Search results for: renal cancer
Commenced in January 2007
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Edition: International
Paper Count: 2398

Search results for: renal cancer

628 Pre-Cancerigene Injuries Related to Human Papillomavirus: Importance of Cervicography as a Complementary Diagnosis Method

Authors: Denise De Fátima Fernandes Barbosa, Tyane Mayara Ferreira Oliveira, Diego Jorge Maia Lima, Paula Renata Amorim Lessa, Ana Karina Bezerra Pinheiro, Cintia Gondim Pereira Calou, Glauberto Da Silva Quirino, Hellen Lívia Oliveira Catunda, Tatiana Gomes Guedes, Nicolau Da Costa

Abstract:

The aim of this study is to evaluate the use of Digital Cervicography (DC) in the diagnosis of precancerous lesions related to Human Papillomavirus (HPV). Cross-sectional study with a quantitative approach, of evaluative type, held in a health unit linked to the Pro Dean of Extension of the Federal University of Ceará, in the period of July to August 2015 with a sample of 33 women. Data collecting was conducted through interviews with enforcement tool. Franco (2005) standardized the technique used for DC. Polymerase Chain Reaction (PCR) was performed to identify high-risk HPV genotypes. DC were evaluated and classified by 3 judges. The results of DC and PCR were classified as positive, negative or inconclusive. The data of the collecting instruments were compiled and analyzed by the software Statistical Package for Social Sciences (SPSS) with descriptive statistics and cross-references. Sociodemographic, sexual and reproductive variables were analyzed through absolute frequencies (N) and their respective percentage (%). Kappa coefficient (κ) was applied to determine the existence of agreement between the DC of reports among evaluators with PCR and also among the judges about the DC results. The Pearson's chi-square test was used for analysis of sociodemographic, sexual and reproductive variables with the PCR reports. It was considered statistically significant (p<0.05). Ethical aspects of research involving human beings were respected, according to 466/2012 Resolution. Regarding the socio-demographic profile, the most prevalent ages and equally were those belonging to the groups 21-30 and 41-50 years old (24.2%). The brown color was reported in excess (84.8%) and 96.9% out of them had completed primary and secondary school or studying. 51.5% were married, 72.7% Catholic, 54.5% employed and 48.5% with income between one and two minimum wages. As for the sexual and reproductive characteristics, prevailed heterosexual (93.9%) who did not use condoms during sexual intercourse (72.7%). 51.5% had a previous history of Sexually Transmitted Infection (STI), and HPV the most prevalent STI (76.5%). 57.6% did not use contraception, 78.8% underwent examination Cancer Prevention Uterus (PCCU) with shorter time interval or equal to one year, 72.7% had no cases of Cervical Cancer in the family, 63.6% were multiparous and 97% were not vaccinated against HPV. DC identified good level of agreement between raters (κ=0.542), had a specificity of 77.8% and sensitivity of 25% when compared their results with PCR. Only the variable race showed a statistically significant association with CRP (p=0.042). DC had 100% acceptance amongst women in the sample, revealing the possibility of other experiments in using this method so that it proves as a viable technique. The DC positivity criteria were developed by nurses and these professionals also perform PCCU in Brazil, which means that DC can be an important complementary diagnostic method for the appreciation of these professional’s quality of examinations.

Keywords: gynecological examination, human papillomavirus, nursing, papillomavirus infections, uterine lasmsneop

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627 KCBA, A Method for Feature Extraction of Colonoscopy Images

Authors: Vahid Bayrami Rad

Abstract:

In recent years, the use of artificial intelligence techniques, tools, and methods in processing medical images and health-related applications has been highlighted and a lot of research has been done in this regard. For example, colonoscopy and diagnosis of colon lesions are some cases in which the process of diagnosis of lesions can be improved by using image processing and artificial intelligence algorithms, which help doctors a lot. Due to the lack of accurate measurements and the variety of injuries in colonoscopy images, the process of diagnosing the type of lesions is a little difficult even for expert doctors. Therefore, by using different software and image processing, doctors can be helped to increase the accuracy of their observations and ultimately improve their diagnosis. Also, by using automatic methods, the process of diagnosing the type of disease can be improved. Therefore, in this paper, a deep learning framework called KCBA is proposed to classify colonoscopy lesions which are composed of several methods such as K-means clustering, a bag of features and deep auto-encoder. Finally, according to the experimental results, the proposed method's performance in classifying colonoscopy images is depicted considering the accuracy criterion.

Keywords: colorectal cancer, colonoscopy, region of interest, narrow band imaging, texture analysis, bag of feature

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626 Attitudes of Nurses towards End-of-Life Care for Themselves

Authors: H. N. S. Silva, S. N. Silva

Abstract:

Introduction: 88.3% of physicians decided to choose a ‘no-code’ or a DNR order if hospitalized and would choose to die less aggressively at home. However, their wishes were mostly over ridden. Objective: To assess the attitudes of nurses towards the end-of-the-life care they would like to receive for themselves and their attitudes towards terminal illnesses. Methods: A mixed method approach was used. A closed and open-ended questionnaire was administered to 73 participants and 5 registered nurses, who have more than 10 years of experience, working in hospitals both in Sri Lanka and abroad, were interviewed. Results: 94.1% of the participants stated that they would like to die at home, spending their last hours at home surrounded by their loved ones and engaging in religious activities but 57.7% of unmarried nurse said they would agree on euthanasia if they had a terminal disease, and also 66.2% of them stated they would agree in DNR order if they happen to be admitted to the ICU, but 82.5% wanted to diagnose if they had a terminal illness or cancer but did not agree on euthanasia. Qualitative analysis confirmed the findings and revealed that despite having adequate confidence about the hospital care, nurses would choose to die at home, surrounded by their loved once and engaging in religious activities. Euthanasia was believed to be inappropriate as it is religiously incorrect and as death is a natural process. Conclusion: The perception of death among nurses depends on their religious belief.

