Search results for: drug of abuse

Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

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The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

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Authors: Sylvie Ekanga Lumumba

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Background and Significance of the Study: Over the past three decades, the perception of sexual violence has changed significantly, it is now recognized that men and boys are victims of sexual violence. However, the body of research on male victims and particularly on their attackers is much more limited. Research on the above is thus more than required. To contribute to the above quest for further studies, the researcher conducted this study on sexual violence perpetrated against men and boys by women, in the Municipality of Ibanda, Town of Bukavu, Province of South Kivu, Democratic Republic of Congo. The main study objectives were the following: to investigate on the statement of sexual violence perpetrated against men and boys in the Municipality of Ibanda, to investigate into its consequences and the statement of medical and psycho-social care given to victims. Methodology: Data were collected using valid and reliable Survey Questionnaire and Interview Schedule. Study population: the 85,882 men and boys from the Municipality of Ibanda. Sampling: led to 150 men and boys, received discreetly by the researcher during November-December 2015. Major findings: First, findings related to sexual abuse and its procedure: 74.2% of men and boys were victims of sexual violence perpetrated by a woman, more than a year ago. 13.3% however, were victims for less than a year now. 79.7% of victims have experienced sexual violence by a sexual act; 3.9% through the intention of the woman to cause the death of the victim, by serious injury to the genitals. The Second group of findings related to the consequences of sexual violence revealed that HIV/AIDS is the most important physical consequence experienced by 77.3 % of victims. Physical psychological consequences are: urinary or defecation problems (72.7%); while key psycho-emotional and behavioral consequence is: living a state of deep shame and humiliation: 68.8%. As for sexual consequences: 71.1% indicated a chronic avoidance of sexual activity and 57% reported sexual dysfunctions. The third group of findings is related to medical and psycho-social care: repetitively, more than 80% of male victims affirmed that with the help of friends and traditional healers, they took care of themselves for all the eight WHO phases of clinical care of rape victims, this was hence not effectively done. Concluding Statement: for this study, the statement of sexual violence of men and boys by women in the Eastern Congo and its consequences are not researched upon and are underestimated; the study also revealed that the care of male victims is grossly ill-conducted, as opposed to female victims care. It therefore calls for further research and further vulgarization of the research results, to convince other stakeholders (politicians for example) to immediately take action.

Keywords: sexual violence, men and boys, medical care, psycho-social care

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Authors: Bashar Al-Sabti, Jehad Harbali

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Background: Pyridine is a reactive base that might be used in preparing sitagliptin. International Agency for Research on Cancer classifies pyridine in group 2B; this classification means that pyridine is possibly carcinogenic to humans. Therefore, pyridine should be monitored at the allowed limit in sitagliptin pharmaceutical ingredients. Objective: The aim of this study was to develop a novel ultra high performance liquid chromatography mass spectrometry (UHPLC-MS) method to estimate the quantity of pyridine impurity in sitagliptin pharmaceutical ingredients. Methods: The separation was performed on C8 shim-pack (150 mm X 4.6 mm, 5 µm) in reversed phase mode using a mobile phase of water-methanol-acetonitrile containing 4 mM ammonium acetate in gradient mode. Pyridine was detected by mass spectrometer using selected ionization monitoring mode at m/z = 80. The flow rate of the method was 0.75 mL/min. Results: The method showed excellent sensitivity with a quantitation limit of 1.5 ppm of pyridine relative to sitagliptin. The linearity of the method was excellent at the range of 1.5-22.5 ppm with a correlation coefficient of 0.9996. Recoveries values were between 93.59-103.55%. Conclusions: The results showed good linearity, precision, accuracy, sensitivity, selectivity, and robustness. The studied method was applied to test three batches of sitagliptin raw materials. Highlights: This method is useful for monitoring pyridine in sitagliptin during its synthesis and testing sitagliptin raw materials before using them in the production of pharmaceutical products.

Keywords: genotoxic impurity, pyridine, sitagliptin, UHPLC -MS

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Authors: Yu Zhang, Il Kim

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Polypeptides with defined peptide sequences illustrate the power of remarkable applications in drug delivery, tissue engineering, sensing and catalysis. Especially the cyclic polypeptides, the distinctive topological architecture imparts many characteristic properties comparing to linear polypeptides. Here, a facile and highly efficient strategy for the synthesis of linear and cyclic polypeptides is reported using N-heterocyclic carbenes (NHCs)-mediated ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCA) in the presence or absence of primary amine initiator. The polymerization proceeds rapidly in a quasi-living manner, allowing access to linear and cyclic polypeptides of well-defined chain length and narrow polydispersity, as evidenced by nuclear magnetic resonance spectrum (1H NMR and 13C NMR spectra) and size exclusion chromatography (SEC) analysis. The cyclic architecture of the polypeptides was further verified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectra (MALDI-TOF MS) and electrospray ionization (ESI) mass spectra, as well as viscosity studies. This approach can also simplify workup procedures and make bulk scale synthesis possible, which thereby opens avenues for practical uses in diverse areas, opening up the new generation of polypeptide synthesis.

