Search results for: breast conserving therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2513

Search results for: breast conserving therapy

653 Physicians’ Knowledge and Perception of Gene Profiling in Malaysia: A Pilot Study

Authors: Farahnaz Amini, Woo Yun Kin, Lazwani Kolandaiveloo

Abstract:

Availability of different genetic tests after completion of Human Genome Project increases the physicians’ responsibility to keep themselves update on the potential implementation of these genetic tests in their daily practice. However, due to numbers of barriers, still many of physicians are not either aware of these tests or are not willing to offer or refer their patients for genetic tests. This study was conducted an anonymous, cross-sectional, mailed-based survey to develop a primary data of Malaysian physicians’ level of knowledge and perception of gene profiling. Questionnaire had 29 questions. Total scores on selected questions were used to assess the level of knowledge. The highest possible score was 11. Descriptive statistics, one way ANOVA and chi-squared test was used for statistical analysis. Sixty three completed questionnaires was returned by 27 general practitioners (GPs) and 36 medical specialists. Responders’ age range from 24 to 55 years old (mean 30.2 ± 6.4). About 40% of the participants rated themselves as having poor level of knowledge in genetics in general whilst 60% believed that they have fair level of knowledge. However, almost half (46%) of the respondents felt that they were not knowledgeable about available genetic tests. A majority (94%) of the responders were not aware of any lab or company which is offering gene profiling services in Malaysia. Only 4% of participants were aware of using gene profiling for detection of dosage of some drugs. Respondents perceived greater utility of gene profiling for breast cancer (38%) compared to the colorectal familial cancer (3%). The score of knowledge ranged from 2 to 8 (mean 4.38 ± 1.67). Non-significant differences between score of knowledge of GPs and specialists were observed, with score of 4.19 and 4.58 respectively. There was no significant association between any demographic factors and level of knowledge. However, those who graduated between years 2001 to 2005 had higher level of knowledge. Overall, 83% of participants showed relatively high level of perception on value of gene profiling to detect patient’s risk of disease. However, low perception was observed for both statements of using gene profiling for general population in order to alter their lifestyle (25%) as well as having the full sequence of a patient genome for the purpose of determining a patient’s best match for treatment (18%). The lack of clinical guidelines, limited provider knowledge and awareness, lack of time and resources to educate patients, lack of evidence-based clinical information and cost of tests were the most barriers of ordering gene profiling mentioned by physicians. In conclusion Malaysian physicians who participate in this study had mediocre level of knowledge and awareness in gene profiling. The low exposure to the genetic questions and problems might be a key predictor of lack of awareness and knowledge on available genetic tests. Educational and training workshop might be useful in helping Malaysian physicians incorporate genetic profiling into practice for eligible patients.

Keywords: gene profiling, knowledge, Malaysia, physician

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652 Clinical Outcomes and Surgical Complications in Patients with Cervical Disk Degeneration

Authors: Mirzashahi Babak, Mansouri Pejman, Najafi Arvin, Farzan Mahmoud

Abstract:

Introduction: There are several surgical treatment choices for cervical spondylotic myelopathy (CSM). The aim of this study is to evaluate clinical outcomes and surgical complications in patients with cervical disk degeneration (CDD) undergoing either anterior cervical discectomy with or without fusion or cervical laminectomy and fusion. Methods: This prospective case series study included 45 consecutive patients with cervical spondylotic myelopathy between January 2010 and November 2014. There were 28 males and 17 females, with a mean age of 47 (range 37-68) years. The mean clinical follow-up was 14 months (range 3-24 months). The Neck Disability Index (NDI), visual analog scale (VAS) neck and arm pain, Short Form-36 (SF-36) were used as the functional outcome measurements. All of the complications in our patients were recorded. Results: In our study group, 26 patients underwent only one or two level anterior cervical discectomy. Ten patients underwent anterior cervical discectomy and fusion (ACDF) and nine cases underwent posterior laminectomy and fusion. We have found a statistically significant improvement between mean preoperative (29, range 19-43) and postoperative (7, range 0-12) NDI scores following surgery (P < 0.05). Also, there was a statistically significant difference between pre and post-operative VAS and SF-36 score (p < 0.05). There was a 7% overall complication rate (n = 3). The only complication in our patients was surgical site cellulitis which has been managed with oral antibiotic therapy. Conclusion: Both anterior cervical discectomy with or without fusion or posterior laminectomy and fusion are safe and efficacious treatment options for the management of CSM. The clinical outcomes seem to be fairly reproducible.

Keywords: cervical, myelopathy, discectomy, fusion, laminectomy

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651 Erectile Dysfunction among Bangladeshi Men with Diabetes

Authors: Shahjada Selim

Abstract:

Background: Erectile dysfunction (ED) is an important impediment to quality of life of men. ED is approximate, three times more common in diabetic than non-diabetic men, and diabetic men develop ED earlier than age-matched non-diabetic subjects. Glycemic control and other factors may contribute in developing and or deteriorating ED. Aim: The aim of the study was to determine the prevalence of ED and its risk factors in type 2 diabetic (T2DM) men in Bangladesh. Methods: During 2013-2014, 3980 diabetic men aged 30-69 years were interviewed at the out-patient departments of seven diabetic centers in Dhaka by using the validated Bengali version of the questionnaire of the International index of erectile function (IIEF) for evaluation of baseline erectile function (EF). The indexes indicate a very high correlation between the items and the questionnaire is consistently reliable. Data were analyzed with Chi-squared (χ²) test using SPSS software. P ≤ 0.05 was considered significant. Results: Out of 3790, ED was found in 2046 (53.98%) of T2DM men. The prevalence of ED was increased with age from 10.5% in men aged 30-39 years to 33.6% in those aged over 60 years (P < 0.001). In comparison with patients with reported diabetes lasting ≤ 5 years (26.4%), the prevalence of ED was less than in those with diabetes of 6-11 years (35.3%) and of 12-30 years (42.5%, P <0.001). ED increased significantly in those who had poor glycemic control. The prevalence of ED in patients with good, fair and poor glycemic control was 22.8%, 42.5% and 47.9% respectively (P = 0.004). Treatment modalities (medical nutrition therapy, oral agents, insulin, and insulin plus oral agents) had significant association with ED and its severity (P < 0.001). Conclusion: Prevalence of ED is very high among T2DM men in Bangladesh and can be reduced the burden by improving glycemic status. Glycemic control, duration of diabetes, treatment modalities, increasing age are associated with ED.