Keywords: death, do not resuscitate, euthanasia, nurses

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625 Biological Activity of Hibiscus sabdariffa Extract

Authors: Chanasit Chaocharoenphat

Abstract:

Hibiscus sabdariffa is a herbal plant that is commonly used for home remedies in Thailand. This study aims to determine the antioxidant activity of polyphenols, as oxidative stress plays a vital role in the development of cancer, and H. sabdariffa was used in this study. The total flavonoids content was determined using the aluminium chloride colourimetric method and expressed as quercetin equivalents (QE)/g and the antioxidant capacity of the flavonoids using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging capacity assays. The IC50 values of H. sabdariffa extract were 167.14 μg/mL ± 0.843 and 77.59 μg/mL ± 0.798, respectively. In the DPPH assay, vitamin C was used as a positive control, whereas Trolox was used as a positive control in the ABTS assay. To summarise, H. sabdariffa extract contains a high concentration of total flavonoids and exhibits potent antioxidant activity. However, additional antioxidant activity assays such as superoxide dismutase (SOD), reactive oxygen species (ROS), and reactive nitrogen species (RNS) scavenging assays and in vitro antioxidant experiments should be carried out to investigate the molecular mechanism of the compound.

Keywords: ABTS assay, antioxidant activity, Gracilaria fisheri, DPPH assays, total flavonoid content

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624 Peg@GDF3:TB3+ – Rb Nanocomposites for Deep-Seated X-Ray Induced Photodynamic Therapy in Oncology

Authors: E.A. Kuchma

Abstract:

Photodynamic therapy (PDT) is considered an alternative and minimally invasive cancer treatment modality compared to chemotherapy and radiation therapy. PDT includes three main components: a photosensitizer (PS), oxygen, and a light source. PS is injected into the patient's body and then selectively accumulates in the tumor. However, the light used in PDT (spectral range 400–700 nm) is limited to superficial lesions, and the light penetration depth does not exceed a few cm. The problem of PDT (poor visible light transmission) can be solved by using X-rays. The penetration depth of X-rays is ten times greater than that of visible light. Therefore, X-ray radiation easily penetrates through the tissues of the body. The aim of this work is to develop universal nanocomposites for X-ray photodynamic therapy of deep and superficial tumors using scintillation nanoparticles of gadolinium fluoride (GdF3), doped with Tb3+, coated with a biocompatible coating (PEG) and photosensitizer RB (Rose Bengal). PEG@GdF3:Tb3+(15%) – RB could be used as an effective X-ray, UV, and photoluminescent mediator to excite a photosensitizer for generating reactive oxygen species (ROS) to kill tumor cells via photodynamic therapy. GdF3 nanoparticles can also be used as contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI).

Keywords: X-ray induced photodynamic therapy, scintillating nanoparticle, radiosensitizer, photosensitizer

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623 New Bioactive Compounds from Two Chrysanthemum Saharian Species (Asteraceae) Growing in Algeria

Authors: Zahia Kabouche, Ouissem Gherboudj, Naima Boutaghane, Ahmed Kabouche, Laurence Voutquenne-Nazabadioko

Abstract:

Chrysanthemum herbs (Asteraceae) are extensively used as food additives and in folk medicine. Anti-cancer, anti-human immunodeficiency virus type 1 (HIV-1), anti-inflammatory, antinociceptive and antiproliferative activities as well as antioxidant effects have been reported for Chrysanthemum species. We report the isolation and identification of flavonoids and new and known terpenoids from the endemic species, C. macrocarpum and C. deserticolum “guertoufa”, used in Algerian Sahara as tea drinks and in “couscous” and soups “Chorba”. Structures of the isolated compounds were established by 1-D and 2-D homo and hetero-nuclear NMR (1H, 13C, COSY, HSQC, HMBC, and NOESY), mass spectrometry, UV and comparison with literature data. C. deserticolum extracts were tested by four methods to identify the antioxidant activity namely, ABTS•+, DPPH• scavenging, CUPRAC and ferrous-ions chelating activity methods. Anti-inflammatory, antinociceptive, antiproliferative and antioxidant activities of C. macrocarpum extracts and isolated compounds are also reported here.

Keywords: Chrysanthemum macrocarpum, C. deserticolum, flavonoids, terpenoids, antioxidant, anti-inflammatory, anti-proliferative

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622 Integrating Non-Psychoactive Phytocannabinoids and Their Cyclodextrin Inclusion Complexes into the Treatment of Glioblastoma

Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

Abstract:

Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

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621 Clonal Evaluation of Malignant Mesothelioma

Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

Abstract:

Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

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620 Content-Based Mammograms Retrieval Based on Breast Density Criteria Using Bidimensional Empirical Mode Decomposition

Authors: Sourour Khouaja, Hejer Jlassi, Nadia Feddaoui, Kamel Hamrouni

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Most medical images, and especially mammographies, are now stored in large databases. Retrieving a desired image is considered of great importance in order to find previous similar cases diagnosis. Our method is implemented to assist radiologists in retrieving mammographic images containing breast with similar density aspect as seen on the mammogram. This is becoming a challenge seeing the importance of density criteria in cancer provision and its effect on segmentation issues. We used the BEMD (Bidimensional Empirical Mode Decomposition) to characterize the content of images and Euclidean distance measure similarity between images. Through the experiments on the MIAS mammography image database, we confirm that the results are promising. The performance was evaluated using precision and recall curves comparing query and retrieved images. Computing recall-precision proved the effectiveness of applying the CBIR in the large mammographic image databases. We found a precision of 91.2% for mammography with a recall of 86.8%.