Keywords: α-amino acid N-carboxyanhydrides, living polymerization, polypeptides, N-heterocyclic carbenes, ring-opening polymerization

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Authors: Ahmed Jibrin Uttu, Maimuna Waziri

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The root bark of Glossonema boveanum (Decne), a member of Apocynaceae family, is used by traditional medicine practitioner to treat urinary and respiratory tract infections, bacteremia, typhoid fever, bacillary dysentery, diarrhea and stomach pain. This present study aims to validate the medicinal claims ascribed to the root bark of the plant. Preliminary phytochemical study of the root bark extracts (n-hexane, ethyl acetate, chloroform and methanol extracts) showed the presence of alkaloids, carbohydrates, steroids, triterpenes, cardiac glycosides, saponins, tannins and flavonoids. Antimicrobial study of the extracts showed activities against Staphylococus aureus, Bacillus subtilis, Salmonella typhii, Shigella dysenteriae, Escherichia coli, Enterobacter cloacae, Streptococcus agalactiae and Candida albicans while Micrococcus luteus, Pseudomonas aeruginosa and Klebsiella Pneumoniae showed resistance to all the extracts. The inhibitory effect was compared with the standard drug ciprofloxacin and fluconazole. MIC and MBC for both extracts were also determined using the tube dilution method. This study concluded that the root bark of G. boveanum, used traditionally as a medicinal plant, has antimicrobial activities against some causative organisms.

Keywords: Glossonema boveanum (Decne.), phytochemical, antimicrobial, minimum inhibitory concentration, minimum bactericidal concentration

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Authors: Gwendolyn Royal-Smith

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Cocaine ranks as one of the world’s most addictive and commonly abused stimulant drugs. Recent evidence indicates that the abuse of cocaine has risen so quickly among females that this group now accounts for about 40 percent of all users in the United States. Neuropsychological studies have demonstrated that specific neural activation patterns carry higher risks for neurocognitive and executive function in cocaine addicted females thereby increasing their vulnerability for poorer treatment outcomes and more frequent post-treatment relapse when compared to males. This study examined secondary data with a convenience sample of 164 cocaine addicted male and females to assess neurocognitive and executive function. The principal objective of this study was to assess whether individual performance on the Stroop Word Color Task is predictive of treatment success by gender. A second objective of the study evaluated whether individual performance employing neurocognitive measures including the Stroop Word-Color task, the Rey Auditory Verbal Learning Test (RALVT), the Iowa Gambling Task, the Wisconsin Card Sorting Task (WISCT), the total score from the Barratte Impulsiveness Scale (Version 11) (BIS-11) and the total score from the Frontal Systems Behavioral Scale (FrSBE) test demonstrated differences in neurocognitive and executive function performance by gender. Logistic regression models were employed utilizing a covariate adjusted model application. Initial analyses of the Stroop Word color tasks indicated significant differences in the performance of males and females, with females experiencing more challenges in derived interference reaction time and associate recall ability. In early testing including the Rey Auditory Verbal Learning Test (RALVT), the number of advantageous vs disadvantageous cards from the Iowa Gambling Task, the number of perseverance errors from the Wisconsin Card Sorting Task (WISCT), the total score from the Barratte Impulsiveness Scale (Version 11) (BIS-11) and the total score from the Frontal Systems Behavioral Scale, results were mixed with women scoring lower in multiple indicators in both neurocognitive and executive function.

Keywords: cocaine addiction, gender, neuropsychology, neurocognitive, executive function

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Authors: Salem Abdalla

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Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

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Authors: Joe Modise, Bamidel Joseph Okoli, Nas Molefe, Imelda Ledwaba

