Search results for: drug prevention programme

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Nyimas Annissa Mutiara Andini

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There are 325,000 children younger than age 15 in the U.S. have epilepsy. In Indonesia, 40% of 3,5 millions cases of epilepsy happens in children. The most common type of epilepsy, which affects 6 out of 10 people with the disorder, is called idiopathic epilepsy and which has no identifiable cause. One of the most commonly used medications in the treatment of this childhood epilepsy is sodium valproate. Administration of sodium valproat in children has a problem to fail. Nearly 60% of pediatric patients known were mildly, moderately, or severely non-adherent with therapy during the first six months of treatment. Many parents or caregiver took far less medication than prescribed, and the treatment-adherence pattern for the majority of patients was established during the first month of treatment. 42% of the patients were almost always given their medications as prescribed but 13% had very poor adherence even in the early weeks and months of treatment. About 7% of patients initially gave the medication correctly 90% of the time, but adherence dropped to around 20% within six months of starting treatment. Over the six months of observation, the total missing of administration is about four out of 14 doses in any given week. This fail can cause the epilepsy to relapse. Whereas, current reported epilepsy disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P< 0.05). They had a greater risk of limitation in the ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), and potentially having unmet medical and mental health needs. In the other side, technology can help to make our life easier. One of the technology, that we can use is a mobile application. A mobile app is a software program we can download and access directly using our phone. Indonesians are highly mobile centric. They use, on average, 6.7 applications over a 30 day period. This paper is aimed to describe an application that could help to control a sodium valproat administration in children; we call it as D-Epi app. D-Epi app is a downloadable application that can help parents or caregiver alert by a timer-related application to warn whether it is the time to administer the sodium valproat. It works not only as a standard alarm, but also inform important information about the drug and emergency stuffs to do to children with epilepsy. This application could help parents and caregiver to take care a child with epilepsy in Indonesia.

Keywords: application, children, D-Epi, epilepsy

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Authors: Mamiko Orii

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This study reports on primary school second language teachers’ sources of language insecurity. Furthermore, it aims to develop an in-service training course to reduce anxiety and build sufficient English communication skills. Language/Linguistic insecurity refers to a lack of confidence experienced by language speakers. In particular, second language/non-native learners often experience insecurity, influencing their learning efficacy. While language learner insecurity has been well-documented, research on the insecurity of language teaching professionals is limited. Teachers’ language insecurity or anxiety in target language use may adversely affect language instruction. For example, they may avoid classroom activities requiring intensive language use. Therefore, understanding teachers’ language insecurity and providing continuing education to help teachers to improve their proficiency is vital to improve teaching quality. This study investigated Japanese primary school teachers’ language insecurity. In Japan, teachers are responsible for teaching most subjects, including English, which was recently added as compulsory. Most teachers have never been professionally trained in second language instruction during college teacher certificate preparation, leading to low confidence in English teaching. Primary source of language insecurity is a lack of confidence regarding English communication skills. Their actual use of English in classrooms remains unclear. Teachers’ classroom speech remains a neglected area requiring improvement. A more refined programme for second language teachers could be constructed if we can identify areas of need. Two questionnaires were administered to primary school teachers in Tokyo: (1) Questionnaire A: 396 teachers answered questions (using a 5-point scale) concerning classroom teaching anxiety and general English use and needs for in-service training (Summer 2021); (2) Questionnaire B: 20 teachers answered detailed questions concerning their English use (Autumn 2022). Questionnaire A’s responses showed that over 80% of teachers have significant language insecurity and anxiety, mainly when speaking English in class or teaching independently. Most teachers relied on a team-teaching partner (e.g., ALT) and avoided speaking English. Over 70% of the teachers said they would like to participate in training courses in classroom English. Questionnaire B’s results showed that teachers could use simple classroom English, such as greetings and basic instructions (e.g., stand up, repeat after me), and initiate conversation (e.g., asking questions). In contrast, teachers reported that conversations were mainly carried on in a simple question-answer style. They had difficulty continuing conversations. Responding to learners’ ‘on-the-spot’ utterances was particularly difficult. Instruction in turn-taking patterns suitable in the classroom communication context is needed. Most teachers received grammar-based instruction during their entire English education. They were predominantly exposed to displayed questions and form-focused corrective feedback. Therefore, strategies such as encouraging teachers to ask genuine questions (i.e., referential questions) and responding to students with content feedback are crucial. When learners’ utterances are incorrect or unsatisfactory, teachers should rephrase or extend (recast) them instead of offering explicit corrections. These strategies support a continuous conversational flow. These results offer benefits beyond Japan’s English as a second Language context. They will be valuable in any context where primary school teachers are underprepared but must provide English-language instruction.

Keywords: english as a second/non-native language, in-service training, primary school, teachers’ language insecurity

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Authors: Laura Struik, Sarah Dow-Fleisner, Robert Janke

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Introduction: The use of e-cigarettes, also known as vaping, has risen exponentially among North American youth and young adults (YYA) in recent years and has become a critical public health concern. The marketing strategies used by e-cigarette companies have been associated with the uptick in use among YYA, with video advertisements on TV and other electronic platforms being the most pervasive strategy. It is unknown if or how these advertisements capitalize on the recently documented multi-faceted influences that contribute to the initiation of vaping among this demographic (e.g., stress, anxiety, gender, peers, etc.), which is examined in this study. Methods: This content analysis is phase one of a two-phased research project that aims to inform meaningful approaches to anti-vaping messaging and campaigns. As part of this first phase, a scoping review has been conducted to identify various influences (environmental, cognitive, contextual, social, and emotional) on e-cigarette uptake among YYA. The results of this scoping review will inform the development of a coding framework to analyze the multiple influences present in vaping advertisements, as seen on two popular television channels (Discovery and AMC). In addition, advertisement characteristics will be incorporated into the coding framework (e.g., the number of people present, demographic details, context, and setting, etc.), and analyzed. Findings: Findings will reveal the types of influences being leveraged in vaping advertisements, and identify the underlying messages that may be particularly attractive to YYA. This will contribute to a more nuanced understanding of how e-cigarette companies market their products and to whom. The results will also inform the next phase of this research project, which will encompass an analysis of anti-vaping advertisements and how the underpinning strategies align with those of the pro-vaping advertisements. Conclusions: Findings of this will study bring forward important implications for developing effective anti-vaping messages, and assist public health professionals in providing more comprehensive prevention and cessation support as it relates to e-cigarette use. Understanding which marketing strategies e-cigarette companies use is vital to our understanding of how to combat them. Findings will inform recommendations for public health efforts aimed at curbing e-cigarette use among YYA, and ultimately contribute to the health and well-being of YYA.