Keywords: erectile dysfunction, diabetes, men, Bangladesh

Procedia PDF Downloads 241
650 Posttraumatic Distress, Hope and Growth in Survivors of Commercial Sexual Exploitation and Sex Trafficking in Nepal

Authors: Rebekah Volgin, Jane Shakespeare-Finch, Ian Shochet

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Commercial sexual exploitation (CSE) and sex trafficking affect between 5000-7000 girls and women in Nepal each year and can have devastating physical and psychological consequences. Much research has documented these effects, however, there is no published longitudinal research that focuses on whether healing and growth outcomes are possible for survivors of CSE and sex trafficking. The narratives of 27 girls and women (13-22 years) were taken at two-time points during participation in a six-week group psychoeducation and art therapy program which was delivered across three NGO’s in Kathmandu, Nepal. These narratives form part of a larger ethnographic project. Thematic analysis of the data was undertaken. Themes emerging from time point 1 were: psychological distress in the form of anxiety and grief over loss of family, psychosomatic symptoms, empathy and compassion, and posttraumatic growth (PTG) in the form of new possibilities, relating to others and personal strength. Posttraumatic growth refers to positive changes in the aftermath of trauma. The themes emerging from time point 2, were: empathy and compassion and PTG (cognitive restructuring, new possibilities, relating to others and personal strength). Alongside the distress that these participants experienced, they also experienced positive outcomes such as empathy and compassion and psychological growth. Future research would advance knowledge by further examining the process of PTG in this population, if the changes observed were lasting, and if so, ways in which PTG can be facilitated or promoted.

Keywords: commercial sexual exploitation, human trafficking, posttraumatic growth, sexual trauma

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649 Allopurinol Prophylactic Therapy in the Prevention of Contrast Induced Nephropathy in High Risk Patients Undergoing Coronary Angiography: A Prospective Randomized Controlled Trial

Authors: Seyed Fakhreddin Hejazi, Leili Iranirad, Mohammad Sadeghi, Mohsen Talebizadeh

Abstract:

Background: Contrast-induced nephropathy (CIN) remains to be a potentially serious complication of radiographic procedures. We performed this clinical trial to assess the preventive effect of allopurinol against CIN in high-risk patients undergoing coronary angiography. Methods: In this prospective randomized controlled trial, 140 patients with at least two risk factors for CIN undergoing coronary angiography were randomly assigned to either the allopurinol group or the control group. Patients in the allopurinol group received 300 mg allopurinol 24 hours before a procedure and intravenous hydration for 12 hours before and after coronary angiography, whereas patients in the control group received intravenous hydration. Serum creatinine (SCr), blood urea nitrogen (BUN) and uric acid were measured before contrast exposure and at 48 hours. CIN was defined as an increase of 25% in serum creatinine (SCr) or >0.5 mg/dl 48 hours after contrast administration. Results: CIN occurred in 11 out of 70 (7.9%) patients in the control group and in 8 out of 70 (5.7%) patients in the allopurinol group. There was no significant difference in the incidence of CIN between the two groups at 48 hours after administering the radiocontrast agent (p = 0.459). However, there were significant differences between the two groups in SCr, BUN, uric acid, and eGFR 48 hours after radiocontrast administration (p < 0.05). Conclusion: Our findings revealed that allopurinol had no substantial efficacy over hydration protocol in high-risk patients for the development of CIN.

Keywords: contrast-induced nephropathy, allopurinol, coronary angiography, contrast agent

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648 Ultrasound Guided Treatment of Carpal Tunnel Syndrome

Authors: Kazem Shakouri, Alireza Pishgahi, Homayoun Sadeghi-bBazargani, Shahla Dareshiri

Abstract:

Introduction: Carpal Tunnel Syndrome has numerous nonsurgical treatments including splint, physical therapy and corticosteroid injections. Aim: The purpose of this study was to evaluate the effectiveness of an ultrasound guided treatment procedure, for individuals with severe carpal tunnel syndrome. Materials and Method: 20 patients with an electrodiagnostic evidence of severe carpal tunnel syndrome were treated by an office-based ultrasound guided procedure (combination of percutaneous needle release of carpal tunnel and corticosteroid injection). Electrodiagnostic (nerve conduction study), clinical (Boston Carpal Tunnel Questionnaire, grip strength) and ultrasonic (median nerve and carpal tunnel cross-sectional area) measurements were recorded at baseline and one month after intervention. Results: Our preliminary data analysis showed that in one month follow up, patients had a significantly smaller cross-sectional area of the median nerve compared to pretreatment values (mean difference 0.06; 95%CI: 0.02-0.1; p < 0.001). In addition, patients had significantly less functional impairment (mean difference 35; 95% CI:28.7-43.4 ; p < 0.001), and an improved hand grip strength in one month follow up (mean difference 5.4; 95%CI: 3.1-7.8; p < 0.001;). There were no significant complications. Conclusion: Patients with severe carpal tunnel syndrome, who are candidates for surgical intervention, can consider office-based ultrasound guided needle release of carpal tunnel as an alternative safe treatment.