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The present study describes the chemical profile and antioxidant potential of the stem bark of Acacia decurrens. The methanol fraction of A. decurrens stem bark gave the highest yield (20 %), while the hexane fraction had the lowest yield (0.2 %). The GC-MS spectra of the hexane, chloroform and ethyl acetate fractions confirm the presence of fifty two major compounds and the ICP-OES analysis of the stem bark was found to contain Co(0.41), Zn(1.75), Mn(3.69), Ca(8.67), Ni(10.54), Mg(12.98), Cr(24.38), K(47.88), Fe(154.62) ppm; which is an indication of hyper-accumulation capacity. The UV-Visible spectra of showed four absorption maxima for hexane fraction at 665 (0.028), 410 (0.116), 335 (0.278) and 250 (0.007) nm, three for chloroform fraction at 665 (0.028), 335 (0.278) and 250 (0.007) nm , three for ethyl acetate fraction at 665 (0.070), 390 (0.648) and 345 (0.663) nm and three for methanol fraction at 385 (0.508), 310 (0.886) and 295 (0.899) nm respectively. Quantitative phytochemical screening indicated that the alkaloid (0.6-3.3) % and saponins (5.1-8.6) % contents of the various fractions were significantly lower than the tannin (30.9-55.8) mg TAE/g, steroid(13.92-41.2) %, phenol (40.6-65.5) mgGAE/g and flavonoids (210.2 -284.9) mg RUE/g contents. The antioxidant activity of the fractions was analysed by different methods and revealed good to moderate antioxidant potential with different IC50 values viz. (42.2-49.6) mg/mL for ABTS and (37.8-75.0) μg/ml for DPPH respectively, compared to standard antioxidants. Based on obtained results, the A.decurrens stem bark fractions can be a source of safe, sustainable natural antioxidant drug and can be exploited as a source of controlled green-heavy metal cleaner.

Keywords: Acacia decurrens, antioxidant, DPPH, ABTS, hyperaccumulation, Menstruum, ICP-OES, GC-MS, UV/visible

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

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Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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Authors: Elham Zarenezhad, Ali Zarenezhad, Mehdi Mardkhoshnood

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We described the synthesis and biological study of O-oxime ethers having a-amino acid residues as new analogs of IPS-339. In this synthesis, the reaction of fluorene O-oxime with epichlorohydrin or epibromohydrin afforded the corresponding O-oxime ether adducts. The N-alkylation of valine amino acid with O-oxime ether adducts led to the synthesis of new analogs of IPS-339. The cardiovascular properties of the compound have been studied. In this regard, six clinically healthy same sex mongrel dogs were examined. The dogs were randomly divided into 3 groups of two members. 1 groups received 2 mg kg-1 body weight of compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) intravenously, whereas group 2 and 3 received only DMSO–water (distil.) and propranolol (Inderal) (2 mg kg-1), respectively. The electrocardiograph (ECG) was recorded with lead II. The recording was run successively by 5 min time interval on each dog before, simultaneously, and after compound infusion. Data after administration were taken from normal sinus beats that were closely related to the arrhythmias whenever they occurred. In general, no detectable arrhythmia was observed in all ECG records regardless of increasing the heart rate that likely caused by stress origin from invasive procedure just after infusion. Compound diminished the heart rate during study especially at 20th minute compared to propranolol as a reference drug. Compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) was the most effective compound with remarkable ability in declining of the heart rate.

Keywords: electrocardiograph (ECG), cardiovascular, IPS-339, dogs

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Authors: Abdullah Mohammad, Abdullah Alshemali, Esmaeil Alsaleh

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The chemical composition of desalinated water is modified to make it more acceptable to the end-user. Sometimes, this modification is approached by mixing with brackish water that is known to contain a variety of minerals. Expectedly, besides minerals, brackish water indigenous bacterial communities access the final mixture hence reaching the end consumer. The current project examined the safety of using brackish water as an ingredient in potable water. Pseudomonas aeruginosa strains were detected in potable and brackish water samples collected from storage facilities in residential areas as well as from main water distribution and storage tanks. The application of molecular and biochemical fingerprinting methods, including phylogeny, RFLP (restriction fragment length polymorphism), MLST (multilocus sequence typing) and substrate specificity testing, suggested that the potable water P. aeruginosa strains were most probably originated from brackish water. Additionally, all the sixty-four isolates showed multi-drug resistance (MDR) phenotype and harboured the three genes responsible for biofilm formation. These virulence factors represent serious health hazards compelling the scientific community to revise the WHO (World Health Organization) and USEP (US Environmental Protection Agency) A potable water quality guidelines, particularly those related to the types of bacterial genera that evade the current water quality guidelines.

Keywords: potable water, brackish water, pseudomonas aeroginosa, multidrug resistance

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Authors: Saji George, Eng Khuan Seng, Christof Luda

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Nanotechnology has been recognized as an important tool for modern agriculture and has the potential to overcome some of the pressing challenges faced by aquaculture industry. A strategy for optimizing nanotechnology-based therapeutic delivery platform for immunizing farmed fish was developed. Accordingly, a compositional library of nanomaterials of natural chemistry (Halloysite (clay), Chitosan, Hydroxyapatite, Mesoporous Silica and a composite material of clay-chitosan) was screened for their toxicity and efficiency in delivering models antigens in cellular and zebrafish embryo models using high throughput screening platforms. Through multi-parametric optimization, chitosan modified halloysite (clay) nanomaterial was identified as an optimal vaccine delivery platform. Further, studies conducted in juvenile seabass showed the potential of clay-chitosan in delivering outer membrane protein of Tenacibaculum maritimum- TIMA (pathogenic bacteria) to and its efficiency in eliciting immune responses in fish. In short, as exemplified by this work, the strategy of using compositional nanomaterial libraries and their biological profiling using high-throughput screening platform could fasten the discovery process of nanomaterials with potential applications in food and agriculture.

