Search results for: therapeutic efficacy
411 The Administration of Infection Diseases During the Pandemic COVID-19 and the Role of the Differential Diagnosis with Biomarkers VB10
Authors: Sofia Papadimitriou
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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score
Procedia PDF Downloads 146410 Community Based Psychosocial Intervention Reduces Maternal Depression and Infant Development in Bangladesh
Authors: S. Yesmin, N. F.Rahman, R. Akther, T. Begum, T. Tahmid, T. Chowdury, S. Afrin, J. D. Hamadani
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Abstract: Maternal depression is one of the risk factors of developmental delay in young children in low-income countries. Maternal depressions during pregnancy are rarely reported in Bangladesh. Objectives: The purpose of the present study was to examine the efficacy of a community based psychosocial intervention on women with mild to moderate depressive illness during the perinatal period and on their children from birth to 12 months on mothers’ mental status and their infants’ growth and development. Methodology: The study followed a prospective longitudinal approach with a randomized controlled design. Total 250 pregnant women aged between 15 and 40 years were enrolled in their third trimester of pregnancy of which 125 women were in the intervention group and 125 in the control group. Women in the intervention group received the “Thinking Healthy (CBT based) program” at their home setting, from their last month of pregnancy till 10 months after delivery. Their children received psychosocial stimulation from birth till 12 months. The following instruments were applied to get the outcome information- Bangla version of Edinburgh Postnatal Depression Scale (BEPDS), Prenatal Attachment Inventory (PAI), Maternal Attachment Inventory (MAI), Bayley Scale of Infant Development-Third version (Bayley–III) and Family Care Indicator (FCI). In addition, sever morbidity; breastfeeding, immunization, socio-economic and demographic information were collected. Data were collected at three time points viz. baseline, midline (6 months after delivery) and endline (12 months after delivery). Results: There was no significant difference between any of the socioeconomic and demographic variables at baseline. A very preliminary analysis of the data shows an intervention effect on Socioemotional behaviour of children at endline (p<0.001), motor development at midline (p=0.016) and at endline (p=0.065), language development at midline (p=0.004) and at endline (p=0.023), cognitive development at midline (p=0.008) and at endline (p=0.002), and quality of psychosocial stimulation at midline (p=0.023) and at endline (p=0.010). EPDS at baseline was not different between the groups (p=0.419), but there was a significant improvement at midline (p=0.027) and at endline (p=0.024) between the groups following the intervention. Conclusion: Psychosocial intervention is found effective in reducing women’s low and moderate depressive illness to cope with mental health problem and improving development of young children in Bangladesh.Keywords: mental health, maternal depression, infant development, CBT, EPDS
Procedia PDF Downloads 267409 Date Palm Fruits from Oman Attenuates Cognitive and Behavioral Defects and Reduces Inflammation in a Transgenic Mice Model of Alzheimer's Disease
Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein
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Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation
Procedia PDF Downloads 419408 Critical Core Skills Profiling in the Singaporean Workforce
Authors: Bi Xiao Fang, Tan Bao Zhen
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Soft skills, core competencies, and generic competencies are exchangeable terminologies often used to represent a similar concept. In the Singapore context, such skills are currently being referred to as Critical Core Skills (CCS). In 2019, SkillsFuture Singapore (SSG) reviewed the Generic Skills and Competencies (GSC) framework that was first introduced in 2016, culminating in the development of the Critical Core Skills (CCS) framework comprising 16 soft skills classified into three clusters. The CCS framework is part of the Skills Framework, and whose stated purpose is to create a common skills language for individuals, employers and training providers. It is also developed with the objectives of building deep skills for a lean workforce, enhance business competitiveness and support employment and employability. This further helps to facilitate skills recognition and support the design of training programs for skills and career development. According to SSG, every job role requires a set of technical skills and a set of Critical Core Skills to perform well at work, whereby technical skills refer to skills required to perform key tasks of the job. There has been an increasing emphasis on soft skills for the future of work. A recent study involving approximately 80 organizations across 28 sectors in Singapore revealed that more enterprises are beginning to recognize that soft skills support their employees’ performance and business competitiveness. Though CCS is of high importance for the development of the workforce’s employability, there is little attention paid to the CCS use and profiling across occupations. A better understanding of how CCS is distributed across the economy will thus significantly enhance SSG’s career guidance services as well as training providers’ services to graduates and workers and guide organizations in their hiring for soft skills. This CCS profiling study sought to understand how CCS is demanded in different occupations. To achieve its research objectives, this study adopted a quantitative method to measure CCS use across different occupations in the Singaporean workforce. Based on the CCS framework developed by SSG, the research team adopted a formative approach to developing the CCS profiling tool to measure the importance of and self-efficacy in the use of CCS among the Singaporean workforce. Drawing on the survey results from 2500 participants, this study managed to profile them into seven occupation groups based on the different patterns of importance and confidence levels of the use of CCS. Each occupation group is labeled according to the most salient and demanded CCS. In the meantime, the CCS in each occupation group, which may need some further strengthening, were also identified. The profiling of CCS use has significant implications for different stakeholders, e.g., employers could leverage the profiling results to hire the staff with the soft skills demanded by the job.Keywords: employability, skills profiling, skills measurement, soft skills
Procedia PDF Downloads 90407 Determination of 1-Deoxynojirimycin and Phytochemical Profile from Mulberry Leaves Cultivated in Indonesia
Authors: Yasinta Ratna Esti Wulandari, Vivitri Dewi Prasasty, Adrianus Rio, Cindy Geniola
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Mulberry is a plant that widely cultivated around the world, mostly for silk industry. In recent years, the study showed that the mulberry leaves have an anti-diabetic effect which mostly comes from the compound known as 1-deoxynojirimycin (DNJ). DNJ is a very potent α-glucosidase inhibitor. It will decrease the degradation rate of carbohydrates in digestive tract, leading to slower glucose absorption and reducing the post-prandial glucose level significantly. The mulberry leaves also known as the best source of DNJ. Since then, the DNJ in mulberry leaves had received a considerable attention, because of the increased number of diabetic patients and the raise of people awareness to find a more natural cure for diabetic. The DNJ content in mulberry leaves varied depend on the mulberry species, leaf’s age, and the plant’s growth environment. Few of the mulberry varieties that were cultivated in Indonesiaare Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The lack of data concerning phytochemicals contained in the Indonesian mulberry leaves are restraining their use in the medicinal field. The aim of this study is to fully utilize the use of mulberry leaves cultivated in Indonesia as a medicinal herb in local, national, or global community, by determining the DNJ and other phytochemical contents in them. This study used eight leaf samples which are the young leaves and mature leaves of both Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The DNJ content was analyzed using reverse phase high performance liquid chromatography (HPLC). The stationary phase was silica C18 column and the mobile phase was acetonitrile:acetic acid 0.1% 1:1 with elution rate 1 mL/min. Prior to HPLC analysis the samples were