Search results for: drug reaction with eosinophilia and systemic symptoms
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6158

Search results for: drug reaction with eosinophilia and systemic symptoms

3938 Women Empowerment and Sustainable Community Development: Understanding the Challenges for Responsive Action

Authors: Albert T. Akume, Ankama G. Rosecana, Micheal Solomon

Abstract:

Every citizen has rights that must be respected by others in the community. Ironically however, women in most communities are not accorded some of those rights as the male folks. This has not only facilitated their disempowerment but inhibited them from being treated with equal dignity that they deserve as their male counterpart; despite their valuable contribution to the society. Those forces against women empowerment are not limited to socio-cultural practices alone, but the character and nature of the state in Nigeria point to indicators of systemic and structural exclusion embedded in its framework. The consequence of this is that the vital contributions of women to sustainable community development have eluded many communities in Nigeria with adverse tell-tell signs on the environment. It is for this reason that the objective of this study is not only to highlight the causes and challenges associated with women disempowerment, but also to draw attention to the need to correct those anomaly against women in order to genuinely empower them to contribute to sustainable community development in Nigeria.

Keywords: capacity development, community, social sustainability, sustainable development, women empowerment

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3937 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

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3936 The Development of Congeneric Elicited Writing Tasks to Capture Language Decline in Alzheimer Patients

Authors: Lise Paesen, Marielle Leijten

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People diagnosed with probable Alzheimer disease suffer from an impairment of their language capacities; a gradual impairment which affects both their spoken and written communication. Our study aims at characterising the language decline in DAT patients with the use of congeneric elicited writing tasks. Within these tasks, a descriptive text has to be written based upon images with which the participants are confronted. A randomised set of images allows us to present the participants with a different task on every encounter, thus allowing us to avoid a recognition effect in this iterative study. This method is a revision from previous studies, in which participants were presented with a larger picture depicting an entire scene. In order to create the randomised set of images, existing pictures were adapted following strict criteria (e.g. frequency, AoA, colour, ...). The resulting data set contained 50 images, belonging to several categories (vehicles, animals, humans, and objects). A pre-test was constructed to validate the created picture set; most images had been used before in spoken picture naming tasks. Hence the same reaction times ought to be triggered in the typed picture naming task. Once validated, the effectiveness of the descriptive tasks was assessed. First, the participants (n=60 students, n=40 healthy elderly) performed a typing task, which provided information about the typing speed of each individual. Secondly, two descriptive writing tasks were carried out, one simple and one complex. The simple task contains 4 images (1 animal, 2 objects, 1 vehicle) and only contains elements with high frequency, a young AoA (<6 years), and fast reaction times. Slow reaction times, a later AoA (≥ 6 years) and low frequency were criteria for the complex task. This task uses 6 images (2 animals, 1 human, 2 objects and 1 vehicle). The data were collected with the keystroke logging programme Inputlog. Keystroke logging tools log and time stamp keystroke activity to reconstruct and describe text production processes. The data were analysed using a selection of writing process and product variables, such as general writing process measures, detailed pause analysis, linguistic analysis, and text length. As a covariate, the intrapersonal interkey transition times from the typing task were taken into account. The pre-test indicated that the new images lead to similar or even faster reaction times compared to the original images. All the images were therefore used in the main study. The produced texts of the description tasks were significantly longer compared to previous studies, providing sufficient text and process data for analyses. Preliminary analysis shows that the amount of words produced differed significantly between the healthy elderly and the students, as did the mean length of production bursts, even though both groups needed the same time to produce their texts. However, the elderly took significantly more time to produce the complex task than the simple task. Nevertheless, the amount of words per minute remained comparable between simple and complex. The pauses within and before words varied, even when taking personal typing abilities (obtained by the typing task) into account.

Keywords: Alzheimer's disease, experimental design, language decline, writing process

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3935 Determinants of Post-Psychotic Depression in Schizophrenia Patients in ACSH and Mekellle Hospital Tigray, Ethiopia, 2019

Authors: Ashenafi Ayele, Shewit Haftu, Tesfalem Araya

Abstract:

Background: “Post-psychotic depression”, “post schizophrenic depression”, and “secondary depression” have been used to describe the occurrence of depressive symptoms during the chronic phase of schizophrenia. Post-psychotic depression is the most common cause of death due to suicide in schizophrenia patients. Overall lifetime risk for patients with schizophrenia is 50% for suicide attempts and 9-13% lifetime risk for completed suicide and also it is associated with poor prognosis and poor quality of life. Objective: To assess determinant of post psychotic depression in schizophrenia patients ACSH and Mekelle General Hospital, Tigray Ethiopia 2019. Methods: An institutional based unmatched case control study was conducted among 69 cases and 138 controls with the ratio of case to control 1 ratio 2. The sample is calculated using epi-info 3.1 to assess the determinant factors of post-psychotic depression in schizophrenia patients. The cases were schizophrenia patients who have been diagnosed at least for more than one-year stable for two months, and the controls are any patients who are diagnosed as schizophrenia patients. Study subjects were selected using a consecutive sampling technique. The Calgary depression scale for schizophrenia self-administered questionnaire was used. Before the interview, it was assessed the client’s capacity to give intended information using a scale called the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC). Bivariant and multiple Logistic regression analysis was performed to determine between the independent and dependent variables. The significant independent predictor was declared at 95% confidence interval and P-value of less than 0.05. Result: Females were affected by post psychotic depression with the (AOR=2.01, 95%CI: 1.003- 4.012, P= 0.49).Patients who have mild form of positive symptom of schizophrenia affected by post psychotic depression with (AOR =4.05, 95%CI: 1.888- 8.7.8, P=0001).Patients who have minimal form of negative symptom of schizophrenia are affected by post psychotic depression with (AOR =4.23, 95%CI: 1.081-17.092, P=.038). Conclusion: In this study, sex (female) and presence of positive and negative symptoms of schizophrenia were significantly associated. It is recommended that the post psychotic depression should be assessed in every schizophrenia patient to decrease the severity of illness, and to improve patient’s quality of life.