Keywords: nanotechnology, fish-vaccine, drug-delivery, halloysite-chitosan

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Authors: Jhonas Geraldo Peixoto Flauzino, Pedro Pompeo Boechat Araujo, Alexia Allis Rocha Lima, Giovanna Biângulo Lacerda Chaves, Victor Ryan Ferrão Chaves

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Schizophrenia is characterized as a set of psychiatric signs and symptoms (syndrome) that commonly erupt in the stages of adolescence or early adulthood, being recognized as one of the most serious diseases, as it causes important problems during the life of the patient. carrier - both in mental health and in physical health and in social life. Objectives: This is an integrative literature review that aimed to verify what has been produced of scientific knowledge in the field of child and adolescent psychiatry regarding schizophrenia in these stages of life, correlated to the most discussed themes and methodologies of choice for the preparation of studies. Methods: Articles were selected from the following databases: Virtual Health Library and CAPES Journal Portal, published in the last five years; and on Google Scholar, published in 2021, totaling 62 works, searched in September 2021. Results: The studies focus mainly on diagnosis through the DSM-V (25.8%), on drug treatment (25.8%) and in psychotherapy (24.2%), most of them in the literature review format: integrative (27.4%) and systematic (24.2%). Conclusion: The themes and study methods are redundant, and do not cover in depth the immense aspects that encompass Schizophrenia in Childhood and Adolescence, giving attention to the disease in a general way or focusing on the adult patient.

Keywords: schizophrenia, mental health, childhood, adolescence

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Authors: Shuafeng Yuan, Bojian Zheng

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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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Authors: Ingrid van der Heijden, Kristen Dunkle, Rachel Jewkes

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Background: Emerging literature on prevalence shows that men with disabilities are four more times likely than men without disabilities to experience sexual violence during their lifetime. However, compared to women with disabilities, men with disabilities still have lesser experiences of violence. While empirical evidence on the prevalence of victimization of men with disabilities is emerging, there is scarcer evidence highlighting disabled men’s perpetration of different forms of violence, particularly intimate partner violence. We can assume that men are likely to be both perpetrators and victims of violence, making more complex the causes and risks of violence. Gender norms and disability stigma play important roles in men’s experiences of violence. Men may be stigmatized because of their inability to attain hegemonic masculine ideals of strength, control over women and sexual conquest, which makes them more susceptible to emotional, physical and sexual abuse. Little to no evidence exists of men with disabilities’ experiences of perpetration of intimate partner violence, family violence or community violence. So far studies on male victimization do not succeed to offer contextual evidence that would highlight why and how men with disabilities perpetrate and/or are victims of sexual or other forms of violence. Objective: The overall aim to highlight men with disabilities’ experiences of both victimization and perpetration, and how living up to normative and hegemonic ideals of masculinity and ‘ability’ shape their experiences. It will include: identifying how gender and impairments intersect and shape their experiences of violence; identifying the contexts of and risks for violence; identifying the impacts and consequences of violence on their lives (including mental health impacts), and identifying obstacles and enablers to support and interventions to prevent violence. Methodology: In-depth qualitative interviews with 20 men with disabilities participating in interventions conducted by the What Works Global Programme for violence prevention (DIFD) in Africa and Asia. Men with a range of disabilities will be invited to share their lifetime experiences of violence. Implications for Practice: The data from this study will be used to start thinking about strategies to include men with disabilities in violence prevention strategies for both men and women. Limitations: Because men will be participating in interventions, it is assumed that they will not have severe impairments that hamper their cognitive or physical ability to participate in the intervention activities - and therefore will be able to participate in the in-depth interviews. Of course, this is a limitation of the study as it does not include those men with severe disabilities – measured by the World Health Organization’s International Classification of Functioning - who may be more vulnerable and at higher risk of experiencing violence, and who are less likely to be able to access services and interventions.

