Search results for: dual antiplatelet therapy (DAPT)
Commenced in January 2007
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Edition: International
Paper Count: 2660

Search results for: dual antiplatelet therapy (DAPT)

410 Role of Imaging in Alzheimer's Disease Trials: Impact on Trial Planning, Patient Recruitment and Retention

Authors: Kohkan Shamsi

Abstract:

Background: MRI and PET are now extensively utilized in Alzheimer's disease (AD) trials for patient eligibility, efficacy assessment, and safety evaluations but including imaging in AD trials impacts site selection process, patient recruitment, and patient retention. Methods: PET/MRI are performed at baseline and at multiple follow-up timepoints. This requires prospective site imaging qualification, evaluation of phantom data, training and continuous monitoring of machines for acquisition of standardized and consistent data. This also requires prospective patient/caregiver training as patients must go to multiple facilities for imaging examinations. We will share our experience form one of the largest AD programs. Lesson learned: Many neurological diseases have a similar presentation as AD or could confound the assessment of drug therapy. The inclusion of wrong patients has ethical and legal issues, and data could be excluded from the analysis. Centralized eligibility evaluation read process will be discussed. Amyloid related imaging abnormalities (ARIA) were observed in amyloid-β trials. FDA recommended regular monitoring of ARIA. Our experience in ARIA evaluations in large phase III study at > 350 sites will be presented. Efficacy evaluation: MRI is utilized to evaluate various volumes of the brain. FDG PET or amyloid PET agents has been used in AD trials. We will share our experience about site and central independent reads. Imaging logistic issues that need to be handled in the planning phase will also be discussed as it can impact patient compliance thereby increasing missing data and affecting study results. Conclusion: imaging must be prospectively planned to include standardizing imaging methodologies, site selection process and selecting assessment criteria. Training should be transparently conducted and documented. Prospective patient/caregiver awareness of imaging requirement is essential for patient compliance and reduction in missing imaging data.

Keywords: Alzheimer's disease, ARIA, MRI, PET, patient recruitment, retention

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409 Rooibos Extract Antioxidants: In vitro Models to Assess Their Bioavailability

Authors: Ntokozo Dambuza, Maryna Van De Venter, Trevor Koekemoer

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Oxidative stress contributes to the pathogenesis of many diseases and consequently antioxidant therapy has attracted much attention as a potential therapeutic strategy. Regardless of the quantities ingested, antioxidants need to reach the diseased tissues at concentrations sufficient to combat oxidative stress. Bioavailability is thus a defining criterion for the therapeutic efficacy of antioxidants. In addition, therapeutic antioxidants must possess biologically relevant characteristics which can target the specific molecular mechanisms responsible for disease related oxidative stress. While many chemical antioxidant assays are available to quantify antioxidant capacity, they relate poorly to the biological environment and provide no information as to the bioavailability. The present comparative study thus aims to characterise green and fermented rooibos extracts, well recognized for their exceptional antioxidant capacity, in terms of antioxidant bioavailability and efficacy in a disease relevant cellular setting. Chinese green tea antioxidant activity was also evaluated. Chemical antioxidant assays (FRAP, DPPH and ORAC) confirmed the potent antioxidant capacity of both green and fermented rooibos, with green rooibos possessing antioxidant activity superior to that of fermented rooibos and Chinese green tea. Bioavailability was assessed using the PAMPA assay and the results indicate that green and fermented rooibos have a permeation coefficient of 5.7 x 10-6 and 6.9 x 10-6 cm/s, respectively. Chinese green tea permeability coefficient was 8.5 x 10-6 cm/s. These values were comparable to those of rifampicin, which is known to have a high permeability across intestinal epithelium with a permeability coefficient of 5 x 10 -6 cm/s. To assess the antioxidant efficacy in a cellular context, U937 and red blood cells were pre-treated with rooibos and Chinese green tea extracts in the presence of a dye DCFH-DA and then exposed to oxidative stress. Green rooibos exhibited highest activity with an IC50 value of 29 μg/ml and 70 μg/ml, when U937 and red blood cells were exposed oxidative stress, respectively. Fermented rooibos and Chinese green tea had IC50 values of 61 μg/ml and 57 μg/ml for U937, respectively, and 221 μg/ml and 405 μg/ml for red blood cells, respectively. These results indicate that fermented and green rooibos extracts were able to permeate the U937 cells and red blood cell membrane and inhibited oxidation of DCFH-DA to a fluorescent DCF within the cells.

Keywords: rooibos, antioxidants, permeability, bioavailability

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408 Therapeutic Nihilism: Challenging Aging Diseases in Cameroon

Authors: Chick Loveline Ayoh Epse Ndi

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Our cultural stance has deep implications for the psychological and physical well-being of the old. Cameroon is still rooted on the traditional belief that stipulates that; the aged are best catered for in the family setting where the children and grandchildren are supposed to give in return for services invested on them by the former. This is why up till date, there are no “Rest Homes” or “Convalescent hospitals” despite the rising challenges faced by the aged in this context. Beside the special measure set aside to cater for the aged, such as “Rest Homes” for the healthy, “Convalescent hospitals” are created set to cater for the health of the aged in the Western context with other facilities such as geriatric units. The health care practitioners are aware of aging diseases and have trained human resources like Gerontologists to cater for the aged and aging diseases. Meanwhile, in Africa and Cameroon in particular, such infrastructural and human resources are still to be considered in the health care system. It can be assumed that the aged and aging diseases are still to be considered in the health care system in this context. This is why we talk of therapeutic nihilism, where the aged are mixed up with other categories of patients with no special attention given to them. This qualitative study carried out in the Yaounde, the capital city of Cameroon, with their best referent hospitals, reveal that; the aged and aging diseases are still a myth in this context. Data collected in both private and public health institutions show that there is only one public institution in Cameroon that has a geriatric unit with no specialists. Patients who aretreated in this unit are considered as aged with terminal diseases that need palliative care and not intensive care. Cameroon is still lacking in terms of health care to the aged and ageing diseases. Like other patients, the aged are treated with a lot of laxity and no value. There is an emergency to create special health care units for geriatrics and and train gerontologist. Mentally or physically ill aged faced medical rational with psychodynamic treatment considered as waste of time. The aged are less likely to be regarded salvageable when they enter a hospital in serious conditions due to the lack of specialists and geriatric units for them. The implication of this study is to sensitization the stake holders for an urgent need to extend special care units for the aged and aging diseases in this context.

