Search results for: breast tissue marker
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2627

Search results for: breast tissue marker

497 PCR Detection, Histopathological Characterization, and Autogenous Immunization of Bovine Papillomatosis (Wart) in Cattle, in Mekelle, Northern Ethiopia

Authors: Kidane Workelul, Yohans Tekle, Guesh Negash, Haftay Abraha, Nigus Abebe Shumuye, Yisehak Tsegaye Redda

Abstract:

Bovine papillomatosis (wart) is one of the economically important bovine skin diseases worldwide, caused by a group of viruses named papillomaviruses (PVs). However, it has often been misdiagnosed as other skin diseases and remained untreated. In order to determine the status of the diseases, twenty-two farms were visited, and fourteen infected cattle with cutaneous papillomatosis were identified from a total of 235. Papilloma biopsies were taken for molecular and histopathological characterization, the therapeutic trial of an autogenous vaccine was evaluated on infected animals. The overall status of bovine papillomatosis in this study was calculated as 5.96% (14/235). The disease was found to be statistically significant in the age groups less than two years (X² = 26.69, P = 0.0001). The more prominent histologically characterized lesions in the sampled tissue were identified as squamous papilloma and fibro-papilloma. The Polymerase Chain Reaction (PCR) based identification revealed that all the clinically and histo-pathologically characterized papillomatosis cases were found to be infected with Bovine Papilloma Virus1(BPV1), indicating that BPV1 was the most common and sole causative agent of the diseases in the study area. In immunizing active bovine papillomatosis, an autogenous vaccine therapeutic trial demonstrated excellent results, with practically full recovery and no recurrence of the infection. Hence, it is concluded that bovine papillomatosis is an economically important disease of young age group cattle as well as a treatable disease. So, the production of marketable autogenous vaccines against bovine papillomatosis should be started and given at an early stage.

Keywords: autogenous vaccine, bovine papillomatosis, bovine papilloma virus1 clinical-pathology, polymerase chine reaction, wart

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496 The New Insight about Interspecies Transmission of Iranian H9N2 Influenza Viruses from Avian to Human

Authors: Masoud Soltanialvar, Ali Bagherpour

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Documented cases of human infection with H9N2 avian influenza viruses, first detected in 1999 in Hong Kong and China, indicate that these viruses can be directly transmitted from birds to humans. In this study, we characterized the mutation in the Hemagglutinin (HA) genes and proteins that correlates with a shift in affinity of the Hemagglutinin (HA) protein from the “avian” type sialic receptors to the “human” type in 10 Iranian isolates. We delineated the genomes and receptor binding profile of HA gene of some field isolates and established their phylogenetic relationship to the other Asian H9N2 sub lineages. A total of 1200 tissue samples collected from 40 farms located in various states of Iran during 2008 – 2010 as part of a program to monitor Avian Influenza Viruses (AIV) infection. To determine the genetic relationship of Iranian viruses, the Hemagglutinin (HA) genes from ten isolates were amplified and sequenced (by RT-PCR method). Nucleotide sequences (orf) of the (HA) genes were used for phylogenetic tree construction. Deduced amino acid sequences showed the presence of L226 (234 in H9 numbering) in all ten Iranian isolates which indicates a preference to binding of α (2–6) sialic acid receptors, so these Iranian H9N2 viruses have the potential to infect human beings. These isolates showed high degree of homology with 2 human H9N2 isolates A/HK/1073/99, A/HK/1074/99. Phylogenetic analysis of showed that all the HA genes of the Iranian H9N2 viruses fall into a single group within a G1-like sublineage which had contributed as donor of six internal genes to H5N1 highly pathogenic avian influenza. The results of this study indicated that all Iranian viruses have the potential to emerge as highly pathogenic influenza virus, and considering the homology of these isolates with human H9N2 strains, it seems that the potential of these avian influenza isolates to infect human should not be overlooked.

Keywords: influenza virus, hemagglutinin, neuraminidase, Iran

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495 The Effect of Colloidal Metals Nanoparticles on Quarantine Bacterium - Clavibacter michiganensis Ssp. sepedonicus

Authors: Włodzimierz Przewodowski, Agnieszka Przewodowska

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Colloidal metal nanoparticles have drawn increasing attention in the field of phytopathology because of their unique properties and possibilities of applications. Their antibacterial activity, no induction of the development of pathogen resistance and the ability to penetrate most of biological barriers make them potentially useful in the fighting against dangerous pathogens. These properties are very important in the case of protection of strategic crops in the world, like potato - fourth crop in the world - which is host to numerous pathogenic microorganisms causing serious diseases, significantly affecting yield and causing the economic losses. One of the most important and difficult to reduce pathogen of potato plant is quarantine bacterium Clavibacter michiganensis ssp. sepedonicus (Cms) responsible for ring rot disease. Control and detection of these pathogens is very complicated. Application of healthy, certified seed material as well as hygiene in potato production and storage are the most efficient ways of preventing of ring rot disease. Currently used disinfectants and pesticides, have many disadvantages, such as toxicity, low efficiency, selectivity, corrosiveness, and the inability to eliminate the pathogens in potato tissue. In this situation, it becomes important to search for new formulations based on components harmful to health, yet efficient, stable during prolonged period of time and a with wide range of biocide activity. Such capabilities are offered by the latest generation of biocidal nanoparticles such as colloidal metals. Therefore the aim of the presented research was to develop newly antibacterial preparation based on colloidal metal nanoparticles and checking their influence on the Cms bacteria. Our preliminary results confirmed high efficacy of the nano-colloids in controlling the this selected pathogen.

