Search results for: drug therapy problems
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9451

Search results for: drug therapy problems

9121 Isolation, Identification and Antimicrobial Susceptibility of Mycobacterium tuberculosis among Pulmonary Tuberculosis Patients

Authors: Naima Nur, Safa Islam, Saeema Islam, Faridul Alam

Abstract:

Background: Drug-resistant pulmonary tuberculosis (DR-PTB), particularly multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant (pre-XDR), is a major challenge in effectively controlling TB, especially in developing. This study aimed to identify the strains of M. tuberculosis complex (MTC) and drug resistance patterns among the pulmonary tuberculosis patients. Methods: The study used a cross-sectional design, and 815 patients were recruited randomly in three study periods. In the first-period, 210 treated PTB patients, who were completed their treatment, received their diagnoses using light microscopy, fluorescence microscopy and cultured on Lowenstein-Jensen (L-J) slant, and then strains were identified as MTC by biochemical tests, and then sensitivity test in National Institute of Diseases of the Chest and Hospital. In the second-period, 220 re-treated PTB patients, who were completed their treatment, received their diagnoses using culture on L-J slant, line probe assay (LPA), and GeneXpert in the same hospital. In the last-period, during treatment, 385 MDR-PTB patients received their diagnoses using culture on L-J slant and LPA in the same hospital. Results: Among sixty-two (29.5%) PTB patients, 13% were sensitive to all first-line anti-TB drugs, 26% were MDR-TB patients, and 14.2% were pre-XDR-TB among 14 MDR-TB patients. After three years, 31% were MDR-TB among 220 re-treated PTB patients. After five years, 16.4% was pre-XDR-TB among 385 MDR-TB patients. Compared to females, male patients were significantly higher at all times. Conclusion: The current study demonstrated that in three study periods, the proportions of DR-TB, MDR-TB, and pre-XDR patients were an alarming issue and increasing daily.

Keywords: multi-drug resistant, drug-resistant, pre-extensive drug resistant, pulmonary tuberculosis

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9120 Suggestion of Two-Step Traction Therapy for Safer and More Effective Conservative Treatment for Low Back Pain

Authors: Won Man Park, Dae Kyung Choi, Kyungsoo Kim, Yoon Hyuk Kim

Abstract:

Traction therapy has been used in the treatment of spinal pain for decades. However, a case study reported the occurrence of large disc protrusion during motorized traction therapy. In this study, we hypothesized that additional local decompression with a global axial traction could be helpful for risk reduction of intervertebral disc damage. A validated three dimensional finite element model of the lumbar spine was used. Two-step traction therapy using the axial global traction (the first step) with 1/3 body weight and the additional local decompression (the second step) with 7 mm translation of L4 spinal bone was determined for the traction therapy. During two-step traction therapy, the sacrum was constrained in all translational directions. Reduced lordosis angle by the global axial traction recovered with the additional local decompression. Stress on fibers of the annulus fibrosus by the axial global traction decreased with the local decompression by 17%~96% in the posterior region of intervertebral disc. Stresses on ligaments except anterior longitudinal ligaments in all motion segments decreased till 4.9 mm~5.6 mm translation of L4 spinal bone. The results of this study showed that the additional local decompression is very useful for reducing risk of damage in the intervertebral disc and ligaments caused by the global axial traction force. Moreover, the local decompression could be used to enhance reduction of intradiscal pressure.

Keywords: lumbar spine, traction-therapy, biomechanics, finite element analysis

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9119 Polypharmacy Overdose: Case Report on Mixed Overdose of Ramipril, Quetiapine, Lercanidipine and Duloxetine

Authors: Chui Ling Teng, R. Matsa

Abstract:

We report a case with combined overdose of Lercanidipine (non-dihydropyridine calcium channel blocker), Quetiapine (Atypical antipsychotic), Ramipril and Duloxetine. A 66-year old male presented to the Emergency Department 12-hours after the ingestion of 1.2g Lercanidipine, 3g Quetiapine, 280mg of Ramipril and 420mg of Duloxetine. He describes lethargic, drowsiness and was unable to pass any urine since overdosed. He was found to be bradycardic, hypotensive and anuric. He had refractory hypotension and anuric despite fluid resuscitation, glucagon therapy and intravenous naloxone. His care was escalated to Intensive care, requiring noradrenaline, adrenaline, vasopressin, and hyperinsulinaemic euglycaemia therapy. He achieved haemodynamic stability and kidney function improved gradually with the support received. The total length of therapy lasted for 30 horus in which individual therapy was weaned down based on the requirement. He was then transferred to medical ward for further psychiatric assessment. This is a the first repored case of mixed overdose with lercanidipine, Quetiapine, Rampmipril and Duloxetine.

