Search results for: aggressive
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 371

Search results for: aggressive

161 Self-Healing Phenomenon Evaluation in Cementitious Matrix with Different Water/Cement Ratios and Crack Opening Age

Authors: V. G. Cappellesso, D. M. G. da Silva, J. A. Arndt, N. dos Santos Petry, A. B. Masuero, D. C. C. Dal Molin

Abstract:

Concrete elements are subject to cracking, which can be an access point for deleterious agents that can trigger pathological manifestations reducing the service life of these structures. Finding ways to minimize or eliminate the effects of this aggressive agents’ penetration, such as the sealing of these cracks, is a manner of contributing to the durability of these structures. The cementitious self-healing phenomenon can be classified in two different processes. The autogenous self-healing that can be defined as a natural process in which the sealing of this cracks occurs without the stimulation of external agents, meaning, without different materials being added to the mixture, while on the other hand, the autonomous seal-healing phenomenon depends on the insertion of a specific engineered material added to the cement matrix in order to promote its recovery. This work aims to evaluate the autogenous self-healing of concretes produced with different water/cement ratios and exposed to wet/dry cycles, considering two ages of crack openings, 3 days and 28 days. The self-healing phenomenon was evaluated using two techniques: crack healing measurement using ultrasonic waves and image analysis performed with an optical microscope. It is possible to observe that by both methods, it possible to observe the self-healing phenomenon of the cracks. For young ages of crack openings and lower water/cement ratios, the self-healing capacity is higher when compared to advanced ages of crack openings and higher water/cement ratios. Regardless of the crack opening age, these concretes were found to stabilize the self-healing processes after 80 days or 90 days.

Keywords: sealf-healing, autogenous, water/cement ratio, curing cycles, test methods

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160 The Superiority of 18F-Sodium Fluoride PET/CT for Detecting Bone Metastases in Comparison with Other Bone Diagnostic Imaging Modalities

Authors: Mojtaba Mirmontazemi, Habibollah Dadgar

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Bone is the most common metastasis site in some advanced malignancies, such as prostate and breast cancer. Bone metastasis generally indicates fewer prognostic factors in these patients. Different radiological and molecular imaging modalities are used for detecting bone lesions. Molecular imaging including computed tomography, magnetic resonance imaging, planar bone scintigraphy, single-photon emission tomography, and positron emission tomography as noninvasive visualization of the biological occurrences has the potential to exact examination, characterization, risk stratification and comprehension of human being diseases. Also, it is potent to straightly visualize targets, specify clearly cellular pathways and provide precision medicine for molecular targeted therapies. These advantages contribute implement personalized treatment for each patient. Currently, NaF PET/CT has significantly replaced standard bone scintigraphy for the detection of bone metastases. On one hand, 68Ga-PSMA PET/CT has gained high attention for accurate staging of primary prostate cancer and restaging after biochemical recurrence. On the other hand, FDG PET/CT is not commonly used in osseous metastases of prostate and breast cancer as well as its usage is limited to staging patients with aggressive primary tumors or localizing the site of disease. In this article, we examine current studies about FDG, NaF, and PSMA PET/CT images in bone metastases diagnostic utility and assess response to treatment in patients with breast and prostate cancer.

Keywords: skeletal metastases, fluorodeoxyglucose, sodium fluoride, molecular imaging, precision medicine, prostate cancer (68Ga-PSMA-11)

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159 Development of the Religious Out-Group Aggression Scale

Authors: Rylle Evan Gabriel Zamora, Micah Dennise Malia, Abygail Deniese Villabona

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When examining studies on aggression, the studies about individual aggression vastly outnumbers those studies on group aggression. Given the nature of aggression to be violent and cyclical, and the amount violent events that have occurred in the near present, the study of group aggression is relevant now more than ever. This discrepancy is parallel with the number of valid and reliable psychological tests that measure group aggression. Throughout history, one of the biggest causes of group based violence and aggression is religion. This is particularly true within the context of the Philippines as there are a large number of religious groups. Thus, this study aimed to develop a standardized test that measures an individual’s tendency to be aggressive to those who are in conflict with his or her religious beliefs. This study employs a test development design that employs a qualitative phase to ensure the validity of the scale. Thus, the study was divided into three phases. First is a pilot test wherein an instrument was designed from existing literature which was then administered to 173 respondents from the four largest religious groups in the Philippines. After extensive factor analysis and reliability testing, new items were then formed from the qualitative data collected from eight participants, consisting of two individuals per religious group. The final testing integrates all statistically significant items from the first phase, and the newly formed items from the second phase, which was then administered to 200 respondents. The results were then tested further for reliability using Cronbach’s alpha and validity through factor analysis. The items that were proven to be significant were then combined to create a final instrument that may be used by future studies.

