Search results for: early stage breast cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8142

Search results for: early stage breast cancer

7272 The Importance of Artificial Intelligence in Various Healthcare Applications

Authors: Joshna Rani S., Ahmadi Banu

Abstract:

Artificial Intelligence (AI) has a significant task to carry out in the medical care contributions of things to come. As AI, it is the essential capacity behind the advancement of accuracy medication, generally consented to be a painfully required development in care. Albeit early endeavors at giving analysis and treatment proposals have demonstrated testing, we anticipate that AI will at last dominate that area too. Given the quick propels in AI for imaging examination, it appears to be likely that most radiology, what's more, pathology pictures will be inspected eventually by a machine. Discourse and text acknowledgment are now utilized for assignments like patient correspondence and catch of clinical notes, and their utilization will increment. The best test to AI in these medical services areas isn't regardless of whether the innovations will be sufficiently skilled to be valuable, but instead guaranteeing their appropriation in day by day clinical practice. For far reaching selection to happen, AI frameworks should be affirmed by controllers, coordinated with EHR frameworks, normalized to an adequate degree that comparative items work likewise, instructed to clinicians, paid for by open or private payer associations, and refreshed over the long haul in the field. These difficulties will, at last, be survived, yet they will take any longer to do as such than it will take for the actual innovations to develop. Therefore, we hope to see restricted utilization of AI in clinical practice inside 5 years and more broad use inside 10 years. It likewise appears to be progressively evident that AI frameworks won't supplant human clinicians for a huge scope, yet rather will increase their endeavors to really focus on patients. Over the long haul, human clinicians may advance toward errands and work plans that draw on remarkably human abilities like sympathy, influence, and higher perspective mix. Maybe the lone medical services suppliers who will chance their professions over the long run might be the individuals who will not work close by AI

Keywords: artificial intellogence, health care, breast cancer, AI applications

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7271 Beliefs, Attitudes, and Understanding of Childhood Cancer Among White and Latino Parents in the Phoenix Metropolitan Area: A Comparative Study

Authors: Florence Awde

Abstract:

In 2023, it was expected 350 parents in Arizona would have a child receive a cancer diagnosis (Welcome Arizona Cancer Foundation For Children, n.d.). The news of a child’s diagnosis with cancer can be overwhelming and confusing, especially for those lucky enough to lack a personal tie to the disease that takes approximately 1800 children’s lives each year in the United States (Deegan et al., n.d.). A parent’s beliefs, attitudes, and understandings surrounding cancer are vital for medical staff to provide adequate and culturally competent care for each patient, especially across cultural and ethnic lines in regions housing multicultural populations. Arizona's cultural/linguistic mosaic houses many White and Latino populations and English and Spanish speakers. Variations in insurance coverage, from those insured through public insurance programs (e.g., Medicaid) or private insurance plans (e.g., employee-sponsored insurance) versus those uninsured, also factor into health-seeking attitudes and behaviors. To further understand parental attitudes, understandings, and beliefs towards childhood cancer, 22 parents (11 of Latino ethnicity, 11 of White ethnicity) were interviewed on these facets of childhood cancer, despite 21 of the 22 never having a child receive a cancer diagnosis. The exploration of these perceptions across ethnic lines revealed a higher report of fear-orientated beliefs amongst Latino parents--hypothesized to be rooted in the starkly contrasting lack of belief in the possibility of recovering for children with cancer, compared to their white counterparts who displayed more optimism in the recovery process. Further, this study’s results lay the foundation for future scholarship to explore avenues of information dispersal to Latino parents that correct misconceptions of health outcomes and enable earlier intervention to be possible, ultimately correlating to better health and treatment outcomes by increasing parental health literacy rates for childhood cancer in the Phoenix Metropolitan.

Keywords: Childhood Cancer, Parental Beliefs, Parental Attitudes, Parental Understandings, Phoenix Metropolitan, Culturally Competent Care, Health Disparities, Health Inequities

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7270 Assessment of Germination Loss Due to Dusky Cotton Bug (Oxycarenus laetus) in Relation to Cotton Boll Stage and Bug Intensity

Authors: Ali Hassan, Mian Muhammad Awais, Muhammad Rafique Shahid, Farazia Hassan, Shumaila Rasool

Abstract:

Dusky cotton bug (Oxycarenus laetus) has attained the status of major insect pest of cotton. It is also known as seed bug due to its property of feeding on seeds. It causes floral abscission at flowering stage and reduction in seed germination. Present study was carried out to assess germination loss caused by dusky bug with respect to crop stage and insect intensity. Treatments consisted of three stages immature boll, mature boll and opened boll as well three levels of dusky bug i.e., 50 bugs per boll, 40 bugs per boll along with zero level kept as control. Results showed that the germination percentage was highest in control treatment where no insect was released followed by treatment where 40 insects released and minimum germination showed by treatment in which 50 insects were released. The germination percentage of seeds surpassed after control treatment in the treatment where dusky bugs exposure was given at boll opening stage than on mature boll stage. Minimum germination was observed in immature boll stage. Interaction between crop stages and dusky bug levels showed that germination percentage of seeds was maximum in control treatment then boll opening stage followed by mature boll stage. Minimum seed germination was recorded in dusky bug treatment at immature boll stage which was 34% where 50 insects were released. From the results it is clear that dusky bug should be managed properly at all reproductive stages but immature stage is most critical.