derivatized with FMOC to ensure the DNJ detectable by VWD detector at 254 nm. Results showed that the DNJ content in samples are ranging from 2.90-0.07 mg DNJ/ g leaves, with the highest content found in M. cathayana mature leaves (2.90 ± 0.57 mg DNJ/g leaves). All of the mature leaf samples also found to contain higher amount of DNJ from their respective young leaf samples. The phytochemicals in leaf samples was tested using qualitative test. Result showed that all of the eight leaf samples contain alkaloids, phenolics, flavonoids, tannins, and terpenes. The presence of this phytochemicals contribute to the therapeutic effect of mulberry leaves. The pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) analysis was also performed to the eight samples to quantitatively determine their phytochemicals content. The pyrolysis temperature was set at 400 °C, with capillary column Phase Rtx-5MS 60 × 0.25 mm ID stationary phase and helium gas mobile phase. Few of the terpenes found are known to have anticancer and antimicrobial properties. From all the results, all of four samples of mulberry leaves which are cultivated in Indonesia contain DNJ and various phytochemicals like alkaloids, phenolics, flavonoids, tannins, and terpenes which are beneficial to our health.Keywords: Morus, 1-deoxynojirimycin, HPLC, Py-GC-MS
Procedia PDF Downloads 320406 De-Pigmentary Effect of Ayurvedic Treatment on Hyper-Pigmentation of Skin Due to Chloroquine: A Case Report
Authors: Sunil Kumar, Rajesh Sharma
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Toxic epidermal necrolysis, pruritis, rashes, lichen planus like eruption, hyper pigmentation of skin are rare toxic effects of choloroquine used over a long time. Skin and mucus membrane hyper pigmentation is generally of a bluish black or grayish color and irreversible after discontinuation of the drug. According to Ayurveda, Dushivisha is the name given to any poisonous substance which is not fully endowed with the qualities of poison by nature (i.e. it acts as an impoverished or weak poison) and because of its mild potency, it remains in the body for many years causing various symptoms, one among them being discoloration of skin.The objective of this case report is to investigate the effect of Ayurvedic management of chloroquine induced hyper-pigmentation on the line of treatment of Dushivisha. Case Report: A 26-year-old female was suffering from hyper-pigmentation of the skin over the neck, forehead, temporo-mandibular joints, upper back and posterior aspect of both the arms since 8 years had history of taking Chloroquine came to Out Patient Department of National Institute of Ayurveda, Jaipur, India in Jan. 2015. The routine investigations (CBC, ESR, Eosinophil count) were within normal limits. Punch biopsy skin studied for histopathology under hematoxylin and eosin staining showed epidermis with hyper-pigmentation of the basal layer. In the papillary dermis as well as deep dermis there were scattered melanophages along with infiltration by mononuclear cells. There was no deposition of amyloid-like substances. These histopathological findings were suggestive of Chloroquine induced hyper-pigmentation. The case was treated on the line of treatment of Dushivisha and was given Vamana and Virechana (therapeutic emesis and purgation) every six months followed by Snehana karma (oleation therapy) with Panchatikta Ghrit and Swedana (sudation). Arogyavardhini Vati -1 g, Dushivishari Vati 500 mg, Mahamanjisthadi Quath 20 ml were given twelve hourly and Aragwadhadi Quath 25 ml at bed time orally. The patient started showing lightening of the pigments after six months and almost complete remission after 12 months of the treatment. Conclusion: This patient presented with the Dushivisha effect of Chloroquineandwas administered two relevant procedures from Panchakarma viz. Vamana and Virechana. Both Vamana and Virechanakarma here referred to Shodhana karma (purification procedures) eliminates accumulated toxins from the body. In this process, oleation dislodge the toxins from the tissues and sudation helps to bring them to the alimentary tract. The line of treatment did not target direct hypo pigmentary effects; rather aimed to eliminate the Dushivisha. This gave promising results in this condition.Keywords: Ayurveda, chloroquine, Dushivisha, hyper-pigmentation
Procedia PDF Downloads 230405 Investigating the Influence of Activation Functions on Image Classification Accuracy via Deep Convolutional Neural Network
Authors: Gulfam Haider, sana danish
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Convolutional Neural Networks (CNNs) have emerged as powerful tools for image classification, and the choice of optimizers profoundly affects their performance. The study of optimizers and their adaptations remains a topic of significant importance in machine learning research. While numerous studies have explored and advocated for various optimizers, the efficacy of these optimization techniques is still subject to scrutiny. This work aims to address the challenges surrounding the effectiveness of optimizers by conducting a comprehensive analysis and evaluation. The primary focus of this investigation lies in examining the performance of different optimizers when employed in conjunction with the popular activation function, Rectified Linear Unit (ReLU). By incorporating ReLU, known for its favorable properties in prior research, the aim is to bolster the effectiveness of the optimizers under scrutiny. Specifically, we evaluate the adjustment of these optimizers with both the original Softmax activation function and the modified ReLU activation function, carefully assessing their impact on overall performance. To achieve this, a series of experiments are conducted using a well-established benchmark dataset for image classification tasks, namely the Canadian Institute for Advanced Research dataset (CIFAR-10). The selected optimizers for investigation encompass a range of prominent algorithms, including Adam, Root Mean Squared Propagation (RMSprop), Adaptive Learning Rate Method (Adadelta), Adaptive Gradient Algorithm (Adagrad), and Stochastic Gradient Descent (SGD). The performance analysis encompasses a comprehensive evaluation of the classification accuracy, convergence speed, and robustness of the CNN models trained with each optimizer. Through rigorous experimentation and meticulous assessment, we discern the strengths and weaknesses of the different optimization techniques, providing valuable insights into their suitability for image classification tasks. By conducting this in-depth study, we contribute to the existing body of knowledge surrounding optimizers in CNNs, shedding light on their performance characteristics for image classification. The findings gleaned from this research serve to guide researchers and practitioners in making informed decisions when selecting optimizers and activation functions, thus advancing the state-of-the-art in the field of image classification with convolutional neural networks.Keywords: deep neural network, optimizers, RMsprop, ReLU, stochastic gradient descent
Procedia PDF Downloads 112404 ATR-IR Study of the Mechanism of Aluminum Chloride Induced Alzheimer Disease - Curative and Protective Effect of Lepidium sativum Water Extract on Hippocampus Rats Brain Tissue
Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali
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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum
Procedia PDF Downloads 354403 Graduates Construction of Knowledge and Ability to Act on Employable Opportunities
Authors: Martabolette Stecher
