Search results for: drug synergy

Authors: Arpit Kumar Shrivastava, Subrat Kumar, Rajani Kanta Mohapatra, Priyadarshi Soumyaranjan Sahu

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Computational approaches to predict structure, function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are not effective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical epitopic protein in C. hominis genome through BLASTP analysis. A 3D model of the hypothetical protein was generated using I-Tasser server through threading methodology. The quality of the model was validated through Ramachandran plot by PROCHECK server. The functional annotation of the hypothetical protein through DALI server revealed structural similarity with human Transportin 3. Phylogenetic analysis for this hypothetical protein also showed C. hominis hypothetical protein (CUV04613) was the closely related to human transportin 3 protein. The 3D protein model is further subjected to virtual screening study with inhibitors from the Zinc Database by using Dock Blaster software. Docking study reported N-(3-chlorobenzyl) ethane-1,2-diamine as the best inhibitor in terms of docking score. Docking analysis elucidated that Leu 525, Ile 526, Glu 528, Glu 529 are critical residues for ligand–receptor interactions. The molecular dynamic simulation was done to access the reliability of the binding pose of inhibitor and protein complex using GROMACS software at 10ns time point. Trajectories were analyzed at each 2.5 ns time interval, among which, H-bond with LEU-525 and GLY- 530 are significantly present in MD trajectories. Furthermore, antigenic determinants of the protein were determined with the help of DNA Star software. Our study findings showed a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for control as well as prevention of cryptosporidiosis among humans and animals.

Keywords: cryptosporidium hominis, hypothetical protein, molecular docking, molecular dynamics simulation

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Authors: Elachouri Mostafa, Fakchich Jamila, Lazaar Jamila, Elmadmad Mohammed, Marhom Mostafa

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Of course, there has been a great growth in scientific information about medicinal plants in recent decades, but in many ways this has proved poor compensation, because such information is accessible, in practice, only to a very few people and anyway, rather little of it is relevant to problems of management and utilization, as encountered in the field. Active compounds are used in most traditional medicines and play an important role in advancing sustainable rural livelihoods through their conservation, cultivation, propagation, marketing and commercialization. Medicinal herbs are great resources for various pharmaceutical compounds and urgent measures are required to protect these plant species from their natural destruction and disappearance. Indeed, there is a real danger of indigenous Arab medicinal practices and knowledge disappearing altogether, further weakening traditional Arab culture and creating more insecurity, as well as forsaking a resource of inestimable economic and health care importance. As scientific approach, the ethnopharmacological investigation remains the principal way to improve, evaluate, and increase the odds of finding of biologically active compounds derived from medicinal plants. As developing country, belonging to the Mediterranean basin, Morocco country is endowed with resources of medicinal and aromatic plants. These plants have been used over the millennia for human welfare, even today. Besides, Morocco has a large plant biodiversity, in fact, its medicinal flora account more than 4200 species growing on various bioclimatic zones from subhumide to arid and Saharan. Nevertheless, the human and animal pressure resulting from the increase of rural population needs has led to degradation of this patrimony. In this paper, we focus our attention on ethnopharmacological studies carried out in Morocco. The goal of this work is to clarify the importance of herbs as platform for drugs discovery and further development, to highlight the importance of ethnopharmacological study as approach on discovery of natural products in the health care field, and to discuss the limit of ethnopharmacological investigation of drug discovery in Morocco.

Keywords: Morocco, medicinal plants, ethnopharmacology, natural products, drug-discovery

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Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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Authors: Nour Elhouda Abed, Bedj Mimi, Wahid Slimani, Mourad Atif, Abdelhakim Ouzzane, Hocine Irekti, Abdelkader Bekki

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The most frequent system of cereal production in Algeria is fallow-wheat. This is an extensive system that meets only the half needs some cereals and fodder demand. Resorption of fallow has become a strategic necessity to ensure food security in response to the instability of supply and the persistence of higher food prices on the world market. Despite several attempts to replace the fallow by crop cultures, choosing the best crop remains. Today, the agronomic and economic interests of legumes are demonstrated. However, their crop culture remains marginalized because of the weakness and instability of their performance. In the context of improving legumes and cereals crops as well as fallow resorption, we undertook to test, in the field, the effect of rhizobial inoculation of Phaseolus vulgaris in association with Zea Mays. We firstly studied the genetic diversity of rhizobial strains that nodulate P.vulgaris isolated from fifteen (15) different regions. ARDRA had shown 18 different genetic profiles. Symbiotic characterization highlighted a strain that highly significantly improved the fresh and dry weight of the host plant, in comparison to the negative control (un-inoculated) and the positive control (inoculated with the reference strain CIAT 899). In the field, the selected strain increased significantly the growth and yield of P.vulgaris and Zea Mays comparing to the non-inoculated control. However, the mix inoculation (selected strain+ Ciat 899) had not given the best parameters showing, thus, no synergy between the strains. These results indicate the replacing fallow by a crop legume in intercropping with cereals crops.