Keywords: determinants, post-psychotic depression, Mekelle city

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3934 Concepts of the Covid-19 Pandemic and the Implications of Vaccines for Health Security in Nigeria and Diasporas

Authors: Wisdom Robert Duruji

Abstract:

The outbreak of SARS-CoV-2 serotype infection was recorded in January 2020 in Wuhan City, Hubei Province, China. This study examines the concepts of the COVID-19 pandemic and the implications of vaccines for health security in Nigeria and Diasporas. It challenges the widely accepted assumption that the first case of coronavirus infection in Nigeria was recorded on February 27th, 2020, in Lagos. The study utilizes a range of research methods to achieve its objectives. These include the double-layered culture technique, literature review, website knowledge, Google search, news media information, academic journals, fieldwork, and on-site observations. These diverse methods allow for a comprehensive analysis of the concepts and the implications being studied. The study finds that coronavirus infection can be asymptomatic; it may be the antigenicity of the leukocytes (white blood cells), which produce immunogenic hapten or interferons (α, β and γ) that fight infectious parasites, was an immune response that prevented severe virulence in healthy individuals; the reason healthy patients of coronavirus infection in Nigeria naturally recovered after two to three weeks of on-set of infection and test negative. However, the fatality data from the Nigerian Centre for Disease Control (NCDC) is incorrect in this study’s finding; it perused that the fatalities were primarily due to underlying ailments, hunger, and malnutrition in debilitated, comorbid, or compromised patients. This study concluded that the kits and Polymerase Chain Reaction (PCR) machine currently used by the Nigerian Centre for Disease Control (NCDC) in testing and confirming COVID-19 in Nigeria is not ideal; it is programmed and negates separating the strain to its specific serotypes amongst its genera coronavirus, and family Coronaviridae; and might have confirmed patients with the symptoms of febrile caused by cough, catarrh, typhoid and malaria parasites as Covid-19 positive. Therefore, it is recommended that the coronavirus species infected in Nigeria are opportunistic parasites that thrive in human immuno-suppressed conditions like the herpesvirus; it cannot be eradicated by vaccines; the only virucides are interferons, immunoglobulins, and probably synthetic antiviral guanosine drugs like copegus or ribavirin. The findings emphasized that COVID-19 is not the primary pandemic disease in Nigeria; the lockdown was a mirage and not necessary; but rather, pandemic diseases in Nigeria are corruption, nepotism, hunger, and malnutrition caused by ineptitude in governance, religious dichotomy, and ethnic conflicts.

Keywords: coronavirus, corruption, Covid-19 pandemic, lock-down, Nigeria, vaccine

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3933 Identifying Pathogenic Mycobacterium Species Using Multiple Gene Phylogenetic Analysis

Authors: Lemar Blake, Chris Oura, Ayanna C. N. Phillips Savage

Abstract:

Improved DNA sequencing technology has greatly enhanced bacterial identification, especially for organisms that are difficult to culture. Mycobacteriosis with consistent hyphema, bilateral exophthalmia, open mouth gape and ocular lesions, were observed in various fish populations at the School of Veterinary Medicine, Aquaculture/Aquatic Animal Health Unit. Objective: To identify the species of Mycobacterium that is affecting aquarium fish at the School of Veterinary Medicine, Aquaculture/Aquatic Animal Health Unit. Method: A total of 13 fish samples were collected and analyzed via: Ziehl-Neelsen, conventional polymerase chain reaction (PCR) and real-time PCR. These tests were carried out simultaneously for confirmation. The following combination of conventional primers: 16s rRNA (564 bp), rpoB (396 bp), sod (408 bp) were used. Concatenation of the gene fragments was carried out to phylogenetically classify the organism. Results: Acid fast non-branching bacilli were detected in all samples from homogenized internal organs. All 13 acid fast samples were positive for Mycobacterium via real-time PCR. Partial gene sequences using all three primer sets were obtained from two samples and demonstrated a novel strain. A strain 99% related to Mycobacterium marinum was also confirmed in one sample, using 16srRNA and rpoB genes. The two novel strains were clustered with the rapid growers and strains that are known to affect humans. Conclusions: Phylogenetic analysis demonstrated two novel Mycobacterium strains with the potential of being zoonotic and one strain 99% related to Mycobacterium marinum.

Keywords: polymerase chain reaction, phylogenetic, DNA sequencing, zoonotic

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3932 An Automated Magnetic Dispersive Solid-Phase Extraction Method for Detection of Cocaine in Human Urine

Authors: Feiyu Yang, Chunfang Ni, Rong Wang, Yun Zou, Wenbin Liu, Chenggong Zhang, Fenjin Sun, Chun Wang

Abstract:

Cocaine is the most frequently used illegal drug globally, with the global annual prevalence of cocaine used ranging from 0.3% to 0.4 % of the adult population aged 15–64 years. Growing consumption trend of abused cocaine and drug crimes are a great concern, therefore urine sample testing has become an important noninvasive sampling whereas cocaine and its metabolites (COCs) are usually present in high concentrations and relatively long detection windows. However, direct analysis of urine samples is not feasible because urine complex medium often causes low sensitivity and selectivity of the determination. On the other hand, presence of low doses of analytes in urine makes an extraction and pretreatment step important before determination. Especially, in gathered taking drug cases, the pretreatment step becomes more tedious and time-consuming. So developing a sensitive, rapid and high-throughput method for detection of COCs in human body is indispensable for law enforcement officers, treatment specialists and health officials. In this work, a new automated magnetic dispersive solid-phase extraction (MDSPE) sampling method followed by high performance liquid chromatography-mass spectrometry (HPLC-MS) was developed for quantitative enrichment of COCs from human urine, using prepared magnetic nanoparticles as absorbants. The nanoparticles were prepared by silanizing magnetic Fe3O4 nanoparticles and modifying them with divinyl benzene and vinyl pyrrolidone, which possesses the ability for specific adsorption of COCs. And this kind of magnetic particle facilitated the pretreatment steps by electromagnetically controlled extraction to achieve full automation. The proposed device significantly improved the sampling preparation efficiency with 32 samples in one batch within 40mins. Optimization of the preparation procedure for the magnetic nanoparticles was explored and the performances of magnetic nanoparticles were characterized by scanning electron microscopy, vibrating sample magnetometer and infrared spectra measurements. Several analytical experimental parameters were studied, including amount of particles, adsorption time, elution solvent, extraction and desorption kinetics, and the verification of the proposed method was accomplished. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.1 ng·mL-1 with recoveries ranging from 75.1 to 105.7%. Compared to traditional sampling method, this method is time-saving and environmentally friendly. It was confirmed that the proposed automated method was a kind of highly effective way for the trace cocaine and cocaine metabolites analyses in human urine.