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Introductory: How is knowledge and ability to act on employable opportunities constructed among students and graduates at higher educations? This question have been drawn much attention by researchers, governments and universities in Denmark, since there has been an increases in the rate of unemployment among graduates from higher education. The fact that more than ten thousand graduates from higher education without the opportunity to get a job in these years has a tremendous impact upon the social economy in Denmark. Every time a student graduate from higher education and become unemployed, it is possible to trace upon the person´s chances to get a job many years ahead. This means that the tremendous rate of graduate unemployment implies a decrease in employment and lost prosperity in Denmark within a billion Danish Kroner scale. Basic methodologies: The present study investigates the construction of knowledge and ability to act upon employable opportunities among students and graduates at higher educations in Denmark in a literature review as well as a preliminary study of students from Aarhus University. 15 students from the candidate of drama have been engaging in an introductory program at the beginning of their candidate study, which included three workshops focusing upon the more personal matters of their studies and life. They have reflected upon this process during the intervention and afterwards in a semi-structured interview. Concurrently a thorough literature review has delivered key concepts for the exploration of the research question. Major findings of the study: It is difficult to find one definition of what employability encompasses, hence the overall picture of how to incorporate the concept is difficult. The present theory of employability has been focusing upon the competencies, which students and graduates are going to develop in order to become employable. In recent years there has been an emphasis upon the mechanism which supports graduates to trust themselves and to develop their self-efficacy in terms of getting a sustainable job. However, there has been little or no focus in the literature upon the idea of how students and graduates from higher education construct knowledge about and ability to act upon employable opportunities involving network of actors both material and immaterial network and meaningful relations for students and graduates in developing their enterprising behavior to achieve employment. The Act-network-theory combined with theory of entrepreneurship education suggests an alternative strategy to focus upon when explaining sustainable ways of creating employability among graduates. The preliminary study also supports this theory suggesting that it is difficult to emphasize a single or several factors of importance rather highlighting the effect of a multitude network. Concluding statement: This study is the first step of a ph.d.-study investigating this problem in Denmark and the USA in the period 2015 – 2019.Keywords: employablity, graduates, action, opportunities
Procedia PDF Downloads 193402 Production, Characterization and In vitro Evaluation of [223Ra]RaCl2 Nanomicelles for Targeted Alpha Therapy of Osteosarcoma
Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira
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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy
Procedia PDF Downloads 107401 DNA Hypomethylating Agents Induced Histone Acetylation Changes in Leukemia
Authors: Sridhar A. Malkaram, Tamer E. Fandy
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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics
Procedia PDF Downloads 139400 Glycosaminoglycan, a Cartilage Erosion Marker in Synovial Fluid of Osteoarthritis Patients Strongly Correlates with WOMAC Function Subscale
Authors: Priya Kulkarni, Soumya Koppikar, Narendrakumar Wagh, Dhanshri Ingle, Onkar Lande, Abhay Harsulkar
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Cartilage is an extracellular matrix composed of aggrecan, which imparts it with a great tensile strength, stiffness and resilience. Disruption in cartilage metabolism leading to progressive degeneration is a characteristic feature of Osteoarthritis (OA). The process involves enzymatic depolymerisation of cartilage specific proteoglycan, releasing free glycosaminoglycan (GAG). This released GAG in synovial fluid (SF) of knee joint serves as a direct measure of cartilage loss, however, limited due to its invasive nature. Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used for assessing pain, stiffness and physical-functions in OA patients. The scale is comprised of three subscales namely, pain, stiffness and physical-function, intends to measure patient’s perspective of disease severity as well as efficacy of prescribed treatment. Twenty SF samples obtained from OA patients were analysed for their GAG values in SF using DMMB based assay. LK 1.0 vernacular version was used to attain WOMAC scale. The results were evaluated using SAS University software (Edition 1.0) for statistical significance. All OA patients revealed higher GAG values compared to the control value of 78.4±30.1µg/ml (obtained from our non-OA patients). Average WOMAC calculated was 51.3 while pain, stiffness and function estimated were 9.7, 3.9 and 37.7, respectively. Interestingly, a strong statistical correlation was established between WOMAC function subscale and GAG (p = 0.0102). This subscale is based on day-to-day activities like stair-use, bending, walking, getting in/out of car, rising from bed. However, pain and stiffness subscale did not show correlation with any of the studied markers and endorsed the atypical inflammation in OA pathology. On one side, where knee pain showed poor correlation with GAG, it is often noted that radiography is insensitive to cartilage degenerative changes; thus OA remains undiagnosed for long. Moreover, active cartilage degradation phase remains elusive to both, patient and clinician. Through analysis of large number of OA patients we have established a close association of Kellgren-Lawrence grades and increased cartilage loss. A direct attempt to correlate WOMAC and radiographic progression of OA with various biomarkers has not been attempted so far. We found a good correlation in GAG levels in SF and the function subscale.Keywords: cartilage, Glycosaminoglycan, synovial fluid, western ontario and McMaster Universities Arthritis Index
Procedia PDF Downloads 435399 Sensory Interventions for Dementia: A Review
Authors: Leigh G. Hayden, Susan E. Shepley, Cristina Passarelli, William Tingo
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Introduction: Sensory interventions are popular therapeutic and recreational approaches for people living with all stages of dementia. However, it is unknown which sensory interventions are used to achieve which outcomes across all subtypes of dementia. Methods: To address this gap, we conducted a scoping review of sensory interventions for people living with dementia. We conducted a search of the literature for any article published in English from 1 January 1990 to 1 June 2019, on any sensory or multisensory intervention targeted to people living with any kind of dementia, which reported on patient health outcomes. We did not include complex interventions where only a small aspect was related to sensory stimulation. We searched the databases Medline, CINHAL, and Psych Articles using our institutional discovery layer. We conducted all screening in duplicate to reduce Type 1 and Type 2 errors. The data from all included papers were extracted by one team member, and audited by another, to ensure consistency of extraction and completeness of data. Results: Our initial search captured 7654 articles, and the removal of duplicates (n=5329), those that didn’t pass title and abstract screening (n=1840) and those that didn’t pass full-text screening (n=281) resulted in 174 articles included. The countries with the highest publication in this area were the United States (n=59), the United Kingdom (n=26) and Australia (n=15). The most common type of interventions were music therapy (n=36), multisensory rooms (n=27) and multisensory therapies (n=25). Seven articles were published in the 1990’s, 55 in the 2000’s, and the remainder since 2010 (n=112). Discussion: Multisensory rooms have been present in the literature since the early 1990’s. However, more recently, nature/garden therapy, art therapy, and light therapy have emerged since 2008 in the literature, an indication of the increasingly diverse scholarship in the area. The least popular type of intervention is a traditional food intervention. Taste as a sensory intervention is generally avoided for safety reasons, however it shows potential for increasing quality of life. Agitation, behavior, and mood are common outcomes for all sensory interventions. However, light therapy commonly targets sleep. The majority (n=110) of studies have very small sample sizes (n=20 or less), an indicator of the lack of robust data in the field. Additional small-scale studies of the known sensory interventions will likely do little to advance the field. However, there is a need for multi-armed studies which directly compare sensory interventions, and more studies which investigate the use of layering sensory interventions (for example, adding an aromatherapy component to a lighting intervention). In addition, large scale studies which enroll people at early stages of dementia will help us better understand the potential of sensory and multisensory interventions to slow the progression of the disease.Keywords: sensory interventions, dementia, scoping review
Procedia PDF Downloads 127398 Advanced Techniques in Semiconductor Defect Detection: An Overview of Current Technologies and Future Trends
Authors: Zheng Yuxun