Keywords: BEMD, breast density, contend-based, image retrieval, mammography

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619 Impact of Variability in Delineation on PET Radiomics Features in Lung Tumors

Authors: Mahsa Falahatpour

Abstract:

Introduction: This study aims to explore how inter-observer variability in manual tumor segmentation impacts the reliability of radiomic features in non–small cell lung cancer (NSCLC). Methods: The study included twenty-three NSCLC tumors. Each patient had three tumor segmentations (VOL1, VOL2, VOL3) contoured on PET/CT scans by three radiation oncologists. Dice coefficients (DCS) were used to measure the segmentation variability. Radiomic features were extracted with 3D-slicer software, consisting of 66 features: first-order (n=15), second-order (GLCM, GLDM, GLRLM, and GLSZM) (n=33). The inter-observer variability of radiomic features was assessed using the intraclass correlation coefficient (ICC). An ICC > 0.8 indicates good stability. Results: The mean DSC of VOL1, VOL2, and VOL3 was 0.80 ± 0.04, 0.85 ± 0.03, and 0.76 ± 0.06, respectively. 92% of all extracted radiomic features were found to be stable (ICC > 0.8). The GLCM texture features had the highest stability (96%), followed by GLRLM features (90%) and GLSZM features (87%). The DSC was found to be highly correlated with the stability of radiomic features. Conclusion: The variability in inter-observer segmentation significantly impacts radiomics analysis, leading to a reduction in the number of appropriate radiomic features.

Keywords: PET/CT, radiomics, radiotherapy, segmentation, NSCLC

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618 Towards Value-Based Healthcare through a Nursing Sector Management Approach

Authors: Hadeer Hegazy, Wael Ewieda, Ranin Soliman, Samah Elway, Asmaa Tawfik, Ragaa Sayed, Sahar Mousa

Abstract:

The current healthcare system is facing major challenges in terms of cost, quality of care, and access to services. In response, the concept of value-based healthcare has emerged as a new approach to healthcare delivery. This concept puts the focus on patient values rather than on the traditional medical model of care. To achieve this, healthcare organizations must be agile and able to anticipate and respond quickly to changing needs. Agile management is essential for healthcare organizations to achieve value-based care, as it allows them to rapidly adjust their strategies to changing circumstances. Additionally, it is argued that agile management can help healthcare organizations gain a better understanding of the needs of their patients and develop better care delivery models. Besides, it can help healthcare organizations develop new services, innovate, and become more efficient. The authors provide evidence to support their argument, drawing on examples from successful value-based healthcare initiatives at children’s cancer hospital Egypt-57357. The paper offers insight into how agile management can be used to facilitate the shift towards value-based healthcare and how it can be used to maximize value in the healthcare system.

Keywords: value-based healthcare, agility in healthcare, nursing department, patients outcomes

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617 Establishment and Evaluation of a Nutrition Therapy Guide and 7-Day Menu for Educating Hemodialysis Patients: A Case Study of Douala General Hospital, Cameroon

Authors: Ngwa Lodence Njwe

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This study investigated the response of hemodialysis patients to an established nutrition therapy guide accompanied by a 7-day menu plan administered for a month. End Stage Renal Disease (ESRD), also known as End Stage Kidney Disease (ESKD), is a non-communicable disease primarily caused by hypertension and diabetes, posing significant challenges in both developed and developing nations. Hemodialysis is a key treatment for these patients. In this experimental study, 100 hemodialysis patients from Douala General Hospital in Cameroon participated. A questionnaire was used to collect data on sociodemographic and anthropometric characteristics, health status, and dietary intake, while medical records provided biomedical data. The levels of the biochemical parameters (Phosphorus, calcium and hemoglobin) were determined before and one month after the distribution of the nutrition education guide and the use of a 7-day menu plan. The Phosphorus and Calcium levels were measured using an LTCC03 semi-automatic chemistry analyzer. Blood was collected from each patient into a test tube, allowed to clot and centrifuged. 50µl of the serum was aspirated by the analyzer for Ca and P level analysis, and results were read from the display. The hemoglobin level was measured using the URIT–12 hemoglobin Meter. The blood sample was collected by hand prick and placed in a strip, and the results were read from the screen. The means of the biochemical parameters were then computed. The most prevalent age group was 40-49 years, with males constituting 70% and females 30% of respondents. Among these patients, 80% were hypertensive, 3% had both hypertension and diabetes, 9% were hypertensive, diabetic, and obese, and 1% suffered from hypertension and heart failure. Analysis of anthropometric parameters revealed a high prevalence of underweight, overweight, and obesity, highlighting the urgent need for targeted nutrition interventions to modify cooking methods, enhance food choices, and increase dietary variety for improved quality of life. Before the nutrition therapy guide was implemented, average calcium levels were 73.05 mg/L for males and 89.44 mg/L for females; post-implementation, these values increased to 77.55 mg/L and 91.44 mg/L, respectively. Conversely, average phosphorus levels decreased from 42.05 mg/L for males and 43.55 mg/L for females to 41.05 mg/L and 39.3 mg/L, respectively, after the intervention. Additionally, average hemoglobin levels increased from 8.35 g/dL for males and 8.5 g/dL for females to 9.2 g/dL and 8.95 g/dL, respectively. The findings confirm that the nutrition therapy guide and the 7-day menu significantly impacted the biomedical parameters of hemodialysis patients, underscoring the need for ongoing nutrition education and counseling for this population.

