Search results for: drug delivery to the brain

Authors: Keyvan Kashkouli Nejad, Motoaki Sugiura, Atsushi Sato, Takayuki Nozawa, Hyeonjeong Jeong, Sugiko Hanawa , Yuka Kotozaki, Ryuta Kawashima

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The perception of agency/control is altered with presence of discrepancies in the environment or mismatch of predictions (of possible results) and actual results the sense of agency might become altered. Synofzik et al. proposed a two layer model of agency: In the first layer, the Feeling of Agency (FoA) is not directly available to awareness; a slight mismatch in the environment/outcome might cause alterations in FoA, while the agent still feels in control. If the discrepancy passes a threshold, it becomes available to consciousness and alters Judgment of Agency (JoA), which is directly available in the person’s awareness. Most experiments so far only investigate subjects rather conscious JoA, while FoA has been neglected. In this experiment we target FoA by using subliminal discrepancies that can not be consciously detectable by the subjects. Here, we explore whether we can detect this two level model in the subjects behavior and then try to map this in their brain activity. To do this, in a fMRI study, we incorporated both consciously detectable mismatching between action and result and also subliminal discrepancies in the environment. Also, unlike previous experiments where subjective questions from the participants mainly trigger the rather conscious JoA, we also tried to measure the rather implicit FoA by asking participants to rate their performance. We compared behavioral results and also brain activation when there were conscious discrepancies and when there were subliminal discrepancies against trials with no discrepancies and against each other. In line with our expectations, conditions with consciously detectable incongruencies triggered lower JoA ratings than conditions without. Also, conditions with any type of discrepancies had lower FoA ratings compared to conditions without. Additionally, we found out that TPJ and angular gyrus in particular to have a role in coding of JoA and also FoA.

Keywords: agency, fMRI, TPJ, two layer model

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Authors: F. O. Adeosun, I. O. Orubuloye, O. O. Babalola

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Although caesarean section has greatly improved obstetric care throughout the world, in developing countries there is a great aversion to caesarean section. This study was carried out to examine the rate at which pregnant women with pre-eclampsia choose caesarean section over natural birth. A cross-sectional study was conducted among 500 pre-eclampsia antenatal clients seen at the States University Teaching Hospitals in the last one year. The sample selection was purposive. Information on their educational background, beliefs and attitudes were collected. Data analysis was presented using simple percentages. Out of 500 women studied, 38% favored caesarean section while 62% were against it. About 89% of them understood what caesarean section is, 57.3% of those who understood what caesarean section is will still not choose it as an option. Over 85% of the women believed caesarean section is done for medical reasons. If caesarean section is given as an option for childbirth, 38% would go for it, 29% would try religious intervention, 5.5% would not choose it because of fear, while 27.5% would reject it because they believe it is culturally wrong. Majority of respondents (85%) who favored caesarean delivery are aware of the risk attached to choosing virginal birth but go an extra mile in sourcing funds for a caesarean session while over 64% cannot afford the cost of caesarean delivery. It is therefore pertinent to encourage research in prediction methods and prevention of occurrence, since this would assist patients to plan on how to finance treatment.

Keywords: caesarean section, choice, cost, pre eclampsia, prediction methods

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Authors: Tamar Bikashvili, Tamar Lordkipanidze, Ilia Lazrishvili

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Heavy metals remain one of serious environmental problems due to their toxic effects. The effect of arsenic and manganese compounds on rat behavior and neuromorphology was studied. Wistar rats were assigned to four groups: rats in control group were given regular water, while rats in other groups drank water with final manganese concentration of 10 mg/L (group A), 20 mg/L (group B) and final arsenic concentration 68 mg/L (group C), respectively, for a month. To study exploratory and anxiety behavior and also to evaluate aggressive performance in “home cage” rats were tested in “Open Field” and to estimate learning and memory status multi-branched maze was used. Statistically significant increase of motor and oriental-searching activity in experimental groups was revealed by an open field test, which was expressed in increase of number of lines crossed, rearing and hole reflexes. Obtained results indicated the suppression of fear in rats exposed to manganese. Specifically, this was estimated by the frequency of getting to the central part of the open field. Experiments revealed that 30-day exposure to 10 mg/ml manganese did not stimulate aggressive behavior in rats, while exposure to the higher dose (20 mg/ml), 37% of initially non-aggressive animals manifested aggressive behavior. Furthermore, 25% of rats were extremely aggressive. Obtained data support the hypothesis that excess manganese in the body is one of the immediate causes of enhancement of interspecific predatory aggressive and violent behavior in rats. It was also discovered that manganese intoxication produces non-reversible severe learning disability and insignificant, reversible memory disturbances. Studies of rodents exposed to arsenic also revealed changes in the learning process. As it is known, the distribution of metal ions differs in various brain regions. The principle manganese accumulation was observed in the hippocampus and in the neocortex, while arsenic was predominantly accumulated in nucleus accumbens, striatum, and cortex. These brain regions play an important role in the regulation of emotional state and motor activity. Histopathological analyzes of brain sections illustrated two morphologically distinct altered phenotypes of neurons: (1) shrunk cells with indications of apoptosis - nucleus and cytoplasm were very difficult to be distinguished, the integrity of neuronal cytoplasm was not disturbed; and (2) swollen cells - with indications of necrosis. Pyknotic nucleus, plasma membrane disruption and cytoplasmic vacuoles were observed in swollen neurons and they were surrounded by activated gliocytes. It’s worth to mention that in the cortex the majority of damaged neurons were apoptotic while in subcortical nuclei –neurons were mainly necrotic. Ultrastructural analyses demonstrated that all cell types in the cortex and the nucleus caudatus represent destructed mitochondria, widened neurons’ vacuolar system profiles, increased number of lysosomes and degeneration of axonal endings.