Keywords: Gossypium hirsutum, Oxycarenus laetus, seed bug, seed germination

Procedia PDF Downloads 303
7269 Unusual Presentation of Colorectal Cancer within Inguinal Hernia: A Systemic Review of Reported Cases

Authors: Sena Park

Abstract:

Background: The concurrent presentation with colorectal cancer in the inguinal hernia has been extremely rare. Due to its rarity, its presentation may lead to diagnostic and therapeutic dilemmas. We aim to review all the reported cases on colorectal cancer incarcerated in the inguinal hernia in the last 20 years, and discuss the operative approaches. Methods: We identified all case reports on colorectal cancer within inguinal hernia using PUBMED (2002-2022) and MEDLINE (2002-2022). The search strategy included the following keywords: colorectal cancer (title/abstract) AND inguinal hernia (title/abstract) OR incarceration (title/abstract). The search did not include letters, book chapters, systemic reviews, meta-analysis and editorials. Results: In the last 20 years, a total of 19 cases on colorectal cancer within the inguinal hernia were identified. The age of the patients ranged between 48 and 89. Majority of the patients were male (95%). Most commonly involved part of the large intestine was sigmoid colon (79%). Of all the cases, 79 percent of patients received open procedure and 21 percent had laparoscopic procedure. Discussion: Inguinal hernias are common with an incidence of approximately 1.7 percent. Colorectal cancer is the one of the leading causes of cancer-related mortality worldwide. However, their concurrent presentation has been extremely rare. In the last 20 years, 19 cases on concurrent presentation of colorectal cancer and inguinal hernia have been reported. Most patients who had open procedures had two incisions of groin incision and a midline laparotomy. There were 4 cases where the oncological resection was performed laparoscopically. The advantages of laparoscopic resection include reduced blood lost, reduced post-operative pain, reduced length of hospital stay and similar number of lymph nodes taken. From the review of the cases in the last 20 years, both open and laparoscopic approaches seemed to be safe and achieve adequate oncological resections. Conclusion: This is a brief overview of reported cases of colorectal cancer presenting with inguinal hernia concurrently. Due to its rarity, there are no current guidelines on operative approach in clinical practice. The experience in the last 20 years supports both open and laparoscopic approach.

Keywords: colorectal cancer, inguinal hernia, incarceration, operative approach

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7268 Further Evidence for the Existence of Broiler Chicken PFN (Pale, Firm and Non-Exudative Meat) and PSE (Pale, Soft and Exudative) in Brazilian Commercial Flocks

Authors: Leila M. Carvalho, Maria Erica S. Oliveira, Arnoud C. Neto, Elza I. Ida, Massami Shimokomaki, Marta S. Madruga

Abstract:

The quality of broiler breast meat is changing as a result of the continuing emphasis on genetic selection for a more efficient meat production. Breast meat has been classified as PSE (pale, soft, exudative), DFD (dark, firm, dry) and normal color meat, and recently a third group has emerged: the so-called PFN (pale, firm, non-exudative) meat. This classification was based on pH, color and functional properties. The aim of this work was to confirm the existence of PFN and PSE meat by biochemical characterization and functional properties. Twenty four hours of refrigerated fillet, Pectoralis major, m. samples (n= 838) were taken from Cobb flocks 42-48 days old, obtained in Northeastern Brazil tropical region, the Northeastern, considered to have only dry and wet seasons. Color (L*), pH, water holding capacity (WHC), values were evaluated and compared with PSE group samples. These samples were classified as Normal (465.8), PSE meat (L*≥53; pH<5.8) and PFN (L*≥53; pH>5.8). The occurrence of control meat, PSE and PFN was 69.09%, 11.10% and 19.81%, respectively. Samples from PFN presented 4.0-5.0% higher WHC in relation to PSE meat and similar to control group. These results are explained by the fact that PSE meat syndrome occurs because of higher protein denaturation as the consequence of a simultaneous lower pH values under warm carcass sooner after slaughtering impairing the myofibril proteins functional properties. Conversely, PFN samples follow normal glycolysis rate maintaining the normal proteins activities. In conclusion, the results reported herein confirm the existence of this emerging broiler meat group with similar properties as control group and it should be considered as normal breast meat group.

Keywords: broiler breast meat, funcional properties, PFN, PSE

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7267 Key Issues in Transfer Stage of BOT Project: Experience from China

Authors: Wang Liguang, Zhang Xueqing

Abstract:

The build-operate-transfer (BOT) project delivery system has provided effective routes to mobilize private sector funds, innovative technologies, management skills and operational efficiencies for public infrastructure development and have been widely used in China during the last 20 years. Many BOT projects in China will be smoothly transferred to the government soon and the transfer stage, which is considered as the last stage, must be studied carefully and handled well to achieve the overall success of BOT projects. There will be many issues faced by both the public sector and private sector in the transfer stage of BOT projects, including project post-assessment, technology and documents transfer, personal training and staff transition, etc. and sometimes additional legislation is needed for future operation and management of facilities. However, most previous studies focused on the bidding, financing, and building and operation stages instead of transfer stage. This research identifies nine key issues in the transfer stage of BOT projects through a comprehensive study on three cases in China, and the expert interview and expert discussion meetings are held to validate the key issues and give detail analysis. A proposed framework of transfer management is prepared based on the experiences derived and lessons drawn from the case studies and expert interview and discussions, which is expected to improve the transfer management of BOT projects in practice.