Keywords: Carpal Tunnel Syndrome, needle release, pain, ultrasound

Procedia PDF Downloads 217
647 Replica-Exchange Metadynamics Simulations of G-Quadruplex DNA Structures Under Substitution of K+ by Na+ Ions

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure conformed by stacked planes of four base paired guanines (G-quartet). The guanine rich DNA sequences are present in many sites of genomic DNA and can potentially lead to the formation of G-quadruplexes, especially at the 3'-terminus of the human telomeric DNA with many TTAGGG repeats. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to regulate oncogene expression making the G-quadruplex an attractive target for anticancer therapy. Clearly, the G-quadruplex structured in the telomeric DNA is of fundamental importance for rational drug design. In this context, we investigate two G-quadruplex structures, the first follows from the sequence TTAGGG(TTAGGG)3TT (HUT1), and the second from AAAGGG(TTAGGG)3AA (HUT2), both in a K+ solution. We determine the free energy surfaces of the HUT1 and HUT2 structures and investigate their conformations using replica-exchange metadynamics simulations. The carbonyl-carbonyl distances belonging to different guanines residues are selected as the main collective variables to determine the free energy surfaces. The surfaces exhibit two main local minima, compatible with experiments on the conformational transformations of HUT1 and HUT2 under substitution of the K+ ions by the Na+ ions. The conformational transitions are not observed in short MD simulations without the use of the metadynamics approach. The results of this work should be of help to understand the formation and stability of human telomeric G-quadruplex in environments including the presence of K+ and Na+ ions.

Keywords: g-quadruplex, metadynamics, molecular dynamics, replica-exchange

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646 Investigation of Cold Atmospheric Plasma Exposure Protocol on Wound Healing in Diabetic Foot Ulcer

Authors: P. Akbartehrani, M. Khaledi Pour, M. Amini, M. Khani, M. Mohajeri Tehrani, E. Ghasemi, P. Charipoor, B. Shokri

Abstract:

A common problem between diabetic patients is foot ulcers which are chronic and require specialized treatment. Previous studies illustrate that Cold atmospheric plasma (CAP) has beneficial effects on wound healing and infection. Nevertheless, the comparison of different cap exposure protocols in diabetic ulcer wound healing remained to be studied. This study aims to determine the effect of two different exposure protocols on wound healing in diabetic ulcers. A prospective, randomized clinical trial was conducted at two clinics. Diabetic patients with G1 and G2 wanger classification diabetic foot ulcers were divided into two groups of study. One group was treated by the first protocol, which was treating wounds by argon-generated cold atmospheric plasma jet once a week for five weeks in a row. The other group was treated by the second protocol, which was treating wounds every three days for five weeks in a row. The wounds were treated for 40 seconds/cubic centimeter, while the nozzle tip was moved nonlocalized 1 cm above the wounds. A patient with one or more wounds could participate in different groups as wounds were separately randomized, which allow a participant to be treated several times during the study. The study's significant findings were two different reductions rate in wound size, microbial load, and two different healing speeds. This study concludes that CAP therapy by the second protocol yields more effective healing speeds, reduction in wound sizes, and microbial loads of foot ulcers in diabetic patients.

Keywords: wound healing, diabetic ulcers, cold atmospheric plasma, cold argon jet

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645 HRCT of the Chest and the Role of Artificial Intelligence in the Evaluation of Patients with COVID-19

Authors: Parisa Mansour

Abstract:

Introduction: Early diagnosis of coronavirus disease (COVID-19) is extremely important to isolate and treat patients in time, thus preventing the spread of the disease, improving prognosis and reducing mortality. High-resolution computed tomography (HRCT) chest imaging and artificial intelligence (AI)-based analysis of HRCT chest images can play a central role in the treatment of patients with COVID-19. Objective: To investigate different chest HRCT findings in different stages of COVID-19 pneumonia and to evaluate the potential role of artificial intelligence in the quantitative assessment of lung parenchymal involvement in COVID-19 pneumonia. Materials and Methods: This retrospective observational study was conducted between May 1, 2020 and August 13, 2020. The study included 2169 patients with COVID-19 who underwent chest HRCT. HRCT images showed the presence and distribution of lesions such as: ground glass opacity (GGO), compaction, and any special patterns such as septal thickening, inverted halo, mark, etc. HRCT findings of the breast at different stages of the disease (early: andlt) 5 days, intermediate: 6-10 days and late stage: >10 days). A CT severity score (CTSS) was calculated based on the extent of lung involvement on HRCT, which was then correlated with clinical disease severity. Use of artificial intelligence; Analysis of CT pneumonia and quot; An algorithm was used to quantify the extent of pulmonary involvement by calculating the percentage of pulmonary opacity (PO) and gross opacity (PHO). Depending on the type of variables, statistically significant tests such as chi-square, analysis of variance (ANOVA) and post hoc tests were applied when appropriate. Results: Radiological findings were observed in HRCT chest in 1438 patients. A typical pattern of COVID-19 pneumonia, i.e., bilateral peripheral GGO with or without consolidation, was observed in 846 patients. About 294 asymptomatic patients were radiologically positive. Chest HRCT in the early stages of the disease mostly showed GGO. The late stage was indicated by such features as retinal enlargement, thickening and the presence of fibrous bands. Approximately 91.3% of cases with a CTSS = 7 were asymptomatic or clinically mild, while 81.2% of cases with a score = 15 were clinically severe. Mean PO and PHO (30.1 ± 28.0 and 8.4 ± 10.4, respectively) were significantly higher in the clinically severe categories. Conclusion: Because COVID-19 pneumonia progresses rapidly, radiologists and physicians should become familiar with typical TC chest findings to treat patients early, ultimately improving prognosis and reducing mortality. Artificial intelligence can be a valuable tool in treating patients with COVID-19.

