Search results for: exposure therapy
2431 Effectiveness of Medication and Non-Medication Therapy on Working Memory of Children with Attention Deficit and Hyperactivity Disorder
Authors: Mohaammad Ahmadpanah, Amineh Akhondi, Mohammad Haghighi, Ali Ghaleiha, Leila Jahangard, Elham Salari
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Background: Working memory includes the capability to keep and manipulate information in a short period of time. This capability is the basis of complicated judgments and has been attended to as the specific and constant character of individuals. Children with attention deficit and hyperactivity are among the people suffering from deficiency in the active memory, and this deficiency has been attributed to the problem of frontal lobe. This study utilizes a new approach with suitable tasks and methods for training active memory and assessment of the effects of the trainings. Participants: The children participating in this study were of 7-15 year age, who were diagnosed by the psychiatrist and psychologist as hyperactive and attention deficit based on DSM-IV criteria. The intervention group was consisted of 8 boys and 6 girls with the average age of 11 years and standard deviation of 2, and the control group was consisted of 2 girls and 5 boys with an average age of 11.4 and standard deviation of 3. Three children in the test group and two in the control group were under medicinal therapy. Results: Working memory training meaningfully improved the performance in not-trained areas as visual-spatial working memory as well as the performance in Raven progressive tests which are a perfect example of non-verbal, complicated reasoning tasks. In addition, motional activities – measured based on the number of head movements during computerized measuring program – was meaningfully reduced in the medication group. The results of the second test showed that training similar exercise to teenagers and adults results in the improvement of cognition functions, as in hyperactive people. Discussion: The results of this study showed that the performance of working memory is improved through training, and these trainings are extended and generalized in other areas of cognition functions not receiving any training. Trainings resulted in the improvement of performance in the tasks related to prefrontal. They had also a positive and meaningful impact on the moving activities of hyperactive children.Keywords: attention deficit hyperactivity disorder, working memory, non-medical treatment, children
Procedia PDF Downloads 3652430 Acute Myeloid Leukemia Relapse in an a Rare form After Treating his Tuberculosis TB
Authors: Sheikha Turki Alketbi
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Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML
Procedia PDF Downloads 592429 Metal Binding Phage Clones in a Quest for Heavy Metal Recovery from Water
Authors: Tomasz Łęga, Marta Sosnowska, Mirosława Panasiuk, Lilit Hovhannisyan, Beata Gromadzka, Marcin Olszewski, Sabina Zoledowska, Dawid Nidzworski
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Toxic heavy metal ion contamination of industrial wastewater has recently become a significant environmental concern in many regions of the world. Although the majority of heavy metals are naturally occurring elements found on the earth's surface, anthropogenic activities such as mining and smelting, industrial production, and agricultural use of metals and metal-containing compounds are responsible for the majority of environmental contamination and human exposure. The permissible limits (ppm) for heavy metals in food, water and soil are frequently exceeded and considered hazardous to humans, other organisms, and the environment as a whole. Human exposure to highly nickel-polluted environments causes a variety of pathologic effects. In 2008, nickel received the shameful name of “Allergen of the Year” (GILLETTE 2008). According to the dermatologist, the frequency of nickel allergy is still growing, and it can’t be explained only by fashionable piercing and nickel devices used in medicine (like coronary stents and endoprostheses). Effective remediation methods for removing heavy metal ions from soil and water are becoming increasingly important. Among others, methods such as chemical precipitation, micro- and nanofiltration, membrane separation, conventional coagulation, electrodialysis, ion exchange, reverse and forward osmosis, photocatalysis and polymer or carbon nanocomposite absorbents have all been investigated so far. The importance of environmentally sustainable industrial production processes and the conservation of dwindling natural resources has highlighted the need for affordable, innovative biosorptive materials capable of recovering specific chemical elements from dilute aqueous solutions. The use of combinatorial phage display techniques for selecting and recognizing material-binding peptides with a selective affinity for any target, particularly inorganic materials, has gained considerable interest in the development of advanced bio- or nano-materials. However, due to the limitations of phage display libraries and the biopanning process, the accuracy of molecular recognition for inorganic materials remains a challenge. This study presents the isolation, identification and characterisation of metal binding phage clones that preferentially recover nickel.Keywords: Heavy metal recovery, cleaning water, phage display, nickel
Procedia PDF Downloads 982428 The Struggle to teach/learn English as a Foreign Language in Turkiye: A Critical Report
Authors: Gizem Yilmazel
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Turkiye has been facing failure in English language teaching despite long years of English studies during mandatory education. A body of research studying the reasons of the failure in the literature exists yet the problem has not been solved and English language education is still a phenomenon in Turkiye. The failure is mostly attributed to the methods used in English education (Grammar Translation Method), lack of exposure to the language, inability to practice the language, financial difficulties, the belief of abroad experience necessity, national examinations, and conservative institutional policies. The findings are evident and tangible yet the problem persists. This paper aims to bring the issue a critical perspective and discuss the reasons of the failure.Keywords: EFL, failure, critical perspective, language education
