Search results for: therapeutic agents

Authors: Maimona A. E. Elimam, Suhair Rehan, Miskelyemen A. Elmekki, Mogahid M. Elhassan

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Staphylococcus aureus (Staph. aureus), a major cause of potentially life-threatening infections acquired in healthcare and community settings, has developed resistance to most classes of antimicrobial agents as determined by the dramatic increase. The present study aimed to determine the prevalence of MRSA, and VRSA in patients with different clinical manifestations in Khartoum state. The study population (n, 426) were males and females with different age categories, suffering either from wound infections (105), ear infections (121), or UTI (101), in addition to nasal carriers of medical staff (100). Cultures, Gram staining, and other biochemical tests were performed for conventional identification. Modified Kirby-Bauer disk diffusion method was applied and DNA was extracted from MRSA and VRSA isolates and PCR was then performed for amplification of arc, mecA, VanA, and VanB genes. The results confirmed the existence of Staph. aureus in 49/426 (11.5%) cases among which MRSA were isolated from 34/49 (69.4%) when modified Kirby-Bauer disk diffusion method was applied. Ten out of these 34 MRSA were confirmed as VRSA by cultures on BHI agar containing 6μg/ml vancomycin according to NCCLS criteria. PCR revealed that out of the 34 MRSA isolates, 26 were mecA positive (76.5%) while 8 (23.5%) were arcC positive. No vanA or VanB genes were detected. Molecular method confirmed the results for MRSA through the presence of either arcC or mecA genes while it failed to approve the occurrence of VRSA since neither VanA or VanB genes were detected. Thus, VRSA may be attributed to other factors.

Keywords: antibiotic resistance, Staphylococcus aureus, VRSA, MRSA, Khartoum, Sudan

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Authors: Ying Sun, Biao Cheng, Qing Lu, Xuefei Tao, Xiaoyu Lai, Cheng Guo, Dan Wang

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Fibrinogen-like protein 2 (FGL2) has recently been identified to play an important role in inflammatory diseases such as atherosclerosis through a thrombin-dependent manner. Here, a murine monoclonal antibody was raised against the critical residue Ser(89) of FGL2, and the effects of the anti-FGL2 mAb (SPF89) were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Firstly, it was proved that SPF89, which belongs to the IgG1 subtype with a KD value of 44.5 pM, could specifically show the expression levels of protein FGL2 in different cell lines of known target gene status. The lipopolysaccharide (LPS)-mediated endothelial cell proliferation was significantly inhibited with a decline of phosphorylation nuclear factor-κB (NF-κB) in a dose-dependent manner after SPF89 treatment. Furthermore, SPF89 reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1, tumor necrosis factor-α, Matrix metalloproteinase MMP-2, Integrin αvβ3, and interleukin-6 in HUVECs. In macrophage-like THP-1 cells, SPF89 effectively inhibited LPS and low-density lipoprotein-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of anti-FGL2 mAb in HUVECs and THP-1 cells were significantly reduced after treatment with an NF-κB inhibitor PDTC. All the above suggest, by efficiently inhibiting LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB dependent pathway, the new anti-FGL2 mAb SPF89 could to be a potential therapeutic candidate for protecting the vascular endothelium against inflammatory diseases such as atherosclerosis. This work was supported by the Program of Sichuan Science and Technology Department (2017FZ0069) and Collaborative Innovation Program of Sichuan for Elderly Care and Health(YLZBZ1511).

Keywords: monoclonal antibody, fibrinogen like protein 2, inflammation, endothelial cells

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Authors: Navpreet Kaur, Randhir Singh

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Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. The present study targeted oxidative stress mediated nerve damage in diabetic rats using a hydro-alcohol extract of Cucurbita pepo L. (Family: Cucurbitaceae) and its potential in treatment of diabetic neuropathy. Diabetes neuropathy was induced in Wistar rats by injection of streptozotocin (65 mg/kg, i.p.) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Hydro-alcohol extract of C. pepo seeds was assessed by oral administration at 100, 200 and 400 mg/kg in STZ-nicotinamide induced diabetic rats. Thermal hyperalgesia (Eddy's hot plate and tail immersion), mechanical hyperalgesia (Randall-Selitto) and tactile allodynia (Von Frey hair tests) were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy. Tissue (sciatic nerve) antioxidant enzymes (SOD, CAT, GSH and LPO) levels were measured along with the formation of AGEs in serum to assess the effect of hydro-alcohol extract of C. pepo in ameliorating oxidative stress. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test and decreased paw withdrawal threshold in both Randall-Selitto and von-Frey hair test. A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress in sciatic nerve of diabetic rats. Treatment with the C. pepo hydro-alcohol extract significantly attenuated all the behavioral and biochemical alterations in a dose-dependent manner. C. pepo attenuated the diabetic condition and also reversed neuropathic pain through modulation of oxidative stress and thus it may find application as a possible therapeutic agent against diabetic neuropathy.