Keywords: challeng, therapy, agtng, diseases cameroon

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407 Oral Versus Iontophoresis Nonsteroidal Anti-Inflammatory Drugs in Tennis Elbow

Authors: Moustafa Ali Elwan, Ibrahim Salem Abdelrafa, Ashraf Moharm

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed oral and topical drugs worldwide. Moreover, NSAIDs are responsible for most of all adverse drug reactions. For several decades, there are numerous attempts to use the cutaneous layers as a gate into the body for the local delivery of the therapeutic agent. Transdermal drug delivery is a validated technology contributing significantly to global pharmaceutical care. Transdermal Drug Delivery systems can be improved by using therapeutic agents. Moreover, Transdermal Drug Delivery systems can be improved by using chemical enhancers like ultrasound or iontophoresis. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. Objective: to compare the drug administration by ‘iontophoresis’ versus the oral rule. Methods: This study was conducted at the Faculty of Physical Therapy, Modern University for technology and information, Cairo, Egypt, on 20 participants (8 female & 12 male) who complained of tennis elbow. Their mean age was (25.45 ± 3.98) years, and all participants were assessed in many aspects: Pain threshold was assessed by algometer. Range of motion was assessed by electro goniometer, and isometric strength was assessed by a portable hand-held dynamometer. Then Participants were randomly assigned into two groups: group A was treated with oral NSAID (diclofenac) while group B was treated via administration of NSAIDs (diclofenac) via an iontophoresis device. All the participants were subjected to blood samples analysis in both pre-administration of the drug and post-administration of the drug for 24 hours (sample/every 6 hours). Results: The results demonstrated that there was a significant improvement in group b, “iontophoresis NSAIDs group,” more than in group B,” oral NSAIDs group,” in all measurements ‘ pain threshold, strength, and range of motion. Also, the iontophoresis method shows higher maximum plasma concentrations (Cmax) and concentration-time curves than the oral method.

Keywords: diclofenac, iontophoresis, NSAIDs, oral, tennis elbow

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406 Expert Opinions about Barriers to Physical Activity among Ghanaian Adults with Type 2 Diabetes Mellitus: A Qualitative Descriptive Study

Authors: Mohammed Amin, Debra Kerr, Yacoba Atiase, Andrea Driscoll

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Background: Physical activity (PA) is a major component of diabetes self-care management; although this is often stressed to patients, many adults with Type 2 Diabetes Mellitus (T2DM)lead sedentary lifestyles, and barriers exist for uptake of PA. Aim: To explore opinions of healthcare professionals about barriers to PA for adults with T2DM in Ghana. Methods: This qualitative descriptive study included 13healthcare professionals (3 Physiotherapists, 3 exercise physiologists, 3 nurses, and 4 physicians) who provide care to individuals with T2DM in Ghana. Data was collected by semi-structured interviews. The social cognitive theory guided the design of the interview schedule. Data was analysed using thematic analysis. Results: Four main themeswere identified: 1) Individual-related factors, 2) Interpersonal factors, 3) Environment-related factors, and 4) Health system-related factors. Fear of injury, existing co-morbidities, and lack of time make it difficult for people with T2DM to engage in PA. Lack of family support, fear of social ridicule, and cultural beliefs prevent uptake of PA. Poorly designed community spaces, including safe walkways and lack of exercise facilities, inhibit PA participation. Few physical therapists and physical therapy centres exist to support PA participation among people with T2DM. Some nurses and doctors lack adequate knowledge to deliver proper PA education to clients, thereby making clients lack the needed support. Conclusion: Adults with T2DM may be restricted from partaking in PA arising from personal and external factors. This study has identified that barriers to exercise need consideration when designing PA programs that aim to improve health outcomes for people with T2DM in Ghana.

Keywords: type 2 diabetes, physical activity, exercise, ghana, qualitative, barriers

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405 Development of Methotrexate Nanostructured Lipid Carriers for Topical Treatment of Psoriasis: Optimization, Evaluation, and in vitro Studies

Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

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404 Understanding Childhood Sexual Abuse and Its Association with Psychological Traumatization, Re-Traumatization, and Shame in Adult South Asian Women: A Scoping Review

Authors: Manisha Massey, Mariette Berndsen, Helen McLaren

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The existing body of literature concerning the incidence, prevalence, and experiences of childhood sexual abuse (CSA) lacked cultural inclusivity, primarily reflecting Euro-centric perspectives. This study investigated and reviewed the existing literature to understand the experiences of women of color from South Asia, addressing the gap in understanding how culture and diversity impact CSA. While individualist cultures emphasize autonomy, collectivist societies prioritize interdependence. South Asia's diverse intersections, including gender, caste, religion, and class, have intensified child sexual exploitation, challenging assumed homogeneity and safety. Additionally, the power exploitation in the space of abuse and grooming supplementing with the prevalence of honor violence makes disclosures of sexual abuse for children daunting and unsafe in these cultures. This scoping review examined the connection between CSA, psychological trauma, re-traumatization, and shame among adult South Asian women from India, Pakistan, and Bangladesh. Despite distinct borders, these countries share historical, linguistic, and traditional ties. Following PRISMA guidelines, the review employed thematic analysis. Findings underscored cultural factors' influence on CSA incidence, help-seeking barriers, and treatment challenges. The pivotal role of shame (sharam) and honor (izzat) in disclosure and healing processes was highlighted. The study emphasized the need for culturally sensitive interventions while noting limited literature on re-traumatisation. Incorporating a culturally informed perspective, this research aims to decolonize trauma therapy by contributing to the CSA discourse, shedding light on its intricate interaction with trauma, shame, and healing among South Asian women.

