Search results for: clinical markers

Authors: Salaam Mujeeb, Adeola Segun, Abdullahi Olasunkanmi

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Dementia is becoming a major concern as the world population is increasing and elderly populations are being neglected. Liver and kidney Diseases have been implicated as risk factors in the etiology of Dementia. This study, therefore, evaluates the plasma Gamma Glutamyl Transferase (GGT) activity and plasma Electrolytes in other to find an association between the biomarkers and Dementia. The subjects (38) were age and sex-matched with their corresponding controls and structured questionnaires were used to obtain medical information. Using spectrophotometric and ion selective Electrode techniques respectively, we found and elevated GGT activity in the Dementia Subjects. Remarkably, no association was found between the plasma Electrolytes level and Dementia subjects. It was also observed that severity of Dementia worsens with age. Moreover, the condition of the dementia subjects worsens with reducing weight. Furthermore, the presence of Comorbidity e.g. Hypertension, Obesity, Diabetes and Habits like Smoking, Drugs and Alcohol consumption interferes with Electrolyte balance. Weight loss monitoring and IBM check are advised in Elderly individuals particularly females as they may be inductive of early or future cognitive impairments. Therefore, it might be useful as an early detection tool. Government and society should invest more on the Geriatric population by establishing Old people's home and providing social care services.

Keywords: clinical characteristics, dementia, electrolytes, gamma glutamyl transpeptidase, GGT

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Authors: Vandana Singh, Subash Singh

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Introduction: Oral squamous cell carcinoma is the most common malignant tumor of the oral cavity. Normally the death of cell and the growth are active processes and depend not only on external factors but also on the expression of genes like Bcl-2, which activate and inhibit apoptosis. The term Bcl-2 is an acronym for B-cell lymphoma/ leukemia -2 genes. Objectives: An attempt was made to evaluate Bcl-2 oncoprotein expression in patients with oral precancer and cancer and to assess possible correlation between Bcl-2 oncoprotein expression and clinicopathological features of oral precancer and cancer. Material and Methods: This is a selective prospective clinical and immunohistochemical study. Clinicopathological examination is correlated with immunohistochemical findings. The immunolocalization of Bcl-2 protein is performed using the labeled streptavidin biotin (LSAB) method. To visualize the reaction, 3, 3-diaminobenzidine (DAB) is used. Results: Bcl-2 expression was positive in 11 [36.66 %, low Bcl-2 expression 3 (10.00 %), moderate Bcl-2 expression 7 (23.33 %), and high Bcl-2 expression 1 (3.33 %)] oral cancer cases and in 14 [87.50 %, low expression 8 (50 %), moderate expression 6 (37.50 %)] precancer cases. Conclusion: On the basis of the results of our study we conclude that positive Bcl-2 expression may be an indicator of poor prognosis in oral cancer and precancer. Relevance: It has been reported that there is deregulation of Bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. It can be used for revealing progression of epithelial dysplasia to malignancy and as a prognostic marker in oral precancer and cancer.

Keywords: BcL-2, immunohistochemistry, oral cancer, oral precancer

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Authors: Fardis Teifoori, Mehdi Dehghani, Idoia Postigo, Jorge Martinez

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Introduction: Many skin disorders, such as atopic dermatitis (AD), is characterized by inflammation, infection, and hyperplasia. In this work, keratinocytes from AD patients are used to study the pomegranate seed oil properties for skin care. Material and methods: Isolated keratinocytes from patients with AD were cultured and stimulated by IL-9 (20 ng/ml) and TNF-α (50ng/ml) for 48h to induce vascular endothelial growth factor (VEGF) and Regulated upon activation, normal T cell expressed and secreted (RANTES) production, respectively, in the presence of different concentrations of pomegranate seed oil (20, 50, 100, and 200 µM). Finally, the concentrations of RANTES and VEGF in the cell culture supernatant were quantified according to the standard protocol of commercial ELISA kits. Results: The results indicated that pomegranate seed oil concentrations of 50, 100, and 200 µM could significantly inhibit the production of VEGF and RANTES by stimulating keratinocytes with IL-9 (20 ng/ml) and TNF-α (50ng/ml), respectively. The decrease in VEGF and RANTES concentration in the presence of the pomegranate seed oil concentrations of 20 and 50 uM was not significant. Conclusion: It was concluded that pomegranate seed oil (PSO) counteracts atopic dermatitis conditions dose-dependently: with the highest effect at the concentration of 200 µM. We suggest that the inexpensive and easily available pomegranate seed oil is a good candidate for cosmetics and clinical utilization for skin care.

