Search results for: anticancer drug delivery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3651

Search results for: anticancer drug delivery

2871 Effectual Role of Local Level Partnership Schemes in Affordable Housing Delivery

Authors: Hala S. Mekawy

Abstract:

Affordable housing delivery for low and lower middle income families is a prominent problem in many developing countries; governments alone are unable to address this challenge due to diverse financial and regulatory constraints, and the private sector's contribution is rare and assists only middle-income households even when institutional and legal reforms are conducted to persuade it to go down market. Also, the market-enabling policy measures advocated by the World Bank since the early nineties have been strongly criticized and proven to be inappropriate to developing country contexts, where it is highly unlikely that the formal private sector can reach low income population. In addition to governments and private developers, affordable housing delivery systems involve an intricate network of relationships between diverse ranges of actors. Collaboration between them was proven to be vital, and hence, an approach towards partnership schemes for affordable housing delivery has emerged. The basic premise of this paper is that addressing housing affordability challenges in Egypt demands direct public support, as markets and market actors alone would never succeed in delivering decent affordable housing to low and lower middle income groups. It argues that this support would ideally be through local level partnership schemes, with a leading decentralized local government role, and partners being identified according to specific local conditions. It attempts to identify major attributes that would ensure the fulfilment of the goals of such schemes in the Egyptian context. This is based upon evidence from diversified worldwide experiences, in addition to the main outcomes of a questionnaire that was conducted to specialists and chief actors in the field.

Keywords: affordable housing, partnership schemes, housing, urban environments

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2870 Screening for Non-hallucinogenic Neuroplastogens as Drug Candidates for the Treatment of Anxiety, Depression, and Posttraumatic Stress Disorder

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

Abstract:

With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 127
2869 pH and Thermo-Sensitive Nanogels for Anti-Cancer Therapy

Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar

Abstract:

The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.

Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU

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2868 Coumestrol Induced Apoptosis in Breast Cancer MCF-7 Cells via Redox Cycling of Copper and ROS Generation: Implications of Copper Chelation Strategy in Cancer Treatment

Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem

Abstract:

Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.

Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling

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2867 The Underestimation of Cultural Risk in the Execution of Megaprojects

Authors: Alan Walsh, Peter Walker, Michael Ellis

Abstract:

There is a real danger that both practitioners and researchers considering risks associated with megaprojects ignore or underestimate the impacts of cultural risk. The paper investigates the potential impacts of a failure to achieve cultural unity between the principal actors executing a megaproject. The principle relationships include the relationships between the principle Contractors and the project stakeholders or the project stakeholders and their principle advisors, Western Consultants. This study confirms that cultural dissonance between these parties can delay or disrupt the megaproject execution and examines why cultural issues should be prioritized as a significant risk factor in megaproject delivery. This paper addresses the practical impacts and potential mitigation measures, which may reduce cultural dissonance for a megaproject's delivery. This information is retrieved from on-going case studies in live infrastructure megaprojects in Europe and the Middle East's GCC states, from Western Consultants' perspective. The collaborating researchers each have at least 30 years of construction experience and are engaged in architecture, project management and contracts management, dealing with megaprojects in Europe or the GCC. After examining the cultural interfaces they have observed during the execution of megaprojects, they conclude that globally, culture significantly influences their efficient delivery. The study finds that cultural risk is ever-present, where different nationalities co-manage megaprojects and that cultural conflict poses a real threat to the timely delivery of megaprojects. The study indicates that the higher the cultural distance between the principal actors, the more pronounced the risk, with the risk of cultural dissonance more prominent in GCC megaprojects. The findings support a more culturally aware and cohesive team approach and recommend cross-cultural training to mitigate the effects of cultural disparity.