Keywords: religious aggression, group aggression, test development, psychological assessment, social psychology

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158 Properties of Triadic Concrete Containing Rice Husk Ash and Wood Waste Ash as Partial Cement Replacement

Authors: Abdul Rahman Mohd. Sam, Olukotun Nathaniel, Dunu Williams

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Concrete is one of the most popular materials used in construction industry. However, one of the setbacks is that concrete can degrade with time upon exposure to an aggressive environment that leads to decrease in strength. Thus, research works and innovative ways are needed to enhance the strength and durability of concrete. This work tries to look into the potential use of rice husk ash (RHA) and wood waste ash (WWA) as cement replacement material. These are waste materials that may not only enhance the properties of concrete but also can serves as a viable method of disposal of waste for sustainability. In addition, a substantial replacement of Ordinary Portland Cement (OPC) with these pozzolans will mean reduction in CO₂ emissions and high energy requirement associated with the production of OPC. This study is aimed at assessing the properties of triadic concrete produced using RHA and WWA as a partial replacement of cement. The effects of partial replacement of OPC with 10% RHA and 5% WWA on compressive and tensile strength of concrete among other properties were investigated. Concrete was produced with nominal mix of 1:2:4 and 0.55 water-cement ratio, prepared, cured and subjected to compressive and tensile strength test at 3, 7, 14, 28 and 90days. The experimental data demonstrate that concrete containing RHA and WWA produced lighter weight in comparison with OPC sample. Results also show that combination of RHA and WWA help to prolong the initial and final setting time by about 10-30% compared to the control sample. Furthermore, compressive strength was increased by 15-30% with 10% RHA and 5% WWA replacement, respectively above the control, RHA and WWA samples. Tensile strength test at the ages of 3, 7, 14, 28 and 90 days reveals that a replacement of 15% RHA and 5% WWA produced samples with the highest tensile capacity compared to the control samples. Thus, it can be concluded that RHA and WWA can be used as partial cement replacement materials in concrete.

Keywords: concrete, rice husk ash, wood waste ash, ordinary Portland cement, compressive strength, tensile strength

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157 Challenges of Management of Acute Pancreatitis in Low Resource Setting

Authors: Md. Shakhawat Hossain, Jimma Hossain, Md. Naushad Ali

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Acute pancreatitis is a dangerous medical emergency in the practice of gastroenterology. Management of acute pancreatitis needs multidisciplinary approach with support starts from emergency to ICU. So, there is a chance of mismanagement in every steps, especially in low resource settings. Other factors such as patient’s financial condition, education, social custom, transport facility, referral system from periphery may also challenge the current guidelines for management. The present study is intended to determine the clinico-pathological profile, severity assessment and challenges of management of acute pancreatitis in a government laid tertiary care hospital to image the real scenario of management in a low resource place. A total 100 patients of acute pancreatitis were studied in this prospective study, held in the Department of Gastroenterology, Rangpur medical college hospital, Bangladesh from July 2017 to July 2018 within one year. Regarding severity, 85 % of the patients were mild, whereas 13 were moderately severe, and 2 had severe acute pancreatitis according to the revised Atlanta criteria. The most common etiologies of acute pancreatitis in our study were gall stone (15%) and biliary sludge (15%), whereas 54% were idiopathic. The most common challenges we faced were delay in hospital admission (59%) and delay in hospital diagnosis (20%). Others are non-adherence of patient party, and lack of investigation facility, physician’s poor knowledge about current guidelines. We were able to give early aggressive fluid to only 18% of patients as per current guideline. Conclusion: Management of acute pancreatitis as per guideline is challenging when optimum facility is lacking. So, modified guidelines for assessment and management of acute pancreatitis should be prepared for low resource setting.

Keywords: acute pancreatitis, challenges of management, severity, prognosis

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156 Determination of Klebsiella Pneumoniae Susceptibility to Antibiotics Using Infrared Spectroscopy and Machine Learning Algorithms

Authors: Manal Suleiman, George Abu-Aqil, Uraib Sharaha, Klaris Riesenberg, Itshak Lapidot, Ahmad Salman, Mahmoud Huleihel

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Klebsiella pneumoniae is one of the most aggressive multidrug-resistant bacteria associated with human infections resulting in high mortality and morbidity. Thus, for an effective treatment, it is important to diagnose both the species of infecting bacteria and their susceptibility to antibiotics. Current used methods for diagnosing the bacterial susceptibility to antibiotics are time-consuming (about 24h following the first culture). Thus, there is a clear need for rapid methods to determine the bacterial susceptibility to antibiotics. Infrared spectroscopy is a well-known method that is known as sensitive and simple which is able to detect minor biomolecular changes in biological samples associated with developing abnormalities. The main goal of this study is to evaluate the potential of infrared spectroscopy in tandem with Random Forest and XGBoost machine learning algorithms to diagnose the susceptibility of Klebsiella pneumoniae to antibiotics within approximately 20 minutes following the first culture. In this study, 1190 Klebsiella pneumoniae isolates were obtained from different patients with urinary tract infections. The isolates were measured by the infrared spectrometer, and the spectra were analyzed by machine learning algorithms Random Forest and XGBoost to determine their susceptibility regarding nine specific antibiotics. Our results confirm that it was possible to classify the isolates into sensitive and resistant to specific antibiotics with a success rate range of 80%-85% for the different tested antibiotics. These results prove the promising potential of infrared spectroscopy as a powerful diagnostic method for determining the Klebsiella pneumoniae susceptibility to antibiotics.