Keywords: fallow, intercropping, inoculation, legumes-cereals

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Authors: M. Mirmohammadi, S. Taghdisi, F. Anali

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Gossypol is a yellow anti-nutritional compound found in the cotton plant. This substance exists in the cottonseed and other parts of the cotton plant, such as bark, leaves, and stems. Chemically, gossypol is a very active polyphenolic aldehyde compound, and due to this polyphenolic structure, it has antioxidant and therapeutic properties. On the other hand, this compound, especially in free form, has many toxic effects, that its excessive consumption can be very dangerous for humans and animals. In this study, gossypol was extracted as a derivative compound of gossypol acetic acid from cottonseed using the n-hexane solvent with an efficiency of 0.84 ± 0.04, which compared to the Gossypol extracted from cottonseed oil with the same method (cold press) showed a significant difference with its efficiency of 1.14 ± 0.06. Therefore, it can be suggested to use cottonseed oil to extract this valuable compound. In the other part of this research, cottonseed extracts and cotton bolls extracts were obtained by two methods of soaking and Soxhlet with hydroalcoholic solvent taken with a ratio of (25:75), then by using extracts and corn starch powder, four herbal medicine code was created and after receiving the code of ethics (IR.SSU.REC.1398.136) the therapeutic effect of each one on the Cutaneous leishmaniasis resistant to drugs (caused by the leishmaniasis parasite) was investigated in real patients and its results was compared with the common drug glucantime (local ampoule) (n = 36). Statistical studies showed that the use of herbal medicines prepared with cottonseed extract and cotton bolls extract has a significant positive effect on the treatment of the disease’s wounds (p-value > 0.05) compared to the control group (only ethanol). Also, by comparing the average diameter of the wounds after a two-month treatment period, no significant difference was found between the use of ointment containing extracts and local glucantime ampoules (p-value < 0.05). Bolls extract extracted with the Soxhlet method showed the best therapeutic effects, although there was no significant difference between them (p-value < 0.05). Therefore, there is acceptable reliability to recommend this medicine for the treatment of Cutaneous leishmaniasis resistant to drugs without the side effects of the chemical drug glucantime and the pain of injecting the ampoule.

Keywords: cottonseed oil, gossypol, cotton boll, cutaneous leishmaniasis

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Authors: Fadhl Alakwaa

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One of the sustainable goals of the system biology is understanding gene-gene interactions. Hence, gene regulatory networks (GRN) need to be constructed for understanding the disease ontology and to reduce the cost of drug development. To construct gene regulatory from gene expression we need to overcome many challenges such as data denoising and dimensionality. In this paper, we develop an integrated system to reduce data dimension and remove the noise. The generated network from our system was validated via available interaction databases and was compared to previous methods. The result revealed the performance of our proposed method.

Keywords: gene regulatory network, biclustering, denoising, system biology

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Authors: Wondale Getinet Alemu, Lillian Mwanri, Clemence Due, Telake Azale, Anna Ziersch

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Background: Mental illness is one of the most severe, chronic, and disabling public health problems that affect patients' Quality of life (QoL). Improving the QoL for people with mental illness is one of the most critical steps in stopping disease progression and avoiding complications of mental illness. Therefore, we aimed to assess the QoL and its determinants in patients with mental illness in outpatient clinics in Northwest Ethiopia in 2023. Methods: A facility-based cross-sectional study was conducted among people with mental illness in an outpatient clinic in Ethiopia. The sampling interval was decided by dividing the total number of study participants who had a follow-up appointment during the data collection period (2400) by the total sample size of 638, with the starting point selected by lottery method. The interviewer-administered WHOQOL BREF-26 tool was used to measure the QoL of people with mental illness. The domains and Health-Related Quality of Life (HRQoL) were identified. The indirect and direct effects of variables were calculated using structural equation modeling with SPSS-28 and Amos-28 software. A p-value of < 0.05 and a 95% CI were used to evaluate statistical significance. Results: A total of 636 (99.7%) participants responded and completed the WHOQOL-BREF questionnaire. The mean score of overall HRQoL of people with mental illness in the outpatient clinic was (49.6 ± 10 Sd). The highest QoL was found in the physical health domain (50.67 ±9.5 Sd), and the lowest mean QoL was found in the psychological health domain (48.41±10 Sd). Rural residents, drug nonadherence, suicidal ideation, not getting counseling, moderate or severe subjective severity, the family does not participate in patient care, and a family history of mental illness had an indirect negative effect on HRQoL. Alcohol use and psychological health domain had a direct positive effect on QoL. Furthermore, objective severity of illness, having low self-esteem, and having a history of mental illness in the family had both direct and indirect effects on QoL. Furthermore, sociodemographic factors (residence, educational status, marital status), social support-related factors (self-esteem, family not participating in patient care), substance use factors (alcohol use, tobacco use,) and clinical factors (objective and subjective severity of illness, not getting counseling, suicidal ideation, number of episodes, comorbid illness, family history of mental illness, poor drug adherence) directly and indirectly affected QoL. Conclusions: In this study, the QoL of people with mental illness was poor, with the psychological health domain being the most affected. Sociodemographic factors, social support-related factors, drug use factors, and clinical factors directly and indirectly, affect QoL through the mediator variables of physical health domains, psychological health domains, social relation health domains, and environmental health domains. In order to improve the QoL of people with mental illnesses, we recommend that emphasis be given to addressing the scourge of mental health, including the development of policy and practice drivers that address the above-identified factors.