Keywords: arsenic, manganese, behavior, learning, neuron

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Authors: Zayed Alsulami, Asma Aldosseri, Ahmed Ezziden, Abdulrahman Alonazi

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Children are more susceptible to medication errors than adults. Medication administration process is the last stage in the medication treatment process and most of the errors detected in this stage. Little research has been undertaken about medication errors in children in the Middle East countries. This study was aimed to evaluate how the paediatric nurses adhere to the medication administration policy and also to identify any medication preparation and administration errors or any risk factors. An observational, prospective study of medication administration process from when the nurses preparing patient medication until administration stage (May to August 2014) was conducted in Saudi Arabia. Twelve paediatric nurses serving 90 paediatric patients were observed. 456 drug administered doses were evaluated. Adherence rate was variable in 7 steps out of 16 steps. Patient allergy information, dose calculation, drug expiry date were the steps in medication administration with lowest adherence rates. 63 medication preparation and administration errors were identified with error rate 13.8% of medication administrations. No potentially life-threating errors were witnessed. Few logistic and administrative factors were reported. The results showed that the medication administration policy and procedure need an urgent revision to be more sensible for nurses in practice. Nurses’ knowledge and skills regarding the medication administration process should be improved.

Keywords: medication sasfety, paediatric, medication errors, paediatric ward

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Authors: Ma. Eliza Jijeth V. dela Cruz

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Technology is a recent prodigy in people’s everyday life that has taken off. It infiltrated almost every aspect of one’s lives, changing how people work, how people learn and how people perceive things. Academic Institutions, just like other organizations, have deeply modified its strategies to integrate technology into the institutional vision and corporate strategy that has never been greater. Information and Communications Technology (ICT) continues to be recognized as a major factor in organizations realizing its aims and objectives. Consequently, ICT has an important role in the mobilization of an academic institution’s strategy to support the delivery of operational, strategic or transformational objectives. This ICT strategy should align the institution with the radical changes of the ICT world through the use of Enterprise Architecture (EA). Hence, EA’s objective is to optimize the islands of legacy processes to be integrated that is receptive to change and supportive of the delivery of the strategy. In this paper, the focus is to explore the motivational antecedents during the adoption of EA in a Higher Education Institution in the Philippines for its ICT strategic plan. The seven antecedents (viewpoint, stakeholders, human traits, vision, revolutionary innovation, techniques and change components) provide understanding into EA adoption and the antecedents that influences the process of EA adoption.

Keywords: Enterprise Architecture, Adoption, Antecedents, Higher Educational Institutions

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Authors: Vasudha Devi, Arul Amuthan, K. Narayanan, Praveen KS, Venkata Rao J

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Background: Siddha Medicine is one of the Indian traditional medical systems, in which the cancer disease is mentioned as 'putrunoi' which literally means the disease of growth like termite mound. There are number of formulations available for the treatment of cancer disease. Neeradi muthu vallathymezugu (NMV) and thamira kattu chendooram (TKC) are two drugs commonly prescribed by Siddha physicians. These drugs have been clinically reported to be safe and effective when given orally. Though these formulations are in practice for centuries, no efforts have been made to standardize them and explore their anti-cancer potential systematically. Objective: To compare the cytotoxic activity of NMV and TKC with doxorubicin using cancer cell lines. Materials and methods: For this study, ethanol extract of NMV was taken, whereas TKC was used as such. In vitro cytotoxic activity was evaluated by sulphorhodamine (SRB) assay against human hepatic cancer cells (HepG2), human breast cancer cells (MCF-7) and human cervical cancer cells [KeLa]. Doxorubicin was used as the standard. The SRB assay is based on the ability of cellular proteins to bind with sulphorhodamine-B. The number of live cells in drug treated cell lines directly affects the color formation in the assay, which is estimated calorimetrically by measuring the absorbance at 540 nm to calculate the cytotoxicity (inhibitory concentration - IC50 value) of the drug. Results: The IC50values of NMV, TKC and doxorubicin against HepG2 were 3.08 µg/ml, 20.21 µg/ml and 1.21µg/ml respectively. In MCF-7, it was 11.75 µg/ml, 17.67 µg/ml and 2.8µg/ml. In HeLa, the values were 24.76 µg/ml, 73.35 µg/ml and 1.12µg/ml. Conclusions: The study proves the possible anti-cancer potential of these two formulations. Compared to TKC, NMV showed good cytotoxic effect even at low dose. Human hepatic cancer cells responded well even at very low dose, when compared to other cancer cells. Though, cytotoxic potential of these compounds was found to be less compared to doxorubicin, the isolated lead compound may have the potential to be used as an anticancer drug clinically.

