Search results for: cancer therapy

Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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Authors: Ifeoma Anozie, Teka Apalata, Dominic Abaver

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Introduction: Despite use of Anti-retroviral therapy to reduce the incidence of opportunistic infections among HIV/AIDS patients, rapid episodes of re-infection after deworming are still common occurrences because pharmaceutical intervention alone does not prevent reinfection. Unsafe water and inadequate personal hygiene and parasitic infections are widely expected to accelerate the progression of HIV infection. This is because the chronic immunosuppression of HIV infection encourages susceptibility to opportunistic (including parasitic) infections which is linked to CD4+ cell count of <200 cells/μl. Intestinal parasites such as G. intestinalis and Entamoeba spp are ubiquitous protozoa that remain infectious over a long time in an environment and show resistance to standard disinfection. To control re-infection, the social factors that underpin the prevention need to be controlled. This study aims at prevention of intestinal parasites in people living with HIV/AIDS by using a treatment, hygiene education and sanitation (THEdS) bundle approach. Methods: This study was conducted in four clinics (Ngangelizwe health centre, Tsolo gateway clinic, Idutywa health centre and Nqamakwe health centre) across the seven districts in Eastern cape, South Africa. The four clinics were divided in two: experimental and control, for the purpose of intervention. Data was collected from March 2019 to February 2020. Six hundred participants were screened for intestinal parasitic infections. Stool samples were collected and analysed twice: before (Pre-test infection screening) and after (Post-test re-infection) THEdS bundle intervention. The experimental clinics received full intervention package, which include therapeutic treatment, health education on personal hygiene and sanitation training, while the control clinics received only therapeutic treatment for those found with intestinal parasitic infections. Results: Baseline prevalence of Intestinal Parasites isolated shows 12 intestinal parasites with overall frequency of 65, with Ascaris lumbricoides having most frequency (44.6%). The intervention had a cure rate of 60%, with odd ratio of 1.42, which indicates that the intervention group is 1.42 times more likely of parasite clearing as compared to the control group. The relative risk ratio of 1.17 signifies that there is 1.17 times more likelihood to clear intestinal parasite if there no intervention. Discussion and conclusion: Infection with multiple parasites can cause health defects, especially among HIV/AIDS patients. Efficiency of some HIV vaccines in HIV/AIDS patients is affected because treatment of re-infection amplifies drug resistance, affects the efficacy of the front-line drugs, and still permits transmission. In South Africa, treatment of intestinal parasites is usually offered to clinic attending HIV/AIDS patients upon suspicion but not as a mandate for patients being initiated into Antiretroviral (ART) program. The effectiveness of THEdS bundle advocates for inclusiveness of mandatory screening for intestinal parasitic infections among attendees of HIV/Aids clinics on regular basis.

Keywords: cure rate, , HIV/AIDS patients, intestinal parasites, intervention studies, reinfection rate

Procedia PDF Downloads 59

Authors: O. O. Sufyani, M. E. Oraiby, S. A. Qumaiy, A. I. Alaamri, Z. M. Eisa, A. M. Hakami, M. A. Attafi, O. M. Alhassan, W. M. Elsideeg, E. M. Noureldin, Y. A. Hobani, Y. Q. Majrabi, I. A. Khardali, A. B. Maashi, A. A. Al Mane, A. H. Hakami, I. M. Alkhyat, A. A. Sahly, I. M. Attafi

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According to the Food and Agriculture Organization (FAO) Pesticides Use Database, pesticide use in agriculture in Saudi Arabia has more than doubled from 4539 tons in 2009 to 10496 tons in 2019. Among pesticides, pyrethroids is commonly used in Saudi Arabia. Pesticides may increase susceptibility to a variety of diseases, particularly among pesticide workers, due to their extensive use, indiscriminate use, and long-term exposure. Therefore, analyzing blood chemo-profiles and evaluating the detected substances as biomarkers for pyrethroid pesticide exposure may assist to identify and predicting adverse effects of exposure, which may be used for both preventative and risk assessment purposes. The purpose of this study was to (a) analyze chemo-profiling by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, (b) identify the most commonly detected chemicals in a time-exposure-dependent manner using a Venn diagram, and (c) identify their associated disease among pesticide workers using analyzer tools on the Comparative Toxicogenomics Database (CTD) website, (250 healthy male volunteers (20-60 years old) who deal with pesticides in the Jazan region of Saudi Arabia (exposure intervals: 1-2, 4-6, 6-8, more than 8 years) were included in the study. A questionnaire was used to collect demographic information, the duration of pesticide exposure, and the existence of chronic conditions. Blood samples were collected for biochemistry analysis and extracted by solid-phase extraction for gas chromatography-mass spectrometry (GC-MS) analysis. Biochemistry analysis reveals no significant changes in response to the exposure period; however, an inverse association between the albumin level and the exposure interval was observed. The blood chemo-profiling was differentially expressed in an exposure time-dependent manner. This analysis identified the common chemical set associated with each group and their associated significant occupational diseases. While some of these chemicals are associated with a variety of diseases, the distinguishing feature of these chemically associated disorders is their applicability for prevention measures. The most interesting finding was the identification of several chemicals; erucic acid, pelargonic acid, alpha-linolenic acid, dibutyl phthalate, diisobutyl phthalate, dodecanol, myristic Acid, pyrene, and 8,11,14-eicosatrienoic acid, associated with pneumoconiosis, asbestosis, asthma, silicosis and berylliosis. Chemical-disease association study also found that cancer, digestive system disease, nervous system disease, and metabolic disease were the most often recognized disease categories in the common chemical set. The hierarchical clustering approach was used to compare the expression patterns and exposure intervals of the chemicals found commonly. More study is needed to validate these chemicals as early markers of pyrethroid insecticide-related occupational disease, which might assist evaluate and reducing risk. The current study contributes valuable data and recommendations to public health.