Keywords: quality of life, mental wellbeing, mental illness, mental disorder, Ethiopia

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Authors: Hlaing Zaw Oo, N. Kostromina, V. Osipchik, T. Kravchenko, K. Yakovleva

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The process of modification of ed-20 epoxy resin synthesized by vinyl-containing compounds is considered. It is shown that the introduction of vinyl-containing compounds into the composition based on epoxy resin ED-20 allows adjusting the technological and operational characteristics of the binder. For improvement of the properties of epoxy resin, following modifiers were selected: polyvinylformalethyl, polyvinyl butyral and composition of linear and aromatic amines (Аramine) as a hardener. Now the big range of hardeners of epoxy resins exists that allows varying technological properties of compositions, and also thermophysical and strength indicators. The nature of the aramin type hardener has a significant impact on the spatial parameters of the mesh, glass transition temperature, and strength characteristics. Epoxy composite materials based on ED-20 modified with polyvinyl butyral were obtained and investigated. It is shown that the composition of resins based on derivatives of polyvinyl butyral and ED-20 allows obtaining composite materials with a higher complex of deformation-strength, adhesion and thermal properties, better water resistance, frost resistance, chemical resistance, and impact strength. The magnitude of the effect depends on the chemical structure, temperature and curing time. In the area of concentrations, where the effect of composite synergy is appearing, the values of strength and stiffness significantly exceed the similar parameters of the individual components of the mixture. The polymer-polymer compositions form their class of materials with diverse specific properties that ensure their competitive application. Coatings with high performance under cyclic loading have been obtained based on epoxy oligomers modified with vinyl-containing compounds.

Keywords: epoxy resins, modification, vinyl-containing compounds, deformation, strength properties

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Authors: Jing-Ma

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Digital transformation (DT) is an important way for manufacturing enterprises to shape new competitive advantages, and how to choose an effective DT strategy is crucial for enterprise growth and sustainable development. Rooted in strategic change theory, this paper incorporates the dimensions of managers' digital cognition, organizational conditions, and external environment into the same strategic analysis framework and integrates the dynamic QCA method and PSM method to study the antecedent grouping of the DT strategy mode of manufacturing enterprises and its impact on corporate profitability based on the data of listed manufacturing companies in China from 2015 to 2019. We find that the synergistic linkage of different dimensional elements can form six equivalent paths of high-level DT, which can be summarized as the proactive change mode of resource-capability dominated as well as adaptive response mode such as industry-guided resource replenishment. Capacity building under complex environments, market-industry synergy-driven, forced adaptation under peer pressure, and the managers' digital cognition play a non-essential but crucial role in this process. Except for individual differences in the market industry collaborative driving mode, other modes are more stable in terms of individual and temporal changes. However, it is worth noting that not all paths that result in high levels of DT can contribute to enterprise profitability, but only high levels of DT that result from matching the optimization of internal conditions with the external environment, such as industry technology and macro policies, can have a significant positive impact on corporate profitability.

Keywords: digital transformation, strategy mode, enterprise profitability, dynamic QCA, PSM approach

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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Authors: Sara Segura, Diego Nuñez, Miryam Villamil

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In this work, we studied the microscale interaction of foreign substances with blood inside an artificial transparent artery system that represents medium and small muscular arteries. This artery system had channels ranging from 75 μm to 930 μm and was fabricated using glass and transparent polymer blends like Phenylbis(2,4,6-trimethylbenzoyl) phosphine oxide, Poly(ethylene glycol) and PDMS in order to be monitored in real time. The setup was performed using a computer controlled precision micropump and a high resolution optical microscope capable of tracking fluids at fast capture. Observation and analysis were performed using a real time software that reconstructs the fluid dynamics determining the flux velocity, injection dependency, turbulence and rheology. All experiments were carried out with fully computer controlled equipment. Interactions between substances like water, serum (0.9% sodium chloride and electrolyte with a ratio of 4 ppm) and blood cells were studied at microscale as high as 400nm of resolution and the analysis was performed using a frame-by-frame observation and HD-video capture. These observations lead us to understand the fluid and mixing behavior of the interest substance in the blood stream and to shed a light on the use of implantable devices for drug delivery at arteries with different Endothelial dysfunction. Several substances were tested using the artificial artery system. Initially, Milli-Q water was used as a control substance for the study of the basic fluid dynamics of the artificial artery system. However, serum and other low viscous substances were pumped into the system with the presence of other liquids to study the mixing profiles and behaviors. Finally, mammal blood was used for the final test while serum was injected. Different flow conditions, pumping rates, and time rates were evaluated for the determination of the optimal mixing conditions. Our results suggested the use of a very fine controlled microinjection for better mixing profiles with and approximately rate of 135.000 μm3/s for the administration of drugs inside arteries.