Keywords: urinary tract infection (UTI), Klebsiella pneumoniae, bacterial susceptibility, infrared spectroscopy, machine learning

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155 Impact of Adolescent Smoking on the Behaviour, Academic and Health Aspects in Qatar

Authors: Abdelsalam Gomaa, Mahjabeen Ramzan, Tooba Ali Akbar, Huma Nadeem

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The use of tobacco and the health risks linked to it are well known in this day and age due to the presence of easily available information through the internet. The media is a powerful platform that is used by many anti-smoking awareness campaigns to reach their target audience; yet, it has been found that adolescents are taking up smoking every passing day. Half of this smoking population of youngsters resides in Asia alone, which includes Qatar, the focus country of this study. As smoking happens to be one of the largest avoidable causes of serious diseases like cancers and heart problems, children are taking up smoking at an alarming rate everywhere including Qatar. Importance of the health of the citizens of Qatar is one of the pillars of the Qatar vision 2030, which is to ensure a healthy population, both physically and mentally. Since the youth makes up a significant percentage of the population and in order to achieve the health objectives of the Qatar vision 2030, it is essential to ensure the health and well-being of this part of the population of the country as they are the future of Qatar. Children, especially boys who tend to be more aggressive by nature, are highly likely to develop behavioral and health issues due to smoking at an early age. Research conducted around the world has also emphasized on this association between the smokers developing a bad behaviour as well as poor social communication skills. However, due to lack of research into this association, very little is known about the extent to which smoking impacts the children’s academics, health and behaviour. Moreover, a study of this nature has not yet been conducted in Qatar previously as most of the studies focus on adult smokers and ways to minimize the number of smoking habits in universities and workplaces. This study solely focuses on identifying a relationship between smoking and its impacts on the adolescents by conducting a research on different schools across Qatar.

Keywords: adolescents, modelling techniques, Qatar, smoking

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154 Wearable Devices Could Reduce the Risk of Injury in Parasomnias Phenotypes

Authors: Vivian Correa

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Hypothesis There are typical patterns - phenotypes - of sleep behaviors by age and biological sex groups of parasomnia patients where wearable devices could avoid injuries. Materials and methods We analyzed public video records on sleep-related behaviors likely representing parasomnias, looking for phenotypes in different groups. We searched public internet databases using the keywords “sleepwalking”, “sleep eating,” “sleep sex”, and “aggression in sleep” in six languages. Poor-quality vide-records and those showing apparently faked sleep behaviors were excluded. We classified the videos into estimated sex and age (children, adults, elderly) groups; scored the activity types by a self-made scoring scale; and applied binary logistic regression for analyzing the association between sleep behaviors versus the groups by STATA package providing 95% confidence interval and the probability of statistical significance. Results 224 videos (102 women) were analyzed. The odds of sleepwalking and related dangerous behaviors were lower in the elderly than in adults (P<0.025). Females performed complex risky behaviors during sleepwalking more often than males (P<0.012). Elderly people presented emotional behaviors less frequently than adults (P<0.004), and females showed them twice often as males. Elderly males had 40-fold odds compared to adults and children to perform aggressive movements and 70-fold odds of complex movements in the bed compared to adults. Conclusion Unlike other groups, the high chances of adults being sleepwalkers and elderly males performing intense and violent movements in bed showed us the importance of developing wearable parasomnia devices to prevent injuries.

Keywords: parasomnia, wearable devices, sleepwalking, RBD

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153 Malignant Idiopathic Intracranial Hypertension Revealed a Hidden Primary Spinal Leptomeningeal Medulloblastoma

Authors: Naim Izet Kajtazi

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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.

Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma

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152 Role of Ologen in Previously Failed Trabeculectomy in Advanced Glaucoma

Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: Advanced Glaucoma with Failed trab is not an uncommon sight in glaucoma clinic, and such cases usually tend to present with high intraocular pressure (IOP) and advanced cupping, or even glaucomatous atrophy stage. Re-surgery is needed for such cases, and wound modulation poses a major challenge in these cases. We share our experience in this case series with the use of Ologen (collagen matrix implant) along with MMC 0.04% used in surgery. The purpose of the study was to evaluate the efficacy and outcome of collagen matrix implant in re-trabeculectomy in advanced glaucoma cases. Methodology: Eleven eyes of 11 patients (one eye of one patient) underwent re-trabeculectomy surgery with MMC and Ologen. Ologen implant was used in sub scleral and subconjunctival space, as a spacer and wound modulator. In five cases, triple modulation with implant soaked in anti-VEGF was used. Results: All patients had cupping more than 0.9, and one case was GOA. All cases were on maximal medication at presentation and majority were on systemic anti-glaucoma therapy also. Post-surgery, follow-up ranged from 13 – 34 months, and all cases had a follow longer than the gap between previous surgery (which was failed) and re-trab. One case needed AC reformation and one needling was done. Phaco was done at same sitting in four cases. All cases had their IOP lowered post surgery, and vision was maintained in all, however one case was considered as failed re-surgery case. Topical medication was needed in seven cases post-surgery also. Conclusion: Ologen as adjuvant should be considered in all re-trab cases and all high risk and advanced cases, and triple modulation can be next step in these cases. Aggressive IOP control and non- reluctance to continue topical medications post second surgery should be considered in such cases, to give them best possible vision.