Keywords: end stage kidney disease, nutrition therapy guide, nutritional status, anthropometric parameters, food frequency, biomedical data

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616 Rauvolfine B Isolated from the Bark of Rauvolfia reflexa (Apocynaceae) Induces Apoptosis through Activation of Caspase-9 Coupled with S Phase Cell Cycle Arrest

Authors: Mehran Fadaeinasab, Hamed Karimian, Najihah Mohd Hashim, Hapipah Mohd Ali

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In this study, three indole alkaloids namely; rauvolfine B, macusine B, and isoreserpiline have been isolated from the dichloromethane crude extract of Rauvolfia reflexa bark (Apocynaceae). The structural elucidation of the isolated compounds has been performed using spectral methods such as UV, IR, MS, 1D, and 2D NMR. Rauvolfine B showed anti proliferation activity on HCT-116 cancer cell line, its cytotoxicity induction was observed using MTT assay in eight different cell lines. Annexin-V is serving as a marker for apoptotic cells and the Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS). Apoptosis was confirmed by using caspase-8 and -9 assays. Cell cycle arrest was also investigated using flowcytometric analysis. rauvolfine B had exhibited significantly higher cytotoxicity against HCT-116 cell line. The treatment significantly arrested HCT-116 cells in the S phase. Together, the results presented in this study demonstrated that rauvolfine B inhibited the proliferation of HCT-116 cells and programmed cell death followed by cell cycle arrest.

Keywords: apocynacea, indole alkaloid, apoptosis, cell cycle arrest

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615 Electroactive Ferrocenyl Dendrimers as Transducers for Fabrication of Label-Free Electrochemical Immunosensor

Authors: Sudeshna Chandra, Christian Gäbler, Christian Schliebe, Heinrich Lang

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Highly branched dendrimers provide structural homogeneity, controlled composition, comparable size to biomolecules, internal porosity and multiple functional groups for conjugating reactions. Electro-active dendrimers containing multiple redox units have generated great interest in their use as electrode modifiers for development of biosensors. The electron transfer between the redox-active dendrimers and the biomolecules play a key role in developing a biosensor. Ferrocenes have multiple and electrochemically equivalent redox units that can act as electron “pool” in a system. The ferrocenyl-terminated polyamidoamine dendrimer is capable of transferring multiple numbers of electrons under the same applied potential. Therefore, they can be used for dual purposes: one in building a film over the electrode for immunosensors and the other for immobilizing biomolecules for sensing. Electrochemical immunosensor, thus developed, exhibit fast and sensitive analysis, inexpensive and involve no prior sample pre-treatment. Electrochemical amperometric immunosensors are even more promising because they can achieve a very low detection limit with high sensitivity. Detection of the cancer biomarkers at an early stage can provide crucial information for foundational research of life science, clinical diagnosis and prevention of disease. Elevated concentration of biomarkers in body fluid is an early indication of some type of cancerous disease and among all the biomarkers, IgG is the most common and extensively used clinical cancer biomarkers. We present an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as glassy carbon electrode material for immobilizing the antibody. The electrochemical performance of the modified electrodes was assessed in both aqueous and non-aqueous media using varying scan rates to elucidate the reaction mechanism. The potential shift was found to be higher in an aqueous electrolyte due to presence of more H-bond which reduced the electrostatic attraction within the amido groups of the dendrimers. The cyclic voltammetric studies of the G2Fc-modified GCE in 0.1 M PBS solution of pH 7.2 showed a pair of well-defined redox peaks. The peak current decreased significantly with the immobilization of the anti-goat IgG. After the immunosensor is blocked with BSA, a further decrease in the peak current was observed due to the attachment of the protein BSA to the immunosensor. A significant decrease in the current signal of the BSA/anti-IgG/G2Fc/GCE was observed upon immobilizing IgG which may be due to the formation of immune-conjugates that blocks the tunneling of mass and electron transfer. The current signal was found to be directly related to the amount of IgG captured on the electrode surface. With increase in the concentration of IgG, there is a formation of an increasing amount of immune-conjugates that decreased the peak current. The incubation time and concentration of the antibody was optimized for better analytical performance of the immunosensor. The developed amperometric immunosensor is sensitive to IgG concentration as low as 2 ng/mL. Tailoring of redox-active dendrimers provides enhanced electroactivity to the system and enlarges the sensor surface for binding the antibodies. It may be assumed that both electron transfer and diffusion contribute to the signal transformation between the dendrimers and the antibody.