Keywords: automatic magnetic dispersive solid-phase extraction, cocaine detection, magnetic nanoparticles, urine sample testing

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3931 Effect of Z-VAD-FMK on in Vitro Viability of Dog Follicles

Authors: Leda Maria Costa Pereira, Maria Denise Lopes, Nucharin Songsasen

Abstract:

Mammalian ovaries contain thousands of follicles that eventually degenerate or die after culture in vitro. Caspase-3 is a key enzyme that regulating cell death. Our objective was to examine the influence of anti-apoptotic drug Z-VAD-FMK (pan-caspase inhibitor) on in vitro viability of dog follicles within the ovarian cortex. Ovaries were obtained from prepubertal (age, 2.5–6 months) and adult (age, 8 months to 2 years) bitches and ovarian cortical fragments were recovered. The cortices were then incubated on 1.5% (w/v) agarose gel blocks within a 24-wells culture plate (three cortical pieces/well) containing Minimum Essential Medium Eagle - Alpha Modification (Alpha MEM) supplemented with 4.2 µg/ml insulin, 3.8 µg/ml transferrin, 5 ng/ml selenium, 2 mM L-glutamine, 100 µg/mL of penicillin G sodium, 100 µg/mL of streptomycin sulfate, 0.05 mM ascorbic acid, 10 ng/mL of FSH and 0.1% (w/v) polyvinyl alcohol in humidified atmosphere of 5% CO2 and 5% O2. The cortices were divided in six treatment groups: 1) 10 ng/mL EGF (EGF V0); 2) 10 ng/mL of EGF plus 1 mM Z-VAD-FMK (EGF V1); 3) 10 ng/mL of EGF and 10 mM Z-VAD-FMK (EGF V10); 4) 1 mM Z-VAD-FMK; 5) 10 mM Z-VAD-FMK and (6) no EGF and Z-VAD-FMK supplementation. Ovarian follicles within the tissues were processed for histology and assessed for follicle density, viability (based on morphology) and diameter immediately after collection (Control) or after 3 or 7 days of in vitro incubation. Comparison among fresh and culture treatment group was performed using ANOVA test. There were no differences (P > 0.05) in follicle density and viability among different culture treatments. However, there were differences in this parameter between culture days. Specifically, culturing tissue for 7 days resulted in significant reduction in follicle viability and density, regardless of treatments. We found a difference in size between culture days when these follicles were cultured using 10 mM Z-VAD-FMK or 10 ng/mL EGF (EGF V0). In sum, the finding demonstrated that Z-VAD-FMK at the dosage used in the present study does not provide the protective effect to ovarian tissue during in vitro culture. Future studies should explore different Z-VAD-FMK dosages or other anti-apoptotic agent, such as surviving in protecting ovarian follicles against cell death.

Keywords: anti apoptotic drug, bitches, follicles, Z-VAD-FMK

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3930 The Dark Side of Tourism's Implications: A Structural Equation Modeling Study of the 2016 Earthquake in Central Italy

Authors: B. Kulaga, A. Cinti, F. J. Mazzocchini

Abstract:

Despite the fact that growing academic attention on dark tourism is a fairly recent phenomenon, among the various reasons for travelling death-related ones, are very ancient. Furthermore, the darker side of human nature has always been fascinated and curious regarding death, or at least, man has always tried to learn lessons from death. This study proposes to describe the phenomenon of dark tourism related to the 2016 earthquake in Central Italy, deadly for 302 people and highly destructive for the rural areas of Lazio, Marche, and Umbria Regions. The primary objective is to examine the motivation-experience relationship in a dark tourism site, using the structural equation model, applied for the first time to a dark tourism research in 2016, in a study conducted after the Beichuan earthquake. The findings of the current study are derived from the calculations conducted on primary data compiled from 350 tourists in the areas mostly affected by the 2016 earthquake, including the town of Amatrice, near the epicenter, Castelluccio, Norcia, Ussita and Visso, through conducting a Likert scale survey. Furthermore, we use the structural equation model to examine the motivation behind dark travel and how this experience can influence the motivation and emotional reaction of tourists. Expected findings are in line with the previous study mentioned above, indicating that: not all tourists visit the thanatourism sites for dark tourism purpose, tourists’ emotional reactions influence more heavily the emotional tourist experience than cognitive experiences do, and curious visitors are likely to engage cognitively by learning about the incident or related issues.

Keywords: dark tourism, emotional reaction, experience, motivation, structural equation model

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3929 Comparison of Analgesic Efficacy of Paracetamol and Tramadol for Pain Relief in Active Labor

Authors: Krishna Dahiya

Abstract:

Introduction: Labour pain has been described as the most severe pain experienced by women in their lives. Pain management in labour is one of the most important challenges faced by the obstetrician. The opioids are the primary treatment for patients with moderate and severe pain but these drugs are not always tolerated and are associated with dose-dependent side effects. Nonsteroidal anti-inflammatory drugs, too, are associated with variable adverse effects. Considering these factors, our study compared the efficacy and side effect of intravenous tramadol and paracetamol. Objective: To evaluate the efficacy and adverse effects of an intravenous infusion of 1000 mg of paracetamol as compared with an intravenous injection of 50mg of tramadol for intrapartum analgesia. Methods: In a randomized prospective study at Pt. BDS PGIMS, 200 women in active labor were allocated to received either paracetamol (n=100) or tramadol (n=100). The primary outcome was the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various times after drug administration. The secondary outcomes included the need for additional rescue analgesia and the presence of adverse maternal or fetal events. Results: The mean age of cases were 25.55 ± 3.849 years and 25.60 ± 3.655 years respectively As recorded by the VAS score, there was significant pain reduction at 30 minutes, and at 1 and 2 hours in both groups (P<0.01). In comparison, between group I and II, a significantly higher rate of nausea and vomiting in tramadol group (14% vs 8%; P < 0.03) patients. Similarly, drowsiness (0% vs 11%; P<0.01), dry mouth (0% vs 8%; P<0.04) and dizziness (0% vs 9%; P<0.02) was also significant in group II. Conclusion: Due to difficulty in administering epidural analgesia to all parturients, administration of paracetamol and tramadol infusion for analgesia is simple and less invasive alternative. In the present study, both paracetamol and tramadol were equally effective for labour analgesia but paracetamol has emerged as safe alternative as compared to tramadol due to a low incidence of side effects.