Keywords: Childhood sexual abuse, decolonizing psychology, trauma, re-trauma, shame

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403 The Effect of the COVID-19 Pandemic on Frailty, Sarcopenia, and Other Comorbidities in Liver Transplant Candidates: A Retrospective Review of an Extensive Frailty Database

Authors: Sohaib Raza, Parvez Mantry

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Frailty is a multi-system impairment associated with stressors such as age, disease, and invasive surgical procedures. This multi-system impairment can lead to increased post-transplant mortality and functional decline. Additionally, the prevalence and/or severity of frailty increases when patient pre-habilitation is unsatisfactory or lacking. We conducted a retrospective study to examine whether the COVID-19 Pandemic, and subsequent lack of patient access to pre-habilitation and physical therapy resources, led to an increase in the prevalence and severity of frailty, sarcopenia, and other comorbidities including diabetes, hypertension, and COPD. Secondarily, we examined the correlation between patient survival rate and liver frailty index as well as muscle wasting/sarcopenia. Data were analyzed in order to correlate variables associated with these parameters. Three hundred sixty-nine liver transplant candidates at Methodist Dallas Medical Center were administered pre-transplant frailty assessments, which consisted of chair stands, grip strength, and position balance time. A frailty score less than 3.2 indicated a robust condition, a score from 3.3 to 4.4 indicated a pre-frail condition, and a score greater than 4.5 indicated a frail condition. Greater than 50 percent of patients were found to have muscle wasting in the COVID-19 period (March 13, 2020 to February 28, 2022), an increase of 16.5 percent from the pre-COVID period (April 1st, 2018 to March 12, 2020). Additionally, sarcopenia was associated with a two-fold increase in patient mortality rate. Furthermore, high liver frailty index scores were associated with increased patient mortality. However, there was no significant difference in liver frailty index or number of comorbidities between patients in the two cohorts. Conclusion: The COVID-19 Pandemic exacerbated sarcopenia-related muscle wasting in liver transplant candidates, and patient survival rate was directly correlated with liver frailty index score and the presence of sarcopenia.

Keywords: frailty, sarcopenia, covid-19, patient mortality, pre-habilitation, liver transplant candidates

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402 Comparison of 18F-FDG and 11C-Methionine PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma

Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

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Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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401 Effect of Blood Sugar Levels on Short Term and Working Memory Status in Type 2 Diabetics

Authors: Mythri G., Manjunath ML, Girish Babu M., Shireen Swaliha Quadri

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Background: The increase in diabetes among the elderly is of concern because in addition to the wide range of traditional diabetes complications, evidence has been growing that diabetes is associated with increased risk of cognitive decline. Aims and Objectives: To find out if there is any association between blood sugar levels and short-term and working memory status in patients of type 2 diabetes. Materials and Methods: The study was carried out in 200 individuals aged between 40-65 years consisting of 100 diagnosed cases of Type 2 Diabetes Mellitus and 100 non-diabetics from OPD of Mc Gann Hospital, Shivamogga. Rye’s Auditory Verbal Learning Test, Verbal Fluency Test and Visual Reproduction Test, Working Digit Span Test and Validation Span Test were used to assess short-term and working memory. Fasting and Post Prandial blood sugar levels were estimated. Statistical analysis was done using SPSS 21. Results: Memory test scores of type 2 diabetics were significantly reduced (p < 0.001) when compared to the memory scores of age and gender matched non-diabetics. Fasting blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.837), VFT (r=-0.888), VRT(r=-0.787), WDST (r=-0.795) and VST (r=-0.943). Post- Prandial blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.922), VFT (r=-0.848), VRT(r=-0.707),WDST (r=-0.729) and VST (r=-0.880) Memory scores in all 5 tests were found to be negatively correlated with the FBS and PPBS levels in diabetic patients (p < 0.001). Conclusion: The decreased memory status in diabetic patients may be due to many factors like hyperglycemia, vascular disease, insulin resistance, amyloid deposition and also some of the factor combine to produce additive effects like, type of diabetes, co-morbidities, age of onset, duration of the disease and type of therapy. These observed effects of blood sugar levels of diabetics on memory status are of potential clinical importance because even mild cognitive impairment could interfere with todays’ activities.

Keywords: diabetes, cognition, diabetes, HRV, respiratory medicine

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400 Effectiveness of Project Grit in Building Resilience among At-Risk Adolescents: A Case Study

Authors: Narash Narasimman, Calvin Leong Jia Jun, Raksha Karthik, Paul Englert

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Background: Project Grit, a 12-week youth resilience program implemented by Impart and Spartans Boxing Club, aimed to help at-risk adolescents develop resilience through psychoeducation and mental health techniques for dealing with everyday stressors and adversity. The programme consists of two parts-1.5 hours of group therapy followed by 1 hour of boxing. Due to the novelty of the study, 6 male participants, aged 13 to 18, were recruited to participate in the study. Aim: This case study aims to examine the effectiveness of Project Grit in building resilience among at-risk adolescents. Methods: A case study design was employed to capture the complexity and uniqueness of the intervention, without oversimplifying or generalizing it. A 15-year-old male participant with a history of behavioural challenges, delinquency and gang involvement was selected for the study. Teacher, parent and child versions of the Strengths and Difficulties Questionnaire (SDQ) were administered to the facilitators, parents and participants respectively before and after the programme. Relevant themes from the qualitative interviews will be discussed. Results: Scores from all raters revealed improvements in most domains of the SDQ. Total difficulties scores across all raters improved from “very high” to “close to average”. High interrater reliability was observed (κ= .81). The participant reported learning methods to effectively deal with his everyday concerns using healthy coping strategies, developing a supportive social network, and building on his self efficacy. Themes from the subject’s report concurred with the improvement in SDQ scores. Conclusions: The findings suggest that Project Grit is a promising intervention for promoting resilience among at-risk adolescents. The teleological behaviourism framework and the combination of sports engagement and future orientation may be particularly effective in fostering resilience among this population. Further studies need to be conducted with a larger sample size to further validate the effectiveness of Project Grit.

