaviral replicase to amplify a protein-coding short transreplicon-RNA (STR) in trans. To investigate the possibility of simultaneously delivering protein expression and gene silencing, we tested whether a taRNA system can carry and release functional miRNA to target cells. Here, we show that mature miRNA is released from STRs and silences specific targets in a replication-dependent manner for several days without compromising the expression of STR-encoded proteins. Our findings suggest that incorporating miRNAs into the taRNA vector platform has the potential for gene regulation alongside the expression of therapeutic genes.

Targeting MDM2-p53 Axis through Drug Repurposing for Cancer Therapy: A Multidisciplinary Approach.

Cancer remains a major cause of morbidity and mortality worldwide, and while current therapies, such as chemotherapy, immunotherapy, and cell therapy, have been effective in many patients, the development of novel therapeutic options remains an urgent priority. Mouse double minute 2 (MDM2) is a key regulator of the tumor suppressor protein p53, which plays a critical role in regulating cellular growth, apoptosis, and DNA repair. Consequently, MDM2 has been the subject of extensive research aimed at developing novel cancer therapies. In this study, we employed a machine learning-based approach to establish a quantitative structure-activity relationship model capable of predicting the potential in vitro efficacy of small molecules as MDM2 inhibitors. Our model was used to screen 5883 FDA-approved drugs, resulting in the identification of promising hits that were subsequently evaluated using molecular docking and molecular dynamics simulations. Two antihistamine drugs, cetirizine (CZ) and rupatadine (RP), exhibited particularly favorable results in the initial in silico analyses. To further assess their potential use as the activators of the p53 pathway, we investigated the antiproliferative capability of the abovementioned drugs on human glioblastoma and neuroblastoma cell lines. Both the compounds exhibited significant antiproliferative effects on the abovementioned cell lines in a dose-dependent manner. The half-maximal inhibitory concentration (IC50) of CZ was found to be 697.87 and 941.37 µM on U87 and SH-SY5Y cell lines, respectively, while the IC50 of RP was found to be 524.28 and 617.07 µM on the same cell lines, respectively. Further investigation by quantitative reverse transcriptase polymerase chain reaction analysis revealed that the CZ-treated cell lines upregulate the expression of the p53-regulated genes involved in cell cycle arrest, apoptosis, and DNA damage response compared to their respective vehicle controls. These findings suggest that CZ activates the p53 pathway by inhibiting MDM2. Our results provide compelling preclinical evidence supporting the potential use of CZ as a modulator of the MDM2-p53 axis and its plausible repurposing for cancer treatment.

The effect of video-based fistula care education on hemodialysis patients' self-care behaviors: A randomized controlled study.

OBJECTIVE: This study aimed to determine the effect of face-to-face and video-based education for fistula care on hemodialysis patients' self-care behaviors. METHODS: The study was conducted as a randomized controlled experimental study. Accordingly, 60 patients were included in the study for 95% strength. Fistula care training was given to the patients in the control group using face-to-face education technique. Fistula care training was given to the patients in the experimental group using a video-based technique. RESULTS: The analysis showed that the post-test second week (p = 0.044) and fourth week (p = 0.00) mean scores of the experimental group were higher compared to those of the control group. CONCLUSION: These results showed that the video-based education given to hemodialysis patients was more memorable and instructive than the verbal education, and it was observed that the video-based education showed a higher level of success in developing self-care skills.