Keywords: e-cigarettes, youth and young adults, advertisements, public health

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Authors: Simon Nyarko

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This study examined the microbial flora contamination of the Ghanaian paper currency notes and antibiotic resistance in Ejura Municipal, Ashanti Region, Ghana. This is a descriptive cross-sectional study designed to assess the profile of microflora contamination of the Ghanaian paper currency notes and antibiotic-resistant in the Ejura Municipality. The research was conducted in Ejura, a town in the Ejura Sekyeredumase Municipal of the Ashanti region of Ghana. 70 paper currency notes which were freshly collected from the bank, consisting of 15 pieces of GH ¢1, GH ¢2, and GH ¢5, 10 pieces of GH ¢10 and GH ¢20, and 5 pieces of GH ¢50, were randomly sampled from people by exchanging their money in usage with those freshly secured from the bank. The surfaces of each GH¢ note were gently swabbed and sent to the lab immediately in sterile Zip Bags and sealed, and tenfold serial dilution was inoculated on plate count agar (PCA), MacConkey agar (MCA), mannitol salt agar (MSA), and deoxycholate citrate agar (DCA). For bacterial identification, the study used appropriate laboratory and biochemical tests. The data was analyzed using SPSS-IBM version 20.0. It was found that 95.2 % of the 70 GH¢ notes tested positive for one or more bacterial isolates. On each GH¢ note, mean counts on PCA ranged from 3.0 cfu/ml ×105 to 4.8 cfu/ml ×105. Of 124 bacteria isolated. 36 (29.03 %), 32 (25.81%), 16 (12.90 %), 20 (16.13%), 13 (10.48 %), and 7 (5.66 %) were from GH¢1, GH¢2, GH¢10, GH¢5, GH¢20, and GH¢50, respectively. Bacterial isolates were Escherichia coli (25.81%), Staphylococcus aureus (18.55%), coagulase-negative Staphylococcus (15.32%), Klebsiella species (12.10%), Salmonella species (9.68%), Shigella species (8.06%), Pseudomonas aeruginosa (7.26%), and Proteus species (3.23%). Meat shops, commercial drivers, canteens, grocery stores, and vegetable shops contributed 25.81 %, 20.16 %, 19.35 %, 17.74 %, and 16.94 % of GH¢ notes, respectively. There was 100% resistance of the isolates to Erythromycin (ERY), and Cotrimoxazole (COT). Amikacin (AMK) was the most effective among the antibiotics as 75% of the isolates were susceptible to it. This study has demonstrated that the Ghanaian paper currency notes are heavily contaminated with potentially pathogenic bacteria that are highly resistant to the most widely used antibiotics and are a threat to public health.

Keywords: microflora, antibiotic resistance, staphylococcus aureus, culture media, multi-drug resistance

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Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn

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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.

Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins

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Authors: Janet Ige, Paul Pilkington, Selena Gray, Jane Powell

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Older adults from socially disadvantaged groups and Black and Minority Ethnic (BME) groups experience a higher burden of physical inactivity. Physical inactivity among BME groups is associated with the disproportionately higher level of health inequalities. People from minority ethnic groups encounter more barriers to physical activity. However, this is not often reported. There is very limited review-level evidence on the barriers and facilitators of physical activity among older adults from BME groups in the UK. This study aims to answer the following research question: what are the barriers and facilitators of physical activity participation among adults and older adults from BME background in the UK? To address this, we conducted a review of qualitative studies investigating the barriers and opportunities for physical activity among of BME adults and older adults in the UK. Method: This study is nested in an interpretive paradigm of meta-ethnography. A structured search for published literature was conducted on 6 electronic databases (MEDLINE, PsychINFO, Cumulative Index to Nursing & Allied Health Literature, Applied Social Sciences Index and Abstracts, Cochrane Database of Systematic Reviews, Allied and Complementary Medicine) from January 2007 to July 2017. Hand searching of the reference list of publications was performed in addition to a search conducted on Google Scholar to identify grey literature. Studies were eligible provided they employed any qualitative method and included participants identified as being BME, aged 50 and above, living in any community within the UK. In total, 1036 studies were identified from the structured search for literature, 718 studies were screened by titles after duplicates were removed. On applying the inclusion and exclusion criteria, a final selection of 10 studies was considered eligible for synthesis. Quality assessment was performed using the Critical Appraisal Skills Programme tool. Logic maps were used to show the relationship between factors that impact on physical activity participation among adults and older adults Result: Six key themes emerged from the data: awareness of the links between physical activity and health, interaction, and engagement with health professionals, cultural expectations and social responsibilities, appropriate environment, religious fatalism and practical challenges. Findings also showed that the barriers and facilitators of physical activity exist at the individual, community, and socio-economic, cultural and environmental level. There was a substantial gap in research among Black African groups. Findings from the review also informed the design of an ongoing survey investigating the experience and attitude of adults from Somali backgrounds towards physical activity in the UK. Conclusion: Identifying the barriers and facilitators of physical activity among BME groups is a crucial step in addressing the widening inequality gap. Findings from this study highlight the importance of engaging local BME residents in the design of exercise facilities within the community. This will ensure that cultural and social concerns are recognized and properly addressed.