Keywords: atopic dermatitis, pomegranate, Punica granatum, RANTES, VEGF

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Authors: Adem Pala, Mustafa Biner

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Nowadays, despite the fact that technology and internet shorten the virtual distance, too much use and misuse of internet create distance among people. There is a considerable number of people living in the same house even sitting at the same table but busy themselves with mobiles and computers for long hours without talking to each other. Internet usage is very common among young people especially university students. Evolving out of this problem, internet addiction of university students and effect on their loneliness, and relationship between them consist of the purpose of this study. The study is important because it discusses what can be done in order to make the young people more social via determining the university students’ loneliness and their internet addiction. The study was carried out with 440 university students studying at different universities and departments. The group consists of 200 female and 240 male students with average of age 20,9. In the study, 19 questions, “internet addiction scale” consisting of 3 subscales, and UCLA loneliness scale were used as data collection tools. As a result, it is found out that the loneliness of individuals with internet addiction is higher than the other individuals. The males’ loneliness related to internet addiction is higher than the females; on the other hand, it is determined females feel more lonesome in general loneliness. It is thought that the findings of the study will determine the individuals under risk, prevent them, help researchers and people doing clinical studies during rehabilitation progress.

Keywords: internet addiction, loneliness, Turkey, university students

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Chien-Lin Wang, Cha-Ling Ko, Tainsong Chen

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Pulse Blood pressure (BP) is one of the vital signs, and is an index that helps determining the stability of life. In this respect, some spinal cord injury patients need to take the tilt table test. While doing the test, the posture changes abruptly, and may cause a patient’s BP to change abnormally. This may cause patients to feel discomfort, and even feel as though their life is threatened. Therefore, if a continuous non-invasive BP assessment system were built, it could help to alert health care professionals in the process of rehabilitation when the BP value is out of range. In our research, BP assessed by the pulse transit time technique was developed. In the system, we use a self-made photoplethysmograph (PPG) sensor and filter circuit to detect two PPG signals and to calculate the time difference. The BP can immediately be assessed by the trend line. According to the results of this study, the relationship between the systolic BP and PTT has a highly negative linear correlation (R2=0.8). Further, we used the trend line to assess the value of the BP and compared it to a commercial sphygmomanometer (Omron MX3); the error rate of the system was found to be in the range of ±10%, which is within the permissible error range of a commercial sphygmomanometer. The continue blood pressure measurement from pulse transit time technique may have potential to become a convenience method for clinical rehabilitation.

Keywords: continous blood pressure measurement, PPG, time transit time, transit velocity

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Authors: B. Farahani, R. Fadil, A. Aboonabi, B. Hoffmann, J. Loscheider, K. Tavakolian, S. Arzanpour

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Wheelchair users spend long hours in a sitting position, and selecting the right cushion is highly critical in preventing pressure ulcers in that demographic. Pressure mapping systems (PMS) are typically used in clinical settings by therapists to identify the sitting profile and pressure points in the sitting area to select the cushion that fits the best for the users. A PMS is a flexible mat composed of arrays of distributed networks of flexible sensors. The output of the PMS systems is a color-coded image that shows the intensity of the pressure concentration. Therapists use the PMS images to compare different cushions fit for each user. This process is highly subjective and requires good visual memory for the best outcome. This paper aims to develop an image processing technique to analyze the images of PMS and provide an objective measure to assess the cushions based on their pressure distribution mappings. In this paper, we first reviewed the skeletal anatomy of the human sitting area and its relation to the PMS image. This knowledge is then used to identify the important features that must be considered in image processing. We then developed an algorithm based on those features to analyze the images and rank them according to their fit to the users' needs.

Keywords: dynamic cushion, image processing, pressure mapping system, wheelchair

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Authors: Sat Sharma, Antonella Conflitti, Hilary Reiter

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Introduction: The study's purpose was to assess the efficacy of the oral appliance device O2Vent Optima + ExVent as compared to Optima in the treatment of OSA. Methods: A prospective, open-label study conducted at 3 sites included subjects with mild to moderate OSA (AHI ≥ 5 and ≤ 30). Screening Phase: A diagnostic in-lab PSG study was performed to confirm a diagnosis of mild to moderate OSA. Treatment I: Subjects used O2Vent Optima for 6 weeks and underwent an in-lab PSG sleep night while using the O2Vent Optima. Treatment II: Subjects used O2Vent Optima + ExVent for 6 weeks and underwent an in-lab PSG sleep night while using the O2Vent Optima + ExVent Primary Effectiveness Measure: Change in AHI between baseline vs. O2Vent Optima MAD vs. O2Vent Optima + ExVent. Results: Treatment with Optima, Optima + ExVent reduced AHI from 22.5±6.4/hr to 12.6±4.5/hr to 5.9±2.7 (p< 0.005 baseline vs. Optima and Optima + ExVent; p<0.05 Optima MAD vs. Optima + ExVent). The average reduction in AHI with Optima was 43%, and with Optima + ExVent was 72%. The lowest oxygen during sleep increased from 84.6±2.7% to 88.6±2.9% to 91.6±3.2% (p< 0.005 baseline vs. Optima and Optima + ExVent; p<0.05 Optima vs. Optima + ExVent). During the trial, patients on treatment with Optima and Optima + ExVent demonstrated no excessive adverse events or device malfunction. Conclusion: Treatment with O2Vent Optima and O2Vent Optima + ExVent significantly improved OSA compared to the baseline. An even greater benefit was observed with the addition of ExVent to the Optima in mild to moderate OSA.