Keywords: advanced glycation end products, antioxidant enzymes, cucurbita pepo, hyperglycemia

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Authors: Bara M Yousef, Naresh B Raj, Nadiah W Arfah, Brightlin N Dhas

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Background: Executive function (EF) impairment is common in children with autism spectrum disorder (ASD). EF strategies are considered effective in improving the therapeutic outcomes of children with ASD. Aims: This study primarily aims to explore whether integrating EF strategies combined with regular occupational therapy intervention is more effective in improving daily life skills (DLS) and sensory integration/processing (SI/SP) skills than regular occupational therapy alone in children with ASD and secondarily aims to assess treatment outcomes on improving visual motor integration (VMI) skills. Procedures: A total of 92 children with ASD will be recruited and, following baseline assessments, randomly assigned to the treatment group (45-min once weekly individual occupational therapy plus EF strategies) and control group (45-min once weekly individual therapy sessions alone). Results and Outcomes: All children will be evaluated systematically by assessing SI/SP, DLS, and VMI, skills at baseline, 7 weeks, and 14 weeks of treatment. Data will be analyzed using ANCOVA and T-test. Conclusions and Implications: This single-blind, randomized controlled trial will provide empirical evidence for the effectiveness of EF strategies when combined with regular occupational therapy programs. Based on trial results, EF strategies could be recommended in multidisciplinary programs for children with ASD. Trial Registration: The trial has been registered in the clinicaltrail.gov for a registry, protocol ID: MRC-01-22-509 ClinicalTrials.gov Identifier: NCT05829577, registered 25th April 2023

Keywords: autism spectrum disorder, executive function strategies, daily life skills, sensory integration/processing, visual motor integration, occupational therapy, effectiveness

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Authors: L. Kloetzer, M. Poştaru, A. I. Galaction, D. Caşcaval

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Gentamicin is an aminoglycoside antibiotic industrially obtained by biosynthesis of Micromonospora purpurea or echinospora, the product being a complex mixture of components with very similar structures. Among them, three exhibit the most important biological activity: gentamicins C1, C1a, C2, and C2a. The separation of gentamicin from the fermentation broths at industrial scale is rather difficult and it does not allow the fractionation of the complex mixture of gentamicins in order to increase the therapeutic activity of the product. The aim of our experiments is to analyze the possibility to selectively separate the less active gentamicin, namely gentamicin C1, from the biosynthetic mixture by reactive extraction with di-(2-ethylhexyl) phosphoric acid (D2EHPA) dissolved in dichloromethane, followed selective re-extraction of the most active gentamicins C1a, C2, and C2a. The experiments on the reactive extraction of gentamicins indicated the possibility to separate selectively the gentamicin C1 from the mixture obtained by biosynthesis. The extraction selectivity is positively influenced by increasing the pH-value of an aqueous solution and by using a D2EHPA concentration in organic phase closer to the value needed for an equimolecular ratio between the extractant and this gentamicin. For quantifying the selectivity of separation, the selectivity factor, calculated as the ratio between the degree of reactive extraction of gentamicin C1 and the overall extraction degree of gentamicins were used. The possibility to remove the gentamicin C1 at an extractant concentration of 10 g l-1 and pH = 8 is presented. In these conditions, it was obtained the maximum value of the selectivity factor of 2.14, which corresponds to the modification of the gentamicin C1 concentration from 31.92% in the biosynthetic mixture to 72% in the extract. The re-extraction of gentamicins C1, C1a, C2, and C2a with sulfuric acid from the extract previously obtained by reactive extraction (mixture A – extract obtained by non-selective reactive extraction; mixture B – extract obtained by selective reactive extraction) allows for separating selectively the most active gentamicins C1a, C2, and C2a. For recovering only the active gentamicins C1a, C2, and C2a, the re-extraction must be carried out at very low acid concentrations, far below those corresponding to the stoichiometry of its chemical reactions with these gentamicins. Therefore, the mixture resulted by re-extraction contained 92.6% gentamicins C1a, C2, and C2a. By bringing together the aqueous solutions obtained by reactive extraction and re-extraction, the overall content of the active gentamicins in the final product becomes 89%, their loss reaching 0.3% related to the initial biosynthetic product.

Keywords: di-(2-ethylhexyl) phosphoric acid, gentamicin, reactive extraction, selectivity factor

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Authors: Ioannis Panagiotopoulos, Efstathios Kastritis, Anastasia Katinioti, Georgios Efthymiadis, Argyrios Doumas, Maria Koutelou

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Introduction: Transthyretin amyloidosis (ATTR) is a rare but serious infiltrative disease. Myocardial scintigraphy with DPD has emerged as the most effective, non-invasive, highly sensitive, and highly specific diagnostic method for cardiac ATTR amyloidosis. However, there are cases in which additional laboratory investigations reveal AL amyloidosis or other diseases despite a positive DPD scintigraphy. We describe the experience from the Onassis Cardiac Surgery Center and the monitoring center for infiltrative myocardial diseases of the cardiology clinic at AHEPA. Materials and Methods: All patients with clinical suspicion of cardiac or extracardiac amyloidosis undergo a myocardial scintigraphy scan with Tc-99m DPD. In this way, over 500 patients have been examined. Further diagnostic approach based on clinical and imaging findings includes laboratory investigation and invasive techniques (e.g., biopsy). Results: Out of 76 patients in total with positive myocardial scintigraphy Grade 2 or 3 according to the Perugini scale, 8 were proven to suffer from AL Amyloidosis during the investigation of paraproteinemia. Among these patients, 3 showed Grade 3 uptake, while the rest were graded as Grade 2, or 2 to 3. Additionally, one patient presented diffuse and unusual radiopharmaceutical uptake in soft tissues throughout the body without cardiac involvement. These findings raised suspicions, leading to the analysis of κ and λ light chains in the serum, as well as immunostaining of proteins in the serum and urine of these specific patients. The final diagnosis was AL amyloidosis. Conclusion: The value of DPD scintigraphy in the diagnosis of cardiac amyloidosis from transthyretin is undisputed. However, positive myocardial scintigraphy with DPD should not automatically lead to the diagnosis of ATTR amyloidosis. Laboratory differentiation between ATTR and AL amyloidosis is crucial, as both prognosis and therapeutic strategy are dramatically altered. Laboratory exclusion of paraproteinemia is a necessary and essential step in the diagnostic algorithm of ATTR amyloidosis for all positive myocardial scintigraphy with diphosphonate tracers since >20% of patients with Grade 3 and 2 uptake may conceal AL amyloidosis.