Keywords: ferrocenyl dendrimers, electrochemical immunosensors, immunoglobulin, amperometry

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614 Prevention of Biocompounds and Amino Acid Losses in Vernonia amygdalina duringPost Harvest Treatment Using Hot Oil-Aqueous Mixture

Authors: Nneka Nkechi Uchegbu, Temitope Omolayo Fasuan

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This study investigated how to reduce bio-compounds and amino acids in V. amygdalina leaf during processing as a functional food ingredient. Fresh V. amygdalina leaf was processed using thermal oil-aqueous mixtures (soybean oil: aqueous and palm oil: aqueous) at 1:40 and 130 (v/v), respectively. Results indicated that the hot soybean oil-aqueous mixture was the most effective in preserving the bio-compounds and amino acids with retention potentials of 80.95% of the bio-compounds at the rate of 90-100%. Hot palm oil-aqueous mixture retained 61.90% of the bio-compounds at the rate of 90-100% and hot aqueous retained 9.52% of the bio-compounds at the same rate. During the debittering process, seven new bio-compounds were formed in the leaves treated with hot soybean oil-aqueous mixture, six in palm oil-aqueous mixture, and only four in hot aqueous leaves. The bio-compounds in the treated leaves have potential functions as antitumor, antioxidants, antihistaminic, anti-ovarian cancer, anti-inflammatory, antiarthritic, hepatoprotective, antihistaminic, haemolytic 5-α reductase inhibitor, nt, immune-stimulant, diuretic, antiandrogenic, and anaemiagenic. Alkaloids and polyphenols were retained at the rate of 81.34-98.50% using oil: aqueous mixture while aqueous recorded the rate of 33.47-41.46%. Most of the essential amino acids were retained at a rate above 90% through the aid of oil. The process is scalable and could be employed for domestic and industrial applications.

Keywords: V. amygdalina leaf, bio-compounds, oil-aqueous mixture, amino acids

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613 Optimization of Monascus Orange Pigments Production Using pH-Controlled Fed-Batch Fermentation

Authors: Young Min Kim, Deokyeong Choe, Chul Soo Shin

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Monascus pigments, commonly used as a natural colorant in Asia, have many biological activities, such as cholesterol level control, anti-obesity, anti-cancer, and anti-oxidant, that have recently been elucidated. Especially, amino acid derivatives of Monascus pigments are receiving much attention because they have higher biological activities than original Monascus pigments. Previously, there have been two ways to produce amino acid derivatives: one-step production and two-step production. However, the one-step production has low purity, and the two-step production—precursor(orange pigments) fermentation and derivatives synthesis—has low productivity and growth rate during its precursor fermentation step. In this study, it was verified that pH is a key factor that affects the stability of orange pigments and the growth rate of Monascus. With an optimal pH profile obtained by pH-stat fermentation, we designed a process of precursor(orange pigments) fermentation that is a pH-controlled fed-batch fermentation. The final concentration of orange pigments in this process increased to 5.5g/L which is about 30% higher than the concentration produced from the previously used precursor fermentation step.

Keywords: cultivation process, fed-batch fermentation, monascus pigments, pH stability

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612 Study of Non-hodgkin’s Lymphoma

Authors: Zidani Abla

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Lymphoma is a common type of cancer that affects the lymphatic system, including the lymph nodes, spleen and other associated organs. There are two main types of lymphoma: Hodgkin's lymphoma and non-Hodgkin's lymphoma. The epidemiological, clinical and biological features of lymphoma are poorly studied in Algeria. The main objective of our study is to investigate the epidemiological, clinical, paraclinical, etiological, evolutionary and biological characteristics of non-Hodgkin's lymphoma (NHL) in the hematology department of the University Hospital Center (HUC) of Batna. This is a study of 10 patients diagnosed at Batna University Hospital. 70% were male and 30% female (sex ratio M/F= 2.33). Median age was 51.7 years. Pain, especially abdominal pain, was the main reason for consultation. Stage IV predominated (40%), followed by stage III (20%). Abdominal adenopathies (34%) were the most abundant. Secondary hepatic localization was predominant. Large B-cell NHL predominated, accounting for 60% of cases, followed by small B-cell NHL (30%). Serology for hepatitis B and C, and human immunodeficiency virus (HIV) was negative. Biologically, a predominance of hyperleukocytosis, polynuclear neutrophilic leukocytosis, lymphopenia and hypoalbuminemia were present in the majority of cases. In summary, our results remain to be compared with other works for other periods and other regions in order to generalize lymphoma percentages for the entire Algerian population.

Keywords: non Hodgkin's lymphoma, epidemiology, clinic, biology

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611 Some Trace and Toxic Metal Content of Crude Ethanol Leaf Extract of Globimetula Oreophila (Hook. F) Danser Azadirachta Indica Using Atomic Absorption Spectroscopy

Authors: Dauda G., Bila Ha Sani Y. M., Magaji M. G., Musa A. M., Hassan H. S.

Abstract:

Introduction: Globimetula oreophila is a parasitic plant with a known therapeutic value that is widely used in the treatment of various ailments, including malaria, hypertension, cancer, diabetes, epilepsy and as a diuretic agent. Objectives: The present study is aimed at analyzing and documenting the level of trace and toxic metals in the crude ethanol leaf extract of G. oreophila. Methods: After collection and authentication, the leaves were air-dried, mashed into powder, weighed and extracted using aqueous ethanol (70%). The crude extract (0.5g) was digested with HNO₃: HCl (3:1); then heated to 2000C and analyzed for its metal content by atomic absorption spectroscopy (AAS). Results: Fe had the highest concentration (32.73mg/kg), while Pb was not detected. The concentrations of Co, Cu, Ni, Zn and Cd detected were 5.97, 10.8, 8.01 and 0.9mg/kg, respectively. The concentration of Cd, Fe and Ni were above the permissible limit of FAO/WHO. Conclusion: The results also show that the analyzed plant is a beneficial source of appropriate and essential trace metals. However, the leaf of G. oreophila in the present study was probably unsafe for long-term use because of the level of Fe, Ni, and Cd concentration.