Keywords: oral appliance, O2Vent, sleep dentistry, sleep apnea

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Authors: Hiroyuki Aoki

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Molecular imaging has attracted much attention recently, which visualizes biological molecules, cells, tissue, and so on. Among various in vivo imaging techniques, the fluorescence imaging method has been widely employed as a useful modality for small animals in pre-clinical researches. However, the higher signal intensity is needed for highly sensitive in vivo imaging. The objective of the current study is the development of a fluorescent imaging agent with high brightness for the tumor imaging of a mouse. The strategy to enhance the fluorescence signal of a bio-imaging agent is the increase of the absorption of the excitation light and the fluorescence conversion efficiency. We developed a nano-particle fluorescence imaging agent consisting of a π-conjugated polymer emitting a fluorescence signal in a near infrared region. A large absorption coefficient and high emission intensity at a near infrared optical window for biological tissue enabled highly sensitive in vivo imaging with a tumor-targeting ability by an EPR (enhanced permeation and retention) effect. The signal intensity from the π-conjugated fluorescence imaging agent is larger by two orders of magnitude compared to a quantum dot, which has been known as the brightest imaging agent. The π-conjugated polymer nano-particle would be a promising candidate in the in vivo imaging of small animals.

Keywords: fluorescence, conjugated polymer, in vivo imaging, nano-particle, near-infrared

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Authors: Chun-Lang Chang, Chun-Kai Liu

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In this study, the patients that have undergone total knee replacement surgery from the 2010 National Health Insurance database were adopted as the study participants. The important factors were screened and selected through literature collection and interviews with physicians. Through the Cross Entropy Method (CE), Genetic Algorithm Logistic Regression (GALR), and Particle Swarm Optimization (PSO), the weights of the factors were obtained. In addition, the weights of the respective algorithms, coupled with the Excel VBA were adopted to construct the Case Based Reasoning (CBR) system. The results through statistical tests show that the GALR and PSO produced no significant differences, and the accuracy of both models were above 97%. Moreover, the area under the curve of ROC for these two models also exceeded 0.87. This study shall serve as a reference for medical staff as an assistance for clinical assessment of infections in order to effectively enhance medical service quality and efficiency, avoid unnecessary medical waste, and substantially contribute to resource allocations in medical institutions.

Keywords: Case Based Reasoning, Cross Entropy Method, Genetic Algorithm Logistic Regression, Particle Swarm Optimization, Total Knee Replacement Surgery

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Authors: Sagarjyoti Roy

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Dengue is an arboviral infection, belonging to family flaviviridae, comprising of four serotypes; DENV1, DENV2, DENV3 and DENV4. All four serotypes are capable of causing full-spectrum of clinical features, ranging from self-limiting fever to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Complications may affect any organ system, including those involving gastrointestinal system and serositis. We report a case, of a 28 years, non-alcoholic male, presenting with a 7 day history of fever and malaise followed by abdominal pain and distension, from 4th day of fever. He was admitted in medicine department of RG KAR medical college hospital. Dengue fever was confirmed by NS1 and dengue IgM positivity. Platelet count was 30,000/cc (1.5- 4 lac/cc) and haematocrit was 52% (38- 50% for men). Clinicoradiological findings revealed bilateral pleural effusion, ascites and splenomegaly. Ascitic fluid was hemorrhagic in nature, with a high protein and RBC content. Liver function tests revealed mild transaminitis with normal coagulation profile. Patient was managed conservatively. A diagnosis of dengue fever complicated by serositis and spontaneous haemoperitoneum was made. The symptoms subsided after a hospital stay of 10 days. The case highlights haemorrhage into peritoneal cavity as a possible complication of dengue fever. Although a definite explanation requires more detailed studies, platelet or endothelial cell dysfunction might be contributory.

Keywords: ascites, dengue, haemoperitoneum, serositis

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Authors: Faith-Michael E. Uzoka, Boluwaji A. Akinnuwesi, Taiwo Amoo, Flora Aladi, Stephen Fashoto, Moses Olaniyan, Joseph Osuji

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The overarching aim of this study is to develop a soft-computing system for the differential diagnosis of tropical diseases. These conditions are of concern to health bodies, physicians, and the community at large because of their mortality rates, and difficulties in early diagnosis due to the fact that they present with symptoms that overlap, and thus become ‘confusable’. We report on the first phase of our study, which focuses on the development of a fuzzy cognitive map model for early differential diagnosis of tropical diseases. We used malaria as a case disease to show the effectiveness of the FCM technology as an aid to the medical practitioner in the diagnosis of tropical diseases. Our model takes cognizance of manifested symptoms and other non-clinical factors that could contribute to symptoms manifestations. Our model showed 85% accuracy in diagnosis, as against the physicians’ initial hypothesis, which stood at 55% accuracy. It is expected that the next stage of our study will provide a multi-disease, multi-symptom model that also improves efficiency by utilizing a decision support filter that works on an algorithm, which mimics the physician’s diagnosis process.