Keywords: BOT project, key issues, transfer management, transfer stage

Procedia PDF Downloads 242
7266 The Effect of Group Logotherapy on Depression and Life Quality in Cancer Patients

Authors: Fatemeh Ghaemi, Padideh Feyzi, Zohreh Dortaj

Abstract:

Cancer is one of the common diseases that may cause death due to malignancy. The physical problems of cancer patients can have an impact on the psychological and social aspects of their lives. Depression is one of these problems that threaten the lives of these patients and can also reduce their quality of life. Helping patients with cancer to find meaning in life can increase their level of health and improve their quality of life. This study thus examines the effectiveness of group logotherapy on the depression and quality of life of women with cancer. Depression was measured using the Beck Depression Inventory (BDI) and quality of life was measured using Quality of Life Questionnaire (WHOQL) with acceptable and reliable indicators in the pre-test and post-test stages. The experimental group received group therapy in eight, sixty-minute sessions and the control group did not receive any intervention. After collecting the questionnaires, the mean and standard deviations were used to describe the data and the statistical method of multivariate analysis of covariance was used at the significant level (P≤0.05). The results were analyzed using SPSS(22). The results showed that there was a significant difference between post-test depression scores in the experimental group and the control group. Also, there was a significant difference between the post-test scores of quality of life and its components (psychological, physical, social and environmental health) in the experimental group and control group. The findings of this study showed the effectiveness of group logotherapy in decreasing depression and improving the quality of life of cancer patients. By focusing the minds of the people on the present and changing the attitude of the human being towards themselves, life and environment can help the depressed people, and by influencing the individual's view of himself, accepting responsibility, accepting life with purpose, paying attention to life uniformly, it allows a person to maintain his quality of life even with cancer. Therefore, it is recommended that this approach be used as a group intervention in hospitals and care units for cancer patients and even in people with certain diseases.

Keywords: cancer, depression, group psychiatry, quality of life

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7265 Cloning and Expression of Azurin: A Protein Having Antitumor and Cell Penetrating Ability

Authors: Mohsina Akhter

Abstract:

Cancer has become a wide spread disease around the globe and takes many lives every year. Different treatments are being practiced but all have potential side effects with somewhat less specificity towards target sites. Pseudomonas aeruginosa is known to secrete a protein azurin with special anti-cancer function. It has unique cell penetrating peptide comprising of 18 amino acids that have ability to enter cancer cells specifically. Reported function of Azurin is to stabilize p53 inside the tumor cells and induces apoptosis through Bax mediated cytochrome c release from mitochondria. At laboratory scale, we have made recombinant azurin through cloning rpTZ57R/T-azu vector into E.coli strain DH-5α and subcloning rpET28-azu vector into E.coli BL21-CodonPlus (DE3). High expression was ensured with IPTG induction at different concentrations then optimized high expression level at 1mM concentration of IPTG for 5 hours. Purification has been done by using Ni+2 affinity chromatography. We have concluded that azurin can be a remarkable improvement in cancer therapeutics if it produces on a large scale. Azurin does not enter into the normal cells so it will prove a safe and secure treatment for patients and prevent them from hazardous anomalies.

Keywords: azurin, pseudomonas aeruginosa, cancer, therapeutics

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7264 Normal Hematopoietic Stem Cell and the Toxic Effect of Parthenolide

Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.

Abstract:

Most conventional chemotherapeutic agents which are used for the treatment of cancers not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that leads to severe pancytopenia during treatment. Therefore, a need exists for novel approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential new chemotherapeutic agent for the treatment of many cancers such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: In this study, 24 samples of bone marrow and cord blood were collected with consent, and mononuclear cells were separated using density gradient separation. These cells were then exposed to various concentrations of PTL for 24 hours. Cell viability after culture was determined using 7ADD in a flow cytometry test. Additionally, the impact of PTL on hematopoietic stem cells (HSCs) was evaluated using a colony forming unit assay (CFU). Furthermore, the levels of NFҝB expression were assessed by using a PE-labelled anti-pNFκBP65 antibody. Results: this study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4) on the other hand was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Discussion &Conclusion: At concentrations ≤25 μM PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs. This could be due to the higher percentage of T-lymphocytes, which are resistant to PTL, in CB samples (85% in CB vs. 56% in BM. Additionally, CB samples contained a higher proportion of CD34+ cells, with 14.5% of brightly CD34+ cells compared to only 1% in normal BM. These bright CD34+ cells in CB were mostly negative for early-stage stem cell maturation antigens, making them young and resilient to oxidative stress and high concentrations of PTL.

Keywords: stem cell, parthenolide, NFKB, CLL

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7263 Epidemiological-Anatomopathological-Immunohistochemical Profile of Gastric Cancer throughout Eastern Algeria

Authors: S. Tebibel, R. L. Bouchouka, C. Mechati, S. Messaoudi

Abstract:

The stomach cancer or gastric cancer is an aggressive cancer with a significant geographic disparity. The decrease in frequency is attributed to refrigeration, which has several beneficial consequences, increased consumption of fresh fruits and vegetables, reduced consumption of salt, which was widely used as a food preservative, and less contamination of food by carcinogenic compounds. The infection with Helicobacter pylori is responsible for progressive inflammatory changes in the gastric mucosa usually evolving into stomach cancer in 80% of cases. Methodology: This epidemiological and analytical study concerns 65 patients (46 men and 19 women) with gastric adenocarcinomas with an average age of 56.5 years and a male predominance with a sex ratio of 2.4. Results and Discussion: In this series, the clinical symptoms are dominated by epigastralgia (72.31%), vomiting (27,69%), and slimming (24,62%). The FOGD (Oeso-Gastro Duodenal Fibroscopy) performed in the 65 patients revealed a predominance of the antro-pyloric localization in 19 cases (i.e., 29.23%) and anulcerative budding appearance in 33 subjects (50,77%). Histologically, the moderately differentiated adenocarcinoma is found in 30.77% of patients, followed by well differentiated adenocarcinoma with 26.15% of patients. The immunohistochemical study revealed a positive labeling of half of the T cells by anti-CD3 AC, and a positive labeling of anti-CD20 AC in a diffuse and intense manner, with the presence of CD20-positive lymphoepithelial lesions compatible with CD20 a low grade MALT non-Hodgkin's lymphoma. Conclusion: This framework of analysis revealed some risk factors for gastric cancer, such as food, hygiene, Helicobacter pylori infection, smoking and family history.

Keywords: cancer, Helicobacter pylori, immunohistochemistry, stomach

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7262 Robust Segmentation of Salient Features in Automatic Breast Ultrasound (ABUS) Images

Authors: Lamees Nasser, Yago Diez, Robert Martí, Joan Martí, Ibrahim Sadek

Abstract:

Automated 3D breast ultrasound (ABUS) screening is a novel modality in medical imaging because of its common characteristics shared with other ultrasound modalities in addition to the three orthogonal planes (i.e., axial, sagittal, and coronal) that are useful in analysis of tumors. In the literature, few automatic approaches exist for typical tasks such as segmentation or registration. In this work, we deal with two problems concerning ABUS images: nipple and rib detection. Nipple and ribs are the most visible and salient features in ABUS images. Determining the nipple position plays a key role in some applications for example evaluation of registration results or lesion follow-up. We present a nipple detection algorithm based on color and shape of the nipple, besides an automatic approach to detect the ribs. In point of fact, rib detection is considered as one of the main stages in chest wall segmentation. This approach consists of four steps. First, images are normalized in order to minimize the intensity variability for a given set of regions within the same image or a set of images. Second, the normalized images are smoothed by using anisotropic diffusion filter. Next, the ribs are detected in each slice by analyzing the eigenvalues of the 3D Hessian matrix. Finally, a breast mask and a probability map of regions detected as ribs are used to remove false positives (FP). Qualitative and quantitative evaluation obtained from a total of 22 cases is performed. For all cases, the average and standard deviation of the root mean square error (RMSE) between manually annotated points placed on the rib surface and detected points on rib borders are 15.1188 mm and 14.7184 mm respectively.

Keywords: Automated 3D Breast Ultrasound, Eigenvalues of Hessian matrix, Nipple detection, Rib detection

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7261 Leadership Development for Nurses as Educators

Authors: Abeer Alhazmi

Abstract:

Introduction: Clinical education is considered a significant part of the learning process for nurses and nursing students. However, recruiting high- caliber individuals to train them to be tomorrow’s educators/teachers has been a recurrent challenge. One of the troubling challenges in this field is the absent of proper training programmes to train educators to be future education professionals and leaders. Aim: To explore the impact of a stage 1 and stage 2 clinical instructor courses on developing leadership skills for nurses as educators.Theoretical Framework: Informed by a symbolic interactionist framework, this research explored the Impact of stage 1 and stage 2 clinical instructor courses on nurses' knowledge, attitudes, and leadership skills. Method: Using Glaserian grounded theory method the data were derived from 3 focus groups and 15 in-depth interviews with nurse educators/clinical instructors and nurses who attended stage 1 and stage 2 clinical instructor courses at King Abdu-Aziz University Hospital (KAUH). Findings: The findings of the research are represented in the core category exploring new identity as educator and its two constituent categories Accepting change, and constructing educator identity. The core and sub- categories were generated through a theoretical exploration of the development of educator’s identity throughout stage 1 and stage 2 clinical instructor courses. Conclusion: The social identity of the nurse educators was developed and changed during and after attending stage 1 and stage 2 clinical instructor courses. In light of an increased understanding of the development process of educators identity and role, the research presents implications and recommendations that may contribute to the development of nursing educators in general and in Saudi Arabia in specific.

Keywords: clinical instructor course, educators, identity work, clinical nursing

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7260 High Efficient Biohydrogen Production from Cassava Starch Processing Wastewater by Two Stage Thermophilic Fermentation and Electrohydrogenesis

Authors: Peerawat Khongkliang, Prawit Kongjan, Tsuyoshi Imai, Poonsuk Prasertsan, Sompong O-Thong

Abstract:

A two-stage thermophilic fermentation and electrohydrogenesis process was used to convert cassava starch processing wastewater into hydrogen gas. Maximum hydrogen yield from fermentation stage by Thermoanaerobacterium thermosaccharolyticum PSU-2 was 248 mL H2/g-COD at optimal pH of 6.5. Optimum hydrogen production rate of 820 mL/L/d and yield of 200 mL/g COD was obtained at HRT of 2 days in fermentation stage. Cassava starch processing wastewater fermentation effluent consisted of acetic acid, butyric acid and propionic acid. The effluent from fermentation stage was used as feedstock to generate hydrogen production by microbial electrolysis cell (MECs) at an applied voltage of 0.6 V in second stage with additional 657 mL H2/g-COD was produced. Energy efficiencies based on electricity needed for the MEC were 330 % with COD removals of 95 %. The overall hydrogen yield was 800-900 mL H2/g-COD. Microbial community analysis of electrohydrogenesis by DGGE shows that exoelectrogens belong to Acidiphilium sp., Geobacter sulfurreducens and Thermincola sp. were dominated at anode. These results show two-stage thermophilic fermentation, and electrohydrogenesis process improved hydrogen production performance with high hydrogen yields, high gas production rates and high COD removal efficiency.