Keywords: clavibacter michiganensis ssp. sepedonicus, colloidal metal nanoparticles, phytopathology, bacteria

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494 Extraskeletal Ewing Sarcoma- Experience in a Tertiary Cancer Care Centre of India

Authors: Himanshu Rohela

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BACKGROUND: Ewing sarcoma can arise in either bone or soft tissue. Extraskeletal Ewing sarcoma (EES) is an uncommon primary tumor of the soft tissues, accounting for 20 30% of all reported cases of ES. AIM: Was to investigate demographic distribution, survival analysis and factors affecting the survival and recurrence in patients of EES. METHODS: Retrospective study of 19 biopsy-proven EES was performed. Overall survival (OS) using log-rank test and factors affecting OS and local recurrence (LR) were evaluated for the entire cohort. RESULTS: Patients with EES had a mean age of 19.5 and it was more commonly seen in males (63%). Axial location (58%) and solitary presentation (84%) were more common. The average size was 11 cm, 3 of 19 were metastatic at presentation, with the lung beings the most common site for metastasis. 17 received NACT, 16 with VAC-IE regimen and 1 underwent a second line with GEM/DOCE regimen. Unplanned surgery was done in 2 of 19. 3 patients received definitive RT and 13 underwent surgical-wide local excision. 2 of 13 showed good response to NACT. 10 patients required readmission out of which 6 patients had chemotherapy-related complications, 2 had surgical site complications and one patient developed secondary AML post-completion of treatment. A total of 4 patients had a recurrence. One had local recurrence alone, one had distant recurrence alone and 2 patients had a distant and local recurrence both. Tumor size >10 cm, axial location, and previous unplanned surgery was associated with higher LR rate. The mean overall survival was 32 months (2.66 years), with higher rates seen in non-metastatic and non-recurrent settings. CONCLUSIONS: Early and accurate diagnosis is the key to the management of EES, with promising results seen via NACT and RO resection regimens. But further studies with larger study groups are needed to standardize the treatment protocol and evaluate its efficacy.

Keywords: Ewings, sarcoma, extraskeletal, chemotherapy

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493 Stress-Controlled Senescence and Development in Arabidopsis thaliana by Root Associated Factor (RAF), a NAC Transcription Regulator

Authors: Iman Kamranfar, Gang-Ping Xue, Salma Balazadeh, Bernd Mueller-Roeber

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Adverse environmental conditions such as salinity stress, high temperature and drought limit plant growth and typically lead to precocious tissue degeneration and leaf senescence, a process by which nutrients from photosynthetic organs are recycled for the formation of flowers and seeds to secure reaching the next generation under such harmful conditions. In addition, abiotic stress affects developmental patterns that help the plant to withstand unfavourable environmental conditions. We discovered an NAC (for NAM, ATAF1, 2, and CUC2) transcription factor (TF), called RAF in the following, which plays a central role in abiotic drought stress-triggered senescence and the control of developmental adaptations to stressful environments. RAF is an ABA-responsive TF; RAF overexpressors are hypersensitive to abscisic acid (ABA) and exhibit precocious senescence while knock-out mutants show delayed senescence. To explore the RAF gene regulatory network (GRN), we determined its preferred DNA binding sites by binding site selection assay (BSSA) and performed microarray-based expression profiling using inducible RAF overexpression lines and chromatin immunoprecipitation (ChIP)-PCR. Our studies identified several direct target genes, including those encoding for catabolic enzymes acting during stress-induced senescence. Furthermore, we identified various genes controlling drought stress-related developmental changes. Based on our results, we conclude that RAF functions as a central transcriptional regulator that coordinates developmental programs with stress-related inputs from the environment. To explore the potential agricultural applications of our findings, we are currently extending our studies towards crop species.

Keywords: abiotic stress, Arabidopsis, development, transcription factor

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492 Vitamin C Supplementation Modulates Zinc Levels and Antioxidant Values in Blood and Tissues of Diabetic Rats Fed Zinc-Deficient Diet

Authors: W. Fatmi, F. Kriba, Z. Kechrid

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The aim of this study was to investigate the effect of vitamin C on blood biochemical parameters, tissue zinc, and antioxidants enzymes in diabetic rats fed a zinc-deficient diet. For that purpose, Alloxan-induced diabetic rats were divided into four groups. The first group was fed a zinc-sufficient diet while the second group was fed a zinc-deficient diet. The third and fourth groups received zinc-sufficient or zinc-deficient diets plus oral vitamin C (1mg/l) for 27 days. Body weight and food intake were recorded regularly during 27 days. On day 28, animals were killed and glucose, total lipids, triglycerides, protein, urea, serum zinc , tissues zinc concentrations, liver glycogen, GSH, TBARS concentrations and serum GOT, GPT, ALP and LDH, liver GSH-Px, GST and Catalase activities were determined. Body weight gain and food intake of zinc deficient diabetic animals at the end of experimental period was significantly lower than that of zinc adequate diabetic animals. Dietary zinc intake significantly increased glucose, lipids, triglycerides, urea, and liver TBARS levels of zinc deficient diabetic rats. In contrast, serum zinc, tissues zinc, protein, liver glycogen and GSH levels were decreased. The consumption of zinc deficient diet led also to an increase in serum GOT, GPT and liver GST accompanied with a decrease in serum ALP, LDH and liver GSH-Px, CAT activities. Meanwhile, vitamin C treatment was ameliorated all the previous parameters approximately to their normal levels. Vitamin C supplementation presumably acting as an antioxidant, and it probably led to an improvement of insulin activity, which significantly reduced the severity of zinc deficiency in diabetes.

Keywords: antioxidant, experimental diabetes, liver enzymes, vitamin c, zinc deficiency

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491 Growth and Differentiation of Mesenchymal Stem Cells on Titanium Alloy Ti6Al4V and Novel Beta Titanium Alloy Ti36Nb6Ta

Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel

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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.

Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant

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490 An Analysis on Clustering Based Gene Selection and Classification for Gene Expression Data

Authors: K. Sathishkumar, V. Thiagarasu

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Due to recent advances in DNA microarray technology, it is now feasible to obtain gene expression profiles of tissue samples at relatively low costs. Many scientists around the world use the advantage of this gene profiling to characterize complex biological circumstances and diseases. Microarray techniques that are used in genome-wide gene expression and genome mutation analysis help scientists and physicians in understanding of the pathophysiological mechanisms, in diagnoses and prognoses, and choosing treatment plans. DNA microarray technology has now made it possible to simultaneously monitor the expression levels of thousands of genes during important biological processes and across collections of related samples. Elucidating the patterns hidden in gene expression data offers a tremendous opportunity for an enhanced understanding of functional genomics. However, the large number of genes and the complexity of biological networks greatly increase the challenges of comprehending and interpreting the resulting mass of data, which often consists of millions of measurements. A first step toward addressing this challenge is the use of clustering techniques, which is essential in the data mining process to reveal natural structures and identify interesting patterns in the underlying data. This work presents an analysis of several clustering algorithms proposed to deals with the gene expression data effectively. The existing clustering algorithms like Support Vector Machine (SVM), K-means algorithm and evolutionary algorithm etc. are analyzed thoroughly to identify the advantages and limitations. The performance evaluation of the existing algorithms is carried out to determine the best approach. In order to improve the classification performance of the best approach in terms of Accuracy, Convergence Behavior and processing time, a hybrid clustering based optimization approach has been proposed.