Keywords: Neeradi muthu vallathymezugu (Hydnocarpus laurifolia), thamira kattu chendooram, cytotoxicity, in-vitro, Siddha Medicine

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Authors: M. Saard, A. Kolk, K. Sepp, L. Pertens, L. Reinart, C. Kööp

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Introduction: Social competence is often impaired in children with acquired brain injury (ABI), but evidence-based rehabilitation for social skills has remained undeveloped. Modern technology-based methods create effective and safe learning environments for pediatric social skills remediation. The aim of the study was to implement our structured model of neuro rehab for socio-cognitive deficit using multitouch-multiuser tabletop (MMT) computer-based platforms and virtual reality (VR) technology. Methods: 40 children aged 8-13 years (yrs) have participated in the pilot study: 30 with ABI -epilepsy, traumatic brain injury and/or tic disorder- and 10 healthy age-matched controls. From the patients, 12 have completed the training (M = 11.10 yrs, SD = 1.543) and 20 are still in training or in the waiting-list group (M = 10.69 yrs, SD = 1.704). All children performed the first individual and paired assessments. For patients, second evaluations were performed after the intervention period. Two interactive applications were implemented into rehabilitation design: Snowflake software on MMT tabletop and NoProblem on DiamondTouch Table (DTT), which allowed paired training (2 children at once). Also, in individual training sessions, HTC Vive VR device was used with VR metaphors of difficult social situations to treat social anxiety and train social skills. Results: At baseline (B) evaluations, patients had higher deficits in executive functions on the BRIEF parents’ questionnaire (M = 117, SD = 23.594) compared to healthy controls (M = 22, SD = 18.385). The most impaired components of social competence were emotion recognition, Theory of Mind skills (ToM), cooperation, verbal/non-verbal communication, and pragmatics (Friendship Observation Scale scores only 25-50% out of 100% for patients). In Sentence Completion Task and Spence Anxiety Scale, the patients reported a lack of friends, behavioral problems, bullying in school, and social anxiety. Outcome evaluations: Snowflake on MMT improved executive and cooperation skills and DTT developed communication skills, metacognitive skills, and coping. VR, video modelling and role-plays improved social attention, emotional attitude, gestural behaviors, and decreased social anxiety. NEPSY-II showed improvement in Affect Recognition [B = 7, SD = 5.01 vs outcome (O) = 10, SD = 5.85], Verbal ToM (B = 8, SD = 3.06 vs O = 10, SD = 4.08), Contextual ToM (B = 8, SD = 3.15 vs O = 11, SD = 2.87). ToM Stories test showed an improved understanding of Intentional Lying (B = 7, SD = 2.20 vs O = 10, SD = 0.50), and Sarcasm (B=6, SD = 2.20 vs O = 7, SD = 2.50). Conclusion: Neurorehabilitation based on the Structured Model of Neurorehab for Socio-Cognitive Deficit in children with ABI were effective in social skills remediation. The model helps to understand theoretical connections between components of social competence and modern interactive computerized platforms. We encourage therapists to implement these next-generation devices into the rehabilitation process as MMT and VR interfaces are motivating for children, thus ensuring good compliance. Improving children’s social skills is important for their and their families’ quality of life and social capital.

Keywords: acquired brain injury, children, social skills deficit, technology-based neurorehabilitation

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Authors: Salina Budin, Shaira Ismail

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Students learn effectively in a learning environment with a suitable teaching approach that matches their learning preferences. The main objective of the study is to examine the learning preferences amongst the students in the Science and Technology (S&T), and Social Science (SS) fields of study at the Universiti Teknologi Mara (UiTM), Pulau Pinang. The measurement instrument is based on the Dunn and Dunn Learning Styles which measure five elements of learning styles; environmental, sociological, emotional, physiological and psychological. Questionnaires are distributed amongst undergraduates in the Faculty of Mechanical Engineering and Faculty of Business Management. The respondents comprise of 131 diploma students of the Faculty of Mechanical Engineering and 111 degree students of the Faculty of Business Management. The results indicate that, both S&T and SS students share a similar learning preferences on the environmental aspect, emotional preferences, motivational level, learning responsibility, persistent level in learning and learning structure. Most of the S&T students are concluded as analytical learners and the majority of SS students are global learners. Both S&T and SS students are concluded as visual learners, preferred to be in an active mobility in a relaxing and enjoying mode with some light of refreshments during the learning process and exhibited reflective characteristics in learning. Obviously, the S&T students are considered as left brain dominant, whereas the SS students are right brain dominant. The findings highlighted that both categories of students exhibited similar learning preferences except on psychological preferences.

Keywords: learning preferences, Dunn and Dunn learning style, teaching approach, science and technology, social science

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Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero

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The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.

Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration

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Authors: Auxeeliya Jesudoss, Ashraph Sulaiman, Ratnakar Kotnana

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V2V communication brings up several questions of scalability issues although message sharing in vehicular ad-hoc networks comprises of both Vehicle-to-Vehicle communications (V2V) and Vehicle to Infrastructure communication (V2I). It is not an easy task for a vehicle to verify all signatures of the messages sent by its neighboring vehicles in a timely manner, without resulting in message loss. Moreover, the communication overhead of a vehicle to authenticate another vehicle would increase together with the security of the system. Another issue to be addressed is the continuous mobility of vehicles which requires at least some information on the node’s own position to be revealed to the neighboring vehicles. This may facilitate the attacker to congregate information on a node’s position or its mobility patterns. In order to tackle these issues, this paper introduces a RSU aggregated message deliverance scheme called RAMeD. With RAMeD, roadside units (RSUs) are responsible for verifying the identity of the vehicles entering in its range, collect messages from genuine vehicles and to aggregate similar messages into groups before sending them to all the vehicles in its communication range. This aggregation will tremendously improve the rate of message delivery and reduce the message lose ratio by avoiding similar messages being sent to the vehicles redundantly. The proposed protocol is analyzed extensively to evaluate its merits and efficiency for vehicular communication.

Keywords: vehicular ad-hoc networks, V2V, V2I, VANET communication, scalability, message aggregation

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Authors: Sarah Gounden, Mukesh Dheda, Boikhutso Tlou, Elizabeth Ojewole, Frasia Oosthuizen

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Background: Antiretroviral therapy (ART) has been effective in the reduction of mortality and resulted in an improvement in the prognosis of HIV-infected patients. However, treatment with antiretrovirals (ARVs) has led to the development of many adverse drug reactions (ADRs). It is, therefore, necessary to determine the safety profile of these medicines in a South African population in order to ensure safe and optimal medicine use. Objectives: The aim of this study was to quantify ADRs experienced with the different ARVs currently used in South Africa, to determine the safety profile of ARV medicine in South Africa based on reported ADRs, and to determine the ARVs with the lowest risk profile based on specific patient populations. Methodology: This was a quantitative study. Individual case safety reports for the period January 2010 – December 2013 were obtained from the National Pharmacovigilance Center; these reports contained information on ADRs, ARV medicine, and patient demographics. Data was analysed to find associations that may exist between ADRs experienced, ARV medicines used and patient demographics. Results: A total of 1916 patient reports were received of which 1534 met the inclusion criteria for the study. The ARV with the lowest risk of ADRs were found to be lamivudine (0.51%, n=12), followed by lopinavir/ritonavir combination (0.8%, n=19) and abacavir (0.64%, n=15). A higher incidence of ADRs was observed in females compared to males. The age group 31–50 years and the weight group 61–80 kg had the highest incidence of ADRs reported. Conclusion: This study found that the safest ARVs to be used in a South African population are lamivudine, abacavir, and the lopinavir/ritonavir combination. Gender differences play a significant role in the occurrence of ADRs and both anatomical and physiological differences account for this. An increased BMI (body mass index) in both men and women showed an increase in the incidence of ADRs associated with ARV therapy.

Keywords: adverse drug reaction, antiretrovirals, HIV/AIDS, pharmacovigilance, South Africa

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Authors: Wid Kattan, Rahaf Albarraq

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Background: Tokophobia is a pathological fear of pregnancy that can lead to the avoidance of childbirth. It is classified as primary or secondary. This report describes a patient with tokophobia, as well as her presentation, risk factors, comorbidities, and treatment. Case Presentation: A 43-year-old Saudi woman experienced tokophobia upon becoming pregnant for the fifth time. She was assessed in two clinical interviews by a consultant psychiatrist specializing in women’s mental health. In addition, she completed several questionnaires for assessment of different aspects of her mental health: overall depression, perinatal depression, generalized anxiety, maternal functioning, and fear of childbirth (FOC). Several risk factors and comorbidities that may have contributed to the development of tokophobia in this patient were discussed, including traumatic experiences in previous deliveries, the unplanned nature of the pregnancy, perinatal depression, and pronounced symptoms of anxiety. A collaborative decision to perform a C-section was made, in line with obstetric guidelines and good mental health practice. Full symptomatic recovery was achieved immediately after delivery. Conclusions: We hope to increase clinical awareness of the assessment and management of tokophobia, which is a relatively new concept and, as yet, understudied.

Keywords: tokophobia, fear of childbirth, mental health, anxiety, case report, depression, fear of delivery, psychiatry, cesarean section, perinatal depression

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Authors: Ikenna Stephen Ezennia, Sebnem Onal Hoscara