Keywords: occupational, toxicology, chemo-profiling, pesticide, pyrethroid, GC-MS

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Authors: Arsyam Mawardi, Sony Suhandono, Azzania Fibriani, Fifi Fitriyah Masduki

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Malaria is an infectious disease caused by Plasmodium sp. This disease has a high prevalence in Indonesia, especially in Jayapura. The vaccine that is currently being developed has not been effective in overcoming malaria. This is due to the high polymorphism in the Plasmodium genome especially in areas that encode Plasmodium surface proteins. Merozoite Surface Protein 1 (MSP1) Plasmodium falciparum is a surface protein that plays a role in the invasion process in human erythrocytes through the interaction of Glycophorin A protein receptors and sialic acid in erythrocytes with Reticulocyte Binding Proteins (RBP) and Duffy Adhesion Protein (DAP) ligands in merozoites. MSP1 can be targeted to be a specific antigen and predicted epitope area which will be used for the development of diagnostic and malaria vaccine therapy. MSP1 consists of 17 blocks, each block is dimorphic, and has been marked as the K1 and MAD20 alleles. Exceptions only in block 2, because it has 3 alleles, among others K1, MAD20 and RO33. These polymorphisms cause allelic variations and implicate the severity of patients infected P. falciparum. In addition, polymorphism of MSP1 in Jayapura isolates has not been reported so it is interesting to be further identified and projected as a specific antigen. Therefore, in this study, we analyzed the allele polymorphism as well as detected the MSP1 epitope antigen candidate on block 2 P. falciparum. Clinical samples of selected malaria patients followed the consecutive sampling method, examining malaria parasites with blood preparations on glass objects observed through a microscope. Plasmodium DNA was isolated from the blood of malarial positive patients. The block 2 MSP1 gene was amplified using PCR method and cloned using the pGEM-T easy vector then transformed to TOP'10 E.coli. Positive colonies selection was performed with blue-white screening. The existence of target DNA was confirmed by PCR colonies and DNA sequencing methods. Furthermore, DNA sequence analysis was done through alignment and formation of a phylogenetic tree using MEGA 6 software and insilico analysis using IEDB software to predict epitope candidate for P. falciparum. A total of 15 patient samples have been isolated from Plasmodium DNA. PCR amplification results show the target gene size about ± 1049 bp. The results of MSP1 nucleotide alignment analysis reveal that block 2 MSP1 genes derived from the sample of malarial patients were distributed in four different allele family groups, K1 (7), MAD20 (1), RO33 (0) and MSP1_Jayapura (10) alleles. The most commonly appears of the detected allele is MSP1_Jayapura single allele. There was no significant association between sex variables, age, the density of parasitemia and alel variation (Mann Whitney, U > 0.05), while symptomatic signs have a significant difference as a trigger of detectable allele variation (U < 0.05). In this research, insilico study shows that there is a new epitope antigen candidate from the MSP1_Jayapura allele and it is predicted to be recognized by B cells with 17 amino acid lengths in the amino acid sequence 187 to 203.

Keywords: epitope candidate, insilico analysis, MSP1 P. falciparum, polymorphism

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Authors: Arup Dutta, Badrul Alam, Sayed M. Wazed, Taslima Newaz, Srobonti Dutta

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Background: In today's world, with modern science and contemporary technology, a lot of diseases may be quickly identified and ruled out, but children's fever of unknown origin (FUO) still presents diagnostic difficulties in clinical settings. Any fever that reaches 38 °C and lasts for more than seven days without a known cause is now classified as a fever of unknown origin (FUO). Despite tremendous progress in the medical sector, fever of unknown origin, or FOU, persists as a major health issue and a major contributor to morbidity and mortality, particularly in children, and its spectrum is sometimes unpredictable. The etiology is influenced by geographic location, age, socioeconomic level, frequency of antibiotic resistance, and genetic vulnerability. Since there are currently no known diagnostic algorithms, doctors are forced to evaluate each patient one at a time with extreme caution. A persistent fever poses difficulties for both the patient and the doctor. This prospective, observational study was carried out in a Bangladeshi tertiary care hospital from June 2018 to May 2019 with the goal of identifying the epidemiological patterns of fever of unknown origin in pediatric patients. Methods: It was a hospital-based prospective observational study carried out on 106 children (between 2 months and 12 years) with prolonged fever of >38.0 °C lasting for more than 7 days without a clear source. Children with additional chronic diseases or known immunodeficiency problems were not allowed. Clinical practices that helped determine the definitive etiology were assessed. Initial testing included a complete blood count, a routine urine examination, PBF, a chest X-ray, CRP measurement, blood cultures, serology and additional pertinent investigations. The analysis focused mostly on the etiological results. The standard program SPSS 21 was used to analyze all of the study data. Findings: A total of 106 patients identified as having FUO were assessed, with over half (57.5%) being female and the majority (40.6%) falling within the 1 to 3-year age range. The study categorized the etiological outcomes into five groups: infections, malignancies, connective tissue conditions, miscellaneous, and undiagnosed. In the group that was being studied, infections were found to be the main cause in 44.3% of cases. Undiagnosed cases came in at 31.1%, cancers at 10.4%, other causes at 8.5%, and connective tissue disorders at 4.7%. Hepato-splenomegaly was seen in people with enteric fever, malaria, acute lymphoid leukemia, lymphoma, and hepatic abscesses, either by itself or in combination with other conditions. About 53% of people who were not diagnosed also had hepato-splenomegaly at the same time. Conclusion: Infections are the primary cause of PUO (pyrexia of unknown origin) in children, with undiagnosed cases being the second most common cause. An incremental approach is beneficial in the process of diagnosing a condition. Non-invasive examinations are used to diagnose infections and connective tissue disorders, while invasive investigations are used to diagnose cancer and other ailments. According to this study, the prevalence of undiagnosed diseases is still remarkable, so extensive historical analysis and physical examinations are necessary in order to provide a precise diagnosis.

Keywords: children, diagnostic challenges, fever of unknown origin, pediatric fever, undiagnosed diseases

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Authors: Tatjana Kadifkova Panovska, Svetlana Kulevanova, Blagica Jovanova

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Biological systems possess the ability to neutralize the excess of reactive oxygen species (ROS) and to protect cells from destructive alterations. However, many pathological conditions (cardiovascular diseases, autoimmune disorders, cancer) are associated with inflammatory processes that generate an excessive amount of reactive oxygen species (ROS) that shift the balance between endogenous antioxidant systems and free oxygen radicals in favor of the latter, leading to oxidative stress. Therefore, an additional source of natural compounds with antioxidant properties that will reduce the amount of ROS in cells is much needed despite their broad utilization; many plant species remain largely unexplored. Therefore, the purpose of the present study is to investigate the antioxidant activity of twenty-five selected medicinal and aromatic plant species. The antioxidant activity of the ethanol extracts was evaluated with in vitro assays: 2,2’-diphenyl-1-pycryl-hydrazyl (DPPH), ferric reducing antioxidant power (FRAP), non-site-specific- (NSSOH) and site-specific hydroxyl radical-2-deoxy-D-ribose degradation (SSOH) assays. The Folin-Ciocalteu method and AlCl3 method were performed to determine total phenolic content (TPC) and total flavonoid content (TFC). All examined plant extracts manifested antioxidant activity to a different extent. Cinnamomum verum J.Presl bark and Ocimum basilicum L. Herba demonstrated strong radical scavenging activity and reducing power with the DPPH and FRAP assay, respectively. Additionally, significant hydroxyl scavenging potential and metal chelating properties were observed using the NSSOH and SSOH assays. Furthermore, significant variations were determined in the total polyphenolic content (TPC) and total flavonoid content (TFC), with Cinnamomum verum and Ocimum basilicum showing the highest amount of total polyphenols. The considerably strong radical scavenging activity, hydroxyl scavenging potential and reducing power for the species mentioned above suggest of a presence of highly bioactive phytochemical compounds, predominantly polyphenols. Since flavonoids are the most abundant group of polyphenols that possess a large number of available reactive OH groups in their structure, it is considered that they are the main contributors to the radical scavenging properties of the examined plant extracts. This observation is supported by the positive correlation between the radical scavenging activity and the total polyphenolic and flavonoid content obtained in the current research. The observations from the current research nominate Cinnamomum verum bark and Ocimum basilicum herba as potential sources of bioactive compounds that could be utilized as antioxidative additives in the food and pharmaceutical industries. Moreover, the present study will help the researchers as basic data for future research in exploiting the hidden potential of these important plants that have not been explored so far.