Keywords: Globimetula oreophila, minerals, trace element, crude extract

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610 Inpatient Glycemic Management Strategies and Their Association with Clinical Outcomes in Hospitalized SARS-CoV-2 Patients

Authors: Thao Nguyen, Maximiliano Hyon, Sany Rajagukguk, Anna Melkonyan

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Introduction: Type 2 Diabetes is a well-established risk factor for severe SARS-CoV-2 infection. Uncontrolled hyperglycemia in patients with established or newly diagnosed diabetes is associated with poor outcomes, including increased mortality and hospital length of stay. Objectives: Our study aims to compare three different glycemic management strategies and their association with clinical outcomes in patients hospitalized for moderate to severe SARS-CoV-2 infection. Identifying optimal glycemic management strategies will improve the quality of patient care and improve their outcomes. Method: This is a retrospective observational study on patients hospitalized at Adventist Health White Memorial with severe SARS-CoV-2 infection from 11/1/2020 to 02/28/2021. The following inclusion criteria were used: positive SARS-CoV-2 PCR test, age >18 yrs old, diabetes or random glucose >200 mg/dL on admission, oxygen requirement >4L/min, and treatment with glucocorticoids. Our exclusion criteria included: ICU admission within 24 hours, discharge within five days, death within five days, and pregnancy. The patients were divided into three glycemic management groups: Group 1, managed solely by the Primary Team, Group 2, by Pharmacy; and Group 3, by Endocrinologist. Primary outcomes were average glucose on Day 5, change in glucose between Days 3 and 5, and average insulin dose on Day 5 among groups. Secondary outcomes would be upgraded to ICU, inpatient mortality, and hospital length of stay. For statistics, we used IBM® SPSS, version 28, 2022. Results: Most studied patients were Hispanic, older than 60, and obese (BMI >30). It was the first CV-19 surge with the Delta variant in an unvaccinated population. Mortality was markedly high (> 40%) with longer LOS (> 13 days) and a high ICU transfer rate (18%). Most patients had markedly elevated inflammatory markers (CRP, Ferritin, and D-Dimer). These, in combination with glucocorticoids, resulted in severe hyperglycemia that was difficult to control. Average glucose on Day 5 was not significantly different between groups primary vs. pharmacy vs. endocrine (220.5 ± 63.4 vs. 240.9 ± 71.1 vs. 208.6 ± 61.7 ; P = 0.105). Change in glucose from days 3 to 5 was not significantly different between groups but trended towards favoring the endocrinologist group (-26.6±73.6 vs. 3.8±69.5 vs. -32.2±84.1; P= 0.052). TDD insulin was not significantly different between groups but trended towards higher TDD for the endocrinologist group (34.6 ± 26.1 vs. 35.2 ± 26.4 vs. 50.5 ± 50.9; P=0.054). The endocrinologist group used significantly more preprandial insulin compared to other groups (91.7% vs. 39.1% vs. 65.9% ; P < 0.001). The pharmacy used more basal insulin than other groups (95.1% vs. 79.5% vs. 79.2; P = 0.047). There were no differences among groups in the clinical outcomes: LOS, ICU upgrade, or mortality. Multivariate regression analysis controlled for age, sex, BMI, HbA1c level, renal function, liver function, CRP, d-dimer, and ferritin showed no difference in outcomes among groups. Conclusion: Given high-risk factors in our population, despite efforts from the glycemic management teams, it’s unsurprising no differences in clinical outcomes in mortality and length of stay.

Keywords: glycemic management, strategies, hospitalized, SARS-CoV-2, outcomes

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609 Providing Emotional Support to Children under Long-Term Health Treatments

Authors: Ramón Cruzat, Sergio F. Ochoa, Ignacio Casas, Luis A. Guerrero, José Bravo

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Patients under health treatments that involve long stays at a hospital or health centre (e.g. cancer, organ transplants and severe burns), tend to get bored or depressed because of the lack of social interaction with family and friends. Such a situation also affects the evolution and effectiveness of their treatments. In many cases, the solution to this problem involves extra challenges, since many patients need to rest quietly (or remain in bed) to their being contagious. Considering the weak health condition in which usually are these kinds, keeping them motivated and quiet represents an important challenge for nurses and caregivers. This article presents a mobile ubiquitous game called MagicRace, which allows hospitalized kinds to interact socially with one another without putting to risk their sensitive health conditions. The game does not require a communication infrastructure at the hospital, but instead, it uses a mobile ad hoc network composed of the handheld devices used by the kids to play. The usability and performance of this application was tested in two different sessions. The preliminary results show that users experienced positive feelings from this experience.