Keywords: paracetamol, tramadol, labor, analgesia

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3928 Emergence of Ciprofloxacin Intermediate Susceptible Salmonella Typhi in India

Authors: Meenakshi Chaudhary, V .S. Randhawa, M. Jais, R. Dutta

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Introduction: An outbreak of Multi drug resistant S. Typhi (i.e. resistance to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) occurred in 1990's in India which peaked in 1992-93 and resulted in the change of drug of choice from chloramphenicol to ciprofloxacin for enteric fever. Currently an emergence of Ciprofloxacin susceptible S. Typhi isolates in the region is being reported which appears to be chromosomally mediated. Methodology: Six hundred sixty four strains were randomly selected from the time period between January 2008-December 2011 at the National Salmonella Phage Typing Centre, LHMC, New Delhi. The strains were representative of the north, central and south zones of India. All isolates were subjected to serotyping, biotyping, phage typing and then to antimicrobial susceptibility testing by CLSI disk diffusion (CLSI) technique to Ciprofloxacin, Cefotaxime, Ampicillin, Chloramphenicol, Trimethoprim-Sulfomethoxazole and Tetracycline. Subsequently MIC of the isolates was determined by E-test (AB-Biodisc). Results: More than 80% of the tested strains had intermediate susceptibility to ciprofloxacin. The E test revealed the MIC (Ciprofloxacin) of these strains to be in the range of 0.12 to 0.5 µg/ml. Sixty nine percent of ciprofloxacin intermediate susceptible strains belonged to Phage type E1 and fourteen percent of these were Vi- Negative i.e these could not be typed by the phage typing scheme of Craigie and Yen. All the strains remained susceptible to cefotaxime. Conclusion: Predominant isolation of intermediate susceptible S. Typhi strains from India would alter the recommendations of empiric treatment of enteric fever in the region. Alternative to the low cost ciprofloxacin will have to be sought or increased dosage and/or duration of ciprofloxacin will have to be recommended. The reasons for the trend of increase in percentage of intermediate susceptible S. Typhi strains are not clear but may be attributed partly to the revision of CLSI guidelines in 2013.

Keywords: salmonella typhi, decreased ciprofloxacin susceptibility, ciprofloxacin, minimum inhibitory concentration

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3927 Developing a Systemic Approach for Understanding the Factors Influencing Participation in Recreational Angling

Authors: Daniel Phillip Svozil, Eileen Petrie, Kristy Robson, Lee Baumgartner, Max Finlayson

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Recreational angling is recognized for its potential to improve health and wellbeing which has translated into policy initiatives to increase participation in the sport. However, these benefits have been examined mostly among voluntary participants. Thus, there is an assumption that recreational angling is perceived equally and that these benefits may be evident even to non-anglers. This paper reviews the published benefits to health and wellbeing of recreational angling and proposes an approach to systemically analyze interactions among the perceptions, socio-economic barriers, and knowledge of these benefits among people at different levels of participation (including non-participants). The outcomes of this study will assist in identifying the feasibility of recreational angling for improving health and wellbeing outcomes among participants (i.e., fishing may not be for everyone) and designing interventions that address the perceptions and socio-economic barriers among individuals that may benefit from participation in recreational angling.

Keywords: angling, health, wellbeing, connecting with nature

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3926 The Fake News Impact on the Public Policy Cycle: A Systemic Analysis through Documentary Survey

Authors: Aron Miranda Burgos, Ergon Cugler de Moraes Silva

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In the present article, it is observed that the constant advancement of issues related to misinformation impacts the guarantee of the public policy cycle. Thus, it is found that the dissemination of false information has a direct influence on each of the component stages of this cycle. Therefore, in order to maintain scientific and theoretical credibility in the qualitative analysis process, it was necessary to logically interpose the concepts of firehosing of falsehood, fake news, public policy cycle, as well as using the epistemological and pragmatic mechanism at the intersection of such academic concepts, such as the scientific method. It was found, through the analysis of official documents and public notes, how the multiple theoretical perspectives evidence the commitment of the provision and elaboration of public policies, verifying the way in which the fake news impact each part of the process in this atmosphere.

Keywords: firehosing of falsehood, governance, misinformation, post-truth

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3925 Screening of Selected Medicinal Plants from Jordan for Their Protective Properties against Oxidative DNA Damage and Mutagenecity

Authors: Karem H. Alzoubi, Ahmad S. Alkofahi, Omar F. Khabour, Nizar M. Mhaidat

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Herbal medicinal products represent a major focus for drug development and industry and it holds a significant share in drug-market all over the globe. In here, selected medicinal plant extracts from Jordan with high antioxidative capacity were tested for their protective effect against oxidative DNA damage using in vitro 8-hydroxydeoxyguanisine and sister chromatid exchanges (SCEs) assays in cultured human lymphocytes. The following plant extracts were tested Cupressus sempervirens L., Psidium guajava (L.) Gaerth., Silybum marianum L., Malva sylvestris L., Varthemia iphionoides Boiss., Eminium spiculatum L. Blume, Pistachia palaestina Boiss., Artemisia herba-alba Asso, Ficus carica L., Morus alba Linn , Cucumis sativus L., Eucalyptus camaldulensis Dehnh., Salvia triloba L., Zizyphus spina-christi L. Desf., and Laurus nobilis L. A fractionation scheme for the active plant extracts of the above was followed. Plants extract fractions with best protective properties against DNA damage included hexane fraction of S. marianum L. (aerial parts), chloroform fractions of P. palaestina Boiss. (Fruits), ethanolic fractions of E. camaldulensis Dehnh (leaves), S. triloba L. (leaves), and ethanolic fractions of Z. spina-christi L. Desf. (Fruits/leaves). On the other hand, the ethanolic extracts of V. iphionoides Boiss was found to increase oxidative DNA damage. Results of the SCEs are undergoing. In conclusion, plant extracts with antioxidative DNA damage properties might have clinical applications in cancer prevention.

Keywords: medicinal plants extract, fractionation, oxidative DNA damage, 8-hydroxydeoxyguanisine, SCEs, Jordan

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3924 In Silico Exploration of Quinazoline Derivatives as EGFR Inhibitors for Lung Cancer: A Multi-Modal Approach Integrating QSAR-3D, ADMET, Molecular Docking, and Molecular Dynamics Analyses

Authors: Mohamed Moussaoui

Abstract:

A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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3923 The System-Dynamic Model of Sustainable Development Based on the Energy Flow Analysis Approach