Keywords: microarray technology, gene expression data, clustering, gene Selection

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489 3D-Printed Collagen/Chitosan Scaffolds Loaded with Exosomes Derived from Neural Stem Cells Pretreated with Insulin Growth Factor-1 for Neural Regeneration after Traumatic Brain Injury

Authors: Xiao-Yin Liu, Liang-Xue Zhou

Abstract:

Traumatic brain injury (TBI), as a kind of nerve trauma caused by an external force, affects people all over the world and is a global public health problem. Although there are various clinical treatments for brain injury, including surgery, drug therapy, and rehabilitation therapy, the therapeutic effect is very limited. To improve the therapeutic effect of TBI, scaffolds combined with exosomes are a promising but challenging method for TBI repair. In this study, we examined whether a novel 3D-printed collagen/chitosan scaffold/exosomes derived from neural stem cells (NSCs) pretreated with insulin growth factor-1 (IGF-I) scaffolds (3D-CC-INExos) could be used to improve TBI repair and functional recovery after TBI. Our results showed that composite scaffolds of collagen-, chitosan- and exosomes derived from NSCs pretreated with IGF-I (INExos) could continuously release the exosomes for two weeks. In the rat TBI model, 3D-CC-INExos scaffold transplantation significantly improved motor and cognitive function after TBI, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that the recovery of damaged nerve tissue in the injured area was significantly improved by 3D-CC-INExos implantation. In conclusion, our data suggest that 3D-CC-INExos might provide a potential strategy for the treatment of TBI and lay a solid foundation for clinical translation.

Keywords: traumatic brain injury, exosomes, insulin growth factor-1, neural stem cells, collagen, chitosan, 3D printing, neural regeneration, angiogenesis, functional recovery

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488 Ectopic Pregnancy: A Case of Consecutive Occurrences of Different Types

Authors: Wania Mohammad Akram, Swetha Kannan, Urooj Shahid, Aisha Sajjad

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Ovarian ectopic pregnancy, a rare manifestation of ectopic gestation, involves the implantation of a fertilized egg on the ovarian surface. This condition poses diagnostic challenges and is associated with significant maternal morbidity if not promptly managed. This report presents the case of a 33-year-old nulliparous woman with a history of polycystic ovary syndrome (PCOS) undergoing ovulation induction therapy. Following her first conception in October 2021, she presented with symptoms of per vaginal spotting and low back pain, prompting a diagnosis of left adnexal ectopic pregnancy confirmed by transvaginal ultrasound and serum beta-human chorionic gonadotropin (B-HCG) levels. Medical management with methotrexate was initiated successfully. In August 2022, the patient conceived again, with subsequent ultrasound revealing a large pelvic collection suggestive of a complex ectopic pregnancy involving both ovaries. Despite initial stability, she developed abdominal pain necessitating emergency laparoscopy, which revealed an ovarian ectopic pregnancy with hemoperitoneum. Laparotomy was performed due to the complexity of the presentation, and histopathology confirmed viable chorionic villi within ovarian tissue. This case underscores the clinical management challenges posed by ovarian ectopic pregnancies, particularly in patients with previous ectopic pregnancies. The discussion reviews current literature on diagnostic modalities, treatment strategies, and outcomes associated with ovarian ectopic pregnancies, emphasizing the role of surgical intervention in cases refractory to conservative management. Tailored approaches considering individual patient factors are crucial to optimize outcomes and preserve fertility in such complex scenarios.

Keywords: obgyn, ovarian ectopic pregnancy, laproscopy, pcos

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487 Radiation Skin Decontamination Formulation

Authors: Navneet Sharma, Himanshu Ojha, Dharam Pal Pathak, Rakesh Kumar Sharma

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Radio-nuclides decontamination is an important task because any extra second of deposition leads to deleterious health effects. We had developed and characterise nanoemulsion of p-tertbutylcalix[4]arens using phase inversion temperature (PIT) method and evaluate its decontamination efficacy (DE). The solubility of the drug was determined in various oils and surfactants. Nanoemulsion developed with an HLB value of 11 and different ratios of the surfactants 10% (7:3, w/w), oil (20%, w/w), and double distilled water (70%) were selected. Formulation was characterised by multi-photon spectroscopy and parameters like viscosity, droplet size distribution, zeta potential and stability were optimised. In vitro and Ex vivo decontamination efficacy (DE) was evaluated against Technetium-99m, Iodine-131, and Thallium-201 as radio-contaminants applied over skin of Sprague-Dawley rat and human tissue equivalent model. Contaminants were removed using formulation soaked in cotton swabs at different time intervals and whole body imaging and static counts were recorded using SPECT gamma camera before and after decontamination attempt. Data were analysed using one-way analysis of variance (ANOVA) and was found to be significant (p <0.05). DE of the nanoemulsion loaded with p-tertbutylcalix[4]arens was compared with placebo and recorded to be 88±5%, 90±3% and 89±3% for 99mTc, 131I and 201Tl respectively. Ex-vivo complexation study of p-tertbutylcalix[4]arene nanoemulsion with surrogate nuclides of radioactive thallium and Iodine, were performed on rat skin mounted on Franz diffusion cell using high-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICPMS). More than 90% complexation of the formulation with these nuclides was observed. Results demonstrate that the prepared nanoemulsion formulation was found efficacious for the decontamination of radionuclides from a large contaminated population.