Keywords: failed trabeculectomy, ologen, trabeculectomy, advanced glaucoma

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151 Emotional, Behavioral and Social Problems in Children with Fecal Incontinence by Child Behavior Checklist (CBCL): A Cross-sectional Study

Authors: Roshanak Farjad, Amirhossein Hosseini

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Fecal incontinence (FI) is a stressful condition for children and their parents that may affect the patient’s psychological well-being. Evaluating the patients’ psychological status may help physicians manage the disease effectively. This study aimed to assess the emotional and behavioral disturbances in children with FI who were referred to the pediatric gastroenterology clinic in Mofid Children’s Hospital from April 2021 to 2022. This cross-sectional study included children (over four years old) with chronic constipation and fecal incontinence. The diagnosis of chronic constipation and FI were made according to Rome-IV criteria. The Child Behavior Checklist (CBCL) evaluated patients’ emotional, behavioral, and social problems. One hundred one patients with a mean age of 7.96 years were enrolled in the study; 67.32% were males. According to CBCL, 12% (12 patients) indicated emotional and behavioral problems, with CBCL scores in the clinical or at-risk range. We detected anxious/depressed problems in five (4.95%), withdrawn/depressed problems in eight (7.92%), somatic complaints in seven (6.93%), social problems in eight (7.92%), thought problems in nine (8.91%), attention problems in seven (6.93%), rule-breaking behavior in two (1.98%), and aggressive behavior in nine (8.91%) patients. The risk of internalizing and externalizing disorders was reported in four (3.96%) and five (4.95%) patients. Also, eight (7.92%) and seven (6.93%) patients had clinical symptoms of internalizing and externalizing disorders, respectively. There was no significant relationship between patients’ age and gender with the CBCL scores in any subscales. However, there was a significant difference in the total score among the age groups (P = 0.04). The relatively high prevalence of emotional, behavioral, and social problems in our study corroborates the importance of psychological screening of children with FI during the treatment process.

Keywords: chronic constipation, child behavior checklist (CBCL), fecal incontinence, rome-IV criteria

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150 The Causes and Effects of Delinquent Behaviour among Students in Juvenile Home: A Case Study of Osun State

Authors: Baleeqs, O. Adegoke, Adeola, O. Aburime

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Juvenile delinquency is fast becoming one of the largest problems facing many societies due to many different factors ranging from parental factors to bullying at schools all which had led to different theoretical notions by different scholars. Delinquency is an illegal or immoral behaviour, especially by the young person who behaves in a way that is illegal or that society does not approve of. The purpose of the study was to investigate causes and effects of delinquent behaviours among adolescent in juvenile home in Osun State. A descriptive survey research type was employed. The random sampling technique was used to select 100 adolescents in Juvenile home in Osun State. Questionnaires were developed and given to them. The data collected from this study were analyzed using frequency counts and percentage for the demographic data in section A, while the two research hypotheses postulated for this study were tested using t-test statistics at the significance level of 0.05. Findings revealed that the greatest school effects of delinquent behaviours among adolescent in juvenile home in Osun by respondents were their aggressive behaviours. Findings revealed that there was a significant difference in the causes and effects of delinquent behaviours among adolescent in juvenile home in Osun State. It was also revealed that there was no significant difference in the causes and effects of delinquent behaviours among secondary school students in Osun based on gender. These recommendations were made in order to address the findings of this study: More number of teachers should be appointed in the observation home so that it will be possible to provide teaching to the different age group of delinquents. Developing the infrastructure facilities of short stay homes and observation home is a top priority. Proper counseling session’s interval is highly essential for these juveniles.

Keywords: behaviour, delinquency, juvenile, random sampling, statistical techniques, survey

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149 An Exploration of Parenting By Perpetrator Fathers and Victim Mothers in the Context of Domestic Violence

Authors: Gunendra Rathnawali Kumarihamy Dissanayake

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Research on parenting of both perpetrators and victims of domestic violence (DV) is growing but limited. Further, much of this research in the Asian context is limited to explorations of victim mothers' parenting capacities, not shedding much light on the parenting of the perpetrator fathers. The current qualitative study aimed to explore how both the perpetrators and victims of DV engaged in parenting in the Sri Lankan cultural context. Twenty case studies were conducted with a sample of help-seeking women aged 20 to 40 years representing working to upper-middle social class. Participants have interviewed about their own as well as their partners´ parenting behaviors. The majority of women reported that their partners were often aggressive, controlling and authoritarian, less consistent, and engaged in a variety of manipulative behaviors intending to harm the relationship between their child and them. Further, victim mothers' styles of parenting and authority as parents have been severely undermined by their partners through frequent criticism, ridicule, and insulting in front of the children. As a result, mothers experienced great difficulty specifically trying to discipline their adolescent children as the children have started to disregard the mothers' authority. Most of the children also have shown treatment similar to that of their fathers', treating the mother as a personal servant not worthy of being listened to, thereby increasing the mothers' parenting stress. The mothers were often blamed and held responsible for the problems of the children by their partners, encouraging the children to disrespect and blame the mother for their problems leading them to take the side of the father who had more power. Findings are similar to those of the western context. This study highlights the intersection between domestic violence and parenting, and specific implications and recommendations for DV service providers are offered.