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This review critically assesses the advancements and prospective developments in defect detection methodologies within the semiconductor industry, an essential domain that significantly affects the operational efficiency and reliability of electronic components. As semiconductor devices continue to decrease in size and increase in complexity, the precision and efficacy of defect detection strategies become increasingly critical. Tracing the evolution from traditional manual inspections to the adoption of advanced technologies employing automated vision systems, artificial intelligence (AI), and machine learning (ML), the paper highlights the significance of precise defect detection in semiconductor manufacturing by discussing various defect types, such as crystallographic errors, surface anomalies, and chemical impurities, which profoundly influence the functionality and durability of semiconductor devices, underscoring the necessity for their precise identification. The narrative transitions to the technological evolution in defect detection, depicting a shift from rudimentary methods like optical microscopy and basic electronic tests to more sophisticated techniques including electron microscopy, X-ray imaging, and infrared spectroscopy. The incorporation of AI and ML marks a pivotal advancement towards more adaptive, accurate, and expedited defect detection mechanisms. The paper addresses current challenges, particularly the constraints imposed by the diminutive scale of contemporary semiconductor devices, the elevated costs associated with advanced imaging technologies, and the demand for rapid processing that aligns with mass production standards. A critical gap is identified between the capabilities of existing technologies and the industry's requirements, especially concerning scalability and processing velocities. Future research directions are proposed to bridge these gaps, suggesting enhancements in the computational efficiency of AI algorithms, the development of novel materials to improve imaging contrast in defect detection, and the seamless integration of these systems into semiconductor production lines. By offering a synthesis of existing technologies and forecasting upcoming trends, this review aims to foster the dialogue and development of more effective defect detection methods, thereby facilitating the production of more dependable and robust semiconductor devices. This thorough analysis not only elucidates the current technological landscape but also paves the way for forthcoming innovations in semiconductor defect detection.Keywords: semiconductor defect detection, artificial intelligence in semiconductor manufacturing, machine learning applications, technological evolution in defect analysis
Procedia PDF Downloads 29397 An Analysis of Teacher Knowledge of Recognizing and Addressing the Needs of Traumatized Students
Authors: Tiffany Hollis
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Childhood trauma is well documented in mental health research, yet has received little attention in urban schools. Child trauma affects brain development and impacts cognitive, emotional, and behavioral functioning. When educators understand that some of the behaviors that appear to be aggressive in nature might be the result of a hidden diagnosis of trauma, learning can take place, and the child can thrive in the classroom setting. Traumatized children, however, do not fit neatly into any single ‘box.’ Although many children enter school each day carrying with them the experience of exposure to violence in the home, the symptoms of their trauma can be multifaceted and complex, requiring individualized therapeutic attention. The purpose of this study was to examine how prepared educators are to address the unique challenges facing children who experience trauma. Given the vast number of traumatized children in our society, it is evident that our education system must investigate ways to create an optimal learning environment that accounts for trauma, addresses its impact on cognitive and behavioral development, and facilitates mental and emotional health and well-being. The researcher describes the knowledge, attitudes, dispositions, and skills relating to trauma-informed knowledge of induction level teachers in a diverse middle school. The data for this study were collected through interviews with teachers, who are in the induction phase (the first three years of their teaching career). The study findings paint a clear picture of how ill-prepared educators are to address the needs of students who have experienced trauma and the implications for the development of a professional development workshop or series of workshops that train teachers how to recognize and address and respond to the needs of students. The study shows how teachers often lack skills to meet the needs of students who have experienced trauma. Traumatized children regularly carry a heavy weight on their shoulders. Children who have experienced trauma may feel that the world is filled with unresponsive, threatening adults, and peers. Despite this, supportive interventions can provide traumatized children with places to go that are safe, stimulating, and even fun. Schools offer an environment that potentially meets these requirements by creating safe spaces where students can feel at ease and have fun while also learning via stimulating educational activities. This study highlights the lack of preparedness of educators to address the academic, behavioral, and cognitive needs of students who have experienced trauma. These findings provide implications for the creation of a professional development workshop that addresses how to recognize and address the needs of students who have experienced some type of trauma. They also provide implications for future research with a focus on specific interventions that enable the creation of optimal learning environments where students who have experienced trauma and all students can succeed, regardless of their life experiences.Keywords: educator preparation, induction educators, professional development, trauma-informed
Procedia PDF Downloads 119396 Fear of Falling and Physical Activities: A Comparison Between Rural and Urban Elderly People
Authors: Farhad Azadi, Mohammad Mahdi Mohammadi, Mohsen Vahedi, Zahra Mahdiin
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Context: The aging population is growing all over the world and maintaining physical activity is essential for healthy aging. However, fear of falling is a major obstacle to physical activity among the elderly. The aim of this study is to investigate and compare the relationship between fear of falling and physical activity in Iranian urban and rural elderly. Research Aim: The main aim of this cross-sectional analytical study is to investigate and compare the relationship between fear of falling and physical activity in Iranian rural and urban elderly. Methodology: The study used simple non-probability sampling to select 350 participants aged 60 years and older from rural and urban areas of Konarak, Sistan and Baluchistan provinces in Iran. The Persian versions of the Falls Efficacy Scale - International, Rapid Physical Activity Assessment, Activities of Daily Living, and Instrumental Activities of Daily Living questionnaires were used to assess fear of falling and physical activity. The data were analyzed using Pearson correlation tests. Findings: The study found a statistically significant negative correlation between fear of falling and physical activity, as measured by ADL, IADL, and RAPA1(aerobic ), in all elderly and rural and urban elderly (p<0.001). Fear of falling was higher in rural areas, while physical activity levels measured by ADL and RAPA1 were higher in urban areas. No significant difference was found between the two groups in IADL and RAPA2 (strength and flexibility) scores. Theoretical Importance: This study highlights the importance of considering the fear of falling as a significant obstacle to proper physical activity, especially among the elderly living in rural areas. Furthermore, the study provides insight into the difference between rural and urban elderly people in terms of fear of falling and physical activity. Data Collection and Analysis Procedures: Data was collected through questionnaires and analyzed using Pearson correlation tests. Questions Addressed: The study attempted to answer the following questions: Is there a relationship between fear of falling and physical activity in Iranian urban and rural elderly people? Is there a difference in fear of falling and physical activity between rural and urban elderly? Conclusion: Fear of falling is a major obstacle to physical activity among the elderly, especially in rural areas. The study found a significant negative correlation between fear of falling and physical activity in all elderly and rural and urban elderly. In addition, urban and rural elderly have differences in aerobic activity levels, but they do not differ in terms of flexibility and strength. Therefore, proper interventions are required to ensure that the elderly can maintain physical activity, especially in rural and deprived areas.Keywords: aged, fear of falling, physical activity, urban population, rural population