Procedia PDF Downloads 522427 Oestrogen Replacement In Post-Oophorectomy Women
Authors: Joana Gato, Ahmed Abotabekh, Panayoti Bachkangi
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Introduction: Oestrogen is an essential gonadal hormone that plays a vital role in the reproductive system of women1. The average age of menopause in the UK is 512. Women who go through premature menopause should be offered Hormone replacement therapy (HRT). Similarly, women who undergo surgical menopause should be offered HRT, unless contraindicated, depending on the indication of their surgery2,3. Aim: To assess if the patients in our department are counselled regarding HRT after surgical treatment and if HRT was prescribed. Methodology: A retrospective audit in a busy district hospital, examining all the patients who had a hysterectomy. The audit examined if HRT was discussed pre-operatively, prescribed on discharge and if a follow up was arranged. For women with contraindication to HRT, the audit assessed if the reasons were discussed pre-operatively and communicated to the Inclusion criteria: woman having a total or subtotal hysterectomy, with or without bilateral salpingo-ophorectomy (BSO), between April and September 2022. Exclusion criteria: woman having a vaginal hysterectomy. Results: 40 patients in total had hysterectomy; 27 (68%) were under the age of 51. 15 out of 27 patients bad BSO. 9 women were prescribed HRT, but 8 were offered HRT immediately, and 1 of them were offered a follow up. Of women who underwent surgical menopause, 7 were not given any HRT. The HRT choice was diverse, however, the majority was prescribed oral HRT. 40% of women undergoing surgical menopause did not have a discussion about HRT prior to their surgery. In postmenopausal women (n=13; 33%), still two were given HRT for preexisting menopausal symptoms. Discussion: Only 59% of the pre-menopausal patients had oophorectomy, therefore undergoing surgical menopause. Of these, 44% were not given any HRT, and 40% had no discussion about HRT prior to surgery. Interestingly, the majority of these women have no obvious contraindication to HRT. The choice of HRT was diverse, but the majority was commenced on oral HRT. Our unit is still working towards meeting all the NICE guidance standards of offering HRT and information prior to surgery to women planning to undergo surgical menopause. Conclusion: Starting HRT at the onset of menopause has been shown to improve quality of life and reduce the risk of cardiovascular disease and osteoporotic fractures4. Our unit still has scope for improvement to comply with the current NICE guidance. All pre-menopausal women undergoing surgical menopause should have a discussion regarding HRT prior to surgery and be offered it if there are no contraindications. This discussion should be clearly documented in the notes. At the time of this report, some of the patients have not yet had a follow up, which we recognize as a limitation to our audit.Keywords: hormone replacement therapy, menopause, premature ovarian insufficiency, surgical management
Procedia PDF Downloads 962426 Investigation the Effect of Nano-Alumina Particles on Physical Adsorption Property of Acrylic Fiber
Authors: Mehdi Ketabchi, Shamsollah Alijanlou
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The flue gas from fossil fuels combustion contains harmful pollutants dangerous for human health and the environment. One of the air pollution control methods to restrict the emission of these pollutants is based on using the nanoparticle in the adsorption process. In the present research gamma, Nano-alumina particle is added to Polyacrylonitrile (PAN) polymer through simple loading method and the adsorption capacity of the wet spun fiber is investigated. The results of exposure the fiber to the acid gasses including SO2, CO, NO2, NO and CO2 show the noticeable increase of gas adsorption capacity on fiber contains nanoparticle. The research has been conducted in Acrylic II Plant of Polyacryl Iran Corporation.Keywords: acrylic fiber, adsorbent, wet spun, nano gamma alumina
Procedia PDF Downloads 3132425 Interdisciplinary Expressive Artistic Activities within Prevention of Crisis Situations and Pathological Strains in Educational Facilities of Juvenile Detention Centres
Authors: Marie Bajnarová
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The core part of the research project is represented by taking a perspective on the role of an educator in Juvenile Institutional Centres. In accordance with the research questions, the research explores impact of the environment, situations, practices, attitudes, values and also experience of the respondents. Art activities minimize risky behaviours and contribute to a healthy lifestyle. They also help children and adolescents with conduct disorders develop positive social behaviour, psychosocial skills and cope with difficult life situations.Keywords: Juvenile Detention Centres, drawing, conduct disorders, art therapy
Procedia PDF Downloads 2812424 Improvement of Fatigue and Fatigue Corrosion Resistances of Turbine Blades Using Laser Cladding
Authors: Sami I. Jafar, Sami A. Ajeel, Zaman A. Abdulwahab
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The turbine blades used in electric power plants are made of low alloy steel type 52. These blades will be subjected to fatigue and also at other times to fatigue corrosion with aging time. Due to their continuous exposure to cyclic rotational stresses in corrosive steam environments, The current research aims to deal with this problem using the laser cladding method for low alloy steel type 52, which works to re-compose the metallurgical structure and improve the mechanical properties by strengthening the resulting structure, which leads to an increase in fatigue and wears resistance, therefore, an increase in the life of these blades is observed.Keywords: fatigue, fatigue corrosion, turbine blades, laser cladding
Procedia PDF Downloads 1962423 Spatial Variability of Renieramycin-M Production in the Philippine Blue Sponge, Xestospongia Sp.