Authors: Inese Trusina, Elita Jermolajeva, Viktors Gopejenko, Viktor Abramov

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Global challenges require a transition from the existing linear economic model to a model that will consider nature as a life support system for the development of the way to social well-being in the frame of the ecological economics paradigm. The objective of the article is to present the results of the analysis of socio-economic systems in the context of sustainable development using the systems power (energy flows) changes analyzing method and structural Kaldor's model of GDP. In accordance with the principles of life's development and the ecological concept was formalized the tasks of sustainable development of the open, non-equilibrium, stable socio-economic systems were formalized using the energy flows analysis method. The methodology of monitoring sustainable development and level of life were considered during the research of interactions in the system ‘human - society - nature’ and using the theory of a unified system of space-time measurements. Based on the results of the analysis, the time series consumption energy and economic structural model were formulated for the level, degree and tendencies of sustainable development of the system and formalized the conditions of growth, degrowth and stationarity. In order to design the future state of socio-economic systems, a concept was formulated, and the first models of energy flows in systems were created using the tools of system dynamics. During the research, the authors calculated and used a system of universal indicators of sustainable development in the invariant coordinate system in energy units. In order to design the future state of socio-economic systems, a concept was formulated, and the first models of energy flows in systems were created using the tools of system dynamics. In the context of the proposed approach and methods, universal sustainable development indicators were calculated as models of development for the USA and China. The calculations used data from the World Bank database for the period from 1960 to 2019. Main results: 1) In accordance with the proposed approach, the heterogeneous energy resources of countries were reduced to universal power units, summarized and expressed as a unified number. 2) The values of universal indicators of the life’s level were obtained and compared with generally accepted similar indicators.3) The system of indicators in accordance with the requirements of sustainable development can be considered as a basis for monitoring development trends. This work can make a significant contribution to overcoming the difficulties of forming socio-economic policy, which is largely due to the lack of information that allows one to have an idea of the course and trends of socio-economic processes. The existing methods for the monitoring of the change do not fully meet this requirement since indicators have different units of measurement from different areas and, as a rule, are the reaction of socio-economic systems to actions already taken and, moreover, with a time shift. Currently, the inconsistency or inconsistency of measures of heterogeneous social, economic, environmental, and other systems is the reason that social systems are managed in isolation from the general laws of living systems, which can ultimately lead to a systemic crisis.

Keywords: sustainability, system dynamic, power, energy flows, development

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3922 Silymarin Reverses Scopolamine-Induced Memory Deficit in Object Recognition Test in Rats: A Behavioral, Biochemical, Histopathological and Immunohistochemical Study

Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

Abstract:

Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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3921 Development of One-Pot Sequential Cyclizations and Photocatalyzed Decarboxylative Radical Cyclization: Application Towards Aspidospermatan Alkaloids

Authors: Guillaume Bélanger, Jean-Philippe Fontaine, Clémence Hauduc

Abstract:

There is an undeniable thirst from organic chemists and from the pharmaceutical industry to access complex alkaloids with short syntheses. While medicinal chemists are interested in the fascinating wide range of biological properties of alkaloids, synthetic chemists are rather interested in finding new routes to access these challenging natural products of often low availability from nature. To synthesize complex polycyclic cores of natural products, reaction cascades or sequences performed one-pot offer a neat advantage over classical methods for their rapid increase in molecular complexity in a single operation. In counterpart, reaction cascades need to be run on substrates bearing all the required functional groups necessary for the key cyclizations. Chemoselectivity is thus a major issue associated with such a strategy, in addition to diastereocontrol and regiocontrol for the overall transformation. In the pursuit of synthetic efficiency, our research group developed an innovative one-pot transformation of linear substrates into bi- and tricyclic adducts applied to the construction of Aspidospermatan-type alkaloids. The latter is a rich class of indole alkaloids bearing a unique bridged azatricyclic core. Despite many efforts toward the synthesis of members of this family, efficient and versatile synthetic routes are still coveted. Indeed, very short, non-racemic approaches are rather scarce: for example, in the cases of aspidospermidine and aspidospermine, syntheses are all fifteen steps and over. We envisaged a unified approach to access several members of the Aspidospermatan alkaloids family. The key sequence features a highly chemoselective formamide activation that triggers a Vilsmeier-Haack cyclization, followed by an azomethine ylide generation and intramolecular cycloaddition. Despite the high density and variety of functional groups on the substrates (electron-rich and electron-poor alkenes, nitrile, amide, ester, enol ether), the sequence generated three new carbon-carbon bonds and three rings in a single operation with good yield and high chemoselectivity. A detailed study of amide, nucleophile, and dipolarophile variations to finally get to the successful combination required for the key transformation will be presented. To complete the indoline fragment of the natural products, we developed an original approach. Indeed, all reported routes to Aspidospermatan alkaloids introduce the indoline or indole early in the synthesis. In our work, the indoline needs to be installed on the azatricyclic core after the key cyclization sequence. As a result, typical Fischer indolization is not suited since this reaction is known to fail on such substrates. We thus envisaged a unique photocatalyzed decarboxylative radical cyclization. The development of this reaction as well as the scope and limitations of the methodology, will also be presented. The original Vilsmeier-Haack and azomethine ylide cyclization sequence as well as the new photocatalyzed decarboxylative radical cyclization will undoubtedly open access to new routes toward polycyclic indole alkaloids and derivatives of pharmaceutical interest in general.

Keywords: Aspidospermatan alkaloids, azomethine ylide cycloaddition, decarboxylative radical cyclization, indole and indoline synthesis, one-pot sequential cyclizations, photocatalysis, Vilsmeier-Haack Cyclization

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3920 HIV Incidence among Men Who Have Sex with Men Measured by Pooling Polymerase Chain Reaction, and Its Comparison with HIV Incidence Estimated by BED-Capture Enzyme-Linked Immunosorbent Assay and Observed in a Prospective Cohort

Authors: Mei Han, Jinkou Zhao, Yuan Yao, Liangui Feng, Xianbin Ding, Guohui Wu, Chao Zhou, Lin Ouyang, Rongrong Lu, Bo Zhang

Abstract:

To compare the HIV incidence estimated using BED capture enzyme linked immunosorbent assay (BED-CEIA) and observed in a cohort against the HIV incidence among men who have sex with men (MSM) measured by pooling polymerase chain reaction (pooling-PCR). A total of 617 MSM subjects were included in a respondent driven sampling survey in Chongqing in 2008. Among the 129 that were tested HIV antibody positive, 102 were defined with long-term infection, 27 were assessed for recent HIV infection (RHI) using BED-CEIA. The remaining 488 HIV negative subjects were enrolled to the prospective cohort and followed-up every 6 months to monitor HIV seroconversion. All of the 488 HIV negative specimens were assessed for acute HIV infection (AHI) using pooling-PCR. Among the 488 negative subjects in the open cohort, 214 (43.9%) were followed-up for six months, with 107 person-years of observation and 14 subjects seroconverted. The observed HIV incidence was 12.5 per 100 person-years (95% CI=9.1-15.7). Among the 488 HIV negative specimens, 5 were identified with acute HIV infection using pooling-PCR at an annual rate of 14.02% (95% CI=1.73-26.30). The estimated HIV-1 incidence was 12.02% (95% CI=7.49-16.56) based on BED-CEIA. The HIV incidence estimated with three different approaches was different among subgroups. In the highly HIV prevalent MSM, it costs US$ 1724 to detect one AHI case, while detection of one case of RHI with BED assay costs only US$ 42. Three approaches generated comparable and high HIV incidences, pooling PCR and prospective cohort are more close to the true level of incidence, while BED-CEIA seemed to be the most convenient and economical approach for at-risk population’s HIV incidence evaluation at the beginning of HIV pandemic. HIV-1 incidences were alarmingly high among MSM population in Chongqing, particularly within the subgroup under 25 years of age and those migrants aged between 25 to 34 years.