Keywords: resilience, project grit, adolescents, at-risk, boxing, future orientation

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399 Autophagy Suppresses Bladder Tumor Formation in a Mouse Orthotopic Bladder Tumor Formation Model

Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

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Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

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398 Polymeric Micelles Based on Block Copolymer α-Tocopherol Succinate-g-Carboxymethyl Chitosan for Tamoxifen Delivery

Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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397 A Brief Trauma Treatment Program for Survivors of Trauma: A Single-Case Design

Authors: Duane Booysen, Ashraf Kagee

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There is a high prevalence of violent crime and trauma exposure in South African society. Considering the prevalence of continuous violent crimes and traumatization in South Africa, the public mental health sector is required to combat the burgeoning effect of traumatic stress in South Africa. Trauma counselors, especially, provide important mental health services at primary health care to persons affected by traumatic events. Therefore, the evaluation and implementation of evidence-based trauma therapies is essential at a primary health care level in treating traumatic stress. A single-case design was used to evaluate the treatment effect of a Brief Trauma Treatment Programme treating persons who present with symptoms of posttraumatic stress disorder at a primary care trauma centre in Cape Town, South Africa. The sample consisted of six adult participants who presented with symptoms of posttraumatic stress and were assessed at baseline, during treatment, post-intervention and at 3-month follow. All participants received six sessions of trauma therapy. Assessment measures included the posttraumatic stress disorder symptom scale interviews for Diagnostic and Statistical Manual fifth edition (DSM5), the posttraumatic disorder checklist for DSM5, Beck Depression Inventory and Beck Anxiety Inventory. Results demonstrate that participants had noticeable reduced symptoms for traumatic stress, anxiety and depression despite living in contexts of violent crime and trauma. In conclusion, the article critically reflects on the need to evaluate and implement evidence-based treatments for the South African context, and how evidence-based treatments are used in developing socio-economic and cultural diverse contexts with continuous levels of violence and traumatization.

Keywords: psychological interventions, public mental health, traumatic stress, single-case design

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396 Calibration of Mini TEPC and Measurement of Lineal Energy in a Mixed Radiation Field Produced by Neutrons

Authors: I. C. Cho, W. H. Wen, H. Y. Tsai, T. C. Chao, C. J. Tung

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Tissue-equivalent proportional counter (TEPC) is a useful instrument used to measure radiation single-event energy depositions in a subcellular target volume. The quantity of measurements is the microdosimetric lineal energy, which determines the relative biological effectiveness, RBE, for radiation therapy or the radiation-weighting factor, WR, for radiation protection. TEPC is generally used in a mixed radiation field, where each component radiation has its own RBE or WR value. To reduce the pile-up effect during radiotherapy measurements, a miniature TEPC (mini TEPC) with cavity size in the order of 1 mm may be required. In the present work, a homemade mini TEPC with a cylindrical cavity of 1 mm in both the diameter and the height was constructed to measure the lineal energy spectrum of a mixed radiation field with high- and low-LET radiations. Instead of using external radiation beams to penetrate the detector wall, mixed radiation fields were produced by the interactions of neutrons with TEPC walls that contained small plugs of different materials, i.e. Li, B, A150, Cd and N. In all measurements, mini TEPC was placed at the beam port of the Tsing Hua Open-pool Reactor (THOR). Measurements were performed using the propane-based tissue-equivalent gas mixture, i.e. 55% C3H8, 39.6% CO2 and 5.4% N2 by partial pressures. The gas pressure of 422 torr was applied for the simulation of a 1 m diameter biological site. The calibration of mini TEPC was performed using two marking points in the lineal energy spectrum, i.e. proton edge and electron edge. Measured spectra revealed high lineal energy (> 100 keV/m) peaks due to neutron-capture products, medium lineal energy (10 – 100 keV/m) peaks from hydrogen-recoil protons, and low lineal energy (< 10 keV/m) peaks of reactor photons. For cases of Li and B plugs, the high lineal energy peaks were quite prominent. The medium lineal energy peaks were in the decreasing order of Li, Cd, N, A150, and B. The low lineal energy peaks were smaller compared to other peaks. This study demonstrated that internally produced mixed radiations from the interactions of neutrons with different plugs in the TEPC wall provided a useful approach for TEPC measurements of lineal energies.

Keywords: TEPC, lineal energy, microdosimetry, radiation quality

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395 Development of Building Information Modeling in Property Industry: Beginning with Building Information Modeling Construction

Authors: B. Godefroy, D. Beladjine, K. Beddiar

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In France, construction BIM actors commonly evoke the BIM gains for exploitation by integrating of the life cycle of a building. The standardization of level 7 of development would achieve this stage of the digital model. The householders include local public authorities, social landlords, public institutions (health and education), enterprises, facilities management companies. They have a dual role: owner and manager of their housing complex. In a context of financial constraint, the BIM of exploitation aims to control costs, make long-term investment choices, renew the portfolio and enable environmental standards to be met. It assumes a knowledge of the existing buildings, marked by its size and complexity. The information sought must be synthetic and structured, it concerns, in general, a real estate complex. We conducted a study with professionals about their concerns and ways to use it to see how householders could benefit from this development. To obtain results, we had in mind the recurring interrogation of the project management, on the needs of the operators, we tested the following stages: 1) Inculcate a minimal culture of BIM with multidisciplinary teams of the operator then by business, 2) Learn by BIM tools, the adaptation of their trade in operations, 3) Understand the place and creation of a graphic and technical database management system, determine the components of its library so their needs, 4) Identify the cross-functional interventions of its managers by business (operations, technical, information system, purchasing and legal aspects), 5) Set an internal protocol and define the BIM impact in their digital strategy. In addition, continuity of management by the integration of construction models in the operation phase raises the question of interoperability in the control of the production of IFC files in the operator’s proprietary format and the export and import processes, a solution rivaled by the traditional method of vectorization of paper plans. Companies that digitize housing complex and those in FM produce a file IFC, directly, according to their needs without recourse to the model of construction, they produce models business for the exploitation. They standardize components, equipment that are useful for coding. We observed the consequences resulting from the use of the BIM in the property industry and, made the following observations: a) The value of data prevail over the graphics, 3D is little used b) The owner must, through his organization, promote the feedback of technical management information during the design phase c) The operator's reflection on outsourcing concerns the acquisition of its information system and these services, observing the risks and costs related to their internal or external developments. This study allows us to highlight: i) The need for an internal organization of operators prior to a response to the construction management ii) The evolution towards automated methods for creating models dedicated to the exploitation, a specialization would be required iii) A review of the communication of the project management, management continuity not articulating around his building model, it must take into account the environment of the operator and reflect on its scope of action.