Procedia PDF Downloads 65395 The Type II Immune Response in Acute and Chronic Pancreatitis Mediated by STAT6 in Murine
Authors: Hager Elsheikh
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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response
Procedia PDF Downloads 30394 Suitable Operating Conditions of Hot Water Generators Combined with Central Air Package Units: A Case Study of Tipco Building Group
Authors: Chalermporn Jindapeng
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The main objective of the study of the suitable operating conditions of hot water generators combined with central air package units: a case study of Tipco Building Group was to analyze the suitable operating conditions and energy-related costs in each operating condition of hot water generators combined with central air package units which resulted in water-cooled packages. Thermal energy from vapor form refrigerants at high pressures and temperatures was exchanged with thermal energy of the water in the swimming pool that required suitable temperature control for users with the use of plate heat exchangers before refrigerants could enter the condenser in its function to change the status of vapor form refrigerants at high pressures and temperatures to liquid form at high pressures and temperatures. Thus, if this was used to replace heat pumps it could reduce the electrical energy that was used to make hot water and reduce the cost of the electrical energy of air package units including the increased efficacy of air package units. Of the analyses of the suitable operating conditions by means of the study of the elements involved with actual measurements from the system that had been installed at the Tipco Building Group hot water generators were combined with air package units which resulted in water-cooled packages with a cooling capacity of 75 tonnes. Plate heat exchangers were used in the transfer of thermal energy from refrigerants to one set of water with a heat exchanger area of 1.5 m² which was used to increase the temperature of swimming pool water that has a capacity of 240 m³. From experimental results, it was discovered after continuous temperature measurements in the swimming pool every 15 minutes that swimming pool water temperature increased by 0.78 ⁰C 0.75 ⁰C 0.74 ⁰C and 0.71 ⁰C. The rates of flow of hot water through the heat exchangers were equal to 14, 16, 18 and 20 litres per minute respectively where the swimming pool water temperature was at a constant value and when the rate of flow of hot water increased this caused hot water temperatures to decrease and the coefficient of performance of the air package units to increase from 5.9 to 6.3, 6.7, 6.9 and 7.6 while the rates of flow of hot water were equal to 14, 16, 18 and 20 litres per minute, respectively. As for the cooling systems, there were no changes and the system cooling functions were normal as the cooling systems were able to continuously transfer incoming heat for the swimming pool water which resulted in a constant pressure in the cooling system that allowed its cooling functions to work normally.Keywords: central air package units, heat exchange, hot water generators, swimming pool
Procedia PDF Downloads 252393 Biological Significance of Long Intergenic Noncoding RNA LINC00273 in Lung Cancer Cell Metastasis
Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal
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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma
Procedia PDF Downloads 148392 Probiotics as an Alternative to Antibiotic Use in Pig Production
Authors: Z. C. Dlamini, R. L. S. Langa, A. I. Okoh, O. A. Aiyegoro
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The indiscriminate usage of antibiotics in swine production have consequential outcomes; such as development of bacterial resistance to prophylactic antibiotics and possibility of antibiotic residues in animal products. The use of probiotics appears to be the most effective procedure with positive metabolic nutritional implications. The aim of this study was to investigate the efficacy of probiotic bacteria (Lactobacillus reuteri ZJ625, Lactobacillus reuteri VB4, Lactobacillus salivarius ZJ614 and Streptococcus salivarius NBRC13956) administered as direct-fed microorganisms in weaned piglets. 45 weaned piglets blocked by weight were dived into 5 treatments groups: diet with antibiotic, diet with no-antibiotic and no probiotic, and diet with probiotic and diet with combination of probiotics. Piglets performance was monitored during the trials. Faecal and Ileum samples were collected for microbial count analysis. Blood samples were collected from pigs at the end of the trial, for analysis of haematological, biochemical and IgG stimulation. The data was analysed by Split-Plot ANOVA using SAS statistically software (SAS 9.3) (2003). The difference was observed between treatments for daily weight and feed conversion ratio. No difference was observed in analysis of faecal samples in regards with bacterial counts, difference was observed in ileums samples with enteric bacteria colony forming unit being lower in P2 treatment group as compared with lactic acid and total bacteria. With exception of globulin and albumin, biochemistry blood parameters were not affected, likewise for haematology, only basophils and segmented neutrophils were differed by having higher concentration in NC treatment group as compared with other treatment groups. Moreover, in IgG stimulation analysis, difference was also observed, with P2 treatment group having high concentration of IgG in P2 treatment group as compared to other groups. The results of this study suggest that probiotics have a beneficial effect on growth performances, blood parameters and IgG stimulation of pigs, most effective when they are administered in synergy form. This means that it is most likely that these probiotics will offer a significant benefit in pig farming by reducing risk of morbidity and mortality and produce quality meat that is more affordable to poorer communities, and thereby enhance South African pig industry’s economy. In addition, these results indicate that there is still more research need to be done on probiotics in regards with, i.e. dosage, shelf life and mechanism of action.Keywords: antibiotics, biochemistry, haematology, IgG-stimulation, microbial count, probiotics
Procedia PDF Downloads 287391 Consensual A-Monogamous Relationships: Challenges and Ways of Coping
Authors: Tal Braverman Uriel, Tal Litvak Hirsch
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Background and Objectives: Little or only partial emphasis has been placed on exploring the complexity of consensual non-monogamous relationships. The term "polyamory" refers to consensual non-monogamy, and it is defined as having emotional and/or sexual relations simultaneously with two or more people, the consent and knowledge of all the partners concerned. Managing multiple romantic relationships with different people evokes more emotions, leads to more emotional conflicts arising from different interests, and demands practical strategies. An individual's transition from a monogamous lifestyle to a consensual non-monogamous lifestyle yields new challenges, accompanied by stress, uncertainty, and question marks, as do other life-changing events, such as divorce or transition to parenthood. The study examines both the process of transition and adaptation to a consensually non-monogamous relationship, as well as the coping mechanism involved in the daily conduct of this lifestyle. The research focuses on understanding the consequences, challenges, and coping methods from a personal, marital, and familial point of view and focuses on 40 middle-aged individuals (20 men and 20 women ages 40-60). The research sheds light on a way of life that has not been previously studied in Israel and is still considered unacceptable. Theories of crisis (e.g., as Folkman and Lazarus) were applied, and as a result, a deeper understanding of the subject was reached, all while focusing on multiple aspects of dealing with stress. The basic research question examines the consequences of entering a polyamorous life from a personal point of view as an individual, partner, and