Keywords: artificial artery, drug delivery, microfluidics dynamics, arteriosclerosis

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Authors: Igor A. Bessmertny, Bidru C. Enkomaryam

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Active involving patients and communities in health decisions can improve both people’s health and the healthcare system. Adopting artificial intelligence can lead to more accurate and complete patient record management. This review aims to identify the current state of researches conducted using artificial intelligence techniques to improve patient engagement and wellbeing, medical domains used in patient engagement context, and lastly, to assess opportunities and challenges for patient engagement in the wellness process. A search of peer-reviewed publications, reviews, conceptual analyses, white papers, author’s manuscripts and theses was undertaken. English language literature published in 2013– 2022 period and publications, report and guidelines of World Health Organization (WHO) were also assessed. About 281 papers were retrieved. Duplicate papers in the databases were removed. After application of the inclusion and exclusion criteria, 41 papers were included to the analysis. Patient counseling in preventing adverse drug events, in doctor-patient risk communication, surgical, drug development, mental healthcare, hypertension & diabetes, metabolic syndrome and non-communicable chronic diseases are implementation areas in healthcare where patient engagement can be implemented using artificial intelligence, particularly machine learning and deep learning techniques and tools. The five groups of factors that potentially affecting patient engagement in safety are related to: patient, health conditions, health care professionals, tasks and health care setting. Active involvement of patients and families can help accelerate the implementation of healthcare safety initiatives. In sub-Saharan Africa, using digital technologies like artificial intelligence in patient engagement context is low due to poor level of technological development and deployment. The opportunities and challenges available to implement patient engagement strategies vary greatly from country to country and from region to region. Thus, further investigation will be focused on methods and tools using the potential of artificial intelligence to support more simplified care that might be improve communication with patients and train health care professionals.

Keywords: artificial intelligence, patient engagement, machine learning, patient involvement

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Authors: Felix Lankester, Alicia Davis, Safari Kinung'hi, Catherine Bunga, Shayo Alkara, Imam Mzimbiri, Jonathan Yoder, Sarah Cleaveland, Guy H. Palmer

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Achieving the London Declaration goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires cost-effective strategies that attain high and comprehensive coverage. The first objective of this trial was to assess the impact on cost and coverage of employing a novel integrative One Health approach linking two NTD control programs: mass drug administration (MDA) for soil-transmitted helminths in humans (STH) and mass dog rabies vaccination (MDRV). The second objective was to compare the coverage achieved by the MDA, a community-wide deworming intervention, with that of the existing national primary school-based deworming program (NSDP), with particular focus on the proportion of primary school-age children reached and their school enrolment status. Our approach was unconventional because, in line with the One Health approach to disease control, it coupled the responsibilities and resources of the Ministries responsible for human and animal health into one program with the shared aim of preventing multiple NTDs. The trial was carried out in hard-to-reach pastoral communities comprising 24 villages of the Ngorongoro District, Tanzania, randomly allocated to either Arm A (MDA and MDRV), Arm B (MDA only) or Arm C (MDRV only). Objective one: The percentage of people in each target village that received treatment through MDA in Arms A and B was 63% and 65%, respectively (χ2 = 1, p = 0.32). The percentage of dogs vaccinated in Arm A and C was 70% and 81%, respectively (χ2 =9, p = 0.003). It took 33% less time for a single person and a dog to attend the integrated delivery than two separate events. Cost per dose (including delivery) was lower under the integrated strategy, with delivery of deworming and rabies vaccination reduced by $0.13 (54%) and $0.85 (19%) per dose, respectively. Despite a slight reduction in the proportion of village dogs vaccinated in the integrated event, both the integrated and non-integrated strategies achieved the target threshold of 70% required to eliminate rabies. Objective two: The percentages of primary school age children enrolled in school that was reached by this trial (73%) and the existing NSDP (80%) were not significantly different (F = 0.9, p = 0.36). However, of the primary school age children treated in this trial, 46% were not enrolled in school. Furthermore, 86% of the people treated would have been outside the reach of the NSDP because they were not primary school age or were primary school age children not enrolled in school. The comparable reach, the substantial reductions in cost per dose delivered and the decrease in participants’ time support this integrated One Health approach to control multiple NTDs. Further, the recorded level of non-enrolment at primary school suggests that, in remote areas, school-based delivery strategies could miss a large fraction of school-age children and that programs that focus delivery solely at the level of the primary school will miss a substantial proportion of both primary school age children as well as other individuals from the community. We have shown that these populations can be effectively reached through extramural programs.