Keywords: BME, UK, meta-ethnographic, adults

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Authors: L. J. de Jager

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In the South African English school curriculum, one of the aims is to achieve communicative competence, the knowledge of using language competently and appropriately in a speech community. Communicatively competent speakers should not only produce grammatically correct sentences but also produce contextually appropriate sentences for various purposes and in different situations. As most speakers of English are non-native speakers, achieving communicative competence remains a complex challenge. Moreover, the changing needs of society necessitate not merely language proficiency, but also technological proficiency. One of the burning issues in the South African educational landscape is the replacement of the standardised literacy model by the pedagogy of multiliteracies that incorporate, by default, the exploration of technological text forms that are part of learners’ everyday lives. It foresees learners as decoders, encoders, and manufacturers of their own futures by exploiting technological possibilities to constantly create and recreate meaning. As such, 21st century learners will feel comfortable working with multimodal texts that are intrinsically part of their lives and by doing so, become authors of their own learning experiences while teachers may become agents supporting learners to discover their capacity to acquire new digital skills for the century of multiliteracies. The aim is transformed practice where learners use their skills, ideas, and knowledge in new contexts. This paper reports on a research project on the integration of technology for language learning, based on the technological pedagogical content knowledge framework, conceptually founded in the theory of multiliteracies, and which aims to achieve communicative competence. The qualitative study uses the community of inquiry framework to answer the research question: How does the integration of technology transform language teaching of preservice teachers? Pre-service teachers in the Postgraduate Certificate of Education Programme with English as methodology were purposively selected to source and evaluate apps for teaching and learning English. The participants collaborated online in a dedicated Blackboard module, using discussion threads to sift through applicable apps and develop interactive lessons using the Apps. The selected apps were entered on to a predesigned Qualtrics form. Data from the online discussions, focus group interviews, and reflective journals were thematically and inductively analysed to determine the participants’ perceptions and experiences when integrating technology in lesson design and the extent to which communicative competence was achieved when using these apps. Findings indicate transformed practice among participants and research team members alike with a better than average technology acceptance and integration. Participants found value in online collaboration to develop and improve their own teaching practice by experiencing directly the benefits of integrating e-learning into the teaching of languages. It could not, however, be clearly determined whether communicative competence was improved. The findings of the project may potentially inform future e-learning activities, thus supporting student learning and development in follow-up cycles of the project.

Keywords: apps, communicative competence, English teaching, technology integration, technological pedagogical content knowledge

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Authors: Nasrin Amirrajab, Yasaman Razavi Ghahfarokhi, Zahra Tootak, Maryam Hadian, Fatemeh Abooali Shamshiri

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Urinary tract infections (UTIs) have been reported in children with nephrotic syndrome. However, the only causes for the infection reported to date are bacteria, but not many prior reported occurrences of fungi or yeast as causative organisms. Hence, the present study aimed to describe the epidemiology of urinary tract fungal infections in a tertiary care pediatric. A single-center cross-sectional study was conducted at the nephrology ward of Aboozar Pediatric Hospital between March 21, 2021, and April 28, 2022. Urine was collected aseptically from children, inoculated onto culture media, and incubated at 37 °C for 18–48 hours. Yeast was identified following standard procedures. Antifungal susceptibility testing was determined by the disk diffusion method according to the CLSI guideline. Descriptive statistics and logistical regressions were used to estimate the crude ratio with a 95% confidence interval. P-value < 0.05 was considered significant. Among 68 individuals referred to the mycology lab, the result of direct examination and culture of all patients approved for C.albicans. Of these, 38 individuals (55.8%) were male, and 30 (44.2%) were female. The patients' age ranges were between one month and an 18-year-old. In the study of infection intensity, the patients were classified into three levels such as few (73.5%), moderate (20.6%), and many (5.9%). In the present study, all the patients were sensitive to Posaconazole. Also, the eagle effect was found in Amphotericin B, Voriconazole, and Fluconazole with frequencies of 91.7%, 91.7%, and 83%, respectively. In addition, just 8.3% of isolates were resistant to Itraconazole. It has not shown resistance in other mentioned medicine. The patients showed an intermediate response to Itraconazole (91.7%), Fluconazole (17%), Voriconazole (8.3%), and Amphotericin B (8.3%). There is a high prevalence of yeast infections in children with suspected UTIs. Also, boys are more likely to get yeast infections, and the severity of the infection is higher than girls. The present study demonstrated the importance of diagnosing and selecting the appropriate drug for urinary tract fungal infections in hospitalized children.

Keywords: urinary tract infections, children, fungal infections, yeast, antifungal susceptibility

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Authors: Abdullah Faqihi, John Hedley

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Biosensors play a significant role in the healthcare sectors, scientific and technological progress. Developing electrodes that are easy to manufacture and deliver better electrochemical performance is advantageous for diagnostics and biosensing. They can be implemented extensively in various analytical tasks such as drug discovery, food safety, medical diagnostics, process controls, security and defence, in addition to environmental monitoring. Development of biosensors aims to create high-performance electrochemical electrodes for diagnostics and biosensing. A biosensor is a device that inspects the biological and chemical reactions generated by the biological sample. A biosensor carries out biological detection via a linked transducer and transmits the biological response into an electrical signal; stability, selectivity, and sensitivity are the dynamic and static characteristics that affect and dictate the quality and performance of biosensors. In this research, a developed experimental study for laser scribing technique for graphene oxide inside a vacuum chamber for processing of graphene oxide is presented. The processing of graphene oxide (GO) was achieved using the laser scribing technique. The effect of the laser scribing on the reduction of GO was investigated under two conditions: atmosphere and vacuum. GO solvent was coated onto a LightScribe DVD. The laser scribing technique was applied to reduce GO layers to generate rGO. The micro-details for the morphological structures of rGO and GO were visualised using scanning electron microscopy (SEM) and Raman spectroscopy so that they could be examined. The first electrode was a traditional graphene-based electrode model, made under normal atmospheric conditions, whereas the second model was a developed graphene electrode fabricated under a vacuum state using a vacuum chamber. The purpose was to control the vacuum conditions, such as the air pressure and the temperature during the fabrication process. The parameters to be assessed include the layer thickness and the continuous environment. Results presented show high accuracy and repeatability achieving low cost productivity.