Keywords: AL amyloidosis, amyloidosis, ATTR, myocardial scintigraphy, Tc-99m DPD

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Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

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Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

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Authors: Salve Alessandria Alcantara, John Armand E. Aquino, Ma. Veronica Aranda, Nikki Francine Balde, Angeli Therese F. Cruz, Elise Danielle Garcia, Antonie Kyna Lim, Divina Gracia Lucero, Nikolai Thadeus Mappatao, Maylan N. Ocat, Jamille Dyanne L. Pajarillo, Jane Mierial A. Pesigan, Grace Kristin Viva, Jasmine Arielle C. Yap, Kathleen Michelle T. Yu, Joanna J. Orejola, Joanna V. Toralba

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Lead is a neurotoxic metallic element that is slowly accumulated in bones and tissues especially if present in products taken in a regular basis such as herbal tea supplements. Although sensitive analytical instruments are already available, the USP limit test for lead is still widely used. However, because of its serious shortcomings, Lang Lang and his colleagues developed a spectrophotometric method for determination of lead in all types of samples. This method was the one adapted in this study. The actual procedure performed was divided into three parts: digestion, extraction and analysis. For digestion, HNO3 and CH3COOH were used. Afterwards, masking agents, 0.003% and 0.001% dithizone in CHCl3 were added and used for the extraction. For the analysis, standard addition method and colorimetry were performed. This was done in triplicates under two conditions. The 1st condition, using 25µg/mL of standard, resulted to very low absorbances with an r2 of 0.551. This led to the use of a higher concentration, 1mg/mL, for condition 2. Precipitation of lead cyanide was observed and the absorbance readings were relatively higher but between 0.15-0.25, resulting to a very low r2 of 0.429. LOQ and LOD were not computed due to the limitations of the Milton-Roy Spectrophotometer. The method performed has a shorter digestion time, and used less but more accessible reagents. However, the optimum ratio of dithizone-lead complex must be observed in order to obtain reliable results while exploring other concentration of standards.

Keywords: herbal tea supplement, lead-dithizone complex, standard addition, visible spectroscopy

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Authors: Shuji Fujimoto, Fumiko Kojima, Mika Shigematsu

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Biorisk management (Biosafety/Biosecurity) is required for anyone working in a clinical laboratory (including medical/clinical research laboratories) where infectious agents and potentially hazardous biological materials are examined/stored. Proper education and training based on international standards of biorisk management should be provided not only as a part of laboratory safety program in work place but also as a part of introductory training at educational institutions for continuity and to elevate overall baseline of the biorisk management. We reported results of the pilot study of biorisk management education for graduate students majored in laboratory diagnostics previously. However, postgraduate education is still late in their profession and the participants’ interview also revealed importance and demands of earlier biorisk management education for undergraduates. The aim of this study is to identify the need for biosafety/biosecurity education and training program which is designed for undergraduate students who are entering the profession in clinical microbiology. We modified the previous program to include more basic topics and explanations (risk management, principles of safe clinical lab practices, personal protective equipment, disinfection, disposal of biological substances) and provided incorporating in the routine educational system for faculty of medical sciences in Kyushu University. The results of the pre and post examinations showed that the knowledge of the students on biorisk control had developed effectively as a proof of effectiveness of the program even in the undergraduate students. Our study indicates that administrating the basic biorisk management program in the earlier stage of learning will add positive impact to the understanding of biosafety to the health professional education.

Keywords: biorisk management, biosafety, biosecurity, clinical microbiology, education for undergraduates

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Authors: Daniela Panico

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Framed by language socialization and family language policy theories, the present study explores the ways the language choice patterns of bilingual siblings contribute to the shaping of the language environment and the language practices of Italian/English families residing in Sydney. The main source of data is video recordings of naturally occurring parent-children and child-to-child interactions during everyday routines (i.e., family mealtimes and siblings playtime) in the home environment. Recurrent interactional practices are analyzed in detail through a conversational analytical approach. This presentation focuses on the interactional trajectories developing during the negotiation of language choices between all family members and between siblings in face-to-face interactions. Fine-grained analysis is performed on language negotiation sequences of multiparty bilingual conversations in order to uncover the sequential patterns through which a) the children respond to the parental strategies aiming to minority language maintenance, and b) the siblings influence each other’s language use and choice (e.g., older siblings positioning themselves as language teachers and language brokers, younger siblings accepting the role of apprentices). The findings show that, along with the parents, children are active socializing agents in the family and, with their linguistic behavior, they contribute to the establishment of a bilingual or a monolingual context in the home. Moreover, by orienting themselves towards the use of one or the other language in family talk, bilingual siblings are a major internal micro force in the language ecology of a bilingual family and can strongly support language maintenance or language shift processes in such domain. Overall, the study provides insights into the dynamic ways in which family language policy is interactionally negotiated and instantiated in bilingual homes as well as the challenges of intergenerational language transmission.