Keywords: ubiquitous game, children's emotional support, social isolation, mobile collaborative interactions

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608 Management of Gastrointestinal Metastasis of Invasive Lobular Carcinoma

Authors: Sally Shepherd, Richard De Boer, Craig Murphy

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Background: Invasive lobular carcinoma (ILC) can metastasize to atypical sites within the peritoneal cavity, gastrointestinal, or genitourinary tract. Management varies depending on the symptom presentation, extent of disease burden, particularly if the primary disease is occult, and patient wishes. Case Series: 6 patients presented with general surgical presentations of ILC, including incomplete large bowel obstruction, cholecystitis, persistent lower abdominal pain, and faecal incontinence. 3 were diagnosed with their primary and metastatic disease in the same presentation, whilst 3 patients developed metastasis from 5 to 8 years post primary diagnosis of ILC. Management included resection of the metastasis (laparoscopic cholecystectomy), excision of the primary (mastectomy and axillary clearance), followed by a combination of aromatase inhibitors, biologic therapy, and chemotherapy. Survival post diagnosis of metastasis ranged from 3 weeks to 7 years. Conclusion: Metastatic ILC must be considered with any gastrointestinal or genitourinary symptoms in patients with a current or past history of ILC. Management may not be straightforward to chemotherapy if the acute pathology is resulting in a surgically resectable disease.

Keywords: breast cancer, gastrointestinal metastasis, invasive lobular carcinoma, metastasis

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607 Development and in vitro Evaluation of Polymer-Drug Conjugates Containing Potentiating Agents for Combination Therapy

Authors: Blessing A. Aderibigbe

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Combination therapy is a treatment approach that is used to prevent the emergence of drug resistance. This approach is used for the treatment of many chronic and infectious diseases. Potentiating agents are currently explored in combination therapy, resulting in excellent therapeutic outcomes. Breast cancer and malaria are two chronic conditions responsible globally for high death rates. In this research, a class of polymer-drug conjugates containing potentiating agents with either antimalarial or anticancer drugs were prepared by Michael Addition Polymerization reaction and ring-opening polymerization reaction. Conjugation of potentiating agents with bioactive compounds into the polymers resulted in conjugates with good water solubility, highly selective and non-toxic. In vitro cytotoxicity and in vitro antiplasmodial evaluation on the conjugates revealed that the conjugates were more effective when compared to the free drugs. The drug release studies further showed that the release profile of the drugs from the conjugates was sustained. The findings revealed the potential of polymer-drug conjugates to overcome drug toxicity and drug resistance, which is common with the currently used antimalarial and anticancer drugs.

Keywords: anticancer, antimalarials, combination therapy, polymer-drug conjugates

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606 Thyroid-Stimulating Hormone as a Stress Biomarker in Thyroidectomy Patients: A Cohort Study

Authors: Jeonghun Lee

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In this study, we investigated the relationship between stress and thyroid dysfunction in such patients who underwent thyroidectomy. This study included 101 patients who underwent thyroidectomy from January 2015 to June 2020 and experienced hypothyroidism. The included patients had good drug compliance with the same dosage of levothyroxine (LT4). The male-to-female ratio was 1:4.6, and the mean age was 45.4 years at surgery and 50.2 years at stressful events. Eighteen patients underwent lobectomies and, of these, 12 did not take LT4. The mean follow-up period was 49(8-93) months. Statistical analyses were performed using the paired t-test, Wilcoxon signed-rank test, and McNemer test using PROC MIXED with SAS 9.4. Forty-five patients (44.6%) had hypothyroidism with thyroid-stimulating hormone (TSH) >10 μIU/mL. There was distress in 81 patients and eustress in 10 patients. TSH levels increased during a mean 5.8 months (min 1, max 12) in 24 patients who specified the date of their life events. Even though each patient took the same dose of LT4, when the patients were under stress, both the free T4 and T3 decreased and TSH increased, regardless of whether the patient experienced distress or eustress (P <0.001). While adjusting for the effect of the free T4 and T3, TSH increased significantly in the patients after stress (P <0.001). For patients with thyroid cancer who are simultaneously experiencing life events, TSH may be used as a stress biomarker to enable the implementation of appropriate treatment and counseling strategies.

Keywords: endocrine, thyroid, thyroid function, biomarker, stress

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605 Walnut (Juglans Regia) Extracts: Investigation of Antioxidant Effect, Total Phenols and Tyrosinase Inhibitory Activity

Authors: N. Saki, S. Nalbantoglu, M. Akin, G. Arabaci

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Walnut has a great range of phenolic profile and it is used in Asia and Africa for treatment of many diseases and cancer. Phenolic compounds play a number of crucial roles in complex metabolism of plants and of also fruit trees. Consumption of certain phenolics in the food is considered beneficial for human nutrition. Phenolic compounds known as anti-radical inactivators with their high antioxidant activities and these activities play an important role in inhibition of multi-metal corrosion. Many common corrosion inhibitors that are still in use today are health hazards. Therefore, there is still an increased attention directed towards the development of environmentally compatible, nonpolluting corrosion inhibitors. The present study reports the total phenols content, antioxidant potentials and tyrosinase inhibitory activity of the walnut (Juglans regia L.) produced in Turkey. The anti-tyrosinase activity was investigated for walnut at 2 h extraction time and all extracts exhibited tyrosinase activity. The results of this study suggested that walnut can be used as an excellent, easily accessible source of natural antioxidant.