Keywords: ethanol extracts, radical scavenging activity, reducing power, total polyphenols.

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: K. A.Veselova, N. V.Gromova, I. N.Antonova, I. N. Kalakutskii

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There are many diseases and incidents that may result facial defects and deformities: cancer, trauma, burns, congenital anomalies, and autoimmune diseases. In some cases, patient may acquire atypically extensive facial defect, including more than one anatomical region or, by contrast, atypically small defect (e.g. partial auricular defect). The anaplastology gives us opportunity to help patient with facial disfigurement in cases when plastic surgery is contraindicated. Using of implant retention for facial prosthesis is strongly recommended because improves both aesthetic and functional results and makes using of the prosthesis more comfortable. Prostheticly oriented fixture position is extremely important for aesthetic and functional long-term result; however, the optimal site for fixture placement is not clear in cases with atypical configuration of facial defect. The objective of this report is to demonstrate challenges in fixture position determination we have faced with and offer the solution. In this report, four cases of implant-supported facial prosthesis are described. Extra-oral implants with four millimeter length were used in all cases. The decision regarding the quantity of surgical stages was based on anamnesis of disease. Facial prostheses were manufactured according to conventional technique. Clinical and technological difficulties and mistakes are described, and prostheticly oriented approach for determination of fixture position is demonstrated. The case with atypically large combined orbital and nasal defect resulting after arteriovenous malformation is described: the correct positioning of artificial eye was impossible due to wrong position of the fixture (with suprastructure) located in medial aspect of supraorbital rim. The suprastructure was unfixed and this fixture wasn`t used for retention in order to achieve appropriate artificial eye placement and better aesthetic result. In other case with small partial auricular defect (only helix and antihelix were absent) caused by squamoized cell carcinoma T1N0M0 surgical template was used to avoid the difficulties. To achieve the prostheticly oriented fixture position in case of extremely small defect the template was made on preliminary cast using vacuum thermoforming method. Two radiopaque markers were incorporated into template in preferable for fixture placement positions taking into account future prosthesis configuration. The template was put on remaining ear and cone-beam CT was performed to insure, that the amount of bone is enough for implant insertion in preferable position. Before the surgery radiopaque markers were extracted and template was holed for guide drill. Fabrication of implant-retained facial prostheses gives us opportunity to improve aesthetics, retention and patients’ quality of life. But every inaccuracy in planning leads to challenges on surgery and prosthetic stages. Moreover, in cases with atypically small or extended facial defects prostheticly oriented approach for determination of fixture position is strongly required. The approach including surgical template fabrication is effective, easy and cheap way to avoid mistakes and unpredictable result.

Keywords: anaplastology, facial prosthesis, implant-retained facial prosthesis., maxillofacil prosthese

Procedia PDF Downloads 88

Authors: Neerja Gupta

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Objective-Reconstruction of large cavities of the breast without contralateral symmetrisation Background- Reconstruction of breast includes a wide spectrum of procedures from displacement to regional and distant flaps. The pedicled Perforator flaps cover a wide spectrum of reconstruction surgery for all quadrants of the breast, especially in patients with comorbidities. These axial flaps singly or adjunct are based on a near constant perforator vessel, a ratio of 2:1 at its entry in a flap is good to maintain vascularity. The perforators of lateral chest wall viz LICAP, LTAP have overlapping perfurosomes without clear demarcation. LTAP is localized in the narrow zone between the lateral breast fold and anterior axillary line,2.5-3.8cm from the fold. MICAP are localized at 1-2 cm from sternum. Being 1-2mm in diameter, a Single perforator is good to maintain the flap. LICAP has a dominant perforator in 6th-11th spaces, while LTAP has higher placed dominant perforators in 4th and 5th spaces. Methodology-Six consecutive patients who underwent reconstruction of the breast with pedicled perforator flaps were retrospectively analysed. Selections of the flap was done based on the size and locations of the tumour, anticipated volume loss, willingness to undergo contralateral symmetrisation, cosmetic expectations, and finances available.3 patients underwent vertical LTAP, the distal limit of the flap being the inframammary crease. 3 patients underwent MICAP, oriented along the axis of rib, the distal limit being the anterior axillary line. Preoperative identification was done using a unidirectional hand held doppler. The flap was raised caudal to cranial, the pivot point of rotation being the vessel entry into the skin. The donor area is determined by the skin pinch. Flap harvest time was 20-25 minutes. Intra operative vascularity was assessed with dermal bleed. The patient immediate pre, post-operative and follow up pics were compared independently by two breast surgeons. Patients were given a breast Q questionnaire (licensed) for scoring. Results-The median age of six patients was 46. Each patient had a hospital stay of 24 hours. None of the patients was willing for contralateral symmetrisation. The specimen dimensions were from 8x6.8x4 cm to 19x16x9 cm. The breast volume reconstructed range was 30 percent to 45 percent. All wide excision had free margins on frozen. The mean flap dimensions were 12x5x4.5 cm. One LTAP underwent marginal necrosis and delayed wound healing due to seroma. Three patients were phyllodes, of which one was borderline, and 2 were benign on final histopathology. All other 3 patients were invasive ductal cancer and have completed their radiation. The median follow up is 7 months the satisfaction scores at median follow of 7 months are 90 for physical wellbeing and 85 for surgical results. Surgeons scored fair to good in Harvard score. Conclusion- Pedicled perforator flaps are a valuable option for 3/8th volume of breast defects. LTAP is preferred for tumours at the Central, upper, and outer quadrants of the breast and MICAP for the inner and lower quadrant. The vascularity of the flap is dependent on the angiosomalterritories; adequate venous and cavity drainage.