Keywords: p-tertbutylcalix[4]arens, skin decontamination, radiological emergencies, nanoemulsion, iodine-131, thallium-201

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486 Heart and Plasma LDH and CK in Response to Intensive Treadmill Running and Aqueous Extraction of Red Crataegus pentagyna in Male Rats

Authors: A. Abdi, A. Barari, A. Hojatollah Nikbakht, Khosro Ebrahim

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Aim: The purpose of the current study was to investigate the effect of a high intensity treadmill running training (8 weeks) with or without aqueous extraction of Crataegus pentagyna on heart and plasma LDH and CK. Design: Thirty-two Wistar male rats (4-6 weeks old, 125-135 gr weight) were used. Animals were randomly assigned into training (n = 16) and control (n = 16) groups and further divided into saline-control (SC, n = 8), saline-training (ST, n = 8), red Crataegus pentagyna extraction -control (CPEC, n = 8), and red Crataegus pentagyna extraction -training (CPET, n = 8) groups. Training groups have performed a high-intensity running program 34 m/min on 0% grade, 60 min/day, 5 days/week) on a motor-driven treadmill for 8 weeks. Animals were fed orally with Crataegus extraction and saline solution (500mg/kg body weight/or 10ml/kg body weight) for last six weeks. Seventy- two hours after the last training session, rats were sacrificed; plasma and heart were excised and immediately frozen in liquid nitrogen. LDH and CK levels were measured by colorimetric method. Statistical analysis was performed using a one way analysis of variance and Tukey test. Significance was accepted at P = 0.05. Results: Result showed that consumption crataegus lowers LDH and CK in heart and plasma. Also the heart LDH and CK were lower in the CPET compared to the ST, while plasma LDH and CK in CPET was higher than the ST. The results of ANOVA showed that the due high-intensity exercise and consumption crataegus, there are significant differences between levels of hearth LDH (P < 0/001), plasma (P < 0/006) and hearth (P < 0/001) CK. Conclusion: It appears that high-intensity exercise led to increased tissue damage and inflammatory factors in plasma. In other hand, consumption aqueous extraction of Red Crataegus maybe inhibits these factors and prevents muscle and heart damage.

Keywords: LDH, CK, crataegus, intensity

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485 Biosafety Study of Genetically Modified CEMB Sugarcane on Animals for Glyphosate Tolerance

Authors: Aminah Salim, Idrees Ahmed Nasir, Abdul Qayyum Rao, Muhammad Ali, Muhammad Sohail Anjum, Ayesha Hameed, Bushra Tabassum, Anwar Khan, Arfan Ali, Mariyam Zameer, Tayyab Husnain

Abstract:

Risk assessment of transgenic herbicide tolerant sugarcane having CEMB codon optimized cp4EPSPS gene was done in present study. Fifteen days old chicks taken from K&Ns Company were randomly assorted into four groups with eight chicks in each group namely control chicken group fed with commercial diet, non-transgenic group fed with non-experimental sugarcane and transgenic group fed with transgenic sugarcane with minimum and maximum level. Body weights, biochemical analysis for Urea, alkaline phosphatase, alanine transferase, aspartate transferase, creatinine and bilirubin determination and histological examination of chicks fed with four types of feed was taken at fifteen days interval and no significant difference was observed in body weight biochemical and histological studies of all four groups. Protein isolated from the serum sample was analyzed through dipstick and SDS-PAGE, showing the absence of transgene protein in the serum sample of control and experimental groups. Moreover the amplification of cp4EPSPS gene with gene specific primers of DNA isolated from chicks blood and also from commercial diet was done to determine the presence and mobility of any nucleotide fragment of the transgene in/from feed and no amplification was obtained in feed as well as in blood extracted DNA of any group. Also no mRNA expression of cp4EPSPS gene was obtained in any tissue of four groups of chicks. From the results it is clear that there is no deleterious or harmful effect of the CEMB codon optimized transgenic cp4EPSPS sugarcane on the chicks health.

Keywords: chicks, cp4EPSPS, glyphosate, sugarcane

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484 Shifting to Electronic Operative Notes in Plastic surgery

Authors: Samar Mousa, Galini Mavromatidou, Rebecca Shirley

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Surgeons carry out numerous operations in the busy burns and plastic surgery department daily. Writing an accurate operation note with all the essential information is crucial for communication not only within the plastics team but also to the multi-disciplinary team looking after the patient, including other specialties, nurses and GPs. The Royal college of surgeons of England, in its guidelines of good surgical practice, mentioned that the surgeon should ensure that there are clear (preferably typed) operative notes for every procedure. The notes should accompany the patient into recovery and to the ward and should give sufficient detail to enable continuity of care by another doctor. The notes should include the Date and time, Elective/emergency procedure, Names of the operating surgeon and assistant, Name of the theatre anesthetist, Operative procedure carried out, Incision, Operative diagnosis, Operative findings, Any problems/complications, Any extra procedure performed and the reason why it was performed, Details of tissue removed, added or altered, Identification of any prosthesis used, including the serial numbers of prostheses and other implanted materials, Details of closure technique, Anticipated blood loss, Antibiotic prophylaxis (where applicable), DVT prophylaxis (where applicable), Detailed postoperative care instructions and Signature. Fourteen random days were chosen in December 2021 to assess the accuracy of operative notes and post-operative care. A total of 163 operative notes were examined. The average completion rates in all domains were 85.4%. An electronic operative note template was designed to cover all domains mentioned in the Royal College of surgeons' good surgical practice. It is kept in the hospital drive for all surgeons to use.

Keywords: operative notes, plastic surgery, documentation, electronic

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483 The Effect of the COVID-19 on Alzheimer’s Disease

Authors: Ayşe Defne Öz, Özlem Bozkurt

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Alzheimer's Disease (AD) is counted as one of the most important global health problems and the main cause of dementia. The term dementia refers to a wide spectrum of disorders characterized by global, chronic, and generally irreversible cognitive deterioration. It is estimated that %60 % to 80 of the cases of dementia are because of AD. Alzheimer's is a slowly progressive brain disease. The reason for AD is unknown to the author's best knowledge, yet it is one of the topics that is most researched. AD shows the histopathologically abnormal accumulation of the protein beta-amyloid (plague) outside neurons and twisted strands of the protein tau (tangles) inside neurons in the brain. These changes are accompanied by damage to the brain tissue and the death of neurons. AD causes people to have difficulty remembering names or conversations. Some of the later symptoms are difficulty in talking and walking. Alzheimer's Disease is elevated by the illness and mortality of COVID-19. COVID-19 has affected many lives globally and had profound effects on human lives. COVID-19 is caused by SARS-CoV-2, which is a virus that attacks the respiratory and central nervous system and has neuroinvasive potential. More than %80 of COVID-19 patients have ageusia or anosmia, representing the pathognomic features of the disease. Patients with dementia are frail, and with the COVID-19 pandemic, including isolation, cognitive decline may exacerbate. Furthermore, patients with AD can be unable to follow the directions, such as covering their mouth and nose while coughing and can live in nursing homes which makes them more open to being infected. As COVID-19 is highly infectious and its management requires isolation and quarantine, the need for caregivers for AD management conflicts with that of COVID-19 and adds an extra burden on AD patients, caregivers, families, society, and the economy. Due to the entry of SARS-CoV-2 into the central nervous system, inflammation caused by COVID-19, prolonged hospitalization, and delirium, it has been reported that COVID-19 causes many neurological disorders and predisposition to AD.