Keywords: information system, interoperability, models for exploitation, property industry

Procedia PDF Downloads 134
394 Increasing Prevalence of Multi-Allergen Sensitivities in Patients with Allergic Rhinitis and Asthma in Eastern India

Authors: Sujoy Khan

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There is a rising concern with increasing allergies affecting both adults and children in rural and urban India. Recent report on adults in a densely populated North Indian city showed sensitization rates for house dust mite, parthenium, and cockroach at 60%, 40% and 18.75% that is now comparable to allergy prevalence in cities in the United States. Data from patients residing in the eastern part of India is scarce. A retrospective study (over 2 years) was done on patients with allergic rhinitis and asthma where allergen-specific IgE levels were measured to see the aero-allergen sensitization pattern in a large metropolitan city of East India. Total IgE and allergen-specific IgE levels were measured using ImmunoCAP (Phadia 100, Thermo Fisher Scientific, Sweden) using region-specific aeroallergens: Dermatophagoides pteronyssinus (d1); Dermatophagoides farinae (d2); cockroach (i206); grass pollen mix (gx2) consisted of Cynodon dactylon, Lolium perenne, Phleum pratense, Poa pratensis, Sorghum halepense, Paspalum notatum; tree pollen mix (tx3) consisted of Juniperus sabinoides, Quercus alba, Ulmus americana, Populus deltoides, Prosopis juliflora; food mix 1 (fx1) consisted of Peanut, Hazel nut, Brazil nut, Almond, Coconut; mould mix (mx1) consisted of Penicillium chrysogenum, Cladosporium herbarum, Aspergillus fumigatus, Alternaria alternate; animal dander mix (ex1) consisted of cat, dog, cow and horse dander; and weed mix (wx1) consists of Ambrosia elatior, Artemisia vulgaris, Plantago lanceolata, Chenopodium album, Salsola kali, following manufacturer’s instructions. As the IgE levels were not uniformly distributed, median values were used to represent the data. 92 patients with allergic rhinitis and asthma (united airways disease) were studied over 2 years including 21 children (age < 12 years) who had total IgE and allergen-specific IgE levels measured. The median IgE level was higher in 2016 than in 2015 with 60% of patients (adults and children) being sensitized to house dust mite (dual positivity for Dermatophagoides pteronyssinus and farinae). Of 11 children in 2015, whose total IgE ranged from 16.5 to >5000 kU/L, 36% of children were polysensitized (≥4 allergens), and 55% were sensitized to dust mites. Of 10 children in 2016, total IgE levels ranged from 37.5 to 2628 kU/L, and 20% were polysensitized with 60% sensitized to dust mites. Mould sensitivity was 10% in both of the years in the children studied. A consistent finding was that ragweed sensitization (molecular homology to Parthenium hysterophorus) appeared to be increasing across all age groups, and throughout the year, as reported previously by us where 25% of patients were sensitized. In the study sample overall, sensitizations to dust mite, cockroach, and parthenium were important risks in our patients with moderate to severe asthma that reinforces the importance of controlling indoor exposure to these allergens. Sensitizations to dust mite, cockroach and parthenium allergens are important predictors of asthma morbidity not only among children but also among adults in Eastern India.

Keywords: aAeroallergens, asthma, dust mite, parthenium, rhinitis

Procedia PDF Downloads 184
393 Rheumatoid Arthritis, Periodontitis and the Subgingival Microbiome: A Circular Relationship

Authors: Isabel Lopez-Oliva, Akshay Paropkari, Shweta Saraswat, Stefan Serban, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa Grant, Purnima Kumar

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Objective: We aimed to explicate the role of the subgingival microbiome in the causal link between rheumatoid arthritis (RA) and periodontitis (PD). Methods: Subjects with/without RA and with/without PD were randomized for treatment with scaling and root planing (SRP) or oral hygiene instructions. Subgingival biofilm, gingival crevicular fluid, and serum were collected at baseline and at 3- and 6-months post-operatively. Correlations were generated between 72 million 16S rDNA sequences, immuno-inflammatory mediators, circulating antibodies to oral microbial antigens, serum inflammatory molecules, and clinical metrics of RA. The dynamics of inter-microbial and host-microbial interactions were modeled using differential network analysis. Results: RA superseded periodontitis as a determinant of microbial composition, and DAS28 score superseded the severity of periodontitis as a driver of microbial assemblages (p=0.001, ANOSIM). RA subjects evidenced higher serum anti-PPAD (p=0.0013), anti-Pg-enolase (p=0.0031), anti-RPP3, anti- Pg-OMP and anti- Pi-OMP (p=0.001) antibodies than non-RA controls (with and without periodontitis). Following SRP, bacterial networks anchored by IL-1b, IL-4, IL-6, IL-10, IL-13, MIP-1b, and PDGF-b underwent ≥5-fold higher rewiring; and serum antibodies to microbial antigens decreased significantly. Conclusions: Our data suggest a circular relationship between RA and PD, beginning with an RA-influenced dysbiosis within the healthy subgingival microbiome that leads to exaggerated local inflammation in periodontitis and circulating antibodies to periodontal pathogens and positive correlation between severity of periodontitis and RA activity. Periodontal therapy restores host-microbial homeostasis, reduces local inflammation, and decreases circulating microbial antigens. Our data highlights the importance of integrating periodontal care into the management of RA patients.