Keywords: canine mediated human rabies, integrated health interventions, mass drug administration, neglected tropical disease, One Health, soil-transmitted helminths

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Authors: Jonathan Ogwal, Louis H. Kamulegeya, John M. Bwanika, Davis Musinguzi

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Introduction: Community retail Pharmacy drug distribution points (CRPDDP) were implemented in the Lango sub-region as part of the Ministry of Health’s response to improving access and adherence to antiretroviral treatment (ART). Clients received their ART refills from nearby local pharmacies; as such, the need for continuous engagement through mobile phone appointment reminders and health messages. We share learnings from the implementation of mobile text reminders and voice call follow-ups among ART clients attending the CRPDDP program in northern Uganda. Methods: A retrospective data review of electronic medical records from four pharmacies allocated for CRPDDP in the Lira and Apac districts of the Lango sub-region in Northern Uganda was done from February to August 2022. The process involved collecting phone contacts of eligible clients from the health facility appointment register and uploading them onto a messaging platform customized by Rapid-pro, an open-source software. Client information, including code name, phone number, next appointment date, and the allocated pharmacy for ART refill, was collected and kept confidential. Contacts received appointment reminder messages and other messages on positive living as an ART client. Routine voice call follow-ups were done to ascertain the picking of ART from the refill pharmacy. Findings: In total, 1,354 clients were reached from the four allocated pharmacies found in urban centers. 972 clients received short message service (SMS) appointment reminders, and 382 were followed up through voice calls. The majority (75%) of the clients returned for refills on the appointed date, 20% returned within four days after the appointment date, and the remaining 5% needed follow-up where they reported that they were not in the district by the appointment date due to other engagements. Conclusion: The use of mobile text reminders and voice call follow-ups improves the attendance of community retail pharmacy refills.

Keywords: antiretroviral treatment, community retail drug distribution points, mobile text reminders, voice call follow-up

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Authors: Lovorka Galetic, Zeljko Vukelic

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The advanced concepts of strategic and innovation management in the sphere of company dynamic and innovation capabilities, and achieving their mutual alignment and a synergy effect, are important elements in business today. This paper analyses the theory and empirically investigates the influence of a company’s dynamic capabilities on its innovation capabilities. A new multidimensional model of dynamic capabilities is presented, consisting of five factors appropriate to real time requirements, while innovation capabilities are considered pursuant to the official OECD and Eurostat standards. After examination of dynamic and innovation capabilities indicated their theoretical links, the empirical study testing the model and examining the influence of a company’s dynamic capabilities on its innovation capabilities showed significant results. In the study, a research model was posed to relate company dynamic and innovation capabilities. One side of the model features the variables that are the determinants of dynamic capabilities defined through their factors, while the other side features the determinants of innovation capabilities pursuant to the official standards. With regard to the research model, five hypotheses were set. The study was performed in late 2014 on a representative sample of large and very large Croatian enterprises with a minimum of 250 employees. The research instrument was a questionnaire administered to company top management. For both variables, the position of the company was tested in comparison to industry competitors, on a fivepoint scale. In order to test the hypotheses, correlation tests were performed to determine whether there is a correlation between each individual factor of company dynamic capabilities with the existence of its innovation capabilities, in line with the research model. The results indicate a strong correlation between a company’s possession of dynamic capabilities in terms of their factors, due to the new multi-dimensional model presented in this paper, with its possession of innovation capabilities. Based on the results, all five hypotheses were accepted. Ultimately, it was concluded that there is a strong association between the dynamic and innovation capabilities of a company. 

Keywords: dynamic capabilities, innovation capabilities, competitive advantage, business results

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Authors: Fabrizio Albion

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In response to the escalating recognition of the need to combat climate change, renewable energy sources (RES), particularly solar energy, have witnessed exponential growth. The intricate nature of agriphotovoltaics, which combines agriculture and solar energy production, demands rapid legislative and technological development, facing various challenges and multifaceted design. This complexity is also represented by its application for orchard cultivation (APVO), which, in the first part of this research, was studied in its environmental, economic, and sociocultural aspects. Insights from literature, case studies, and consultations with experts contributed valuable perspectives, forming a robust foundation for understanding and integrating APVO into rural environments, including those in the South Tyrolean context. For its harmonious integration into the sensitive Alpine landscape, the second part was then dedicated to the development of guidelines, from the identification of the requirements to be defined as APVO to its design flexibilities for being integrated into the context. As a basis for further considerations, the drafting of these guidelines was preceded by a program of interviews conducted to investigate the social perceptions of farmers, citizens and tourists on the potential integration of APVO in the fruit-growing valleys of the province. Conclusive results from the data collected in the first phase are, however, still pending. Due to ongoing experiments and data collection, the current results, although being generally positive, cannot guarantee a definitive exclusion of potential negative impacts on the crop. The guidelines developed should, therefore, be understood as an initial exploration, providing a basis for future updates, also in synergy with the evolution of existing local projects.