Keywords: Alzheimer's disease, COVID-19, dementia, SARS-CoV-2

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482 A Time and Frequency Dependent Study of Low Intensity Microwave Radiation Induced Endoplasmic Reticulum Stress and Alteration of Autophagy in Rat Brain

Authors: Ranjeet Kumar, Pravin Suryakantrao Deshmukh, Sonal Sharma, Basudev Banerjee

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With the tremendous increase in exposure to radiofrequency microwaves emitted by mobile phones, globally public awareness has grown with regard to the potential health hazards of microwaves on the nervous system in the brain. India alone has more than one billion mobile users out of 4.3 billion globally. Our studies have suggested that radio frequency able to affect neuronal alterations in the brain, and hence, affecting cognitive behaviour. However, adverse effect of low-intensity microwave exposure with endoplasmic reticulum stress and autophagy has not been evaluated yet. In this study, we explore whether low-intensity microwave induces endoplasmic reticulum stress and autophagy with varying frequency and time duration in Wistar rat. Ninety-six male Wistar rat were divided into 12 groups of 8 rats each. We studied at 900 MHz, 1800 MHz, and 2450 MHz frequency with reference to sham-exposed group. At the end of the exposure, the rats were sacrificed to collect brain tissue and expression of CHOP, ATF-4, XBP-1, Bcl-2, Bax, LC3 and Atg-4 gene was analysed by real-time PCR. Significant fold change (p < 0.05) of gene expression was found in all groups of 1800 MHz and 2450 MHz exposure group in comparison to sham exposure group. In conclusion, the microwave exposure able to induce ER stress and modulate autophagy. ER (endoplasmic reticulum) stress and autophagy vary with increasing frequency as well as the duration of exposure. Our results suggested that microwave exposure is harmful to neuronal health as it induces ER stress and hampers autophagy in neuron cells and thereby increasing the neuron degeneration which impairs cognitive behaviour of experimental animals.

Keywords: autophagy, ER stress, microwave, nervous system, rat

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481 Standardization of the Roots of Gnidia stenophylla Gilg: A Potential Medicinal Plant of South Eastern Ethiopia Traditionally Used as an Antimalarial

Authors: Mebruka Mohammed, Daniel Bisrat, Asfaw Debella, Tarekegn Birhanu

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Lack of quality control standards for medicinal plants and their preparations is considered major barrier to their integration in to effective primary health care in Ethiopia. Poor quality herbal preparations led to countless adverse reactions extending to death. Denial of penetration for the Ethiopian medicinal plants in to the world’s booming herbal market is also another significant loss resulting from absence of herbal quality control system. Thus, in the present study, Gnidia stenophylla Gilg (popular antimalarial plant of south eastern Ethiopia), is standardized and a full monograph is produced that can serve as a guideline in quality control of the crude drug. Morphologically, the roots are found to be cylindrical and tapering towards the end. It has a hard, corky and friable touch with saddle brown color externally and it is relatively smooth and pale brown internally. It has got characteristic pungent odor and very bitter taste. Microscopically it has showed lignified xylem vessels, wider medullary rays with some calcium oxalate crystals, reddish brown secondary metabolite contents and slender shaped long fibres. Physicochemical standards quantified and resulted: foreign matter (5.25%), moisture content (6.69%), total ash (40.80%), acid insoluble ash (8.00%), water soluble ash (2.30%), alcohol soluble extractive (15.27%), water soluble extractive (10.98%), foaming index (100.01 ml/g), swelling index (7.60 ml/g). Phytochemically: Phenols, flavonoids, steroids, tannins and saponins were detected in the root extract; TLC and HPLC fingerprints were produced and an analytical marker was also tentatively characterized as 3-(3,4-dihydro-3,5-dihydroxy-2-(4-hydroxy-5-methylhex-1-en-2-yl)-7-methoxy-4-oxo-2H-chromen-8-yl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one. Residue wise pesticides (i.e. DDT, DDE, g-BHC) and radiochemical levels fall below the WHO limit while Heavy metals (i.e. Co, Ni, Cr, Pb, and Cu), total aerobic count and fungal load lie way above the WHO limit. In conclusion, the result can be taken as signal that employing non standardized medicinal plants could cause many health risks of the Ethiopian people and Africans’ at large (as 80% of inhabitants in the continent depends on it for primary health care). Therefore, following a more universal approach to herbal quality by adopting the WHO guidelines and developing monographs using the various quality parameters is inevitable to minimize quality breach and promote effective herbal drug usage.

Keywords: Gnidia stenophylla Gilg, standardization/monograph, pharmacognostic, residue/impurity, quality

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480 Self-Assembly of TaC@Ta Core-Shell-Like Nanocomposite Film via Solid-State Dewetting: Toward Superior Wear and Corrosion Resistance

Authors: Ping Ren, Mao Wen, Kan Zhang, Weitao Zheng

Abstract:

The improvement of comprehensive properties including hardness, toughness, wear, and corrosion resistance in the transition metal carbides/nitrides TMCN films, especially avoiding the trade-off between hardness and toughness, is strongly required to adapt to various applications. Although incorporating ductile metal DM phase into the TMCN via thermally-induced phase separation has been emerged as an effective approach to toughen TMCN-based films, the DM is just limited to some soft ductile metal (i.e. Cu, Ag, Au immiscibility with the TMCN. Moreover, hardness is highly sensitive to soft DM content and can be significantly worsened. Hence, a novel preparation method should be attempted to broaden the DM selection and assemble much more ordered nanocomposite structure for improving the comprehensive properties. Here, we provide a new strategy, by activating solid-state dewetting during layered deposition, to accomplish the self-assembly of ordered TaC@Ta core-shell-like nanocomposite film consisting of TaC nanocrystalline encapsulated with thin pseudocrystal Ta tissue. That results in the superhard (~45.1 GPa) dominated by Orowan strengthening mechanism and high toughness attributed to indenter-induced phase transformation from the pseudocrystal to body-centered cubic Ta, together with the drastically enhanced wear and corrosion resistance. Furthermore, very thin pseudocrystal Ta encapsulated layer (~1.5 nm) in the TaC@Ta core-shell-like structure helps for promoting the formation of lubricious TaOₓ Magnéli phase during sliding, thereby further dropping the coefficient of friction. Apparently, solid-state dewetting may provide a new route to construct ordered TMC(N)@TM core-shell-like nanocomposite capable of combining superhard, high toughness, low friction, superior wear with corrosion resistance.