Keywords: breast, oncoplasty, pedicled, perforator

Procedia PDF Downloads 173

Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

Procedia PDF Downloads 245

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

Procedia PDF Downloads 178

Authors: Li Jiuen Ong, Magdalin Cheong, Sri Rahayu, Lek Alexander, Pei Ting Tan

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Background: Previous programme evaluations from the diabetes training programme conducted in Changi General Hospital revealed that healthcare professionals (HCPs) are keen to receive advance diabetes training and education, specifically in medical, nutritional therapy. HCPs also expressed a preference for interactive activities over didactic teaching methods to enhance their learning. Since the War on Diabetes was initiated by MOH in 2016, HCPs are challenged to be actively involved in continuous education to be better equipped to reduce the growing burden of diabetes. Hence, streamlining training to incorporate an element of fun is of utmost importance. Aim: The nutrition programme incorporates game play using an interactive board game that aims to provide a more conducive and less stressful environment for learning. The board game could be adapted for training of community HCPs, health ambassadors or caregivers to cope with the increasing demand of diabetes care in the hospital and community setting. Methodology: Stages for game’s conception (Jaffe, 2001) were adopted in the development of the interactive board game ‘Sweet Score™ ’ Nutrition concepts and topics in diabetes self-management are embedded into the game elements of varying levels of difficulty (‘Easy,’ ‘Medium,’ ‘Hard’) including activities such as a) Drawing/ sculpting (Pictionary-like) b)Facts/ Knowledge (MCQs/ True or False) Word definition) c) Performing/ Charades To study the effects of game play on knowledge acquisition and perceived experiences, participants were randomised into two groups, i.e., lecture group (control) and game group (intervention), to test the difference. Results: Participants in both groups (control group, n= 14; intervention group, n= 13) attempted a pre and post workshop quiz to assess the effectiveness of knowledge acquisition. The scores were analysed using paired T-test. There was an improvement of quiz scores after attending the game play (mean difference: 4.3, SD: 2.0, P<0.001) and the lecture (mean difference: 3.4, SD: 2.1, P<0.001). However, there was no significance difference in the improvement of quiz scores between gameplay and lecture (mean difference: 0.9, 95%CI: -0.8 to 2.5, P=0.280). This suggests that gameplay may be as effective as a lecture in terms of knowledge transfer. All the13 HCPs who participated in the game rated 4 out of 5 on the likert scale for the favourable learning experience and relevance of learning to their job, whereas only 8 out of 14 HCPs in the lecture reported a high rating in both aspects. 16. Conclusion: There is no known board game currently designed for diabetes training for HCPs.Evaluative data from future training can provide insights and direction to improve the game format and cover other aspects of diabetes management such as self-care, exercise, medications and insulin management. Further testing of the board game to ensure learning objectives are met is important and can assist in the development of awell-designed digital game as an alternative training approach during the COVID-19 pandemic. Learning through gameplay increases opportunities for HCPs to bond, interact and learn through games in a relaxed social setting and potentially brings more joy to the workplace.

Keywords: active learning, game, diabetes, nutrition

Procedia PDF Downloads 160

Authors: Hyemi Kim, Jay Kim, Kyunghoon Han, Ra-Yeong Choi, In-Woo Kim, Hyung Joo Suh, Ki-Bae Hong, Sung Hee Han

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Chitosan is used in various industries such as food and medical care because it is known to have various functions such as anti-obesity, anti-inflammatory and anti-cancer benefits. Most of the commercial chitosan is extracted from crustaceans. As the harvest rate of snow crabs and red snow crabs decreases and safety issues arise due to environmental pollution, research is underway to extract chitosan from insects. In this study, we used Response Surface Methodology (RSM) to predict the optimal conditions to produce chitosan oligosaccharides from mealworms (MCOS), which can be absorbed through the intestine as low-molecular-weight chitosan. The experimentally confirmed optimal conditions for MCOS production using chitosanase were found to be a substrate concentration of 2.5%, enzyme addition of 30 mg/g and a reaction time of 6 hours. The chemical structure and physicochemical properties of the produced MCOS were measured using MALDI-TOF mass spectra and FTIR spectra. The MALDI-TOF mass spectra revealed peaks corresponding to the dimer (375.045), trimer (525.214), tetramer (693.243), pentamer (826.296), and hexamer (987.360). In the FTIR spectra, commercial chitosan oligosaccharides exhibited a weak peak pattern at 3500-2500 cm-1, unlike chitosan or chitosan oligosaccharides. There was a difference in the peak at 3200~3500 cm-1, where different vibrations corresponding to OH and amine groups overlapped. Chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide showed peaks at 2849, 2884, and 2885 cm-1, respectively, attributed to the absorption of the C-H stretching vibration of methyl or methine. The amide I, amide II, and amide III bands of chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide exhibited peaks at 1620/1620/1602, 1553/1555/1505, and 1310/1309/1317 cm-1, respectively. Furthermore, the solubility of MCOS was 45.15±3.43, water binding capacity (WBC) was 299.25±4.57, and fat binding capacity (FBC) was 325.61±2.28 and the solubility of commercial chitosan oligosaccharides was 49.04±9.52, WBC was 280.55±0.50, and FBC was 157.22±18.15. Thus, the characteristics of MCOS and commercial chitosan oligosaccharides are similar. The results of investigating the impact of chitosan oligosaccharide on the proliferation of probiotics revealed increased growth in L. casei, L. acidophilus, and Bif. Bifidum. Therefore, the major short-chain fatty acids produced by gut microorganisms, such as acetic acid, propionic acid, and butyric acid, increased within 24 hours of adding 1% (p<0.01) and 2% (p<0.001) MCOS. The impact of MCOS on the overall gut microbiota was assessed, revealing that the Chao1 index did not show significant differences, but the Simpson index decreased in a concentration-dependent manner, indicating a higher species diversity. The addition of MCOS resulted in changes in the overall microbial composition, with an increase in Firmicutes and Verrucomicrobia (p<0.05) compared to the control group, while Proteobacteria and Actinobacteria (p<0.05) decreased. At the genus level, changes in microbiota due to MCOS supplementation showed an increase in beneficial bacteria like lactobacillus, Romboutsia, Turicibacter, and Akkermansia (p<0.0001) while harmful bacteria like Enterococcus, Morganella, Proterus, and Bacteroides (p<0.0001) decreased. In this study, chitosan oligosaccharides were successfully produced under established conditions from mealworms, and these chitosan oligosaccharides are expected to have prebiotic effects, similar to those obtained from crabs.