parent and the ways of coping with these consequences. Method: The research is conducted with a narrative qualitative approach in the interpretive paradigm, including semi-structured in-depth interviews. The method of analysis is thematic. Results: The findings indicate that in most cases, an individual's motivation to open the relationship is mainly a longing for better sexuality and for an added layer of excitement to their lives. Most of the interviewees were assisted by their spouses in the process, as well as by social networks and podcasts on the subject. Some of them therapeutic professionals from the field are helpful. It also clearly emerged that among those who experienced acute emotional crises with the primary partner or painful separations from secondary partners, all believed polyamory to be the adequate way of life for them. Finally, a key resource for managing tension and stress is the ability to share and communicate with the primary partner. Conclusions: The study points to the challenges and benefits of a non-monogamous lifestyle as well as the use of coping mechanisms and resources that are consistent with the existing theory and research in the field in the context of life changes. The study indicates the need to expand the research canvas in the future in the context of parenting and the consequences for children.Keywords: a-monogamy, consent, family, stress, tension
Procedia PDF Downloads 66390 Efficacy of Ergonomics Ankle Support on Squatting Pushing Skills during the Second Stage of Labor
Authors: Yu-Ching Lin, Meei-Ling Gau, Ghi-Hwei Kao, Hung-Chang Lee
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Objective: To compare the pushing experiences and birth outcomes of three different pushing positions during the second stage of labor. The three positions were: semi-recumbent, squatting, and squatting with the aid of ergonomically designed ankle supports. Methods: A randomized controlled trial was conducted at a regional teaching hospital in northern Taiwan. Data were collected from 168 primiparous women in their 38th to 42nd gestational week. None of the participants received epidural analgesia during labor and all were free of pregnancy and labor-related complications. Intervention: During labor, after full cervical dilation and when the fetal head had descended to at least the +1 station and had turned to the occiput anterior position, the experimental group was asked to push in the squatting position while wearing the ergonomically designed ankle supports; comparison group A was asked to push in the squatting position without the use of these supports; and comparison group B was asked to push in a standard semi-recumbent position. Measures: The participants completed a demographic and obstetrics datasheet, the Short Form McGill Pain Questionnaire (MPQ-SF), and the Labor Pushing Experience scale within 4-hours postpartum. Conclusion: In terms of delivery time, the duration between the start of pushing to crowning for the experimental group (squatting with ankle supports) averaged 25.52 minutes less (F =6.02, p< .05) than the time for comparison group B (semi-recumbent). Furthermore, the duration between the start of pushing to infant birth averaged 25.21 minutes less for the experimental group than for comparison group B (F =6.14, p< .05). Moreover, the experimental group had a lower average VAS pain score (5.05±3.22) than comparison group B and the average McGill pain score for the experimental group was lower than both comparison groups (F=18.12, p< .001). In summary, the participants in the group that delivered from a squatting position with ankle supports had better labor pushing experiences than their peers in the comparison groups. Results: In comparison to both unsupported squatting and semi-recumbent pushing, squatting with the aid of ergonomically designed ankle supports reduced pushing times, ameliorated labor pain, and improved the pushing experience. Clinical application and suggestion: The squatting with ankle-support intervention introduced in the present study may significantly reduce tiredness and difficulties in maintaining balance as well as increase pushing efficiency. Thus, this intervention may reduce the caring needs of women during the second stage of labor. This intervention may be introduced in midwifery education programs and in clinical practice as a method to improve the care of women during the second stage of labor.Keywords: second stage of labor, pushing, squatting with ankle supports, squatting
Procedia PDF Downloads 269389 Traumatic Brain Injury Induced Lipid Profiling of Lipids in Mice Serum Using UHPLC-Q-TOF-MS
Authors: Seema Dhariwal, Kiran Maan, Ruchi Baghel, Apoorva Sharma, Poonam Rana
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Introduction: Traumatic brain injury (TBI) is defined as the temporary or permanent alteration in brain function and pathology caused by an external mechanical force. It represents the leading cause of mortality and morbidity among children and youth individuals. Various models of TBI in rodents have been developed in the laboratory to mimic the scenario of injury. Blast overpressure injury is common among civilians and military personnel, followed by accidents or explosive devices. In addition to this, the lateral Controlled cortical impact (CCI) model mimics the blunt, penetrating injury. Method: In the present study, we have developed two different mild TBI models using blast and CCI injury. In the blast model, helium gas was used to create an overpressure of 130 kPa (±5) via a shock tube, and CCI injury was induced with an impact depth of 1.5mm to create diffusive and focal injury, respectively. C57BL/6J male mice (10-12 weeks) were divided into three groups: (1) control, (2) Blast treated, (3) CCI treated, and were exposed to different injury models. Serum was collected on Day1 and day7, followed by biphasic extraction using MTBE/Methanol/Water. Prepared samples were separated on Charged Surface Hybrid (CSH) C18 column and acquired on UHPLC-Q-TOF-MS using ESI probe with inhouse optimized parameters and method. MS peak list was generated using Markerview TM. Data were normalized, Pareto-scaled, and log-transformed, followed by multivariate and univariate analysis in metaboanalyst. Result and discussion: Untargeted profiling of lipids generated extensive data features, which were annotated through LIPID MAPS® based on their m/z and were further confirmed based on their fragment pattern by LipidBlast. There is the final annotation of 269 features in the positive and 182 features in the negative mode of ionization. PCA and PLS-DA score plots showed clear segregation of injury groups to controls. Among various lipids in mild blast and CCI, five lipids (Glycerophospholipids {PC 30:2, PE O-33:3, PG 28:3;O3 and PS 36:1 } and fatty acyl { FA 21:3;O2}) were significantly altered in both injury groups at Day 1 and Day 7, and also had VIP score >1. Pathway analysis by Biopan has also shown hampered synthesis of Glycerolipids and Glycerophospholipiods, which coincides with earlier reports. It could be a direct result of alteration in the Acetylcholine signaling pathway in response to TBI. Understanding the role of a specific class of lipid metabolism, regulation and transport could be beneficial to TBI research since it could provide new targets and determine the best therapeutic intervention. This study demonstrates the potential lipid biomarkers which can be used for injury severity diagnosis and identification irrespective of injury type (diffusive or focal).Keywords: LipidBlast, lipidomic biomarker, LIPID MAPS®, TBI
Procedia PDF Downloads 108388 In vivo Alterations in Ruminal Parameters by Megasphaera Elsdenii Inoculation on Subacute Ruminal Acidosis (SARA)
Authors: M. S. Alatas, H. D. Umucalilar