Keywords: corrosion, nanocomposite film, solid-state dewetting, tribology

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479 The Impact of Lipids on Lung Fibrosis

Authors: G. Wojcik, J. Gindlhuber, A. Syarif, K. Hoetzenecker, P. Bohm, P. Vesely, V. Biasin, G. Kwapiszewska

Abstract:

Pulmonary fibrosis is a rare disease where uncontrolled wound healing processes damage the lung structure. Intensive changes within the extracellular matrix (ECM) and its interaction with fibroblasts have a major role in pulmonary fibrosis development. Among others, collagen is one of the main components of the ECM, and it is important for lung structure. In IPF, constant production of collagen by fibroblast, through TGFβ1-SMAD2/3 pathways, leads to an uncontrolled deposition of matrix and hence lung remodeling. Abnormal changes in lipid production, alterations in fatty acids (FAs) metabolism, enhanced oxidative stress, and lipid peroxidation in fibrotic lung and fibrotic fibroblasts have been reported; however, the interplay between the collagen and lipids is not yet established. One of the FAs influx regulators is Angiopoietin-like 4 (ANGPTL4), which inhibits lipoprotein lipase work, decreasing the availability of FAs. We hypothesized that altered lipid composition or availability could have the capability to influence the phenotype of different fibroblast populations in the lung and hence influence lung fibrosis. To prove our hypothesis, we aim to investigate lipids and their influence on human, animal, and in vitro levels. In the bleomycin model, treatment with the well-known metabolic drugs Rosiglitazone or Metformin significantly lower collagen production. Similar results were noticed in ANGPTL4 KO animals, where the KO of ANGPTL4 leads to an increase of FAs availability and lower collagen deposition after the bleomycin challenge. Currently, we study the treatment of different FAs on human lung para fibroblasts (hPF) isolated from donors. To understand the lipid composition, we are collecting human lung tissue from donors and pulmonary fibrosis patients for Liquid chromatography-mass spectrometry. In conclusion, our results suggest the lipid influence on collagen deposition during lung fibrosis, but further research needs to be conducted to understand the matter of this relationship.

Keywords: collagen, fibroblasts, lipidomics, lung, pulmonary fibrosis

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478 Progress Towards Optimizing and Standardizing Fiducial Placement Geometry in Prostate, Renal, and Pancreatic Cancer

Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

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Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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477 Molecular Modeling of Structurally Diverse Compounds as Potential Therapeutics for Transmissible Spongiform Encephalopathy

Authors: Sanja O. Podunavac-Kuzmanović, Strahinja Z. Kovačević, Lidija R. Jevrić

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Prion is a protein substance whose certain form is considered as infectious agent. It is presumed to be the cause of the transmissible spongiform encephalopathies (TSEs). The protein it is composed of, called PrP, can fold in structurally distinct ways. At least one of those 3D structures is transmissible to other prion proteins. Prions can be found in brain tissue of healthy people and have certain biological role. The structure of prions naturally occurring in healthy organisms is marked as PrPc, and the structure of infectious prion is labeled as PrPSc. PrPc may play a role in synaptic plasticity and neuronal development. Also, it may be required for neuronal myelin sheath maintenance, including a role in iron uptake and iron homeostasis. PrPSc can be considered as an environmental pollutant. The main aim of this study was to carry out the molecular modeling and calculation of molecular descriptors (lipophilicity, physico-chemical and topological descriptors) of structurally diverse compounds which can be considered as anti-prion agents. Molecular modeling was conducted applying ChemBio3D Ultra version 12.0 software. The obtained 3D models were subjected to energy minimization using molecular mechanics force field method (MM2). The cutoff for structure optimization was set at a gradient of 0.1 kcal/Åmol. The Austin Model 1 (AM-1) was used for full geometry optimization of all structures. The obtained set of molecular descriptors is applied in analysis of similarities and dissimilarities among the tested compounds. This study is an important step in further development of quantitative structure-activity relationship (QSAR) models, which can be used for prediction of anti-prion activity of newly synthesized compounds.

Keywords: chemometrics, molecular modeling, molecular descriptors, prions, QSAR

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476 Isolation and Expansion of Human Periosteum-Derived Mesenchymal Stem Cells in Defined Serum-Free Culture Medium

Authors: Ainur Mukhambetova, Miras Karzhauov, Vyacheslav Ogay

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Introduction: Mesenchymal stem cells (MSCs) have the capacity to be differentiated into several cell lineages and are a promising source for cell therapy and tissue engineering. However, currently most MSCs culturing protocols use media supplemented with fetal bovine serum (FBS), which limits their application in clinic due to the possibility of zoonotic infections, contamination and immunological reactions. Consequently, formulating effective serum free culture medium becomes one of the important problems in contemporary cell biotechnology. Objectives: The aim of this study was to define an optimal serum-free medium for culturing of periosteum derived MSCs. Materials and methods: The MSCs were extracted from human periosteum and transferred to the culture flasks pretreated with CELLstart™. Immunophenotypic characterization, proliferation and in vitro differentiation of cells grown on STEM PRO® MSC SFM were compared to the cells cultured in the standard FBS containing media. Chromosome analysis and flow cytometry were also performed. Results: We have shown that cells were grown on STEM PRO® MSC SFM retained all the morphological, immunophenotypic (CD73, CD90, CD105, vimentin and Stro-1) and cell differentiation characteristics specific to MSCs. Chromosome analysis indicated no anomalies in the chromosome structure. Flow cytometry showed a high expression of cell adhesion molecules CD44 (98,8%), CD90 (97,4%), CD105 (99,1%). In addition, we have shown that cell is grown on STEM PRO® MSC SFM have higher proliferation capacity compared to cell expanded on standard FBS containing the medium. Conclusion: We have shown that STEM PRO® MSC SFM is optimal for culturing periosteum derived human MSCs which subsequently can be safely used in cell therapy.