Keywords: agriphotovoltaics, Alpin agricultural landscapes, landscape impact assessment, renewable energy

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Authors: Heba A. Hazzah, Ragwa M. Farid, Maha M. A. Nasra, Mennatallah Zakria, Magda A. El Massik, Ossama Y. Abdallah

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Introduction: Curcumin (Cur) is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. The buccal delivery of curcumin can be useful for both systemic and local disease treatments such as gingivitis, periodontal diseases, oral carcinomas, and precancerous oral lesions. Despite of its high activity, it suffers a limited application due to its low oral bioavailability, poor aqueous solubility, and instability. Aim: Preparation and characterization of curcumin solid lipid nanoparticles with a high loading capacity into a mucoadhesive gel for buccal application. Methodology: Curcumin was formulated as nanoparticles using different lipids, namely Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and Polaxomer 407 as a surfactant. The SLN were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. All formulations were evaluated for their content, entrapment efficiency, particle size, in vitro drug dialysis, ex vivo mucoadhesion test, and ex vivo permeation study using chicken buccal mucosa. Clinical evaluation was conducted on 15 cases suffering oral erythroplakia and erosive lichen planus. Results: The results showed high entrapment efficiency reaching almost 90 % using Gelucire 50, the loaded gel with Cur-SLN showed good adhesion property and 25 minutes in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated however, a significant amount of Cur was retained within the mucosal tissue. Pain and lesion sizes were significantly reduced upon topical treatment. Complete healing was observed after 6 weeks of treatment. Conclusion: These results open a room for the pharmaceutical technology to optimize the use of this golden magical powder to get the best out of it. In addition, the lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Keywords: curcumin, erythroplakia, mucoadhesive, pain, solid lipid nanoparticles

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Authors: Fatima Zohra Belghait, Nawal Cheikh, Oscar Palacios, Ramon Barnadas, Pau Bayon

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Metalloporphyrin and its derivatives play an important role in different scientific areas due to its tetradentate vacant site in the center that is suitable for metal coordination. Metalosomes (MTS) are supramolecular aggregates (similar to liposomes) generated by the self-assembly of compounds similar to phospholipids (with a polar and a hydrophobic part), but incorporating, as part of their membrane, molecules that contain bound metals. The aim of our work is to synthesise metalosomes containing catioinc amphiphilic porphyrin and their complexes with Fe and Cu to study their therapeutical applications. All synthesized compounds were confirmed with Dynamic Light Scattering; elemental analysis, Ultraviolet–visible spectroscopy

Keywords: metalloporphyrin, amphiphilique porphyrin, metalosomes, supramolecular

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Authors: Shorena Sadzaglishvili, Teona Gotsiridze, Ketevan Lekishvili, Darejan Javakhishvili, Alida Bouris

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Globally, adolescents and young people experience high levels of HIV vulnerability and risk. Estimates suggest that AIDS-related deaths among young people are increasing, suggesting poor prioritization of adolescents in national plans for HIV testing and treatment services. HIV/AIDS is currently the sixth leading cause of death in people aged 10-24 years. Among young people, street connected youth are clearly distinguished as being among the most at risk for HIV infection. The present study recognizes the urgent need to scale up effective HIV responses that are tailored to the unique needs of street connected youth for the global HIV agenda and especially, the former Soviet country - Georgia, where 'street kids' are a new phenomenon and estimated to be about 2,500. During two months trained interviewers conducted individual semi-structured qualitative interviews with 22 key informants from the local governmental and nongovernmental service organizations, including psychologists, social workers, peer educators, mobile health workers, and managers. Informants discussed social network characteristics influencing street connected youth’s sexual risk behaviors. Data were analyzed using Dedoose. It was revealed that there are three types of homogeneous networks of street-connected youth aged 10-19 based on ethnical background: (1) Georgians; (2) migrant kids of Azeri-Kurdish origin, and (3) local Roma-Moldavian kids. These networks are distinguished with various HIV risk through both risky sexual and drug-related behaviors. In addition, there are several cases of HIV infection identified through reactive social services. Street connected youth do not have basic information about the HIV related sexual, alcohol and drug behaviors nor there are any systematic programs providing HIV testing and consultation for reducing the vulnerability of HIV infection. There is a need to systematically examine street-connected youth risk-taking behaviors by applying an integrated, multilevel framework to a population at great risk of HIV. Acknowledgment: This work was supported by Shota Rustaveli National Science Foundation of Georgia (SRNSFG) [#FR 17_31], Ilia State University.