Keywords: chest, HRCT, covid-19, artificial intelligence, chest HRCT

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644 The Low-Cost Design and 3D Printing of Structural Knee Orthotics for Athletic Knee Injury Patients

Authors: Alexander Hendricks, Sean Nevin, Clayton Wikoff, Melissa Dougherty, Jacob Orlita, Rafiqul Noorani

Abstract:

Knee orthotics play an important role in aiding in the recovery of those with knee injuries, especially athletes. However, structural knee orthotics is often very expensive, ranging between $300 and $800. The primary reason for this project was to answer the question: can 3D printed orthotics represent a viable and cost-effective alternative to present structural knee orthotics? The primary objective for this research project was to design a knee orthotic for athletes with knee injuries for a low-cost under $100 and evaluate its effectiveness. The initial design for the orthotic was done in SolidWorks, a computer-aided design (CAD) software available at Loyola Marymount University. After this design was completed, finite element analysis (FEA) was utilized to understand how normal stresses placed upon the knee affected the orthotic. The knee orthotic was then adjusted and redesigned to meet a specified factor-of-safety of 3.25 based on the data gathered during FEA and literature sources. Once the FEA was completed and the orthotic was redesigned based from the data gathered, the next step was to move on to 3D-printing the first design of the knee brace. Subsequently, physical therapy movement trials were used to evaluate physical performance. Using the data from these movement trials, the CAD design of the brace was refined to accommodate the design requirements. The final goal of this research means to explore the possibility of replacing high-cost, outsourced knee orthotics with a readily available low-cost alternative.

Keywords: 3D printing, knee orthotics, finite element analysis, design for additive manufacturing

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643 Layer-by-Layer Coated Dexamethasone Microcrystals for Experimental Inflammatory Bowel Disease Therapy

Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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642 Role of Pakistani Physicians in the Pharmacotherapy of Obesity

Authors: Sadia Suri Kashif, Raheeda Fatima, Maqsood Ahmed Khan

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Purpose of the study: The objective of this research was to determine the perception of Pakistani physicians (whether primary care, specialists or residents) in Karachi, being one of the largest and highly populated cities of Pakistan, regarding clinical approaches towards diet, exercise, and therapy in obese patients. This research determines their understanding of obesity and employability of obesity management in their daily practices. Research methodology: This is a questionnaire-based survey. A minimum of 300 questionnaires (N=300) were distributed and filled by practicing physicians in a random selection of medical setups in Karachi. Randomly 246 physicians responded to the survey. The survey tested their views regarding weight management, importance of general awareness and their strategies to control weight. Results: In the first part of survey the physicians responded to almost 66% regarding the seriousness of obesity management with advising diet modification, physical exercise and decreasing calorie intake; 57% failed to employ Body Mass Index and Waist Hip Ratio as weight measurement tools in their daily practice; 50% disagreed on using pharmacotherapy as an option; 67% were not sure about the proper dosage and indication of anti-obesity medication while almost same disagreed on using surgical options for management of obesity; 83.3% physicians agreed on the increased obesity pandemic in Pakistan. Conclusion: The findings indicate that there is a gap between awareness and knowledge among Pakistani practicing physicians regarding pharmacotherapy for obesity. There is a need to frequently update latest guidelines to help manage this condition, which is becoming more prevalent in our country day by day. Physicians should be obligated to use updated knowledge for managing obesity.

Keywords: obesity, physicians, BMI, weight management, obesity awareness

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641 From Transference Love to Self Alienation in the Therapeutic Relationship: A Case Study

Authors: Efi Koutantou

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The foundation of successful therapy is the bond between the psychotherapist and the patient, Psychoanalysis would argue. The present study explores lived experiences of a psychotherapeutic relationship in different moments, initial and final with special reference to the transference love developed through the process. The fight between moments of ‘leaving a self’ behind and following ‘lines of flight’ in the process of creating a new subjectivity and ‘becoming-other’ will be explored. Moments between de-territorialisation – surpassing given constraints such as gender, family and religion, kinship bonds - freeing the space in favor of re-territorialisation – creation of oneself creation of oneself will also be analyzed. The generation of new possibilities of being, new ways of self-actualization for this patient will be discussed. The second part of this study will explore the extent to which this ‘transference love’ results for this specific patient to become ‘the discourse of the other’; it is a desideratum whether the patient finally becomes a subject of his/her own through his/her own self-exploration of new possibilities of existence or becomes alienated within the thought of the therapist. The way in which the patient uses or is (ab)used by the transference love in order to experience and undergo alienation from an ‘authority’ which may or may not sacrifice his/her own thought in favor of satisfying the therapist will be investigated. Finally, from an observer’s perspective and from the analysis of the results of this therapeutic relationship, the counter-transference will also be analyzed, in terms of an attempt of the analyst to relive and satisfy his/her own desires through the life of the analysand. The accession and fall of an idealized self will be analyzed, the turn of the transference love into ‘hate’ will conclude this case study through a lived experience in the therapeutic procedure; a relationship which can be called to be a mixture of a real relationship and remnants from a past object relationship.