Keywords: gender, men with disabilities, perpetration of violence, victimization

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Authors: Gergely G. Karacsony

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Fundamental rights are the result of thousand years’ progress of legislation, adjudication and legal practice. They serve as the framework of peaceful cohabitation of people, protecting the individual from any abuse by the government or violation by other people. Artificial intelligence, however, is the development of the very recent past, being one of the most important prospects to the future. Artificial intelligence is now capable of communicating and performing actions the same way as humans; such acts are sometimes impossible to tell from actions performed by flesh-and-blood people. In a world, where human-robot interactions are more and more common, a new framework of peaceful cohabitation is to be found. Artificial intelligence, being able to take part in almost any kind of interaction where personal presence is not necessary without being recognized as a non-human actor, is now able to break the law, violate people’s rights, and disturb social peace in many other ways. Therefore, a code of peaceful coexistence is to be found or created. We should consider the issue, whether human rights can serve as the code of ethical and rightful conduct in the new era of artificial intelligence and human coexistence. In this paper, we will examine the applicability of fundamental rights to human-robot interactions as well as to the actions of artificial intelligence performed without human interaction whatsoever. Robot ethics has been a topic of discussion and debate of philosophy, ethics, computing, legal sciences and science fiction writing long before the first functional artificial intelligence has been introduced. Legal science and legislation have approached artificial intelligence from different angles, regulating different areas (e.g. data protection, telecommunications, copyright issues), but they are only chipping away at the mountain of legal issues concerning robotics. For a widely acceptable and permanent solution, a more general set of rules would be preferred to the detailed regulation of specific issues. We argue that human rights as recognized worldwide are able to be adapted to serve as a guideline and a common basis of coexistence of robots and humans. This solution has many virtues: people don’t need to adjust to a completely unknown set of standards, the system has proved itself to withstand the trials of time, legislation is easier, and the actions of non-human entities are more easily adjudicated within their own framework. In this paper we will examine the system of fundamental rights (as defined in the most widely accepted source, the 1966 UN Convention on Human Rights), and try to adapt each individual right to the actions of artificial intelligence actors; in each case we will examine the possible effects on the legal system and the society of such an approach, finally we also examine its effect on the IT industry.

Keywords: human rights, robot ethics, artificial intelligence and law, human-robot interaction

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Authors: Nusrat Zabeen Islam

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Partnership between local Non-Government organizations (NGO) and International development organizations has become an important feature in the development sector of Bangladesh. It is an important challenge for International development organizations to work with local NGOs with proper HR practice. Local NGOs have a lack of quality working environment and this affects the employee’s work experiences and overall performance at individual, partnership with International development organizations and organizational level. Many local development organizations due to the size of the organization and scope do not have a human resource (HR) unit. Inadequate Human Resource Policies, skills, leadership and lack of effective strategy is now a common scenario in Non-Government organization sector of Bangladesh. So corruption, nepotism, and fraud, risk of Political Contribution in office /work space, Sexual/ gender based abuse, insecurity take place in work place of development sector. The Complaint Management Mechanism (CMM) in human resource management could be one way to improve human resource competence in these organizations. The responsibility of Complaint Management Unit (CMU) of an International development organization is to make workplace maltreating, discriminating communities free. The information of impact of CMM was collected through case study of an International organization and some of its partner national organizations in Bangladesh who are engaged in different projects/programs. In this mechanism International development organizations collect complaints from beneficiaries/ staffs by complaint management unit and investigate by segregating the type and mood of the complaint and find out solution to improve the situation within a very short period. A complaint management committee is formed jointly with HR and management personnel. Concerned focal point collect complaints and share with CM unit. By conducting investigation, review of findings, reply back to CM unit and implementation of resolution through this mechanism, a successful bridge of communication and feedback can be established within beneficiaries, staffs and upper management. The overall result of Complaint management mechanism application indicates that by applying CMM accountability and transparency of workplace and workforce in development organization can be increased significantly. Evaluations based on outcomes, and measuring indicators such as productivity, satisfaction, retention, gender equity, proper judgment will guide organizations in building a healthy workforce, and will also clearly articulate the return on investment and justify any need for further funding.

Keywords: human resource management in NGOs, challenges in human resource, workplace environment, complaint management mechanism

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Authors: Mehmet Akoz, Mustafa Kul

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Ewes and goats are seasonally polyestrus animals. Their reproductive activities are associated with the reduction or extending of daylight. Melatonin releasing from pineal gland regulates the sexual activities depending on daylight. In recent years, number of ewes decreased in our country. This situation dispatched to developing of some methods to increase productivity. Small ruminants can be synchronized with the natural and medical methods. known methods from natural light set with ram and goat participation. The most important natural methods of male influence, daylight is regulated and feed. On the other hand, progestagens, PGF2α, melatonin, and gonadotropins are commonly used for the purpose of estrus synchranization. But it is not effective PGF2α anestrous season The short-term and long-term progesterone treatment was effective to synchronize estrus in small ruminats during both breeding and anestrus seasons. Alternative choices of progesterone/progestagen have been controlled internal drug release (CIDR) devices, supplying natural progesterone, norgestomet implants, and orally active melengestrol acetate Melatonin anestrous season and should be applied during the transition period, but the season can be synchronized. Estrus synchronisation shortens anestrus season, decreases labor for mating/insemination and estrus pursuit, and induces multiple pregnancies.