Keywords: laser scribing, lightscribe DVD, graphene oxide, scanning electron microscopy

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Authors: Valentina Manna, Oscar Pisanti

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The term sibling has been adopted by Italian brothers and sisters of people with disabilities, to define themselves as a group with shared features. This choice is due to the importance of underlying the centrality of what being a brother/sister means to these people because of and beyond the disability. Being a sibling offers great opportunities to develop empathy and relational skills but it may also amplify the typical dynamics of fraternal relationships dealing with envy, rivalry and concern. This outlines a condition of potential developmental risk for the non-disabled sibling, being at the same time a great resource for the child with special needs, as actor of an intimate relationship usually lasting after that one with parents. However, young siblings are often unheeded in their needs for comprehension of disability and not considered as persons requiring attention themselves. Moreover, scholars have scarcely undertaken an exploration of siblings’ perspective as competent contributors for producing knowledge useful to the benefit of families with special needs children. This contribution describes a preventive intervention for young siblings (6 – 16 years) of children with Down syndrome, by means of a psychodynamic-oriented group where participants could communicate, explore and share their emotional experiences as siblings. Based on a participatory approach, the program represents an action-research project, involving siblings as key experts for our understanding of siblings’ lives. The initiative used social media and video technologies to rise children’s voice: as a final product, participants were involved in the realization of a video campaign –which they defined ‘a difficult advertising’– built on the insights generated by the program and addressed to other siblings to help them facing and recognizing resources and difficulties related to their status. The final video campaign realized by the participants summarizes the main themes emerged during the intervention; as revealed by a thematic analysis, they are related to the difficulty in feeling to have a personal identity, to face disability as a form of ‘untought known’ and to integrate ambivalent emotions. In conclusion, the group device revealed its efficacy as a preventive tool: it allowed participants to deeply reflect on their own experiences and to communicate them for the first time in a verbal and mentalized form.

Keywords: down syndrome, group, siblings, prevention

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Authors: Zenaida Chitu, Roxana Bojariu, Liliana Velea, Roxana Burcea

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A number of studies show that extreme air temperature affects mortality related to cardiovascular diseases, particularly among elderly people. In Romania, the summer thermal discomfort expressed by Universal Thermal Climate Index (UTCI) is highest in the Southern part of the country, where Bucharest, the largest Romanian urban agglomeration, is also located. The urban characteristics such as high building density and reduced green areas enhance the increase of the air temperature during summer. In Bucharest, as in many other large cities, the effect of heat urban island is present and determines an increase of air temperature compared to surrounding areas. This increase is particularly important during heat wave periods in summer. In this context, the researchers performed a temperature-mortality analysis based on daily deaths related to cardiovascular diseases, recorded between 2010 and 2019 in Bucharest. The temperature-mortality relationship was modeled by applying distributed lag non-linear model (DLNM) that includes a bi-dimensional cross-basis function and flexible natural cubic spline functions with three internal knots in the 10th, 75th and 90th percentiles of the temperature distribution, for modelling both exposure-response and lagged-response dimensions. Firstly, this study applied this analysis for the present climate. Extrapolation of the exposure-response associations beyond the observed data allowed us to estimate future effects on mortality due to temperature changes under climate change scenarios and specific assumptions. We used future projections of air temperature from five numerical experiments with regional climate models included in the EURO-CORDEX initiative under the relatively moderate (RCP 4.5) and pessimistic (RCP 8.5) concentration scenarios. The results of this analysis show for RCP 8.5 an ensemble-averaged increase with 6.1% of heat-attributable mortality fraction in future in comparison with present climate (2090-2100 vs. 2010-219), corresponding to an increase of 640 deaths/year, while mortality fraction due to the cold conditions will be reduced by 2.76%, corresponding to a decrease by 288 deaths/year. When mortality data is stratified according to the age, the ensemble-averaged increase of heat-attributable mortality fraction for elderly people (> 75 years) in the future is even higher (6.5 %). These findings reveal the necessity to carefully plan urban development in Bucharest to face the public health challenges raised by the climate change. Paper Details: This work is financed by the project URCLIM which is part of ERA4CS, an ERA-NET initiated by JPI Climate, and funded by Ministry of Environment, Romania with co-funding by the European Union (Grant 690462). A part of this work performed by one of the authors has received funding from the European Union’s Horizon 2020 research and innovation programme from the project EXHAUSTION under grant agreement No 820655.

Keywords: cardiovascular diseases, climate change, extreme air temperature, mortality

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Authors: Alice Carter, Lucy Dumbell, Lorna Cameron, Victoria Lewis

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The Olympic discipline of eventing is the triathlon of equestrian sport, consisting of dressage, cross-country and show jumping. Falls on the cross-country are common and can be serious even causing death to rider. Research identifies an increased risk of a fall with an increasing number of obstacles and for jumping efforts later in the course suggesting fatigue maybe a contributing factor. Advice based on anecdotal evidence suggests riders undertake strength and conditioning programs to improve their ‘core’, thus improving their ability to maintain and control their riding position. There is little empirical evidence to support this advice. Therefore, the aim of this study is to investigate truck muscle fatigue and cognitive function during a simulated jumping test. Eight adult riders participated in a riding test on a Racewood Event simulator for 10 minutes, over a continuous jumping programme. The SEMG activity of six trunk muscles were bilaterally measured at every minute, and normalised root mean squares (RMS) and median frequencies (MDF) were computed from the EMG power spectra. Visual analogue scales (VAS) measuring Fatigue and Pain levels and Cognitive Function ‘tapping’ tests were performed before and after the riding test. Average MDF values for all muscles differed significantly between each sampled minute (p = 0.017), however a consistent decrease from Minute 1 and Minute 9 was not found, suggesting the trunk muscles fatigued and then recovered as other muscle groups important in maintaining the riding position during dynamic movement compensated. Differences between the MDF and RMS of different muscles were highly significant (H=213.01, DF=5, p < 0.001), supporting previous anecdotal evidence that different trunk muscles carry out different roles of posture maintenance during riding. RMS values were not significantly different between the sampled minutes or between riders, suggesting the riding test produced a consistent and repeatable effect on the trunk muscles. MDF values differed significantly between riders (H=50.8, DF = 5, p < 0.001), suggesting individuals may experience localised muscular fatigue of the same test differently, and that other parameters of physical fitness should be investigated to provide conclusions. Lumbar muscles were shown to be important in maintaining the position, therefore physical training program should focus on these areas. No significant differences were found between pre- and post-riding test VAS Pain and Fatigue scores or cognitive function test scores, suggesting the riding test was not significantly fatiguing for participants. However, a near significant correlation was found between time of riding test and VAS Pain score (p = 0.06), suggesting somatic pain may be a limiting factor to performance. No other correlations were found between the factors of participant riding test time, VAS Pain and Fatigue, however a larger sample needs to be tested to improve statistical analysis. The findings suggest the simulator riding test was not sufficient to provoke fatigue in the riders, however foundations for future studies have been laid to enable methodologies in realistic eventing settings.