Keywords: parenting, domestic violence, impact, children

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148 Role of Imaging in Predicting the Receptor Positivity Status in Lung Adenocarcinoma: A Chapter in Radiogenomics

Authors: Sonal Sethi, Mukesh Yadav, Abhimanyu Gupta

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The upcoming field of radiogenomics has the potential to upgrade the role of imaging in lung cancer management by noninvasive characterization of tumor histology and genetic microenvironment. Receptor positivity like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genotyping are critical in lung adenocarcinoma for treatment. As conventional identification of receptor positivity is an invasive procedure, we analyzed the features on non-invasive computed tomography (CT), which predicts the receptor positivity in lung adenocarcinoma. Retrospectively, we did a comprehensive study from 77 proven lung adenocarcinoma patients with CT images, EGFR and ALK receptor genotyping, and clinical information. Total 22/77 patients were receptor-positive (15 had only EGFR mutation, 6 had ALK mutation, and 1 had both EGFR and ALK mutation). Various morphological characteristics and metastatic distribution on CT were analyzed along with the clinical information. Univariate and multivariable logistic regression analyses were used. On multivariable logistic regression analysis, we found spiculated margin, lymphangitic spread, air bronchogram, pleural effusion, and distant metastasis had a significant predictive value for receptor mutation status. On univariate analysis, air bronchogram and pleural effusion had significant individual predictive value. Conclusions: Receptor positive lung cancer has characteristic imaging features compared with nonreceptor positive lung adenocarcinoma. Since CT is routinely used in lung cancer diagnosis, we can predict the receptor positivity by a noninvasive technique and would follow a more aggressive algorithm for evaluation of distant metastases as well as for the treatment.

Keywords: lung cancer, multidisciplinary cancer care, oncologic imaging, radiobiology

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147 Effect of Various Durations of Type 2 Diabetes on Muscle Performance

Authors: Santosh Kumar Yadav, Shobha Keswani, Nishat Quddus, Sohrab Ahmad Khan, Zuheb Ahmad Shiddiqui, Varsha Chorsiya

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Introduction: Early onset diabetes is more aggressive than the late onset diabetes. Diabetic individual has a greater spectrum of life period to suffer from its damage, complications, and long-term disability. This study aimed at assessing knee joint muscle performance under various durations of diabetes. Method and Materials: A total of 30 diabetic subjects (18 male and 12 females) without diabetic neuropathy were included for the study. They were divided into three groups with 5 years, 10 years and 15 years of duration of disease each. Muscle performance was evaluated through strength and flexibility. Peak torque for quadriceps muscle was measured using isokinetic dynamometer. Flexibility for quadriceps and hamstring muscles were measured through Ducan’s Elys test and 90/90 test. Results: The result showed significant difference in muscle strength (p<0.05), flexibility (p≤0.05) between groups. Discussion: Optimal muscle strength and flexibility are vital for musculoskeletal health and functional independence. Conclusion: The reduced muscle performance and functional impairment in nonneuropathic diabetic patients suggest that other mechanism besides neuropathy that contribute to altered biomechanics. These findings of this study project early management of these altered parameters through disease-specific physical therapy and assessment-based intervention. Clinical Relevance: Managing disability is more costly than managing disease. Prompt and timely identification and management strategy can dramatically reduce the cost of care for diabetic patients.

Keywords: muscle flexibility, muscle performance, muscle torque, type 2 diabetes

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146 Grassroots Feminist Organizing in the Shadow of State Feminism in Ethiopia

Authors: Tina Beyene

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In this paper examines the state of grassroots feminist activism in the backdrop of state feminism in Ethiopia. Specifically, I examine the impact of the Charities and Societies Proclamation (aka CSO law), a 2009 law that banned so-called foreign NGOs—i.e., those receiving more than 10% of its operating budget from non-local sources— from working in the areas of human rights, democracy, governance, and gender equality. Viewed as government retribution for the NGO opposition to the government in the 2005 elections, the law aimed to halt the work groups such as the Ethiopian Women Lawyers Association (EWLA), who were defined as a “foreign” NGO. Based on interviews with prominent Ethiopian women’s rights leaders in Addis Ababa, Ethiopia, I assess how grassroots feminist organizing adapts to state suppression on the one hand, and the aggressive entry of the state into women’s rights work on the other hand. While the 2009 law has slowed down the work of women’s rights activism, displaced feminists view feminist advocacy as cyclical and the state as neither fully adversarial nor an ally but rather as an instable entity that at times provides political openings to push ambitious feminist agendas. Grassroots activists are regrouping and developing new political responses strategies such as coding rights issues to fit state mandate; dissembling rights work in permissible social provision language; rechanneling political work into informal spaces and unregistered social clubs; innovating new funding partnerships, and reassembling as privately held research and advocacy companies. my study reveals how grassroots feminist politics operates in the shadow of a hostile state and within the confines of local politics.