Keywords: medical diagnosis, tropical diseases, fuzzy cognitive map, decision support filters, malaria differential diagnosis

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Authors: Sadaf Ilyas

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Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.

Keywords: Interleukin 15, pET expression system, immune therapy, protein purification

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Authors: Alexa L. Walsh, Christine Hartl, Juliette Ferdschneider, Lezode Kipoliongo, Eleonora Feketeova

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The investigation of COVID-19 and its effects has been at the forefront of clinical research since its emergence in the United States in 2020. Although the possibility of severe infection in immunocompromised individuals has been documented, within the general population of pregnant individuals, there remains to be vaccine hesitancy and uncertainty regarding how the virus may affect the individual and fetus. To combat this hesitancy, this study aims to evaluate the effects of COVID-19 infection on maternal and neonatal complication rates. This retrospective study was conducted by manual chart review of women who were diagnosed with COVID-19 during pregnancy (n = 78) and women who were not diagnosed with COVID-19 during pregnancy (n = 1,124) that gave birth at Garnet Health Medical Centers between 1/1/2019-1/1/2021. Both the COVID+ and COVID- groups exhibited similar median ages, BMI, and parity. The rates of complications were compared between the groups and statistical significance was determined using Chi-squared analysis. Results demonstrated a statistically higher rate of PROM, polyhydramnios, oligohydramnios, GDM, DVT/PE, preterm birth, and the overall incidence of any birth complication in the population that was infected with COVID-19 during their pregnancy. With this information, obstetrical providers can be better prepared for the management of COVID-19+ pregnancies and continue to educate their patients on the benefits of vaccination.

Keywords: complications, COVID-19, Gynecology, Obstetrics

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Authors: Freddy Patricio Moncayo-Matute, Pablo Gerardo Peña-Tapia, Vázquez-Silva Efrén, Paúl Bolívar Torres-Jara, Diana Patricia Moya-Loaiza, Gabriela Abad-Farfán

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This study describes a clinical case and the results on the application of additive manufacturing for the surgical planning in the removal of a cranial spheno-orbital meningioma. It is verified that the use of personalized anatomical models and cutting guides helps to manage the cranial anomalies approach. The application of additive manufacturing technology: Fused Deposition Modeling (FDM), as a low-cost alternative, enables the printing of the test anatomical model, which in turn favors the reduction of surgery time, as well the morbidity rate reduction too. And the printing of the personalized cutting guide, which constitutes a valuable aid to the surgeon in terms of improving the intervention precision and reducing the invasive effect during the craniotomy. As part of the results, post-surgical follow-up is included as an instrument to verify the patient's recovery and the validity of the procedure.

Keywords: surgical planning, additive manufacturing, rapid prototyping, fused deposition modeling, custom anatomical model

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Authors: Shahriar Farzam, Maryam Rastgarpour

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Image denoising plays extremely important role in digital image processing. Enhancement of clinical image research based on Curvelet has been developed rapidly in recent years. In this paper, we present a method for image contrast enhancement for cone beam CT (CBCT) images based on fast discrete curvelet transforms (FDCT) that work through Unequally Spaced Fast Fourier Transform (USFFT). These transforms return a table of Curvelet transform coefficients indexed by a scale parameter, an orientation and a spatial location. Accordingly, the coefficients obtained from FDCT-USFFT can be modified in order to enhance contrast in an image. Our proposed method first uses a two-dimensional mathematical transform, namely the FDCT through unequal-space fast Fourier transform on input image and then applies thresholding on coefficients of Curvelet to enhance the CBCT images. Consequently, applying unequal-space fast Fourier Transform leads to an accurate reconstruction of the image with high resolution. The experimental results indicate the performance of the proposed method is superior to the existing ones in terms of Peak Signal to Noise Ratio (PSNR) and Effective Measure of Enhancement (EME).

Keywords: curvelet transform, CBCT, image enhancement, image denoising

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Authors: Ilirian Laçi, Alketa Spahiu

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Ageing causes an increase in the number of patients with spinal canal stenosis. Most of the patients have back pain, leg pain, numbness of the legs, as well as urinary incontinence as a very common symptoms. Urinary incontinence impairs the quality of life. Correction of the symptom of urinary incontinence is possible in the early and adequate treatment of spinal stenosis. Methods: This study observed patients with urinary incontinence and spinal canal stenosis. These patients underwent mechanical decompression of the spinal stenosis through surgery. At the same time, these patients were observed clinically with clinical consultations. Cystoscopy and urodynamic tests were conducted at intervals of 2 and 6 months. As a result of treatment, 60% of patients did recover. The patients in this group who benefit from treatment were the patients who were early diagnosed and treated. Conclusions: An important factor in the prognosis of this pathology is the early diagnosis and treatment. The proper treatment of this pathology makes it curable in most cases. An important role in this pathology is played by the neurosurgeon. Surgery accompanied by laminotomy and mechanical decompression is the best way of treatment. Other factors that played a role in this pathology are also a large number of childbirths for women, obesity, etc.

