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Abstract Highly efficient adeno associated viruses (AAVs) targeting the central nervous system (CNS) are needed to deliver safe and effective therapies for inherited neurological disorders. The goal of this study was to compare the organ-specific transduction efficiencies of two AAV capsids across three different delivery routes. We compared AAV9-CBA-fLucYFP to AAV-DJ-CBA-fLucYFP using the following delivery routes in mice: intracerebroventricular (ICV) 1 × 1012 vg/kg, intrathecal (IT) 1 × 1012 vg/kg, and intravenous (IV) 1 × 1013 vg/kg body weight. Our evaluations revealed that following ICV and IT administrations, AAV-DJ demonstrated significantly increased vector genome (vg) uptake throughout the CNS as compared to AAV9. Through the IV route, AAV9 demonstrated significantly increased vg uptake in the CNS. However, significantly fewer vgs were detected in the off-target organs (kidney and liver) following administration of AAV-DJ using the IT and IV delivery routes as compared to AAV9. Distributions of vgs correlate well with transgene transcript levels, luciferase enzyme activities, and immunofluorescence detection of YFP. Overall, between the two vectors, AAV-DJ resulted in better targeting and expression in CNS tissues paired with de-targeting and reduced expression in liver and kidneys. Our findings support further examination of AAV-DJ as a gene therapy capsid for the treatment of neurological disorders.

Gen Z stands out as a new age learner group in the context of open and distance learning. Research shows that Gen Z has different needs and expectations form their predecessors; therefore, new educational interventions are required. The purpose of this study is to examine the suggestions of the scientific articles on Gen Z to draw educational conclusions. This systematic review includes educational suggestions (n = 77) of 59 articles selected from search results on Scopus, Google Scholar and ULAKBIM. The suggestions were coded and themed. Then, percentage and frequency analyses were made with the codes obtained. The main categories that emerged were speed, motivation, content, learning environment and active learning. Highlights of these suggestion categories are: rapid delivery of student feedback under the speed category, job-oriented education under the motivation category, use of student-produced content under the content category, paying attention to updating and following the digital contents under the learning environment category, learning autonomy acquisition practices under the active learning category. These educational suggestions are thought to help researchers and educational specialists who try to understand the generational differences and especially the features of Gen Z.

Aim:Idiopathic peripheral facial paralysis [Bell’s palsy (BP)] is the most common cause of acute, one-sided facial paralysis, whose etiopathogenesis is currently unknown. However, inflammation is considered to play a role in etiopathogenesis. In this study, we examined the relationship between hematologic parameters and indices in children with BP.Methods:The study included 60 pediatric patients diagnosed with BP between December 2017 and May 2022 and 60 healthy controls of the same age and gender. The relationship between the patient and control cohorts and between the severity of the disease and inflammation markers was analyzed. Low-severe BP (House-Brackmann classification grade 2-3) and high-severe BP (House-Brackmann classification grade 4-5) were grouped. Complete blood count parameters and hematologic indices [neutrophil count/lymphocyte count (NLR), platelet count/lymphocyte count (PLR), monocyte count/lymphoid count (MLR), and platelet mass index] were recorded as inflammation markers.Results:55% of the patients had BP on the right side, 48.3% had grade 3, and 30.0% had grade 4 facial paralysis. Leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts were significantly higher in the patient group than in the control group (p-values p