Keywords: bilingual siblings, family interactions, family language policy, language maintenance

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Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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Authors: Gramza-Michalowska Anna, Skrety Joanna, Anna Zywica, Kobus-Cisowska Joanna, Kmiecik Dominik, Korczak Jozef

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Background: Modern consumer highly appreciates the positive influence of consumed products on well-being and overall health. High acceptance of new food is a result of intensified research showing many proofs confirming that food offers significant prophylactic and therapeutic potential, next to its basic nutritional function. Objective: Proposition of the technology of unsweetened oat drinks enriched with plant extracts for pro-health oriented individuals. We investigated the effects of selected plant extracts addition on antioxidative capacity and consumer’s acceptance of drinks as representative of all day diet product. Methods: The analysis of the basic composition and antioxidant properties of the drinking product was conducted. Basic composition included protein, lipids and fiber content. Antioxidant capacity of drink was evaluated with use radical scavenging methods (DPPH, ABTS), ORAC value and FRAP. Proposed drink as new product was also characterized with sensory analysis, which included color, aroma, taste, consistency and overall acceptance. Results: Results showed that addition of plant extracts into a oat drink allowed to enhance its antioxidant potential and influenced significantly its sensory values. The preferred composition and properties of designed beverage permit claim that it can have a positive impact on the health of the consumers. Conclusion: Designed oat drink would be an answer for pro-healthy life style of the consumers. Results showed that product with plant extracts addition would be accepted by the consumers and because of its antioxidative potential could be an important factor in prevention of free radicals influence on human organism.

Keywords: phytonutrients, pro-health, well-being, antioxidant potential, sensory value

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Authors: Daniela V. Bavaresco, Tamy Colonetti, Antonio Jose Grande, Francesc Colom, Joao Quevedo, Samira S. Valvassori, Maria Ines da Rosa

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Objective: Performed a systematic review and meta-analysis to evaluated the potential effect of the cyclo-oxygenases (Cox)-2 inhibitor Celecoxib adjunct treatment in Bipolar Disorder (BD), through of randomized controlled trials. Method: A search of the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO (American Psychological Association), Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published from January 1990 to February 2018. A search strategy was developed using the terms: 'Bipolar disorder' or 'Bipolar mania' or 'Bipolar depression' or 'Bipolar mixed' or 'Bipolar euthymic' and 'Celecoxib' or 'Cyclooxygenase-2 inhibitors' or 'Cox-2 inhibitors' as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched. The therapeutic effects of adjunctive treatment with Celecoxib were analyzed, it was possible to carry out a meta-analysis of three studies included in the systematic review. The meta-analysis was performed including the final results of the Young Mania Rating Scale (YMRS) at the end of randomized controlled trials (RCT). Results: Three primary studies were included in the systematic review, with a total of 121 patients. The meta-analysis had significant effect in the YMRS scores from patients with BD who used Celecoxib adjuvant treatment in comparison to placebo. The weighted mean difference was 5.54 (95%CI=3.26-7.82); p < 0.001; I2 =0%). Conclusion: The systematic review suggests that adjuvant treatment with Celecoxib improves the response of major treatments in patients with BD when compared with adjuvant placebo treatment.

Keywords: bipolar disorder, Cox-2 inhibitors, Celecoxib, systematic review, meta-analysis

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Authors: Mohammed Jarrar, Shalini Behl, Nadia Shaheen, Abeer Fatima, Reem Nasab

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Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is crucial on aging of skin by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photo-damage is highly valued. Retinoids and Alpha Hydroxy Acids protective and or repairing effects of UV have been endorsed by some researchers. For consolidating a better understanding of anti and protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblasts elastin levels exposed to UV. The UV exposed cells showed significant reduction in the elastin levels. A combination of drugs with a higher concentration of lactic acid (30-35 mM) and a lower concentration of retinol (10-15mg/mL) showed to work better in enhancing elastin concentration in UV exposed cells. We assume this enhancement could be the result of increased tropo-elastin gene expression stimulated by retinol and lactic acid probably repaired the UV irradiated damage by enhancing the amount and integrity of the elastin fibers.

Keywords: alpha hydroxy acid, elastin, retinol, ultraviolet radiations

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Authors: Jamal Alasiri, Naif Hakeem, Saoud Almaslmani

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Background: Patients with humeral shaft fractures have two different treatment options. Surgical therapy has lesser risks of non-union, mal-union, and re-intervention than non-surgical therapy. These positive clinical outcomes of the surgical approach make it a preferable treatment option despite the risks of radial nerve palsy and additional surgery-related risk. We aimed to evaluate patients’ outcomes and return to work after surgical vs. non-surgical management of shaft humeral fracture. Methods: We used databases, including PubMed, Medline, and Cochrane Register of Controlled Trials, from 2010 to January 2022 to search for potential randomised controlled trials (RCTs) and cohort studies comparing the patients’ related outcome measures and return to work between surgical and non-surgical management of humerus fracture. Results: After carefully evaluating 1352 articles, we included three RCTs (232 patients) and one cohort study (39 patients). The surgical intervention used plate/nail fixation, while the non-surgical intervention used a splint or brace procedure to manage shaft humeral fracture. The pooled DASH effects of all three RCTs at six (M.D: -7.5 [-13.20, -1.89], P: 0.009) I2:44%) and 12 months (M.D: -1.32 [-3.82, 1.17], p:0.29, I2: 0%) were higher in patients treated surgically than in non-surgical procedures. The pooled constant Murley score at six (M.D: 7.945[2.77,13.10], P: 0.003) I2: 0%) and 12 months (M.D: 1.78 [-1.52, 5.09], P: 0.29, I2: 0%) were higher in patients who received non-surgical than surgical therapy. However, pooled analysis for patients returning to work for both groups remained inconclusive. Conclusion: Altogether, we found no significant evidence supporting the clinical benefits of surgical over non-surgical therapy. Thus, the non-surgical approach remains the preferred therapeutic choice for managing shaft humeral fractures due to its lesser side effects.