Keywords: cell technologies, periosteum-derived MSCs, regenerative medicine, serum-free medium

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475 Adjustments of Mechanical and Hydraulic Properties of Wood Formed under Environmental Stresses

Authors: B. Niez, B. Moulia, J. Dlouha, E. Badel

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Trees adjust their development to the environmental conditions they experience. Storms events of last decades showed that acclimation of trees to mechanical stresses due to wind is a very important process that allows the trees to sustain for long years. In the future, trees will experience new wind patterns, namely, more often strong winds and fewer daily moderate winds. Moreover, these patterns will go along with drought periods that may interact with the capacity of trees to adjust their growth to mechanical stresses due to wind. It is necessary to understand the mechanisms of wood functional acclimations to environmental conditions in order to predict their behaviour and in order to give foresters and breeders the relevant tools to adapt their forest management. This work aims to study how trees adjust the mechanical and hydraulic functions of their wood to environmental stresses and how this acclimation may be beneficial for the tree to resist to future stresses. In this work, young poplars were grown under controlled climatic conditions that include permanent environmental stress (daily mechanical stress of the stem by bending and/or hydric stress). Then, the properties of wood formed under these stressed conditions were characterized. First, hydraulic conductivity and sensibility to cavitation were measured at the tissue level in order to evaluate the changes in water transport capacity. Secondly, bending tests and Charpy impact tests were carried out at the millimetric scale to locally measure mechanical parameters such as elastic modulus, elastic limit or rupture energy. These experimental data allow evaluating the impacts of mechanical and water stress on the wood material. At the stem level, they will be merged in an integrative model in order to evaluate the beneficial aspect of wood acclimation for trees.

Keywords: acclimation, environmental stresses, hydraulics, mechanics, wood

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474 Case Presentation Ectopic Cushing's Syndrome Secondary to Thymic Neuroendocrine Tumors Secreting ACTH

Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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473 Incorporation of Growth Factors onto Hydrogels via Peptide Mediated Binding for Development of Vascular Networks

Authors: Katie Kilgour, Brendan Turner, Carly Catella, Michael Daniele, Stefano Menegatti

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In vivo, the extracellular matrix (ECM) provides biochemical and mechanical properties that are instructional to resident cells to form complex tissues with characteristics to develop and support vascular networks. In vitro, the development of vascular networks can be guided by biochemical patterning of substrates via spatial distribution and display of peptides and growth factors to prompt cell adhesion, differentiation, and proliferation. We have developed a technique utilizing peptide ligands that specifically bind vascular endothelial growth factor (VEGF), erythropoietin (EPO), or angiopoietin-1 (ANG1) to spatiotemporally distribute growth factors to cells. This allows for the controlled release of each growth factor, ultimately enhancing the formation of a vascular network. Our engineered tissue constructs (ETCs) are fabricated out of gelatin methacryloyl (GelMA), which is an ideal substrate for tailored stiffness and bio-functionality, and covalently patterned with growth factor specific peptides. These peptides mimic growth factor receptors, facilitating the non-covalent binding of the growth factors to the ETC, allowing for facile uptake by the cells. We have demonstrated in the absence of cells the binding affinity of VEGF, EPO, and ANG1 to their respective peptides and the ability for each to be patterned onto a GelMA substrate. The ability to organize growth factors on an ETC provides different functionality to develop organized vascular networks. Our results demonstrated a method to incorporate biochemical cues into ETCs that enable spatial and temporal control of growth factors. Future efforts will investigate the cellular response by evaluating gene expression, quantifying angiogenic activity, and measuring the speed of growth factor consumption.

Keywords: growth factor, hydrogel, peptide, angiogenesis, vascular, patterning

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472 Microstructural Mechanical Properties of Human Trabecular Bone Based on Nanoindentation Test

Authors: K. Jankowski, M. Pawlikowski, A. Makuch, K. Skalski

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Depth-sensing indentation (DSI) or nanoindentation is becoming a more and more popular method of measuring mechanical properties of various materials and tissues at a micro-scale. This technique allows measurements without complicated sample preparation procedures which makes this method very useful. As a result of measurement force and displacement of the intender are obtained. It is also possible to determine three measures of hardness i.e. Martens hardness (HM), nanohardness (HIT), Vickers hardness (HV) and Young modulus EIT. In this work trabecular bone mechanical properties were investigated. The bone samples were harvested from human femoral heads during hip replacement surgery. Patients were of different age, sexes and stages of tissue degeneration caused by osteoarthritis. The specimens were divided into three groups. Each group contained samples harvested from patients of different range of age. All samples were investigated with the same measurement conditions. The maximum load was Pmax=500 mN and the loading rate was 500 mN/min. The tests were held without hold at the peak force. The tests were conducted with indenter Vickers tip and spherical tip of the diameter 0.2 mm. Each trabecular bone sample was tested 7 times in a close area of the same trabecula. The measured loading P as a function of indentation depth allowed to obtain hysteresis loop and HM, HIT, HV, EIT. Results for arbitrarily chosen sample are HM=289.95 ± 42.31 MPa, HIT=430.75 ± 45.37 MPa, HV=40.66 ± 4.28 Vickers, EIT=7.37 ± 1.84 GPa for Vickers tip and HM=115.19 ± 15.03 MPa, HIT=165.80 ± 19.30 MPa, HV=16.90 ± 1.97 Vickers, EIT=5.30 ± 1.31 GPa for spherical tip. Results of nanoindentation tests show that this method is very useful and is perfect for obtaining mechanical properties of trabecular bone. Estimated values of elastic modulus are similar. The differences between hardness are significant but it is a result of using two different types of tips. However, it has to be emphasised that the differences in the values of elastic modulus and hardness result from different testing protocols, anisotropy and asymmetry of the micro-samples and the hydration of bone.