Keywords: alienation, authority, counter-transference, hate, transference love

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640 The Impact of Direct and Indirect Pressure Measuring Systems on the Pressure Mapping for the Medical Compression Garments

Authors: Arash M. Shahidi, Tilak Dias, Gayani K. Nandasiri

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While graduated compression is the foundation of treatment and management of many medical complications such as leg ulcer, varicose veins, and lymphedema, monitoring the interface pressure has been conducted using different sensors that operate based on diverse approaches. The variations existed from the pressure readings collected using different interface pressure measurement systems would cause difficulties in taking a decision regarding the compression therapy. It is crucial to acknowledge the differences existing between direct and indirect pressure measurement systems while considering the commercially available systems such as AMI, Picopress and OPM which are under direct measurements systems, and HATRA (BSI), HOSY (RAL-GZ) and FlexiForce which comes under the indirect measurement system. Furthermore, Piezo-resistive sensors (Flexiforce) can measure the changes in resistance corresponding to the applied force on the sensing area. Direct pressure measuring systems are capable of measuring interface pressure on the three-dimensional states, while the indirect pressure measuring systems stretch the fabric in the two-dimensional direction and extrapolate pressure from surface tension measured on the device and neglect the vital factor which is the radius of curvature. In this study, a leg mannequin of known dimensions is selected with a knitted class 3 compression stocking. It has been decided to evaluate the data collected from different available systems (AMI, PicoPress, FlexiForce, and HATRA) and compare the results. The results showed a discrepancy between Hatra, AMI, Picopress, and Flexiforce against the pressure standard used to generate class 3 compression stocking. As predicted a higher pressure value with direct interface measuring systems were monitored against HATRA due to the effect of the radius of curvature.

Keywords: AMI, FlexiForce, graduated compression, HATRA, interface pressure, PicoPress

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639 Inhibitory Effect of Lactic Acid Bacteria on Uropathogenic Escherichia coli-Induced Urinary Tract Infections

Authors: Cheng-Chih Tsai, Yu-Hsuan Liu, Cheng-Ying Ho, Chun-Chin Huang

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The aim of this study evaluated the in vitro and in vivo antimicrobial activity of selected lactic acid bacteria (LAB) against Uropathogenic Escherichia coli (UPEC) for prevention and amelioration of UTIs. We screened LAB strains with antimicrobial effects on UPEC using a well-diffusion assay, bacterial adherence to the uroepithelium cell line SV-HUC-1 (BCRC 60358), and a coculture inhibition assay. The results showed that the 7 LAB strains (Lactobacillus paracasei, L. salivarius, two Pediococcus pentosaceus strains, two L. plantarum strains, and L. crispatus) and the fermented probiotic products produced by these multi-LAB strains exhibited potent zones of inhibition against UPEC. Moreover, the LAB strains and probiotic products adhered strongly to the uroepithelium SV-HUC-1 cell line. The growth of UPEC strains was also markedly inhibited after co-culture with the LAB strains and probiotic products in human urine. In addition, the enhanced levels of IL-6, IL-8 and lactic acid dehydrogenase were significantly decreased by treatments with the LAB strains and probiotic products in UPEC-induced SV-HUC-1 cells. Furthermore, oral administration of probiotic products reduced the number of viable UPEC in the urine of UPEC-challenged BALB/c mice. Taken together, this study demonstrates that probiotic supplementation may be useful as an adjuvant therapy for the treatment of bacterial-induced urinary tract infections.

Keywords: lactic acid bacterium, SV-HUC-1 uroepithelium, urinary tract infection, uropathogenic Escherichia coli, BALB/c mice

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638 Artificial Intelligence in Melanoma Prognosis: A Narrative Review

Authors: Shohreh Ghasemi

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Introduction: Melanoma is a complex disease with various clinical and histopathological features that impact prognosis and treatment decisions. Traditional methods of melanoma prognosis involve manual examination and interpretation of clinical and histopathological data by dermatologists and pathologists. However, the subjective nature of these assessments can lead to inter-observer variability and suboptimal prognostic accuracy. AI, with its ability to analyze vast amounts of data and identify patterns, has emerged as a promising tool for improving melanoma prognosis. Methods: A comprehensive literature search was conducted to identify studies that employed AI techniques for melanoma prognosis. The search included databases such as PubMed and Google Scholar, using keywords such as "artificial intelligence," "melanoma," and "prognosis." Studies published between 2010 and 2022 were considered. The selected articles were critically reviewed, and relevant information was extracted. Results: The review identified various AI methodologies utilized in melanoma prognosis, including machine learning algorithms, deep learning techniques, and computer vision. These techniques have been applied to diverse data sources, such as clinical images, dermoscopy images, histopathological slides, and genetic data. Studies have demonstrated the potential of AI in accurately predicting melanoma prognosis, including survival outcomes, recurrence risk, and response to therapy. AI-based prognostic models have shown comparable or even superior performance compared to traditional methods.

Keywords: artificial intelligence, melanoma, accuracy, prognosis prediction, image analysis, personalized medicine

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637 Doxorubicin and Cyclosporine Loaded PLGA Nanoparticles to Combat Multidrug Resistance

Authors: Senthil Rajan Dharmalingam, Shamala Nadaraju, Srinivasan Ramamurthy

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Doxorubicin is the most widely used anticancer drugs in chemotherapy treatment. However, problems related to the development of multidrug resistance (MDR) and acute cardiotoxicity have led researchers to investigate alternative forms of administering doxorubicin for cancer therapy. Several methods have been attempted to overcome MDR, including the co-administration of a chemosensitizer inhibiting the efflux caused by ATP binding cassette transporters with anticancer drugs, and the bypass of the efflux mechanism. Co encapsulation of doxorubicin (Dox) and cyclosporine A (CSA) into poly (DL-lactide-co-glycolide) nanoparticles was emulsification-solvent evaporation method using polyvinyl alcohol as emulsion stabilizers. The Dox-CSA loaded nanoparticles were evaluated for particle size, zeta potential and PDI by light scattering analysis and thermal characterizations by differential scanning calorimetry (DSC). Loading efficiency (LE %) and in-vitro dissolution samples were evaluated by developed and validated HPLC method. The optimum particle size obtained is 298.6.8±39.4 nm and polydispersity index (PDI) is 0.098±0.092. Zeta potential is found to be -29.9±4.23. Optimum pH to increase Dox LE% was found 7.1 which gave 42.5% and 58.9% increase of LE% for pH 6.6 and pH 8.6 compared respectively. LE% achieved for Dox is 0.07±0.01 % and CSA is 0.09±0.03%. Increased volume of PVA and weight of PLGA shows increase in size of nanoparticles. DSC thermograms showed shift in the melting peak for the nanoparticles compared to Dox and CSA indicating encapsulation of drugs. In conclusion, these preliminary studies showed the feasibility of PLGA nanoparticles to entrap Dox and CSA and require future in-vivo studies to be performed to establish its potential.