The expression levels of certain genes or proteins may exhibit various features regardless of the tissue type. The housekeeping genes and reference proteins are often used during the normalization of expression studies. Herein, we aim to determine and validate the most stable reference gene and protein for a healthy human fibroblast cell line. This study used a finite fibroblast cell line derived from healthy human skin (CCD1079Sk). The samples between 25 and until senescence occurs at passage 55 were collected. Morphological changes during aging by cultivation were observed in each passage. Seven genes (ACTB, SDHA, GAPDH, RPLP0, VCL, TBP, 18S) were evaluated during cultivation and ranked according to their stability via the RefFinder interface. This study reports strong variations for both gene and protein expression studies and the morphology of the cells. Notably, during cultivation, the cell morphology showed an irreversible change starting from passage 43, before the known replicative lifespan of CCD1079Sk. The lack of an RPLP0 subunit after passage 39 may limit the cultivation range when protein expression is required. GAPDH is also an ideal reference gene and protein when studies include gene and protein expression. Or, as a second option, Vinculin may be the first choice when mRNA expression is required, and β-Actin is the best choice for reference protein when the studies include only protein expression. Plus, such as SDHA, RPLP0, and TBP should be avoided. These results will benefit further studies, including normalization for both gene, protein, and cell type.

Conclusion: The significantly higher trimethylamine n-oxide levels in patients with coronary artery ectasia without coronary artery disease suggest that the microbiota and its metabolites independently play a role in the pathophysiology or progression of vascular remodeling or endothelial dysfunctions. Also, its effect on the endothelial surface may depend on the threshold value.

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 μg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.

Purpose: One of the modeling methods used in the training of all design disciplines is physical model making. This study investigates the model-making technique and emphasizes the positive effects of model-making and its utility in the academic setting in order to understand its effects on design and learning. The "Equipment Design" course, taken in the 3rd academic semester at the Landscape Architecture Department at Karadeniz Technical University, was addressed as the application for this study. This course aims to convey to students the knowledge of how to utilize equipment in the design process in terms of ergonomics and aesthetics. The objective of the course is to design creative equipment that has appropriate dimensions and form that integrates with the selected activity. During the course, the students were assigned a sitting activity as a design problem and asked to design unique seating equipment and to express it through a model. Research Methods: In the first phase, the intention was to explore how students analyzed the seating activity through the model and how they interpreted the relationships among the dimensions, form and equipment in their designs, and thus equipment models were investigated accordingly. In the second phase, a survey study developed examines the effects of the model technique on the design process and student learning. Thus, the effects of the model-making technique on the level of teaching in the Equipment Design course were determined. Findings: Consequently, it was determined that students' notions of design develops through model making and that making a model of the seating equipment was found to be an instructive method for students of landscape architecture in terms of dimensions, form and material. Implications for Research and Practice: the "Equipment Design" course can contribute to the design processes of students especially in terms of creativity and realism. The model making approach facilitates students' understanding of dimension, form and the dimension-form relationship and material and the material-form relationship in the learning process, while contributing greatly to the development of the students' design processes.

There has been an increasing interest in patient-reported outcome (PRO) measures in both the clinical and research settings to improve the quality of life among patients and to identify when clinical intervention may be needed. The primary purpose of this prospective study was to validate an acute breast skin toxicity PRO measure across a broad sample of patient body types undergoing radiation therapy. Between August 2018 and September 2019, 134 women undergoing adjuvant breast radiotherapy (RT) consented to completing serial PRO measures both during and post-RT treatment and to having their skin assessed by trained trial radiation therapists. There was high patient compliance, with 124 patients (92.5%) returning to the clinic post-RT for at least one staff skin assessment. Rates of moist desquamation (MD) in the infra-mammary fold (IMF) by PRO were compared with skin assessments completed by trial radiation therapists. There was high sensitivity (86.5%) and good specificity (79.4%) between PRO and staff-reported presence of MD in the IMF, and there was a moderate correlation between the peak severity of the MD reported by PRO and assessed by staff (rho = 0.61, p < 0.001). This prospective study validates a new PRO measure to monitor the presence of MD in the IMF among women receiving breast RT.