Keywords: cassava starch processing wastewater, biohydrogen, thermophilic fermentation, microbial electrolysis cell

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7259 DNA Fragmentation and Apoptosis in Human Colorectal Cancer Cell Lines by Sesamum indicum Dried Seeds

Authors: Mohd Farooq Naqshbandi

Abstract:

The four fractions of aqueous extract of Sesame Seeds (Sesamum indicum L.) were studied for invitro DNA fragmentation, cell migration, and cellular apoptosis on SW480 and HTC116 human colorectal cancer cell lines. The seeds of Sesamum indicum were extracted with six solvents, including Methanol, Ethanol, Aqueous, Chloroform, Acetonitrile, and Hexane. The aqueous extract (IC₅₀ value 154 µg/ml) was found to be the most active in terms of cytotoxicity with SW480 human colorectal cancer cell lines. Further fractionation of this aqueous extract on flash chromatography gave four fractions. These four fractions were studied for anticancer and DNA binding studies. Cell viability was assessed by colorimetric assay (MTT). IC₅₀ values for all these four fractions ranged from 137 to 548 µg/mL for the HTC116 cancer cell line and 141 to 402 µg/mL for the SW480 cancer cell line. The four fractions showed good anticancer and DNA binding properties. The DNA binding constants ranged from 10.4 ×10⁴ 5 to 28.7 ×10⁴, showing good interactions with DNA. The DNA binding interactions were due to intercalative and π-π electron forces. The results indicate that aqueous extract fractions of sesame showed inhibition of cell migration of SW480 and HTC116 human colorectal cancer cell lines and induced DNA fragmentation and apoptosis. This was demonstrated by calculating the low wound closure percentage in cells treated with these fractions as compared to the control (80%). Morphological features of nuclei of cells treated with fractions revealed chromatin compression, nuclear shrinkage, and apoptotic body formation, which indicate cell death by apoptosis. The flow cytometer of fraction-treated cells of SW480 and HTC116 human colorectal cancer cell lines revealed death due to apoptosis. The results of the study indicate that aqueous extract of sesame seeds may be used to treat colorectal cancer.

Keywords: Sesamum indicum, cell migration inhibition, apoptosis induction, anticancer activity, colorectal cancer

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7258 Comparison of Radiation Dosage and Image Quality: Digital Breast Tomosynthesis vs. Full-Field Digital Mammography

Authors: Okhee Woo

Abstract:

Purpose: With increasing concern of individual radiation exposure doses, studies analyzing radiation dosage in breast imaging modalities are required. Aim of this study is to compare radiation dosage and image quality between digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM). Methods and Materials: 303 patients (mean age 52.1 years) who studied DBT and FFDM were retrospectively reviewed. Radiation dosage data were obtained by radiation dosage scoring and monitoring program: Radimetrics (Bayer HealthCare, Whippany, NJ). Entrance dose and mean glandular doses in each breast were obtained in both imaging modalities. To compare the image quality of DBT with two-dimensional synthesized mammogram (2DSM) and FFDM, 5-point scoring of lesion clarity was assessed and the better modality between the two was selected. Interobserver performance was compared with kappa values and diagnostic accuracy was compared using McNemar test. The parameters of radiation dosages (entrance dose, mean glandular dose) and image quality were compared between two modalities by using paired t-test and Wilcoxon rank sum test. Results: For entrance dose and mean glandular doses for each breasts, DBT had lower values compared with FFDM (p-value < 0.0001). Diagnostic accuracy did not have statistical difference, but lesion clarity score was higher in DBT with 2DSM and DBT was chosen as a better modality compared with FFDM. Conclusion: DBT showed lower radiation entrance dose and also lower mean glandular doses to both breasts compared with FFDM. Also, DBT with 2DSM had better image quality than FFDM with similar diagnostic accuracy, suggesting that DBT may have a potential to be performed as an alternative to FFDM.

Keywords: radiation dose, DBT, digital mammography, image quality

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7257 Factors Influencing the Uptake of Family Planning Services among Young People (18-24 Years) at Community Level in Rural Budaka District, Uganda

Authors: Mathew Nyashanu, George K. Kiggundu, Mandu S. Ekpenyong

Abstract:

There is an increased number of young people engaging in early sexual relationships worldwide. Furthermore, statistics for early pregnancy among young people have also increased, especially in low and middle-income countries. This has health implications for both the parents and the baby. High uptake in family planning contraception among young people can reduce early pregnancy and subsequent negative health outcomes on the young parents and the baby. This study was set to explore the factors influencing the uptake of family planning contraceptive services among young people (18-24 years) at a community level in rural Budaka district, Uganda. The study utilised an explorative qualitative approach. The study found out that religion, partner resistance; perceived loss of libido, perceived barren, long waiting time and distance from the health facility, lack of privacy/confidentiality, excessive menstrual bleeding, cancer, and fear of having disabled babies, limited the utilisation of family planning contraceptive services while contraception as HIV prevention and child spacing encouraged young people to use family planning contraceptive services. There is a need for a culturally orientated community-based contraceptive health promotion approach to increase the uptake of family planning contraception services among young people.