Keywords: grassroots feminism, ethiopian feminism, civil society and gender, state feminism

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145 Bionaut™: A Microrobotic Drug-Device Platform for the Local Treatment of Brainstem Gliomas

Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

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Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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144 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells

Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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143 Factors Influencing Violence Experienced by Medical Staff in Primary Health Care Centers, Taif City

Authors: Turki Adnan Kamal, Abdulmajeed Ahmad Alsofiany, Nemer Khidhran Husain Alghamdi, Ali Eissa Hassan Al-Rajhi

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Background:- Health care workers are ranked as one of the most vulnerable groups experiencing violence and aggressive behavior compared to other occupational groups. Objectives:- To estimate the prevalence rate and characteristics and assess the avoidance measures, and notification of the violence among medical staff working in primary health care centers in Taif city. Subject and methods:- A cross-sectional study design was applied among all physicians and a representative sample of nurses working in primary health care centers affiliated with the Ministry of Health (MOH) in Taif city. A predesigned Arabic/English validated self-administered questionnaire was used. Results:- In this study, 56 physicians and 145 nurses responded, giving a response rate of 77.6%. Their age ranged from 25 and 60 years (36.2±8.2), with 59.7% of them aged between 25 and 35 years. Males represent 55.7% of them. More than half of them (52.2%) were Saudis. The prevalence of workplace violence was 30.3%. Verbal abuse was the commonest reported type (86.9%). The absence of security, training on the procedures that must be followed and special uniforms at the workplace were significantly associated with workplace violence. We concluded that workplace violence is a significant problem facing a considerable proportion of HCWs in primary health care centers in Taif, Saudi Arabia. Most violence incidents were verbal. Conclusion:- Findings of this study revealed that HCWs who were dealing with male patients only were at high risk of workplace violence and the absence of measures to avoid workplace violence, particularly security, training on the procedures that must be followed and special uniform at the workplace was significantly associated with workplace violence.

Keywords: violence, workplace, primary health care, prevalence, avoidance

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142 Client Importance and Audit Quality under Civil Law versus Common Law Societies

Authors: Kelly Grani Yuen

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Accounting scandals and auditing frauds are perceived to be driven by aggressive companies and misrepresentation of audit reports. However, local legal systems and law enforcements may affect the services auditors provide to their ‘important’ clients. Under the civil law and common law jurisdictions, the standard setters, the government, and the regulatory bodies treat cases differently. As such, whether or not different forms of legal systems and extent of law enforcement plays an important role in auditor’s Audit Quality is a question this paper attempts to explore. The paper focuses on the investigation in Asia, where Hong Kong represents the common-law jurisdiction, while Taiwan and China represent the civil law jurisdiction. Only the ten reputable accounting firms are used in this study due to the differences in rankings and establishments of some of the small local audit firms. This will also contribute to the data collected between the years 2007-2013. By focusing on the use of multiple regression based on the dependent (Audit Quality) and independent variables (Client Importance, Law Enforcement, and Press Freedom), six different models are established. Results demonstrate that since different jurisdictions have different legal systems and market regulations, auditor’s treatment on ‘important’ clients will vary. However, with the moderators in place (law enforcement and press freedom), the relationship between client importance and audit quality may be smoothed out. With that in mind, this study contributes to local governments and standard setters’ consideration on legal reform and proper law enforcement in the market. Perhaps, with such modifications on the economic systems, collusion between companies and auditors can finally be put to a halt.

Keywords: audit quality, client importance, jurisdiction, modified audit opinions

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141 Acute Cartilage Defects of the Knee Treated With Chondral Restoration Procedures and Patellofemoral Stabilisation

Authors: John Scanlon, Antony Raymond, Randeep Aujla, Peter D’Alessandro, Satyen Gohil

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Background: The incidence of significant acute chondral injuries with patella dislocation is around 10-15%. It is accepted that chondral procedures should only be performed in the presence of joint stability Methods:Patients were identified from surgeon/hospital logs. Patient demographics, lesion size and location, surgical procedure, patient reported outcome measures, post-operative MR imaging, and complications were recorded. PROMs and patient satisfaction was obtained. Results:20 knees (18 patients) were included. Mean age was 18.6 years (range; 11-39), and the mean follow-up was 16.6 months (range; 2-70). The defect locations were the lateral femoral condyle (9/20; 45%), patella (9/20; 45%), medial femoral condyle (1/20; 5%) and the trochlea (1/20; 5%). The mean defect size was 2.6cm2. Twelve knees were treated with cartilage fixation, 5 with microfracture, and 3 with OATS. At follow up, the overall mean Lysholm score was 77.4 (± 17.1), with no chondral regenerative procedure being statistically superior. There was no difference in Lysholm scores between those patients having acute medial patellofemoral ligament reconstruction versus medial soft tissue plication (p=0.59). Five (25%) knees required re-operation (one arthroscopic arthrolysis; one patella chondroplasty; two removal of loose bodies; one implant adjustment). Overall, 90% responded as being satisfied with surgery. Conclusion: Our aggressive pathway to identify and treat acute cartilage defects with early operative intervention and patella stabilisation has shown high rates of satisfaction and Lysholm scores. The full range of chondral restoration options should be considered by surgeons managing these patients.