Authors: Geminne Manzano, Porfirio Aliño, Clairecynth Yu, Lilibeth Salvador-Reyes, Viviene Santiago
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Many marine benthic organisms produce secondary metabolites that serve as ecological roles to different biological and environmental factors. The secondary metabolites found in these organisms like algae, sponges, tunicates and worms exhibit variation at different scales. Understanding the chemical variation can be essential in deriving the evolutionary and ecological function of the secondary metabolites that may explain their patterns. Ecological surveys were performed on two collection sites representing from two Philippine marine biogeographic regions – in Oriental Mindoro located on the West Philippine Sea (WPS) and in Zamboanga del Sur located at Celebes Sea (CS), where a total of 39 Xestospongia sp. sponges were collected using SCUBA. The sponge samples were transported to the laboratory for taxonomic identification and chemical analysis. Biological and environmental factors were investigated to determine their relation to the abundance and distribution patterns and its spatial variability of their secondary metabolite production. Extracts were subjected to thin-layer chromatography and anti-proliferative assays to confirm the presence of Renieramycin-M and to test its cytotoxicity. The blue sponges were found to be more abundant on the WPS than in CS. Both the benthic community and the fish community in Oriental Mindoro, WPS and Zamboanga del Sur, CS sites are characterized by high species diversity and abundance and a very high biomass category. Environmental factors like depth and monsoonal exposure were also compared showing that wave exposure and depth are associated with the abundance and distribution of the sponges. Renieramycin-M presence using the TLC profiles between the sponge extracts from WPS and from CS showed differences in the Reniermycin-M presence and the presence of other functional groups were observed between the two sites. In terms of bioactivity, different responses were also exhibited by the sponge extracts coming from the different region. Different responses were also noted on its bioactivity depending on the cell lines tested. Exploring the influence of ecological parameters on the chemical variation can provide deeper chemical ecological insights in the knowledge and their potential varied applications at different scales. The results of this study provide further impetus in pursuing studies into patterns and processes of the chemical diversity of the Philippine blue sponge, Xestospongia sp. and the chemical ecological significance of the coral triangle.Keywords: chemical ecology, porifera, renieramycin-m, spatial variability, Xestospongia sp.
Procedia PDF Downloads 2102422 Ecotoxicity Evaluation and Suggestion of Remediation Method of ZnO Nanoparticles in Aqueous Phase
Authors: Hyunsang Kim, Younghun Kim, Younghee Kim, Sangku Lee
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We investigated ecotoxicity and performed an experiment for removing ZnO nanoparticles in water. Short-term exposure of hatching test using fertilized eggs (O. latipes) showed deformity in 5 ppm of ZnO nanoparticles solution, and in 10ppm ZnO nanoparticles solution delayed hatching was observed. Herein, chemical precipitation method was suggested for removing ZnO nanoparticles in water. The precipitated ZnO nanoparticles showed the form of ZnS after addition of Na2S, and the form of Zn3(PO4)2 for Na2HPO4. The removal efficiency of ZnO nanoparticles in water was closed to 100% for two case. In ecotoxicity evaluation of as-precipitated ZnS and Zn3(PO4)2, they did not cause any acute toxicity for D. magna. It is noted that this precipitation treatment of ZnO is effective to reduce the potential cytotoxicity.Keywords: ZnO nanopraticles, ZnS, Zn3(PO4)2, ecotoxicity evaluation, chemical precipitation
Procedia PDF Downloads 2772421 The Impact of Hosting an On-Site Vocal Concert in Preschool on Music Inspiration and Learning Among Preschoolers
Authors: Meiying Liao, Poya Huang
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The aesthetic domain is one of the six major domains in the Taiwanese preschool curriculum, encompassing visual arts, music, and dramatic play. Its primary objective is to cultivate children’s abilities in exploration and awareness, expression and creation, and response and appreciation. The purpose of this study was to explore the effects of hosting a vocal music concert on aesthetic inspiration and learning among preschoolers in a preschool setting. The primary research method employed was a case study focusing on a private preschool in Northern Taiwan that organized a school-wide event featuring two vocalists. The concert repertoires included children’s songs, folk songs, and arias performed in Mandarin, Hakka, English, German, and Italian. In addition to professional performances, preschool teachers actively participated by presenting a children’s song. A total of 5 classes, comprising approximately 150 preschoolers, along with 16 teachers and staff, participated in the event. Data collection methods included observation, interviews, and documents. Results indicated that both teachers and children thoroughly enjoyed the concert, with high levels of acceptance when the program was appropriately designed and hosted. Teachers reported that post-concert discussions with children revealed the latter’s ability to recall people, events, and elements observed during the performance, expressing their impressions of the most memorable segments. The concert effectively achieved the goals of the aesthetic domain, particularly in fostering response and appreciation. It also inspired preschoolers’ interest in music. Many teachers noted an increased desire for performance among preschoolers after exposure to the concert, with children imitating the performers and their expressions. Remarkably, one class extended this experience by incorporating it into the curriculum, autonomously organizing a high-quality concert in the music learning center. Parents also reported that preschoolers enthusiastically shared their concert experiences at home. In conclusion, despite being a single event, the positive responses from preschoolers towards the music performance suggest a meaningful impact. These experiences extended into the curriculum, as firsthand exposure to performances allowed teachers to deepen related topics, fostering a habit of autonomous learning in the designated learning centers.Keywords: concert, early childhood music education, aesthetic education, music develpment