Keywords: shaft humeral fracture, surgical treatment, Patient-related outcomes, return to work, DASH

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Authors: Husham Bayazed

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Purpose of Presentation: The eye is one of a few sites in the body with immune privilege (IP). However, this IP is relatively easily bypassed in the face of sufficient strong local or systemic immunological responses. As immune responses are crucial elements of the repair response, the eye has developed distinct mechanisms to deliver immune responses to injury in the avascular regions of the eye. This presentation may cover and provide an overview of the mechanisms that dictate immune cell trafficking to the local ocular microenvironment in response to different autoimmune and inflammatory-mediated diseases. Recent Findings: Literature reviews declare that immune responses and inflammation play a key role in a diverse range of eye diseases. In recent years, our understanding of ocular immune responses has widely spread in ocular surface inflammation, uveitis, age-related macular degeneration (AMD), glaucoma, transplantation rejection, and other ocular diseases. It is becoming increasingly clear that multiple seemingly unrelated diseases involve immune responses with common themes in their ocular pathogenesis. Recent studies are focusing on elucidating the pathogenesis of ocular inflammatory disease to identify new targets for immunotherapy that will not only improve efficacy but also minimize adverse effects from traditional therapy. Summary: While IP was believed to protect the eye from day-to-day inflammatory insults, however, it is relatively easily breached in the face of different strong local or systemic immunological and inflammatory responses. Therefore, the ocular immune response encapsulates the full range of classical and non-classical immune responses and demonstrates many features which are reflected in other tissues, but eye tissues, by modifying these responses, may reveal unexpected and novel findings which are relevant to immune responses generally. This may have therapeutic potential for new targeting immunotherapy, restoring immune tolerance in ocular autoimmune and inflammatory diseases, and preventing rejection such as stem cells, currently being considered for treatment of worldwide blinding diseases such as AMD.

Keywords: ocular diseases, immunology, immune privilege, immunotherapy

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Authors: N. G. Vepkhvadze, T. Enukidze

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Anthrax is a fatal disease caused by strains of Bacillus anthracis, a spore-forming gram-positive bacillus that causes the disease anthrax in animals and humans. Anthrax is a zoonotic disease that is also well-recognized as a potential agent of bioterrorism. Infection in humans is extremely rare in the developed world and is generally due to contact with infected animals or contaminated animal products. Testing of this zoonotic disease began in 1907 in Georgia and is still being tested routinely to provide accurate information and efficient testing results at the State Laboratory of Agriculture of Georgia. Each clinical sample is analyzed by RT-PCR and bacteriology methods; this study used Real-Time PCR assays for the detection of B. anthracis that rely on plasmid-encoded targets with a chromosomal marker to correctly differentiate pathogenic strains from non-anthracis Bacillus species. During the period of 2015-2022, the State Laboratory of Agriculture (SLA) tested 250 clinical and environmental (soil) samples from several different regions in Georgia. In total, 61 out of the 250 samples were positive during this period. Based on the results, Anthrax cases are mostly present in Eastern Georgia, with a high density of the population of livestock, specifically in the regions of Kakheti and Kvemo Kartli. All laboratory activities are being performed in accordance with International Quality standards, adhering to biosafety and biosecurity rules by qualified and experienced personnel handling pathogenic agents. Laboratory testing plays the largest role in diagnosing animals with anthrax, which helps pertinent institutions to quickly confirm a diagnosis of anthrax and evaluate the epidemiological situation that generates important data for further responses.

Keywords: animal disease, baccilus anthracis, edp, laboratory molecular diagnostics

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Authors: Seyed Reza Aghili, Tahereh Shokohi, Lotfollah Davoodi, Zahra Kashi, Azam Moslemi, Mahdi Abastabar, Iman Haghani, Sabah Mayahi, Asoudeh A.

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Introduction: In diabetic foot ulcers, if fungal agents such as Candida species penetrate into the cutaneous or depth of ulcer, can increase the degree of the wound and cause Candia infection and make it more difficult to heal. Material & Methods: A cross-sectional study was performed on 100 diabetic foot ulcer patients in 2020 in Sari, Iran. patient's data and wound grade were recorded in a questionnaire. Candida infection was diagnosed with direct microscopic examination and culture of samples. Colony-PCR molecular method was used for ITS region of DNA and then PCR-RFLP with Msp1 enzyme and using HWP1 specific gene to determine species of Candida agent. Results: Of 100 patients, the mean age 62.1 ± 10.8 years, 95% type 2 diabetes, 83%>10 years duration diabetes, 59% male, 66%> poor education level, 99% married, 52% rural, 95% neuropathic symptoms, 88% using antibiotics, 69%HbA1C >9%, and mean ulcer degree 2.6±1.05 were. Candida infection was seen in 13% of the deep tissue of the wound and 7% cutaneous around the wound. The predominant Candida isolated was C. parapsilosis (71.5%), C .albicans (14.3%). Fungal infections caused by mold fungi were not detected. There was a statistically significant relationship between yeast infection and gender, rural, HbA1C and ulcer degree. Conclusion: Mycological evaluations often are ignored. Candida parapsilosis is the most common infectious agent in these patients and may require specific treatment. Therefore, more attention of physicians to Candida infections particularly, early diagnosis and effective treatment can help faster recovery and prevent amputation.