Keywords: BED-CEIA, HIV, incidence, pooled PCR, prospective cohort

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3919 Evaluation of Naringenin Role in Inhibiton of Lung Tumor Progression in Mice

Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

Abstract:

Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

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3918 KAP Study on Breast Cancer Among Women in Nirmala Educational Institutions-A Prospective Observational Study

Authors: Shaik Asha Begum, S. Joshna Rani, Shaik Abdul Rahaman

Abstract:

INTRODUCTION: Breast cancer is a disease that creates in breast cells. "KAP" study estimates the Knowledge, Attitude, and Practices of a local area. More than 1.5 million ladies (25% of all ladies with malignancy) are determined to have bosom disease consistently all through the world. Understanding the degrees of Knowledge, Attitude and Practice will empower a more effective cycle of mindfulness creation as it will permit the program to be custom-made all the more properly to the necessities of the local area. OBJECTIVES: The objective of this study is to assess the knowledge on signs and symptoms, risk factors, provide awareness on the practicing of the early detection techniques of breast cancer and provide knowledge on the overall breast cancer including preventive techniques. METHODOLOGY: This is an expressive cross-sectional investigation. This investigation of KAP was done in the Nirmala Educational Institutions from January to April 2021. A total of 300 participants are included from women students in pharmacy graduates & lecturers, and also from graduates other than the pharmacy. The examiners are taken from the BCAM (Breast Cancer Awareness Measure), tool compartment (Version 2). RESULT: According to the findings of the study, the majority of the participants were not well informed about breast cancer. A lump in the breast was the most commonly mentioned sign of breast cancer, followed by pain in the breast or nipple. The percentage of knowledge related to the breast cancer risk factors was also very less. The correct answers for breast cancer risk factors were radiation exposure (58.20 percent), a positive family history (47.6 percent), obesity (46.9 percent), a lack of physical activity (43.6 percent), and smoking (43.2 percent). Breast cancer screening, on the other hand, was uncommon (only 30 and 11.3 percent practiced clinical breast examination and mammography respectively). CONCLUSION: In this study, the knowledge on the signs and symptoms, risk factors of breast cancer - pharmacy graduates have more knowledge than the non-pharmacy graduates but in the preventive techniques and early detective tools of breast cancer -had poor knowledge in the pharmacy and non-pharmacy graduate. After the awareness program, pharmacy and non-pharmacy graduates got supportive knowledge on the preventive techniques and also practiced the early detective techniques of breast cancer.

Keywords: breast cancer, mammography, KAP study, early detection

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3917 Natural Bio-Active Product from Marine Resources

Authors: S. Ahmed John

Abstract:

Marine forms-bacteria, actinobacteria, cynobacteria, fungi, microalgae, seaweeds mangroves and other halophytes an extremely important oceanic resources and constituting over 90% of the oceanic biomass. The marine natural products have lead to the discovery of many compounds considered worthy for clinical applications. The marine sources have the highest probability of yielding natural products. Natural derivatives play an important role to prevent the cancer incidences as synthetic drug transformation in mangrove. 28.12% of anticancer compound extracted from the mangroves. Exchocaria agollocha has the anti cancer compounds. The present investigation reveals the potential of the Exchocaria agollocha with biotechnological applications for anti cancer, antimicrobial drug discovery, environmental remediation, and developing new resources for the industrial process. The anti-cancer activity of Exchocaria agollocha was screened from 3.906 to 1000 µg/ml of concentration with the dilution leads to 1:1 to 1:128 following methanol and chloroform extracts. The cell viability in the Exchocaria agollocha was maximum at the lower concentration where as low at the higher concentration of methanol and chloroform extracts when compare to control. At 3.906 concentration, 85.32 and 81.96 of cell viability was found at 1:128 dilution of methanol and chloroform extracts respectively. At the concentration of 31.25 following 1:16 dilution, the cell viability was 65.55 in methanol and 45.55 in chloroform extracts. However, at the higher concentration, the cell viability 22.35 and 8.12 was recorded in the extracts of methanol and chloroform. The cell viability was more in methanol when compare to chloroform extracts at lower concentration. The present findings gives current trends in screening and the activity analysis of metabolites from mangrove resources and to expose the models to bring a new sustain for tackling cancer. Bioactive compounds of Exchocaria agollocha have extensive use in treatment of many diseases and serve as a compound and templates for synthetic modification.

Keywords: bio-active product, compounds, natural products and microalgae

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3916 Mordenite as Catalyst Support for Complete Volatile Organic Compounds Oxidation

Authors: Yuri A. Kalvachev, Totka D. Todorova

Abstract:

Zeolite mordenite has been investigated as a transition metal support for the preparation of efficient catalysts in the oxidation of volatile organic compounds (VOCs). The highly crystalline mordenite samples were treated with hydrofluoric acid and ammonium fluoride to get hierarchical material with secondary porosity. The obtained supports by this method have a high active surface area, good diffusion properties and prevent the extraction of metal components during catalytic reactions. The active metal phases platinum and copper were loaded by impregnation on both mordenite materials (parent and acid treated counterparts). Monometalic Pt and Cu, and bimetallic Pt/Cu catalysts were obtained. The metal phases were fine dispersed as nanoparticles on the functional porous materials. The catalysts synthesized in this way were investigated in the reaction of complete oxidation of propane and benzene. Platinum, copper and platinum/copper were loaded and there catalytic activity was investigated and compared. All samples are characterized by X-ray diffraction analysis, nitrogen adsorption, scanning electron microscopy (SEM), X-ray photoelectron measurements (XPS) and temperature programed reduction (TPR). The catalytic activity of the samples obtained is investigated in the reaction of complete oxidation of propane and benzene by using of Gas Chromatography (GC). The oxidation of three organic molecules was investigated—methane, propane and benzene. The activity of metal loaded mordenite catalysts for methane oxidation is almost the same for parent and treated mordenite as a support. For bigger molecules as propane and benzene, the activity of catalysts based on treated mordenite is higher than those based on parent zeolite.