Keywords: Young people, Family Planning, Contraceptives, Black sub-Sahara African

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7256 Radiological Analysis of Skeletal Metastases from Cervical Cancer

Authors: Jacklynn Walters, Amanda A. Alblas, Linda M. Greyling

Abstract:

Cervical carcinoma is the second most common cancer found in women. Diagnosis of skeletal metastases is uncommon in cervical cancer patients. The aim of this study was to determine the prevalence of skeletal metastases in in a Western Cape skeletal population. Skeletal samples (n=14) from the Kirsten Skeletal Collection at Stellenbosch University, diagnosed pre-mortem with cervical cancer, were examined. Macroscopic analysis was done using low magnification to examine each skeletal element for signs of disease. Skeletons were also x-rayed using the Lodox® Statscan® Imaging system and the scans evaluated by a musculoskeletal radiologist. Three (21%) of the skeletons showed metastases, with the os coxae and lower vertebral column affected in all three cases. Furthermore, metastases occurred in the scapulae and ribs in two of the cases and in one case the skull, mandible, and long bones were affected. Additionally, three skeletons without evidence of skeletal metastases presented with a periosteal reaction on the os coxae in response to the diseased adjacent soft tissue. Previous studies observed that skeletal metastases are more common than what is diagnosed pre-mortem with the vertebral spine most commonly affected. The findings of this study agree with previous reports and illustrate the effectiveness of the Lodox® scanner in diagnoses of metastases in skeletal material.

Keywords: cancer, cervix, radiology, skeletal metastases

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7255 Formulation and Evaluation of Silver Nanoparticles as Drug Carrier for Cancer Therapy

Authors: Abdelhadi Adam Salih Denei

Abstract:

Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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7254 Targeted Photoactivatable Multiagent Nanoconjugates for Imaging and Photodynamic Therapy

Authors: Shazia Bano

Abstract:

Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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7253 Synthesis and Anti-Cancer Evaluation of Uranyle Complexes

Authors: Abdol-Hassan Doulah

Abstract:

In this research, some of the inorganic complexes of uranyl with N- donor ligands were synthesized. Complexes were characteriezed by FT-IR and UV spectra, ¹HNMR, ¹³CNMR and some physical properties. The uranyl unit (UO2) is composed of a center of uranium atom with the charge (+6) and two oxygen atom by forming two U=O double bonds. The structure is linear (O=U=O, 180) and usually stable. So other ligands often coordinate to the U atom in the plane perpendicularly to the O=U=O axis. The antitumor activity of some of ligand and their complexes against a panel of human tumor cell lines (HT29: Haman colon adenocarcinoma cell line T47D: human breast adenocarcinoma cell line) were determined by MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay. These data suggest that some of these compounds provide good models for the further design of potent antitumor compounds.

Keywords: inorganic, uranyl complex-donor ligands, Schiff bases, anticancer activity

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7252 Non-Canonical Beclin-1-Independent Autophagy and Apoptosis in Cell Death Induced by Rhus coriaria in Human Colon HT-29 Cancer Cells

Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

Abstract:

Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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7251 Anticancer Activity of Calyx of Diospyros kaki Thunb. through Downregulation of Cyclin D1 Protein Level in Human Colorectal Cancer Cells

Authors: Jin Boo Jeong

Abstract:

In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).

Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer

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7250 Risk of Androgen Deprivation Therapy-Induced Metabolic Syndrome-Related Complications for Prostate Cancer in Taiwan

Authors: Olivia Rachel Hwang, Yu-Hsuan Joni Shao

Abstract:

Androgen Deprivation Therapy (ADT) has been a primary treatment for patients with advanced prostate cancer. However, it is associated with numerous adverse effects related to Metabolic Syndrome (MetS), including hypertension, diabetes, hyperlipidaemia, heart diseases and ischemic strokes. However, complications associated with ADT for prostate cancer in Taiwan is not well documented. The purpose of this study is to utilize the data from NHIRD (National Health Insurance Research Database) to examine the trajectory changes of MetS-related complications in men receiving ADT. The risks of developing complications after the treatment were analyzed with multivariate Cox regression model. Covariates including in the model were the complications before the diagnosis of prostate cancer, the age, and the year at cancer diagnosis. A total number of 17268 patients from 1997-2013 were included in this study. The exclusion criteria were patients with any other types of cancer or with the existing MetS-related complications. Changes in MetS-related complications were observed among two treatment groups: 1) ADT (n=9042), and 2) non-ADT (n=8226). The ADT group appeared to have an increased risk in hypertension (hazard ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001) and hyperlipidemia (hazard ratio 1.09, 95% confidence interval 1.01-1.17, P = 0.02) when compared with non-ADT group in the multivariate Cox regression analyses. In the risk of diabetes, heart diseases, and ischemic strokes, ADT group appeared to have an increased but not significant hazard ratio. In conclusion, ADT was associated with an increased risk in hypertension and hyperlipidemia in prostate cancer patients in Taiwan. The risk of hypertension and hyperlipidemia should be considered while deciding on ADT, especially those with the known history of hypertension and hyperlipidemia.