Keywords: doxorubicin, cyclosporine, PLGA, nanoparticles

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636 The Efficacy of Vestibular Rehabilitation Therapy for Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Authors: Ammar Aljabri, Alhussain Halawani, Alaa Ashqar, Omar Alageely

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Objective: mild Traumatic Brain Injury (mTBI) or concussion is a common yet undermanaged and underreported condition. This systematic review and meta-analysis aim to determine the efficacy of VRT as a treatment option for mTBI. Method: This review and meta-analysis was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included RCTs and pre-VRT/post-VRT retrospective chart reviews. Records meeting the inclusion criteria were extracted from the following databases: Medline, Embase, and Cochrane Register of Controlled Trials (CENTRAL). Results: Eight articles met the inclusion criteria, and six RCTs were included in the meta-analysis. VRT demonstrated significant improvement in decreasing perceived dizziness at the end of the intervention program, as shown by DHI scores (SMD= -0.33, 95% CI -0.62 to -0.03, p=0.03, I2= 0%). However, no significant reduction in DHI was evident after two months of follow-up (SMD= 0.15, 95% CI -0.23 to 0.52, p=0.44, I2=0%). Quantitative analysis also depicts significant reduction in both VOMS (SMD=-0.40, 95% CI -0.60 to -0.20, p<0.0001, I2=0%) and PCSS (SMD= -0.39, 95% CI -0.71 to -0.07, p=0.02, I2=0%) following the intervention. Lastly, there was no significant difference between intervention groups on BESS scores (SMD= -31, 95% CI -0.71 to 0.10, p=0.14, I2=0%) and return to sport/function (95% CI 0.32 to 30.80, p=0.32, I2=82%). Conclusions: Current evidence on the efficacy of VRT for mTBI is limited. This review and analysis provide evidence that supports the role of VRT in improving perceived symptoms following concussion. There is still a need for high-quality trials evaluating the benefit of VRT using a standardized approach.

Keywords: concussion, traumatic brain injury, vestibular rehabilitation, neurorehabilitation

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635 Denial among Women Living with Cancer: An Exploratory Study to Understand the Consequences of Cancer and the Denial Mechanism

Authors: Judith Partouche-Sebban, Saeedeh Rezaee Vessal

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Because of the rising number of new cases of cancer, especially among women, it is more than essential to better understand how women experience cancer in order to bring them adapted to support and care and enhance their well-being and patient experience. Cancer stands for a traumatic experience in which the diagnosis, its medical treatments, and the related side effects lead to deep physical and psychological changes that may arouse considerable stress and anxiety. In order to reduce these negative emotions, women tend to use various defense mechanisms, among which denial has been defined as the most frequent mechanism used by breast cancer patients. This study aims to better understand the consequences of the experience of cancer and their link with the adoption of a denial strategy. The empirical research was done among female cancer survivors in France. Since the topic of this study is relatively unexplored, a qualitative methodology and open-ended interviews were employed. In total, 25 semi-directive interviews were conducted with a female with different cancers, different stages of treatment, and different ages. A systematic inductive method was performed to analyze data. The content analysis enabled to highlight three different denial-related behaviors among women with cancer, which serve a self-protective function. First, women who expressed high levels of anxiety confessed they tended to completely deny the existence of their cancer immediately after the diagnosis of their illness. These women mainly exhibit many fears and a deep distrust toward the medical context and professionals. This coping mechanism is defined by the patient as being unconscious. Second, other women deliberately decided to deny partial information about their cancer, whether this information is related to the stages of the illness, the emotional consequences, or the behavioral consequences of the illness. These women use this strategy as a way to avoid the reality of the illness and its impact on the different aspects of their life as if cancer does not exist. Third, some women tend to reinterpret and give meaning to their cancer as a way to reduce its impact on their life. To this end, they may use magical thinking or positive reframing, or reinterpretation. Because denial may lead to delays in medical treatments, this topic deserves a deep investigation, especially in the context of oncology. As denial is defined as a specific defense mechanism, this study contributes to the existing literature in service marketing which focuses on emotions and emotional regulation in healthcare services which is a crucial issue. Moreover, this study has several managerial implications for healthcare professionals who interact with patients in order to implement better care and support for the patients.