Keywords: metal loaded catalysts, mordenite, VOCs oxidation, zeolites

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3915 Synthesis and Physiochemical Properties of 3-Propanenitrile Imidazolium - Based Dual Functionalized Ionic Liquids Incorporating Dioctyl Sulfosuccinate Anion

Authors: Abobakr Khidir Ziyada, Cecilia Devi Wilfred

Abstract:

In the present work, a new series of 3-propanenitrile imidazolium-based Room Temperature Ionic Liquids (RTILs), incorporating dioctyl sulfosuccinate (DOSS) were prepared by reacting imidazole with acrylonitrile and then reacting the product with allyl chloride, 2-chloroethanol, and benzyl chloride. After the reaction had been completed, metathesis reaction was carried out using sodium dioctyl sulfosuccinate. The densities and viscosities of the present RTILs were measured at atmospheric pressure at T=293.15 to 353.15 K, the refractive index was measured at T=293.15 to 333.15 K, whereas, the start and decomposition temperatures were determined at heating rate 10°C. min^-1. The thermal expansion coefficient, densities at a range of temperatures and pressures, molecular volume, molar refraction, standard entropy and the lattice energy of these RTILs were also estimated. The present RTILs showed higher densities, similar refractive indices, and higher viscosities compared to the other 1-alkyl-3-propanenitrile imidazolium-based RTILs. The densities of the present synthesized RTILs are lower compared to the other nitrile-functionalized ILs. These present RTILs showed a weak temperature dependence on the thermal expansion coefficients, αp=5.0 × 10^−4 to 7.50 × 10−4 K^-1. Empirical correlations were proposed to represent the present data on the physical properties. The lattice energy for the present RTILs was similar to other nitrile–based imidazolium RTILs. The present RTILs showed very high molar refraction when compared similar RTILs incorporating other anions.

Keywords: dioctyl sulfosuccinate, nitrile ILs, 3-propanenitrile, anion, room temperature ionic liquids, RTIL

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3914 Effects of Active Muscle Contraction in a Car Occupant in Whiplash Injury

Authors: Nisha Nandlal Sharma, Julaluk Carmai, Saiprasit Koetniyom, Bernd Markert

Abstract:

Whiplash Injuries are usually associated with car accidents. The sudden forward or backward jerk to head causes neck strain, which is the result of damage to the muscle or tendons. Neck pain and headaches are the two most common symptoms of whiplash. Symptoms of whiplash are commonly reported in studies but the Injury mechanism is poorly understood. Neck muscles are the most important factor to study the neck Injury. This study focuses on the development of finite element (FE) model of human neck muscle to study the whiplash injury mechanism and effect of active muscle contraction on occupant kinematics. A detailed study of Injury mechanism will promote development and evaluation of new safety systems in cars, hence reducing the occurrence of severe injuries to the occupant. In present study, an active human finite element (FE) model with 3D neck muscle model is developed. Neck muscle was modeled with a combination of solid tetrahedral elements and 1D beam elements. Muscle active properties were represented by beam elements whereas, passive properties by solid tetrahedral elements. To generate muscular force according to inputted activation levels, Hill-type muscle model was applied to beam elements. To simulate non-linear passive properties of muscle, solid elements were modeled with rubber/foam material model. Material properties were assigned from published experimental tests. Some important muscles were then inserted into THUMS (Total Human Model for Safety) 50th percentile male pedestrian model. To reduce the simulation time required, THUMS lower body parts were not included. Posterior to muscle insertion, THUMS was given a boundary conditions similar to experimental tests. The model was exposed to 4g and 7g rear impacts as these load impacts are close to low speed impacts causing whiplash. The effect of muscle activation level on occupant kinematics during whiplash was analyzed.

Keywords: finite element model, muscle activation, neck muscle, whiplash injury prevention

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3913 Anti-Bacterial Activity Studies of Derivatives of 6β-Hydroxy Betunolic Acid against Selected Stains of Gram (+) and Gram (-) Bacteria

Authors: S. Jayasinghe, W. G. D. Wickramasingha, V. Karunaratne, D. N. Karunaratne, A. Ekanayake

Abstract:

Multi-drug resistant microbial pathogens are a serious global health problem, and hence, there is an urgent necessity for discovering new drug therapeutics. However, finding alternatives is a one of the biggest challenges faced by the global drug industry due to the spiraling high cost and serious side effects associated with modern medicine. On the other hand, plants and their secondary metabolites can be considered as good sources of scaffolds to provide structurally diverse bioactive compounds as potential therapeutic agents. 6β-hydroxy betunolic acid is a triterpenoid isolated from bark of Schumacheria castaneifolia which is an endemic plant to Sri Lanka which has shown antibacterial activity against both Staphylococcus aureus (ATCC 29213) and methicillin-resistant S. aureus with Minimum Inhibition Concentration (MIC) of 16 µg/ml. The objective of this study was to determine the anti-bacterial activity for the derivatives of 6β- hydroxy betunolic acid against standard strains of Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), carbepenemas produce Kebsiella pneumonia (ATCC BAA 1705) and carbepenemas non produce Kebsiella pneumonia (ATCC BAA 1706) and four stains of clinically isolated methicillin resistance S. aureus and Acinetobacter. Structural analogues of 6β-hydroxy betunolic acid were synthesized by modifying the carbonyl group at C-3 to obtain olefin and oxime, the hydroxyl group at C-6 position to a ketone, the carboxylic acid at C-17 to obtain amide and halo ester and the olefin group at C-20 position to obtain epoxide. Chemical structures of the synthesized analogues were confirmed with spectroscopic data and antibacterial activity was determined through broth micro dilution assay. Results revealed that 6β- hydroxy betunolic acid shows significant antibacterial activity only against the Gram positive strains and it was inactive against all the tested Gram negative strains for the tested concentration range. However, structural modifications into oxime and olefin at C-3, ketone at C-6 and epoxide at C-20 decreased its antibacterial activity against the gram positive organisms and it was totally lost with the both modifications at C-17 into amide and ester. These results concluded that the antibacterial activity of 6β- hydroxy betunolic acid and derivatives is predominantly depending on the cell wall difference of the bacteria and the presence of carboxylic acid at C-17 is highly important for the antibacterial activity against Gram positive organisms.