Keywords: cultural risk underestimation, cultural distance, megaproject characteristics, megaproject execution

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2866 Need of Medicines Information OPD in Tertiary Health Care Settings: A Cross Sectional Study

Authors: Swanand Pathak, Kiran R. Giri, Reena R. Giri, Kamlesh Palandurkar, Sangita Totade, Rajesh Jha, S. S. Patel

Abstract:

Background: Population burden, illiteracy, availability of few doctors for larger group of population leads to many unanswered questions left in a patient’s mind. Incomplete information results into noncompliance, therapeutic failure, and adverse drug reactions (ADR). It is very important to establish a system which will provide noncommercial, independent, unbiased source of medicine information. Medicines Info OPD is a concept and step towards safe and appropriate use of medicines. Objective: (1) to assess the present status of knowledge about the medicines in the patients and its correlation with education; (2) to assess the medicine information dispensing modalities, their use and sufficiency from the patients view point; (3) to assess the overall need for Medicines Information OPD in present scenario. Materials and Methods: A pre-validated questionnaire based study was conducted amongst 500 patients of tertiary health care hospital. The questionnaire consisted of specific questions regarding understanding of prescription, knowledge about adverse drug reaction, view about self-medication and opinion regarding the need of Medicines Info OPD. Results: Significantly large proportion of patients opined that doctors do not have sufficient time in current Indian healthcare to explain the prescription and they are not aware of adverse drug reactions, expiry date or use the package inserts etc. Conclusion: Clinically relevant, up to date, user specific, independent, objective and unbiased Medicines Info OPD is essential for appropriate drug use and can help in a big way to common public to address many problems faced by them.

Keywords: information, prescription, unbiased, clinically relevant

Procedia PDF Downloads 438
2865 Therapeutic Drug Monitoring by Dried Blood Spot and LC-MS/MS: Novel Application to Carbamazepine and Its Metabolite in Paediatric Population

Authors: Giancarlo La Marca, Engy Shokry, Fabio Villanelli

Abstract:

Epilepsy is one of the most common neurological disorders, with an estimated prevalence of 50 million people worldwide. Twenty five percent of the epilepsy population is represented in children under the age of 15 years. For antiepileptic drugs (AED), there is a poor correlation between plasma concentration and dose especially in children. This was attributed to greater pharmacokinetic variability than adults. Hence, therapeutic drug monitoring (TDM) is recommended in controlling toxicity while drug exposure is maintained. Carbamazepine (CBZ) is a first-line AED and the drug of first choice in trigeminal neuralgia. CBZ is metabolised in the liver into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent. This develops the need for an assay able to monitor the levels of both CBZ and CBZE. The aim of the present study was to develop and validate a LC-MS/MS method for simultaneous quantification of CBZ and CBZE in dried blood spots (DBS). DBS technique overcomes many logistical problems, ethical issues and technical challenges faced by classical plasma sampling. LC-MS/MS has been regarded as superior technique over immunoassays and HPLC/UV methods owing to its better specificity and sensitivity, lack of interference or matrix effects. Our method combines advantages of DBS technique and LC-MS/MS in clinical practice. The extraction process was done using methanol-water-formic acid (80:20:0.1, v/v/v). The chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50 mL/min. The method was linear over the range 1-40 mg/L and 0.25-20 mg/L for CBZ and CBZE respectively. The limit of quantification was 1.00 mg/L and 0.25 mg/L for CBZ and CBZE, respectively. Intra-day and inter-day assay precisions were found to be less than 6.5% and 11.8%. An evaluation of DBS technique was performed, including effect of extraction solvent, spot homogeneity and stability in DBS. Results from a comparison with the plasma assay are also presented. The novelty of the present work lies in being the first to quantify CBZ and its metabolite from only one 3.2 mm DBS disc finger-prick sample (3.3-3.4 µl blood) by LC-MS/MS in a 10 min. chromatographic run.