Keywords: human bone, mechanical properties, nano hardness nanoindentation, trabecular bone

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471 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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470 Syndecan -1 as Regulator of Ischemic-Reperfusion Damage Limitation in Experiment

Authors: M. E. Kolpakova, A. A. Jakovleva, L. S. Poliakova, H. El Amghari, S. Soliman, D. R. Faizullina, V. V. Sharoyko

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Brain neuroplasticity is associated with blood-brain barrier vascular endothelial proteoglycans and post-stroke microglial activation. The study of the mechanisms of reperfusion injury limitation by remote ischemic postconditioning (RC) is of interest due to the effects on functional recovery after cerebral ischemia. The goal of the study is the assessment of the role of syndecan-1 (SDC-1) in restriction of ischemic-reperfusion injury on middle cerebral artery model in rats using RC protocol. Randomized controlled trials were conducted. Ischemia was performed by middle cerebral artery occlusion by Belayev L. (1996) on the Wistar rat-males (n= 87) weighting 250 ± 50 g. under general anesthesia (Zoletil 100 и Xylazine 2%). Syndecan-1 (SDC-1) concentration difference in plasma samples of false operated animals and animals with brain ischemia was 30% (30 min. МСАо: 41.4 * ± 1.3 ng/ml). SDC-1 concentration in animal plasma samples with ischemia + RC protocol was 112% (30 min МСАо+ RC): 67.8**± 5.8 ng/ml). Calculation of infarction volume in the ischemia group revealed brain injury in 31.97 ± 2.5%; the volume of infarction was 13.6 ± 1.3% in 30 min. МCАо + RC group. Swelling of tissue in the group 30 min. МCАо + RC was 16 ± 2.1%; it was 47 ± 3.3%. in 30 min. МCАо group. Correlation analysis showed a high direct correlation relationship between infarct area and muscle strength in the right forelimb (КК=0.72) in the 30 min. МCАо + RC group. Correlation analysis showed very high inverse correlation between infarct area and capillary blood flow in the 30 min. МCАо + RC group (p <0.01; r = -0.98). We believe the SDC-1 molecule in blood plasma may play role of potential messenger of ischemic-reperfusion injury restriction mechanisms. This leads to infarct-limiting effect of remote ischemic postconditioning and early functioning recovery.

Keywords: ischemia, МСАо, remote ischemic postconditioning, syndecan-1

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469 Detection of JC Virus DNA and T-Ag Expression in a Subpopulation of Tunisian Colorectal Carcinomas

Authors: Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Dalila Gargouri, Jamel Kharrat, Abderraouf Cherif, Ahmed Bouhafa, Slim Jarboui, Mohamed Zili, Ridha Khelifa

Abstract:

Background & aims: Colorectal cancer (CRC) is one of the most common malignancies throughout the world. Several risk factors, both genetic and environmental, including viral infections, have been linked to colorectal carcinogenesis. A few studies report the detection of human polyomavirus JC (JCV) DNA and transformation antigen (T-Ag) in a fraction of the colorectal tumors studied and suggest an association of this virus with CRC. In order to investigate whether such an association of JCV with CRC will hold in a different epidemiological setting, we looked for the presence of JCV DNA and T-Ag expression in a group of Tunisian CRC patients. Methods: Fresh colorectal mucosa biopsies were obtained from 17 healthy volunteers and from both colorectal tumors and adjacent normal tissues of 47 CRC patients. DNA was extracted from fresh biopsies or from formalin-fixed, paraffin-embedded tissue sections using the Invitrogen Purelink Genomic DNA mini Kit. A simple PCR and a nested PCR were used to amplify a region of the T-Ag gene. The obtained PCR products revealed a 154 bp and a 98 bp bands, respectively. Specificity was confirmed by sequencing of the PCR products. T-Ag expression was determined by immunohistochemical staining using a mouse monoclonal antibody (clone PAb416) directed against SV40 T-Ag that cross reacts with JCV T-Ag. Results: JCV DNA was found in 12 (25%) and 22 (46%) of the CRC tumors by simple PCR and by nested PCR, respectively. All paired adjacent normal mucosa biopsies were negative for viral DNA. Sequencing of the DNA amplicons obtained confirmed the authenticity of T-Ag sequences. Immunohistochemical staining showed nuclear T-Ag expression in all 22 JCV DNA- positive samples and in 3 additional tumor samples which appeared DNA-negative by PCR. Conclusions: These results suggest an association of JCV with a subpopulation of Tunisian colorectal tumors.

Keywords: colorectal cancer, immunohistochemistry, Polyomavirus JC, PCR

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468 Association of Musculoskeletal and Radiological Features with Clinical and Serological Findings in Systemic Sclerosis: A Single-Centre Registry Study

Authors: Rezvan Hosseinian

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Aim: Systemic sclerosis (SSc) is a chronic connective tissue disease with the clinical hallmark of skin thickening and tethering. The correlation of musculoskeletal features with other parameters should be considered in SSc patients. Methods: We reviewed the records of all patients who had more than one visit and standard anteroposterior radiography of hand. We used univariate analysis, and factors with p<0.05 were included in logistic regression to find out dependent factors. Results: Overall, 180 SSc patients were enrolled in our study, 161 (89.4%) of whom were women. The median age (IQR) was 47.0 years (16), and 52% had a diffuse subtype of the disease. In multivariate analysis, tendon friction rubs (TFRs) were associated with the presence of calcinosis, muscle tenderness, and flexion contracture (FC) on physical examination (p<0.05). Arthritis showed no differences in the two subtypes of the disease (p=0.98), and in multivariate analysis, there were no correlations between radiographic arthritis and serological and clinical features. The radiographic results indicated that disease duration correlated with joint erosion, acro-osteolysis, resorption of the distal ulna, calcinosis and radiologic FC (p< 0.05). Acro-osteolysis was more frequent in the dcSSc subtype, TFRs, and anti-TOPO I antibody. Radiologic FC showed an association with skin score, calcinosis and haematocrit <30% (p<0.05). Joint flexion on radiography was associated with disease duration, modified Rodnan skin score, calcinosis, and low hematocrit (P<0.01). Conclusion: Disease duration was a main dependent factor for developing joint erosion, acro-osteolysis, bone resorption, calcinosis, and flexion contracture on hand radiography. Acro-osteolysis presented in the severe form of the disease. Acro-osteolysis was the only dependent variable associated with bone demineralization.

Keywords: disease subsets, hand radiography, joint erosion, sclerosis

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