Keywords: antibacterial activity, 6β- hydroxy betunolic acid, broth micro dilution assay, structure activity relationship

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3912 Carbon Blacks: A Broad Type of Carbon Materials with Different Electrocatalytic Activity to Produce H₂O₂

Authors: Alvaro Ramírez, Martín Muñoz-Morales, Ester López- Fernández, Javier Llanos, C. Ania

Abstract:

Carbon blacks are value-added materials typically produced through the incomplete combustion or thermal decomposition of hydrocarbons. Traditionally, they have been used as catalysts in many different applications, but in the last decade, their potential in green chemistry has gained significant attention. Among them, the electrochemical production of H₂O₂ has attracted interest because of their properties as high oxidant capacity or their industrial interest as a bleaching agent. Carbon blacks are commonly used in this application in a catalytic ink that is drop-casted on supporting electrodes and acts as catalysts for the electrochemical production of H₂O₂ through oxygen reduction reaction (ORR). However, the different structural and electrochemical behaviors of each type of carbon black influence their applications. In this line, the term ‘carbon black’, has to be considered as a generic name that does not guarantee any physicochemical properties if any further description is mentioned. In fact, different specific surface area (SSA), surface functional groups, porous structure, and electro catalysts effect seem very important for electrochemical applications, and considerable differences were found during the analysis of four types of carbon blacks. Thus, the aim of this work is to evaluate the influence of SSA, porous structure, oxygen functional groups, and structural defects to differentiate among these carbon blacks (e.g. Vulcan XC72, Superior Graphite Co, Printex XE2, and Prolabo) for H₂O₂ production via ORR, using carbon paper as electrode support with improved selectivity and efficiency. Results indicate that the number and size of pores, along with surface functional groups, are key parameters that significantly affect the overall process efficiency.

Keywords: carbon blacks, oxygen reduction reaction, hydrogen peroxide, porosity, surface functional groups

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3911 A Prospective Study on the Evaluation of Statins Usage on HbA1c Control among Type 2 Diabetes Mellitus in an Outpatients Setting

Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Abeer Kharshid, Nor Azizah Aziz, Tarek M. Elsayed

Abstract:

Medication safety is always an issue. In 2015, the National Pharmaceutical Control Bureau released a statement requesting all statins manufacturers in Malaysia to include the risk of diabetes information in the drug information leaflet in response to United States Food and Drug Administration (U.S. FDA) report. However, the data regarding this warning label in Malaysia is limited, so there is still some uncertainty whether such risk can also be observed in the Malaysian population or not. The study aims to determine the effect of statins on HbA1c% in type 2 diabetic outpatients in endocrine clinics at Hospital Pulau Pinang between June 2015 and May 2016 in Malaysia. In a prospective cohort study, records of 400 type 2 diabetic patients (control group 104 patients not using statin and treatment group 296 patients using statin) were reviewed to identify demographic criteria and lab tests. The prevalence of glycemic control (Glycated hemoglobin, HbA1C ≤ 7% for patient < 65 years, and < 8% for patient ≥ 65 years) was estimated, according to American Diabetes Association guidelines 2015. The results were presented as descriptive statistics. From 296 patients with Type 2 diabetes using statins cohort with a mean age of 57.52 ± 12.2 years, only 81 (27.4%) cases had controlled glycemia, and 215 (72.6%) had uncontrolled glycemia, CI: 95% (6.3–11.1). While the control group 104 diabetic patients had a mean age 46.1 ± 18 years and distributed among 59 (56.7%) patients with controlled diabetes and 45 (43.3%) cases, had uncontrolled glycemia, CI: 95% (5.2–10.3). The relative risk (RR) of uncontrolled glycemia in diabetic patients used statins was 1.68, and the excessive relative risk (ERR) was 68%. The absolute risk (AR) was 29.3%, and the number needed to harm (NNH) was 4. Diabetic patients using statins have more risk of uncontrolled glycemia than the patients with Type 2 diabetes non-using statins.

Keywords: diabetes mellitus, HbA1c, Malaysia, outpatients, statin, type 2, uncontrolled glycemia

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3910 Aspirin Loaded Poly-L-Lactic Acid Nanofibers and Their Potentials as Small Diameter Vascular Grafts

Authors: Mahboubeh Kabiri, Saba Aslani

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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

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3909 Improvement of Autism Diagnostic Observation Schedule Scores after Comprehensive Intensive Early Interventions in a Clinical Setting

Authors: Nils Haglund, Svenolof Dahlgren, Maria Rastam, Peik Gustafsson, Karin Kalien

Abstract:

In Sweden, like in most developed countries, there is a substantial increase of children diagnosed with autism and other conditions within the autism spectrum (ASD). The rapid increase of ASD rates stresses the importance of developing care programs to provide support and comprehensive interventions for affected families. The current observational study was conducted in order to evaluate an ongoing Comprehensive Intensive Early Intervention (CIEI) program for children with autism in southern Sweden. The change in autism symptoms among children participating in CIEI (intervention group, n=67) was compared with children who received traditional habilitation services only (comparison group, n=27). Children of parents who accepted the offered CIEI-program, constituted the intervention group, whereas children, whose parents (for some reason) were not interested in the offered CIEI-program, constituted the comparison group. The CIEI-program was individualized to each child by experienced applied behavior analysis (ABA) specialists with different backgrounds as psychologists, speech pathologists or special education teachers, in cooperation with parents and preschool staff. Due to the individualization, the intervention could vary in intensity and techniques. The intensity was calculated to 15-25 hours each week at home and the preschool altogether. Each child was assigned one 'trainer', who was often employed as a preschool teacher but could have another educational background. An agreement between supervisor- parents and preschool staff was reached to confirm the intensity and content of the CIEI- program over an approximately two-year intervention period. Symptom changes were measured as evaluation-ADOS-2-scores, total- and severity-scores, minus the corresponding baseline-scores, divided by the time between baseline and evaluation. The difference between the study-groups regarding change of ADOS-2-scores was estimated using ANCOVA. In the current study, children in the CIEI-group improved their ADOS-2-total scores between baseline and evaluation (-0.8 scores per year; 95%CI: -1.2 to -0.4), whereas no such improvement was detected in the comparison group (+0.1 scores per year; 95%CI: -0.7 to +0.9). The change difference (change in the CIEI-group vs. change in the comparison group) was statistically significant, both crude and after adjusting for possible confounders (-1.1; 95%CI -1.9 to -0.4). Children in the CIEI-group also significantly improved their ADOS-calibrated severity scores, but not significantly differently so from the comparison group. The results from the current study indicate that the CIEI program significantly improves social and communicative skills among children with autism and that children with developmental delay could benefit to a similar degree as other children. The results support earlier studies reporting on the improvement of autism symptoms after early intensive interventions. The results from observational studies are difficult to interpret, but it is nevertheless of uttermost importance to evaluate costly autism intervention programs. Such results may be of immediate importance to healthcare organizations when allocating the already strained resources to different patient groups. Albeit the obvious limitation of the current naturalistic study, the results support previous positive studies and indicate that children with autism benefit from participating in early comprehensive, intensive programs and that investments in these programs may be highly justifiable.

Keywords: autism symptoms, ADOS-scores, evaluation, intervention program

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