Abstract Background A novel device for supine positioning in breast radiotherapy for patients with large or pendulous breasts has been developed and tested in phase II studies. This trial is designed to assess the efficacy of the device to reduce skin toxicity and unwanted normal tissue dose in comparison to the current clinical standard for supine breast support during breast radiotherapy. Methods Patients at high risk for moist desquamation, having infra-mammary fold or lateral ptosis, will be randomized into two arms. Patients in the control arm will receive breast radiotherapy with supine positioning using current standard of care. Patients in the experimental arm will be positioned supine with the novel device. The primary endpoint is the incidence of moist desquamation in the infra-mammary fold. We hypothesize a 20% reduction (from 50 to 30%) in the rate of moist desquamation in the study arm versus the control arm. For 80% power, two-tailed α = 0.05 and 10% loss to follow up, 110 patients will be assigned to each arm. The proportion of patients experiencing moist desquamation in the two arms will be compared using logistic regression adjusting for brassiere cup size, skin fold size, body mass index, smoking status, and dose fractionation schedule. An unadjusted comparison will also be made using the chi-square test, or Fisher’s exact test, if appropriate. Secondary endpoints include dose-volume statistics for the lung and heart, skin dose and clinical parameters including setup time, reproducibility, and staff experience with setup procedures. Patient-reported pain, skin condition interference with sleep and daily activities, and comfort during treatment are also secondary endpoints. Discussion Based on results from earlier phase II studies, it is expected that the device-enabled elimination of infra-mammary fold should reduce toxicity and improve quality of life for this patient population. Earlier studies showed reduction in dose to organs at risk including lung and heart, indicating potential for other long-term benefits for patients using the device. This study is limited to acute skin toxicity, patient-reported outcomes, and clinical factors to inform integration of the device into standard breast radiotherapy procedures. Trial registration Clinicaltrials.gov identifier: NCT04257396 . Registered February 6 2020.

Introduction: It is now known that the microbiota is far beyond the microbial communities living in certain parts of our body and functions like a metabolic organ. In addition, the microbiota, through its metabolites, is involved in the pathophysiology or progression of a wide range of diseases, from atherosclerotic diseases to metabolic diseases and even neurological diseases. Among these metabolites, trimethylamine n‐oxide metabolite has been shown to be particularly effective in atherosclerotic heart diseases. Materials and Methods: A total of 155 patients, who underwent coroner angiography for stable angina were included in the study. Of these patients, 81 patients with coronary artery ectasia (patient group) and 74 patients without coronary artery ectasia (control group) were evaluated for trimethylamine n‐oxide metabolite. Results: Statistically significantly higher trimethylamine n‐oxide metabolite levels were observed in the coronary artery ectasia group compared to the control group. Conclusion: The significantly higher trimethylamine n‐oxide levels in patients with coronary artery ectasia without coronary artery disease suggest that the microbiota and its metabolites independently play a role in the pathophysiology or progression of vascular remodeling or endothelial dysfunctions. Also, its effect on the endothelial surface may depend on the threshold value. [ABSTRACT FROM AUTHOR]

Background: Geleophysic dysplasia (GD) and Weill–Marchesani syndrome (WMS) are two rare genetic disorders that are classified as acromelic dysplasias and have many common features that overlap clinically and genetically in some patients. Both diseases are characterized by acromelic features, including short stature, brachydactyly, joint limitations, and cardiac involvement. WMS is distinguished from GD mainly by ocular abnormalities, including high myopia, microspherophakia, ectopia lentis, and glaucoma and the absence of the life-threatening airway stenosis and early lethality. These two syndromes are allelic diseases of the FBN1 gene, with the gene families including A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) and latent transforming growth factor-beta-binding protein (LTBP). Although the ADAMTSL2 gene has been associated only with GD within the acromelic dysplasias, there have been reports of patients with ADAMTSL2-related GD exhibiting ocular abnormalities that resemble WMS. Methods and Results: We present a 24-year-old female patient with microspherophakia, ectopia lentis, myopia, short stature, joint stiffness, thick skin, short hands and feet, and cardiac valve disease consistent with WMS. The virtual panel analysis, including WMS and GD-related genes, revealed a homozygous c.493 G>A (p.Ala165Thr) variant in the ADAMTSL2 gene (NM_014694.4), which has been previously reported in a geleophysic dysplasia patient. Conclusions: Mounting evidence suggests that GD and WMS may be allelic diseases of the ADAMTSL2 gene. [ABSTRACT FROM AUTHOR]