Keywords: antioxidant activity, Juglans Regia, total phenols, tyrosinase activity

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604 Title: Real World Evidence a Tool to Overcome the Lack of a Comparative Arm in Drug Evaluation in the Context of Rare Diseases

Authors: Mohamed Wahba

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Objective: To build a comparative arm for product (X) in specific gene mutated advanced gastrointestinal cancer using real world evidence to fulfill HTA requirements in drug evaluation. Methods: Data for product (X) were collected from phase II clinical trial while real world data for (Y) and (Z) were collected from US database. Real-world (RW) cohorts were matched to clinical trial base line characteristics using weighting by odds method. Outcomes included progression-free survival (PFS) and overall survival (OS) rates. Study location and participants: Internationally (product X, n=80) and from USA (Product Y and Z, n=73) Results: Two comparisons were made: trial cohort 1 (X) versus real-world cohort 1 (Z), trial cohort 2 (X) versus real-world cohort 2 (Y). For first line, the median OS was 9.7 months (95% CI 8.6- 11.5) and the median PFS was 5.2 months (95% CI 4.7- not reached) for real-world cohort 1. For second line, the median OS was 10.6 months (95% CI 4.7- 27.3) for real-world cohort 2 and the median PFS was 5.0 months (95% CI 2.1- 29.3). For OS analysis, results were statistically significant but not for PFS analysis. Conclusion: This study provided the clinical comparative outcomes needed for HTA evaluation.

Keywords: real world evidence, pharmacoeconomics, HTA agencies, oncology

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603 Analysis of Vocal Pathologies Through Subglottic Pressure Measurement

Authors: Perla Elizabeth Jimarez Rocha, Carolina Daniela Tejeda Franco, Arturo Minor Martínez, Annel Gomez Coello

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One of the biggest problems in developing new therapies for the management and treatment of voice disorders is the difficulty of objectively evaluating the results of each treatment. A system was proposed that captures and records voice signals, in addition to analyzing the vocal quality (fundamental frequency, zero crossings, energy, and amplitude spectrum), as well as the subglottic pressure (cm H2O) during the sustained phonation of the vowel / a /; a recording system is implemented, as well as an interactive system that records information on subglottic pressure. In Mexico City, a control group of 31 patients with phoniatric pathology is proposed; non-invasive tests were performed for these most common vocal pathologies (Nodules, Polyps, Irritative Laryngitis, Ventricular Dysphonia, Laryngeal Cancer, Dysphonia, and Dysphagia). The most common pathology was irritative laryngitis (32%), followed by vocal fold paralysis (unilateral and bilateral,19.4 %). We take into consideration men and women in the pathological groups due to the physiological difference. They were separated in gender by the difference in the morphology of the respiratory tract.

Keywords: amplitude spectrum, energy, fundamental frequency, subglottic pressure, zero crossings

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602 Clinico-pathological Study of Xeroderma Pigmentosa: A Case Series of Eight Cases

Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

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Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

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601 Synthesis and Evaluation of Antioxidant Behavior of Some Indole-Based Melatonin Derivatives

Authors: Eddy Neuhaus, Hanif Shirinzadeh, Cigdem Karaaslan, Elif Ince, Hande Gurer-Orhan, Sibel Suzen

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Reactive oxygen species (ROS) and oxidative stress can cause fatal damage to essential cell structures, including DNA. It is known that use of antioxidants could be advantageous in the prevention of various diseases such as cancer, cardiovascular diseases and neurodegenerative disorders. Since antioxidant properties of the indole ring-containing melatonin (MLT) has been described and evaluated, MLT-related compounds such as MLT metabolites and synthetic analogues are under investigation to determine which exhibit the highest activity with the lowest side-effects. Owing to indole and hydrazones appealing physiological properties and are mostly found in numerous biologically active compounds a series of indole-7-carbaldehyde hydrazone derivatives were synthesized, characterized and in vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Cytotoxicity potential of all indole-based MLT analogues was investigated both by lactate dehydrogenase leakage assay and by MTT assay. This work was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) Research and Development Grant 112S599.

Keywords: melatonin, antioxidant activity, indole, hydrazone, oxidative stress

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600 Genome-Wide Homozygosity Analysis of the Longevous Phenotype in the Amish Population

Authors: Sandra Smieszek, Jonathan Haines

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Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

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599 Synthesis, Characterization, and Biological Evaluation of 1,3,4-Mercaptooxadiazole Ether Derivatives Analogs as Antioxidant, Cytotoxic, and Molecular Docking Studies

Authors: Desta Gebretekle Shiferaw, Balakrishna Kalluraya

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Oxadiazoles and their derivatives with thioether functionalities represent a new and exciting class of physiologically active heterocyclic compounds. Several molecules with these moieties play a vital role in pharmaceuticals because of their diverse biological activities. This paper describes a new class of 1,3,4- oxadiazole-2-thioethers with acetophenone, coumarin, and N-phenyl acetamide residues (S-alkylation), with the hope that the addition of various biologically active molecules will have a synergistic effect on anticancer activity. The structure of the synthesized title compounds was determined by the combined methods of IR, proton-NMR, carbon-13-NMR, and mass spectrometry. Further, all the newly prepared molecules were assessed against their antioxidant activity. Furthermore, four compounds were assessed for their molecular docking interactions and cytotoxicity activity. The synthesized derivatives have shown moderate antioxidant activity compared to the standard BHA. The IC50 of the tilted molecules (11b, 11c, 13b, and 14b) observed for in vitro anti-cancer activities were 11.20, 15.73, 59.61, and 27.66 g/ml at 72-hour treatment time against the A549 cell lines, respectively. The tested compounds' biological evaluation showed that 11b is the most effective molecule in the series.

Keywords: antioxidant activity, cytotoxicity activity, molecular docking, 1, 3, 4-Oxadiazole-2 thioether derivatives

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