Procedia PDF Downloads 482420 Post-bladder Catheter Infection
Authors: Mahla Azimi
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Introduction: Post-bladder catheter infection is a common and significant healthcare-associated infection that affects individuals with indwelling urinary catheters. These infections can lead to various complications, including urinary tract infections (UTIs), bacteremia, sepsis, and increased morbidity and mortality rates. This article aims to provide a comprehensive review of post-bladder catheter infections, including their causes, risk factors, clinical presentation, diagnosis, treatment options, and preventive measures. Causes and Risk Factors: Post-bladder catheter infections primarily occur due to the colonization of microorganisms on the surface of the urinary catheter. The most common pathogens involved are Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus species. Several risk factors contribute to the development of these infections, such as prolonged catheterization duration, improper insertion technique, poor hygiene practices during catheter care, compromised immune system function in patients with underlying conditions or immunosuppressive therapy. Clinical Presentation: Patients with post-bladder catheter infections may present with symptoms such as fever, chills, malaise, suprapubic pain or tenderness, and cloudy or foul-smelling urine. In severe cases or when left untreated for an extended period of time, patients may develop more severe symptoms like hematuria or signs of systemic infection. Diagnosis: The diagnosis of post-bladder catheter infection involves a combination of clinical evaluation and laboratory investigations. Urinalysis is crucial in identifying pyuria (presence of white blood cells) and bacteriuria (presence of bacteria). A urine culture is performed to identify the causative organism(s) and determine its antibiotic susceptibility profile. Treatment Options: Prompt initiation of appropriate antibiotic therapy is essential in managing post-bladder catheter infections. Empirical treatment should cover common pathogens until culture results are available. The choice of antibiotics should be guided by local antibiogram data to ensure optimal therapy. In some cases, catheter removal may be necessary, especially if the infection is recurrent or associated with severe complications. Preventive Measures: Prevention plays a vital role in reducing the incidence of post-bladder catheter infections. Strategies include proper hand hygiene, aseptic technique during catheter insertion and care, regular catheter maintenance, and timely removal of unnecessary catheters. Healthcare professionals should also promote patient education regarding self-care practices and signs of infection. Conclusion: Post-bladder catheter infections are a significant healthcare concern that can lead to severe complications and increased healthcare costs. Early recognition, appropriate diagnosis, and prompt treatment are crucial in managing these infections effectively. Implementing preventive measures can significantly reduce the incidence of post-bladder catheter infections and improve patient outcomes. Further research is needed to explore novel strategies for prevention and management in this field.Keywords: post-bladder catheter infection, urinary tract infection, bacteriuria, indwelling urinary catheters, prevention
Procedia PDF Downloads 802419 The Fantasy of the Media and the Sexual World of Adolescents: The Relationship between Viewing Sexual Content on Television and Sexual Behaviour of Adolescents
Authors: Ifeanyi Adigwe
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The influence of television on adolescents is prevalent and widespread because television is a powerful sex educator for adolescents. This study examined the relationship between viewing sexual content on television and sexual behaviour of adolescents in public senior secondary schools in Lagos, Nigeria. The study employed a survey research design with a structured questionnaire as instrument. The multi-stage sampling technique was adopted. Firstly, purposive sampling was adopted in selecting 3 educational districts namely: Agege, Maryland, and Agboju. These educational districts were chosen for convenience and its wide coverage area of public senior secondary schools in Lagos State. Secondly, the researcher adopted systematic sampling to select the schools. The schools were listed in alphabetical order in each district and every 10th school were selected, yielding 13 schools altogether. A total of 501 copies of questionnaire were administered to the students and a total 491 copies of the questionnaire were retrieved. Only 453 copies of the questionnaire met the inclusion criteria and were used for analysis. Data were analyzed using descriptive statistics, Pearson Correlation, Principal components analysis, and regression analysis. Results of correlation analysis showed a positive and significant relationship between adolescent sexual belief and their preference for sexual content in television (r =0.117, N =453, p=0.13), viewing sexual content on television and adolescent sexual behavior, (r =-0.112, N =453, p<0.05), adolescent television preference and their preference for sexual content in television (r =0.328, N =453, p<0.05), adolescent television preference and adolescent’s sexual behavior (r=0.093, N =453, p<0.05). However, a negative but significant relationship exists between adolescent’s sexual knowledge and their sexual behavior (r=-122, N=453, p=0.0009). Pearson’s correlation between adolescents’ sexual knowledge and sexual behavior shows that there is a positive significant but strong relationship between adolescent’s sexual knowledge and their sexual behavior (r=0.967, N=453, p<0.05). The results also show that adolescent’s preference for sexual content in television informs them about their sexuality, development and sexual health. The descriptive and inferential analysis of data revealed that the interaction among adolescent sexual belief, knowledge and adolescents’ preference of sexual in television and its resultant effect on adolescent sexual behavior is apparent because sexual belief and norms about sex of an adolescent can induce his television preference of sexual content on television. The study concludes that exposure to sexual content in television can impact on adolescent sexual behaviour. There is no doubt that the actual outcome of television viewing and adolescent sexual behavior remains controversial because adolescent sexual behavior is multifaceted and multi-dimensional. Since behavior is learned overtime, the frequency of exposure and nature of sexual content viewed overtime induces and hastens sexual activity.Keywords: adolescent sexual behavior, Nigeria, sexual belief, sexual content, sexual knowledge, television preference