Keywords: patella dislocation, chondral restoration, knee, patella stabilisation

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140 The Culex Pipiens Niche: Assessment with Climatic and Physiographic Variables via a Geographic Information System

Authors: Maria C. Proença, Maria T. Rebelo, Marília Antunes, Maria J. Alves, Hugo Osório, Sofia Cunha, João Casaca

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Using a geographic information system (GIS), the relations between a georeferenced data set of Culex pipiens sl. mosquitoes collected in Portugal mainland during seven years (2006-2012) and meteorological and physiographic parameters such as: air relative humidity, air temperature (minima, maxima and mean daily temperatures), daily total rainfall, altitude, land use/land cover and proximity to water bodies are evaluated. Focus is on the mosquito females; the characterization of its habitat is the key for the planning of chirurgical non-aggressive prophylactic countermeasures to avoid ambient degradation. The GIS allow for the spatial determination of the zones were the mosquito mean captures has been above average; using the meteorological values at these coordinates, the limits of each parameter are identified/computed. The meteorological parameters measured at the net of weather stations all over the country are averaged by month and interpolated to produce raster maps that can be segmented according to the thresholds obtained for each parameter. The intersection of the maps obtained for each month show the evolution of the area favorable to the species through the mosquito season, which is from May to October at these latitudes. In parallel, mean and above average captures were related to the physiographic parameters. Three levels of risk could be identified for each parameter, using above average captures as an index. The results were applied to the suitability meteorological maps of each month. The Culex pipiens critical niche is delimited, reflecting the critical areas and the level of risk for transmission of the pathogens to which they are competent vectors (West Nile virus, iridoviruses, rheoviruses and parvoviruses).

Keywords: Culex pipiens, ecological niche, risk assessment, risk management

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139 Increased Cytolytic Activity of Effector T-Cells against Cholangiocarcinoma Cells by Self-Differentiated Dendritic Cells with Down-Regulation of Interleukin-10 and Transforming Growth Factor-β Receptors

Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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138 Computational Screening of Secretory Proteins with Brain-Specific Expression in Glioblastoma Multiforme

Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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137 Suggested Role for Neutrophil Extracellular Traps Formation in Ewing Sarcoma Immune Microenvironment

Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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136 Resistance to the South African Root-Knot Nematode Population Densities in Artemisia annua: An Anti-Malaria Ethnomedicinal Plant

Authors: Kgabo Pofu, Hintsa Araya, Dean Oelofse, Sonja Venter, Christian Du Plooy, Phatu Mashela

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Nematode resistance to the tropical root-knot (Meloidogyne species) nematodes is one of the most preferred nematode management strategies in development of smallholder resource-poor farming systems. Due to its pharmacological and ethnomedicinal applications, Artemisia annua is one of the underutilised crops that have attracted attention of policy-makers in rural agrarian development in South Africa. However, the successful introduction of this crop in smallholder resource-poor farming systems could be upset by the widespread aggressive Meloidogyne species, which have limited management options. The objective of this study therefore was to determine the degree of nematode resistance to the South African M. incognita and M. javanica population densities on A. annua seedlings. Uniform three-week-old seedlings in pots containing pasteurised growing medium under greenhouse conditions were inoculated using a series of eggs and second-stage juveniles of two Meloidogyne species in separate trials. At 56 days after inoculation, treatments were highly significant on reproductive factor (RF) for M. incognita and M. javanica on A. annua, contributing 87 and 89% in total treatment variation of the variables, respectively. At all levels of inoculation, RF values for M. incognita (0.17-0.79) and M. javanica (0.02-0.29) were below unity, without any noticeable root galls. Infection of A. annua by both Meloidogyne species had no significant effects on growth variables. In conclusion, A. annua seedlings are resistant to the South African M. incognita and M. javanica population densities and could therefore be explored further for use in smallholder resource-poor farming systems.

Keywords: ethnomedicial plants, medicinal plants, underutilised crops, plant parasitic nematodes

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135 Fabrication of Durable and Renegerable Superhydrophobic Coatings on Metallic Surfaces for Potential Industrial Applications