Keywords: calcium channel blocker, hyperinsulinaemic Euglycaemia therapy, lercanidipine, overdose

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9118 Vascular Targeted Photodynamic Therapy Monitored by Real-Time Laser Speckle Imaging

Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

Abstract:

Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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9117 The Potential of Hydrophobically Modified Chitosan Cryogels to Be Used as Drug Delivery Systems

Authors: Courtney Evans, Yuto Morimitsu, Tsubasa Hisadome, Futo Inomoto, Masahiro Yoshida, Takayuki Takei

Abstract:

Hydrogels are useful biomaterials due to their highly biocompatible nature and their ability to absorb large quantities of liquid and mimic soft tissue. They are often used as therapeutic drug delivery systems. However, it is sometimes difficult to sustain controlled release when using hydrophobic medicines, as hydrogels are frequently hydrophilic. As such, this research shows the success of chitosan hydrogels modified through hydrophobic interaction. This was done through the imide bonding of the alkyl groups in fatty aldehydes and the amino groups in chitosan, followed by reductive animation. The resulting cryogels could be optimized for strength as well as sorption and desorption (of a hydrophobic dye used to mimic hydrophobic medicine) by varying the alkyl chain length and the substitution degree of the fatty aldehyde. Optimized cryogels showed potential as biomedical materials, particularly as drug delivery systems.

Keywords: biomedical materials, chitosan, drug carriers, hydrophobic modification

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9116 Application of Topical Imiquimod for Treatment Cervical Intraepithelial Neoplasia in Young Women: A Preliminary Result of a Pilot Study

Authors: Phill-Seung Jung, Dae-Yeon Kim

Abstract:

Objectives: In young, especially nulliparous women, it is not easy to decide on excisional therapy for cervical intraepithelial neoplasia (CIN). We aimed to evaluate how effective topical imiquimod is in the treatment of high-grade CIN so that excisional therapy can be avoided in young women. Methods: Patients with CIN were allocated to this pilot study. They did not want excisional therapy and agreed with topical imiquimod therapy, which required once-a-week hospital visit for 8 weeks for the application of imiquimod to the cervix by a gynecologic oncologist. If the lesion got worse during treatment, it was decided to convert imiquimod therapy to excisional therapy. Results: A total of 36 patients with a median age of 29 years (range, 22–41 years) agreed to receive topical imiquimod therapy. Of these, 32 patients (88.9%) were positive for high-risk human papillomavirus (HR HPV). Twenty-five patients (69.4%) had low-grade squamous intraepithelial lesion (LSIL), and 11 (30.6%) had high-grade squamous intraepithelial lesion (HSIL) on their initial LBC. Twenty-eight patients underwent punch biopsy, which showed CIN 1 in 7 (19.4%), CIN 2 in 11 (30.6%), and CIN 3 in 10 (27.8%) patients. Twenty patients finished the 8-week imiquimod therapy. Among them, 14 patients had CIN 2 or 3, and 6 patients had CIN 1. HR HPV was positive in 12 patients. On the last examination, 14 patients (70.0%) had negative intraepithelial lesions, 3 (15.0%) had atypical squamous cells of undetermined significance, and 1 (5.0%) had LSIL. Two patients had persistent HSIL: 1 patient underwent loop electrosurgical excision procedure, resulting in CIN 3 with positive resection margin, and the other patient underwent punch biopsy, resulting in intermediate cells and restarted imiquimod therapy. Only 7 patients were negative for HR HPV. Conclusions: This study showed that topical imiquimod therapy was effective for the treatment of high-grade CIN, with a histologic regression rate of 85.7% (14/20) and HPV eradication rate of 25.0% (8/32). Based on our findings, topical imiquimod therapy might have a successful therapeutic effect in young women with CIN 2-3 so that they can avoid excisional therapy. In addition, it could be a more reassuring treatment option for CIN 1 than just follow-up after few months. To confirm its efficacy, a phase II study with larger cohort would be needed.

Keywords: Imiquimod, Cervical Intraepthelial Neoplasia, Cervical Dysplasia, Human Papillomavirus

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9115 The Effectiveness of Sexual Cognitive Behavioral Therapy on Strategic Thinking and Communication Patterns of Couples in Colostomy Patients

Authors: Alireza Monzavi Chaleshtari, Mahnaz Aliakbari Dehkordi, Seyedeh Somayeh Amiri, Mozhgan Shakhseniaei, Amin Asadi Hieh

Abstract:

The purpose of this research was to determine the effectiveness of sexual cognitive behavioral therapy on strategic thinking and communication patterns of couples in colostomy patients. In this study, experimental research was conducted with a pre-test and post-test design with a control group and a follow-up period. The statistical population studied were married female colostomy patients referring to the Iranian Ostomy Association. 30 qualified people were selected by voluntary sampling and randomly divided into two experimental and control groups (15 people in each group). Both groups responded to Goleman's strategic thinking (2007) and the communication patterns of Christensen and Sulawai questionnaires (1984). The results of covariance analysis showed that sexual cognitive behavioral therapy has an effect on improving strategic thinking. Based on the results of this test, sexual cognitive behavioral therapy is effective in improving the strategic thinking of colostomy patients until the follow-up stage. Also, sexual cognitive behavioral therapy has an effect on improving the communication patterns of couples in colostomy patients. Based on the results of this test, sexual cognitive behavioral therapy is effective in improving communication patterns of couples in patients with colostomy until the follow-up stage. Based on the results of this research, sexual cognitive behavioral therapy can be used to improve strategic thinking and communication patterns of couples of colostomy patients.