Keywords: urinary incontinence, quality of life, spinal canal stenosis, early diagnosis, treatment

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Authors: Kamesh Gupta, Nitin Jain, Anurag Rohatgi

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Objective: To study Vitamin B12 levels and presence of peripheral neuropathy among diabetes mellitus patients on metformin therapy. Method: The observational study was conducted from November 2014 to March 2015. Patients were selected from the Lady Hardinge Medical College, Delhi, India. Exhaustive history regarding dietary habits and metformin usage was taken. Lab tests including HbA1c levels and Vit B12 assays were done, on the basis of which patients were classified into subgroups. Peripheral neuropathy was detected by both clinical scoring and electrophysiological studies. Appropriate Statistical analysis for observational studies was done to evaluate the data. Results: The average duration of metformin usage was higher in patients with definite B12 deficiency (9.4y) than patients with normal B12 levels (5.6 y). Patients in the definite B12 deficiency group had much higher incidence of neuropathy (89%) than patients with no deficiency (27%). The incidence of neuropathy was higher in cases with longer metformin usage (100% with 18-22y of use and 83% with 14-17y of use) than shorter periods (29% with 2-5y of use and 75% with 6-9y of use). Conclusion: Thus patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency. Definite and possible Vitamin B12 deficiency on metformin had an earlier onset of neuropathy than the subgroup with normal Vitamin B12 levels.

Keywords: diabetic neuroptahy, cobalamine deficiency, metformin, nerve conduction studies

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Authors: Scott Ashby, Emily Granger, Mark Connellan

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Objectives: 1) To identify if emergency coronary angiography improves outcomes in studies examining OHCA from assumed cardiac aetiology? 2) If so, is it indicated in all patients resuscitated following OHCA, and if not, who is it indicated for? 3) How effective are investigations for screening for the appropriate patients? Background: Out-of-hospital cardiac arrest is one of the leading mechanisms of death, and the most common causative pathology is coronary artery disease. In-hospital treatment following resuscitation greatly affects outcomes, yet there is debate over the most effective protocol. Methods: A literature search was conducted over multiple databases to identify all relevant articles published from 2005. An inclusion criterion was applied to all publications retrieved, which were then sorted by type. Results: A total of 3 existing reviews and 29 clinical studies were analysed in this review. There were conflicting conclusions, however increased use of angiography has shown to improve outcomes in the majority of studies, which cover a variety of settings and cohorts. Recommendations: Currently, emergency coronary angiography appears to improve outcomes in all/most cases of OHCA of assumed cardiac aetiology, regardless of ECG findings. Until a better tool for screening is available to reduce unnecessary procedures, the benefits appear to outweigh the costs/risks.

Keywords: out of hospital cardiac arrest, coronary angiography, resuscitation, emergency medicine

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Authors: Naouelle Azzag, Nadia Haddad, Benoit Durand, Elisabeth Petit, Ali Ammouche, Bruno Chomel, Henri J. Boulouis

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Bartonella henselae is a small, gram negative, arthropod-borne bacterium that has been shown to cause multiple clinical manifestations in humans including cat scratch disease, bacillary angiomatosis, endocarditis, and bacteremia. In this research, we report the results of a cross sectional study of Bartonella henselae bacteremia in stray cats from Algiers. Whole blood of 227 stray cats from Algiers was tested for the presence of Bartonella species by culture and for the evaluation of the genetic diversity of B. henselae strains by multi-locus variable number of tandem repeats assay (MLVA). Bacteremia prevalence was 17% and only B. henselae was identified. Type I was the predominant type (64%). MLVA typing of 259 strains from 30 bacteremic cats revealed 52 different profiles. 51 of these profiles were specific to Algerian cats/identified for the first time. 20/30 cats (67%) harbored 2 to 7 MLVA profiles simultaneously. The similarity of MLVA profiles obtained from the same cat, neighbor-joining clustering and structure-neighbor clustering showed that such a diversity likely results from two different mechanisms occurring either independently or simultaneously independent infections and genetic drift from a primary strain.