Keywords: street connected youth, social networks, HIV/AIDS, HIV testing

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

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In this study, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of ¹⁷⁷Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: biodistribution, compartmental modeling, ¹⁷⁷Lu, Octreotide

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Authors: Arunas Burinskas, Aurelija Burinskiene

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On average, ten percent of drugs - commercial products are not available in pharmacies due to shortage. The shortage event disbalance sales and requires a recovery period, which is too long. Therefore, one of the critical issues that pharmacies do not record potential sales transactions during shortage and recovery periods. The authors suggest estimating outliers during shortage and recovery periods. To shorten the recovery period, the authors suggest using average sales per sales day prediction, which helps to protect the data from being downwards or upwards. Authors use the outlier’s visualization method across different drugs and apply the Grubbs test for significance evaluation. The researched sample is 100 drugs in a one-month time frame. The authors detected that high demand variability products had outliers. Among analyzed drugs, which are commercial products i) High demand variability drugs have a one-week shortage period, and the probability of facing a shortage is equal to 69.23%. ii) Mid demand variability drugs have three days shortage period, and the likelihood to fall into deficit is equal to 34.62%. To avoid shortage events and minimize the recovery period, real data must be set up. Even though there are some outlier detection methods for drug data cleaning, they have not been used for the minimization of recovery period once a shortage has occurred. The authors use Grubbs’ test real-life data cleaning method for outliers’ adjustment. In the paper, the outliers’ adjustment method is applied with a confidence level of 99%. In practice, the Grubbs’ test was used to detect outliers for cancer drugs and reported positive results. The application of the Grubbs’ test is used to detect outliers which exceed boundaries of normal distribution. The result is a probability that indicates the core data of actual sales. The application of the outliers’ test method helps to represent the difference of the mean of the sample and the most extreme data considering the standard deviation. The test detects one outlier at a time with different probabilities from a data set with an assumed normal distribution. Based on approximation data, the authors constructed a framework for scaling potential sales and estimating outliers with Grubbs’ test method. The suggested framework is applicable during the shortage event and recovery periods. The proposed framework has practical value and could be used for the minimization of the recovery period required after the shortage of event occurrence.

Keywords: drugs, Grubbs' test, outlier, shortage event

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Authors: Ade O. Oyewole, Sunday O. Okoh, Ruth O. Ishola, Adenike D. Odusote, Chima C. Igwe, Gloria N. Elemo, Anthony I. Okoh

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Azadirachta indica (Neem tree) also referred to as an all-purpose tree is used in a wide range of medical preparations in tropical and subtropical countries for prevention and management of various livestock, crops products and human diseases. In Nigeria however, the potentials of this plant have not been fully exploited thus it causes an environmental nuisance during the fruiting season. With a rise in the demand for herbal personal care products globally extracts from different parts of the neem plant were used as the bio-active ingredients in the formulation of personal care products. In this study, formulated neem soap, body cream, lotion, toothpaste and shampoo are analyzed to determine their antibacterial, antifungal, and toxicity properties. The efficacies of these products for management of infectious diseases, both oral and dermal, were also investigated in vitro. Oil from the neem seeds obtained using a mechanical press and acetone extracts of both the neem bark and leaves obtained by the maceration method were used in the formulation and production of the neem personal care products. The antimicrobial and toxicity properties of these products were investigated by agar diffusion, and haemolytic methods respectively. The five neem products (NPs) exhibited strong antibacterial activities against four multi–drug resistant pathogenic and three none pathogenic bacterial strains (Escherichia coli (180), Listeria ivanovii, Staphylococcus aureus, Enterobacter cloacae, Vibro spp., Streptococcus uberis, Mycobacterium smegmatis), except the neem lotion with insignificant activity against E. coli and S. aureus. The minimum inhibitory concentration (MIC) range was between 0.20-0.40 mg/ mL. The 5 NPs demonstrated moderate activity against three clinical dermatophytes isolates (Tinea corporis, Tinea capitis, and Tinea cruiz) as well as one fungal strain (Candida albican) with the MIC ranging between 0.30 - 0.50 mg/ mL and 0.550 mg/mL respectively. The soap and shampoo were the most active against test bacteria and fungi. The haemolytic analysis results on the 5 NPs indicated none toxicity at 0.50 mg/ mL in sheep red blood cells (SRBC).

Keywords: antimicrobial, Azadirachta indica, multi–drug resistant pathogenic bacteria, personal care products

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Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

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Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

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Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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Authors: Diego Liberati

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Standard molecular modeling is traditionally done through Schroedinger equations via the help of powerful tools helping to manage them atom by atom, often needing High Performance Computing. Here, a full portfolio of new tools, conjugating statistical inference in the so called eXplainable Artificial Intelligence framework (in the form of Machine Learning of understandable rules) to the more traditional modeling and simulation control theory of mixed dynamic logic hybrid processes, is offered as quite a general purpose even if making an example to a popular chemical physics set of problems.