Keywords: carbamazepine, carbamazepine-10, 11-epoxide, dried blood spots, LC-MS/MS, therapeutic drug monitoring

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2864 Telomerase, a Biomarker in Oral Cancer Cell Proliferation and Tool for Its Prevention at Initial Stage

Authors: Shaista Suhail

Abstract:

As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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2863 Non-Medical Prescription and Other Drug Use in Relation to Mental Health and World Beliefs: A Study of College Students

Authors: Sarah P. Wuebbolt, Ashlee N. Sawyer-Mays

Abstract:

Non-medical prescription and other drug (NMPOD) use has been a significant public health issue for the last few decades, with problematic use increasing among university students more recently. The current study focused on associations between NMPOD use and mental health, well-being, and world beliefs among young adults. Young adults (N=513) completed online questionnaires assessing stress, demographic characteristics, self-esteem, NMPOD use, coping mechanisms, and anxiety. A substantial portion of participants reported using cannabis (48.5%, n=249), while smaller portions of participants reported using stimulants (26.7%, n = 137), sedatives (17.2%, n=88), opioids (10.8%, n=55), and hallucinogens (14.4%, n=74). Five hierarchical logistic regressions were performed to determine the independent relationships between mental health, well-being, and world belief factors and NMPOD use for the five classes of substances. After controlling for demographic factors (age, gender, race/ethnicity, sexual orientation, and religious affiliation), depression was associated with increased non-medical stimulant, opioid, and cannabis use; coping self-efficacy was associated with increased hallucinogen use, and attendance of worship services was associated with decreased non-medical cannabis and hallucinogen use. Results suggest that depression was strongly associated with non-medical stimulant, opioid, and cannabis use, and attendance of worship services was protective against cannabis and hallucinogen use. To the best of our knowledge, this is one of the first studies to investigate the relationships between mental health, well-being, world beliefs, and NMPOD use among young adults. The present study illuminates future targets for intervention, such as increased access to mental health diagnosis and treatment and the exploration of the roles of religion and shared community in the prevention of drug use among young adults.

Keywords: cannabis, mental health, non-medical prescription and other drug use, world beliefs

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2862 Response Surface Methodology to Obtain Disopyramide Phosphate Loaded Controlled Release Ethyl Cellulose Microspheres

Authors: Krutika K. Sawant, Anil Solanki

Abstract:

The present study deals with the preparation and optimization of ethyl cellulose-containing disopyramide phosphate loaded microspheres using solvent evaporation technique. A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for optimizing the preparation microspheres. The drug:polymer ratio (X1) and speed of the stirrer (X2) were chosen as the independent variables. The cumulative release of the drug at a different time (2, 6, 10, 14, and 18 hr) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable at time 10 hr. Based on the results of multiple linear regression analysis and F statistics, it was concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. The drug release pattern fitted the Higuchi model well. The data of a selected batch were subjected to an optimization study using Box-Behnken design, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

Keywords: disopyramide phosphate, ethyl cellulose, microspheres, controlled release, Box-Behnken design, factorial design

Procedia PDF Downloads 447
2861 Bioresorbable Medicament-Eluting Grommet Tube for Otitis Media with Effusion

Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

Abstract:

Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

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2860 Opioid Administration on Patients Hospitalized in the Emergency Department

Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani

Abstract:

Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.

Keywords: numerical rating score, opioid, pain, emergency department

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2859 Efficacy and Safety of Sublingual Sufentanil for the Management of Acute Pain

Authors: Neil Singla, Derek Muse, Karen DiDonato, Pamela Palmer

Abstract:

Introduction: Pain is the most common reason people visit emergency rooms. Studies indicate however, that Emergency Department (ED) physicians often do not provide adequate analgesia to their patients as a result of gender and age bias, opiophobia and insufficient knowledge of and formal training in acute pain management. Novel classes of analgesics have recently been introduced, but many patients suffer from acute pain in settings where the availability of intravenous (IV) access may be limited, so there remains a clinical need for rapid-acting, potent analgesics that do not require an invasive route of delivery. A sublingual sufentanil tablet (SST), dispensed using a single-dose applicator, is in development for treatment of moderate-to-severe acute pain in a medically-supervised setting. Objective: The primary objective of this study was to demonstrate the repeat-dose efficacy, safety and tolerability of sufentanil 20 mcg and 30 mcg sublingual tablets compared to placebo for the management of acute pain as determined by the time-weighted sum of pain intensity differences (SPID) to baseline over the 12-hour study period (SPID12). Key secondary efficacy variables included SPID over the first hour (SPID1), Total pain relief over the 12-hour study period (TOTPAR12), time to perceived pain relief (PR) and time to meaningful PR. Safety variables consisted of adverse events (AE), vital signs, oxygen saturation and early termination. Methods: In this Phase 2, double-blind, dose-finding study, an equal number of male and female patients were randomly assigned in a 2:2:1 ratio to SST 20 mcg, SS 30 mcg or placebo, respectively, following bunionectomy. Study drug was dosed as needed, but not more frequently than hourly. Rescue medication was available as needed. The primary endpoint was the Summed Pain Intensity Difference to baseline over 12h (SPIDI2). Safety was assessed by continuous oxygen saturation monitoring and adverse event reporting. Results: 101 patients (51 Male/50 Female) were randomized, 100 received study treatment (intent-to-treat [ITT] population), and 91 completed the study. Reasons for early discontinuation were lack of efficacy (6), adverse events (2) and drug-dosing error (1). Mean age was 42.5 years. For the ITT population, SST 30 mcg was superior to placebo (p=0.003) for the SPID12. SPID12 scores in the active groups were superior for both male (ANOVA overall p-value =0.038) and female (ANOVA overall p-value=0.005) patients. Statistically significant differences in favour of sublingual sufentanil were also observed between the SST 30mcg and placebo group for SPID1(p<0.001), TOTPAR12(p=0.002), time to perceived PR (p=0.023) and time to meaningful PR (p=0.010). Nausea, vomiting and somnolence were more frequent in the sufentanil groups but there were no significant differences between treatment arms for the proportion of patients who prematurely terminated due to AE or inadequate analgesia. Conclusions: Sufentanil tablets dispensed sublingually using a single-dose applicator is in development for treatment of patients with moderate-to-severe acute pain in a medically-supervised setting where immediate IV access is limited. When administered sublingually, sufentanil’s pharmacokinetic profile and non-invasive delivery makes it a useful alternative to IM or IV dosing.

Keywords: acute pain, pain management, sublingual, sufentanil

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2858 Combined Orthodontic and Restorative Management of Complex Cases: Concepts and Case Reports

Authors: Awais Ali, Hesham Ali

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The absence of teeth through either premature loss or developmental absence is a common condition with potentially severe impact on affected individuals. Management of these cases presents a clinical challenge which may be difficult to resolve given the effects of tooth loss or hypodontia over the course of a patient’s lifetime. Treatment of such cases is often best provided by a multi-disciplinary team, where the patient’s expectations and care delivery can be optimally managed. Orthodontic treatment is often used to prepare the dentition in advance of restorative replacement of missing teeth. Conversely, the placement of implants may precede the delivery of orthodontic treatment and indeed may function as an adjunctive orthodontic procedure. We discuss the use of both approaches here and illustrate their clinical implementation with two case reports. The first case demonstrates the use of fixed appliances to prepare the mouth for an opposing implant-retained complete denture. A second case demonstrates the use of implant-retained crowns to provide orthodontic anchorage in a partially dentate patient. We propose that complex cases such as these should always be planned and treated by a multi-disciplinary team in order to optimise the delivery of care, patient experience, and treatment outcome. The presented cases add to the body of evidence in this area.

Keywords: orthodontics, dental implantology, hypodontia, multi-disciplinary

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2857 Comparing Student Performance on Standardized Tests at Test Center versus through Online-Proctored Delivery

Authors: Jin Koo

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The main purpose of this study is to investigate the comparability of student scores obtained from Test Center (TC) vs. Online-Proctored (OP) Delivery in the three subject areas of Verbal, Reading, and Mathematics for each level (Middle and Upper). Also, this study examines whether there is an interaction effect between test deliveries (TC vs. OP) and gender/ethnicity/ability level in each subject area. The test used in this study is a multiple-choice standardized test for students in grades 5-11. For this study, data were collected during the 2022-23 test administration. This research used a one-factor between-subjects ANOVA and Cohen’s d to compare the TC and OP groups’ test means for each level and each subject area. Also, 2-factor between-subjects ANOVAs were conducted to investigate examinee characteristics: gender (male and female), ethnicity (African-American, Asian, Hispanic, Multi-racial, and White), and ability level (low, average, and high-ability groups). The author found that students’ test scores in some subject areas varied between TC and OP test deliveries by gender, ethnicity, and ability level, meaning that gender, ethnicity, and ability level were related to the score difference. These results will be discussed according to the current testing systems.