Keywords: Bartonella, cat, MLVA, genetic

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Authors: Agnieszka E. Laudy, Karolina Stępien, Sergiusz Lulinski, Krzysztof Durka, Stefan Tyski

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1,3-dihydro-1-hydroxy-2,1-benzoxaborole and its derivatives are a particularly interesting group of synthetic agents and were successfully employed in supramolecular chemistry medicine. The first important compounds, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole and 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole were identified as potent antifungal agents. In contrast, (S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride is in the second phase of clinical trials as a drug for the treatment of Gram-negative bacterial infections of the Enterobacteriaceae family and Pseudomonas aeruginosa. Equally important and difficult task is to search for compounds active against Gram-negative bacilli, which have multi-drug-resistance efflux pumps actively removing many of the antibiotics from bacterial cells. We have examined whether halogen-substituted benzoxaborole-based derivatives and their analogues possess antibacterial activity and are substrates for multi-drug-resistance efflux pumps. The antibacterial activity of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole and 10 halogen-substituted its derivatives, as well as 1,2-phenylenediboronic acid and 3 synthesised fluoro-substituted its analogs, were evaluated. The activity against the reference strains of Gram-positive (n=5) and Gram-negative bacteria (n=10) was screened by the disc-diffusion test (0.4 mg of tested compounds was applied onto paper disc). The minimal inhibitory concentration values and the minimal bactericidal concentration values were estimated according to The Clinical and Laboratory Standards Institute and The European Committee on Antimicrobial Susceptibility Testing recommendations. During the minimal inhibitory concentration values determination with or without phenylalanine-arginine beta-naphthylamide (50 mg/L) efflux pump inhibitor, the concentrations of tested compounds ranged 0.39-400 mg/L in the broth medium supplemented with 1 mM magnesium sulfate. Generally, the studied benzosiloxaboroles and benzoxadiboroles showed a higher activity against Gram-positive cocci than against Gram-negative rods. Moreover, benzosiloxaboroles have the higher activity than benzoxadiboroles compounds. In this study, we demonstrated that substitution (mono-, di- or tetra-) of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole with halogen groups resulted in an increase in antimicrobial activity as compared to the parent substance. Interestingly, the 6,7-dichloro-substituted parent substance was found to be the most potent against Gram-positive cocci: Staphylococcus sp. (minimal inhibitory concentration 6.25 mg/L) and Enterococcus sp. (minimal inhibitory concentration 25 mg/L). On the other hand, mono- and dichloro-substituted compounds were the most actively removed by efflux pumps present in Gram-negative bacteria mainly from Enterobacteriaceae family. In the presence of efflux pump inhibitor the minimal inhibitory concentration values of chloro-substituted benzosiloxaboroles decreased from 400 mg/L to 3.12 mg/L. Of note, the highest increase in bacterial susceptibility to tested compounds in the presence of phenylalanine-arginine beta-naphthylamide was observed for 6-chloro-, 6,7-dichloro- and 6,7-difluoro-substituted benzosiloxaboroles. In the case of Escherichia coli, Enterobacter cloacae and P. aeruginosa strains at least a 32-fold decrease in the minimal inhibitory concentration values of these agents were observed. These data demonstrate structure-activity relationships of the tested derivatives and highlight the need for further search for benzoxaboroles and related compounds with significant antimicrobial properties. Moreover, the influence of phenylalanine-arginine beta-naphthylamide on the susceptibility of Gram-negative rods to studied benzosiloxaboroles indicate that some tested agents are substrates for efflux pumps in Gram-negative rods.

Keywords: antibacterial activity, benzosiloxaboroles, efflux pumps, phenylalanine-arginine beta-naphthylamide

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Authors: Aaron Derner

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Unlike the histories of France, the UK, or even Spain, the Russian colonial past often dissolves before the seemingly more salient Cold War figurations or Soviet dissolution. The obvious explanation behind Caucasian states’ roles—that of Russian-propped governments obeying the whims of their patron—is but the latest instance of such oversight. Where the results of colonial social and cultural interactions are indelibly stamped across France, Algeria, and every other former (and current) French holding, so to are the Muscovite and Russian colonial ambitions embedded within the modern politics and cultures of both Russia and the Caucasus. Russian colonial artefacts are enhanced and perhaps granted an additional social explanatory edge over those of the ‘typical’ colonizers, by the cyclical adoration for and noisy rejection of European cultural markers over the centuries, along with the somewhat unusual composition of the Cossacks: Russia’s main agents of colonialization within the Caucasian frontier. The story of Russia and Chechnya, of all the Caucasus, is of the manufacture of social and individual identity through “modes of subjectification” inherent within the region’s colonial history and driven by the triangular interactions between three main groups: the Cossacks, the Caucasian Mountain Tribes, and the Russian Metropol. Together, interactions between these social groups worked to shape and transform the lifestyles and institutional pathologies that constitute the Russian and Chechen states and the politics between them. At the core of this (Western) state-building is the simultaneous and seemingly contradictory desire to be more Western and emulate Western cultural and political practices while also desperately grasping for a uniquely Russian identity. This sits somewhat ironically against the backdrop that Russia hosted a frontier-based settler society and had established that distinctly European feature of settler colonialism early in its history—arguably establishing a claim to being the most “colonial” of the colonial powers. There is no doubt that these forces worked to shape contemporary Russian political and social identity—apparent in the mythic popularity of the Cossack in Russian literature, politics, and academic discourse. What needs to be expanded from the current narrative, however, is that beyond the Cossack identity’s attractiveness on the grounds of its tones of freedom and resistance to unjust authority, the identity is rooted in the imperial ambitions and colonial experiences of the Russian state, and is, therefore, a direct marker of domination and subjectification. Adding an unusual dimension to this not-uncommon cultural progression, the Russian state needed to colonize both the Caucases and the Russian Cossacks, appropriating them in much the same way they appropriated the Circassian mountain tribes. The focus of this paper is not to tell yet another story of how one culture entered an area to overpower another but how a ‘powerful,’ ‘modern,’ ‘Western(ish)’ culture was profoundly and continually changed through its contact with a group of tribal ‘savages’ and ‘braves.’