Keywords: mealworms, chitosan, chitosan oligosaccharide, prebiotics

Procedia PDF Downloads 52

Authors: A. Matiushkina, A. Bazhenova, I. Litvinov, E. Kornilova, A. Dubavik, A. Orlova

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Magnetic-luminescent complexes based on superparamagnetic iron oxide nanoparticles (SPIONs) and semiconductor quantum dots (QDs) have been recognized as a new class of materials that have high potential in modern medicine. These materials can serve for theranostics of oncological diseases, and also as a target agent for drug delivery. They combine the qualities characteristic of magnetic nanoparticles, that is, magneto-controllability and the ability to local heating under the influence of an external magnetic field, as well as phosphors, due to luminescence of which, for example, early tumor imaging is possible. The complexity of creating complexes is the energy transfer between particles, which quenches the luminescence of QDs in complexes with SPIONs. In this regard, a relatively new type of alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs is used in our work. The presence of a sufficiently thick gradient semiconductor shell in alloyed QDs makes it possible to reduce the probability of energy transfer from QDs to SPIONs in complexes. At the same time, Forster Resonance Energy Transfer (FRET) is a perfect instrument to confirm the formation of complexes based on QDs and different-type energy acceptors. The formation of complexes in the aprotic bipolar solvent dimethyl sulfoxide is ensured by the coordination of the carboxyl group of the stabilizing QD molecule (L-cysteine) on the surface iron atoms of the SPIONs. An analysis of the photoluminescence (PL) spectra has shown that a sequential increase in the SPIONs concentration in the samples is accompanied by effective quenching of the luminescence of QDs. However, it has not confirmed the formation of complexes yet, because of a decrease in the PL intensity of QDs due to reabsorption of light by SPIONs. Therefore, a study of the PL kinetics of QDs at different SPIONs concentrations was made, which demonstrates that an increase in the SPIONs concentration is accompanied by a symbatic reduction in all characteristic PL decay times. It confirms the FRET from QDs to SPIONs, which indicates the QDs/SPIONs complex formation, rather than a spontaneous aggregation of QDs, which is usually accompanied by a sharp increase in the percentage of the QD fraction with the shortest characteristic PL decay time. The complexes have been studied by the magnetic circular dichroism (MCD) spectroscopy that allows one to estimate the response of magnetic material to the applied magnetic field and also can be useful to check SPIONs aggregation. An analysis of the MCD spectra has shown that the complexes have zero residual magnetization, which is an important factor for using in biomedical applications, and don't contain SPIONs aggregates. Cell penetration, biocompatibility, and stability of QDs/SPIONs complexes in cancer cells have been studied using HeLa cell line. We have found that the complexes penetrate in HeLa cell and don't demonstrate cytotoxic effect up to 25 nM concentration. Our results clearly demonstrate that alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs can be successfully used in complexes with SPIONs reached new hybrid nanostructures, which combine bright luminescence for tumor imaging and magnetic properties for targeted drug delivery and magnetic hyperthermia of tumors. Acknowledgements: This work was supported by the Ministry of Science and Higher Education of Russian Federation, goszadanie no. 2019-1080 and was financially supported by Government of Russian Federation, Grant 08-08.

Keywords: alloyed quantum dots, magnetic circular dichroism, magneto-luminescent complexes, superparamagnetic iron oxide nanoparticles

Procedia PDF Downloads 97

Authors: E. Carraro, Sa. Bonetta, Si. Bonetta, E. Ceretti, G. C. V. Viola, C. Pignata, S. Levorato, T. Salvatori, S. Vannini, V. Romanazzi, A. Carducci, G. Donzelli, T. Schilirò, A. De Donno, T. Grassi, S. Bonizzoni, A. Bonetti, G. Gilli, U. Gelatti

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In 2013, air pollution and particulate matter were classified as carcinogenic to human by the IARC. At present, PM is Europe's most problematic pollutant in terms of harm to health, as reported by European Environmental Agency (EEA) in the EEA Technical Report on Air quality in Europe, 2015. A percentage between 17-30 of the EU urban population lives in areas where the EU air quality 24-hour limit value for PM10 is exceeded. Many studies have found a consistent association between exposure to PM and the incidence and mortality for some chronic diseases (i.e. lung cancer, cardiovascular diseases). Among the mechanisms responsible for these adverse effects, genotoxic damage is of particular concern. Children are a high-risk group in terms of the health effects of air pollution and early exposure during childhood can increase the risk of developing chronic diseases in adulthood. The MAPEC_LIFE (Monitoring Air Pollution Effects on Children for supporting public health policy) is a project founded by EU Life+ Programme (LIFE12 ENV/IT/000614) which intends to evaluate the associations between air pollution and early biological effects in children and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. This work is focused on the micronuclei frequency in child buccal cells in association with airborne PM levels taking into account the influence of other factors associated with the lifestyle of children. The micronucleus test was performed in exfoliated buccal cells of 6–8 years old children from 5 Italian towns with different air pollution levels. Data on air quality during the study period were obtained from the Regional Agency for Environmental Protection. A questionnaire administered to children’s parents was used to obtain details on family socio-economic status, children health condition, exposures to other indoor and outdoor pollutants (i.e. passive smoke) and life-style, with particular reference to eating habits. During the first sampling campaign (winter 2014-15) 1315 children were recruited and sampled for Micronuclei test in buccal cells. In the sampling period the levels of the main pollutants and PM10 were, as expected, higher in the North of Italy (PM10 mean values 62 μg/m3 in Torino and 40 μg/m3 in Brescia) than in the other towns (Pisa, Perugia, Lecce). A higher Micronucleus frequency in buccal cells of children was found in Brescia (0.6/1000 cells) than in the other towns (range 0.3-0.5/1000 cells). The statistical analysis underlines a relation of the micronuclei frequency with PM concentrations, traffic level near child residence, and level of education of parents. The results suggest that, in addition to air pollution exposure, some other factors, related to lifestyle or further exposures, may influence micronucleus frequency and cellular response to air pollutants.

Keywords: air pollution, buccal cells, children, micronucleus cytome assay

Procedia PDF Downloads 234

Authors: Xu Qian

Abstract:

This abstract examines the concept of resilience in adolescents from both adolescent medicine and child psychology perspectives. It discusses the role of healthcare providers in fostering resilience among adolescents, encompassing physical, psychological, and social aspects. The paper highlights evidence-based interventions and practical strategies for promoting resilience in this population. Introduction: Resilience plays a crucial role in the healthy development of adolescents, enabling them to navigate through the challenges of this transitional period. This abstract explores the concept of resilience from the perspectives of adolescent medicine and child psychology, shedding light on the collective efforts of healthcare providers in fostering resilience. By integrating the principles and practices of these two disciplines, this abstract emphasizes the multidimensional nature of resilience and its significance in the overall well-being of adolescents. Methods: A comprehensive literature review was conducted, encompassing research articles, empirical studies, and expert opinions from both adolescent medicine and child psychology fields. The search included databases such as PubMed, PsycINFO, and Google Scholar, focusing on publications from the past decade. The review aimed to identify evidence-based interventions and practical strategies employed by healthcare providers to promote resilience among adolescents. Results: The review revealed several key findings regarding the promotion of resilience in adolescents. Firstly, resilience is a dynamic process influenced by individual characteristics, environmental factors, and the interaction between the two. Secondly, healthcare providers play a critical role in fostering resilience by addressing the physical, psychological, and social needs of adolescents. This entails comprehensive healthcare services that integrate medical care, mental health support, and social interventions. Thirdly, evidence-based interventions such as cognitive-behavioral therapy, social skills training, and positive youth development programs have shown promising outcomes in enhancing resilience. Discussion: The integration of adolescent medicine and child psychology perspectives provides a comprehensive framework for promoting resilience in adolescents. By acknowledging the interplay between physical health, psychological well-being, and social functioning, healthcare providers can tailor interventions to address the specific needs and challenges faced by adolescents. Collaborative efforts between medical professionals, psychologists, educators, and families are vital in creating a supportive environment that fosters resilience. Additionally, the findings highlight the importance of early identification and intervention, emphasizing the need for routine screening and assessment to identify adolescents at risk and provide timely support. Conclusion: Promoting resilience in adolescents requires a holistic approach that integrates adolescent medicine and child psychology perspectives. By recognizing the multifaceted nature of resilience, healthcare providers can implement evidence-based interventions and practical strategies to enhance the well-being of adolescents. The collaboration between healthcare professionals from different disciplines, alongside the involvement of families and communities, is crucial for creating a resilient support system. By investing in the promotion of resilience during adolescence, we can empower young individuals to overcome adversity and thrive in their journey toward adulthood.