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SARA is a common and serious metabolic disorder in early lactation in dairy cattle and in finishing beef cattle, caused by diets with high inclusion of cereal grain. This experiment was performed to determine the efficacy of Megasphaera elsdenii, a major lactate-utilizing bacterium in prevention/treatment of SARA in vivo. In vivo experimentation, it was used eight ruminally cannulated rams and it was applied the rapid adaptation with the mixture of grain based on wheat (%80 wheat, %20 barley) and barley (%80 barley, %20 wheat). During the systematic adaptation, it was followed the probability of SARA formation by being measured the rumen pH with two hours intervals after and before feeding. After being evaluated the data, it was determined the ruminal pH ranged from 5,2-5,6 on the condition of feeding with 60 percentage of grain mixture based on barley and wheat, that assured the definite form of subacute acidosis. In four days SARA period, M. elsdenii (1010 cfu ml-1) was inoculated during the first two days. During the SARA period, it was observed the decrease of feed intake with M. elsdenii inoculation. Inoculation of M. elsdenii was caused to differentiation of rumen pH (P < 0,0001), while it was found the pH level approximately 5,55 in animals applied the inoculation, it was 5,63 pH in other animals. It was observed that total VFA with the bacterium inoculation tended to change in terms of grain feed (P < 0,07). It increased with the effect of total VFA inoculation in barley based diet, but it was more stabilized in wheat based diet. Bacterium inoculation increased the ratio of propionic acid (18,33%-21,38%) but it caused to decrease the butyric acid, and acetic/propionic acid. During the rapid adaptation, the concentration of lactic acid in the rumen liquid increased depending upon grain level (P<0,0001). On the other hand bacterium inoculation did not have an effect on concentration of lactic acid. M. elsdenii inoculation did not affect ruminal ammonia concentration. In the group that did not apply inoculation, the level of ruminal ammonia concentration was higher than the others applied inoculation. M. elsdenii inoculation did not changed protozoa count in barley-based diet whereas it decreased in wheat-based diet. In the period of SARA, it was observed that the level of blood glucose, lactate and hematocrit increased greatly after inoculation (P < 0,0001). When it is generally evaluated, it is seen that M. elsdenii inoculation has not a positive impact on rumen parameters. Therefore, to reveal the full impact of the inoculation with different strains, feedstuffs and animal groups, further research is required.Keywords: In vivo, Subactute ruminal acidosis, Megasphaera elsdenii, Rumen fermentation
Procedia PDF Downloads 633387 Anti-Bacterial Activity Studies of Derivatives of 6β-Hydroxy Betunolic Acid against Selected Stains of Gram (+) and Gram (-) Bacteria
Authors: S. Jayasinghe, W. G. D. Wickramasingha, V. Karunaratne, D. N. Karunaratne, A. Ekanayake
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Multi-drug resistant microbial pathogens are a serious global health problem, and hence, there is an urgent necessity for discovering new drug therapeutics. However, finding alternatives is a one of the biggest challenges faced by the global drug industry due to the spiraling high cost and serious side effects associated with modern medicine. On the other hand, plants and their secondary metabolites can be considered as good sources of scaffolds to provide structurally diverse bioactive compounds as potential therapeutic agents. 6β-hydroxy betunolic acid is a triterpenoid isolated from bark of Schumacheria castaneifolia which is an endemic plant to Sri Lanka which has shown antibacterial activity against both Staphylococcus aureus (ATCC 29213) and methicillin-resistant S. aureus with Minimum Inhibition Concentration (MIC) of 16 µg/ml. The objective of this study was to determine the anti-bacterial activity for the derivatives of 6β- hydroxy betunolic acid against standard strains of Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), carbepenemas produce Kebsiella pneumonia (ATCC BAA 1705) and carbepenemas non produce Kebsiella pneumonia (ATCC BAA 1706) and four stains of clinically isolated methicillin resistance S. aureus and Acinetobacter. Structural analogues of 6β-hydroxy betunolic acid were synthesized by modifying the carbonyl group at C-3 to obtain olefin and oxime, the hydroxyl group at C-6 position to a ketone, the carboxylic acid at C-17 to obtain amide and halo ester and the olefin group at C-20 position to obtain epoxide. Chemical structures of the synthesized analogues were confirmed with spectroscopic data and antibacterial activity was determined through broth micro dilution assay. Results revealed that 6β- hydroxy betunolic acid shows significant antibacterial activity only against the Gram positive strains and it was inactive against all the tested Gram negative strains for the tested concentration range. However, structural modifications into oxime and olefin at C-3, ketone at C-6 and epoxide at C-20 decreased its antibacterial activity against the gram positive organisms and it was totally lost with the both modifications at C-17 into amide and ester. These results concluded that the antibacterial activity of 6β- hydroxy betunolic acid and derivatives is predominantly depending on the cell wall difference of the bacteria and the presence of carboxylic acid at C-17 is highly important for the antibacterial activity against Gram positive organisms.Keywords: antibacterial activity, 6β- hydroxy betunolic acid, broth micro dilution assay, structure activity relationship
Procedia PDF Downloads 120386 The Role of Piceatannol in Counteracting Glyceraldehyde-3-Phosphate Dehydrogenase Aggregation and Nuclear Translocation
Authors: Joanna Gerszon, Aleksandra Rodacka
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In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation
Procedia PDF Downloads 155385 Early Help Family Group Conferences: An Analysis of Family Plans
Authors: Kate Parkinson
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A Family Group Conference (FGC) is a family-led decision-making process through which a family/kinship group, rather than the professionals involved, is asked to develop a plan for the care or the protection of children in the family. In England and Wales, FGCs are used in 76% of local authorities and in recent years, have tended to be used in cases where the local authority are considering the court process to remove children from their immediate family, to explore kinship alternatives to local authority care. Some local authorities offer the service much earlier, when families first come to the attention of children's social care, in line with research that suggests the earlier an FGC is held, the more likely they are to be successful. Family plans that result from FGCs are different from professional plans in that they are unique to a family and, as a result, reflect the diversity of families. Despite the fact that FGCs are arguable the most researched area of social work globally, there is a dearth of research that examines the nature of family plans and their substance. This paper presents the findings of a documentary analysis of 42 Early Help FGC plans from local authorities in England, with the aim of exploring the level and type of support that family members offer at a FGC. A thematic analysis identified 5 broad areas of support: Practical Support, Building Relationships, Child-care Support, Emotional Support and Social Support. In the majority of cases, family members did not want or ask for any formal support from the local authority or other agencies. Rather, the families came together to agree a plan of support, which was within the parameters of the resources that they as a family could provide. Perhaps then the role of the Early Help professional should be one of a facilitating and enabling role, to support families to develop plans that address their own specific difficulties, rather than the current default option, which is to either close the case because the family do not meet service thresholds or refer to formal support if they do, which may offer very specific support, have rigid referral criteria, long waiting lists and may not reflect the diverse and unique nature of families. FGCs are argued to be culturally appropriate social work practices in that they are appropriate for families from a range of cultural backgrounds and can be adapted to meet particular cultural needs. Furthermore, research on the efficacy of FGCs at an Early Help Level has demonstrated that Early Help FGCs have the potential to address difficulties in family life and prevent the need for formal support services, which are potentially stigmatising and do not reflect the uniqueness and diversity of families. The paper concludes with a recommendation for the use of FGCs across Early Help Services in England and Wales.Keywords: family group conferences, family led decision making, early help, prevention
Procedia PDF Downloads 87384 The Role of Rapid Maxillary Expansion in Managing Obstructive Sleep Apnea in Children: A Literature Review
Authors: Suleman Maliha, Suleman Sidra