Keywords: Russia, chechnya, subjectification, caucasus, cossacks, Ukraine

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Authors: PB Venkataraman

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Most of the real-life problems are ill-structured. They do not have a single solution but many competing solutions. The solution paths are non-linear and ambiguous, and the problem definition itself is many times a challenge. Students of professional education learn to solve such problems through internships. The current pandemic situation has constrained on-site internship opportunities; thus the students have no option but to pursue this learning online. This research assessed the learning gain of four undergraduate students in engineering as they undertook an online internship in an organisation over a period of eight weeks. A clinical interview at the end of the internship provided the primary data to assess the team’s problem-solving skills using a tested rubric. In addition to this, change in their learning attitudes were assessed through a pre-post study using a repurposed CLASS instrument for Electrical Engineering. Analysis of CLASS data indicated a shift in the sophistication of their learning attitude. A learning engagement survey adopting a 6-point Likert scale showed active participation and motivation in learning. We hope this new research will stimulate educators to exploit online internships even beyond the time of pandemic as more and more business operations are transforming into virtual.

Keywords: ill-structured problems, learning attitudes, internship, assessment, student engagement

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Authors: Nikhat Iqbal Tamboli

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INTRODUCTION: road traffic accidents (RTAs) are one of the leading and common causes of ocular injuries especially in developing countries like India which are preventable with certain measures and so it is of public health importance. AIM: To study incidence and clinical presentation of ocular morbidity in road traffic accidents. METHOD: Prospective cross-sectional study was conducted on 360 patients reported in department of ophthalmology. Detailed ocular examination and relevant investigations done. RESULTS: Incidence of ocular injuries is 23%. male:female ratio is 4.5:1.Cases having Sub conjunctival haemorrhage [74].eccymosis[217]. lid lcerations [164]orbital fracture[12] corneal tear [7]corneal abrasion[2] sclera tear[6] hyphaema[4] traumatic mydriasis [7]traumatic cataract [2]vitreous haemorrhage [1]traumatic optic neuropathy[1].Maximum cases in age group 20-40 years, with two wheeler vehicles 94.7% .Under influence of alcohol 13.3%. CONCLUSION: Younger age group with male preponderance is involved in ocular trauma due to road traffic accidents .maximum cases reported are with anterior segment injuries. Alcohol and two wheeler vehicles are common risk factors. Injuries involving cornea had bad prognosis and involving retina had worst prognosis.

Keywords: ocular morbidity, eye trauma, RTA, eye injury

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Authors: Hiroyuki Aoki

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Molecular imaging has attracted much attention to visualize a tumor site in a living body on the basis of biological functions. A fluorescence in vivo imaging technique has been widely employed as a useful modality for small animals in pre-clinical researches. However, it is difficult to observe a site deep inside a body because of a short penetration depth of light. A photo-acoustic effect is a generation of a sound wave following light absorption. Because the sound wave is less susceptible to the absorption of tissues, an in vivo imaging method based on the photoacoustic effect can observe deep inside a living body. The current study developed an in vivo imaging agent for a photoacoustic imaging method. Nano-particles of poly(lactic acid) including indocyanine dye were developed as bio-compatible imaging agent with strong light absorption. A tumor site inside a mouse body was successfully observed in a photo-acoustic image. A photo-acoustic imaging with polymer nano-particle agent would be a powerful method to visualize a tumor.

Keywords: nano-particle, photo-acoustic effect, polymer, dye, in vivo imaging

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Authors: Boy Subirosa Sabarguna, Aria Kekalih, Irzan Nurman

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Introduction: Software in the form of Clinical Decision Support System could help students in understanding the mind set of decision-making in diagnosis and treatment at the stage of general practitioners. This could accelerate and ease the learning process which previously took place by using books and experience. Method: Gather 1000 members of the National Medical Multimedia Digital Community (NM2DC) who use the “flowchart of diagnosis and treatment” software, and analyse factors related to: display, speed in learning, convenience in learning, helpfulness and usefulness in the learning process, by using the Likert Scale through online questionnaire which will further be processed using percentage. Results and Discussions: Out of the 1000 members of NM2DC, apparently: 97.0% of the members use the software and 87.5% of them are students. In terms of the analysed factors related to: display, speed in learning, convenience in learning, helpfulness and usefulness of the software’s usage, the results indicate a 90.7% of fairly good performance. Therefore, the “Flowchart of Diagnosis and Treatment” software has helped students in understanding the decision-making of diagnosis and treatment. Conclusion: the use of “Flowchart of Diagnosis and Treatment” software indicates a positive role in helping students understand decision-making of diagnosis and treatment.