Keywords: psychology, clinical psychology, child psychology, adolescent psychology, adolescent

Procedia PDF Downloads 61

Authors: Alok Bapatla, Pamela Lutting, Mariastella Serrano

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Background: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain associated with altered bowel habits in the absence of an underlying organic cause. Although the exact etiology of IBS is not fully understood, one of the leading theories postulates a pathology within the Brain-Gut Axis that leads to an overall increase in gastrointestinal sensitivity and pejorative changes in gastrointestinal motility. Research and clinical practice have shown that Gut Directed Hypnotherapy (GDH) has a beneficial clinical role in improving Mind-Gut control and thereby comorbid conditions such as anxiety, abdominal pain, constipation, and diarrhea. Aims: This study presents a 17-year old male with underlying anxiety and a one-year history of IBS-Constipation Predominant Subtype (IBS-C), who has demonstrated impressive improvement of symptoms following GDH treatment following refractory trials with medications including bisacodyl, senna, docusate, magnesium citrate, lubiprostone, linaclotide. Method: The patient was referred to a licensed clinical psychologist specializing in clinical hypnosis and cognitive-behavioral therapy (CBT), who implemented “The Standardized Hypnosis Protocol for IBS” developed by Dr. Olafur S. Palsson, Psy.D at the University of North Carolina at Chapel Hill. The hypnotherapy protocol consisted of a total of seven weekly 45-minute sessions supplemented with a 20-minute audio recording to be listened to once daily. Outcome variables included the GAD-7, PHQ-9 and DCI-2, as well as self-ratings (ranging 0-10) for pain (intensity and frequency), emotional distress about IBS symptoms, and overall emotional distress. All variables were measured at intake prior to administration of the hypnosis protocol and at the conclusion of the hypnosis treatment. A retrospective IBS Questionnaire (IBS Severity Scoring System) was also completed at the conclusion of the GDH treatment for pre-and post-test ratings of clinical symptoms. Results: The patient showed improvement in all outcome variables and self-ratings, including abdominal pain intensity, frequency of abdominal pain episodes, emotional distress relating to gut issues, depression, and anxiety. The IBS Questionnaire showed a significant improvement from a severity score of 400 (defined as severe) prior to GDH intervention compared to 55 (defined as complete resolution) at four months after the last session. IBS Questionnaire subset questions that showed a significant score improvement included abdominal pain intensity, days of pain experienced per 10 days, satisfaction with bowel habits, and overall interference of life affected by IBS symptoms. Conclusion: This case supports the existing research literature that GDH has a significantly beneficial role in improving symptoms in patients with IBS. Emphasis is placed on the numerical results of the IBS Questionnaire scoring, which reflects a patient who initially suffered from severe IBS with failed response to multiple medications, who subsequently showed full and sustained resolution

Keywords: pediatrics, constipation, irritable bowel syndrome, hypnotherapy, gut-directed hypnosis

Procedia PDF Downloads 177

Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

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The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

Procedia PDF Downloads 572

Authors: Masoume Ehsani, Ning Zhu, Huu Doan, Ali Lohi, Amira Abdelrasoul

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Membrane fouling poses severe challenges in membrane-based wastewater treatment applications. Ultrasound (US) has been considered an effective fouling remediation technique in filtration processes. Bubble cavitation in the liquid medium results from the alternating rarefaction and compression cycles during the US irradiation at sufficiently high acoustic pressure. Cavitation microbubbles generated under US irradiation can cause eddy current and turbulent flow within the medium by either oscillating or discharging energy to the system through microbubble explosion. Turbulent flow regime and shear forces created close to the membrane surface cause disturbing the cake layer and dislodging the foulants, which in turn improve the cleaning efficiency and filtration performance. Therefore, the number, size, velocity, and oscillation pattern of the microbubbles created in the liquid medium play a crucial role in foulant detachment and permeate flux recovery. The goal of the current study is to gain in depth understanding of the influence of the US power intensity and frequency on the microbubble dynamics and its characteristics generated under US irradiation. In comparison with other imaging techniques, the synchrotron in-line Phase Contrast Imaging technique at the Canadian Light Source (CLS) allows in-situ observation and real-time visualization of microbubble dynamics. At CLS biomedical imaging and therapy (BMIT) polychromatic beamline, the effective parameters were optimized to enhance the contrast gas/liquid interface for the accuracy of the qualitative and quantitative analysis of bubble cavitation within the system. With the high flux of photons and the high-speed camera, a typical high projection speed was achieved; and each projection of microbubbles in water was captured in 0.5 ms. ImageJ software was used for post-processing the raw images for the detailed quantitative analyses of microbubbles. The imaging has been performed under the US power intensity levels of 50 W, 60 W, and 100 W, in addition to the US frequency levels of 20 kHz, 28 kHz, and 40 kHz. For the duration of 2 seconds of imaging, the effect of the US power and frequency on the average number, size, and fraction of the area occupied by bubbles were analyzed. Microbubbles’ dynamics in terms of their velocity in water was also investigated. For the US power increase of 50 W to 100 W, the average bubble number and the average bubble diameter were increased from 746 to 880 and from 36.7 µm to 48.4 µm, respectively. In terms of the influence of US frequency, a fewer number of bubbles were created at 20 kHz (average of 176 bubbles rather than 808 bubbles at 40 kHz), while the average bubble size was significantly larger than that of 40 kHz (almost seven times). The majority of bubbles were captured close to the membrane surface in the filtration unit. According to the study observations, membrane cleaning efficiency is expected to be improved at higher US power and lower US frequency due to the higher energy release to the system by increasing the number of bubbles or growing their size during oscillation (optimum condition is expected to be at 20 kHz and 100 W).