Keywords: eventing, fatigue, horse-rider, surface EMG, trunk muscles

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Authors: Sohan Sengupta, Arnab Pramanik, Abhrajyoti Ghosh, Maitree Bhattacharyya

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Newly emerged phyto-pathogens and multi drug resistance have been threating the world for last few decades. Actinomycetes, the most endowed group of microorganisms isolated from unexplored regions of the world may be the ultimate solution to these problems. Thus the aim of this study was to isolate several bioactive actinomycetes strains capable of producing antimicrobial secondary metabolite from Sundarbans, the only mangrove tiger land of the world. Fifty four actinomycetes were isolated and analyzed for antimicrobial activity against fifteen test organisms including three phytopathogens. Nine morphologically distinct and biologically active isolates were subjected to polyphasic identification study. 16s rDNA sequencing indicated eight isolates to reveal maximum similarity to the genus streptomyces, whereas one isolate presented only 93.57% similarity with Streptomyces albogriseolus NRRL B-1305T. Seventy-one carbon sources and twenty-three chemical sources utilization assay revealed their metabolic relatedness. Among these nine isolates three specific strains were found to have notably higher degree of antimicrobial potential effective in a broader range including phyto-pathogenic fungus. PCR base whole genome screen for PKS and NRPS genes, confirmed the occurrence of bio-synthetic gene cluster in some of the isolates for novel antibiotic production. Finally the strain SMS_SU21, which showed antimicrobial activity with MIC value of 0.05 mg ml-1and antioxidant activity with IC50 value of 0.242±0.33 mg ml-1 was detected to be the most potential one. True prospective of this strain was evaluated utilizing GC-MS and the bioactive compound responsible for antimicrobial activity was purified and characterized. Rare bioactive actinomycetes were isolated from unexplored heritage site. Diversity of the biosynthetic gene cluster for antimicrobial compound production has also been evaluated. Antimicrobial compound SU21-C has been identified and purified which is active against a broad range of pathogens.

Keywords: actinomycetes, sundarbans, antimicrobial, pks nrps, phyto-pathogens, GC-MS

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Authors: Marina Arino Martin, John McEvoy, Eakalak Khan

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Endoxifen is an active metabolite responsible for the effectiveness of tamoxifen, a chemotherapeutic drug widely used for endocrine responsive breast cancer and chemo-preventive long-term treatment. Tamoxifen and endoxifen are not completely metabolized in human body and are actively excreted. As a result, they are released to the water environment via wastewater treatment plants (WWTPs). The presence of tamoxifen in the environment produces negative effects on aquatic lives due to its antiestrogenic activity. Because endoxifen is 30-100 times more potent than tamoxifen itself and also presents antiestrogenic activity, its presence in the water environment could result in even more toxic effects on aquatic lives compared to tamoxifen. Data on actual concentrations of endoxifen in the environment is limited due to recent discovery of endoxifen pharmaceutical activity. However, endoxifen has been detected in hospital and municipal wastewater effluents. The detection of endoxifen in wastewater effluents questions the treatment efficiency of WWTPs. Studies reporting information about endoxifen removal in WWTPs are also scarce. There was a study that used chlorination to eliminate endoxifen in wastewater. However, an inefficient degradation of endoxifen by chlorination and the production of hazardous disinfection by-products were observed. Therefore, there is a need to remove endoxifen from wastewater prior to chlorination in order to reduce the potential release of endoxifen into the environment and its possible effects. The aim of this research is to isolate and identify bacteria strain(s) capable of degrading endoxifen into less hazardous compound(s). For this purpose, bacteria strains from WWTPs were exposed to endoxifen as a sole carbon and nitrogen source for 40 days. Bacteria presenting positive growth were isolated and tested for endoxifen biodegradation. Endoxifen concentration and by-product formation were monitored. The Monod kinetic model was used to determine endoxifen biodegradation rate. Preliminary results of the study suggest that isolated bacteria from WWTPs are able to growth in presence of endoxifen as a sole carbon and nitrogen source. Ongoing work includes identification of these bacteria strains and by-product(s) of endoxifen biodegradation.

Keywords: biodegradation, bacterial degraders, endoxifen, wastewater

Procedia PDF Downloads 215

Authors: Ingrid Ruzbarska, Martin Zvonar, Piotr Oleśniewicz, Julita Markiewicz-Patkowska, Krzysztof Widawski, Daniel Puciato

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Obese children will probably become obese adults, consequently exposed to an increased risk of comorbidity and premature mortality. Body weight may be indirectly determined by continuous development of coordination and motor skills. The level of motor skills and abilities is an important factor that promotes physical activity since early childhood. The aim of the study is to thoroughly understand the internal relations between motor coordination abilities and the somatic development of prepubertal children and to determine the effect of excess body weight on motor coordination by comparing the motor ability levels of children with different body mass index (BMI) values. The data were collected from 436 children aged 7–10 years, without health limitations, fully participating in school physical education classes. Body height was measured with portable stadiometers (Harpenden, Holtain Ltd.), and body mass—with a digital scale (HN-286, Omron). Motor coordination was evaluated with the Kiphard-Schilling body coordination test, Körperkoordinationstest für Kinder. The normality test by Shapiro-Wilk was used to verify the data distribution. The correlation analysis revealed a statistically significant negative association between the dynamic balance and BMI, as well as between the motor quotient and BMI (p<0.01) for both boys and girls. The results showed no effect of gender on the difference in the observed trends. The analysis of variance proved statistically significant differences between normal weight children and their overweight or obese counterparts. Coordination abilities probably play an important role in preventing or moderating the negative trajectory leading to childhood overweight and obesity. At this age, the development of coordination abilities should become a key strategy, targeted at long-term prevention of obesity and the promotion of an active lifestyle in adulthood. Motor performance is essential for implementing a healthy lifestyle in childhood already. Physical inactivity apparently results in motor deficits and a sedentary lifestyle in children, which may be accompanied by excess energy intake and overweight.