Keywords: cancer, coping mechanisms, denial, healthcare services

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634 New Targets Promoting Oncolytic Virotherapy

Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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633 The Immediate Effects of Thrust Manipulation for Thoracic Hyperkyphosis

Authors: Betul Taspinar, Eda O. Okur, Ismail Saracoglu, Ismail Okur, Ferruh Taspinar

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Thoracic hyperkyphosis, is a well-known spinal phenomenon, refers to an excessive curvature (> 40 degrees) of the thoracic spine. The aim of this study was to explore the effectiveness of thrust manipulation on thoracic spine alignment. 31 young adults with hyperkyphosis diagnosed with Spinal Mouse® device were randomly assigned either thrust manipulation group (n=16, 11 female, 5 male) or sham manipulation group (n=15, 8 female, 7 male). Thrust and sham manipulations were performed by a blinded physiotherapist who is a certificated expert in musculoskeletal physiotherapy. Thoracic kyphosis degree was measured after the interventions via Spinal Mouse®. Wilcoxon test was used to analyse the data obtained before and after the manipulation for each group, whereas Mann-Whitney U test was used to compare the groups. The mean of baseline thoracic kyphosis degrees in thrust and sham groups were 50.69 o ± 7.73 and 48.27o ± 6.43, respectively. There was no statistically significant difference between groups in terms of initial thoracic kyphosis degrees (p=0.51). After the interventions, the mean of thoracic kyphosis degree in thrust and sham groups were measured as 44.06o ± 6.99 and 48.93o ± 6.57 respectively (p=0.03). There was no statistically significant difference between before and after interventions in sham group (p=0.33), while the mean of thoracic kyphosis degree in thrust group decreased significantly (p=0.00). Thrust manipulation can attenuate thoracic hyperkyphosis immediately in young adults by not using placebo effect. Manipulation might provide accurate proprioceptive (sensory) input to the spine joints and reduce kyphosis by restoring normal segment mobility. Therefore thoracic manipulation might be included in the physiotherapy programs to treat hyperkyphosis.

Keywords: hyperkyphosis, manual therapy, spinal mouse, physiotherapy

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632 Disseminated Tuberculosis: Experience from Tuberculosis Directly Observed Treatment Short Course Center at a Tertiary Care Teaching Hospital in the Philippines

Authors: Jamie R. Chua, Christina Irene D. Mejia, Regina P. Berba

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Disseminated tuberculosis is an infectious disease caused by Mycobacterium tuberculosis involving two or more non-contiguous sites identified through bacteriologic confirmation or clinical diagnosis. Over the five year period included in the study, the UP-PGH TB DOTS clinic had total of 3,967 referrals, and the prevalence of disseminated tuberculosis is 1% (68/3967). The mean age was 33.9 years (range 19-64 years) with a male: female ratio of 1:1. 67% (52 patients) had no predisposing comorbid illness or immune disorder. The most common presenting symptoms were abdominal pain (19%), back pain (13%), abdominal enlargement (11%) and mass (10.2%). Anemia, leukocytosis, hypoalbuminemia, and high-normal serum calcium were common biochemical and hematologic findings. Around 36% (25) of patients were diagnosed clinically with disseminated tuberculosis despite lacking bacteriologic evidence of multi-organ involvement. The lungs (86%) is still the most commonly involved site, followed by intestinal (22%), vertebral/Pott’s (27%), and pelvic/genital (19%). The mean time from presentation to initiation of therapy was 22 days (SD 32.7). Only 18 patients (29.3%) were properly recorded to have been referred to local TB DOTs facilities. Of the 68 patients, only 16% (11 patients) continued follow-up at PGH, and all had documented treatment completion. Treatment outcomes of the remaining were unknown. Due to the variety of involved sites, a high index of suspicion is required. Knowledge on clinical features, common radiographic findings, and histopathologic characteristics of disseminated TB is important as bacteriologic evidence of infection is not always apparent.

Keywords: disseminated tuberculosis, Mycobacterium tuberculosis, miliary tuberculosis, tuberculosis

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631 The Role of Androgens in Prediction of Success in Smoking Cessation in Women

Authors: Michaela Dušková, Kateřina Šimůnková, Martin Hill, Hana Hruškovičová, Hana Pospíšilová, Eva Králíková, Luboslav Stárka

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Smoking represents the most widespread substance dependence in the world. Several studies show the nicotine's ability to alter women hormonal homeostasis. Women smokers have higher testosterone and lower estradiol levels throughout life compared to non-smoker women. We monitored the effect of smoking discontinuation on steroid spectrum with 40 premenopausal and 60 postmenopausal women smokers. These women had been examined before they discontinued smoking and also after 6, 12, 24, and 48 weeks of abstinence. At each examination, blood was collected to determine steroid spectrum (measured by GC-MS), LH, FSH, and SHBG (measured by IRMA). Repeated measures ANOVA model was used for evaluation of the data. The study has been approved by the local Ethics Committee. Given the small number of premenopausal women who endured not to smoke, only the first 6 week period data could be analyzed. A slight increase in androgens after the smoking discontinuation occurred. In postmenopausal women, an increase in testosterone, dihydrotestosterone, dehydroepiandrosterone, and other androgens occurred, too. Nicotine replacement therapy, weight changes, and age does not play any role in the androgen level increase. The higher androgens levels correlated with failure in smoking cessation. Women smokers have higher androgen levels, which might play a role in smoking dependence development. Women successful in smoking cessation, compared to the non-successful ones, have lower androgen levels initially and also after smoking discontinuation. The question is what androgen levels women have before they start smoking.

Keywords: addiction, smoking, cessation, androgens

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630 Deep Learning Approach for Chronic Kidney Disease Complications

Authors: Mario Isaza-Ruget, Claudia C. Colmenares-Mejia, Nancy Yomayusa, Camilo A. González, Andres Cely, Jossie Murcia

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Quantification of risks associated with complications development from chronic kidney disease (CKD) through accurate survival models can help with patient management. A retrospective cohort that included patients diagnosed with CKD from a primary care program and followed up between 2013 and 2018 was carried out. Time-dependent and static covariates associated with demographic, clinical, and laboratory factors were included. Deep Learning (DL) survival analyzes were developed for three CKD outcomes: CKD stage progression, >25% decrease in Estimated Glomerular Filtration Rate (eGFR), and Renal Replacement Therapy (RRT). Models were evaluated and compared with Random Survival Forest (RSF) based on concordance index (C-index) metric. 2.143 patients were included. Two models were developed for each outcome, Deep Neural Network (DNN) model reported C-index=0.9867 for CKD stage progression; C-index=0.9905 for reduction in eGFR; C-index=0.9867 for RRT. Regarding the RSF model, C-index=0.6650 was reached for CKD stage progression; decreased eGFR C-index=0.6759; RRT C-index=0.8926. DNN models applied in survival analysis context with considerations of longitudinal covariates at the start of follow-up can predict renal stage progression, a significant decrease in eGFR and RRT. The success of these survival models lies in the appropriate definition of survival times and the analysis of covariates, especially those that vary over time.