Keywords: bubble dynamics, cavitational bubbles, membrane fouling, ultrasonic cleaning

Procedia PDF Downloads 131

Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Thiago E. Goto, Carla C. Lopes, Helena B. Nader, Anielle C. A. Silva, Noelio O. Dantas, José R. Siqueira Jr., Luciano Caseli

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Quantum dots (QD) are semiconductor nanocrystals that can be employed in biological research as a tool for fluorescence imagings, having the potential to expand in vivo and in vitro analysis as cancerous cell biomarkers. Particularly, cadmium selenide (CdSe) magic-sized quantum dots (MSQDs) exhibit stable luminescence that is feasible for biological applications, especially for imaging of tumor cells. For these facts, it is interesting to know the mechanisms of action of how such QDs mark biological cells. For that, simplified models are a suitable strategy. Among these models, Langmuir films of lipids formed at the air-water interface seem to be adequate since they can mimic half a membrane. They are monomolecular films formed at liquid-gas interfaces that can spontaneously form when organic solutions of amphiphilic compounds are spread on the liquid-gas interface. After solvent evaporation, the monomolecular film is formed, and a variety of techniques, including tensiometric, spectroscopic and optic can be applied. When the monolayer is formed by membrane lipids at the air-water interface, a model for half a membrane can be inferred where the aqueous subphase serve as a model for external or internal compartment of the cell. These films can be transferred to solid supports forming the so-called Langmuir-Blodgett (LB) films, and an ampler variety of techniques can be additionally used to characterize the film, allowing for the formation of devices and sensors. With these ideas in mind, the objective of this work was to investigate the specific interactions of CdSe MSQDs with tumorigenic and non-tumorigenic cells using Langmuir monolayers and LB films of lipids and specific cell extracts as membrane models for diagnosis of cancerous cells. Surface pressure-area isotherms and polarization modulation reflection-absorption spectroscopy (PM-IRRAS) showed an intrinsic interaction between the quantum dots, inserted in the aqueous subphase, and Langmuir monolayers, constructed either of selected lipids or of non-tumorigenic and tumorigenic cells extracts. The quantum dots expanded the monolayers and changed the PM-IRRAS spectra for the lipid monolayers. The mixed films were then compressed to high surface pressures and transferred from the floating monolayer to solid supports by using the LB technique. Images of the films were then obtained with atomic force microscopy (AFM) and confocal microscopy, which provided information about the morphology of the films. Similarities and differences between films with different composition representing cell membranes, with or without CdSe MSQDs, was analyzed. The results indicated that the interaction of quantum dots with the bioinspired films is modulated by the lipid composition. The properties of the normal cell monolayer were not significantly altered, whereas for the tumorigenic cell monolayer models, the films presented significant alteration. The images therefore exhibited a stronger effect of CdSe MSQDs on the models representing cancerous cells. As important implication of these findings, one may envisage for new bioinspired surfaces based on molecular recognition for biomedical applications.

Keywords: biomembrane, langmuir monolayers, quantum dots, surfaces

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Authors: Sugam Kale, Arif Uzair Bin Mohammed Roslan, Cindy Lee, Syed Beevee Mohammed Ismail

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Preemptive analgesia is an established concept in the modern practice of anaesthesia. To be most effective, it is best instituted earlier than the surgical stimulus and should last beyond the offset of surgically induced pain till healing is complete. Whereas the start of afferent pain blockade with regional anaesthesia is common, its effect often falls short to cover the entire period of pain impulses making their way to CNS in the post-operative period. We tried to use a combination of two regional anaesthetic techniques used sequentially to overcome this handicap. Madam S., a 56 year old lady, was scheduled for elective surgery for pancreatic cancer. She underwent laparotomy and distal pancreatectomy, splenectomy, bilateral salpingo oophorectomy, and sigmoid colectomy. Surgery was expected to be extensive, and it was presumed that the standard pain relief with PCA with opiates and oral analgesics would not be adequate. After counselling the patient pre-operative about the technique of regional anaesthesia techniques, including epidural catheterization and rectus sheath catheter placement, their benefits, and potential complications, informed consent was obtained. Epidural catheter was placed awake, and general anaesthesia was then induced. Epidural infusion of local anaesthetics was started prior to surgical incision and was continued till 60 hours into the postoperative period. Before skin closure, the surgeons inserted commercially available rectus sheath catheters bilaterally along the midline incision used for laparotomy. After 46 hours post-op, local anaesthetic infusion via these was started as bridging while the epidural infusion rate was tapered off. The epidural catheter was removed at 75 hours. Elastomeric pumps were used to provide local anaesthetic infusion with the ability to vary infusion rates. Acute pain service followed up the patient’s vital signs and effectiveness of pain relief twice daily or more frequently as required. Rectus sheath catheters were removed 137 hours post-op. The patient had good post-op analgesia with the minimal additional analgesic requirement. For the most part, the visual analog score (VAS) for pain remained at 1-3 on a scale of 1 to 10. Haemodynamics remained stable, and surgical recovery was as expected. Minimal opiate requirement after an extensive laparotomy also translates to the early return of intestinal motility. Our experience was encouraging, and we are hoping to extend this combination of two regional anaesthetic techniques to patients undergoing similar surgeries. Epidural analgesia is denser and offers excellent pain relief for both visceral and somatic pain in the first few days after surgery. As the pain intensity grows weaker, rectus sheath block and oral analgesics provide almost the same degree of pain relief after the epidural catheter is removed. We discovered that the background infusion of local anaesthetic down the rectus sheath catherter largely reduced the requirement for other classes of analgesics. We aim to study this further with a larger patient cohort and hope that it may become an established clinical practice that benefits patients everywhere.

Keywords: rectus sheath, epidural infusion, post operative analgesia, elastomeric

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Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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Authors: Adrienn Kiss, Karoly Zauer, Gyorgy Keglevich, Rita Molnarne Bernath