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Successive governments in Nigeria are faced with the pressing problem of how to house an ever-expanding urban population, usually low-income earners. The question of housing and affordability presents a complex challenge for these governments, as the commodification of housing links it inextricably to markets and capital flows. Therefore, placing it as at the center of the government’s agenda. However, the provision of decent and affordable housing for average Nigerians has remained an illusion, despite copious schemes, policies and programs initiated and carried out by various successive governments. Similarly, this phenomenon has also been observed in many countries of Africa, which is largely a result of economic unpredictability, lack of housing finance and insecurity, among other factors peculiar to a struggling economy. This study reviews recent dynamics and factors challenging the provision and development of affordable housing for the low income urban populace of Nigeria. Thus, the aim of the study is to present a comprehensive approach for understanding recent trends in the provision of affordable housing for Nigerians. The approach is based on a new paradigm of research: transdisciplinarity; a form of inquiry that crosses the boundaries of different disciplines. Therefore, the review takes a retrospective gaze at the various housing development programs/schemes/policies taken by successive governments of Nigeria within the last few decades and exams recent efforts geared towards eradicating the problems of housing delivery. Sources of data included relevant English language articles and the results of literature search of Elsevier Science Direct, ISI Web of Knowledge, Pro Quest Central, Scopus, and Google Scholar. The findings reveal that factors such as; rapid urbanization, inadequate planning and land use control, lack of adequate and favorable finance, high prices of land, high prices of building material, youth/touts harassment of developers, poor urban infrastructure, multiple taxation, and risk share are the major factors posing as a hindrance to adequate housing delivery. The results show that the majority of Nigeria’s affordable housing schemes, programs and policies are in most cases poorly implemented and abandoned without proper coordination. Consequently, the study concludes that the affordable housing delivery strategies in Nigeria are an epitome of lip service politics by successive governments; and the current trend of leaving housing provision to the vagaries of market forces cannot be expected to support affordable housing especially for the low income urban populace.

Keywords: affordable housing, housing delivery, national housing policy, urban poor

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Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

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Authors: M. G. Talasbayen, N. N. Dyussenbayev, Y. D. Kali, R. A. Zholbarysov, Y. N. Duissenbayev, I. Z. Mammadinova, S. M. Nuradilov

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Background. Hemorrhagic stroke is an acute cerebrovascular accident resulting from rupture of a cerebral vessel or increased permeability of the wall and imbibition of blood into the brain parenchyma. Arterial hypertension is a common cause of hemorrhagic stroke. Male gender and age over 55 years is a risk factor for intracerebral hemorrhage. Treatment of intracerebral hemorrhage is aimed at the primary pathophysiological link: the relief of coagulopathy and the control of arterial hypertension. Early surgical treatment can limit cerebral compression; prevent toxic effects of blood to the brain parenchyma. Despite progress in the development of neuroimaging data, the use of minimally invasive techniques, and navigation system, mortality from intracerebral hemorrhage remains high. Materials and methods. The study included 78 patients (62.82% male and 37.18% female) with a verified diagnosis of hemorrhagic stroke in the period from 2019 to 2021. The age of patients ranged from 25 to 80 years, the average age was 54.66±11.9 years. Demographic, brain CT data (localization, volume of hematomas), methods of treatment, and disease outcome were analyzed. Results. The retrospective analyze demonstrate that 78.2% of all patients underwent surgical treatment: decompressive craniectomy in 37.7%, craniotomy with hematoma evacuation in 29.5%, and hematoma draining in 24.59% cases. The study of the proportion of deaths, depending on the volume of intracerebral hemorrhage, shows that the number of deaths was higher in the group with a hematoma volume of more than 60 ml. Evaluation of the relationship between the time before surgery and mortality demonstrates that the most favorable outcome is observed during surgical treatment in the interval from 3 to 24 hours. Mortality depending on age did not reveal a significant difference between age groups. An analysis of the impact of the surgery type on mortality reveals that decompressive craniectomy with or without hematoma evacuation led to an unfavorable outcome in 73.9% of cases, while craniotomy with hematoma evacuation and drainage led to mortality only in 28.82% cases. Conclusion. Even though the multimodal approaches, the development of surgical techniques and equipment, and the selection of optimal conservative therapy, the question of determining the tactics of managing and treating hemorrhagic strokes is still controversial. Nevertheless, our experience shows that surgical intervention within 24 hours from the moment of admission and craniotomy with hematoma evacuation improves the prognosis of treatment outcomes.

Keywords: hemorragic stroke, Intracerebral hemorrhage, surgical treatment, stroke mortality

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: Evangelos Koumparoudis

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The definition of death is a deep philosophical question, and no single meaning can be ascribed to it. This essay focuses on the ontological, epistemological, and ethical aspects of death and dying in view of technological progress in information technology and biomedicine. It starts with the ad hoc 1968 Harvard committee that proposed that the criterion for the definition of death be irreversible coma and then refers to the debate over the whole brain death formula, emphasizing the integrated function of the organism and higher brain formula, taking consciousness and personality as essential human characteristics. It follows with the contribution of information technology in personalized and precision medicine and anti-aging measures aimed at life prolongation. It also touches on the possibility of the creation of human-machine hybrids and how this raises ontological and ethical issues that concern the “cyborgization” of human beings and the conception of the organism and personhood based on a post/transhumanist essence, and, furthermore, if sentient AI capable of autonomous decision-making that might even surpass human intelligence (singularity, superintelligence) deserves moral or legal personhood. Finally, there is the question as to whether death and dying should be redefined at a transcendent level, which is reinforced by already-existing technologies of “virtual after-” life and the possibility of uploading human minds. In the last section, I refer to the current (and future) applications of nanomedicine in diagnostics, therapeutics, implants, and tissue engineering as well as the aspiration to “immortality” by cryonics. The definition of death is reformulated since age and disease elimination may be realized, and the criterion of irreversibility may be challenged.