Keywords: artificial intelligence, chronic kidney disease, deep neural networks, survival analysis

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629 The Interaction between Blood-Brain Barrier and the Cerebral Lymphatics Proposes Therapeutic Method for Alzheimer’S Disease

Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina

Abstract:

The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033

Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music

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628 A Pilot Study of Robot Reminiscence in Dementia Care

Authors: Ryuji Yamazaki, Masahiro Kochi, Weiran Zhu, Hiroko Kase

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In care for older adults, behavioral and psychological symptoms of dementia (BPSD) like agitation and aggression are distressing for patients and their caretakers, often resulting in premature institutionalization with increased costs of care. To improve mood and mitigate symptoms, as a non-pharmaceutical approach, emotion-oriented therapy like reminiscence work is adopted in face-to-face communication. Telecommunication support is expected to be provided by robotic media as a bridge for digital divide for those with dementia and facilitate social interaction both verbally and nonverbally. The purpose of this case study is to explore the conditions in which robotic media can effectively attract attention from older adults with dementia and promote their well-being. As a pilot study, we introduced the pillow-phone Hugvie®, a huggable humanly shaped communication medium to five residents with dementia at a care facility, to investigate how the following conditions work for the elderly when they use the medium; 1) no sound, 2) radio, non-interactive, 3) daily conversation, and 4) reminiscence work. As a result, under condition 4, reminiscence work, the five participants kept concentration in interacting with the medium for a longer duration than other conditions. In condition 4, they also showed larger amount of utterances than under other conditions. These results indicate that providing topics related to personal histories through robotic media could affect communication positively and should, therefore, be further investigated. In addition, the issue of ethical implications by using persuasive technology that affects emotions and behaviors of older adults is also discussed.

Keywords: BPSD, reminiscence, tactile telecommunication, utterances

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627 Comparative Stem Cells Therapy for Regeneration of Liver Fibrosis

Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

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Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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626 A research of Dhuta Characteristic Poems Associated with Traditional Serpent Medicine (From Galkalla and Ratmalavetia Vedaparampara)

Authors: M. S. M. Anjalee Umesha Bandara

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Hela Veda Shastra is a science that is an endowment from generation to generation. There is also an individualistic science and indigenous practice of traditional herbs. There are many effective cures for snakes, fractures, head cancer, cuts, lunatics, reflexology, etc. Hela physicians who rescued them from infections caused by snakes have recognized poems to remember the medicines they used to cure the patients. Due to the harmony of the Hela Osu and Hela Knowledge poetry collection, it has become easy for the juniors of the Hela Veda generation to gain medical knowledge. It is a research problem whether it is possible to arrive at a correct conclusion about the patient form of the snake information thread through the existing Dhuta characteristics of Hela Serpa Vedakam. This research was done with the assumption that snake venom can be successfully treated according to its characteristics. In this research, two generations related to the Ratmalavatiya Vedaparamparava and the Vannihatpattu of the Kalla Veda generation have been identified as Veda Paramparas who treat and created Dutha Kavya, including the form of the Serpent Dasthana. They have collected ancient books, documents and interviews related to qualitative research on snake disease treatment. In addition, collecting data by referring to books related to Hela medicine. The ancient indigenous lineage methods that are superior to modern Western science's snake therapy should save the Hela's amazing wealth of wisdom for the future, leaving aside the selfishness of keeping the teaching to themselves.

Keywords: snake venom medicine, vedic genealogy, Dhuta characteristic, snake

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625 Histone Deacetylases Inhibitor - Valproic Acid Sensitizes Human Melanoma Cells for alkylating agent and PARP inhibitor

Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

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624 Prevalence of Extended Spectrum of Beta Lactamase Producers among Gram Negative Uropathogens

Authors: Y. V. S. Annapurna, V. V. Lakshmi

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Urinary tract infection (UTI) is one of the most common infectious diseases at the community level with a high rate of morbidity . This is further augmented by increase in the number of resistant and multi resistant strains of bacteria particularly by those producing Extended spectrum of beta lactamases. The present study was aimed at analysis of antibiograms of E.coli and Klebsiella sp causing urinary tract infections. Between November 2011 and April 2013, a total of 1120 urine samples were analyzed,. Antibiotic sensitivity testing was done with 542(48%) isolates of E.coli and 446(39%) of Klebsiella sp using the standard disc diffusion method against eleven commonly used antibiotics .Organisms showed high susceptibility to Amikacin and Netilimicin and low susceptibility to Cephalosporins. MAR index was calculated for the multidrug resistant strains. Maximum MAR index detected among the isolates was 0.9. Phenotypic identification for ESBL production was confirmed by double disk synergy test (DDST) according to CLSI guidelines. Plasmid profile of the isolates was carried out using alkaline hydrolysis method. Agarose-gel electrophoresis showed presence of high-molecular weight plasmid DNA among the ESBL strains. This study emphasizes the importance of indiscriminate use of antibiotics which if discontinued, in turn would prevent further development of bacterial drug resistance. For this, a proper knowledge of susceptibility pattern of uropathogens is necessary before prescribing empirical antibiotic therapy and it should be made mandatory.

Keywords: escherichia coli, extended spectrum of beta lactamase, Klebsiella spp, Uropathogens

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