Keywords: sexual cognitive behavioral therapy, strategic thinking, communication patterns of couples, colostomy

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9114 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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9113 Preparation, Characterisation, and Measurement of the in vitro Cytotoxicity of Mesoporous Silica Nanoparticles Loaded with Cytotoxic Pt(II) Oxadiazoline Complexes

Authors: G. Wagner, R. Herrmann

Abstract:

Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

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9112 Preparation of Polymer-Stabilized Magnetic Iron Oxide as Selective Drug Nanocarriers to Human Acute Myeloid Leukemia

Authors: Kheireddine El-Boubbou

Abstract:

Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC50 values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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9111 Prevalence and Factors Associated with Illicit Drug Use Among Undergraduate Students in the University of Lagos, Nigeria

Authors: Abonyi, Emmanuel Ebuka, Amina Jafaru O.

Abstract:

Background: Illicit substance use among students is a phenomenon that has been widely studied, but it remains of interest due to its high prevalence and potential consequences. It is a major mental health concern among university students which may result in behavioral and academic problems, psychiatric disorders, and infectious diseases. Thus, this study was done to ascertain the prevalence and factors associated with the use of illicit drugs among these groups of people. Methods: A cross-sectional and descriptive survey was conducted among undergraduate students of the University of Lagos for the duration of three(3) months (August to October 2021). A total number of 938 undergraduate students were selected from seventeen faculties in the university. Pretested questionnaires were administered, completed, and returned. The data were analyzed using descriptive statistics and multivariate regression analysis. Results: From the data collected, it was observed that out of 938 undergraduate students of the University of Lagos that completed and returned the questionnaires, 56.3% were female and 43.7% were male. No gender differences were observed in the prevalence of use of any of the illicit substances. The result showed that the majority of the students that participated in the research were females(56.6%); it was observed that there were a total of 541 2nd-year students(57.7%) and 397 final-year students(42.3). Students between the age brackets of 20- 24 years had the highest frequency of 648(69.1%) of illicit drug use and students in none health-related disciplines. The result also showed that the majority of the students reported that they use Marijuana (31.7%), while lifetime use of LSD (6.3%), Heroin(4.8%), Cocaine (4.7%), and Ecstasy(4.5), Ketamine (3.4%). Besides, the use of alcohol was below average(44.1%). Additionally, Marijuana was among the ones that were mostly taken by students having a higher percentage and most of these respondents had experienced relationship problems with their family and intentions (50.9%). From the responses obtained, major reasons students indulge in illicit drug use were; curiosity to experiment, relief of stress after rigorous academic activities, social media influence, and peer pressure. Most Undergraduate students are in their most hyperactive stage in life, which makes them vulnerable to always want to explore practically every adventure. Hence, individual factors and social media influence are identified as major contributors to the prevalence of illicit drug use among undergraduate students at the University of Lagos, Nigeria. Conclusion: Control programs are most needed among the students. They should be comprehensive and focused on students' psycho-education about substances and their related negative consequences, plus the promotion of students' life skills, and integration into the family – and peer-based preventive interventions.

Keywords: illicit drugs, addiction, undergraduate students, prevalence, substances

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9110 Analyzing Initial Efficacy of Animal Assisted Therapy for Autism Spectrum Disorders: A Case Study

Authors: Georgitta Joseph Valiyamattam

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Autism spectrum disorders (ASD) are a growing phenomenon in India with over 10 million cases being recorded. Children with various levels and forms of ASD can be a major challenge both within the context of regular or special schooling. According to statistics by the Centers for Disease Control and Prevention (CDC), one in every 88 children today is born with autism spectrum disorder (ASD) against a ratio of one in 110 few years back. The growing number of children with autism spectrum disorders places greater demands on health services and necessitates the roping in of non-traditional modes of treatment to complement or even substitute traditional health care methods when possible. Research evidence, particularly from Western countries, as also some parts of Asia, suggests that animal-assisted therapy, or zootherapy, may be used as an effective individual or complementary therapeutic tool for increasing overall wellbeing and quality of life among children with Autism spectrum disorders. The paper through a case-study format seeks to evaluate the efficacy (initial stage) of animal assisted therapy (canine-therapy with visiting dog: breed-Golden retriever), as a non-conventional treatment modality for improving cognitive functioning and managing the behavioral and psychological symptoms of Autism Spectrum Disorders. As a pilot study forming the basis for subsequent larger application of AAT, it analyses areas of efficacy as also the challenges faced, both with regard to the mode of therapy, as also particular to the Indian setting.