Keywords: usage, software, diagnosis and treatment, medical education

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Authors: Pankaj Prashar, Bimlesh Kumar, Ankita Sood, Anamika Gautam

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Pharmacovigilance (PV) is a rapidly growing discipline in pharmaceutical industries as an integral part of clinical research and drug development over the past few decades. PV carries a breadth of scope from drug manufacturing to its regulation with safer utilization. The fundamental steps of PV not only includes data collection and verification, coding of drugs with adverse drug reactions, causality assessment and timely reporting to the authorities but also monitoring drug manufacturing, safety issues, product quality and conduction of due diligence. Standardization of adverse event information, collaboration of multiple departments in different companies, preparation of documents in accordance to both governmental as well as non-governmental organizations (FDA, EMA, GVP, ICH) are the advancements in discipline of PV. De-harmonization, lack of predictive drug safety models, improper funding by government, non-reporting, and non-acceptability of ADRs by developing countries and reports directly from patients to the monitoring centres respectively are the major road backs of PV. Mandatory pharmacovigilance reporting, frequent inspections, funding by government, educating and training medical students, pharmacists and nurses in this segment can bring about empowerment in PV. This area needs to be addressed with a sense of urgency for the safe utilization of pharmaceuticals.

Keywords: pharmacovigilance, regulatory, adverse event, drug safety

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Authors: Mehdi Tavana, Seyedeh Zeinab Peighambarzadeh

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Pyelography is used for morphologic and especially functional studies of the urinary tracts. There are many indications for excretory Pyelography in humans and animals. Intravenous Pyelography is the most practical method; other Pyelography techniques were manipulated because of difficulties for finding veins in small size of the patients. At the best of times, the combination of small veins and abundant subcutaneous tissue makes vascular access difficult or impossible, therefore, another methods of administration of contrast media is desired. This study was performed to evaluate the feasibility of intraosseous injection of iodixanol in providing a safe and diagnostic urogram in Persian squirrel. Fourteen hundred mg iodine per kilogram body weight of iodixanol was injected subcutaneously over tibial tuberosity on ten clinically healthy adult Persian squirrels with no signs of urinary system disorder. Lateral and ventrodorsal radiographs were taken every 2 minutes until the pyelogram was finished. Intraosseous injection of iodixanol was successful to show nephrogram, pyelogram, uretrogram and cystogram clearly. There were no abnormal clinical signs after one week of experiments. Biochemical and hematological profiles were in normal ranges. It is concluded that intraosseous Pyelography is an effective and reliable method for Pyelography studies in squirrel. Microscopic examinations of the kidneys and the site of injection after one week were normal.

Keywords: pyelography, intraosseous injection, iodixanol, persian squirrel

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Authors: Feng Ju Chuang, Yu Wen Wang, Tai Jung Hsieh, Shyh Ming Kuo

Abstract:

Polylactic acid is a synthetic polymer with good biocompatibility and degradability, is widely used in clinical applications. In this study, we utilized Polylactic acid particles as stimulants for macrophages and the collagen synthesis of co-cultured fibroblasts was evaluated. The results indicated that Polylactic acid particles were nontoxic to cells from 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. No obvious inflammation effect was observed (under the PLLA concentration of 1 mg/mL) after 24-h co-culture of Raw264.7 and NIH3T3 cells (from TNF-α assay). The addition of PLLA particles to the Raw264.7 and NIH3T3 co-cultures increased the synthesis of collagen, the highest collagen synthesis from the fibroblast was the 0.2 mg/mL (approximately 60% increased as compared with without addition Polylactic acid particles). Moreover, a co-axial atomization delivery device was used to percutaneously introduce Polylactic acid particles into the dermis layer and stimulating macrophages to secrete growth factors promoting fibroblasts to produce collagen. The preliminary results demonstrated the synthesis of collagen was increased mildly after the introduction of Polylactic acid particles for 28-d post implantation. The Polylactic acid particles could be successfully introduced into the dermis layer from H&E staining examination, however, the optimum concentration of Polylactic acid particles and the time-period for collagen synthesis still need to be evaluated.

Keywords: collagen synthesis, macrophage, NIH3T3 cells, polylactic acid particles

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Authors: Sibghat Mansoor Rana, Muhammad Islam, Hamid Saeed, Hummera Rafique, Muhammad Majid, Muhammad Tahir Aqeel, Fariha Imtiaz, Zaman Ashraf

Abstract:

The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flur- biprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen –COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an –SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascer- tained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 μg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 μg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.

Keywords: synthetic chemistry, pharmaceutical chemistry, oxadiazole derivatives, anti-inflammatory, anti-cancer compounds

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