Keywords: childhood, KTK test, physical education, psychomotor competence

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Authors: Muhammad Shuaibu Birniwa

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Automobile Independent Workshop Service Technicians (popularly called roadside mechanics) are technical personals that repairs most of the automobile vehicles in Nigeria. Majority of these mechanics acquired their skills through apprenticeship training. Modern vehicle imported into the country posed greater challenges to the present automobile technicians particularly in the area of carrying out maintenance repairs of these latest automobile vehicles (autotronics vehicle) due to their inability to possessed autotronic skills competency. To source for solution to the above mentioned problems, therefore a research is carried out in North – Western region of Nigeria to produce a suitable maintenance training modules that can be used to train the technicians for them to upgrade/acquire the needed competencies for successful maintenance repair of the autotronic vehicles that were running everyday on the nation’s roads. A cluster sampling technique is used to obtain a sample from the population. The population of the study is all autotronic inclined lecturers, instructors and independent workshop service technicians that are within North – Western region of Nigeria. There are seven states (Jigawa, Kaduna, Kano, Katsina, Kebbi, Sokoto and Zamfara) in the study area, these serves as clusters in the population. Five (5) states were randomly selected to serve as the sample size. The five states are Jigawa, Kano, Katsina, Kebbi and Zamfara, the entire population of the five states which serves as clusters is (183), lecturers (44), instructors (49) and autotronic independent workshop service technicians (90), all of them were used in the study because of their manageable size. 183 copies of autotronic maintenance training module questionnaires (AMTMQ) with 174 and 149 question items respectively were administered and collected by the researcher with the help of an assistants, they are administered to 44 Polytechnic lecturers in the department of mechanical engineering, 49 instructors in skills acquisition centres/polytechnics and 90 master craftsmen of an independent workshops that are autotronic inclined. Data collected for answering research questions 1, 3, 4 and 5 were analysed using SPSS software version 22, Grand Mean and standard deviation were used to answer the research questions. Analysis of Variance (ANOVA) was used to test null hypotheses one (1) to three (3) and t-test statistical tool is used to analyzed hypotheses four (4) and five (5) all at 0.05 level of significance. The research conducted revealed that; all the objectives, contents/tasks, facilities, delivery systems and evaluation techniques contained in the questionnaire were required for the development of the autotronic maintenance training modules for independent workshop service technicians in the north – western zone of Nigeria. The skills upgrade training conducted by federal government in collaboration with SURE-P, NAC and SMEDEN was not successful because the educational status of the target population was not considered in drafting the needed training modules. The mode of training used does not also take cognizance of the theoretical aspect of the trainees, especially basic science which rendered the programme ineffective and insufficient for the tasks on ground.

Keywords: autotronics, roadside, mechanics, technicians, independent

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Authors: Pronob Kumar Mozumder M. Nazrul Islam, M. Abdur Rob Mollah

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This study was conducted in Cox’s Bazar-Teknaf Peninsula and Sonadia Island Ecologically Critical Areas during the period of October, 2011 to June, 2013. Six species of marine turtle are found in the Indian Ocean. Among them, olive ridley (Lepidochelys olivacea) listed as endangered in the IUCN Red List of Threatened Species. Marine turtle populations in the Indian Ocean have been depleted through long-term exploitation of eggs and adults, incidental capture (fisheries bycatch) and many other sources of mortality. The specific objective of the study was to conserve the sea turtles specially the olive ridley (Lepidochelys olivacea) with a view to contribute towards protection of the turtle species from extinction and to facilitate hatching of eggs through providing protection to turtle eggs or nest through ex-situ conservation efforts. In order to achieve the desired outputs and success, a total of five turtle hatcheries were established at Pechardwip, Khurermukh, Hazompara, Bodormokam, and Sonadia Eastpara sites. In total, 31,853 eggs were collected from 260 nests and were transferred to five hatcheries. The number of eggs/nest varied from 38 to 190 with an average clutch size of 122 eggs/ nest. Hatching of eggs took place during January to June with a peak in April. Sea turtle eggs were incubated by metabolic heat and the heat of the sun. The incubation period of turtle eggs in Cox’s Bazar-Teknaf Peninsula and Sonadia Island ECAs extended from 54 to 75 days depending on the month with an average of 66 days. During study period the temperature in the ECAs varied between 10.5-34.5°C. A total of 27,937 hatchlings of turtle were produced from the five hatcheries and all the hatchlings produced were released into the sea. Hatching rates varied from 74-98 % depending on the location and months with an average of 88 %. Sea turtles spend the majority of their lives in the sea, only emerging on beaches to nest. Despite the intense conservation efforts on the beaches, some populations have still declined to the edge of extinction. So proper conservation and awareness measure should be taken for prevention of turtle extinction.