Keywords: animal assisted therapy, autism, canine therapy, analyzing initial efficacy

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9109 Prescription of Maintenance Fluids in the Emergency Department

Authors: Adrian Craig, Jonathan Easaw, Rose Jordan, Ben Hall

Abstract:

The prescription of intravenous fluids is a fundamental component of inpatient management, but it is one which usually lacks thought. Fluids are a drug, which like any other can cause harm when prescribed inappropriately or wrongly. However, it is well recognised that it is poorly done, especially in the acute portals. The National Institute for Health and Care Excellence (NICE) recommends 1mmol/kg of potassium, sodium, and chloride per day. With various options of fluids, clinicians tend to face difficulty in choosing the most appropriate maintenance fluid, and there is a reluctance to prescribe potassium as part of an intravenous maintenance fluid regime. The aim was to prospectively audit the prescription of the first bag of intravenous maintenance fluids, the use of urea and electrolytes results to guide the choice of fluid and the use of fluid prescription charts, in a busy emergency department of a major trauma centre in Stoke-on-Trent, United Kingdom. This was undertaken over a week in early November 2016. Of those prescribed maintenance fluid only 8.9% were prescribed a fluid which was most appropriate for their daily electrolyte requirements. This audit has helped to highlight further the issues that are faced in busy Emergency Departments within hospitals that are stretched and lack capacity for prompt transfer to a ward. It has supported the findings of NICE, that emergency admission portals such as Emergency Departments poorly prescribed intravenous fluid therapy. The findings have enabled simple steps to be taken to educate clinicians about their fluid of choice. This has included: posters to remind clinicians to consider the urea and electrolyte values before prescription, suggesting the inclusion of a suggested intravenous fluid of choice in the prescription chart of the trust and the inclusion of a session within the introduction programme revising intravenous fluid therapy and daily electrolyte requirements. Moving forward, once the interventions have been implemented then, the data will be reaudited in six months to note any improvement in maintenance fluid choice. Alongside this, an audit of the rate of intravenous maintenance fluid therapy would be proposed to further increase patient safety by avoiding unintentional fluid overload which may cause unnecessary harm to patients within the hospital. In conclusion, prescription of maintenance fluid therapy was poor within the Emergency Department, and there is a great deal of opportunity for improvement. Therefore, the measures listed above will be implemented and the data reaudited.

Keywords: chloride, electrolyte, emergency department, emergency medicine, fluid, fluid therapy, intravenous, maintenance, major trauma, potassium, sodium, trauma

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9108 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

Abstract:

Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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9107 Computer Based Identification of Possible Molecular Targets for Induction of Drug Resistance Reversion in Multidrug Resistant Mycobacterium Tuberculosis

Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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9106 Effectiveness of Short-Term Cognitive-Behavioral Group Therapy on Binge Eating Disorder in Females

Authors: Saeed Dehnavi, Ismail Asadallahi, Fatemeh Rahmatian, Elahe Rahimian

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Purpose: Due to an increasing prevalence of over eating disorders, this paper aims to investigate the effectiveness of short-term group cognitive-behavioral therapy on reducing binge eating behavior and depression symptoms among females suffered from binge eating disorder (BED) in Qazvin, Iran. Methodology: This is aquasi-experimental study (pre-post testing plan with control group). Using a convenience sampling technique, binge eating scale (BES) and clinical interviews, 30 persons were selected among all clients who had referred to weight loss centers in Qazvin, these persons were randomly placed into two control and experimental groups. The experimental group participated in a seven-session plan on short-term cognitive-behavioral group therapy. Results: The results showed that the short term group cognitive-behavioral therapy results in a significant reduction in binge eating signs and depressive symptoms within the experimental group, compared to the control. Conclusion: Regarding the results, it is known that short-term group cognitive-behavioral therapy is effective in reducing overeating symptoms. Hence, it can be used as an economical and effective treatment method for individuals suffering from BED.