Keywords: ewes, goat, synchronization, progestagen, PGF2α

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Authors: Katharigatta N. Venugopala, Melendhran Pillay, Bander E. Al-Dhubiab

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Tuberculosis (TB) infection is caused mainly by Mycobacterium tuberculosis (MTB) and it is one of the most threatening and wide spread infectious diseases in the world. Benzothiazole derivatives are found to have diverse chemical reactivity and broad spectrum of pharmacological activity. Some of the important pharmacological activities shown by the benzothiazole analogues are antitumor, anti-inflammatory, antimicrobial, anti-tubercular, anti-leishmanial, anticonvulsant and anti-HIV properties. Keeping all these facts in mind in the present investigation it was envisaged to synthesize a series of novel {2-(benzo[d]-thiazol-2-yl-methoxy)-substitutedaryl}-(substitutedaryl)-methanones (4a-f) and characterize by IR, NMR (1H and 13C), HRMS and single crystal x-ray studies. The title compounds are investigated for in vitro anti-tubercular activity against two TB strains such as H37Rv (ATCC 25177) and MDR-MTB (multi drug resistant MTB resistant to Isoniazid, Rifampicin and Ethambutol) by agar diffusion method. Among the synthesized compounds in the series, test compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone (2c) was found to exhibit significant activity with MICs of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively when compared to standard drugs. Single crystal x-ray studies was used to study intra and intermolecular interactions, including polymorphism behavior of the test compounds, but none of the compounds exhibited polymorphism behavior.

Keywords: benzothiazole analogues, characterization, crystallography, anti-TB activity

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Authors: Md. Danish Eqbal, Venkat Gundabala

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Microparticles and microcapsules are basically used as a carrier for cells, tissues, drugs, and chemicals. Due to its biocompatibility, non-toxicity and biodegradability, alginate based microparticles have numerous applications in drug delivery, tissue engineering, organ repair and transplantation, etc. The production of uniform monodispersed microparticles was a challenge for the past few decades. However, emergence of microfluidics has provided controlled methods for the generation of the uniform monodispersed microparticles. In this work, we present a successful method for the generation of both microparticles and microcapsules (single and double core) using merging approach of two droplets, completely inside the microfluidic device. We have fabricated hybrid glass- PDMS (polydimethylsiloxane) based microfluidic device which has coflow geometry as well as the T junction channel. Coflow is used to generate the single as well as double oil-alginate emulsion in oil and T junction helps to form the calcium chloride droplets in oil. The basic idea is to match the frequency of the alginate droplets and calcium chloride droplets perfectly for controlled generation. Using the merging of droplets technique, we have successfully generated the microparticles and the microcapsules having single core as well as double and multiple cores. The cores in the microcapsules are very stable, well separated from each other and very intact as seen through cross-sectional confocal images. The size and the number of the cores along with the thickness of the shell can be easily controlled by controlling the flowrate of the liquids.

Keywords: double-core, droplets, microcapsules, microparticles

Procedia PDF Downloads 254

Authors: Argaw Amare, Abbuna Fuffa, Stringer Andy

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Improving public knowledge and changing their attitudes towards antibiotic use will be a crucial early strategy to contain Antibiotic resistance. The current study was undertaken from November 2015 to June 2016. A cross-sectional survey using a pretested questionnaire was conducted on 392 residents (330 male and 62 female) aged 18 and above. Participants were selected randomly. Data was analyzed using simple descriptive statistics; the Chi-square test was used to determine any significant difference. The majority of participants (81%) were farmers in their occupation. Most of the respondents (76%) were not able to define the difference between antimicrobials and antibiotics. Furthermore, (61%) of participants were not able to define what antibiotics and for what purpose they are used. Thirty-four percent of participants do not know the names of antibiotics they have used for their animals and for themselves. Nearly 68% have no knowledge about the disease they have been treated for. The majority of participants (73.5%) agree to complete their course of treatment even if they feel better. About 72.5% of participants disagree that antibiotics are safe and can be used to treat different diseases, without prescription. Most of the participants (95%) treat their animals after diagnosis; more than 80% of them agree to not purchase veterinary drugs from local traders. This study showed that the participants have poor knowledge and good attitude, with an average score of 41.3±16.1% and 79.6±16, respectively. Knowledge and attitude are significantly correlated (p<0.01). The participants in this study had a good attitude toward the rational use of antibiotics. Whereas they lack knowledge with regard to the kinds of antibiotics and the diseases they are prescribed for. Therefore, further educational interventions are necessary to improve their understanding of the antibiotics currently available and the major bacterial diseases they are prescribed.