Procedia PDF Downloads 3922418 Chloride Transport in Ultra High Performance Concrete
Authors: Radka Pernicova
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Chloride resistance in Ultra High Performance Concrete (UHPC) is determined in this paper. This work deals with the one dimension chloride transport, which can be potentially dangerous particularly for the durability of concrete structures. Risk of reinforcement corrosion due to exposure to the concrete surface to direct the action of chloride ions (mainly in the form de-icing salts or groundwater) is dangerously increases. The measured data are investigated depending on the depth of penetration of chloride ions into the concrete structure. Comparative measurements with normal strength concrete are done as well. The experimental results showed that UHCP have improved resistance of chlorides penetration than NSC and also chloride diffusion depth is significantly lower in UHCP.Keywords: chloride, one dimensional diffusion, transport, salinity, UHPC
Procedia PDF Downloads 4322417 An Interview and PhotoVoice Exploration of Sexual Education Provision to Women with Physical Disability and Potential Experiences of Violence
Authors: D. Beckwith
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This research explored sexual identity for women with physical disability, both congenital and acquired. It also explored whether exposure to violence or negative risk-taking had played a role in their intimate relationships. This phenomenological research used semi-structured interviews and photo elicitation with the researcher’s insider knowledge adding experiential substance and understanding to the discussion. Findings confirm sexuality for women with physical disability is marginalised and de-gendered making it less of a priority for professionals and policy makers and emphasising the need to more effectively support women with disability in relation to their sexuality, sexual expression and violence.Keywords: lived-experience, identity, PhotoVoice, sexuality, violence, women with physical disability
Procedia PDF Downloads 1332416 Perceived Restorativeness Scale– 6: A Short Version of the Perceived Restorativeness Scale for Mixed (or Mobile) Devices
Authors: Sara Gallo, Margherita Pasini, Margherita Brondino, Daniela Raccanello, Roberto Burro, Elisa Menardo
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Most of the studies on the ability of environments to recover people’s cognitive resources have been conducted in laboratory using simulated environments (e.g., photographs, videos, or virtual reality), based on the implicit assumption that exposure to simulated environments has the same effects of exposure to real environments. However, the technical characteristics of simulated environments, such as the dynamic or static characteristics of the stimulus, critically affect their perception. Measuring perceived restorativeness in situ rather than in laboratory could increase the validity of the obtained measurements. Personal mobile devices could be useful because they allow accessing immediately online surveys when people are directly exposed to an environment. At the same time, it becomes important to develop short and reliable measuring instruments that allow a quick assessment of the restorative qualities of the environments. One of the frequently used self-report measures to assess perceived restorativeness is the “Perceived Restorativeness Scale” (PRS) based on Attention Restoration Theory. A lot of different versions have been proposed and used according to different research purposes and needs, without studying their validity. This longitudinal study reported some preliminary validation analyses on a short version of original scale, the PRS-6, developed to be quick and mobile-friendly. It is composed of 6 items assessing fascination and being-away. 102 Italian university students participated to the study, 84% female with age ranging from 18 to 47 (M = 20.7; SD = 2.9). Data were obtained through a survey online that asked them to report their perceived restorativeness of the environment they were in (and the kind of environment) and their positive emotion (Positive and Negative Affective Schedule, PANAS) once a day for seven days. Cronbach alpha and item-total correlations were used to assess reliability and internal consistency. Confirmatory Factor Analyses (CFA) models were run to study the factorial structure (construct validity). Correlation analyses between PRS and PANAS scores were used to check discriminant validity. In the end, multigroup CFA models were used to study measurement invariance (configural, metric, scalar, strict) between different mobile devices and between day of assessment. On the whole, the PRS-6 showed good psychometric proprieties, similar to those of the original scale, and invariance across devices and days. These results suggested that the PRS-6 could be a valid alternative to assess perceived restorativeness when researchers need a brief and immediate evaluation of the recovery quality of an environment.Keywords: restorativeness, validation, short scale development, psychometrics proprieties
Procedia PDF Downloads 2502415 Computer-Aided Drug Repurposing for Mycobacterium Tuberculosis by Targeting Tryptophanyl-tRNA Synthetase
Authors: Neslihan Demirci, Serdar Durdağı
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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis
Procedia PDF Downloads 1212414 Formulation and Evaluation of Curcumin-Zn (II) Microparticulate Drug Delivery System for Antimalarial Activity
Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar
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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics
Procedia PDF Downloads 3922413 Influence of Cucurbitacin-Containing Phytonematicides on Nematode Biocontrol Agent: Trichoderma harzianum
Authors: Jacqueline T. Madaure, Phatu W. Mashela
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Cucurbitacin-containing phytonematicides consistently suppress root-knot (Meloidogyne species) nematode population densities. However, the impact of these products on nematode biocontrol agents is not documented. The objective of this study was to determine the influence of Nemarioc-AL and Nemafric-BL phytonematicides on growth of Trichoderma harzianum under in vitro conditions. The two phytonematicides were separately prepared to concentrations of 3% and used in poison plate assays. After exposure at different times from 0 to 72 h, there was 100% mycelial growth of T. harzianum. In conclusion, at the recommended concentrations of phytonematicides used in managing nematode population densities, there was no evidence of suppressive effects on growth of T. harzianum by the two phytonematicides.Keywords: botanicals, crude extracts, cucumis africanus, cucumis myriocarpus, cucurbitacin a, cucurbitacin b, ethnomedicinal plants
Procedia PDF Downloads 2172412 Siderophore Receptor Protein from Klebsiella pneumoniae as a Promising Immunogen for Serotype-Independent Therapeutic Lead Development
Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri
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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor
Procedia PDF Downloads 1002411 Effect of Whey Proteins and Caffeic Acid Interactions on Antioxidant Activity and Protein Structure
Authors: Tassia Batista Pessato, Francielli Pires Ribeiro Morais, Fernanda Guimaraes Drummond Silva, Flavia Maria Netto
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Proteins and phenolic compounds can interact mainly by hydrophobic interactions. Those interactions may lead to structural changes in both molecules, which in turn could affect positively or negatively their functional and nutritional properties. Here, the structural changes of whey proteins (WPI) due to interaction with caffeic acid (CA) were investigated by intrinsic and extrinsic fluorescence. The effects of protein-phenolic compounds interactions on the total phenolic content and antioxidant activity were also assessed. The WPI-CA complexes were obtained by mixture of WPI and CA stock solutions in deionized water. The complexation was carried out at room temperature during 60 min, using 0.1 M NaOH to adjust pH at 7.0. The WPI concentration was fixed at 5 mg/mL, whereas the CA concentration varied in order to obtain four different WPI:CA molar relations (1:1; 2:1; 5:1; 10:1). WPI and phenolic solutions were used as controls. Intrinsic fluorescence spectra of the complexes (mainly due to Trp fluorescence emission) were obtained at λex = 280 nm and the emission intensities were measured from 290 to 500 nm. Extrinsic fluorescence was obtained as the measure of protein surface hydrophobicity (S0) using ANS as a fluorescence probe. Total phenolic content was determined by Folin-Ciocalteau and the antioxidant activity by FRAP and ORAC methods. Increasing concentrations of CA resulted in decreasing of WPI intrinsic fluorescence. The emission band of WPI red shifted from 332 to 354 nm as the phenolic concentration increased, which is related to the exposure of Trp residue to the more hydrophilic environment and unfolding of protein structure. In general, the complexes presented lower S0 values than WPI, suggesting that CA hindered ANS binding to hydrophobic sites of WPI. The total phenolic content in the complexes was lower than the sum of two compounds isolated. WPI showed negligible AA measured by FRAP. However, as the relative concentration of CA increased in the complexes, the FRAP values enhanced, indicating that AA measure by this technique comes mainly from CA. In contrast, the WPI ORAC value (82.3 ± 1.5 µM TE/g) suggest that its AA is related to the capacity of H+ transfer. The complexes exhibited no important improvement of AA measured by ORAC in relation to the isolated components, suggesting complexation partially suppressed AA of the compounds. The results hereby presented indicate that interaction of WPI and CA occurred, and this interaction caused a structural change in the proteins. The complexation can either hide or expose antioxidant sites of both components. In conclusion, although the CA can undergo an AA suppression due to the interaction with proteins, the AA of WPI could be enhanced due to protein unfolding and exposure of antioxidant sites.Keywords: bioactive properties, milk proteins, phenolic acids, protein-phenolic compounds complexation
Procedia PDF Downloads 5472410 The Investigation of Endogenous Intoxication and Lipid Peroxidation in Patients with Giardiasis Before and After Treatment
Authors: R. H. Begaydarova, B. Zh. Kultanov, B. T. Esilbaeva, G. E. Nasakaeva, Y. Yukhnevich, G. K. Alshynbekova, A. E. Dyusembaeva
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Background: The level of middle molecules of peptides (MMP) allows to evaluate the severity and prognosis of the disease and is a criterion for the effectiveness of the treatment. The detection the products of lipidperoxidation cascade, such as conjugated dienes, malondialdehyde in biological material, has an important role in the development of pathogenesis, the diagnosis and prognosis in different parasitic diseases. Purpose of the study was to evaluate the state of endogenous intoxication and indicators of lipid peroxidation in patients with giardiasis before and after treatment. Materials and methods: Endogenous intoxication was evaluated in patients with giardiasis in the level of middle molecules of peptides (MMP) in the blood. The amount of MMP and products of lipid peroxidation were determined in the blood of 198 patients with giardiasis, 129 of them were women (65%), 69 were men (35%). The MMP level was detected for comparison in the blood of 84 healthy volunteers. The lipid peroxidation were determined in 40 healthy men and women without giardiasis and history of chronic diseases. Data were processed by conventional methods of variation statistics, we calculated the arithmetic mean (M) and standard dispersion (m). t-test (t) was