Keywords: death, posthumanism, infomedicine, nanomedicine, cryonics

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Authors: Haw-Long Lee, Win-Jin Chang, Yu-Ching Yang

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In the paper, the coupled equation of motion for the dynamic displacement of a fullerene moving in a (10,10) single-walled carbon nanotube (SWCNT) is derived using nonlocal Timoshenko beam theory, including the effects of rotary inertia and shear deformation. The effects of confined stiffness between the fullerene and nanotube, foundation stiffness, and nonlocal parameter on the dynamic behavior are analyzed using the Runge-Kutta Method. The numerical solution is in agreement with the analytical result for the special case. The numerical results show that increasing the confined stiffness and foundation stiffness decrease the dynamic displacement of SWCNT. However, the dynamic displacement increases with increasing the nonlocal parameter. In addition, result using the Euler beam theory and the Timoshenko beam theory are compared. It can be found that ignoring the effects of rotary inertia and shear deformation leads to an underestimation of the displacement.

Keywords: single-walled carbon nanotube, nanoparticle delivery, Nonlocal Timoshenko beam theory, Runge-Kutta Method, Van der Waals force

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Authors: Takashi Kaburagi, Masashi Takenaka, Yosuke Kurihara, Takashi Matsumoto

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Major depressive disorder (MDD) is one of the most common mental illnesses today. It is believed to be caused by a combination of several factors, including stress. Stress can be quantitatively evaluated using the State-Trait Anxiety Inventory (STAI), one of the best indices to evaluate anxiety. Although STAI scores are widely used in applications ranging from clinical diagnosis to basic research, the scores are calculated based on a self-reported questionnaire. An objective evaluation is required because the subject may intentionally change his/her answers if multiple tests are carried out. In this article, we present a modified index called the “multi-channel Laterality Index at Rest (mc-LIR)” by recording the brain activity from a wider area of the frontal lobe using multi-channel functional near-infrared spectroscopy (fNIRS). The presented index aims to measure multiple positions near the F_pz defined by the international 10-20 system positioning. Using 24 subjects, the dependencies on the number of measuring points used to calculate the mc-LIR and its correlation coefficients with the STAI scores are reported. Furthermore, a simple linear regression was performed to estimate the STAI scores from mc-LIR. The cross-validation error is also reported. The experimental results show that using multiple positions near the Fpz will improve the correlation coefficients and estimation than those using only two positions.

Keywords: frontal lobe, functional near-infrared spectroscopy, state-trait anxiety inventory score, stress

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Authors: Rachel Fanelwa Ajayi, Anovuyo Jonnas, Emmanuel I. Iwuoha

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Tuberculosis (TB) is an infectious disease caused by the bacterium (Mycobacterium tuberculosis) which has a predilection for lung tissue due to its rich oxygen supply. The mycobacterial cell has a unique innate characteristic which allows it to resist human immune systems and drug treatments; hence, it is one of the most difficult of all bacterial infections to treat, let alone to cure. At the same time, multi-drug resistance TB (MDR-TB) caused by poorly managed TB treatment, is a growing problem and requires the administration of expensive and less effective second line drugs which take much longer treatment duration than fist line drugs. Therefore, to acknowledge the issues of patients falling ill as a result of inappropriate dosing of treatment and inadequate treatment administration, a device with a fast response time coupled with enhanced performance and increased sensitivity is essential. This study involved the synthesis of electroactive platforms for application in the development of nano-biosensors suitable for the appropriate dosing of clinically diagnosed patients by promptly quantifying the levels of the TB drug; Isonaizid. These nano-biosensors systems were developed on gold surfaces using the enzyme N-acetyletransferase 2 coupled to the cysteamine modified poly(8-anilino-1-napthalene sulphonic acid)/zinc oxide nanocomposites. The morphology of ZnO nanoparticles, PANSA/ZnO nano-composite and nano-biosensors platforms were characterized using High-Resolution Transmission Electron Microscopy (HRTEM) and High-Resolution Scanning Electron Microscopy (HRSEM). On the other hand, the elemental composition of the developed nanocomposites and nano-biosensors were studied using Fourier Transform Infra-Red Spectroscopy (FTIR) and Energy Dispersive X-Ray (EDX). The electrochemical studies showed an increase in electron conductivity for the PANSA/ZnO nanocomposite which was an indication that it was suitable as a platform towards biosensor development.

Keywords: N-acetyletransferase 2, isonaizid, tuberculosis, zinc oxide

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Authors: Zerihun Ketema Tadesse, Dabbu Suman Reddy

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Brain-Computer Interfaces (BCIs) give the possibility for disabled people to communicate and control devices. This work aims at developing steady-state visual evoked potential (SSVEP)-based BCI for patients with limb disabilities. In hospitals, devices like nurse emergency call devices, lights, and TV sets are what patients use most frequently, but these devices are operated manually or using the remote control. Thus, disabled patients are not able to operate these devices by themselves. Hence, SSVEP-based BCI system that can allow disabled patients to control nurse calling device and other devices is proposed in this work. Portable LED visual stimulator that flickers at specific frequencies of 7Hz, 8Hz, 9Hz and 10Hz were developed as part of this project. Disabled patients can stare at specific flickering LED of visual stimulator and Emotiv EPOC used to acquire EEG signal in a non-invasive way. The acquired EEG signal can be processed to generate various control signals depending upon the amplitude and duration of signal components. MATLAB software is used for signal processing and analysis and also for command generation. Arduino is used as a hardware interface device to receive and transmit command signals to the experimental setup. Therefore, this study is focused on the design and development of Steady-state visually evoked potential (SSVEP)-based BCI for limb disabled patients, which helps them to operate and control devices in the hospital room/wards.