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Obstructive sleep apnea (OSA) is a sleep disorder that can result in behavioral and psychomotor impairments in children. The classical treatment modalities for OSA have been continuous positive airway pressure and adenotonsillectomy. However, orthodontic intervention through rapid maxillary expansion (RME) has also been commonly used to manage skeletal transverse maxillary discrepancies. Aim and objectives: The aim of this study is to determine the efficacy of rapid maxillary expansion in paediatric patients with obstructive sleep apnea by assessing pre and post-treatment mean apnea-hypopnea index (AHI) and oxygen saturations. Methodology: Literature was identified through a rigorous search of the Embase, Pubmed, and CINAHL databases. Articles published from 2012 onwards were selected. The inclusion criteria consisted of patients aged 18 years and under with no systemic disease, adenotonsillar surgery, or hypertrophy who are undergoing RME with AHI measurements before and after treatment. In total, six suitable papers were identified. Results: Three studies assessed patients pre and post-RME at 12 months. The first study consisted of 15 patients with an average age of 7.5 years. Following treatment, they found that RME resulted in both higher oxygen saturations (+ 5.3%) and improved AHI (- 4.2 events). The second study assessed 11 patients aged 5–8 years and also noted improvements, with mean AHI reduction from 6.1 to 2.4 and oxygen saturations increasing from 93.1% to 96.8%. The third study reviewed 14 patients aged 6–9 years and similarly found an AHI reduction from 5.7 to 4.4 and an oxygen saturation increase from 89.8% to 95.5%. All modifications noted in these studies were statistically significant. A long-term study reviewed 23 patients aged 6–12 years post-RME treatment on an annual basis for 12 years. They found that the mean AHI reduced from 12.2 to 0.4, with improved oxygen saturations from 78.9% to 95.1%. Another study assessed 19 patients aged 9-12 years at two months into RME and four months post-treatment. Improvements were also noted at both stages, with an overall reduction of the mean AHI from 16.3 to 0.8 and an overall increase in oxygen saturations from 77.9% to 95.4%. The final study assessed 26 children aged 7-11 years on completion of individual treatment and found an AHI reduction from 6.9 to 5.3. However, the oxygen saturation remained stagnant at 96.0%, but this was not clinically significant. Conclusion: Overall, the current evidence suggests that RME is a promising treatment option for paediatric patients with OSA. It can provide efficient and conservative treatment; however, early diagnosis is crucial. As there are various factors that could be contributing to OSA, it is important that each case is treated on its individual merits. Going forward, there is a need for more randomized control trials with larger cohorts being studied. Research into the long-term effects of RME and potential relapse amongst cases would also be useful.Keywords: orthodontics, sleep apnea, maxillary expansion, review
Procedia PDF Downloads 76383 The Role of High-Intensity Focused Ultrasound (HIFU) in the Treatment of Fibroadenomas: A Systematic Review
Authors: Ahmed Gonnah, Omar Masoud, Mohamed Abdel-Wahab, Ahmed ElMosalamy, Abdulrahman Al-Naseem
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Introduction: Fibroadenomas are solid, mobile, and non-tender benign breast lumps, with the highest prevalence amongst young women aged between 15 and 35. Symptoms can include discomfort, and they can become problematic, particularly when they enlarge, resulting in many referrals for biopsies, with fibroadenomas accounting for 30-75% of the cases. Diagnosis is based on triple assessment that involves a clinical examination, ultrasound imaging and mammography, as well as core needle biopsies. Current management includes observation for 6-12 months, with the indication of definitive surgery, in cases that are older than 35 years or with fibroadenoma persistence. Serious adverse effects of surgery might include nipple-areolar distortion, scarring and damage to the breast tissue, as well as the risks associated with surgery and anesthesia, making it a non-feasible option. Methods: A literature search was performed on the databases EMBASE. MEDLINE/PubMed, Google scholar and Ovid, for English language papers published between 1st of January 2000 and 17th of March 2021. A structured protocol was employed to devise a comprehensive search strategy with keywords and Boolean operators defined by the research question. The keywords used for the search were ‘HIFU’, ‘High-Intensity Focused Ultrasound’, ‘Fibroadenoma’, ‘Breast’, ‘Lesion’. This review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Recently, a thermal ablative technique, High Intensity Focused Ultrasound (HIFU), was found to be a safe, non-invasive, and technically successful alternative, having displayed promising outcomes in reducing the volume of fibroadenomas, pain experienced by patients, and the length of hospitalization. Quality of life improvement was also evidenced, exhibited by the disappearance of symptoms, and enhanced physical activity post-intervention, in addition to patients’ satisfaction with the cosmetic results and future recommendation of the procedure to other patients. Conclusion: Overall, HIFU is a well-tolerated treatment associated with a low risk of complications that can potentially include erythema, skin discoloration and bruising, with the majority of this self-resolving shortly after the procedure.Keywords: ultrasound, HIFU, breast, efficacy, side effects, fibroadenoma
Procedia PDF Downloads 211382 The Participation of Experts in the Criminal Policy on Drugs: The Proposal of a Cannabis Regulation Model in Spain by the Cannabis Policy Studies Group
Authors: Antonio Martín-Pardo
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With regard to the context in which this paper is inserted, it is noteworthy that the current criminal policy model in which we find immersed, denominated by some doctrine sector as the citizen security model, is characterized by a marked tendency towards the discredit of expert knowledge. This type of technic knowledge has been displaced by the common sense and by the daily experience of the people at the time of legislative drafting, as well as by excessive attention to the short-term political effects of the law. Despite this criminal-political adverse scene, we still find valuable efforts in the side of experts to bring some rationality to the legislative development. This is the case of the proposal for a new cannabis regulation model in Spain carried out by the Cannabis Policy Studies Group (hereinafter referred as ‘GEPCA’). The GEPCA is a multidisciplinary group composed by authors with multiple/different orientations, trajectories and interests, but with a common minimum objective: the conviction that the current situation regarding cannabis is unsustainable and, that a rational legislative solution must be given to the growing social pressure for the regulation of their consumption and production. This paper details the main lines through which this technical proposal is developed with the purpose of its dissemination and discussion in the Congress. The basic methodology of the proposal is inductive-expository. In that way, firstly, we will offer a brief, but solid contextualization of the situation of cannabis in Spain. This contextualization will touch on issues such as the national regulatory situation and its relationship with the international context; the criminal, judicial and penitentiary impact of the offer and consumption of cannabis, or the therapeutic use of the substance, among others. In second place, we will get down to the business properly by detailing the minutia of the three main cannabis access channels that are proposed. Namely: the regulated market, the associations of cannabis users and personal self-cultivation. In each of these options, especially in the first two, special attention will be paid to both, the production and processing of the substance and the necessary administrative control of the activity. Finally, in a third block, some notes will be given on a series of subjects that surround the different access options just mentioned above and that give fullness and coherence to the proposal outlined. Among those related issues we find some such as consumption and tenure of the substance; the issue of advertising and promotion of cannabis; consumption in areas of special risk (work or driving v. g.); the tax regime; the need to articulate evaluation instruments for the entire process; etc. The main conclusion drawn from the analysis of the proposal is the unsustainability of the current repressive system, clearly unsuccessful, and the need to develop new access routes to cannabis that guarantee both public health and the rights of people who have freely chosen to consume it.Keywords: cannabis regulation proposal, cannabis policies studies group, criminal policy, expertise participation
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