used to assess differences. Results: The level of MMP in the blood was significantly higher in patients with giardiasis in comparison with group of healthy men and women. MMP concentration in the blood of women with Giardia was 2.5 times greater than that of the comparison groups of women. The level of MMP exceeds more than 6 times in men with giardiasis. The decrease in the intensity of endogenous intoxication was two weeks after antigiardia therapy, both men and women. According to the study, a statistically significant increase in the level of all the studied parameters lipid peroxidation cascade was observed in the blood of men with giardiasis, with the exception of the total primary production (NGN). The treatment of giardiasis helped to stabilize the level of almost all metabolites of lipid peroxidation cascade. The exception was level of malondialdehyde, it was significantly elevated to compare with the control group and after treatment. Conclusion: Thus, the MMP level was significantly higher in blood of patients with giardiasis than in comparison group. This is evidence of severe endogenous intoxication caused by giardia infection. The accumulation of primary and secondary products of lipid peroxidation was observed in the blood of men and women. These processes tend to be more active in men than in women. Antigiardiasis therapy contributed to the normalization of almost all the studied indicators of lipid peroxidation in the blood of participants, except the level malondialdehyde in the blood of men.Keywords: enzymes of antioxidant protection, giardiasis, blood, treatment
Procedia PDF Downloads 2362409 Evaluation of Occupational Doses in Interventional Radiology
Authors: Fernando Antonio Bacchim Neto, Allan Felipe Fattori Alves, Maria Eugênia Dela Rosa, Regina Moura, Diana Rodrigues De Pina
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Interventional Radiology is the radiology modality that provides the highest dose values to medical staff. Recent researches show that personal dosimeters may underestimate dose values in interventional physicians, especially in extremities (hands and feet) and eye lens. The aim of this work was to study radiation exposure levels of medical staff in different interventional radiology procedures and estimate the annual maximum numbers of procedures (AMN) that each physician could perform without exceed the annual limits of dose established by normative. For this purpose LiF:Mg,Ti (TLD-100) dosimeters were positioned in different body regions of the interventional physician (eye lens, thyroid, chest, gonads, hand and foot) above the radiological protection vests as lead apron and thyroid shield. Attenuation values for lead protection vests were based on international guidelines. Based on these data were chosen as 90% attenuation of the lead vests and 60% attenuation of the protective glasses. 25 procedures were evaluated: 10 diagnostics, 10 angioplasty, and 5-aneurysm treatment. The AMN of diagnostic procedures was 641 for the primary interventional radiologist and 930 for the assisting interventional radiologist. For the angioplasty procedures, the AMN for primary interventional radiologist was 445 and for assisting interventional radiologist was 1202. As for the procedures of aneurism treatment, the AMN for the primary interventional radiologist was 113 and for the assisting interventional radiologist were 215. All AMN were limited by the eye lens doses already considering the use of protective glasses. In all categories evaluated, the higher dose values are found in gonads and in the lower regions of professionals, both for the primary interventionist and for the assisting, but the eyes lens dose limits are smaller than these regions. Additional protections as mobile barriers, which can be positioned between the interventionist and the patient, can decrease the exposures in the eye lens, providing a greater protection for the medical staff. The alternation of professionals to perform each type of procedure can reduce the dose values received by them over a period. The analysis of dose profiles proposed in this work showed that personal dosimeters positioned in chest might underestimate dose values in other body parts of the interventional physician, especially in extremities and eye lens. As each body region of the interventionist is subject to different levels of exposure, dose distribution in each region provides a better approach to what actions are necessary to ensure the radiological protection of medical staff.Keywords: interventional radiology, radiation protection, occupationally exposed individual, hemodynamic
Procedia PDF Downloads 3932408 Applications of AFM in 4D to Optimize the Design of Genetic Nanoparticles
Authors: Hosam Abdelhady
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Filming the behaviors of individual DNA molecules in their environment when they interact with individual medicinal nano-polymers in a molecular scale has opened the door to understand the effect of the molecular shape, size, and incubation time with nanocarriers on optimizing the design of robust genetic Nano molecules able to resist the enzymatic degradation, enter the cell, reach to the nucleus and kill individual cancer cells in their environment. To this end, we will show how we applied the 4D AFM as a guide to finetune the design of genetic nanoparticles and to film the effects of these nanoparticles on the nanomechanical and morphological profiles of individual cancer cells.Keywords: AFM, dendrimers, nanoparticles, DNA, gene therapy, imaging
Procedia PDF Downloads 722407 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent
Authors: Kuladip Jana
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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin
Procedia PDF Downloads 2572406 Features of Normative and Pathological Realizations of Sibilant Sounds for Computer-Aided Pronunciation Evaluation in Children
Authors: Zuzanna Miodonska, Michal Krecichwost, Pawel Badura