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Ginger (Zingiber officinale) is a perennial plant from Southeast Asia, widely used as a spice, herb, and medicine for many illnesses since its beneficial health effects were observed thousands of years ago. Among the compounds found in ginger, zingerone [4-hydroxy-3- methoxyphenyl-2-butanone] deserves special attention: it has an anti-inflammatory and antispasmodic effect, it can be used in case of diarrheal disease, helps to prevent the formation of blood clots, has antimicrobial properties, and can also play a role in preventing the Alzheimer's disease. Ferulic acid [(E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoic acid] is another cinnamic acid derivative in ginger, which has promising properties. Like many phenolic compounds, ferulic acid is also an antioxidant. Based on the results of animal experiments, it is assumed to have a direct antitumoral effect in lung and liver cancer. It also deactivates free radicals that can damage the cell membrane and the DNA and helps to protect the skin against UV radiation. The aim of this work was to synthesize these two compounds by new methods. A few of the reactions were based on the hydrogenation of dehydrozingerone [4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one] to zingerone. Dehydrozingerone can be synthesized by a relatively simple method from acetone and vanillin with good yield (80%, melting point: 41 °C). Hydrogenation can be carried out chemically, for example by the reaction of zinc and acetic acid, or Grignard magnesium and ethyl alcohol. Another way to complete the reduction is the electrochemical pathway. The electrolysis of dehydrozingerone without diaphragm in aqueous media was attempted to produce ferulic acid in the presence of sodium carbonate and potassium iodide using platinum electrodes. The electrolysis of dehydrozingerone in the presence of potassium carbonate and acetic acid to prepare zingerone was carried out similarly. Ferulic acid was expected to be converted to dihydroferulic acid [3-(4-Hydroxy-3-methoxyphenyl)propanoic acid] in potassium hydroxide solution using iron electrodes, separating the anode and cathode space with a Soxhlet paper sheath impregnated with saturated magnesium chloride solution. For this reaction, ferulic acid was synthesized from vanillin and malonic acid in the presence of pyridine and piperidine (yield: 88.7%, melting point: 173°C). Unfortunately, in many cases, the expected transformations did not happen or took place in low conversions, although gas evolution occurred. Thus, a deeper understanding of these experiments and optimization are needed. Since both compounds are found in different plants, they can also be obtained by alkaline extraction or steam distillation from distinct plant parts (ferulic acid from ground bamboo shoots, zingerone from grated ginger root). The products of these reactions are rich in several other organic compounds as well; therefore, their separation must be solved to get the desired pure material. The products of the reactions described above were characterized by infrared spectral data and melting points. The use of these two simple methods may be informative for the formation of the products. In the future, we would like to study the ferulic acid and zingerone content of other plants and extract them efficiently. The optimization of electrochemical reactions and the use of other test methods are also among our plans.

Keywords: ferulic acid, ginger, synthesis, zingerone

Procedia PDF Downloads 157

Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: Tran Tran

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Mental health issues are prevalent among Vietnamese undergraduate students, and they are greatly exacerbated during the COVID-19 pandemic for this population. While there is empirical evidence supporting the effectiveness and efficiency of therapy on mental health issues among college students, the rates of Vietnamese college students seeking professional mental health services were alarmingly low. Multiple factors can prevent those in need from finding support. The Internalized Stigma Model posits that public stigma directly affects intentions to seek psychological help via self-stigma and attitudes toward seeking help. However, little research has focused on what factors can predict public stigma toward seeking professional psychological support, especially among this population. A potential predictor is academic majors since academic majors can influence undergraduate students' perceptions, attitudes, and intentions. A study suggested that students who have completed two or more psychology courses have a more positive attitude toward seeking care for mental health issues and reduced stigma, which might be attributed to increased mental health literacy. In addition, research has shown that women are more likely to utilize mental health services and have lower stigma than men. Finally, studies have also suggested that experience of mental health services can increase endorsement of perceived need and lower stigma. Thus, it is expected that perceived helpfulness from past service uses can reduce stigma. This study aims to address this gap in the literature and investigate which factors can predict public stigma, specifically academic major, gender, and perceived helpfulness, potentially suggesting an avenue of prevention and ultimately improving the well-being of Vietnamese college students. The sample includes 408 undergraduate students (Mage = 20.44; 80.88% female) Hanoi city, Vietnam. Participants completed a pen-and-paper questionnaire. Students completed the Stigma Scale for Receiving Psychological Help, which yielded a mean public stigma score. Participants also completed a measurement assessing their perceived helpfulness of their university’s counseling center, which included eight subscales: future self-development, learning issues, career counseling, medical and health issues, mental health issues, conflicts between teachers and students, conflicts between parents and students, and interpersonal relationships. Items were summed to create a composite perceived helpfulness score. Finally, participants provided demographic information. This included gender, which was dichotomized between female and other. Additionally, it included academic major, which was also similarly dichotomized between psychology and other (e.g., natural science, social science, and pedagogy & social work). Linear relationships between public stigma and gender, academic major, and perceived helpfulness were analyzed individually with a regression model. Findings suggested that academic major, gender, and perceived counseling center's helpfulness predicted stigma against seeking professional psychological help. Specifically, being a psychology major predicted lower levels of public stigma (β = -.25, p < .001). Additionally, gender female predicted lower levels of public stigma (β = -.11, p < .05). Lastly, higher levels of perceived helpfulness of the counseling center also predicted lower levels of public stigma (β = -.16, p < .01). The study’s results offer potential intervention avenues to help reduce stigma and increase well-being for Vietnamese college students.

Keywords: stigma, vietnamese college students, counseling services, help-seeking

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Authors: Swadha Singh

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International Solar Alliance is the foremost treaty-based global organization concerned with tapping the potential of sun-abundant nations between the Tropics of Cancer and Capricorn and enables co-operation among them. As a founding member of the International Solar Alliance, India exhibits its positioning as an upcoming leader in clean energy. India has set ambitious goals and targets to expand the share of solar in its energy mix and is playing a proactive role both at the regional and global levels. ISA aims to serve multiple goals- bring about scale commercialization of solar power, boost domestic manufacturing, and leverage solar diplomacy in African countries, amongst others. Against this backdrop, this paper attempts to examine the ways in which ISA as an intergovernmental organization under Indian leadership can leverage the cause of clean energy (solar) diplomacy and effectively shape partnerships and collaborations with other developing countries in terms of sharing solar technology, capacity building, risk mitigation, mobilizing financial investment and providing an aggregate market. A more specific focus of ISA is on the developing countries, which in the absence of a collective, are constrained by technology and capital scarcity, despite being naturally endowed with solar resources. Solar rich but finance-constrained economies face political risk, foreign exchange risk, and off-taker risk. Scholars argue that aligning India’s climate change discourse and growth prospects in its engagements, collaborations, and partnerships at the bilateral, multilateral and regional level can help promote trade, attract investments, and promote resilient energy transition both in India and in partner countries. For developing countries, coming together in an action-oriented way on issues of climate and clean energy is particularly important since it is developing and underdeveloped countries that face multiple and coalescing challenges such as the adverse impact of climate change, uneven and low access to reliable energy, and pressing employment needs. Investing in green recovery is agreed to be an assured way to create resilient value chains, create sustainable livelihoods, and help mitigate climate threats. If India is able to ‘green its growth’ process, it holds the potential to emerge as a climate leader internationally. It can use its experience in the renewable sector to guide other developing countries in balancing multiple similar objectives of development, energy security, and sustainability. The challenges underlying solar expansion in India have lessons to offer other developing countries, giving India an opportunity to assume a leadership role in solar diplomacy and expand its geopolitical influence through inter-governmental organizations such as ISA. It is noted that India has limited capacity to directly provide financial funds and support and is not a leading manufacturer of cheap solar equipment, as does China; however, India can nonetheless leverage its large domestic market to scale up the commercialization of solar power and offer insights and learnings to similarly placed abundant solar countries. The paper examines the potential of and limits placed on India’s solar diplomacy.

Keywords: climate diplomacy, energy security, solar diplomacy, renewable energy

Procedia PDF Downloads 104