Objective: To reveal the relationship among smoking cessation before surgery, pre- and post-operative anxiety, and pain among chronic smokers. Method: The randomized controlled prospective clinical study was conducted in 2018 on the east of Turkey, in Van Yuzuncu Yil University Dursun Odabas Medical Center in city of Van. After approval from the ethics committee participants of either gender aged 20-60 years scheduled to undergo rhinoplasty surgery and graded as American Society of Anaesthesiologists I–II were included. The participants were categorised into smokers group S and non-smokers group NS. Spielberger State-Trait Anxiety Inventory values for preoperative period, postoperative 0, which is the moment when the modified Aldrete score is 9, as well as for 2, 4 and 6 hours, and visual analogue scale values for the postoperative 0, 2, 4 and 6 hours were recorded. Data was analysed using SPSS 26. Results: Of the 120 patients, there were 60(50%) in group S; 28(46.7%) females, 32(52.3%) males, overall mean age 33.0±9.7 years. In group NS, there were 34(56.7%) females and 26(43.3%) males with an overall mean age of 34.7±10.1 years (p 0.05). Group S had Spielberger State-Trait Anxiety Inventory preoperative and postoperative values significantly higher than group NS (p 0.05). While the values for postoperative 4 and 6 hours increased in group S, corresponding values decreased in group NS (p 0.05). Conclusion: High anxiety scores in preoperative period appeared to be associated with stress from surgery and anaesthesia and could have been caused by smoking dependency during the preoperative and postoperative periods.

Genetic factors play a major role in the formation of allergic rhinitis. The most studied genes for the investigation of the genetic origin of allergic rhinitis are the cytokine genes. We aimed to analyse the relation between susceptibility to allergic rhinitis and IL-4 C-590T and C+33T polymorphisms. For this aim, serum IL-4 levels and IL-4 C-590T and C+33T polymorphisms of 211 allergic rhinitis cases and 232 healthy individuals (control group) were analysed. We found that the individuals carrying IL-4 +33T allele and IL-4 -590TT and +33TT genotypes were much more predisposed to allergic rhinitis than the individuals carrying CC wild type genotypes. Our results also suggest that serum IL-4 levels of control group carrying the IL-4 -590 CT and TT genotypes and T allele and IL-4 +33 CT and TT genotypes, and T allele were significantly higher than the CC genotypes and T alleles carriers. As a result, it is possible to say that IL-4 C-590T and C+33T polymorphisms may increase the susceptibility of allergic rhinitis because of their lowering of IL-4 levels in serum. [Med-Science 2021; 10(2.000): 462-8]

Intensive chemotherapy can cause long-lasting immunosuppression in children who survived cancer. The immunosuppression varies according to the type of cancer, intensity of chemotherapy and age of the patient. A sufficient immune reconstruction when has been completed in childhood cancer survivors, the re-vaccination program can achieve sufficient antibody levels for some of the life-threatening vaccine-preventable infectious diseases. This study evaluates the serological status of pediatric acute lymphoblastic leukemia (ALL) cases before and after the intensive chemotherapy treatment. Antibodies against measles, mumps, rubella, varicella, hepatitis A and B were tested with the enzyme-linked immunosorbent assay (ELISA) method. Antibody titers were measured firstly at the leukemia diagnosis time when the chemotherapy was not started. The second evaluation of antibody titers was studied at 6 months after the cessation of chemotherapy for all patients. Forty-six patients with the mean age of 6.1 ± 4.5 years were participated in this study. Changing to seronegative after treatment was significantly different in measles, rubella, hepatitis A and hepatitis B (p