Keywords: ability level, ethnicity, gender, online-proctored delivery, standardized test, test center

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2856 E-Governance: A Key for Improved Public Service Delivery

Authors: Ayesha Akbar

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Public service delivery has witnessed a significant improvement with the integration of information communication technology (ICT). It not only improves management structure with advanced technology for surveillance of service delivery but also provides evidence for informed decisions and policy. Pakistan’s public sector organizations have not been able to produce some good results to ensure service delivery. Notwithstanding, some of the public sector organizations in Pakistan has diffused modern technology and proved their credence by providing better service delivery standards. These good indicators provide sound basis to integrate technology in public sector organizations and shift of policy towards evidence based policy making. Rescue-1122 is a public sector organization which provides emergency services and proved to be a successful model for the provision of service delivery to save human lives and to ensure human development in Pakistan. The information about the organization has been received by employing qualitative research methodology. The information is broadly based on primary and secondary sources which includes Rescue-1122 website, official reports of organizations; UNDP (United Nation Development Program), WHO (World Health Organization) and by conducting 10 in-depth interviews with the high administrative staff of organizations who work in the Lahore offices. The information received has been incorporated with the study for the better understanding of the organization and their management procedures. Rescue-1122 represents a successful model in delivering the services in an efficient way to deal with the disaster management. The management of Rescue has strategized the policies and procedures in such a way to develop a comprehensive model with the integration of technology. This model provides efficient service delivery as well as maintains the standards of the organization. The service delivery model of rescue-1122 works on two fronts; front-office interface and the back-office interface. Back-office defines the procedures of operations and assures the compliance of the staff whereas, front-office equipped with the latest technology and good infrastructure handles the emergency calls. Both ends are integrated with satellite based vehicle tracking, wireless system, fleet monitoring system and IP camera which monitors every move of the staff to provide better services and to pinpoint the distortions in the services. The standard time of reaching to the emergency spot is 7 minutes, and during entertaining the case; driver‘s behavior, traffic volume and the technical assistance being provided to the emergency case is being monitored by front-office. Then the whole information get uploaded to the main dashboard of Lahore headquarter from the provincial offices. The latest technology is being materialized by Rescue-1122 for delivering the efficient services, investigating the flaws; if found, and to develop data to make informed decision making. The other public sector organizations of Pakistan can also develop such models to integrate technology for improving service delivery and to develop evidence for informed decisions and policy making.

Keywords: data, e-governance, evidence, policy

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2855 Public Private Partnership for Infrastructure Projects: Mapping the Key Risks

Authors: Julinda Keçi

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In many countries, governments have been promoting the involvement of private sector entities to enter into long-term agreements for the development and delivery of large infrastructure projects, with a focus on overcoming the limitations upon public fund of the traditional approach. The involvement of private sector through public-private partnerships (PPP) brings in new capital investments, value for money and additional risks to handle. Worldwide research studies have shown that an objective, systematic, reliable and user-oriented risk assessment process and an optimal allocation mechanism among different stakeholders is crucial to the successful completion. In this framework this paper, which is the first stage of a research study, aims to identify the main risks for the delivery of PPP projects. A review of cross-countries research projects and case studies was performed to map the key risks affecting PPP infrastructure delivery. The matrix of mapping offers a summary of the frequency of factors, clustered in eleven categories: Construction, Design, Economic, Legal, Market, Natural, Operation, Political, Project finance, Project selection and Relationship. Results will highlight the most critical risk factors, and will hopefully assist the project managers in directing the managerial attention in the further stages of risk allocation.