Keywords: understandable rules ML, k-means, PCA, PieceWise Affine Auto Regression with eXogenous input

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Authors: Rafael Mineiro, André Furtado, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The choroid plexus (CP) epithelial cells form the blood-cerebrospinal fluid barrier. This barrier is highly important for brain protection by physically separating the blood from the cerebrospinal fluid, controlling the trafficking of molecules, including therapeutic drugs, from blood to the brain. The control is achieved by tight junctions between epithelial cells, membrane receptors and transport proteins from the solute carrier and ATP-binding cassette superfamily on the choroid plexus epithelial cells membrane. Previous research of our group showed a functional molecular clock in the CP. The key findings included a rhythmic expression of Bmal1, Per2, and Cry2 in female rat CP. and a rhythmic expression of Cry2 and Per2 in male rat CP. Furthermore, in cultured rat CP epithelial cells we already showed that 17β-estradiol upregulates the expression of Bmal1 and Per1, where the Per1 and Per2 upregulation was abrogated in the presence of the estrogen receptors antagonist ICI. These findings, together with the fact that the CP produces robust rhythms, prompt us to understand the impact of sex hormones and circadian rhythms in CP drug transporters expression, which is a step towards the development and optimization of therapeutic strategies for efficiently delivering drugs to the brain. For that, we analyzed the circadian rhythmicity of the Abcb1, Abcc2, Abcc4 Abcg2, and Oat3 drug transporters at the CP of male and female rats. This analysis was performed by accessing the gene expression of the mentioned transporters at 4 time points by RT-qPCR and the presence of rhythms was evaluated by the CircWave software. Our findings showed a rhythmic expression of Abcc1 in the CP of male rats, of Abcg2 in female rats, and of Abcc4 and Oat3 in both male and female rats with an almost antiphasic pattern between male and female rats for Abcc4. In conclusion, these findings translated to a functional point of view may account for daily variations in brain permeability for several therapeutic drugs, making our findings important data for the future establishment and development of therapeutic strategies according to daytime.

Keywords: choroid plexus, circadian rhythm, membrane transporters, sex hormones

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Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi

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Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.

Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths

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Authors: L. Gyansah, Yanfang Shen, Jiqiang Wang, Tianying Xiong

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SiCₚ/ pure Al composites with different SiC fractions (20 wt %, 30 wt %, and 40 wt %) were precisely cold sprayed, followed by hot axial-compression tests at deformation temperatures of 473 K to 673 K, leading to failure of specimens through routine crack propagation in their multiphase. The plastic deformation behaviour with respect to the SiCₚ contents and the deformation temperatures were studied at strain rate 1s-1.As-sprayed and post-failure specimens were analyzed by X-ray computed tomography (XCT), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Quasi-static thermomechanical testing results revealed that compressive strength (UTS = 228 MPa and 30.4 %) was the highest in the composites that was thermomechanically compressed at 473 K compared to those of the as-sprayed, while the as-sprayed exhibited a compressive strength of 182.8 MPa related to the increment in SiC fraction. Strength—plasticity synergy was promoted by dynamic recrystallization (DRX) through strengthening and refinement of the grains. The DRX degree depends relevantly on retainment of the uniformly ultrafine SiCₚ particulates, the pinning effects of the interfaces promoted by the ultrafine grain structures (UFG), and the higher deformation temperature. Reconstructed X-ray computed tomography data revealed different crack propagation mechanisms. A single-plane shear crack with multi-laminates fracture morphology yields relatively through the as-sprayed and as-deformed at 473 K deposits, while a multiphase plane shear cracks preeminently existed in high temperature deformed deposits resulting in multiphase-interface delaminations. Three pertinent strengthening mechanisms, videlicet, SiCp dispersed strengthening, refined grain strengthening, and dislocation strengthening, existed in the gradient microstructure, and their detailed contributions to the thermomechanical properties were discussed.

Keywords: cold spraying, hot deformation, deformation temperature, thermomechancal properties, SiC/Al composite

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Aynura Valiyeva, Basil John Thomas

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Intra-firm communication is critical for building synergy amongst internal business units of a firm, where employees from various functional departments and ranks incorporate their decision-making, understanding of organizational objectives, as well as common norms and culture for better organizational effectiveness. This study builds on and assesses a framework of the causes and consequences of effective communication in business interactions between customer and supplier firms, and the path for efficient communication within a firm. The proposed study’s structural equation modeling (SEM) analysis based on 352 sample responses collected from firm representatives at different job positions ranging from marketing to logistics operations, reveals that, in the frame of reference of intra-organizational communication, organization characteristics and shared values, top management support and style of leadership, as well as information technology, are all significantly related to communication effectiveness. Furthermore, the frequency and variety of interactions enhance the outcome of communication, that improves a company’s performance. The results reveal that cultural factors are significantly related to communication effectiveness, as well as the shared beliefs and goals. In terms of organizational factors, leadership style, top management support and information technology are significant determinants of effective communication. Among the contextual factors, interaction frequency and diversity are found to be priority factors. This study also tests the relationship between supplier and supplier firm performance in the context of communication effectiveness, and finds that they are closely related, when trust and commitment is built between business partners. When firms do business in other multicultural contexts, language and shared values with destination country must be considered significant elements of communication process.

Keywords: business performance, intra-firm communication, inter-firm communication, structural equation modeling

Procedia PDF Downloads 97