Keywords: cognitive-behavioral group therapy, binge eating disorder, depression

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9105 Effect of Aerobics Exercise on the Patient with Anxiety Disorder

Authors: Ahmed A. Abd El Rahim, Andrew Anis Fakhrey Mosaad

Abstract:

Background: An important psychological issue that has an impact on both mental and physical function is anxiety disorders. The general consensus is that aerobic exercise and physical activity are good for lowering anxiety and mood. Purpose: This study's goal was to look into how patients with anxiety disorders responded to aerobic exercise. Subjects: Anxiety disorders were identified in 30 individuals from the psychiatric hospital at Sohag University who were chosen based on inclusive criteria and had ages ranging from 25 to 45. Methods: Patients were split into two equal groups at random: For four weeks, three sessions per week, fifteen patients in group A (the study group), seven men and eight women, underwent medication therapy and aerobic exercise. Age (28.4 ± 2.11 years), weight (72.5 ± 10.06 kg), height (164.8 ± 9.64 cm), and BMI (26.65 ± 2.68 kg/m2) were all mean SD values. And in Group B (Control Group), only medication therapy was administered to 15 patients (9 males and 6 females). Age (29.6 ± 3.68), weight (75 ± 7.07 kg), height (166.9 ± 6.75) cm, and BMI (26.87 ± 1.11) kg/m2 were the mean SD values. Before and after the treatment, the Hamilton Anxiety Scale was used to gauge the patient's degree of anxiety. Results: Within the two groups, there were significant differences both before and after the treatment. Following therapy, there was a significant difference between the two groups; the study group displayed better improvement on the Hamilton Anxiety Scale. Conclusion: Patients with anxiety problems can benefit from aerobic activities and antianxiety drugs as effective treatments for lowering anxiety levels.

Keywords: aerobic exercises, anxiety disorders, antianxiety medications, Hamilton anxiety scale

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9104 Antibacterial Effects of Zinc Oxide Nanoparticles as Alternative Therapy on Drug-Resistant Group B Streptococcus Strains Isolated from Pregnant Women

Authors: Leila Fozouni, Anahita Mazandarani

Abstract:

Background: Maternal infections are the most common cause of infections in infants, and the level of infection and its severity highly depends on the degree of colonization of the bacteria in the mother; so, the occurrence of aggressive diseases is not unpredictable in mothers with very high colonization. Group B Streptococcus is part of the normal flora of the gastrointestinal and genital tracts in women and is the leading cause of septicemia and meningitis in newborns. Today Zinc oxide nanoparticle is regarded as one of the most commonly used and safest nanoparticles for defeating Gram-positive and Gram-negative bacteria. This study aims to determine the antibacterial effects of Zinc oxide on the growth of drug-resistant group B Streptococcus strains isolated from pregnant women. Materials and Methods: This cross-sectional study was conducted on 150 pregnant women of 28–37 weeks admitted to seven hospitals and maternity wards in Golestan province, northeast of Iran. For bacterial identification, rectovaginal swabs were firstly inoculated to the Todd-Hewitt Broth and cultured in blood agar (containing 5% sheep blood). Then microbiologic and PCR methods were performed to detect group B Streptococci. Disk diffusion and broth microdilution tests were used to determine the bacterial susceptibility to antibiotics according to CLSI M100(2021) criteria. The antibacterial properties of Zinc oxide nanoparticles were evaluated using the agar well-diffusion method. Results: The prevalence of group B Streptococcus was 18% in pregnant women. Out of twenty-seven positive cultures, 62.96% were higher than thirty years old. Ninety percent and 45% of isolates were resistant to clindamycin and erythromycin, respectively, and susceptibility to cefazolin was 71%. In addition, susceptibility to ampicillin and penicillin were 74% and 55%, respectively. The results showed that 82% of erythromycin-resistant, 92% clindamycin-resistant, and 78% of cefazolin-resistant isolates were eliminated by zinc oxide nanoparticles at a concentration of 100 mg/L of the nanoparticle. Furthermore, ZnONPs could inhibit all drug-resistant isolates at a concentration of 200 mg/mL (MIC90 ≥ 200). Conclusion: Since the drug resistance of group B streptococci against various antibiotics is increasing, determining and investigating the drug-resistance pattern of this bacterium to different antibiotics in order to prevent arbitrary consumption of antibiotics by pregnant women and ultimately prevent Infant mortality seems necessary. Generally, ZnONPs showed a high antimicrobial effect, and it was revealed that the bactericide effect increases upon the increase in the concentration of the nanoparticle.

Keywords: group B beta-hemolytic streptococcus, pregnant women, zinc oxide nanoparticles, drug resistance

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9103 Family Treatment Drug Court Cost Analysis: An In-depth Look At The Cost And Savings Of A Southeastern Family Treatment Drug Court

Authors: Ashley R. Logsdon, Becky F. Antle, Cynthia M. Kamer

Abstract:

This study examines the cost and benefits of a family treatment drug court in an urban county in a southeastern state. Additionally, this cost analysis will provide a detailed description of the type and cost of activities to produce the services provided to child welfare families. This study utilized return-on-investment analysis, which uses child welfare practices, disaggregates them into separate activities and estimates costs for these activities including child-level placement data for total cost of care for the child. Direct and indirect costs were considered as well as saving calculations what costs would be associated with child welfare outcomes both short and long term. The costs included were general program costs (salaries, drug screens, transportation, childcare, parent education, program evaluation, visitation, incentives) or personnel costs for other team members (judges, court administrators, child welfare workers, child welfare supervisors, and community mental health provider). The savings that were used in the study were length of time in out of home care, Medicaid costs, substance exposed births, emergency room utilization and jail/probation costs. This study documents an overall savings of between $168,993.30 and $837,993.30. The total savings per family divided by the 40 families who have participated in the program was between $4,224.83 to $20,949.83 per family. The results of this cost benefit analysis are consistent with prior research documenting savings associated with out of home care and jail/probation; however, there are also unique contributions of this study to the literature on cost effectiveness of family treatment drug courts. We will present recommendations for further utilization of family treatment drug courts and how to expand the current model.