Keywords: diabetic foot ulcer, candida infection, risk factors, c. parapsilosis

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Authors: Hanlei Yang

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As a kind of popular culture in modern China, advice book on intimate relationship is turning into an important and controversial site with conflicts among neoliberalism, authoritative socialism, market-oriented principles, the science of successful sex and relationship, cosmopolitan notions of nuclear families, and the revitalization of Confucian conservatism and patriarchy. Accelerated modernization and marketization has contributed to great changes in China’s culture and social relations, which accordingly reconceptualizes and reconstructs family structures and moral ethics, particularly urban middle-class nuclear families. To comprehend the meaning of advice book fad in moral and social order, this research proposes to (i) understand the implication of Ayawawa through discourse analysis and how she mobilizes rhetorical devices and cultural resources to present a persuasive and scientific method of managing intimate relationship, (ii) examine the critical role of neoliberalism, post-feminism, and Confucian patriarchy assumed by Ayawawa in her books, (iii) explore how Ayawawa and her fans engage in establishing a model of intimate relationship and sexual subjectivity ordered by neoliberalism, class identity and authoritative socialism. Finally, this research argues that such new fad of a cultural phenomenon is gradually completed in the process of cooperation and negotiation of the state, commercial institutions, and intellectual elite agents. It helps to further learn about (i) the routine life under the influence of neoliberalism and modern hegemony, (ii) the perplexing relationship between China's indigenous cultural forms, global socio-economic and cultural influences in the late modern era.

Keywords: cultural study, intimate relationship, culture sociology, gender study

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Authors: Han Chih Feng, Yi-Cheng Hou, Jing-Huei Wu

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Diabetes is a chronic disease. Nutrition knowledge and skills enable individuals with type 2 diabetes to optimize metabolic self-management and quality of life. This research studies the effect of nutritional education on diabetes inpatients in terms of their cognition, behavior, and attitude. The participants are inpatients diagnosed with diabetes at Taipei Tzu Chi Hospital. A total of 103 participants, 58 male, and 45 females, enrolled in the research between January 2018 and July 2018. The research evaluates cognition, behavior, and attitude level before and after nutritional education conducted by dietitians. The result shows significant improvement in actual consumption (2.5 ± 1.4 vs 3.8 ± 0.7; p<.001), diet control motivation (2.7 ± 0.8 vs 3.4 ± 0.6; p<.001), correct nutrition concept (1.2± 0.4 vs 2.4 ± 0.5; p<.001), learning willingness (2.7± 0.9 vs 3.4 ± 0.6; p<.001), cognitive behaviors (1.4 ± 0.5 vs 2.9 ± 0.7; p<.001). AC sugar (278.5 ± 321.5 vs 152.2 ± 49.1; p<.001) and HbA1C (10.3 ± 2.6 vs 8.6 ± 1.9; p<.001) are significant improvement after nutritional education. After nutritional education, participants oral hypoglycemic agents increased from 16 (9.2%) to 33 (19.0%), insulin decreased from 75 (43.1%) to 68 (39.1%), and hypoglycemic drugs combined with insulin decreased from 83 (47.7%) to 73 (42.0%).Further analysis shows that female inpatients have significant improvement in diet control motivation (3.91 ± 0.85 vs 4.44 ± 0.59; p<0.000), correct nutrition concept (3.24± 0.48 vs 4.47± 0.51; p<0.000), learning willingness (3.89 ± 0.86 vs 4.44 ± 0.59; p<0.000) and cognitive behaviors (2.42 ± 0.58 vs 4.02 ± 0.69; p<0.000); male inpatients have significant improvement in actual food intake (4.41± 0.92 vs 3.97 ± 0.42; p<0.000), diet control motivation (3.62 ± 0.86 vs 4.29 ± 0.62; p<0.000), correct nutrition concept (3.26 ± 0.44 vs 4.36 ± 0.49; p<0.000), learning willingness (3.72± 0.93 vs 4.33± 0.63; p<0.000) and cognitive behaviors (2.45± 0.54 vs 4.03± 0.77; p<0.000). In conclusion, nutritional education proves effective, regardless of gender, in improving an inpatient’s cognition, behavior, and attitude toward diabetes self-management.

Keywords: diabetes, nutrition education, actual consumption, diet control motivation, nutrition concept, learning willingness, cognitive behaviors

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Authors: Rajlakshmi Guha, Sajjad Ansari, Shazia Nasreen, Hirak Banerjee, Jiaul Paik

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Dyslexia is a neurocognitive disorder, affecting around fifteen percent of the Indian population. The symptoms include difficulty in reading alphabet, words, and sentences. This can be difficult at the phonemic or recognition level and may further affect lexical structures. Therapeutic intervention of dyslexic children post assessment is generally done by special educators and psychologists through one on one interaction. Considering the large number of children affected and the scarcity of experts, access to care is limited in India. Moreover, unavailability of resources and timely communication with caregivers add on to the problem of proper intervention. With the development of Educational Technology and its use in India, access to information and care has been improved in such a large and diverse country. In this context, this paper proposes an ICT enabled home-based intervention program for dyslexic children which would support the child, and provide an interactive interface between expert, parents, and students. The paper discusses the details of the database design and system layout of the program. Along with, it also highlights the development of different technical aids required to build out personalized android applications for the Indian dyslexic population. These technical aids include speech database creation for children, automatic speech recognition system, serious game development, and color coded fonts. The paper also emphasizes the games developed to assist the dyslexic child on cognitive training primarily for attention, working memory, and spatial reasoning. In addition, it talks about the specific elements of the interactive intervention tool that makes it effective for home based intervention of dyslexia.