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Sigmatism (lisping) is a speech disorder in which sibilant consonants are mispronounced. The diagnosis of this phenomenon is usually based on the auditory assessment. However, the progress in speech analysis techniques creates a possibility of developing computer-aided sigmatism diagnosis tools. The aim of the study is to statistically verify whether specific acoustic features of sibilant sounds may be related to pronunciation correctness. Such knowledge can be of great importance while implementing classifiers and designing novel tools for automatic sibilants pronunciation evaluation. The study covers analysis of various speech signal measures, including features proposed in the literature for the description of normative sibilants realization. Amplitudes and frequencies of three fricative formants (FF) are extracted based on local spectral maxima of the friction noise. Skewness, kurtosis, four normalized spectral moments (SM) and 13 mel-frequency cepstral coefficients (MFCC) with their 1st and 2nd derivatives (13 Delta and 13 Delta-Delta MFCC) are included in the analysis as well. The resulting feature vector contains 51 measures. The experiments are performed on the speech corpus containing words with selected sibilant sounds (/ʃ, ʒ/) pronounced by 60 preschool children with proper pronunciation or with natural pathologies. In total, 224 /ʃ/ segments and 191 /ʒ/ segments are employed in the study. The Mann-Whitney U test is employed for the analysis of stigmatism and normative pronunciation. Statistically, significant differences are obtained in most of the proposed features in children divided into these two groups at p < 0.05. All spectral moments and fricative formants appear to be distinctive between pathology and proper pronunciation. These metrics describe the friction noise characteristic for sibilants, which makes them particularly promising for the use in sibilants evaluation tools. Correspondences found between phoneme feature values and an expert evaluation of the pronunciation correctness encourage to involve speech analysis tools in diagnosis and therapy of sigmatism. Proposed feature extraction methods could be used in a computer-assisted stigmatism diagnosis or therapy systems.Keywords: computer-aided pronunciation evaluation, sigmatism diagnosis, speech signal analysis, statistical verification
Procedia PDF Downloads 2992405 A Biophysical Model of CRISPR/Cas9 on- and off-Target Binding for Rational Design of Guide RNAs
Authors: Iman Farasat, Howard M. Salis
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The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.Keywords: biophysical model, CRISPR, Cas9, genome editing
Procedia PDF Downloads 4022404 Resistance of Mycobacterium tuberculosis to Daptomycin
Authors: Ji-Chan Jang
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Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis
Procedia PDF Downloads 3822403 Maternal Health Care Mirage: A Study of Maternal Health Care Utilization for Young Married Muslim Women in India
Authors: Saradiya Mukherjee
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Background: Indian Muslims, compared to their counterparts in other religions, generally do not fare well on many yardsticks related to socio-economic progress and the same is true with maternal health care utilization. Due to low age at marriage a major percentage of child birth is ascribed to young (15-24 years) Muslim mothers in, which pose serious concerns on the maternal health care of Young Married Muslim women (YMMW). A thorough search of past literature on Muslim women’s health and health care reveals that studies in India have mainly focused on religious differences in fertility levels and contraceptive use while the research on the determinants of maternal health care utilization among Muslim women are lacking in India. Data and Methods: Retrieving data from the National Family Health Survey -3 (2005-06) this study attempts to assess the level of utilization and factors effecting three key maternal health indicators (full ANC, safe delivery and PNC) among YMMW (15-24 years) in India. The key socio-economic and demographic variables taken as independent or predictor variables in the study was guided by existing literature particularly for India. Bi-variate analysis and chi square test was applied and variables which were found to be significant were further included in binary logistic regression. Results: The findings of the study reveal abysmally low levels of utilization for all three indicators i.e. full ANC, safe delivery and PNC of maternal health care included in the study. Mother’s education, mass media exposure, women’s autonomy, birth order, economic status wanted status of child and region of residence were found to be significant variables effecting maternal health care utilization among YMMW. Multivariate analysis reveals that no mass media exposure, lower autonomy, education, poor economic background, higher birth order and unintended pregnancy are some of the reasons behind low maternal health care utilization. Conclusion: Considering the low level of safe maternal health care utilization and its proximate determinants among YMMW the study suggests educating Muslim girls, promoting family planning use, involving media and collaboration between religious leader and health care system could be some important policy level interventions to address the unmet need of maternity services among YMMW.Keywords: young Muslim women, religion, socio-economic condition, antenatal care, delivery, post natal care
Procedia PDF Downloads 3352402 Impact of Solar Radiation Effects on the Physicochemical Properties of Unformulated Polyethylene (PE) Plastic Film
Authors: A. Adelhafidhi, I. M. Babaghayou, S. F. Chabira, M. Sebaa
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This study deals with the photodegradation of unformulated polyethylene films for greenhouse covering. The UV range of solar light appears as the most deleterious factor of plastic degradation in outdoor exposure. The reasons of this photosensitivity are structural defects which are light-absorbing. The use of FTIR as an investigation tool has revealed that the material reacts with surrounding oxygen via a photooxidation process. Although the photochemical process is quite complex, it appears through this study than crosslinking and chain scissions are the most important events taking place during aging These two key reactions change irremediably the average molecular weight affecting thus drastically the mechanical properties and reducing, in the same way, the service lifetime of the films.Keywords: polyethylene, films, unformulated, FTIR, ageing
Procedia PDF Downloads 366