Keywords: child welfare, cost analysis, family drug court, family treatment drug court

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9102 Successful Management of a Boy with Mild Persistent Asthma: A Longitudinal Case

Authors: A. Lubis, L. Setiawati, A. R. Setyoningrum, A. Suryawan, Irwanto

Abstract:

Asthma is a condition that causing chronic health problems in children. In addition to basic therapy against disease, we must try to reduce the impact of chronic health problems and also optimize their medical aspect of growth and development. A boy with mild asthma attack frequent episode did not showed any improvement with medical treatment and his asthma control test was 11. From radiologic examination he got hyperaerated lung and billateral sinusitis maxillaris; skin test results were house dust, food and pet allergy; an overweight body; bad school grades; psychological and environmental problem. We followed and evaluated this boy in 6 months, treated holistically. Even we could not do much on environmental but no more psychological and school problems, his on a good bodyweight and his asthma control test was 22. A case of a child with mild asthma attack frequent episode was reported. Asthma clinical course show no significant improvement when other predisposing factor is not well-controlled and a child’s growth and development may be affected. Improving condition of the patient can be created with the help of loving and caring way of nurturing from the parents and supportive peer group. Therefore, continuous and consistent monitoring is required because prognosis of asthma is generally good when regularly and properly controlled.

Keywords: asthma, chronic health problems, growth, development

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9101 Effects of Using a Recurrent Adverse Drug Reaction Prevention Program on Safe Use of Medicine among Patients Receiving Services at the Accident and Emergency Department of Songkhla Hospital Thailand

Authors: Thippharat Wongsilarat, Parichat tuntilanon, Chonlakan Prataksitorn

Abstract:

Recurrent adverse drug reactions are harmful to patients with mild to fatal illnesses, and affect not only patients but also their relatives, and organizations. To compare safe use of medicine among patients before and after using the recurrent adverse drug reaction prevention program . Quasi-experimental research with the target population of 598 patients with drug allergy history. Data were collected through an observation form tested for its validity by three experts (IOC = 0.87), and analyzed with a descriptive statistic (percentage). The research was conducted jointly with a multidisciplinary team to analyze and determine the weak points and strong points in the recurrent adverse drug reaction prevention system during the past three years, and 546, 329, and 498 incidences, respectively, were found. Of these, 379, 279, and 302 incidences, or 69.4; 84.80; and 60.64 percent of the patients with drug allergy history, respectively, were found to have caused by incomplete warning system. In addition, differences in practice in caring for patients with drug allergy history were found that did not cover all the steps of the patient care process, especially a lack of repeated checking, and a lack of communication between the multidisciplinary team members. Therefore, the recurrent adverse drug reaction prevention program was developed with complete warning points in the information technology system, the repeated checking step, and communication among related multidisciplinary team members starting from the hospital identity card room, patient history recording officers, nurses, physicians who prescribe the drugs, and pharmacists. Including in the system were surveillance, nursing, recording, and linking the data to referring units. There were also training concerning adverse drug reactions by pharmacists, monthly meetings to explain the process to practice personnel, creating safety culture, random checking of practice, motivational encouragement, supervising, controlling, following up, and evaluating the practice. The rate of prescribing drugs to which patients were allergic per 1,000 prescriptions was 0.08, and the incidence rate of recurrent drug reaction per 1,000 prescriptions was 0. Surveillance of recurrent adverse drug reactions covering all service providing points can ensure safe use of medicine for patients.