Keywords: androgen deprivation therapy, ADT, complications, metabolic syndrome, MetS, prostate cancer

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7249 Retrospective Analysis of Facial Skin Cancer Patients Treated in the Department of Oral and Maxillofacial Surgery Kiel

Authors: Abdullah Saeidi, Aydin Gülses, Christan Flörke

Abstract:

Skin cancer of the face region is the most common type of malignancy and surgical excision is the preferred approach. However, the clinical long term results reported in the literature are still controversial. Objectives: To describe; 1. Demographical characteristics 2. Affected site, distribution and TNM classification regarding tumor type 3. Surgical aspects • Surgical removal: excision principles, safety margins, the need for secondary resection, primary reconstruction/ defect closure, anesthesia protocol, duration of hospital stay (if any) • Secondary intervention for defect closure/reconstruction: Flap technique, anesthesia protocol, duration of hospital stay (if any), postoperative wound management etc. 4. Tumor recurrences 5. Clinical outcomes 6. Studying the possible therapy approach throw Biostatistical relation and correlation between multiple Histological, diagnostics and clinical Faktors. following surgical ablation of the skin cancer of the head and neck region. Methods: Selection and statistical analysis of medical records of patients who had admitted to the Department of Oral and Maxillofacial Surgery, Universitätsklinikum Schleswig Holstein, Campus Kiel during the period of 2015-2019 will be retrospectively evaluated. Data will be collected via ORBIS Information-Management-System (ORBIS AG, Saarbrücken, Germany).

Keywords: non melanoma skin cancer, face skin cancer, skin reconstruction, non melanoma skin cancer recurrence, non melanoma skin cancer metastases

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7248 The Correlation between Clostridium Difficile Infection and Bronchial Lung Cancer Occurrence

Authors: Molnar Catalina, Lexi Frankel, Amalia Ardeljan, Enoch Kim, Marissa Dallara, Omar Rashid

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Introduction: Clostridium difficile (C. diff) is a toxin-producing bacteria that can cause diarrhea and colitis. U.S. Center for Disease Control and Prevention revealed that C. difficile infection (CDI) has increased from 31 cases per 100,000 persons per year in 1996 to 61 per 100,000 in 2003. Approximately 500,000 cases per year occur in the United States. After exposure, the bacteria colonize the colon, where it adheres to the intestinal epithelium where it produces two toxins: TcdA and TcdB. TcdA affects the intestinal epithelium, causing fluid secretion, inflammation, and tissue necrosis, while TcdB acts as a cytotoxin purpose of this study was to evaluate the association between C diff infection and bronchial lung cancer development. Methods: Using ICD- 9 and ICD-10 codes, the data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to assess the patients infected with C diff as opposed to the non-infected patients. The Holy Cross Health, Fort Lauderdale, granted access to the database for the purpose of academic research. Patients were matched for age and Charlson Comorbidity Index (CCI). Standard statistical methods were used. Results: Bronchial lung cancer occurrence in the population not infected with C diff infection was 4741, as opposed to the population infected with C. diff, where 2039 cases of lung cancer were observed. The difference was statistically significant (p-value < 2.2x10^e-16), which reveals that C diff might be protective against bronchial lung cancer. The data was then matched by treatment to create to minimize the effect of treatment bias. Bronchial cancer incidence was 422 and 861 in infected vs. non-infected (p-value of < 2.2x10^e-16), which once more indicates that C diff infection could be beneficial in diminishing bronchial cancer development. Conclusion: This retrospective study conveys a statistical correlation between C diff infection and decreased incidence of lung bronchial cancer. Further studies are needed to comprehend the protective mechanisms of C. Diff infection on lung cancer.

Keywords: C. diff, lung cancer, protective, microbiology

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7247 Local and Systemic Complications after Resection of Rectal Cancer in the Department of General and Abdominal Surgery University Clinical Center Maribor between 2004 and 2014

Authors: Nuhi Arslani, Stojan Potrc, Timotej Mikuljan

Abstract:

Background: In Department of Abdominal and General Surgery of University Medical Centre Maribor, we treated 578 patients for rectal cancer between 2004 and 2014. During and after treatment we especially concentrated on monitoring local and systemic complications. Methods: For analysis, we used data gathered from preoperative diagnostic tests, reports gathered during operation, reports from the pathohistologic review, and reports on complications after surgery and follow up. Results: In the case of 573 (out of 578) patients (99.1%) we performed resection. R0 was achieved in 551 patients (96,1%). R1 was achieved in 8 patients (1,4%). R2 was achieved in 14 patients (2,4%). Local complications were reported in 78 (13.5%) patients and systemic complications were reported in 68 (11.7%). We would like to point out the low number of local and systemic complications. Conclusions: With advances in surgical techniques, with a multimodal-multidisciplinary approach and with the use of total mesorectal excision we experienced a significant improvement in reducing the number of local and systemic complications in patients with rectal cancer. However, there still remains the question for truly optimal care for each patient with rectal cancer and his quality of life after surgical treatment.