Keywords: conservation of sea turtle, Bangladesh, ecologically critical area, ECA, Lepidochelys olivacea

Procedia PDF Downloads 516

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

Procedia PDF Downloads 72

Authors: Ammar Asma, Bouafia Nabiha, Ghammam Rim, Ezzi Olfa, Ben Cheikh Asma, Mahjoub Mohamed, Helali Radhia, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

Abstract:

Background: Central venous catheter associated infections (CVC-AI) are among the serious hospital-acquired infections. The aims of this study are to determine the incidence of CVC-AI, and their risk factors among patients followed in a Tunisian medical intensive care unit (ICU). Materials / Methods: A prospective cohort study conducted between September 15th, 2015 and November 15th, 2016 in an 8-bed medical ICU including all patients admitted for more than 48h. CVC-AI were defined according to CDC of ATLANTA criteria. The enrollment was based on clinical and laboratory diagnosis of CVC-AI. For all subjects, age, sex, underlying diseases, SAPS II score, ICU length of stay, exposure to CVC (number of CVC placed, site of insertion and duration catheterization) were recorded. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: Among 192 eligible patients, 144 patients (75%) had a central venous catheter. Twenty-eight patients (19.4%) had developed CVC-AI with density rate incidence 20.02/1000 CVC-days. Among these infections, 60.7% (n=17) were systemic CVC-AI (with negative blood culture), and 35.7% (n=10) were bloodstream CVC-AI. The mean SAPS II of patients with CVC-AI was 32.76 14.48; their mean Charlson index was 1.77 1.55, their mean duration of catheterization was 15.46 10.81 days and the mean duration of one central line was 5.8+/-3.72 days. Gram-negative bacteria was determined in 53.5 % of CVC-AI (n= 15) dominated by multi-drug resistant Acinetobacter baumani (n=7). Staphylococci were isolated in 3 CVC-AI. Fourteen (50%) patients with CVC-AI died. Univariate analysis identified men (p=0.034), the referral from another hospital department (p=0.03), tobacco (p=0.006), duration of sedation (p=0.003) and the duration of catheterization (p=0), as possible risk factors of CVC-AI. Multivariate analysis showed that independent factors of CVC-AI were, male sex; OR= 5.73, IC 95% [2; 16.46], p=0.001, Ramsay score; OR= 1.57, IC 95% [1.036; 2.38], p=0.033, and duration of catheterization; OR=1.093, IC 95% [1.035; 1.15], p=0.001. Conclusion: In a monocenter cohort, CVC-AI had a high density and is associated with poor outcome. Identifying the risk factors is necessary to find solutions for this major health problem.

Keywords: central venous catheter associated infection, intensive care unit, prospective cohort studies, risk factors

Procedia PDF Downloads 361

Authors: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

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Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

Procedia PDF Downloads 267

Authors: Adepeju Simon-Oke, Olatunji Odeyemi, Mobolanle Oniya

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Urinary tract infection has become the most common bacterial infections in humans, both at the community and hospital settings; it has been reported in all age groups and in both sexes. This study was carried out in order to determine and evaluate the prevalence, current drug susceptibility pattern of the isolated organisms and identify the associated risk factors of UTIs among the pregnant women in Akure, Ondo State, Nigeria. A cross-sectional study was conducted on the urine of pregnant women, and socio-demographic information of the women was collected. A total of 300 clean midstream urine samples were collected, and a general urine microscopic examination and culture were carried out, the Microbact identification system was used to identify gram-negative bacteria. Out of the 300 urine samples cultured, 183(61.0%) yielded significant growth of urinary pathogens while 117(39.0%) yielded either insignificant growth or no growth of any urinary pathogen. Prevalence of UTI was significantly associated with the type of toilet used, symptoms of UTI, and previous history of urinary tract infection (p<0.05). Escherichia coli 58(31.7%) was the dominant pathogen isolated, and the least isolated uropathogens were Citrobacter freudii and Providencia retgerri 2(1.1%) respectively. Gram-negative bacteria showed 77.6%, 67.9%, and 61.2% susceptibility to ciprofloxacin, augmentin, and chloramphenicol, respectively. Resistance against septrin, chloramphenicol, sparfloxacin, amoxicillin, augmentin, gentamycin, pefloxacin, trivid, and streptomycin was observed in the range of 23.1 to 70.1%. Gram-positive uropathogens isolated showed high resistance to amoxicillin (68.4%) and high susceptibility to the remaining nine antibiotics in the range 65.8% to 89.5%. This study justifies that pregnant women are at high risk of UTI. Therefore screening of pregnant women during antenatal clinics should be considered very important to avoid complications. Health education with regular antenatal and personal hygiene is recommended as precautionary measures to UTI.

Keywords: pregnant women, prevalence, risk factor, UTIs

Procedia PDF Downloads 147

Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Djebbar Atmani, Aghiles Karim Aissat, Nadjet Debbache-Benaida, Nassima Chaher-Bazizi, Dina Atmani-Kilani, Meriem Rahmani-Berboucha, Naima Saidene, Malika Benloukil, Lila Azib

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Medicinal plants are believed to be an important source for the discovery of potential antioxidant, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the neuroprotective, anti-inflammatory, anti-diabetic and anti-hyperuricemic potential of Pistacia lentiscus, as well as the identification of active compounds. The antioxidant potential of plant extracts against known radicals was measured using various standard in vitro methods. Anti-inflammatory activity was determined using the paw edema model in mice and by measuring the secretion of the pro-inflammatory cytokine, whereas the anti-diabetic effect was assessed in vivo on streptozotocin-induced diabetic rats and in vitro by inhibition of alpha-amylase. The anti-hyperuricemic activity was evaluated using the xanthine oxidase assay, whereas neuroprotective activity was investigated using an Aluminum-induced toxicity test. Pistacia lentiscus extracts and fractions exhibited high scavenging capacity against DPPH, NO. and ABTS+ radicals in a dose-dependent manner and restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro anti-diabetic effect. Oral administration of plant extracts significantly decreased carrageenan-induced mice paw oedema, similar to the standard drug, diclofenac, was effective in reducing IL-1β levels in cell culture and induced a significant increase in urinary volume in mice, associated to a promising anti-hyperuricemic activity. Plant extracts showed good neuroprotection and restoration of cognitive functions in mice. HPLC-MS and NMR analyses allowed the identification of known and new phenolic compounds that could be responsible for the observed activities. Therefore, Pistacia lentiscus could be beneficial in the treatment of inflammatory conditions and diabetes complications and the enhancement of cognitive functions.