Keywords: recurrent drug, adverse reaction, safety, use of medicine

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9100 Analysis of the Development of Communicative Skills After Participating in the Equine-Assisted-Therapy Program Step-By-Step in Communication

Authors: Leticia Souza Guirra, Márcia Eduarda Vieira Ramos, Edlaine Souza Pereira, Leticia Correa Celeste

Abstract:

Introduction: Studies indicate that equine-assisted therapy enables improvements in several areas of functioning that are impaired in children with autism spectrum disorder (ASD), such as social interaction and communication. Objective: The study proposes to analyze the development of dialogic skills of a verbal child with ASD after participating in the equine-assisted therapy Step By Step in Communication. Method: This is quantitative and qualitative research through a case study. It refers to a 6 years old child diagnosed with ASD belonging to a group of practitioners of the Brazilian National Equine-Assited-Therapy Association. The Behavioral Observation Protocol (PROC) was used to evaluate communicative skills before and after the intervention, which consisted of 24 sessions once a week. Results: All conversational skills increased their frequency, with participation in dialogue and initiation of interaction. The child also increases the habit of waiting for his turn and answering the interlocutor. The emission of topics not related to conversation and echolalia showed a significant decrease after the intervention. Conclusion: The studied child showed improvement in communicative skills after participating in the equine-assisted therapy Step By Step in Communication. Contributions: This study contributes to a greater understanding of the impact of equine-assisted therapy on the communicative abilities of children with ASD.

Keywords: equine-assisted-therapy, autism spectrum disorder, language, communication, language and hearing sciences

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9099 Evaluation of the Microscopic-Observation Drug-Susceptibility Assay Drugs Concentration for Detection of Multidrug-Resistant Tuberculosis

Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

Abstract:

New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

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9098 Financial Problems Met in the Tourism Sector in Turkey: A Survey on the Tourism Businesses

Authors: Raif Parlakkaya, Huseyin Cetin, Halil Akmese, Mesut Murat Adabali

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As the economies of other countries in the Mediterranean Basin, the tourism sector in our country has a high denominator in economics. Tourism businesses, which are building blocks of tourism, sector faces with a variety of problems during their activities. These problems faced make business efficiency and competition conditions of the businesses difficult. Most of the problems faced by the tourism businesses and the information of consumers about consumers’ rights were used in this study, which is conducted to determine the problems of tourism businesses in the Central Anatolia Region. It is aimed to contribute the awareness of staff and executives working at tourism sector and to attract attention of businesses active concurrently with tourism sector and legislators.

Keywords: financial problems, the problems of tourism businesses, tourism businesses, tourism sector in Turkey

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9097 Development and Characterization of Topical 5-Fluorouracil Solid Lipid Nanoparticles for the Effective Treatment of Non-Melanoma Skin Cancer

Authors: Sudhir Kumar, V. R. Sinha

Abstract:

Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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9096 Tobephobia: Fear of Failure in Education Caused by School Violence and Drug Abuse

Authors: Prakash Singh

Abstract:

Schools throughout the world are facing increasing challenges in dealing with school violence and drug abuse by pupils. Therefore, the question of the fear of failure to meet the aims and objectives of education inevitably surfaces as it places increasing and challenging demands on educators and all other stakeholders to address this malaise. Multiple studies on the construct tobephobia (TBP) simply define TBP as the fear of failure in education. This study is a continuation of the exploratory studies on the manifestation of fear in education. The primary purpose of this study was to establish how TBP, caused by school violence and drug abuse affects teaching and learning in our schools. The qualitative research method was used for this study. Teachers admitted that they fear for their safety at school. Working in a fearful situation places a high rate of stress and anxiety on them. Tobephobic educators spend most of their time worrying about their fear of violence and drug abuse by pupils and are too frightened to carry out their normal duties. They prefer to stay in familiar surroundings for fear of being attacked by inebriated learners. This study, therefore, contributes to our understanding of the effects of TBP in our schools caused by school violence and drug abuse. Also, this study supplements the evidence accumulated over the past fifteen years that TBP is not a figment of someone’s imagination; it is a gruesome reality affecting the very foundation of our educational system globally to provide quality and equal education to all our learners in a harmonious, collegial school environment.

Keywords: tobephobia, tobephobic educators, fear of failure in education, school violence, drug abuse

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9095 Intensive Crosstalk between Autophagy and Intracellular Signaling Regulates Osteosarcoma Cell Survival Response under Cisplatin Stress

Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

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Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

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9094 A Preliminary Report of HBV Full Genome Sequencing Derived from Iranian Intravenous Drug Users

Authors: Maryam Vaezjalali, Koroush Rahimian, Maryam Asli, Tahmineh Kandelouei, Foad Davoodbeglou, Amir H. Kashi

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Objectives: The present study was conducted to assess the HBV molecular profiles including genotypes, subgenotypes, subtypes & mutations in hepatitis B genes. Materials/Patients and Methods: This study was conducted on 229 intravenous drug users who referred to three Drop- in-Centers and a hospital in Tehran. HBV DNA was extracted from HBsAg positive serum samples and amplified by Nested PCR. HBV genotype, subgenotypes, subtype and genes mutation were determined by direct sequencing. Phylogenetic tree was constructed using neighbor- joining (NJ) method. Statistical analyses were carried out by SPSS 20. Results: HBV DNA was found in 3 HBsAg positive cases. Phylogenetic tree of derived HBV DNAs showed the existence of genotype D (subgenotype D1, subtype ayw2). Also immune escape mutations were determined in S gene. Conclusion: There were a few variations and genotypes and subtypes among infected intravenous drug users. This study showed the predominance of genotype D among intravenous drug users. Our study concurs with other reports from Iran, that all showing currently only genotype D is the only detectable genotype in Iran.