Keywords: rheumatoid arthritis, periodontal, subgingival, DNA sequence analysis, oral microbiome

Procedia PDF Downloads 90
392 Posterior Circulation Ischemic Strokes in Olympic and Division 1 Wrestlers

Authors: Christen Kutz

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Objective: The aim of this study is to review a case series of 4 high-level Olympic and Division 1 wrestlers who experienced debilitating posterior circulation ischemic strokes during or after a competitive wrestling event and to identify risk factors, etiology and outcomes of stroke in young, healthy elite wrestlers. Background: Stroke occurs in one in 10,000 people under age 64. In young adults, the most common causes of stroke are cardiac embolism, hypercoagulable state, and vasculopathy. One-third of these strokes occur in young, fit individuals. There is little published literature about ischemic strokes that occur in wrestlers. Based on the nature of wrestling, the risk of injury or dissection to neurovascular structures may be a possible theory, but very few case reports exist. Methodology: 4 wrestlers under the age of 44 with a known history of ischemic stroke participated in individual interviews either in person or virtually. Each of the wrestlers provided their demographic information, wrestling background, clinical presentation at the time of stroke, imaging results, identification of potential risk factors, acute treatment and recovery. Results: 3 white male Division 1 wrestlers (2 Lehigh University, 1 Lock Haven University) and 1 black male 2008 Olympian experienced posterior circulation strokes. Case #1 felt a “pop” while wrestling (lateral medullary infarct, possible vertebral artery dissection); Case #2 awoke with severe vertigo, sweating, and vomiting after wrestling the previous day (left cerebellar infarct, (+) protein S deficiency); Case #3 severe vertigo, ataxia, and sensation of impending doom after wrestling earlier that week (left cerebellar infarct, hypoplastic left vertebral artery (+) anti-cardiolipin antibodies). Case #4 severe dizziness, confusion (left cerebellar stroke, vertebral artery dissection, small PFO). Conclusion: 3 wrestlers were started on anti-platelet therapy, risk factors were modified, and returned to their sport. 1 wrestler was placed on anti-coagulation and retired from competition.

Keywords: stroke, wrestling, Olympic, posterior circulation

Procedia PDF Downloads 61
391 The Effect of Nutrition Education on Adherence to the Mediterranean Diet and Sustainable Healthy Eating Behaviors in University Students

Authors: Tuba Tekin, Nurcan Baglam, Emine Dincer

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This study aimed to examine the effects of nutrition education received by university students on sustainable healthy eating behaviors and adherence to the Mediterranean diet. The 2nd, 3rd, and 4th-grade university students studying at the Faculty of Health Sciences, Nutrition and Dietetics, Midwifery, Nursing, Physical Therapy, and Rehabilitation departments of universities in Turkey were included in the study. Students' adherence to the Mediterranean diet was evaluated using the Mediterranean Diet Adherence Scale, and their sustainable and healthy eating behaviors were evaluated using the Sustainable and Healthy Eating Behaviors Scale. In addition, the body weight and height of the students were measured by the researchers, and the Body Mass Index (BMI) value was calculated. A total of 181 students, 85 of whom were studying in the Department of Nutrition and Dietetics and 96 of whom were educated in other departments, were included in the study. 75.7% of the students in the sample are female, while 24.3% are male. The average body weight of the students was 61.17±10.87 kg, and the average BMI was 22.04±3.40 kg/m2. While the mean score of the Mediterranean Diet Adherence Scale was 6.72±1.84, in the evaluation of adherence to the Mediterranean diet, it was determined that 25.4% of the students had poor adherence and 66.9% needed improvement. When the adherence scores of students who received and did not receive nutrition education were compared, it was discovered that the students who received nutrition education had a higher score (p<0.05). Students who received nutrition education had a higher total score on the Sustainable and Healthy Eating Behaviors scale (p<0.05). A moderately positive correlation was found between the Sustainable and Healthy Eating Behaviors scale total score and the Mediterranean Diet Adherence scores (p<0.05). As a result of the linear regression analysis, it was revealed that a 1-unit increase in the Mediterranean diet adherence score would result in a 1.3-point increase in the total score of the Sustainable and Healthy Eating Behaviors scale. Sustainable and healthy diets are important for improving and developing health and the prevention of diseases. The Mediterranean diet is defined as a sustainable diet model. The findings revealed the relationship between the Mediterranean diet and sustainable nutrition and showed that nutrition education increased knowledge and awareness about sustainable nutrition and increased adherence to the Mediterranean diet. For this reason, courses or seminars on sustainable nutrition can be organized during educational periods.

Keywords: healthy eating, Mediterranean diet, nutrition education, sustainable nutrition

Procedia PDF Downloads 68
390 Synergistic Anti-Proliferation Effect of PLK-1 Inhibitor and Livistona Chinensis Fruit Extracts on Lung Adenocarcinoma A549 Cells

Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

Procedia PDF Downloads 130
389 Targeting the EphA2 Receptor Tyrosine Kinases in Melanoma Cancer, both in Humans and Dogs

Authors: Shabnam Abdi, Behzad Toosi

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Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.