Keywords: Pistacia lentiscus, anti-inflammatory, antidiabetic, flavanols, neuroprotective

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Ahilya Singh, Brad Carte, Ramesh Subramani, William Aalbersberg

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A total of 37 actinomycete strains were purified from 25 Solomon Islands marine sediments using four different types of isolation media. Among them, 54% of the strains had obligate requirement of seawater for growth. The ethyl acetate extract of 100 ml fermentation product of each strain was screened for antimicrobial activity against multidrug resistant human pathogens and cytotoxic activity against brine shrimps. A total of 67% of the ethyl acetate extracts showed antimicrobial and/or cytotoxic activities. A strain F-1915 was selected for isolation and evaluation of bioactive compound(s) based on its bioactive properties and chemical profile analysis using the LC-MS. The strain F-1915 was identified to have 96% sequence similarity to Streptomyces violaceusniger on the basis of 16S rDNA sequences using BLAST analysis. The 16S rDNA revealed that the strain F-1915 is a new member of MAR4 clade of actinomycetes. The MAR4 clade is an interesting clade of actinomycetes known for the production of pharmaceutically important hybrid isoprenoid compounds. The ethyl acetate extract of the fermentation product of this strain was purified by silica gel column chromatography and afforded the isolation of one bioactive pure compound. Based on the 1D and 2D NMR spectral data of compound 1 it was identified as a new mono-brominated phenazinone, Marinophenazimycin A, a structure which has already been studied by external collaborators at Scripps Institution of Oceanography but is yet to be published. Compound 1 displayed significant antimicrobial activity against drug resistant human pathogens. The minimum inhibitory concentration (MIC) of compound 1 was against Methicillin Resistant Staphylococcus aureus (MRSA) was about 1.9 μg/ml and MIC recorded against Amphotericin Resistant Candida albicans (ARCA) was about 0.24 μg/ml. The bioactivity of compound 1 against ARCA was found to be better than the standard antifungal agent amphotericin B. Compound 1 however did not show any cytotoxic activity against brine shrimps.

Keywords: actinomycetes, antimicrobial activity, brominated phenazine, MAR4 clade, marine natural products, multidrug resistent, 1D and 2D NMR

Procedia PDF Downloads 339

Authors: Josué Alfredo Tomas Machaca Fajardo, Jhon Elvis Chahua Janampa, Pedro Rau Lavado

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A flood vulnerability index was developed for the Piura River watershed in northern Peru using Principal Component Analysis (PCA) to assess flood risk. The official methodology to assess risk from natural hazards in Peru was introduced in 1980 and proved effective for aiding complex decision-making. This method relies in part on decision-makers defining subjective correlations between variables to identify high-risk areas. While risk identification and ensuing response activities benefit from a qualitative understanding of influences, this method does not take advantage of the advent of national and international data collection efforts, which can supplement our understanding of risk. Furthermore, this method does not take advantage of broadly applied statistical methods such as PCA, which highlight central indicators of vulnerability. Nowadays, information processing is much faster and allows for more objective decision-making tools, such as PCA. The approach presented here develops a tool to improve the current flood risk assessment in the Peruvian basin. Hence, the spatial analysis of the census and other datasets provides a better understanding of the current land occupation and a basin-wide distribution of services and human populations, a necessary step toward ultimately reducing flood risk in Peru. PCA allows the simplification of a large number of variables into a few factors regarding social, economic, physical and environmental dimensions of vulnerability. There is a correlation between the location of people and the water availability mainly found in rivers. For this reason, a comprehensive vision of the population location around the river basin is necessary to establish flood prevention policies. The grouping of 5x5 km gridded areas allows the spatial analysis of flood risk rather than assessing political divisions of the territory. The index was applied to the Peruvian region of Piura, where several flood events occurred in recent past years, being one of the most affected regions during the ENSO events in Peru. The analysis evidenced inequalities for the access to basic services, such as water, electricity, internet and sewage, between rural and urban areas.

Keywords: assess risk, flood risk, indicators of vulnerability, principal component analysis

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Authors: Misty Attwood, Helgi Schioth

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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Vaibhav D. Bhatt, Anju P. Kunjadia, D. S. Nauriyal, Bhumika J. Joshi, Chaitanya G. Joshi

Abstract:

Metagenomic analysis of milk samples collected from local cattle breed, kankrej (Bos indicus), Gir (Bos indicus) and Crossbred (Bos indicus X Bos taurus) cattle harbouring subclinical mastitis was carried out by next-generation sequencing (NGS) 454 GS-FLX technology. Around 56 different species including members of Enterobacteriales, Pseudomonadales, Bacillales and Lactobacillales with varying abundance were detected in infected milk. The interesting presence of bacteriophages against Staphylococcus aureus, Escherichia coli, Enterobacter and Yersinia species were observed, especially Enterobacteria and E. coli phages (0∙32%) in Kankrej, Enterobacteria and Staphylococcus phages (1∙05%) in Gir and Staphylococcus phages (2∙32%) in crossbred cattle. NGS findings suggest that phages may be involved in imparting natural resistance of the cattle against pathogens. Further infected milk samples were subjected for bacterial isolation. Fourteen different isolates were identified, and DNA was extracted. Genes (Tet-K, Msr-A, and Mec-A) providing antibiotic resistance to the bacteria were screened by Polymerase Chain Reaction and results were validated with traditional antibiotic assay. Total 3 bacteriophages were isolated from nearby environment of the cattle farm. The efficacy of phages was checked against multi-drug resistant bacteria, identified by PCR. In-vivo study was carried out for phage therapy in mammary glands of female rats “Wister albino”. Mammary glands were infused with MDR isolates for 3 consecutive days. Recovery was observed in infected rats after intramammary infusion of sterile phage suspension. From day 4th onwards, level of C-reactive protein was significant increases up to day 12th . However, significant reduction was observed between days 12th to 18th post treatment. Bacteriophages have significant potential as antibacterial agents and their ability to replicate exponentially within their hosts and their specificity, make them ideal candidates for more sustainable mastitis control.

Keywords: bacteriophages, c-reactive protein, mastitis, metagenomic analysis

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