Keywords: drug users, genotype, HBV, phylogenetic tree

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9093 Detection of Some Drugs of Abuse from Fingerprints Using Liquid Chromatography-Mass Spectrometry

Authors: Ragaa T. Darwish, Maha A. Demellawy, Haidy M. Megahed, Doreen N. Younan, Wael S. Kholeif

Abstract:

The testing of drug abuse is authentic in order to affirm the misuse of drugs. Several analytical approaches have been developed for the detection of drugs of abuse in pharmaceutical and common biological samples, but few methodologies have been created to identify them from fingerprints. Liquid Chromatography-Mass Spectrometry (LC-MS) plays a major role in this field. The current study aimed at assessing the possibility of detection of some drugs of abuse (tramadol, clonazepam, and phenobarbital) from fingerprints using LC-MS in drug abusers. The aim was extended in order to assess the possibility of detection of the above-mentioned drugs in fingerprints of drug handlers till three days of handling the drugs. The study was conducted on randomly selected adult individuals who were either drug abusers seeking treatment at centers of drug dependence in Alexandria, Egypt or normal volunteers who were asked to handle the different studied drugs (drug handlers). An informed consent was obtained from all individuals. Participants were classified into 3 groups; control group that consisted of 50 normal individuals (neither abusing nor handling drugs), drug abuser group that consisted of 30 individuals who abused tramadol, clonazepam or phenobarbital (10 individuals for each drug) and drug handler group that consisted of 50 individuals who were touching either the powder of drugs of abuse: tramadol, clonazepam or phenobarbital (10 individuals for each drug) or the powder of the control substances which were of similar appearance (white powder) and that might be used in the adulteration of drugs of abuse: acetyl salicylic acid and acetaminophen (10 individuals for each drug). Samples were taken from the handler individuals for three consecutive days for the same individual. The diagnosis of drug abusers was based on the current Diagnostic and Statistical Manual of Mental disorders (DSM-V) and urine screening tests using immunoassay technique. Preliminary drug screening tests of urine samples were also done for drug handlers and the control groups to indicate the presence or absence of the studied drugs of abuse. Fingerprints of all participants were then taken on a filter paper previously soaked with methanol to be analyzed by LC-MS using SCIEX Triple Quad or QTRAP 5500 System. The concentration of drugs in each sample was calculated using the regression equations between concentration in ng/ml and peak area of each reference standard. All fingerprint samples from drug abusers showed positive results with LC-MS for the tested drugs, while all samples from the control individuals showed negative results. A significant difference was noted between the concentration of the drugs and the duration of abuse. Tramadol, clonazepam, and phenobarbital were also successfully detected from fingerprints of drug handlers till 3 days of handling the drugs. The mean concentration of the chosen drugs of abuse among the handlers group decreased when the days of samples intake increased.

Keywords: drugs of abuse, fingerprints, liquid chromatography–mass spectrometry, tramadol

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9092 Healthcare Workers' Attitudes Towards People Living With Hiv And Drug Users

Authors: Delband Yekta Moazami

Abstract:

Background: For proper care and treatment of HIV patients and drug users, the medical staff and physicians must have a correct and positive attitude and knowledge towards such patients. We aimed to assess the attitudes in a sample of health care workers (HCW) working in different hospitals and clinics and medical students in Georgia towards HIV infected people and drug users in Tbilisi. Method: We conducted a cross-sectional study to assess attitudes of health care workers towards people living with HIV and drug users in hospitals and clinics in Tbilisi. The study was carried out from 1st of May 2020 till 30th of September 2020. Data were collected using a self-administered structured online questionnaire. With this tool we evaluated four facets of attitudes: Discrimination, Acceptance of HIV/AIDS patients, Acceptance of drug users and Fear. All data were imported and analyzed with the software SPSS 22 for windows. Results: In total data was collected from168 respondents, that among them 107 (65%) were women and majority of the participants were medical doctors. Women had more acceptance attitudes rather than men towards drug abusers. We found significant differences regarding expressing negative attitudes among HCW who were more than 50 years old comparing with other age groups in all four aspects. Medical doctors expressed more acceptances towards people with HIV and drug users comparing two other groups. Also our study revealed that the group with working experience 21 years and more, showed more discriminatory attitudes comparing other groups. Conclusion: Based on our study findings, there are significant differences regarding respondent’s attitudes based on gender, medical specialty and working experience in health care system. People struggling with HIV and drug use need nonjudgmental and positive behaviors from health care workers and physicians in order to help them for harm reduction and receiving appropriate treatment.

Keywords: hiv, addiction, attitudes, healthcare workers

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