Authors: Priya Varshney, Soumya S. Mohapatra

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Fabrication of anti-corrosion and self-cleaning superhydrophobic coatings for metallic surfaces which are regenerable and durable in the aggressive conditions has shown tremendous interest in materials science. In this work, the superhydrophobic coatings on metallic surfaces (aluminum, steel, copper) were prepared by two-step and one-step chemical etching process. In two-step process, roughness on surface was created by chemical etching and then passivation of roughened surface with low surface energy materials whereas, in one-step process, roughness on surface by chemical etching and passivation of surface with low surface energy materials were done in a single step. Beside this, the effect of etchant concentration and etching time on wettability and morphology was also studied. Thermal, mechanical, ultra-violet stability of these coatings were also tested. Along with this, regeneration of coatings and self-cleaning, corrosion resistance and water repelling characteristics were also studied. The surface morphology shows the presence of a rough microstuctures on the treated surfaces and the contact angle measurements confirms the superhydrophobic nature. It is experimentally observed that the surface roughness and contact angle increases with increase in etching time as well as with concentration of etchant. Superhydrophobic surfaces show the excellent self-cleaning behaviour. Coatings are found to be stable and maintain their superhydrophobicity in acidic and alkaline solutions. Water jet impact, floatation on water surface, and low temperature condensation tests prove the water-repellent nature of the coatings. These coatings are found to be thermal, mechanical and ultra-violet stable. These durable superhydrophobic metallic surfaces have potential industrial applications.

Keywords: superhydrophobic, water-repellent, anti-corrosion, self-cleaning

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134 In-silico Target Identification and Molecular Docking of Withaferin A and Withanolide D to Understand their Anticancer Therapeutic Potential

Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

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Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

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133 Genetic and Virulence Diversity among Alternaria carthami Isolates of India

Authors: Garima Anand, Rupam Kapoor

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Alternaria leaf spot caused by Alternaria carthami is one of the most devastating diseases of safflower. It has resulted in huge losses in crop production and cultivation leading to a fall out of India’s rank as the leading producer of safflower in the world. Understanding the diversity of any pathogen is essential for its management and for the development of disease control strategies. The diversity of A. carthami was therefore analysed on the basis of biochemical, pathogenicity and genetic lines using ISSR markers. Collections and isolations of 95 isolates of A. carthami were made from major safflower producing states of India. Virulence was analysed to evaluate the pathogenic potential of these isolates. The isolates from Bijapur, Dharwad districts (Karnataka), and Parbhani and Solapur districts (Maharashtra) were found to be highly virulent. The virulence assays showed low virulence levels (42%) for the largest part of the population. Biochemical characterization to assess aggressiveness of these isolates was done by estimating the activity of cell wall degrading enzymes where isolates from districts Dharwad, Bijapur of Karnataka and districts Parbhani and Latur of Maharashtra were found to be most aggressive. Genetic diversity among isolates of A. carthami was determined using eighteen ISSR markers. Distance analysis using neighbour joining method and PCoA analysis of the ISSR profiles divided the isolates into three sub-populations. The most virulent isolates clustered in one group in the dendrogram. The study provided no evidence for geographical clustering indicating that isolates are randomly spread across the states, signifying the high potential of the fungus to adapt to diverse regions. The study can, therefore, aid in the breeding and deployment of A. carthami resistant safflower varieties and in the management of Alternaria leaf spot disease.

Keywords: alternaria leaf spot, genetic diversity, pathogenic potential, virulence

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132 Clinical Relevance of TMPRSS2-ERG Fusion Marker for Prostate Cancer

Authors: Shalu Jain, Anju Bansal, Anup Kumar, Sunita Saxena

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Objectives: The novel TMPRSS2:ERG gene fusion is a common somatic event in prostate cancer that in some studies is linked with a more aggressive disease phenotype. Thus, this study aims to determine whether clinical variables are associated with the presence of TMPRSS2:ERG-fusion gene transcript in Indian patients of prostate cancer. Methods: We evaluated the clinical variables with presence and absence of TMPRSS2:ERG gene fusion in prostate cancer and BPH association of clinical patients. Patients referred for prostate biopsy because of abnormal DRE or/and elevated sPSA were enrolled for this prospective clinical study. TMPRSS2:ERG mRNA copies in samples were quantified using a Taqman chemistry by real time PCR assay in prostate biopsy samples (N=42). The T2:ERG assay detects the gene fusion mRNA isoform TMPRSS2 exon1 to ERG exon4. Results: Histopathology report has confirmed 25 cases as prostate cancer adenocarcinoma (PCa) and 17 patients as benign prostate hyperplasia (BPH). Out of 25 PCa cases, 16 (64%) were T2: ERG fusion positive. All 17 BPH controls were fusion negative. The T2:ERG fusion transcript was exclusively specific for prostate cancer as no case of BPH was detected having T2:ERG fusion, showing 100% specificity. The positive predictive value of fusion marker for prostate cancer is thus 100% and the negative predictive value is 65.3%. The T2:ERG fusion marker is significantly associated with clinical variables like no. of positive cores in prostate biopsy, Gleason score, serum PSA, perineural invasion, perivascular invasion and periprostatic fat involvement. Conclusions: Prostate cancer is a heterogeneous disease that may be defined by molecular subtypes such as the TMPRSS2:ERG fusion. In the present prospective study, the T2:ERG quantitative assay demonstrated high specificity for predicting biopsy outcome; sensitivity was similar to the prevalence of T2:ERG gene fusions in prostate tumors. These data suggest that further improvement in diagnostic accuracy could be achieved using a nomogram that combines T2:ERG with other markers and risk factors for prostate cancer.

Keywords: prostate cancer, genetic rearrangement, TMPRSS2:ERG fusion, clinical variables

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