Keywords: Android applications, cognitive training, dyslexia, intervention

Procedia PDF Downloads 289

Authors: Anne R. Fernandez, Mohammad Akmal Adnan, Tanes Prasat, Indu Bala Jaganath, Brian Kirby, Kamalan Jeevaratnam

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Introduction: Plants from the Phyllantus genus have been used indigenously for the treatment of a variety of ailments for generations. A cocktail of phytonutrients prepared from a plant of the genus Phyllanthus has demonstrated the potential to alleviate ailments which include cardiovascular disorders. In this study, we investigated the cholesterol modulating properties of a highly purified proprietary extract of a Phyllanthus species in hypercholesteraemic mice. Methods: Hypercholesteraemia was induced in ICR mice by ad-libitum feeding of high fat diet daily for six weeks. The mice were then divided into 3 groups and force fed with 10mg/kg of atorvastatin, 200mg/kg of the proprietary Phyllanthus extract and water respectively. Blood samples were taken at the end of fourth week of treatment by a tail prick. At the end of the eighth week of treatment, mice were sacrificed and serum levels of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides were measured. Results: The mean cholesterol levels in the mice fed with high fat diet were 44% (p < 0.05) higher than the mice on normal diet thus validating the model developed. The plasma HDL was significantly elevated in mice treated with the formulation (p ˂ 0.05) in comparison to the statin-treated and control mice. The total cholesterol levels in the mice treated with the proprietary extract were reduced significantly (p < 0.05) at the end of 4 weeks of treatment in comparison to the mice treated with atorvastatin. By the end of 8 weeks of treatment, there was no significant difference in the cholesterol levels of the mice in all groups. Conclusion: These results demonstrate that this proprietary extract from Phyllanthus species has the beneficial effect of reducing total cholesterol level more rapidly than atorvastatin and increasing HDL levels. Since an increase in the HDL cholesterol can reduce the risk of heart disease, this proprietary extract is a useful and safe therapeutic option compared to atorvastatin.

Keywords: high-density lipoprotein, hypercholesteraemic mice model, ICR mice, Phyllanthus spp.

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Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

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N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

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Authors: Rita Emília Szabó, Róbert Polanek, Tünde Tőkés, Zoltán Szabó, Szabolcs Czifrus, Katalin Hideghéty

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Purpose: Several feature of zebrafish are making them amenable for investigation on therapeutic approaches such as ionizing radiation. The establishment of zebrafish model for comprehensive radiobiological research stands in the focus of our investigation, comparing the radiation effect curves of neutron and photon irradiation. Our final aim is to develop an appropriate vertebrate model in order to investigate the relative biological effectiveness of laser driven ionizing radiation. Methods and Materials: After careful dosimetry series of viable zebrafish embryos were exposed to a single fraction whole-body neutron-irradiation (1,25; 1,875; 2; 2,5 Gy) at the research reactor of the Technical University of Budapest and to conventional 6 MeV photon beam at 24 hour post-fertilization (hpf). The survival and morphologic abnormalities (pericardial edema, spine curvature) of each embryo were assessed for each experiment at 24-hour intervals from the point of fertilization up to 168 hpf (defining the dose lethal for 50% (LD50)). Results: In the zebrafish embryo model LD50 at 20 Gy dose level was defined and the same lethality were found at 2 Gy dose from the reactor neutron beam resulting RBE of 10. Dose-dependent organ perturbations were detected on macroscopic (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, micrognathia, pericardial edema, and inhibition of yolk sac resorption) and microscopic (marked cellular changes in skin, cardiac, gastrointestinal system) with the same magnitude of dose difference. Conclusion: In our observations, we found that zebrafish embryo model can be used for investigating the effects of different type of ionizing radiation and this system proved to be highly efficient vertebrate model for preclinical examinations.

Keywords: ionizing radiation, LD50, relative biological effectiveness, zebrafish embryo

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Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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Authors: Thabiso Michael Mokotjomela, Jasper Knight

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Intensification of agricultural food production in sub-Saharan Africa is of paramount importance as a means of increasing the food security of communities that are already experiencing a range of environmental and socio-economic stresses. However, achieving this aim faces several challenges including ongoing climate change, increased resistance of diseases and pests, extreme environmental degradation partly due to biological invasions, land tenure and management practices, socio-economic developments of rural populations, and national population growth. In particular, non-native plant species tend to display greater adaptation capacity to environmental stress than native species that form important food resource base for human beings, thus suggesting a potential for usage to shift accordingly. Based on review of the historical benefits of non-native plant species in food production in sub-Saharan Africa, we propose that use of non-invasive, non-native plant species and/or the genetic modification of native species might be viable options for future agricultural sustainability in this region. Coupled with strategic foresight planning (e.g. use of biological control agents that suppress plant species’ invasions), the consumptive use of already-introduced non-native species might help in containment and control of possible negative environmental impacts of non-native species on native species, ecosystems and biodiversity, and soil fertility and hydrology. Use of non-native species in food production should be accompanied by low cost agroecology practices (e.g. conservation agriculture and agrobiodiversity) that may promote the gradual recovery of natural capital, ecosystem services, and promote conservation of the natural environment as well as enhance food security.