Keywords: SSVEP-BCI, Limb Disabled Patients, LED Visual Stimulator, EEG signal, control devices, hospital room/wards

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Authors: Edicio M. Faller

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The use of technology in the delivery of teaching and learning is vital nowadays especially in education. Computer Assisted Learning Module (CALM) software is the use of computer in the delivery of instruction with a tailored fit program intended for a specific lesson or a set of topics. The CALM software developed in this study is intended to supplement the traditional teaching methods in technical-vocational (TECH-VOC) instruction specifically the Consumer Electronics Servicing course. There are three specific objectives of this study. First is to create a learning enhancement and review materials on the selected lessons. Second, is to computerize the end-of-chapter quizzes. Third, is to generate a computerized mock exam and summative assessment. In order to obtain the objectives of the study the researcher adopted the Agile Model where the development of the study undergoes iterative and incremental process of the Software Development Life Cycle. The study conducted an acceptance testing using a survey questionnaire to evaluate the CALM software. The results showed that CALM software was generally interpreted as very satisfactory. To further improve the CALM software it is recommended that the program be updated, enhanced and lastly, be converted from stand-alone to a client/server architecture.

Keywords: computer assisted learning module, software development life cycle, computerized mock exam, consumer electronics servicing

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Authors: Katarina Lazarević, Mirjana Todosijević, Tijana Vulević, Natalija Momirović, Ranka Erić

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Due to increasing demand, climate change, and world population growth, natural resources are getting exploit fast. One of the most important natural resources is soil, which is susceptible to degradation. Erosion as one of the forms of land degradation is also one of the most global environmental problems. Ecosystem services are often defined as benefits that nature provides to humankind. Soil, as the foundation of basic ecosystem functions, provides benefits to people, erosion control, water infiltration, food, fuel, fibers… This research is using the ecosystem approach as a strategy for natural resources management for promoting sustainability and conservation. The research was done on the Topčiderska River basin (Belgrade, Serbia). The InVEST Sediment Delivery Ratio model was used, to quantify erosion intensity with a spatial distribution output map of overland sediment generation and delivery to the stream. InVEST SDR, a spatially explicit model, is using a method based on the concept of hydrological connectivity and (R) USLE model. This, combined with socio-economic and law and policy analysis, gives a full set of information to decision-makers helping them to successfully manage and deliver sustainable ecosystems.

Keywords: ecosystem services, InVEST model, soil erosion, sustainability

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Authors: Iddrisu Ibrahim, Joseph Atia Ayariga, Junhuan Xu, Daniel A. Abugri, Robertson K. Boakai, Olufemi S. Ajayi

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The recalcitrance of pathogenic bacteria indicates that millions of people who are at risk of infection arising from chronic diseases, surgery, organ transplant, diabetes, and several other debilitating diseases present an aura of potentially untreatable illness due to resistance development. Antimicrobial resistance has successfully become a global health menace, and resistances are often acquired by bacteria through health-care-related incidence (HRI) orchestrated by multi-drug resistant (MDR) and extended drug-resistant pathogens (EDRP). To understand the mechanisms S. Typhimurium uses to resist CDB, we study the abundance of LPS modification, Ergosterols, Mysristic palmitic resistance, Oleic acid resistance of susceptible and resistant S. Typhimurium. Using qPCR, we also analyzed the expression of selected genes known for enabling resistance in S. Typhimurium. We found high abundance of LPS, Ergosterols, Mysristic palmitic resistance, Oleic acid resistance of and high expression of resistant genes in S. Typhimurium compared to the susceptible strain. LPS modification, Ergosterols, Mysristic palmitic resistance, Oleic acid and genes such as Fims, integrons, blaTEM are important indicators of resistance development of S. typhimurium.

Keywords: antimicrobials, resistance, Cannabidiol, Salmonella, blaTEM, fimA, Lipopolysaccharide, Ergosterols

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Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah

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Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.

Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes

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Authors: Melissa Langevin, Natalie Ward, Colleen Fitzgibbons, Christa Ramsey, Melanie Hogue, Anna Theresa Lobos