Keywords: ephA2, targeting, melanoma, human, canine

Procedia PDF Downloads 48
388 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 361
387 Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients

Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

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Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: diabetes, T2DM, SLC47A1, Pakistan, polymorphism

Procedia PDF Downloads 142
386 Factors Affecting the Fear of Insulin Injection and Finger Punching in Individuals Diagnosed with Diabetes

Authors: Gaye Demi̇rtaş Adli

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Research: It was conducted to determine the factors affecting the fear of self-injection and self-pricking of fingers of diabetic individuals.The study was conducted as a cross-sectional, relation-seeking, and descriptive study. The study was conducted on 122 patients who had just started insulin therapy. Data were obtained through The Descriptive Patient Form, The Diabetic Self-Injection, and the Fear of Testing Questionnaire Form (D-FISQ). Descriptive statistical methods used in the evaluation of data are the Mann-Whitney U test, Kruskal-Wallis H test, and the Spearman correlation. The factors affecting the scale scores were evaluated with multiple linear regression analysis. The value of P<0.05 was considered statistically significant. Study group: 56.6% of the patients are male patients. Fear of self-injection (injection), fear of self-testing (test), and total fear (total) scores of women were found to be statistically higher than men (p<0.001). Age, gender, and pain experience were important variables that affected patients' fear of injections. With a one-unit increase in age, the injection fear score decreased by 0.13 points, and the mean injection fear score of women was 2.11 points higher than that of men. It was determined that the patient's age, gender, living with whom, and blood donation history were important variables affecting the fear of self-testing. It is seen that the fear test score decreases by 0.18 points with an increase in age by one unit, and the fear test scores of women compared to men are on average 3,358 points, the fear test scores of those living alone are 4,711 points compared to those living with family members, and the fear test scores of those who do not donate blood are 2,572 compared to those who donate blood score, it was determined that those with more pain experience were 3,156 points higher on average than those with less fear of injection. As a result, it was seen that the most important factors affecting the fear of insulin injection and finger punching in individuals with diabetes were age, gender, pain experience, living with whom, and blood donation history.

Keywords: diabetes, needle phobia, fear of injection, insulin injection

Procedia PDF Downloads 56
385 Healing (in) Relationship: The Theory and Practice of Inner-Outer Peacebuilding in North-Western India

Authors: Josie Gardner

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The overall intention of this research is to reimagine peacebuilding in both in theory and practical application in light of the shortcomings and unsustainability of the current peacebuilding paradigm. These limitations are identified here as an overly rational-material approach to peacebuilding that neglects the inner dimension of peace for a fragmented rather than holistic model, and that espouses a conflict and violence-centric approach to peacebuilding. In counter, this presentation is purposed to investigate the dynamics of inner and outer peace as a holistic, complex system towards ‘inner-outer’ peacebuilding. This paper draws from primary research in the protracted conflict context of north-western India (Jammu, Kashmir & Ladakh) as a case study. This presentation has two central aims. First, to introduce the process of inner (psycho-spiritual) peacebuilding, which has thus far been neglected by mainstream and orthodox literature. Second, to examine why inner peacebuilding is essential for realising sustainable peace on a broader scale as outer (socio-political) peace and to better understand how the inner and outer dynamics of peace relate and affect one another. To these ends, Josephine (the researcher/author/presenter) partnered with Yakjah Reconciliation and Development Network to implement a series of action-oriented workshops and retreats centred around healing, reconciliation, leadership, and personal development for the dual purpose of collaboratively generating data, theory, and insights, as well as providing the youth leaders with an experiential, transformative experience. The research team created and used a novel methodological approach called Mapping Ritual Ecologies, which draws from Participatory Action Research and Digital Ethnography to form a collaborative research model with a group of 20 youth co-researchers who are emerging youth peace leaders in Kashmir, Jammu, and Ladakh. This research found significant intra- and inter-personal shifts towards an experience of inner peace through inner peacebuilding activities. Moreover, this process of inner peacebuilding affected their families and communities through interpersonal healing and peace leadership in an inside-out process of change. These insights have generated rich insights and have supported emerging theories about the dynamics between inner and outer peace, power, justice, and collective healing. This presentation argues that the largely neglected dimension of inner (psycho-spiritual) peacebuilding is imperative for broader socio-political (outer) change. Changing structures of oppression, injustice, and violence—i.e. structures of separation—requires individual, interpersonal, and collective healing. While this presentation primarily examines and advocates for inside-out peacebuilding and social justice, it will also touch upon the effect of systems of separation on the inner condition and human experience. This research reimagines peacebuilding as a holistic inner-outer approach. This offers an alternative path forward those weaves together self-actualisation and social justice. While contextualised within north-western India with a small case study population, the findings speak also to other conflict contexts as well as our global peacebuilding and social justice milieu.

Keywords: holistic, inner peacebuilding, psycho-spiritual, systems youth

Procedia PDF Downloads 99
384 Development of Composition and Technology of Vincristine Nanoparticles Using High-Molecular Carbohydrates of Plant Origin

Authors: L. Ebralidze, A. Tsertsvadze, D. Berashvili, A. Bakuridze

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Current cancer therapy strategies are based on surgery, radiotherapy and chemotherapy. The problems associated with chemotherapy are one of the biggest challenges for clinical medicine. These include: low specificity, broad spectrum of side effects, toxicity and development of cellular resistance. Therefore, anti-cance drugs need to be develop urgently. Particularly, in order to increase efficiency of anti-cancer drugs and reduce their side effects, scientists work on formulation of nano-drugs. The objective of this study was to develop composition and technology of vincristine nanoparticles using high-molecular carbohydrates of plant origin. Plant polysacharides, particularly, soy bean seed polysaccharides, flaxseed polysaccharides, citrus pectin, gum arabic, sodium alginate were used as objects. Based on biopharmaceutical research, vincristine containing nanoparticle formulations were prepared. High-energy emulsification and solvent evaporation methods were used for preparation of nanosystems. Polysorbat 80, polysorbat 60, sodium dodecyl sulfate, glycerol, polyvinyl alcohol were used in formulation as emulsifying agent and stabilizer of the system. The ratio of API and polysacharides, also the type of the stabilizing and emulsifying agents are very effective on the particle size of the final product. The influence of preparation technology, type and concentration of stabilizing agents on the properties of nanoparticles were evaluated. For the next stage of research, nanosystems were characterized. Physiochemical characterization of nanoparticles: their size, shape, distribution was performed using Atomic force microscope and Scanning electron microscope. The present study explored the possibility of production of NPs using plant polysaccharides. Optimal ratio of active pharmaceutical ingredient and plant polysacharids, the best stabilizer and emulsifying agent was determined. The average range of nanoparticles size and shape was visualized by SEM.