Keywords: food security, invasive species, agroecology, agrobiodiversity, socio-economic stresses

Procedia PDF Downloads 367

Authors: Hushyar Azari

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Aim and background: Deep brain stimulation (DBS) is regarded as an important therapeutic choice for Parkinson's disease (PD). The two most common targets for DBS are the subthalamic nucleus (STN) and globus pallidus (GPi). This review was conducted to compare the clinical effectiveness of these two targets. Methods: A systematic literature search in electronic databases: Embase, Cochrane Library and PubMed were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies which evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) compared both GPi and STN DBS; (2) had at least three months follow-up period; (3)at least five participants in each group; (4)conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified, of these, 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). According to Modified Jadad Scale, the majority of included studies had low evidence quality which was a limitation of this review. 5 studies reported no statistically significant between-group difference for improvements in UPDRS ш scores. At the same time, there were some results in terms of pain, action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice. Regarding the adverse effects, GPi was superior. Conclusion: It is clear that other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for deep brain stimulation in Parkinson’s disease and imposes fewer adverse effects on the patients. Meanwhile, STN seems more reasonable according to the results of this systematic review.

Keywords: brain stimulation, globus pallidus, Parkinson's disease, subthalamic nucleus

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Authors: Gajanan M. Sonwane

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Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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Authors: Chang Li Yu

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Resistances commonly happened during sexual offenders treatment program (SOTP), and removing resistances was one of the treatment goals on it. Studies concerning treatment effectiveness relied on pre- and post-treatment evaluations, however, no significant difference on resistance revealed after treatment, and the above consequences generally contributed to the low motivation for change instead. Therefore, the aim of this study was to investigate the resistance across each stage of change among sexual offenders (SO). The present study recruited prisoned SO in Taiwan, excluding those with literacy difficulties; finally, 272 participants were included. Of all participants completed revised version of URICA (University of Rhode Island Change Assessment) and resistance scale specifically for SO. The former included four stages of change: pre-contemplation (PC), contemplation (C), action (A), and maintain (M); the later composed eight types of resistance: system blaming, victims blaming, problems with treatment alliance, social justification, hopelessness, isolation, psychological reactance, and passive reactance. Both of the instruments were with well reliability and validity. Descriptive statistics and ANOVA were performed. All of 272 participants, age under 25 were 18(6.6%), 25-39 were 133(48.9%), 40-54 were 102(37.5%), and age over 55 were 19(7.0%); college level and above were 53(19.5%), high school level were 110(40.4%), and under high school level were 109(40.1%); first offended were 117(43.0%), and recidivist were 23(8.5%). Further deleting data with missing values and invalid questionnaires, SO with stage of change on PC were 43(18.9%), C were 109(47.8%), A were 70(30.7%), and on M were 6(2.6%). One-way ANOVA showed significant differences on every kind of resistances, excepting isolation and passive reactance. Post-hoc analysis showed that SO with different stages had their main resistance. There are two contributions to the present study. First, this study provided a clinical and theoretical measurement of evaluation that was never used in the past. Second, this study used an evidence-based methodology to prove a clinical perspective differed from the past, suggesting that resistances to treatment on SO appear the whole therapeutic process, when SO progress into the next stage of change, clinicians have to deal with their main resistance for working through the therapy.

Keywords: resistance, sexual offenders treatment program (SOTP), motivation for change, prisoned sexual offender

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Authors: Cigdem Karaaslan, Yalcin Duydu, Aylin Ustundag, Can Ozgur Yalcın, Hakan Goker

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Benzazole nucleus is found in the structure of many compounds as anticancer agents. Bendamustine (Alkylating agent), Nocodazole (Mitotic inhibitor), Veliparib (PARP inhibitor), Glasdegib (SMO inhibitor) are clinically used as anticancer therapeutics which bearing benzimidazole moiety. Based on the principle of bioisosterism in the present work, 23 compounds belonging to 2-(3,4-dimethoxy-phenyl) benzazoles and imidazopyridine series were synthesized and evaluated for their anticancer activities. N-(5-Chloro-2-hydroxyphenyl)-3,4-dimethoxybenzamide, was obtained by the amidation of 2-hydroxy-5-chloroaniline with 3,4-dimethoxybenzoic acid by using 1,1'-carbonyldiimidazole. Cyclization of benzamide derivative to benzoxazole, was achieved by p-toluenesulfonic acid. Other 1H-benz (or pyrido) azoles were prepared by the reaction between 2-aminothiophenol, o-phenylenediamine, o-pyridinediamine with sodium metabisulfite adduct of 3,4-dimethoxybenzaldehyde. The NMR assignments of the dimethoxy groups were established by the Nuclear Overhauser Effect Spectroscopy. A compound named, 5(4),7(6)-Dichloro-2-(3,4-dimethoxy) phenyl-1H-benzimidazole, bearing two chlorine atoms at the 5(4) and 7(6) positions of the benzene moiety of benzimidazole was found the most potent analogue, against A549 cells with the GI50 value of 1.5 µg/mL. In addition, 2-(3,4-Dimethoxyphenyl)-5,6-dimethyl-1H-benzimi-dazole showed remarkable cell growth inhibition against MCF-7 and HeLa cells with the GI₅₀ values of 7 and 5.5 µg/mL, respectively. It could be concluded that introduction of di-chloro atoms at the phenyl ring of 2-(3,4-dimethoxyphenyl)-1H-benzimidazoles increase significant cytotoxicity to selected human tumor cell lines in comparison to other all benzazoles synthesized in this study. Unsubstituted 2-(3,4-dimethoxyphenyl) imidazopyridines also gave the good inhibitory profile against A549 and HeLa cells.

Keywords: 3, 4-Dimethoxyphenyl, 1H-benzimidazole, benzazole, imidazopyridine

Procedia PDF Downloads 120