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Description: Root Cause Analysis (RCA) is used by health care teams to examine adverse events (AEs) to identify causes which then leads to recommendations for prevention Despite widespread use, RCA has limitations. Best practices have not been established for implementing recommendations or tracking the impact of interventions after AEs. During phase 1 of this study, we used simulation to analyze two fictionalized AEs that occurred in hospitalized paediatric patients to identify and understand how the errors occurred and generated recommendations to mitigate and prevent recurrences. Scenario A involved an error of commission (inpatient drug error), and Scenario B involved detecting an error that already occurred (critical care drug infusion error). Recommendations generated were: improved drug labeling, specialized drug kids, alert signs and clinical checklists. Aim: Use simulation to optimize interventions recommended post critical event analysis prior to implementation in the clinical environment. Methods: Suggested interventions from Phase 1 were designed and tested through scenario simulation in the clinical environment (medicine ward or pediatric intensive care unit). Each scenario was simulated 8 times. Recommendations were tested using different, voluntary teams and each scenario was debriefed to understand why the error was repeated despite interventions and how interventions could be improved. Interventions were modified with subsequent simulations until recommendations were felt to have an optimal effect and data saturation was achieved. Along with concrete suggestions for design and process change, qualitative data pertaining to employee communication and hospital standard work was collected and analyzed. Results: Each scenario had a total of three interventions to test. In, scenario 1, the error was reproduced in the initial two iterations and mitigated following key intervention changes. In scenario 2, the error was identified immediately in all cases where the intervention checklist was utilized properly. Independently of intervention changes and improvements, the simulation was beneficial to identify which of these should be prioritized for implementation and highlighted that even the potential solutions most frequently suggested by participants did not always translate into error prevention in the clinical environment. Conclusion: We conclude that interventions that help to change process (epinephrine kit or mandatory checklist) were more successful at preventing errors than passive interventions (signage, change in memory aids). Given that even the most successful interventions needed modifications and subsequent re-testing, simulation is key to optimizing suggested changes. Simulation is a safe, practice changing modality for institutions to use prior to implementing recommendations from RCA following AE reviews.

Keywords: adverse events, patient safety, pediatrics, root cause analysis, simulation

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Authors: Ebenezer O. Ige, Funmilayo H. Oyelami, Joshua Olutayo-Irheren, Joseph T. Okunlola

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Hyperthermia therapy is an adjuvant procedure during which perfused body tissues is subjected to elevated range of temperature in bid to achieve improved drug potency and efficacy of cancer treatment. While a selected class of hyperthermia techniques is shouldered on the thermal radiations derived from single-sourced electro-radiation measures, there are deliberations on conjugating dual radiation field sources in an attempt to improve the delivery of therapy procedure. This paper numerically explores the thermal effectiveness of combined infrared hyperemia having nanoparticle recirculation in the vicinity of imposed magnetic field on subcutaneous strata of a model lesion as ablation scheme. An elaborate Spectral relaxation method (SRM) was formulated to handle equation of coupled momentum and thermal equilibrium in the blood-perfused tissue domain of a spongy fibrous tissue. Thermal diffusion regimes in the presence of external magnetic field imposition were described leveraging on the renowned Roseland diffusion approximation to delineate the impact of radiative flux within the computational domain. The contribution of tissue sponginess was examined using mechanics of pore-scale porosity over a selected of clinical informed scenarios. Our observations showed for a substantial depth of spongy lesion, magnetic field architecture constitute the control regimes of hemodynamics in the blood-tissue interface while facilitating thermal transport across the depth of the model lesion. This parameter-indicator could be utilized to control the dispensing of hyperthermia treatment in intravenous perfused tissue.

Keywords: spectra relaxation scheme, thermal equilibrium, Roseland diffusion approximation, hyperthermia therapy

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Authors: Donna L. Roberts

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Heroin has appeared on the drug scene before. Yet the current opioid crisis differs in significant ways. In order to address the grave challenges, this epidemic poses, the unique precipitating and sustaining conditions must be thoroughly examined. This research explored the various aspects of the political, economic, and social conditions that created a 'perfect storm' for the evolution and maintenance of the current opioid crisis. Specifically, the epidemiology, demographics, and progression of addiction inherent in the current crisis were compared to the patterns of past opioid use. Additionally, the role of pharmaceutical companies and prescribing physicians, the nature and pharmaceutical properties of the available substances and the changing socioeconomic climate were considered. Results indicated that the current crisis differs significantly with respect to its evolution, magnitude, prevalence, and widespread societal effects. Precipitated by a proliferation of prescription medication and sustained by the availability of cheaper, more potent street drugs, including new versions of synthetic opioids, the current crisis presents unprecedented challenges affecting a wider and more diverse segment of society. The unique aspects of this epidemic demand unique approaches to addressing the problem. Understanding these differences is a key step in working toward a practical and enduring solution.

Keywords: addiction, drug abuse, opioids, opioid crisis

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Authors: Kye Gilder, Kevin Shan, Amy Halseth, Steve Smith

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This study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. Only serious adverse events (SAE) and adverse events leading to discontinuation of study drug (AELDSD) were collected. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focused on AEs in participants on antidepressants at baseline, as these individuals were excluded from Phase 3 trials. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age of 61 yrs, mean BMI 37.3 kg/m2, 22.8% with a history of depression, 23.1% on antidepressants, including 15.4% on an SSRI. SAEs in participants receiving antidepressants was similar between NB (10.7%) and PBO (9.9%) and also similar to overall population (9.5% NB, 8.1% PBO). SAEs in those on SSRIs were similar, 10.1% NB and PBO 9.4%. For those on SSRIs or other antidepressants, AELDSDs were similar to overall population and were primarily GI disorders. Obesity increases the risk of developing depression. For participants taking NB and antidepressants, including SSRIs, there is a similar AE profile as the overall population and data revealed no evidence of an additional health risk with combined use.

Keywords: antidepressant, Contrave, Mysimba, obesity, pharmacotherapy

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