Keywords: local complications, rectal cancer, resection, systemic complications

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7246 Maturity Status of Male Boys in Punjab - India

Authors: Parminder K. Laroiya, Sukhdeep S. Kang

Abstract:

The Present cross-sectional study was conducted on 610 boys (ranging in age bracket of 11 to 17 years) to assess their developmental age to check percentage of early, normal and late maturity among them, and to check whether there is any significant difference in their calendar age and developmental age. Developmental age of these subjects has been accessed by TW2 method (using hand wrist X-rays) and their chronological age was checked from their date of birth certificate. Developmental status of subjects i.e. early, normal or late mature was considered with +2 years or -2 years from their calendar age. Results of this study shows that 50% boys were normal in their maturity status in all age brackets and rest of subjects were either early maturers 24.92% or late maturers 25.08%. When pattern of maturity was studied in each age group it has been found that till the age of 15 years, percentage of normal maturity was less than 50 % whereas in 16 and 17 years age groups, this percentage of normal maturity increased to 60% - 65 % ( this may be because at this age mostly boys attain adolescence) Further investigation of each age group showed that till the age of 14 years percentage of late maturity among these boys were approximately 35% to 40% whereas early maturity lies between 15% to 20%. It has been found from the present study that at the age of 15 years, there is a twist among percentage of late and early maturity among boys-early maturers are 38.61% and late maturers are 16.84%. At the age of 16 and 17 years percentage of late maturity has been decreased to 3% to 6%, whereas percentage of early maturity increased to 35.64 % and 30.69 % respectively.

Keywords: maturity status, developmental age, chronological age, X-rays

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7245 A Proposed Treatment Protocol for the Management of Pars Interarticularis Pathology in Children and Adolescents

Authors: Paul Licina, Emma M. Johnston, David Lisle, Mark Young, Chris Brady

Abstract:

Background: Lumbar pars pathology is a common cause of pain in the growing spine. It can be seen in young athletes participating in at-risk sports and can affect sporting performance and long-term health due to its resistance to traditional management. There is a current lack of consensus of classification and treatment for pars injuries. Previous systems used CT to stage pars defects but could not assess early stress reactions. A modified classification is proposed that considers findings on MRI, significantly improving early treatment guidance. The treatment protocol is designed for patients aged 5 to 19 years. Method: Clinical screening identifies patients with a low, medium, or high index of suspicion for lumbar pars injury using patient age, sport participation and pain characteristics. MRI of the at-risk cohort enables augmentation of existing CT-based classification while avoiding ionising radiation. Patients are classified into five categories based on MRI findings. A type 0 lesion (stress reaction) is present when CT is normal and MRI shows high signal change (HSC) in the pars/pedicle on T2 images. A type 1 lesion represents the ‘early defect’ CT classification. The group previously referred to as a 'progressive stage' defect on CT can be split into 2A and 2B categories. 2As have HSC on MRI, whereas 2Bs do not. This distinction is important with regard to healing potential. Type 3 lesions are terminal stage defects on CT, characterised by pseudarthrosis. MRI shows no HSC. Results: Stress reactions (type 0) and acute fractures (1 and 2a) can heal and are treated in a custom-made hard brace for 12 weeks. It is initially worn 23 hours per day. At three weeks, patients commence basic core rehabilitation. At six weeks, in the absence of pain, the brace is removed for sleeping. Exercises are progressed to positions of daily living. Patients with continued pain remain braced 23 hours per day without exercise progression until becoming symptom-free. At nine weeks, patients commence supervised exercises out of the brace for 30 minutes each day. This allows them to re-learn muscular control without rigid support of the brace. At 12 weeks, bracing ceases and MRI is repeated. For patients with near or complete resolution of bony oedema and healing of any cortical defect, rehabilitation is focused on strength and conditioning and sport-specific exercise for the full return to activity. The length of this final stage is approximately nine weeks but depends on factors such as development and level of sports participation. If significant HSC remains on MRI, CT scan is considered to definitively assess cortical defect healing. For these patients, return to high-risk sports is delayed for up to three months. Chronic defects (2b and 3) cannot heal and are not braced, and rehabilitation follows traditional protocols. Conclusion: Appropriate clinical screening and imaging with MRI can identify pars pathology early. In those with potential for healing, we propose hard bracing and appropriate rehabilitation as part of a multidisciplinary management protocol. The validity of this protocol will be tested in future studies.

Keywords: adolescents, MRI classification, pars interticularis, treatment protocol

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7244 Factors Associated with Ketamine Use in Pancreatic Cancer Patient in a Single Hospice Center

Authors: Kyung Min Kwom, Young Joo Lee

Abstract:

Purpose: Up to 90% of pancreatic cancer patient suffer from neuropathic pain. In palliative care setting, pain control in a pancreatic cancer patient is one of the major goals. Ketamine is a NMDA receptor antagonist effective in neuropathic pain. Also, there have been studies about opioid sparing effect of ketamine. This study was held in palliative care unit among pancreatic cancer patients to find out the factors related to ketamine use and the opioid sparing effect. Methods: Medical records of pancreatic cancer patients admitted to St. Mary’s hospital palliative care unit from 2013.1 to 2014.12 were reviewed. Patients were divided into two categories according to ketamine use. Also, opioid use before and after ketamine use was compared in ketamine group. Results: Compared to non ketamine use group, patients in ketamine group required a higher dose of opioid. Total opioid dose, daily opioid dose, number of daily rescue medication, daily average rescue dose were statistically significantly higher in ketamine group. Opioid requirement was increased after ketamine administration. Conclusion: In this study, ketamine group required more opioid. Ketamine is frequently considered in patients with severe pain, requiring high amount of opioid. Also, ketamine did not have an opioid sparing effect. Future studies about palliative use of ketamine in a larger number of patients are required.

Keywords: ketamine, opioid sparing, palliative care, pancreatic cancer

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7243 MicroRNA Drivers of Resistance to Androgen Deprivation Therapy in Prostate Cancer

Authors: Philippa Saunders, Claire Fletcher

Abstract:

INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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