Keywords: AMR, knoweledge, attitude, perception

Procedia PDF Downloads 66

Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

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Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe₃O₄ nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: tumor tissue, antibody, magnetic nanoparticle, CTCs capturing

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Authors: Sylvie Sossou, Grégoire Gansou, Ildevert Egue

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Introduction: The mission of the family and the school is to educate and train citizens of the city. But the family’s values , parental roles, respect for life collapse in their traditional African form. Indeed laxity with regard to divorce, liberal ideas about child rearing influence the emotional life of the latter. Several causes may contribute to the decline in academic performance. In order to seek a psychological solution to the issue, a study was conducted in 6 schools at the 9th district in Cotonou, cosmopolitan city of Benin. Objective: To evaluate the impact of single parenthood on the psycho child development. Materials and Methods: Questionnaires and interviews were used to gather verbal information. The questionnaires were administered to parents and children (schoolchildren 4, 5 and six form) from 7 to 12 years in lone parenthood. The interview was done with teachers and school leaders. We identified 209 cases of children living with a "single-parent" and 68 single parents. Results: Of the 209 children surveyed the results showed that 116 children are cut relational triangle in early childhood (before 3 years). The psychological effects showed that the separation has caused sadness for 52 children, anger 22, shame 17, crying at 31 children, fear for 14, the silence at 58 children. In front of complete family’s children, these children experience feelings of aggression in 11.48%; sadness in 30.64%; 5.26% the shame, the 6.69% tears; jealousy in 2.39% and 2.87% of indifference. The option to get married in 44.15% of children is a challenge to want to give a happy childhood for their offspring; 22.01% feel rejected, there is uncertainty for 11.48% of cases and 25.36% didn’t give answer. 49, 76% of children want to see their family together; 7.65% are against to avoid disputes and in many cases to save the mother of the father's physical abuse. 27.75% of the ex-partners decline responsibility in the care of the child. Furthermore family difficulties affecting the intellectual capacities of children: 37.32% of children see school difficulties related to family problems despite all the pressure single-parent to see his child succeed. Single parenthood affects inter-family relations: pressure 33.97%; nervousness 24.88%; overprotection 29.18%; backbiting 11.96%, are the lives of these families. Conclusion: At the end of the investigation, results showed that there is a causal relationship between psychological disorders, academic difficulties of children and quality of parental relationships. Other cases may exist, but the lack of resources meant that we have only limited at 6 schools. Early psychological treatment for these children is needed.

Keywords: single-parent, psycho child, school, Cotonou

Procedia PDF Downloads 389

Authors: Hosein Alimadadi, Fatemeh Farahmand, Ali Jafarian, Nasir Fakhar, Mohammad Hassan Sohouli, Neda Raeesi

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Backgroundsː Regarding the important role of liver transplantation as the only treatment in many cases of end-stage liver disease in children, the aim of this study is to investigate the complications of liver transplantation and their management in children referred to the Children's Medical Center. Methods: This study is a cross-sectional study on pediatric patients who have undergone liver transplants in the years 2016 to 2021. The indication for liver transplantation in this population was confirmed by a pediatric gastroenterologist, and a liver transplant was performed by a transplant surgeon. Finally, information about the patient before and after the transplantation was collected and recorded. Results: A total of 53 patients participated in this study, including 25 (47.2%) boys and 28 (52.8%) girls. The most common causes of liver transplantation were cholestatic and metabolic diseases. The most common early complication of liver transplantation in children was acute cellular rejection (ACR) and anastomotic biliary stricture. The most common late complication in these patients was an infection which was observed in 56.6% of patients. Among the drug side effects, neurotoxicity (convulsions) was seen more in patients, and 15.1% of the transplanted patients died. Conclusion: In this study, the most common early complication of liver transplantation in children was ACR and biliary stricture, and the most common late complication was infection. Neurotoxicity (convulsions) was the most common side effect of drugs.