Keywords: construction, infrastructure, public private partnerships, risks

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2854 Virtual Screening of Potential Inhibitors against Efflux Pumps of Mycobacterium tuberculosis

Authors: Gagan Dhawan

Abstract:

Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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2853 Computational Approach to Identify Novel Chemotherapeutic Agents against Multiple Sclerosis

Authors: Syed Asif Hassan, Tabrej Khan

Abstract:

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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2852 Experimental Characterization and Modelling of Microfluidic Radial Diffusers

Authors: Eric Chappel, Dimitry Dumont-Fillon, Hugo Musard, Harald van Lintel

Abstract:

A microfluidic radial diffuser typically comprises a hole in a membrane, a small gap and pillar centred with the hole. The fluid is forced to flow radially in this gap between the membrane and the pillar. Such diffusers are notably used to form flow control valves, wherein several holes are machined into a flexible membrane progressively deflecting against pillars as the pressure increases. The fluidic modelling of such diffuser is made difficult by the presence of a transition region between the hole and the diffuser itself. An experimental investigation has been conducted using SOI wafers to form membranes with only one centred hole and Pyrex wafers for the substrate and pillars, both wafers being anodically bonded after alignment. A simple fluidic model accounting for the specific geometry of the diffuser is proposed and compared to experimental results. A good match is obtained, for Reynolds number in the range 0.5 to 35 using the analytical formula of a radial diffuser in the laminar regime with an effective inner radius that is 40% smaller than the real radius, in order to simulate correctly the flow constriction at the entrance of the diffuser.

Keywords: radial diffuser, flow control valve, numerical modelling, drug delivery

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2851 Synthesis and Biological Activities of Novel -1,2,3-Triazoles Derivatives

Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

Abstract:

1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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2850 Spatial Analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) Patients in Lagos, Nigeria

Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

Abstract:

The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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2849 Polyhydroxybutyrate (PHB): Highly Porous Scaffold for Biomedicine

Authors: Neda Sinaei, Davood Zare, Mehrdad Azin

Abstract:

Polyhydroxyalkanoates (PHAs) are biocompatible and biodegradable polymers produced by a wide range of bacterial strains. These biopolymers are significantly studied for drug delivery and tissue engineering applications because of their fascinating physicochemical properties. Polyhydroxybutyrate (PHB) scaffold that has been extracted from a novel bacteria using oil wastewater was selected to study. Some physical parameters affecting scaffold properties such as PHB concentration, solvent evaporation speed, and ultrasonic time were investigated. Scanning electron microscopy was used to evaluate the porosity. Afterward, the biocompatibility of PHB scaffold was assessed. Initial results showed the highly porous PHB scaffold structure with a variety of pore sizes. Subsequent results indicated that more unique pore sizes can be obtained by optimizing physical factors. It would be noticed that the morphology of the pore structure was accordingly affected by ultrasonic time. Hence, In vitro cell viability tests on the PHB scaffold using human foreskin fibroblasts revealed strong cell attachment and proliferation supports. Therefore, it can be concluded that the cost-effective PHB scaffold has the potential using as a biomaterial cell adhesion substrate in therapeutic applications.

Keywords: Polyhydroxybutyrate, biocompatible, scaffold, porous, tissue engineering

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2848 Treatment of Premalignant Lesions: Curcumin a Promising Non-Surgical Option

Authors: Heba A. Hazzah, Ragwa M. Farid, Maha M. A. Nasra, Mennatallah Zakria, Magda A. El Massik, Ossama Y. Abdallah

Abstract:

Introduction: Curcumin (Cur) is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. The buccal delivery of curcumin can be useful for both systemic and local disease treatments such as gingivitis, periodontal diseases, oral carcinomas, and precancerous oral lesions. Despite of its high activity, it suffers a limited application due to its low oral bioavailability, poor aqueous solubility, and instability. Aim: Preparation and characterization of curcumin solid lipid nanoparticles with a high loading capacity into a mucoadhesive gel for buccal application. Methodology: Curcumin was formulated as nanoparticles using different lipids, namely Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and Polaxomer 407 as a surfactant. The SLN were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. All formulations were evaluated for their content, entrapment efficiency, particle size, in vitro drug dialysis, ex vivo mucoadhesion test, and ex vivo permeation study using chicken buccal mucosa. Clinical evaluation was conducted on 15 cases suffering oral erythroplakia and erosive lichen planus. Results: The results showed high entrapment efficiency reaching almost 90 % using Gelucire 50, the loaded gel with Cur-SLN showed good adhesion property and 25 minutes in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated however, a significant amount of Cur was retained within the mucosal tissue. Pain and lesion sizes were significantly reduced upon topical treatment. Complete healing was observed after 6 weeks of treatment. Conclusion: These results open a room for the pharmaceutical technology to optimize the use of this golden magical powder to get the best out of it. In addition, the lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Keywords: curcumin, erythroplakia, mucoadhesive, pain, solid lipid nanoparticles

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2847 Strategies Considered Effective for Funding Public Tertiary Institutions in Nigeria

Authors: Jacinta Ifeoma Obidile

Abstract:

The study sought to ascertain from the opinions of the business educators, effective strategies for funding public tertiary institutions in Anambra State Nigeria, for effective functioning and delivery. Funding of tertiary institutions has become so important following the dilapidated state of most of the public tertiary institutions in Nigeria. Tertiary institutions are known for the production of competitive and competent workforce in the nation. Considering the state of public tertiary institutions currently, one wonders if their objectives are achieved. Many scholars have identified funding as one of the major barriers to effective functioning of tertiary institutions. Although federal and state governments have been supporting the tertiary institutions, but their support seems not to be adequate. This study therefore ascertained from the perspective of business educators, other strategies for funding public tertiary institutions in Anambra State Nigeria, for effective functioning and delivery. Survey research design was adopted for the study. A total of 104 business educators from the public tertiary institutions in the State constituted the population. There was no sampling, hence the whole population was used. Structured questionnaire validated by three experts with a reliability coefficient of 0.82 was the instrument for data collection. Data collected were analyzed using mean and standard deviation. Findings from the study revealed that public-private partnership and external aids were among the strategies considered effective for funding public tertiary institutions. It was therefore recommended among others that associations like alumni should be strongly instituted in each of the public tertiary institutions so as to assist in the funding of tertiary institutions for effective functioning and delivery.

Keywords: strategies, funding, tertiary institutions, business educators

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2846 Rapid and Easy Fabrication of Collagen-Based Biocomposite Scaffolds for 3D Cell Culture

Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

Abstract:

The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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2845 Pregnancy and Birth Experience, Opinions regarding the Delivery Method of the Patients' Vaginal Deliveries

Authors: Umran Erciyes, Filiz Okumus

Abstract:

The purpose of this study was the determination of factors which impact the pregnancy, birth experience and the opinions regarding the delivery type of the puerperants, after vaginal birth. This descriptive study includes 349 patients who gave births with normal birth in one of the hospital in İstanbul in May- November 2014. After birth, we interview with these women face to face. The descriptive information form and Perception of Birth Scale were used as data collection tool. SPSS (Statistical Package for the Social Sciences) was used for statistical analysis. The average age of patients was 27.13, and the average score was 76.93±20.22. The patients are primary school graduate, and they do not have a job. They expressed an income outcome equality. More than half of women did not get educated before birth. Among educated patients, few women got educated overcoming the pain during labor process. As the time spent in the hospital for the birth increases, the birth perception of mothers is affected negatively. %86.8 of participants gave assisted delivery. Spontaneous vaginal birth has positive effects on birth perception. Establishing a vascular access, induction of labor performing enema, restriction of orally intake and movement, fundal pressure, episiotomy, nor to perform skin to skin contact with the baby after birth has adverse effects on the birth perceptions.