Keywords: nanoparticles, target delivery, natural high molecule carbohydrates, surfactants

Procedia PDF Downloads 261
383 Upon Poly(2-Hydroxyethyl Methacrylate-Co-3, 9-Divinyl-2, 4, 8, 10-Tetraoxaspiro (5.5) Undecane) as Polymer Matrix Ensuring Intramolecular Strategies for Further Coupling Applications

Authors: Aurica P. Chiriac, Vera Balan, Mihai Asandulesa, Elena Butnaru, Nita Tudorachi, Elena Stoleru, Loredana E. Nita, Iordana Neamtu, Alina Diaconu, Liliana Mititelu-Tartau

Abstract:

The interest for studying ‘smart’ materials is entirely justified and in this context were realized investigations on poly(2-hydroxyethylmethacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane), which is a macromolecular compound with sensibility at pH and temperature, gel formation capacity, binding properties, amphilicity, good oxidative and thermal stability. Physico-chemical characteristics in terms of the molecular weight, temperature-sensitive abilities and thermal stability, as well rheological, dielectric and spectroscopic properties were evaluated in correlation with further coupling capabilities. Differential scanning calorimetry investigation indicated Tg at 36.6 °C and a melting point at Tm=72.8°C, for the studied copolymer, and up to 200oC two exothermic processes (at 99.7°C and 148.8°C) were registered with losing weight of about 4 %, respective 19.27%, which indicate just processes of thermal decomposition (and not phenomena of thermal transition) owing to scission of the functional groups and breakage of the macromolecular chains. At the same time, the rheological studies (rotational tests) confirmed the non-Newtonian shear-thinning fluid behavior of the copolymer solution. The dielectric properties of the copolymer have been evaluated in order to investigate the relaxation processes and two relaxation processes under Tg value were registered and attributed to localized motions of polar groups from side chain macromolecules, or parts of them, without disturbing the main chains. According to literature and confirmed as well by our investigations, β-relaxation is assigned with the rotation of the ester side group and the γ-relaxation corresponds to the rotation of hydroxy- methyl side groups. The fluorescence spectroscopy confirmed the copolymer structure, the spiroacetal moiety getting an axial conformation, more stable, with lower energy, able for specific interactions with molecules from environment, phenomena underlined by different shapes of the emission spectra of the copolymer. Also, the copolymer was used as template for indomethacin incorporation as model drug, and the biocompatible character of the complex was confirmed. The release behavior of the bioactive compound was dependent by the copolymer matrix composition, the increasing of 3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane comonomer amount attenuating the drug release. At the same time, the in vivo studies did not show significant differences of leucocyte formula elements, GOT, GPT and LDH levels, nor immune parameters (OC, PC, and BC) between control mice group and groups treated just with copolymer samples, with or without drug, data attesting the biocompatibility of the polymer samples. The investigation of the physico-chemical characteristics of poly(2-hydrxyethyl methacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) in terms of temperature-sensitive abilities, rheological and dielectrical properties, are bringing useful information for further specific use of this polymeric compound.

Keywords: bioapplications, dielectric and spectroscopic properties, dual sensitivity at pH and temperature, smart materials

Procedia PDF Downloads 274
382 In vitro Modeling of Aniridia-Related Keratopathy by the Use of Crispr/Cas9 on Limbal Epithelial Cells and Rescue

Authors: Daniel Aberdam

Abstract:

Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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381 Generation of High-Quality Synthetic CT Images from Cone Beam CT Images Using A.I. Based Generative Networks

Authors: Heeba A. Gurku

Abstract:

Introduction: Cone Beam CT(CBCT) images play an integral part in proper patient positioning in cancer patients undergoing radiation therapy treatment. But these images are low in quality. The purpose of this study is to generate high-quality synthetic CT images from CBCT using generative models. Material and Methods: This study utilized two datasets from The Cancer Imaging Archive (TCIA) 1) Lung cancer dataset of 20 patients (with full view CBCT images) and 2) Pancreatic cancer dataset of 40 patients (only 27 patients having limited view images were included in the study). Cycle Generative Adversarial Networks (GAN) and its variant Attention Guided Generative Adversarial Networks (AGGAN) models were used to generate the synthetic CTs. Models were evaluated by visual evaluation and on four metrics, Structural Similarity Index Measure (SSIM), Peak Signal Noise Ratio (PSNR) Mean Absolute Error (MAE) and Root Mean Square Error (RMSE), to compare the synthetic CT and original CT images. Results: For pancreatic dataset with limited view CBCT images, our study showed that in Cycle GAN model, MAE, RMSE, PSNR improved from 12.57to 8.49, 20.94 to 15.29 and 21.85 to 24.63, respectively but structural similarity only marginally increased from 0.78 to 0.79. Similar, results were achieved with AGGAN with no improvement over Cycle GAN. However, for lung dataset with full view CBCT images Cycle GAN was able to reduce MAE significantly from 89.44 to 15.11 and AGGAN was able to reduce it to 19.77. Similarly, RMSE was also decreased from 92.68 to 23.50 in Cycle GAN and to 29.02 in AGGAN. SSIM and PSNR also improved significantly from 0.17 to 0.59 and from 8.81 to 21.06 in Cycle GAN respectively while in AGGAN SSIM increased to 0.52 and PSNR increased to 19.31. In both datasets, GAN models were able to reduce artifacts, reduce noise, have better resolution, and better contrast enhancement. Conclusion and Recommendation: Both Cycle GAN and AGGAN were significantly able to reduce MAE, RMSE and PSNR in both datasets. However, full view lung dataset showed more improvement in SSIM and image quality than limited view pancreatic dataset.

Keywords: CT images, CBCT images, cycle GAN, AGGAN

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