Keywords: liver transplantation, complication, infection, survival rate

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Authors: Jawad Alzeer

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Natural products are well recognized as sources of drugs in several human ailments. To investigate the impact of variable extraction techniques on the cytotoxic effects of medicinal plant extracts, 5 well-known medicinal plants from Palestine were extracted with 90% ethanol, 80% methanol, acetone, coconut water, apple vinegar, grape vinegar or 5% acetic acid. The resulting extracts were screened for cytotoxic activities against three different cancer cell lines (B16F10, MCF-7, and HeLa) using a standard resazurin-based cytotoxicity assay and Nile Blue A as the positive control. Highly variable toxicities and tissue sensitivity were observed, depending upon the solvent used for extraction. Acetone consistently gave lower extraction yields but higher cytotoxicity, whereas other solvent systems gave much higher extraction yields with lower cytotoxicity. Interestingly, coconut water was found to offer a potential alternative to classical organic solvents; it gave consistently highest extraction yields, and in the case of S. officinalis L., highly toxic extracts towards MCF-7 cells derived from human breast cancer. These results demonstrate how the cytotoxicity of plant extracts can be inversely proportional to the yield, and that solvent selection plays an important role in both factors.

Keywords: plant extract, natural products, anti cancer drug, cytotoxicity

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Authors: Lynn Lehmann, Dinorah Leyva, Ana Lazic, Stefan Duhr, Philipp Baaske

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Characterization of biomolecular interactions, such as protein-protein, protein-nucleic acid or protein-small molecule, provides critical insights into cellular processes and is essential for the development of drug diagnostics and therapeutics. Here we present a novel, label-free, and tether-free technology to analyze picomolar to millimolar affinities of biomolecular interactions by Microscale Thermophoresis (MST). The entropy of the hydration shell surrounding molecules determines thermophoretic movement. MST exploits this principle by measuring interactions using optically generated temperature gradients. MST detects changes in the size, charge and hydration shell of molecules and measures biomolecule interactions under close-to-native conditions: immobilization-free and in bioliquids of choice, including cell lysates and blood serum. Thus, MST measures interactions under close-to-native conditions, and without laborious sample purification. We demonstrate how MST determines the picomolar affinities of antibody::antigen interactions, and protein::protein interactions measured from directly from cell lysates. MST assays are highly adaptable to fit to the diverse requirements of different and complex biomolecules. NanoTemper´s unique technology is ideal for studies requiring flexibility and sensitivity at the experimental scale, making MST suitable for basic research investigations and pharmaceutical applications.

Keywords: biochemistry, biophysics, molecular interactions, quantitative techniques

Procedia PDF Downloads 523

Authors: Luc Conti, Dimitry Dumont-Fillon, Harald van Lintel, Eric Chappel

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Flow control valves comprise a silicon flexible membrane that deflects against a substrate, usually made of glass, containing pillars, an outlet hole, and anti-stiction features. However, there is a strong interest in using silicon instead of glass as substrate material, as it would simplify the process flow by allowing the use of well controlled anisotropic etching. Moreover, specific devices demanding a bending of the substrate would also benefit from the inherent outstanding mechanical strength of monocrystalline silicon. Unfortunately, direct Si-Si bonding is not easily achieved with highly structured wafers since residual stress may prevent the good adhesion between wafers. Using a thermoplastic polymer, such as parylene, as intermediate layer is not well adapted to this design as the wafer-to-wafer alignment is critical. An alternative anodic bonding method using an intermediate borosilicate layer has been successfully tested. This layer has been deposited onto the silicon substrate. The bonding recipe has been adapted to account for the presence of the SOI buried oxide and intermediate glass layer in order not to exceed the breakdown voltage. Flow control valves dedicated to infusion of viscous fluids at very high pressure have been made and characterized. The results are compared to previous data obtained using the standard anodic bonding method.

Keywords: anodic bonding, evaporated glass, flow control valve, drug delivery

Procedia PDF Downloads 200

Authors: Joseph K. A. Johnson

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Hypertension affects 20 percent of the people within the ages 55 upward in Ghana. Of these, almost one-third are unaware of their condition. Also at the age of 55, more men turned to have hypertension than women. After that age, the condition becomes more prevalent with women. Hypertension is significantly more common in African Americans of both sexes than the racial or ethnic groups. This study was conducted to determine the causes of high blood pressure in Ashanti Region, Ghana. The study employed One Hundred and Seventy (170) respondents. The sample population for the study was all the available respondents at the time of the data collection. The research was conducted using primary data where convenience sampling was used to locate the respondents. A set of questionnaire were used to gather the data for the study. The gathered data was analysed using principal component analysis. The study revealed that, personal description, lifestyle behavior and risk awareness as some of the causes of high blood pressure in Ashanti Region. The study therefore recommend that people must be advice to see to their personal characteristics that may contribute to high blood pressure such as controlling of their temper and how to react perfectly to stressful situations. They must be educated on the factors that may increase the level of their blood pressure such as the essence of seeing a medical doctor before taking in any drug. People must also be made known by the public health officers to those lifestyles behaviour such as smoking and drinking of alcohol which are major contributors of high blood pressure.

Keywords: high blood pressure, principal component analysis, hypertension, public health

Procedia PDF Downloads 484