Keywords: antenatal care, birth experience, perception of birth, vaginal birth

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2844 Design and Synthesis of Some Pyrimidine Derivatives as Bruton’s Tyrosine Kinase Inhibitors for Hematologic Malignancies

Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

Abstract:

Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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2843 Prefabrication Technology as an Option for Accelerated Sustainable Social Housing Delivery in South Africa

Authors: Madifedile Thasi, Azola Mayeza

Abstract:

In South Africa, provision of housing to the growing population has been described as one of the greatest challenges facing the government. Between 1994 to 2015, more than 2.5 million housing units were provided by the government for the poorest households and the low-income earners under the Reconstruction and Development Programme (RDP). Yet, the latest census figure revealed that about 2.1 million households still live in shacks and informal dwellings. Human settlements patterns remain dysfunctional across in South Africa because of rapid urbanisation. The housing backlog is growing at a rate of 178 000 units a year. The aforementioned predicament calls the need for innovative approaches to address the issue in a sustainable way and this need not be overemphasized. Aside from the issue of cost, the delivery of more housing units comes with environmental and sustainability issues. The prefabrication building technology has resulted into accelerated housing delivery to a satisfactory level in some countries such as Nigeria and Malaysia that are facing similar issue. It is therefore expected to be a foremost option to address the social housing backlog in South Africa and within the country housing sustainability agenda. This paper appraises the factors responsible for the limited implementation of prefabrication technology in South African housing projects. The objective is to recommend the method and materials that can be best sustained in the country in terms of local availability, cost effectiveness and environmental friendliness. It presents empirical data to support the hypothesis that a wider implementation of prefabrication technology in the social housing projects will be of significant benefit, by providing fast turnaround, cost-effective and sustainable solution that will dent the housing backlog, as well as improving the quality of the social housings. It was found that only 17 000 units of the RDP housings provided were constructed using alternative building technologies. Furthermore, there are variety of prefabricated technologies in the market but mostly have limited production capacity, minimal manufacturing capacity and most materials are imported, which leads to unavailability of the technology for large scale delivery and utilization despite its obvious advantages.

Keywords: prefabrication technology, sustainable social housings, South Africa, housing delivery

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2842 Hospital Acquired Bloodstream Infections Among Patients With Hematological and Solid Malignancies: Epidemiology, Causative Pathogens and Mortality

Authors: Marah El-Beeli, Abdullah Balkhair, Zakaryia Al Muharmi, Samir Al Adawi, Mansoor Al-Jabri, Abdullah Al Rawahi, Hazaa Al Yahyae, Eman Al Balushi, Yahya M. Al-Farsi

Abstract:

The health care service and the anticancer chemotherapeutics has changed the natural history of cancer into manageable chronic disease and improve the cancer patient’s lifestyle and increase the survival time. Despite that, still, infection is the major dilemma opposing the cancer patient either because of the clinical presentation of the cancer type and impaired immune system or as a consequence of anticancer therapy. This study has been conducted to1) track changes in the epidemiology of hospital-acquired bloodstream infections among patients with malignancies in the last five years. 2) To explore the causative pathogens and 3) the outcome of HA-BSIs in patients with a different types of malignancies. An ampi-directional study (retrospective and prospective follow up) of patients with malignancies admitted at Sultan Qaboos University hospital (570-bed tertiary hospital) during the study period (from January 2015 to December 2019). The cumulative frequency and prevalence rates of HA-BSIs by patients and isolates were calculated. In addition, the cumulative frequency of participants with single versus mixed infections and types of causative micro-organisms of HA-BSIs were obtained. A total of 1246 event of HA-BSIs has occurred during the study period. Nearly the third (30.25%) of the HA-BSI events was identified among 288 patients with malignancies. About 20% of cases were mixed infections (more than one isolate). Staphylococcus spp were the predominant isolated pathogen (24.7%), followed by Klebsiella spp (15.8%), Escherichia spp (13%), and Pseudomonas spp (9.3%). About half (51%) of cases died in the same year, and (64%) of the deaths occur within two weeks after the infection. According to the observations, no changes in the trends of epidemiology, causative pathogens, morbidity, and mortality rates in the last five years.

Keywords: epidemiology, haematological malignancies, hospital acquired bloodstream infections, solid malignancies

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