Background and purpose: This study recommends clinical epidermal dose calculation methods based on in‐vivo film measurements and registered skin dose distributions with the Eclipse (Varian Medical Systems) treatment planning system's Analytical Anisotropic Algorithm (AAA) and Acuros XB (AXB) dose calculation algorithms. Materials and methods: Eighteen AAA V13.6 breast plans were recalculated using AXB (dose to medium) V13.5 with the same beam parameters and monitor units as in the original plans. These are compared against in‐vivo Gafchromic film measurements from the lateral and inferior breast regions. Three skin structures in the treatment planning system are evaluated: a surface layer of voxels of the body contour, a 0.2 cm internal skin rind, and a 0.5 cm internal skin rind. Results: Systematic shifts are demonstrated between the film measurements of skin dose and the Eclipse dose calculations. On average, the dose to the surface layer of pixels is underestimated by AAA by 8% and overestimated by AXB by 3%. A 5 mm skin rind extended into the body can increase epidermal dose calculations on average by 8% for AAA and 4% for AXB. Conclusion: This is the first study to register in‐vivo skin dose distributions in the breast to the treatment planning system for comparison. Based on the results from this study it is recommended that epidermal dose is calculated with a 0.5 cm skin rind for the AAA algorithm and with rind thickness up to 0.2 cm for the AXB algorithm. [ABSTRACT FROM AUTHOR]

Aim:Acute rheumatic fever (ARF) is the most common cause of acquired heart disease especially in developing countries. This study is intended to evaluate the relationship between severity of cardiac involvement and hematological parameters in children diagnosed with carditis at the first episode of ARF.Methods:In this study, 45 children with carditis at the first episode of ARF and 30 healthy children of the same age and gender, between September 2015 and February 2019, were retrospectively reviewed. The data of the patients were recorded from the hospital automation system. Patients with acute rheumatic carditis (ARC) were grouped into two as mild (n=30) and moderate-severe ARC (n=15). Hemoglobin, red blood cell distribution width (RDW), leukocyte, neutrophil, monocyte, lymphocyte, platelet counts, neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte ratio (MLR) were compared between control and all carditis patients, mild and moderate-severe carditis.Results:In ARC patients, hemoglobin and RDW values were statistically significantly lower (p

Recombinant proteins have an economical value with their utilization in many areas from food industry to pharmaceutical and chemical industry. Therefore, it is of great importance to establish optimum production systems for the proteins of interest. One of the critical steps in protein production is regulation of the gene expression. Promoters are among the key regulatory elements which can directly control the level of recombinant gene expression in a host cell. Thus, a suitable promoter is required for optimum gene expression. Promoter engineering is an innovative approach to find out the best promoter system for the expression of recombinant genes, which influences the overproduction of proteins of interest. In this review, some of the bacterial hosts highly used in recombinant protein production were discussed. Next, the importance of promoters in recombinant gene expression, and promoter engineering for enhanced protein production were described. Utilization of double promoter systems was highlighted as one of the successful techniques in overproduction of recombinant proteins. Increment in the variety and availability of the novel methodologies especially in the synthetic biology is expected to increase the quality and the quantity of recombinant proteins with an economical value.

According to the TURHEP study, the prevalence of Helicobacter pylori in Turkey is 82.5%. After FDA approval in 1995, many countries have used standard triple therapy (proton pump inhibitor 40 mg b.i.d clarithromycin 500 mg b.i.d and amoxicillin 1 gr b.i.d) for Helicobacter pylori treatment. In the beginning, eradication rates were above 90% in many countries; however, current studies have demonstrated a prominent decrease in successful treatment rates, even down to 60%. This unfavorable reduction stimulated searches for new treatment protocols. Treatment protocols differ according to country, prevalence, cost-effectiveness, antibiotic resistance, CYP2C19 polymorphism and eradication rates. Thus, each country/region needs to revise its own therapeutic results and the efficacy of various eradication regimens in the treatment of Helicobacter pylori. This report aims to review the current status of Helicobacter pylori treatment in Turkey and to provide recommendations for rational therapeutic considerations for the eradication of the bacterium. (NCI-2019-0024.R1)